The Cognitive Enhancement Recearch Institute’s Down’s Syndrome Collection Thank you for downloading the Down’s Syndrome Collection from the Cognitive Enhancement Research Institute. The information in this collection is very advanced and quite powerful. Many people will have difficulty understanding it all on first reading. Don’t worry. You can read it twice, or thrice — as many times as you wish. Each time that you re-read it, more will make sense. About the Contents The articles, editorials, updates, sidebars and questions-and-answers (Q&As) in this collection were originally published in the pages of Smart Drug News (from 1992 through 1997) and Smart Life News (from 1997 to the present). They are arranged chronologically. The first article in the collection, a feature article on Down’s syndrome written by Ward Dean, M.D. (CERI’s Medical Advisor) and Steven Wm. Fowkes (CERI’s Executive Director) was published on Valentine’s Day in 1994. The latest article was published in 2001. This collection consists of 44 items drawn from 26 newsletters. Only the newsletter pages with information on Down’s syndrome are included. Five of the items are full-length feature articles (typically 4-7 pages each). There are also 28 Q&As (one or two pages each), nine sidebars (one page each), an editorial (one page), a notice of a television show (one page) and an update on a conference (one page). The latter two items are now of historical interest only, but are included anyway, in the interest of completeness. The information in the former items is still as valid and relevant today as when first published. Navigating the Collection When using Acrobat Reader to view the Down’s Syndrome Collection, you can access each individual page by using the “thumbnails” tab, which will display all the pages in the document by their “collection” page number. The “thumbnails” feature, if not readily apparent, can be accessed using the menu options in your software. Please note that the collection page numbers do not appear on the actual pages themselves. The page numbers on the bottom of each page are those that appeared on the original newsletters. These are based on a volume- issue-and-page numbering system. To help keep these different systems straight, the table of contents (see next page), lists both page-numbering systems — side by side. If you choose to print these pages, you may wish to write the collection page numbers on each page in a brightly colored ink to make it easier to find your way around. Every page in this collection will have something relating to Down’s syndrome on it. However, because these are whole pages collected from newsletters, many pages will have lead-in or follow-up text that deals with some other subject covered by CERI. You may ignore this unrelated information, or consider it a bonus, whichever you prefer. If you see something interesting, the volume, issue and date information in the footer on each page will allow you to find and obtain the back issue from which it was collected. Subscriptions If you want access to ongoing information of this kind, subscribe to Smart Life News. You can subscribe online with a credit card at http://www.smartlifenews.com/subscriptions.html, or you can send a personal check or money order to CERI, P.O. Box 4029-d4, Menlo Park, California, 94026-4029 USA. You are also welcome to call us at 650-321-CERI. Be sure to mention “d4" on the address or in your phone call, as there is a $20 discount that you will get on the price of your subscription. The discounted subscription price is just $59 for US addresses, $62 for Canadian or Mexican addresses, and $74 for international addresses for ten issues of Smart Life News. Please keep in mind that not every issue will deal with Down’s syndrome. Historically, 26 of 72 issues (36%) have had Down’s syndrome content, but the ratio has risen to approximately 50% in recent issues (volumes 6, 7 and 8). Thanks again for downloading our Down’s Syndrome Collection. I hope you have an enlightening reading experience.

Steven Wm. Fowkes Executive Director Table of Contents Acrobat™ Page Newsletter Footer-Page Brief Description of Content 1 (none) Title Page and Description 2 (none) Table of Contents and Copyright Page (this page) 3 SDN Vol. 2, No. 10, p. 1-7 Feature Article: Smart Drugs and Down’s Syndrome 7 p. 5 Sidebar: Dr. Lee-Benner Visits the Warner House Clinic 10 SDN Vol. 3, No. 4, p. 1-6 Feature Article: An Interview with Dixie Lawrence 16 SDN Vol. 3, No. 7, p. 9-10 Q&A: Report on TNI, Turkel and Warner inquiry 16 p. 10 Q&A: Appreciation for Dixie Lawrence Interview 18 SDN Vol. 3, No. 8, p. 12 Sidebar: Day One Segment Scheduled for January 19 SDN Vol. 3, No. 9, p. 9 Editorial: Dealing with Your Doctor 20 SDN Vol. 4, No. 6, p. 12 Update: Down’s Syndrome Symposium 21 SDN Vol. 4, No. 9, p. 9-10 Q&A: Two questions about piracetam and excitotoxicity? 23 SDN Vol. 4, No. 10, p. 1-6 Feature Article: Antioxidant Intervention in Down’s Syndrome 24 p. 2 Sidebar: What are Free Radicals? 25 p. 3 Sidebar: The Recycling of Glutathione 29 SDN Vol. 5, No. 1, p. 1-5 Feature Article: Nutritional Intervention in Down’s Syndrome 30 p. 2 Sidebar: The SAM Cycle 34 SDN Vol. 5, No. 1, p. 11 Q&A: Will piracetam affect my daughter’s lipid metabolism? 35 SDN Vol. 5, No. 3, p. 6-7 Q&A: TNI and piracetam attack dosing? 36 p. 7 Q&A: Hard to find piracetam information? 36 p. 7-8 Q&A: What is the best age to start piracetam? 38 SDN Vol. 5, No. 3, p. 9-10 Q&A: Melatonin as Glutathione Stimulant? 40 SDN Vol. 5, No. 8, p. 8-9 Q&A: Down with Down’s? 42 SDN Vol. 5, No. 8, p. 10 Q&A: Piracetam and Seizures? 42 p. 10-11 Q&A: Down’s Syndrome Surgery and Nutritional Therapy (TNI)? 43 p. 11 Q&A: Splitting Piracetam Capsules? 44 SDN Vol. 5, No. 9, p. 1-8 Feature Article: The Case for Piracetam in Down’s Syndrome 45 p. 2 Sidebar: The Fiona Study 47 p. 4 Sidebar: Senility Prescription Practices 49 p. 6 Sidebar: Piracetam & Sickle Cell Anemia (& Angelman Syndrome) 52 SDN Vol. 5, No. 10, p. 8-9 Q&A: Down’s Syndrome and Doctors 54 SDN Vol. 6, No. 1, p. 5-6 Q&A: Down’s Syndrome and Doctors? (continued) 56 SDN Vol. 6, No. 3, p. 9-10 Q&A: Down’s Syndrome Basic Questions? 58 SLN Vol. 6, No. 7, p. 8-11 Q&A: Prozac for Down’s Syndrome? 62 SLN Vol. 6, No. 8, p. 5-6 Q&A: Prozac vs Constipation? 64 SLN Vol. 6, No. 9, p. 3 Sidebar: Oxidative Stress in Children during Heart Surgery 65 SLN Vol. 6, No. 9, p. 5-7 Q&A: Antioxidant Supplements? 68 SLN Vol. 6, No. 9, p. 9 Q&A: GABA and Muscle Tone in DS? 69 SLN Vol. 7, No. 1, p. 7-8 Q&A: Dr. Warner on Piracetam? 71 SLN Vol. 7, No. 5, p. 10-11 Q&A: In Utero DS Therapy? 73 SLN Vol. 7, No. 6, p. 8-9 Q&A: Starting TNI Therapy? 74 p. 9-11 Q&A: Pyruvate for Down’s Syndrome? 77 SLN Vol. 7, No. 7, p. 9 Q&A: Allergy to Piracetam? 78 SLN Vol. 7, No. 7, p. 10-11 Q&A: Cell Therapy? 80 SLN Vol. 7, No. 8, p. 8-9 Q&A: No Piracetam for Down’s Syndrome? 82 SLN Vol. 7, No. 9, p. 6-8 Q&A: Antioxidants vs Reductants? 85 SLN Vol. 8, No. 1, p. 10 Q&A: Vinpocetine in Down’s Syndrome? Copyright © 1992-2002 by the Cognitive Enhancement Research Institute. All rights reserved. Phone 650-321-CERI (2374) Smart Drug NewNewss THE NEWSLETTER OF THE COGNITIVE ENHANCEMENT RESEARCH INSTITUTE

Smart Drug News Smart Drug Update: Part 1 ISSN 1060-8427 Published 10 times annually by CERI (the Smart Drugs and Down’s Syndrome Cognitive Enhancement Research Institute) by Steven Wm. Fowkes and Ward Dean, M.D. P. O. Box 4029 If you listen to scientists who specialize medications and refused to issue a New Drug Menlo Park, CA 94026. 415-321-CERI in academic research into Down’s syndrome, Application for them. Nevertheless, (415-321-2374) or to the Down’s Syndrome Association, U-series medications were determined to be Copyright © 1994 there is basically nothing a parent can do to legal for distribution within the state of All rights reserved. prevent the profound mental deficits and Michigan, where over 5,000 patients were Subscription $44/year impaired growth of a Down’s child. But if treated with some success. Canadian $46/year Overseas $55/year you listen to Dixie Lawrence, a devoted Single issue $6 adoptive mother of one Down’s child, or to Jack Warner, M.D. Vol. 2, No. 10 Dr. Jack Warner, a California pediatrician Dr. Turkel’s treatment has now been February 14, 1994 with a ten-year history of treating Down’s refined by California pediatrician Jack Editor children, there is plenty that parents can do. Warner, M.D. Dr. Warner and his wife Steven Wm. Fowkes In fact, this small group of motivated Charlene run The Warner House,acenterfor Medical Editors parents and dedicated practitioners has the study of trisomy disorders, in Fuller- ton, Ward Dean, M.D. succeeded in doing what the authorities California. Dr. Warner’s approach is to Lord Lee-Benner, M.D. have decreed to be impossible — the combine a nutritional/metabolic therapy Contributing Editor normalization of Down’s children’s growth with physical therapy and developmental John Morgenthaler rates and mental abilities. Down’s optometry. He says, “Warner House is Assistant Editor children treated with this new smart- probably the only place that has such a com- T. Michael Hardy nutrient and/or smart-drug treatment prehensive approach to treating Down’s program are now being mainstreamed into syndrome. We have a developmental In This Issue public schools on a routine basis. Their optometrist, and absolutely the world’s best growth rates are equivalent to those of physical therapist. She sits on the floor and Smart Drug Update: normal children, and the IQs of those works with these children for almost an hour, Smart Drugs and children started on the program early in life and we video tape the session so the parents Down’s Syndrome are comparable to normal children. One can take the tape home with them.” by Steven Wm. Fowkes 5-year old Down’s girl even has a Dr. Warner’s program not only signifi- and Ward Dean, M.D. documented IQ of 140! cantly counteracts some of the cognitive page 1 deficits associated with Down’s syndrome, Henry Turkel, M.D. New Practitioners but it prevents and reverses some of the page 2 The pioneering work on a treatment physical and developmental abnormalities program for Down’s syndrome was begun characteristic of the condition. Most of the Dr. Lee-Benner Visits over fifty years ago by the late Henry Turkel, Down’s syndrome children being treated the Warner House Clinic M.D. Dr. Turkel’s treatments, which he with the program are developing near- called his ‘U series’ medications, consisted normal to above-average intelligence, Q&A of a combination of nutrients and drugs without the chronic illnesses typical of Answers to formulated to compensate for some of the Down’s syndrome. Many are competing Readers’ Questions metabolic errors which result from the extra successfully in public schools, and some of page 8 21st chromosome (called trisomy 21)which the children fortunate enough to be placed on causes Down’s syndrome. Turkel’s U-series the program early in life do not have the Source Update page 8 contained vitamins, minerals, fatty acids, pronounced physical features typical of digestive enzymes, lipotropic nutrients, an untreated Down’s children. Effect of DMAE on amino acid, and numerous drugs (thyroid Lifespan of Japanese Quail hormone, antihistamines, nasal deconges- Dixie Lawrence page 9 tants, and a diuretic). The FDA stopped the Dixie Lawrence is the Director of Adop- interstate distribution of Turkel’s U-series tion Options of Louisiana, an organization continued on next page Smart Drug Update: that places Down’s and other children for parents regarded the treatments as success- Smart Drugs adoption. She is also the adopted mother of ful, they complained about the difficulties in Madison, a Down’s child now 4 years old. complying with the program and some of the and Down’s After seeing a relative’s Down’s boy being side effects of the drugs employed. Syndrome successfully treated by Dr. Turkel’s method, Dixie investigated the Turkel and Warner The Warner Program continued from previous page programs and gathered a group of 30 Dr. Warner’s improved program is more Louisiana families together to bring Dr. convenient than Dr. Turkel’s U-series medi- “This small group of Warner’s team to Baton Rouge. She has cations. Dr. Warner avoids the regular use of motivated parents and since developed an independent protocol drugs, and, unlike Dr. Turkel, he does not dedicated practitioners combining elements of both programs with automatically prescribe thyroid supple- both amino acids and smart drugs. Dixie’s ments to all Down’s children. Instead, he has succeeded in doing daughter and several of the other family’s does a thyroid workup which identifies the what the authorities have children have gone on Dixie’s modified majority of Down’s children who do need decreed to be impossible program with spectacular results. A couple thyroid support, and the specific amount they of Down’s infants have even been treated in need. — the normalization of utero. In one case, the delivering obstetri- The basic dietary supplement in Dr. Down’s children’s cian refused to believe that the infant was a Warner’s program are called “Hap Caps.” growth rates and Down’s syndrome baby until presented with They do not contain any drugs or thyroid. a chromosome analysis. The prescription of thyroid or other drugs is mental abilities.” left to the determination of the attending Professional Skepticism physician with due consideration for the In the 1950s, Dr. Turkel’s U-series treat- specific medical needs of each patient. ments were met with skepticism and/or Hap Caps are formulated to counteract hostility by governmental bureaucrats and specific metabolic disturbances seen in mainstream researchers who adhered to the Down’s syndrome. Chief among them are “Down’s children then-dominant view that nutrition is at best a disturbances in the antioxidant enzymes treated with this new trivial influence in such a basic genetic catalase (abnormally low levels) and super- disorder. For every published study that oxide dismutase (abnormally high levels) smart-nutrient and/or indicates that nutrition can have a positive [Groner, et al., 1985; Shah, et al., 1989; smart-drug program are influence in Down’s syndrome, there is at Lejeune, et al., 1992]. This disturbance now being mainstreamed least one that concludes that nutrition is of no responds positively to the high dosages of benefit. Despite authoritative opinion, dietary antioxidants, like vitamins E, A and into public schools parents of Down’s children were willing to C, and the minerals zinc, copper, manganese on a routine basis.” give Turkel’s program a try. Although and selenium. Another metabolic disturbance is the diminished production of digestive enzymes New Practitioners [Abalan, et al., 1990], which is directly coun- Karel Mommeyer, M.D. 011-32-11-821767 teracted by the addition of supplemental Zavelstraat 25, B-3520 Zonhoven, Belgium enzymes to the Hap-Cap formula. Regenerative treatments through cell therapy, ozone therapy, natural therapy A third disturbance is amino acid regu- (procaine injections), and chiropractic adjustments. FAX: lation. Disturbances in the regulation of 011-32-11-821909. cysteine, lysine, methionine, phenylalanine, tyrosine, glutamate, GABA, histidine, Dharma Khalsa, M.D. 602-749-0404 tryptophan and cystathionine have been SuperHealth Ranch, 2545 North Woodland Road, Tucson, AZ 85749 reported [Hyanek, et al., 1970; Airaksinen, Pain, stress and longevity specialist. Medical Director at health ranch 1974; Petre-Quadens and De Lee, 1975; specializing in anti-aging and rejuvenation. Prescribes brain boosters when Shaposhnikov, 1979; Pueschel, et al., 1980; desired and medically indicated. Founder of the Alzheimer’s Prevention Reynolds and Warner, 1988; Lejune, et al., Foundation. FAX: 602-749-0407. 1992]. Some of these disturbances can be Patricia K. Davenport, D.O. 517-487-1808 counteracted by supplemental amino acids, 1808 South Pennsylvania Avenue, Suite One, Lansing MI 48910 like tyrosine and tryptophan. Unfortu- Internal medicine. nately for the Down’s children, the FDA has Raul Vergini, M.D. 011-39-543-922-166 (phone and FAX) banned the tryptophan that they need. For Via Varano Costa Nuova, 2; 47016 Predappio (FO); Italy the last several years, they have had to do Homeopathy, nutritional medicine, orthomolecular medicine, thyroid, without. Other amino acid disturbances can non-conventional cancer treatments, life extension. Smart drug expert. be dealt with by supplemental vitamins, like B6 and B12. 2 Smart Drug News [v2n10] February 14, 1994 Smart Drug Update: Disturbances in carbohydrate metab- Counseling and Physical Therapy Smart Drugs olism have also been reported [Turkel, 1981; Raiti, et al., 1974]. Ardith Meyer and Dr. Stephen Meyer and Down’s Neuroendocrine disturbances are also a are a husband-and-wife team that have been Syndrome feature of Down’s syndrome. The frequency providing physical therapy for Down’s of thyroid abnormalities in Down’s children children and counseling for their parents. continued from previous page is very high compared to normal children Their center, A Child’s Life, is located in [Napolitano, et al., 1990]. In addition, Diamond Bar, California. Steve Meyer is a growth abnormalities have been traced to a clinical psychologist. He counsels the deficiency of insulin-like growth factor parents about behavior problems with the (IGF) type 1 [Anneren, et al., 1986, 1990]. children and assists with physical therapy Both IGF-1 and IGF-2 are stimulated by the evaluations. Ardith Meyer does the “The delivering action of human growth hormone (hGH), but physical therapy and provides the parents obstetrician refused to in Down’s children, IGF-1 does not rise in with a physical-therapy program for use at believe that the infant was infancy. A major amount of research is now home. being directed towards the use of hGH in Steve Meyer states, “Dr. Warner’s nutri- a Down’s syndrome baby treating Down’s syndrome children, with tional program has revolutionized my atti- until presented with a some success [Torrado, et al., 1991]. hGH tude towards Down’s syndrome children. chromosome analysis.” increases IGF-1 levels and growth rates in Prior to my experiences at the clinic, I had Down’s syndrome children, but it also thought that the retardation was a direct increases IGF-2 levels. The use of hGH in factor of the genetic defect. Now I realize the treatment of Down’s syndrome is still that the retardation is a product of an error in highly controversial. metabolism. When we correct this meta- bolic problem, their mental potential moves Beyond Supplements into the normal range. We have seen many Dr. Warner’s program also emphasizes children move into the above-average range. physical therapy and developmental optom- These children have potential!” etry. It is the combination of metabolic Ardith Meyer thinks that one of the support, thyroid support, and physical and biggest problems is that many professionals optometric vision therapies that allows and parents do not see any potential in Down’s children to overcome their develop- Down’s infants and children. “If parents and mental learning disabilities and to compete therapists don’t see that the child has “The use of hGH in with normal children in sports, school and potential, they’ll never try anything,” states social interactions. Many of the children on Ardith Meyer. “People lock Down’s syn- the treatment of Down’s the Warner program have been successfully drome children into a `mentally-retarded’ syndrome is still highly integrated into public schools, and a number label and fail to realize their strengths, their controversial.” of them have gone on to participate in such weaknesses, or their interests. Down’s sports as baseball and skiing. children are like everybody else, they Many of these treated Down’s children gravitate towards what they enjoy, and if you are not easily recognized as such, even by can make the program interesting and fun, professionals. Three years ago, Dr. Warner’s they’ll do it.” The entire team agrees that group set up their first presentation booth at Down’s syndrome is more properly consid- the National Perinatal Association meeting. ered a learning disability than retardation. They had photos of four of their Down’s Ardith Meyer says, “Most of the world does children on display. “We had people coming not understand that yet.” up to us and saying, `Why didn’t you put up Without intervention, Down’s children “If parents and therapists pictures of Down’s syndrome children?’” have “moderate” to “major” developmental don’t see that the child says Ardith Meyer, physical therapist for the impairment with IQs in the 55 range. With has potential, they’ll Warner team. “They didn’t look like Down’s intervention, many move into the “normal” children,” she adds. The physical changes in range [85 to 115]. Some remain in the never try anything.” appearance reflect the underlying “mild” developmentally impaired range. improvements in the children’s metabolism The effectiveness of the program depends on and development. the age at which treatment begins. “It’s Dr. Warner has now treated more than clearly, the earlier, the better,” states Steve 700 Down’s children with his program. He Meyer. “I want to see them at eight days of regularly refers his Down’s patients for age,” states Ardith Meyer. “I can start physical therapy and developmental showing the parents what to do that will optometry. prevent the waddling gait and difficulty in Smart Drug News [v2n10] February 14, 1994 3 Smart Drug Update: running when they are in their teens.” In the on the program for phase B,” explains Steve Smart Drugs 7 years that she has been working with Meyer, “then, for some reason (through a Down’s children on the Warner program, she family crisis or economic issue), the child and Down’s has yet to see a single child that has not temporarily goes off the program. We know Syndrome benefited when started in the first few years which parents are being faithful to the of life. A few of the older children with intervention and which ones aren’t based on continued from previous page autistic tendencies and severe behavioral the number of vitamins they order. When the problems are the only ones that have not children go off the intervention, we benefited from the program. definitely see a decline in their growth, “When I first started with Dr. Warner, I alertness, attentiveness and general health.” was reluctant to talk about the program with AndwhentheygobackontheWarner the other pediatricians with whom I program, their growth and learning is worked,” Ardith Meyer says. “I thought, I’m restored. going to wait and see how this is. Now that “These serendipitous cases fulfill what is I’ve seen so many children go through the called an N-of-one research model, the “I have observed that program, I’m proud to talk about it.” A-B-A-B pattern, which is a very useful Down’s syndrome model commonly used in behavior modifi- Optometric Visual Therapy children cation research,” asserts Steve Meyer. Dr. Phil Klingsheim is a behavioral and “Fortunately for the children, most of the who have been on the developmental optometrist who treats the parents come to us with a positive Warner House clinic vision problems of Down’s children. He expectancy and, after they experience the metabolic program says, “Optometric vision therapy can be a initial improvement in the child, they comply great aid to Down’s syndrome individuals in with the program. When they aren’t faithful, respond better to assisting them to reach their full potential there’s usually some environmental optometric vision therapy academically.” Vision therapy involves circumstance that has hindered them, like a than those not on clinical tests and training procedures that divorce or unemployment. In one family, the correct neurosensory, neuromotor, and husband was very reliable with the morning the program.” neurophysiological visual dysfunctions. Dr. medication and the wife was lax with the Klingsheim is impressed with the Warner afternoon. That’s probably the hardest program. He states, “I have observed that situation to deal with because of the division Down’s syndrome children who have been within the family.” ontheWarnerHouseclinicmetabolic Ardith Meyer describes one A-B-A-B program respond better to optometric vision case of a mother who ran out of Hap Caps. therapy than those not on the program. And because she couldn’t get to the store, she They seem to be more alert and mentally started giving her Down’s son regular milk available to benefit in vision therapy instead of non-dairy products. When she situations.” finally brought him in, he was lethargic and sick. “She told me that she didn’t think the The A-B-A-B Research Design program was working. I had to say, `Wait a Although government and academic minute. You have to keep him on the researchers expect all therapies to be program. Look what has happened when proven in double-blind studies, this would you took him off of it.’ She put him back on require that half of the children receive a the program and he got healthy and alert placebo instead of the treatment formula. again.” The withholding of treatment from the placebo group would be ethically untenable A Mother’s Experience “Most parents would refuse for Dr. Warner’s team, who are now with Piracetam to take their children off completely convinced that the program is Dixie Lawrence has also experienced a the program.” beneficial. “Most parents would refuse to few A-B-A-B instances with her daughter take their children off the program,” adds Madison. One of the most graphic was Steve Meyer. when she ran out of piracetam. Right after Under such situations, researchers Madison first went on piracetam (with resort to the A-B-A-B research model, in phosphatidylcholine and vitamin B5), she which the therapy is purposefully discon- spontaneously potty-trained herself, started tinued for an interval, and then restarted. speaking in phrases, and developed an By chance, this has happened for a few active symbolic immagination. Months children on the Warner program. “The later, when Dixie ran out of piracetam for a child comes to us in condition A, and goes week, within days of ceasing piracetam, 4 Smart Drug News [v2n10] February 14, 1994 Smart Drug Update: Madison broke her potty training and lost results with amino acids and piracetam and Smart Drugs her immagination and much of her verbal is looking into incorporating both into his fluency. Fortunately, when piracetam program. He states, “One of the wonderful and Down’s administration was restored, she regained things that Dixie has come up with is the Syndrome everything. extra amino acids and proteins. There’s a After hearing about Madison’s achieve- Dr. Lejeune in Paris that has been working continued from previous page ments, several other families in Louisiana with this [Lejeune J, 1991; Lejeune, et al., put their Down’s children on piracetam, B5 1992], although I don’t think that what he is and phosphatidylcholine with very positive doing is a complete answer. I think all of results. Dr. Warner is interested in Dixie’s these approaches have to be put together,

I saw eight children, a number of whom were new and just starting Dr. Warner’s Dr. Lee-Benner metabolic program. Some of the children that had been on the program for a while had Visits the Warner recent interruptions, so this group may not have been a fair sampling. Their ages varied from 6 weeks to 11 years, most of whom were between 2 and 5 years. I could see mongoloid House Clinic features in all of the children, even the older ones who were 9 and 11. Although the features were there, the treated children were doing very well. They were We asked CERI active, outgoing and fairly talkative. They were not dull like the untreated children. The Medical Editor Lord growth pattern scores of the children on the program were in the 50th percentile (on a Lee-Benner, M.D. “normal” growth percentile evaluation chart, not a Down’s syndrome growth chart), to drop in on a compared to scores below the 5th percentile for those not on the program. These weekend Down’s “normal” growth results are definitely a significant and interesting factor of the Warner clinic at the program. Based on the serial photographs, there appears to be some improvement in facial features. Warner House. Those on the program for a short time were not quite as “Asiatic” looking. The epicanthal This is his report. folds [vertical folds of skin on each side of the nose which tend to hide the inner corner of the eye, closest to the nose] were hard to see from the photos, and Dr. Warner acknowledged that he had better photos and examples. I did observe that the treated children appeared to have less epicanthal fold than the untreated children. I talked with the family members who are very positive and supportive. I thought the mothers were especially courageous. The parents are very pleased with the program. They reported that their children were healthier and interacted more with their peers and teachers. Their mental abilities were improved and all of them were in or headed towards regular school programs. That was impressive. “The growth pattern All of the new children had nasal or sinus conditions. Those on the program longer had scores of the children fewer or less symptoms. Several hadn’t had colds for a long time. The children on the Warner program are fortunate to have access to a behavioral on the program optometrist who administers a series of tests to the children to discover subtle visual were in the disorders (relating to tracking, fixation, focus, depth perception, peripheral perception, 50th percentile.” binocularity, and coordination). The children are then trained to overcome these vision- related difficulties. A lot of school children with behavioral problems — so-called dyslexia and attention deficit disorders — would benefit from this kind of testing and training. All children should probably see a behavioral optometrist, preferably before they go to school and develop a bad self-image. They’re treating the children with thyroid supplements and keeping the T4 level up around 8.6 (high-normal), or as close to that as possible. They don’t accept “normal” thyroid function tests as an indication not to treat with thyroid. For those that I saw, all had benefited from thyroid supplementation. They use the Broda Barnes method monthly to follow the children. They also use nutritional supplementation. The zinc question is an issue. I just found a “I was impressed study which demonstrates that zinc supplementation stimulates growth and development in with the caring and undersize Japanese children. They were using 2mg/kg/day elemental zinc for six months professionalism of and they measured increased IGF-1 levels without increased hGH levels. They were following zinc clearances (which tested abnormal) rather than zinc levels (which tested the Warner team.” normal). Abnormal zinc clearance may be an indication of a preclinical zinc deficiency. I was impressed with the caring and professionalism of the Warner team. They are definitely doing God’s work. LLB

Smart Drug News [v2n10] February 14, 1994 5 Smart Drug Update: maybe including the use of Nootropil of this attitude among professionals, parents Smart Drugs [piracetam]. I know that Dr. Schmid has left the mainstream to find someone who been using piracetam in Germany for years, would try to help them. “When some parents and Down’s but I didn’t know that it was available [by come to me and talk about some other Syndrome prescription] in the United States until treatment regime, I usually know what they recently.” are going to say because the other programs continued from previous page haven’t changed since the 50s.” A Family Affair “But these children do have potential, At A Child’s Life, the children are and I am thrilled to work with them. I show invited to come to the clinic with their entire them what to do. It’s not me, it’s them. I’m “All of these approaches family. The physical therapy session is just somebody who’s paying attention to have to be put together, videotaped so the parents can refer to it at them. I have learned a great deal about what including the use home if they have trouble remembering new their needs are over the years, and I’ve also exercises. Ardith Meyer says, “It’s my job to learned why they need to have a physical of Nootropil.” help the parents understand what specific therapist working with them. With the needs the children have and give them very Down’s child, their needs change. Early on, specific things to do.” A lot of the parents between birth and three years, their postural are eager to learn what they can do to help muscles, muscle tone and motor skills need a their child develop, and the video tape makes lot of attention. Later, a lot of Down’s it easy. children are hindered by their lack of verbal The contribution that family relation- skills.” “You can even see it in the toddlers ships make to the growth and development of before they walk,” says Ardith Meyer. Down’s children is crucial. One Canadian “They understand everything you are saying family with a young Down’s boy and three but they cannot verbally respond to you.” older siblings came to a Seattle clinic held by Because of these communication Dr. Warner’s team. Ardith Meyer uses what difficulties, Down’s children tend to get she calls “motor-planning cards,” which pegged lower in school. According to “The parents desperately have instructions to get into a specific body Ardith Meyer, one of the hardest thing for want support from position. She relates, “I got down on the Down’s children to learn are perceptual- medical professionals.” floor and into the positions with the boy, and motor activities, like handwriting, spelling the whole family joined us on the floor and and reading words. did the motions with us. It was so spontaneous, like this is just what we do for School and Play recreation. The family support was At A Child’s Life, Ardith and Steve awesome, and the boy was picking it up so Meyer try to incorporate strengthening and quickly.” coordination exercises into play. “You can’t “In another family, the mother brought ask a 9-month-old infant to crawl across the her Down’s syndrome daughter in to us at 8 room towards nothing, they won’t be days and every two months since then. The motivated,” argues Ardith Meyer. “You girl is fortunate to have four older brothers can’t ask a ten-year-old to do push-ups. If who love her dearly and who excel at moti- you want children to do something, you have vating her to do the exercises. She couldn’t to incorporate it into a play activity.” For have a better situation.” She adds, “The example, she has the children load stuff into mother just called me to determine whether a wagon and pull it up a hill. it was worth the trouble to drive in to the center through the earthquake-damaged The Teachers Report freeway system here in Los Angeles, and one Ardith reports that the treated Down’s of the brothers told the mother to come in children are just as willing to go out and play because the daughter `had changed and at recess as normal children. “The teachers needed a new program.’” will write to us and say that the treated According to Ardith Meyer, the parents Down’s children are more motivated,” states desperately want support from medical pro- Ardith Meyer. Many teachers have asked fessionals. “If their doctor doesn’t believe the parents, “What are you doing that their child can change, they will go find differently?” The teachers report that the someone who will, even if the advice they treated children are really paying attention get is not appropriate.” For decades, in class, they are very interested in climbing Down’s children were seen as mentally on the gym at recess, and they are inter- retarded, not as learning disabled. Because acting with their peers. “One mom said that 6 Smart Drug News [v2n10] February 14, 1994 Lejeune J., et al. Aminoacids and 21-trisomy [Acides amines et trisomie Smart Drug Update: the teacher could tell when she ran out of the 21. Ann Genet (France) 35(1): 8-13, 1992. Hap Caps,” says Ardith Meyer. “The child Lockitch G et al. Infection and immunity in Down syndrome: a trial of Smart Drugs long-term low oral doses of zinc. JPediatr114(5): 781-7, May 1989. went right back to being lethargic and Comment in: J Pediatr 116(3): 487-8, Mar 1990. and Down’s uninterested.” She adds, “If the teachers go Menolascino FJ, et al. Vitamin supplements and purported learning enhancement in mentally retarded children. J Nutr Sci Vitaminol (Tokyo) Syndrome to the trouble to report these observations, 35(3): 181-92, Jun 1989. you know the Hap Caps are making a major Napolitano G, et al. Growth delay in Down syndrome and zinc sulphate supplementation. Am J Med Genet 7(Suppl): 63-5, 1990. continued from previous page difference.” Napolitano G, et al. Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome. Ann Genet (France) 33(1): 9-15, Part two of this article will detail the specific 1990. substances and dosages being use to treat Down’s Nehring WM. Down Syndrome article contained ‘erroneous’ information [letter]. Pediatr Nurs (United States) 19(1): 85-6, 100-2, Jan-Feb 1993. children. See also: Pediatr Nurs (United States) 19(3): 257, May-Jun 1993. References Neve J, et al. Selenium and glutathione peroxidase in plasma and erythrocytes of Down’s syndrome (trisomy 21) patients. J Ment Defic Res Abalan F, et al. A study of digestive absorption in four cases of Down’s (England) 28(4): 261-68, 1984. syndrome. Med Hypotheses (UK) 31(1): 35-38, 1990. Palmer S. Influence of vitamin A nutriture on the immune response: Airaksinen EM. Tryptophan treatment of infants with Down’s syndrome. findings in children with Down’s syndrome. Int J Vitam Nutr Res 48(2): Ann Clin Res 6(1): 33-9, Feb 1974. 188-216, 1978. Anneren G, Sara VR, Hall K and Tuvemo T. Growth and somatomedin Petre-Quadens O and De Lee C. 5-Hydroxytryptophan and sleep in responses to growth hormone in Down’s syndrome. Arch Dis Child 61(1): Down’s syndrome. J Neurol Sci 26(3): 443-53, Nov 1975. 48-52, Jan 1986. Pruess JB, Fewell RR and Bennett FC. Vitamin therapy and children with Anneren G, Gustavson KH, Sara VR and Tuvemo T. Growth retardation Down syndrome: a review of research. Except Child 55(4): 336-41, Jan in Down syndrome in relation to insulin-like growth factors and growth 1989. hormone. Am J Med Genet 7(Suppl): 59-62, 1990. (30 Refs.) Pueschel SM, Reed RB, Cronk CE and Goldstein BI. Anneren G, Gustafsson J, Sara VR and Tuvemo T. Normalized growth 5-hydroxytryptophan and pyridoxine. Their effects in young children “Many teachers have velocity in children with Down’s syndrome during growth hormone with Down’s syndrome. Am J Dis Child 134(9): 838-44, Sep 1980. therapy. JIntellectDisabilRes(England) 37(pt.4): 381-7, Aug 1993. Pueschel SM, et al. Vitamin A gastrointestinal absorption in persons with asked the parents, Antila E, Nordberg UR, Syvaoja EL and Westermarck T. Selenium Down’s syndrome. J Ment Defic Res (UK) 34(3): 269-75, 1990. therapy in Down syndrome (DS): a theory and a clinical trial. Adv Exp Med Biol 264: 183-6, 1990. Pueschel SM. Growth hormone response after administration of L-dopa, `What are you doing clonidine, and growth hormone releasing hormone in children with Down Aspillaga MJ, et al. Dimethyl sulfoxide therapy in severe retardation in syndrome. Res Dev Disabil (United States) 14(4): 291-8, Jul-Aug 1993. monogoloid children. AnnNYAcadSci243: 421-31, 27 Jan 1975. differently?’” Raiti S, Lifschitz F, Trias E and Sigman B. Down’s syndrome. Study of Bennett FC, et al. Vitamin and mineral supplementation in Down’s carbohydrate metabolism. Acta Endocrinol (Copenh) 76(3): 506-12, Jul syndrome. Pediatrics 72(5), 707-13, Nov 1983. 1974. Bidder RT, et al. The effects of multivitamins and minerals on children Reading CM. Down’s syndrome: nutritional intervention. Nutr Health with Down syndrome. Dev Med Child Neurol 31(4): 532-7, Aug 1989. 3(1-2): 91-111, 1984. Cantor DS, et al. A report on phosphatidylcholine therapy in a Down Reynolds GP and Warner CE. Amino acid neurotransmitter deficits in syndrome child. Psychol Rep 58(1): 207-17, Feb 1986. adult Down’s syndrome brain tissue. Neurosci Lett 94(1-2): 224-7, 22 Cartlidge PHT and Curnock DA. Specific malabsorption of vitamin B12 Nov 1988. in Down’s syndrome. Arch Dis Child (England) 61(5): 514-15, 1986. Shah SN, Johnson RC and Singh VN. Antioxidant vitamin (A and E) Castells S, Torrado C, Bastian W and Wisniewski KE. Growth hormone status of Down’s syndrome subjects. Nutr Res (USA) 9(7): 709-15, 1989. deficiency in Down’s syndrome children. JIntellect DisabilRes36(pt.1): Shaposhnikov AM, Khal’chitskii SE and Shvarts EI. Narushenie obmena 29-43, Feb 1992. fenilalanina i tirozina pri bolezni Dauna [Disorders of phenylalanine and Chiricolo M, et al. Enhanced DNA repair in lymphocytes of Down tyrosine metabolism in Down’s syndrome]. Vopr Med Khim 25(1): 15-9, syndrome patients: The influence of zinc nutritional supplementation. Jan-Feb 1979. Mutat Res Dnaging Genet Instab Aging (Netherlands) 295(3): 105-11, Smith GF, et al. Failure of vitamin mineral supplementation in Down’s 1993. syndrome [letter]. Lancet 2(8340): 41, 2 Jul 1983. Coburn SP, Mahuren JD and Schaltenbrand WE. Increased activity of Smith GF, et al. Use of megadoses of vitamins with minerals in Down pyridoxal kinase in tongue in Down’s syndrome. J Ment Defic Res (UK) syndrome. J Pediatr 105(2): 228-34, Aug 1984. 35(6): 543-47, 1991. Storm W. Hypercarotenaemia in children with Down’s syndrome. J Ment Coleman M. Infantile spasms associated with 5-hydroxytryptophan Defic Res (UK) 34(3): 283-86, 1990. administration in patients with Down’s syndrome. Neurology 21(9): Torrado C, Bastian W, Wisniewski KE and Castells S. Treatment of 911-9, Sep 1971. children with Down syndrome and growth retardation with recombinant Coleman M, et al. A double blind study of vitamin B6 in Down’s human growth hormone. JPediatr119(3): 478-83, Sept 1991. See also syndrome infants. Part 1—Clinical and biochemical results. J Ment Defic comments: Allen DB. J Pediatr 120(2 Pt 1): 332-3, Feb 1992; Binder ND. Res 29(Pt 3): 233-40, Sep 1985. J Pediatr 120(5): 832-3, May 1992; Underwood LE. J Pediatr 120(5): 833 (discussion 833-4), May 1992. Colombo ML, et al. Ascorbic acid in children with Down’s syndrome. Minerva Pediatr (Italy) 41(4): 189-92, 1989. Turkel H, Nusbaum I and Baker S. Intellectual improvement of a retarded patient treated with the ‘U’ series. J Orthomol Psychiatry (Canada) 13(4): Editorial: Tryptophan and serotonin in Down syndrome. Lancet 2(7896): 272-76, 1984. 1554, 28 Dec 1974. Turkel H and Nusbaum I. A case of Down syndrome with Tourette Frager J, Barnet A, Weiss I and Coleman M. A double blind study of syndrome. J Orthomol Med (Canada) 4(1): 27-32, 1989. vitamin B6 in Down’s syndrome infants. Part 2. Cortical auditory evoked potentials. J Ment Defic Res (England) 29(3): 241-46, 1985. Turkel H. Medical amelioration of Down’s syndrome incorporating the orthomolecular approach. J Orthomolecular Psychiat (Canada) 4(2): Groner Y, et al. Molecular structure and expression of the gene locus on 102-15, 1975. “The teachers report chromosome 21 encoding the Cu/Zn superoxide dismutase and its relevance to Down syndrome. Ann N Y Acad Sci 450: 133-56, 1985. Turkel H. Treatment of a mucopolysaccharide type of storage disease with that the treated the ‘U’ series. J Orthomolecular Psychiatry (Canada) 10(4): 239-48, Harrell RF, et al. Can nutritional supplements help mentally retarded 1981. children? An exploratory study. Proc Natl Acad Sci (USA) 78(1): p574-8, children are really Jan 1981. Vampirelli P. Clinical experimentation of pyracetam in an infantile neuropsychiatry service [Il piracetam in neuropsichiatria infantile. Hestnes A, Borud O, Lunde H and Gjessing L. Cystathioninuria in Sperimentazione clinica in un servizio di neuropsichiatria infantile.] paying attention Down’s syndrome. J Ment Defic Res 33(Pt 3): 261-5, Jun 1989. Minerva Pediatr (Italy) 30(4): 373-76, 1978. Hestnes A, et al. Hormonal and biochemical disturbances in Down’s Vitamin/mineral supplementation for Down syndrome [letter]. Lancet in class.” syndrome. J Ment Defic Res (UK) 35(3): 179-93, 1991. 2(8361): 1255, 26 Nov 1983. Hyanek J, et al. Cystin-lysinurie u Downova syndromu [Cystinuria and Weathers C. Effects of nutritional supplementation on IQ and certain other lysinuria in Down’s syndrome]. Cas Lek Cesk 109(46): 1088-92, Nov variables associated with Down syndrome. Am J Ment Defic 88(2): 214-7, 1970. Sep 1983. Justice PM, et al. Micronutrients status of children with Down syndrome: Weise P, Koch R, Shaw KN and Rosenfeld MJ. The use of 5-HTP in the A comparative study of the effect of megadoses of vitamins with minerals treatment of Down’s syndrome. Pediatrics 54(2): 165-8, Aug 1974. or placebo. Nutr Res (USA) 8(11): 1251-58, 1988. Westermarck T, et al. Selenium supplementation and trace element Kleijnen J and Knipschild P. Niacin and vitamin B6 in mental alterations in Down’s syndrome. J Trace Elem Electrolytes Health Dis functioning: A review of controlled trials in humans. Biol Psychiatry (Germany) 7(2): 125-26, 1993. (USA) 29(9): 931-41, 1991. White D. IQ changes in mongoloid children during post-maturation LaPerchia P. Behavioral disorders, learning disabilities and megavitamin treatment. Am J Ment Defic 73(5): 809-13, Mar 1969. therapy. Adolescence Fall 22(87): 729-38, 1987. Williams CA, Quinn H, Wright EC, et al. Xylose absorption in Down’s Lejeune J. Pathogenie de la debilite de l’intelligence dans la trisomie 21 syndrome. J Ment Defic Res (England) 29(2): 173-77, 1985. [Pathogenesis of mental impairment in trisomy 21]. Ann Genet 34(2): More references will be provided in Part 2. 55-64, 1991. (89 Refs.) Smart Drug News [v2n10] February 14, 1994 7 Smart Drug NewNewss THE NEWSLETTER OF THE COGNITIVE ENHANCEMENT RESEARCH INSTITUTE

Smart Drug News Smart Drugs and Down’s Syndrome: ISSN 1060-8427 Published 10 times annually by CERI (the An Interview with Dixie Lawrence Cognitive Enhancement by Steven Wm. Fowkes Research Institute) P. O. Box 4029 Dixie Lawrence is the Director of Adoption CERI: Can you give our readers a brief and Menlo Park, CA 94026. 415-321-CERI Options, a Louisiana-based adoption agency, simple explanation of Down’s syndrome? (415-321-2374) and a founder of Trisomy 21, Inc., a not-for- Copyright © 1994 profit educational foundation researching Dixie: Down’s syndrome results from All rights reserved. treatments for Down’s syndrome. Dixie is complete or partial duplication of chromo- Subscription $44/year also the mother of three children, ages 26, 22 some 21, one of the smallest of the human Canadian $46/year Overseas $55/year and 4. Her 4-year-old adopted daughter chromosomes. Chromosome 21 contains, Single issue $6 Madison has Down’s syndrome. For the last among other things, the genetic blueprint for Vol. 3, No. 4 2 years, Madison has been on an extremely various proteins, enzymes, and other July 18, 1994 successful treatment program which metabolic substances. Normally, a human Editor incorporates vitamins, minerals, amino acids being has 46 chromosomes, but people with Steven Wm. Fowkes and piracetam. Dixie’s personal experience Down’s syndrome have 47. The duplicated Assistant Editor with body building allowed her to recognize 21st chromosome, called trisomy 21,causes T. Michael Hardy amino acid deficiencies in her daughter and a gene “overdose” that leads to an excess of Medical Editor motivated her to include amino acid therapy some gene products and numerous metabolic Ward Dean, M.D. in the treatment. Dixie’s latest treatment imbalances. innovation has been the incorporation of I could see some of the physical imbal- piracetam into her daughters program. ances in my own child. Down’s syndrome In This Issue Madison’s results are described in the children, for instance, have dry skin, slow- following interview. growing sparse hair, low muscle tone, slow Smart Drugs and continued on next page Down’s Syndrome: An Interview with Dixie Lawrence Book Review: by Steven Wm. Fowkes page 1 Questions and Answers About Prozac Book Review: by T. Michael Hardy Questions and Answers Prozac: Questions and Answers for Patients, his readers with a wealth of information About Prozac Family and Physicians,byRonaldR.Fieve, about not only Prozac but other medica- by T. Michael Hardy M.D., (ISBN 0-380-77718-5 paperback, 212 tions and conditions relating to mental page 1 pages, $4.99, Avon Books, New York, 1994). health. Readers’ Questions Answered Perhaps a better title for this little book Dr. Fieve offers his own insight into the Q&A would have been Everything You Want to reports of “personality transformations” page 7 Know About Prozac. Dr. Fieve (pronounced popularly associated with Prozac in the Fee-vee) delivers the information in a re- press. He discusses the concept, and points New Practitioners page 7 freshingly straightforward manner. Anyone out that the “substantial minority” who are who is taking Prozac, or is giving it consider- said to have undergone radical personality Acetylcholine Metabolism ation, should immediately go out and get this changes are, in his estimation, really no more and Neural Transmission handy little paperback. than 10% of patients at most. He explains page 8 Dr. Ronald Fieve is a distinguished that this seeming contradiction to the Choline Derivatives psychiatrist who, among other things, observations of Peter Kramer, author of page 9 pioneered the use of lithium for manic ListeningtoProzac, is really a matter of depression. He is also the author of the definition. As Dr. Fieve writes, “a person New Source bestselling Moodswing. Dr. Fieve’s exten- who is less depressed becomes, by defini- page 12 sive clinical experience with Prozac provides continued on page 12 Smart Drugs and growth and very loose ligaments. All of these but it won’t be what the recipe intended. With Down's Syndrome: symptoms are complications of amino acid, Down’s syndrome, there are too many ingredients mineral and vitamin deficiencies. in the human “recipe.” Unlike trisomy 18 and An Interview with I want to emphasize the importance of amino trisomy 13 which alter the recipe so much that the acids. A French scientist, Dr. LeJeune, showed fetus dies or the child lives only a short time, the Dixie Lawrence almost identical amino acid deficiencies in 79 trisomy 21 recipe is correctable. We can add the Down’s syndrome individuals. Serine levels are “short” ingredients to balance out the “extra” continued from previous page particularly deficient. Some people might not ingredients. In other words, we use nutrition to think that low serine levels are a serious problem, compensate for the genetic overdose. but Dr. Evan Jones of North Carolina University, I do not believe in vitamin-only therapy “A French scientist, Dr. an expert in the field of amino acids, has advised because it only corrects part of the problem. I do LeJeune, showed almost us that serine deficiency could indeed contribute believe that it helps, but it’s like putting a significantly to many of the problems associated band-aid over a surgical incision. identical amino acid with Down’s syndrome, including mental retar- deficiencies in 79 Down’s dation. CERI: Even Dr. Warner uses tyrosine and tryp- One of the most significant of the metabolic tophan — or at least he used to use tryptophan syndrome individuals.” imbalances is probably the overproduction of before the FDA pulled the plug on it. superoxide dismutase (SOD), an antioxidant enzyme which is encoded on the lower arm of Dixie: Research studies do suggest that Down’s chromosome 21. The increased levels of SOD children are tryptophan deficient, and therefore are associated with decreased catalase levels, serotonin deficient. increased lipid peroxidation, decreased immune response, and possibly increased risks of leukemia. CERI: I wonder if they’re melatonin deficient?

“One of the most signifi- CERI: There are many different genetic forms Dixie: Probably. The levels of serine seem to of Down’s syndrome. Don’t some just have be the lowest. When you are working with an cant of the metabolic pieces of chromosome 21 duplicated. amino acid profile, it is the lowest one determines imbalances is probably what you have to work with. the overproduction of Dixie: Right. There’s translocation which occurs when part or all of chromosome 21 is stuck CERI: Right. The most deficient amino acid superoxide dismutase to the end of another chromosome — usually limits the rate of protein synthesis, and that chromosome 14. This form of Down’s syndrome ultimately limits growth. (SOD), an antioxidant is inherited. The most common form is non- enzyme which is encoded disjunction, where the genetic material doesn’t Dixie: When we supplement the deficient amino separate properly during cell division. acids, we can alter their growth rates. We can’t on the lower arm of just supplement serine, or tyrosine, or tryptophan, chromosome 21.” CERI: The duplicated chromosomes are we’ve got to supplement all of the amino acids supposed to separate, so that one copy goes to that they need, including the ones that may show each side of the newly divided cell. Without up in abundance. Now that might not make much separation... sense, but you can think of the serum as a sludge pool for amino acids. What counts are the amino Dixie: ...both copies of chromosome 21 go to acids which get inside the cells. one side. Then you have 45 chromosomes in one cell and 47 in the other. The 45-chromosome cell CERI: And vitamins and minerals are the “Even Dr. Warner uses tends to die, and the 47-chromosome cell con- essential cofactors for protein synthesis. tinues to reproduce. Non-disjunction probably tyrosine and tryptophan represents about 85-95% of all cases of Down’s Dixie:B6 especially. — or at least he used to syndrome. We’re beginning more and more to recognize When non-disjunction happens after the first the importance of coenzyme Q10 in not just use tryptophan before cell division, you have mosaicism. Mosaics have immune function, but basic brain function too. the FDA pulled the two cell lines, one with the normal 46 chromo- somes and one with 47. Depending on the CERI: You started investigating Down’s plug on it.” percentage of normal cells, mosaics may be syndrome in 1990 after you adopted Madison? significantly less affected than non-mosaics. Dixie: Yes, when she was a small baby. CERI: How old was Madison when you adopted her? CERI: Was doctor Turkel still alive then?

Dixie: She was 12 weeks old. She had skin Dixie: Turkel had left Michigan and was living rashes, constipation and a history of frequent in Israel then. I didn’t find him until 1991. I first respiratory and ear infections. It seemed heard about Turkel because of a Louisiana apparent that she had certain deficiencies which woman whose 9-year-old son Zack kept popping were affecting her immune response. up on the honor roll. I heard that Zack had I liken Down’s syndrome to a cake recipe. If Down’s syndrome because he was my ex- you mix cake batter with too much of some husband’s nephew. But after the divorce, I lost ingredients, it’ll bake into something like a cake, track of the family. Years later, I was more than 2 Smart Drug News [v3n4] 18 July 1994 Smart Drugs and surprised to see his name on the honor roll. He the name of a Canadian biochemist, Kent Down's Syndrome: wasn’t on any Special Ed honor roll, it was the McCleod, and he gave me the name of Dr. honor roll. Zack’s mother had started the local Warner. I called Warner and asked if he was An Interview with Down’s syndrome group here, so I called her and doing the Turkel formula. He said he was doing congratulated her on how lucky she was. I had some- thing similar, and it is similar. Dixie Lawrence assumed that Zack was a true Down’s mosaic in Turkel’s program contained drugs that were which some percentage of body cells are normal, frightening to me. Turkel used a powerful continued from previous page because of his exceptional mental function. I was diuretic, and a Ritalin-like stimulant... wrong. He was on Dr. Turkel’s program. Because of that, Zack is very intelligent. For CERI: Phenylpropanolamine. example, can you spell “elevator” backwards? Dixie: Right, which to me was more of an CERI: No, I can’t. Not quickly. inhibitor and I didn’t want that. I think he was “Years later, I was more working with older children who had a lot of than surprised to see his Dixie: He can, just as quickly backwards as acting-out and attention-deficit problems that he forwards. Immediately. Any word that he was addressing. It’s not so in a baby. name on the honor roll.” knows. Now we’re talking about a child with Down’s syndrome, a child who’s never missed the CERI: But if you treat the baby with the honor roll. physical therapy and optometric therapy like Warner’s team does... CERI: When did he start the Turkel program? Dixie: Yes. His is a whole-body approach. I Dixie: At nine months of age. like it. I like Warner very much because he’s open minded to alternative approaches. He CERI: So he’s been on Turkel’s program for understood that I had looked at what he was doing “I found Dr. Turkel in over ten years? and thought I needed to do more for Madison. Jerusalem in the middle His program is far superior to anything else Dixie: Actually, he was on Turkel’s program for offered to Down’s children by the medical of a bombing raid. I three years, until Turkel quit doing his program. profession, but I couldn’t ignore the amino acid could Fortunately, his grandmother owned a health food problems that I saw in Madison. store. His family duplicated the Turkel program hear the explosions in the as much as they could and he’s been on it ever CERI: In a lot of ways his program is very background as I was since. Because of his family’s dedication, Zack conservative. will never need to be dependent on anyone. He is one of the top students in his school. He is Dixie:It’svery conservative, but you have to essentially a normal kid. He has very few Down’s understand that he’s working within the system. syndrome features. You can tell if you look He actually met with the FDA before he started closely at him and you know what to look for. his program. He’s cute, very attractive, and smart as a whip. CERI: That must have put some serious limits CERI: Does he have any of the classic problems on what he could put in his formula. Dr. Lord like with verbal communication, or did he have Lee-Benner was impressed with Dr. Warner’s any problems as he was developing? results, but he was particularly concerned about “Can you spell the low amount of zinc in Hap Caps. `elevator’ backwards?” Dixie: He has extremely good speech, but he stutters if he gets flustered or tries to talk too fast. Dixie: Yes, very low zinc. When I put Madison The speech centers have not been affected by on the Warner program, I added an additional 15 Turkel’s program as well as they could have been. mg zinc and 25 mg B6 per day. That’s where piracetam comes in. Dr. Puchel’s work on the neurological aspects of Down’s syn- CERI: Dr. Lee-Benner brought to my attention drome has shown that areas of the brain do not a study that was done in Japan where they studied connect properly, and that the transmission of zinc’s effect on not Down’s kids but low-growth information between the two hemispheres of the kids. On zinc, their growth normalized and their brain is garbled. The combination of piracetam insulin-like growth factor type-1 (IGF-1) normal- and choline seems to address that. Just having a ized. It’s the IGF-1 that is deficient in Down’s speech defect does not make one mentally retarded. syndrome. They produce normal amounts of “It’s very conservative, IGF-2 in infancy, but never seems to make the but CERI: No. It may make people think that transition to IGF-1 in childhood. In this study, you’re mentally retarded. zinc acted specifically on IGF1, without altering you have to understand IGF-2 or growth hormone itself. that he’s working within Dixie: Absolutely. And having Down’s syn- drome facial features does not make you mentally Dixie: Madison’s diet is not necessarily restric- the system. He actually retarded. It certainly doesn’t help you. ted to anything in particular. I feed her a lot of met with the FDA before I found Turkel in Jerusalem in the middle of a raw food, raw carrots and raw vegetables, bombing raid. I could hear the explosions in the because of the digestive enzymes they contain. I background as I was talking to him. He gave me avoid giving her raw legumes and nuts because Smart Drug News [v3n4] 18 July 1994 3 Smart Drugs and they have enzyme inhibitors. Down’s kids defi- CERI: This was about two months before you Down's Syndrome: nitely seem to be deficient in digestive enzymes. started the program? An Interview with CERI: Do you also supplement her with diges- Dixie: Yes. The first thing I did was to pump tive enzymes? her full of brewer’s yeast. I started using Dixie Lawrence brewer’s yeast in her cereal for the B-vitamins, ixie: I do, but digestive supplements are so antioxidants, and amino acids she needed. And I continued from previous page D bitter that it’s hard to get them down her. started feeding her yogurt every single day.

CERI: So she’s not old enough to take capsules CERI: Yogurt? Doesn’t that cause a mucous “I feed her a lot of raw and pills. problem? food, raw carrots and Dixie: No. I wouldn’t even try. I shake her Dixie: No, not if you wait until the expiration raw vegetables, because supplements up in her juice. One thing that we date on the container. The yogurt seems to coat of the digestive enzymes have discovered is that apple pectin is a really the intestines and help with digestion. I also good flavor-masking agent. added an extra capsule of milk-free acidophilus they contain.” culture, avoided any kind of rice cereals, and CERI: What supplements do you favor for absolutely avoided uncultured cow’s milk. Madison? We’ve kept her healthy. Of course she was also getting vitamin C three times a day and a Dixie: There are two I would use for Madison. multi-vitamin. One is an over-the-counter product made by Both eye doctors said that her eyes were struc- TwinLab called MaxiLife plus CoQ10,whichwe turally normal, so I figured that the problem must have used with piracetam, choline extra C, B5, be neurological. and a liquid amino-acid formula. The second is a complete product that I helped formulate called CERI: So were you doing any physical training MSB Plus, available through a Canadian exercises with her? “How many other families pharmacy. in your area have put their Dixie: At that point, yes. But when we started CERI: What’s her daily regimen? the treatment program at two years, I pulled her Down’s kids on a nutritional out of absolutely everything and started treating program like Madison’s?” Dixie: She gets a teaspoon of the MSB Plus her like a normal child. At 22 months of age, formula and 800 mg piracetam in the morning in even going to physical therapy once a week, she her juice. When we were using the MaxiLife/ was still nowhere near walking. She could barely liquid amino method, she got one MaxiLife in the crawl. At 26 months, she went on Dr. Warner’s morning, a tsp of liquid amino acids, extra program. vitaminCandB5 plus phosphatidylcholine and I got a group of about 30 families together to piracetam. I mixed it in apple juice, with apple bring Dr. Warner from California to Louisiana. I pectin as a flavor-masking agent. told the parents, “I don’t know all of what this man has to offer, but if we all pitch in, we can fly CERI: Do you have a growth chart of her so far? him and his team here.” So we did. When I got home and read his labels, I thought, Dixie: Yes. She’s only in the tenth percentile, “He’s using taurine and tyrosine, but he’s not “Three weeks into this but she’s supposed to be small — both of her birth using other amino acids to maintain a balance.” parents were tiny. She’s not a big kid, but she’s a So I did. I balanced the amino acids, and added modified Warner program, whole lot bigger than she would have been. more vitamin C, more zinc and more vitamin B6. Madison stood up and CERI: How many other families in your area CERI: So you were using his basic Hap Cap walked — very well have put their Down’s kids on a nutritional formula, and adding these other things? I might add.” program like Madison’s? Dixie: Yes. But I had to add to it too much, and Dixie: About 50. Zack was the first, and it rapidly became a pain in the rear. Three weeks Madison was second. It took me two years to do into this modified Warner program, Madison the research, not only because it was hard to stood up and walked — very well I might add. locate Turkel, but because I was concerned about Her muscles started changing immediately some aspects of his program — the reliance on after starting the program. Within two weeks, I diuretics and nasal sprays, and the one-formula- could see a calf muscle that she never had before. fits-all approach. Within three to four weeks, the calf muscle was Just before her second birthday, Madison was obvious. Her “feel” changed. Holding her was diagnosed with nystagmus [constantly twitching no longer like holding a rag doll. eye movements] and moderate to severe near- At 24 months, she couldn’t climb one step; six sightedness by two of the best pediatric ophthal- weeks after she went on the modified Warner mologists at Children’s Hospital. Both special- program, she could climb a flight of stairs, up and ists said she needed surgery to correct her vision, down. My mother-in-law asked, “What’s hap- but I said no. I wanted to try the program first. pened with Madison? It’s like a light bulb went off in her head.” My pediatrician brother-in-law 4 Smart Drug News [v3n4] 18 July 1994 Smart Drugs and doesn’t think I’m crazy anymore. Last Christmas physical signs of Down’s syndrome. For Down's Syndrome: he gave her a 24-piece puzzle designed for six instance, one of our children was recently year olds. Although she wasn’t even four yet, highlighted on a news broadcast that aired in An Interview with Madison opened the package, took out the puzzle, California. She was chosen, quite frankly, popped the pieces out and put it back together in because she is nothing like a child with Down’s Dixie Lawrence about five seconds, right in front of him. His syndrome. I know she has Down’s because we mouth dropped. Madison is still speech-delayed, placed her for adoption. But because she started continued from previous page but that is the only significant delay still on the metabolic therapy and piracetam in early remaining. infancy, almost no evidence of the Down’s “My pediatrician phenotype remains. You would have to see her CERI: Well, that’s common in Down’s genetic analysis to know she had Down’s brother-in-law doesn’t syndrome children. syndrome. think I’m crazy anymore. Despite all the scientific evidence to support Dixie: She had almost no speech — except what we are doing, the proof is in the pudding. In Last Christmas he gave maybe two or three words — until we started her most ways, Madison functions as a normal four her a 24-piece puzzle on the piracetam. year old. She can operate the television and VCR remote control, she uses the track ball to play designed for six year olds. CERI: OK, to continue with the program... simple computer games, she speaks in complete Although she wasn’t even sentences, and she potty trained herself at 33 Dixie: The modified Warner program was fine, months of age. Basically, she’s a normal kid. Her four yet, Madison opened but I kept having to crush the supplements to add head circumference, by Down’s standards, is the package, took out the it to her food and drinks. Then I found the Maxi- quite impressive. A recent study stated that Life formula mentioned in a book on Alzheimer’s average head circumference for 17 year old puzzle, popped the pieces disease. After calling TwinLab in New York, I Down’s syndrome females is 49 to 50 cm. out and put it back together had my friend at the local health food store stock Madison’s head circumference is 48.75 cm at 4 it for me. I changed to MaxiLife because of the years of age. Most Down’s children are in about five seconds, Coenzyme Q10. There seems to be a CoQ10 noticeably microcephalic. Madison, clearly, is right in front of him.” deficiency involved, and CoQ10 deficiency has not. Neither are any of the other kids who start been linked to lowered immune response. the metabolic therapy early in life.

CERI: That’s probably why they have cardio- CERI: What else have you noticed about the myopathy more often than often than the average children on the piracetam/nutrition program? infant. Dixie: Hair growth. Madison’s hair grew 10 “I now deeply regret Dixie: I think so. Madison was lucky to have inches in one year. Ten inches! Madison’s hair is been born without a heart defect. now so long she sits on it. This is in comparison not starting Madison The greatest change in her facial features to Down’s syndrome children who don’t even on a metabolic formula happened during the first three months on the have any hair, or slow-growing straight hair, program. Madison went from a flat face, typical never curly. Madison’s hangs straight to about in early infancy.” of Down’s syndrome, to almost normal. It was her waist and then the ends form little ringlets — such a dramatic change that some people who had like Shirley Temple curls. not seen her in a while did not recognize her. Untreated Down’s syndrome children have an Some looked at her and said, “What did you do?” under-development of the nasal bridge and the There was always a cognitive level in Madison sinuses, and an under-development of the from eight months forward that was recognizable, mandible and maxilla [lower and upper jaw] but it was like she was locked inside and couldn’t which really interferes with dentition. They have “One of our children was get out. As her mother, I could see it, but a a flattened upper lip because of under- recently highlighted on a stranger probably wouldn’t. She was eight development of the underlying bone. Before months old before I realized that she really had treatment, Madison had all these features. After news broadcast that aired potential. When I would change her diaper, she treatment, her nasal bridge developed, her jaw in California. She was would puff her belly up for me to rub her tummy. (mandible and maxilla grew to normal, and her Then one particular time, I was busy with an crossed teeth straightened out. She didn’t have to chosen, quite frankly, especially dirty diaper, she poked her tummy up have braces; she simply had jaw development. because she is nothing and I said, “Rub your own tummy.” And she did! Her dentition is now normal. Before treatment, Later I felt guilty. When I first adopted Madison, she was missing three teeth buds. The dentist like a child with Down’s I thoroughly expected to raise a seriously said those teeth would never come in. After syndrome. Because she handicapped child who would never leave home treatment, they all did. as an adult. I had done what a lot of parents do, Her vision also improved. At 34 months, her started on the metabolic to become complacent in comfortable ignorance. eye exam was normal. No nystagmus, no therapy and piracetam in strabismus, no nearsightedness. Perfect vision, CERI: Yes, but maybe we can change that. without glasses. Glasses had been prescribed for early infancy, almost no her when she was younger, but she would never evidence of the Down’s Dixie: I now deeply regret not starting Madison wear them. on a metabolic formula in early infancy. Those Normalization of her facial features was phenotype remains.” children started very early in life show few extremely quick. In about six months, her developmental delays, if any, and even fewer appearance changed from a very flat-faced, Smart Drug News [v3n4] 18 July 1994 5 Smart Drugs and weak-eyed, clearly handicapped Down’s CERI: She must have learned the process from Down's Syndrome: syndrome child to a child who did not look your earlier instructions... handicapped. I don’t care what any of those An Interview with “experts” say about this treatment not working. Dixie: I’m sure she watched the other kids in To give you another example, I used to place her nursery school use the potty. Children with Dixie Lawrence six Down’s syndrome babies a month. Now I’m Down’s syndrome seem to understand far more lucky to place six a year. When the parents see than they can verbalize and physically express. continued from previous page Madison, they pick their kid up and go home. They see that there is something that they can do. CERI: Did you see her verbal abilities change? They’re not scared and lost anymore. Dixie: About the fifth or sixth day she started CERI: That’s the big issue, not knowing what saying things. She had a few words, she could to do, and feeling helpless about the situation. So say “cookie” and “outside,” then she started how did you find out about piracetam? saying, “Wanna go outside.” And I asked, “You wanna do what?” She repeated, “Wanna go Dixie: Initially, I was looking for something outside.” which would facilitate communication between the two hemispheres of the brain. I found one CERI: And how much piracetam were you “I used to place six German reference to piracetam, and ultimately, I giving her? Down’s syndrome babies read about it in Ross Pelton’s book, Mind Food and Smart Pills. I then started looking for a Dixie: At that time I was giving her a low a month. Now I’m lucky source. A good friend of mine was being treated dosage of 800 mg a day, split in two 400 mg to place six a year. When for diabetes in Mexico, so I asked him to scout out doses. For a while I reduced it to 200 mg twice a the pharmacies for me. He found a good one that day to see if it had any effect. It did not. She did the parents see Madison, I have been working with ever since. not revert. Now she’s back up to 800 mg a day of they pick their kid up Before I gave the piracetam to Madison, I took the liquid piracetam. it myself. I started with an attack dose of 4800 and go home.” mg. For a month, I recorded my every reaction in CERI: What else have you noticed? a log book. Then, after consulting with a local doctor who is very supportive of what we are Dixie: She’s doing some amazing things. She doing, I started Madison on 400 mg a day. wasn’t just potty trained, she went to her dresser, took out her underwear, put both feet through the CERI: How old was she then? holes, and pulled them up and on. This is highly unusual for a three-year-old Down’s child. Dixie: That was about one year ago. She was The most amazing thing she did was to around 33 months old. Until that point, she was develop an imagination, an unheard of in diapers. Although we had tried to potty-train development in Down’s syndrome children of her, she didn’t seemed to have any understanding that age. She likes to play ball. She overhand of what we wanted her to do. Potty training pitches, and she’s got a strong and accurate arm. begins when a child recognizes that urine is She can knock your head off clear across the something which comes from their own body. room. About a week after starting piracetam, she Madison just didn’t understand this, so we didn’t came in and said, “I wanna play roll ball.” We push the potty training. She was doing well in looked all over and couldn’t find the little other areas, but her higher intellectual and verbal basketball that she usually plays with, so she sat skills were still quite delayed. At this time, she down on the floor and she told me, “Sit down.” I “Madison potty trained was on the metabolic program including amino sat down and she pretended to pick up her roll ball acids, but not yet on piracetam. and throw it at me. I looked at her like she was herself. She took her own nuts, but I pretended to catch it and threw it back diaper off, went to the CERI: What happened after you put her on to her. She pretended that it hit her in the head. piracetam? She ducked her head and she goes, “Oh, bathroom, took the potty boo-boo.” This might just be cute for another seat apart, put the lid on Dixie: Five days after starting piracetam with child, but for a Down’s syndrome child we’re choline and B5, Madison potty trained herself. talking about an extremely important the big potty seat, turned She took her own diaper off, went to the bath- development. the base of the potty seat room, took the potty seat apart, put the lid on the Her imagination has continued to grow. She big potty seat, turned the base of the potty seat now “flies” with Peter Pan whenever she sees the upside down as a stool, upside down as a stool, climbed up on the toilet puppets on the screen, and sometimes when it’s climbed up on the toilet by by herself and pee-pee’d in the potty. She was not on. ignoring us, but my husband and I were watching herself and pee-pee’d in her while she did all this. He said, “If she does CERI: Wonderful! Thank you for this very the potty. My husband said, that again, I’ll be impressed.” About 45 minutes interesting interview. I’m sure we’ll have you later she headed back to the bathroom and did the back for more in a future issue. `If she does that again, same thing again. She’s been completely potty I’ll be impressed.’” trained ever since. She finally understood.

6 Smart Drug News [v3n4] 18 July 1994 Questions & the complete address of the addressee. In with deprenyl-induced MAO-B inactivation. other words, wrap the cash with your When deprenyl is discontinued, will a person Answers: order-letter and seal it into a standard #10 be overwhelmed for a while with excessive (continued from previous page) business envelope. Address that envelope MAO-B production, until MAO-B produc- and then seal it into a Tyvek® envelope (a tion returns to pre-deprenyl levels? RRJ fiber-reinforced, “un-tearable” brand of envelope). Address that envelope and put it Answer: You aptly pointed out the big into a cardboard UPS or FedEx envelope. problem with trying to assess degrees of With this procedure, accidental shredding of depression: the subjective nature of the con- the outer envelope by processing machines dition. Sudden depression is always more “Can users of deprenyl (it does happen!) will not spew your cash on strongly felt, or more strongly noticed. In `crash and burn’ if they the floor. SWF fact, many people who slowly slide into stop suddenly?” depression over years do not even notice that Question: Yesterday I signed up for a one- they are depressed. Because of this dif- year subscription to your newsletter. I have ficulty, your friend’s subjective evaluations read both smart-drug books, but have yet to are not very useful measures of what is or is receive my first newsletter. not happening with enzyme levels and feed- I have been using deprenyl since back loops. Figure 2: November 1993. I found this substance to be Based on the numerous anecdotal reports A Proposed the most beneficial and positive supplement we have received about deprenyl, a rebound Glutamate I have ever used. I have been using vitamins, effect is possible but not obvious. If it exists aminoacids,Hydergine,piracetam,etc.for at all, it is probably very subtle, showing up Cyclization 17 years (not all at the same time) in search only in certain people or after years of use. Mechanism of cognitive enhancement and health Such an effect would be diffi- cult to maintenance. Many of these materials have measure, given the normal metabolic provided profound and satisfying results. changes associated with aging. In other But deprenyl hit the spot. words, how could we determine that the Between my own testimony and the facts measured before-and-after differences were presented in the deprenyl literature, I have a from the cessation of deprenyl as opposed to dozen and growing number of friends who are the myriad of other influences that occur in taking deprenyl with very positive results. The free-living humans? nagging question about deprenyl that haunts One possible rebound effect that you do us is: what happens when you stop taking not mention is the tyramine re-uptake inhi- deprenyl? Moreover, since deprenyl bition property of deprenyl. Deprenyl’s selectively inhibits MAO-B enzyme activity, is inhibition of tyramine re-uptake is respon- there a rebound effect caused by this sible for deprenyl’s lack of a “cheese inhibition? Does the brain produce more reaction” (a hypertensive episode) that is MAO-B to make up for the “inactivated” otherwise typical of both MAO-A and MAO-B? Is there a feedback loop in operation MAO-B inhibitors. If the tyramine-reup- similar to Inderal and the beta-receptor site take inhibition property of deprenyl wears overgrowth that happens with high-dose and off faster than the MAO-B inhibition, there long-term propranolol use? From what I have could be a “cheese effect window.” As far seen in the literature, this does not seem to be as I know, this has not been scientifically a problem. Can users of deprenyl “crash and inves- tigated nor clinically observed. We burn” if they stop suddenly? Two of my friends have heard of occasional headaches with (who were getting major anti-depressant relief deprenyl discontinuation, which might have from deprenyl) stopped taking it for a week and to do with blood pressure changes, or it slowly sank back to where they were in their might not. We wish we had more informa- depression (before deprenyl) and had a tion about these possibilities, but these subjective feeling that they were even more concerns aren’t stopping us from taking depressed than before. I’m not sure what to deprenyl. WD & SWF make of this. My first thought is that the relatively sudden contrast between the Question: Thank you so much for the deprenyl state and the depressed state wonderful interview with Dixie Lawrence. I magnified their sense of “lowness.” Or, they have several children in my medical practice really might have been more depressed after who were started on the regimen described in deprenyl. I am concerned that MAO-B Dr. Turkel’s book, many years into Down’s synthesis is working overtime to keep up syndrome, and they have all improved mark- Smart Drug News [v3n7] 26 October 1994 9 Questions & edly in intelligence and personality. Ihave was enough money or demand for the drugs read your article several times and cannot find I was carrying. He said that in any case, I Answers: any summary of Dr. Warner’s program for the should have a prescription because otherwise (continued from previous page) Down’s child, nor any suggestion of how to alltheywouldhavetodeterminemy contact Dr. Warner. If you can help me learn integrity was an honest face. So I said, “If you can help me learn more about the modern, up-to-date nutri- tional looking him right in the eye, “How’s my more about Dr. Warner’s program for Down’s syndrome, I and my face?” He laughed and said, “Get out of patients would be very appreciative. HW here.” Their’s is not an easy job and I’ve modern, up-to-date always found that if I remember that they are nutritional program Answer: Dr. Warner’s referral listing human and deserving of respect, I never have for Down’s syndrome, appeared in the issue following the first a problem. I’m happy to report a successful article on Down’s syndrome. You can write outcome. I don’t know if that’s the way it I and my patients would or call him at: The Warner House, 1023 E. goes for everyone else. For me it was fun, be very appreciative.” Chapman Avenue, Fullerton, CA 92631, and happily I now have a good supply of 714-441-2600 (Fax: 714-441-2522). He will smart drugs for the next few months. behappytosendyouinformationonthe Love and kisses, from New York. Anon dietary supplement nutrient formula that he uses. SWF Question: Thanks to Mr. Hardy for the book review and the last copy of The Neuroendo- Report: Hi guys. Thanks for the good infor- crine Theory of Aging and Degenerative mation that keeps pouring out from Menlo Disease. Keep the reviews coming. KM Park. “We are sorry to have Last week I was on vacation in California Answer: You are very welcome. We are to announce that from New York and decided to drive to Tijuana sorry to have to announce that The Neuro- The Neuroendocrine to see if I could get some of the drugs I wanted endocrine Theory of Aging is now out of print to try but hadn’t yet made the connection and unavailable. Dr. Dean informs us that he Theory of Aging through the mail. I parked in a lot on the US is hard at work on a revision, but it will is now out of print.” side and walked across the border with a day probably be more than a year before it is pack on my shoulder. I walked to the right after republished. TMH the border point and found numerous farmacias (as they call their drug stores down Comment: Thank you for the interview with there). I was interested in Dilantin and Mrs. Dixie Lawrence. It was fascinating piracetam. Everyone spoke English and were reading. It is almost incredible what very willing to sell me any amount that I could dedicated people who think for themselves afford. Prices were almost all the same. I can achieve. KM purchased six boxes of piracetam (Nootropil, “The American border 30 tablets, 800 mg) and five boxes of Dilantin Comment: The comments about long-term guards noticed my supplies (Epamin, 50 capsules, 100 mg). I then walked storage of powders, capsules, etc., prompted back across the border. I reminded myself that me to write you about a helpful device and asked if I had any FDA policy permitted the purchase of a I’m using, particularly for hygroscopic sub- prescription drugs.” 3-month supply, so I felt comfortable in the stances like DMAE powder. It’s called a event that I would be questioned. All packages Pump’N’Seal, from USA Direct (they have an were scanned as we passed through the border. 800 number, but I don’t have it). This device The American border guards noticed my is one of those things that you see in late-night supplies and asked if I had any prescription infomercials. Strangely, the damn thing drugs. I acknowl- edged that I did and opened works. Using it, I can partially evacuate (with up my pack to show them the contents. I was attendant moisture) a container and its asked if I had a prescription. I said no. I was contents. I like the jars that have a soft-seal informed that I really should have one. I them lid, such as those used for cocktail sauce and mentioned my understanding of the FDA jellies, but I can even use plastic bags (with a “Do you have any ideas personal-use drug-importation policy. The little oil added at the sealing edges). LEB why Durk Pearson said guard was familiar with the policy. He looked that he woke up from me in the eye, looking for furtiveness or Question: I enjoyed John Morgenthaler and uncertainty. Finding none, he informed me Dan Joy’s article on GHB. Do you have any a violent dream swinging that the reason for the prescription ideas why Durk Pearson said that he woke up his arms and legs while requirement was that I might sell the drugs in from a violent dream swinging his arms and using GHB?” the US at a profit and return the next day for legs while using GHB? more. I expressed that I didn’t think there If GABA doesn’t cross the blood brain 10 Smart Drug News [v3n7] 26 October 1994 Questions & progesterone in the US? Where are they and/or small amounts of testosterone. getting it, from Europe? SL Natural medicine outlets also sell proges- Answers: terone creams, even though they may be (continued from previous page) Answer: The term “micronized” refers to obscurely labeled as containing “yam finely ground powders which are better extracts” for legal reasons having to do with absorbed orally. Progesterone can be the FDA. I have been getting progesterone micronized to enhance oral absorption (i.e., cream from the Withers Mill Company in from capsules), but it can also be effectively Missouri (1-800-223-0858). Their product administered topically (in skin creams). was recommended to me by Dr. Lee, author Absorption through the skin is excellent, and of Natural Progesterone. SWF “What mail-order houses progesterone is absorbed into the Correspondence sell progesterone in the subcutaneous fat layer where it is slowly released into the blood stream. And since Please send your questions to: CERI Q&A, United States?” the blood supply from the skin goes into P. O. Box 4029, Menlo Park, CA general circulation before passing through 94026-4029. You may also FAX them to the liver, less progesterone is removed from CERI Q&A at 415-323-3864, or phone them circulation by the liver than with oral dosing. to us at 415-321-CERI and leave a message. The blood supply from the stomach and Note: Initials of the subscriber/author follow each intestines passes through the liver before question (OTP refers to an over-the-phone entering general circulation. question, and Anon refers to a question asked by a Progesterone creams are available in the reader requesting anonymity). If you want us to US both with and without a prescription. use your full name, or if you want us to omit your Compounding pharmacies make them, with initials, please state so in your correspondence. Initials following answers refer to the individual and without estrogen (estradiol or estriol) editors listed on the masthead on page 1.

Political Update: that, it should be specified by law. Bottom function of the human body.” The Pending line: the FDA should be prohibited from structure-and-function definition of “drug” interfering with any legitimate medical and “medical device” is absurdly broad and Congressional treatment being supervised by a licensed should be scrapped in favor of a new, narrow Reform of the FDA physician. definition. Bottom line: the FDA should be Second, medical devices should not prohibited from seizing any consumer (continued from page 1) include 1) exercise and sports equipment, device which they cannot prove to be 2) sound and light machines, 3) classical hazardous. music tapes/CDs, and 4) other recreational Thirdly, the FDA must be forced to detail devices that may “alter the structure or all charges against any individual or company against whom they take enforce- ment action. If the FDA cannot explain the New Sources law and regulations to affected parties, they NutriGuard Research 1-800-433-2404 have no business enforcing it. Bottom line: P. O. Box 865, Encinitas, CA 92023 the FDA should be prohibited from keeping NutriGuard carries arginine pyroglutamate, phosphatidyl choline, Staminex, charges secret after enforcement is initiated. glucosamine, and numerous other multi-nutrient formulas. From outside US Lastly, FDA censorship powers need and Canada call 619-942-3223. to be abolished. The truthful-and-not- ASTAK 813-973-7902 misleading claims provision of last year’s 29949 S.R. 54 West, Wesley Chapel, FL 33543 Hatch/Richardson bills was blocked by Rep. ASTAK distributes the liquid DHEA product developed by Discovery Waxman and associates. With new Experimental & Development, Inc. Congressional leadership, this provision should now be passed. Bottom line: The FDA should not be permitted to prohibit Day One Segment Scheduled for January truthful information of any kind. Please let your Congressional Represen- An ABC TV production crew recently visited CERI and filmed tatives and Senators know how you feel Executive Director Steven Wm. Fowkes for a multi-part feature on smart about FDA powers and what you think they drugs. We hear that one of these parts will focus on the Down’s syndrome should do about it. Hopefully, pending story that we have been reporting. Look for it when Day One returns to momentum for FDA reforms will be the air in January with Diane Sawyer as co-anchorperson with Forest channeled into constructive changes which Sawyer. will be more than superficial. SWF 12 Smart Drug News [v3n8] 28 December 1994 Editorial: Dealing with Your Doctor by Steven Wm. Fowkes For many of us lucky enough to find an is often used to persecute unorthodox enlightened physician willing to prescribe doctors. Such politically and economically FDA-approved drugs for unapproved uses, motivated “investigations” are quite the temptation to ask for prescriptions for common and are often defined by a Fowkes unapproved drugs may seem a natural thing conspicuous absence of patient complaints to do. Although this may be perfectly legal and/or a lack of specific allegations of harm according to federal regulations, the practice or endangerment. Medical regulators would of medicine is regulated at the state level. like us to believe that these actions are for the “Medical licenses are Medical licenses are attached to extensive patients’ benefit, but they are more often attached to extensive state state regulations governing the conduct of based on anti-competitive motives. In other regulations governing the physicians, which includes the prescription words, the initial complaint was motivated of drugs. Unfortunately for consumers, by the desire to eliminate a popular, more conduct of physicians.” these regulations are modeled after an effective, less toxic, and/or less expensive anti-competitive medieval institution — the medical alternative to a standard practice. In guild. addition, some doctor’s file complaints to In the Middle Ages, guilds were set up by stop the flight of their patients from their “Although orthodox medical practitioners to protect the secrets of their practices to another doctor who is better able rhetoric states that there is trade in exchange for compulsory (i.e., to help their patients. These ego-motivations a direct connection between restricted) membership. To become a are not recognized or acknowledged because member of the guild, you had to have the complainant’s identity is rarely generally accepted medical connections, and you probably had to endure disclosed. The accused never gets to face the practices and patient welfare, a long, poverty-level apprenticeship to learn accuser. No cross-examination or impeach- such an argument does not your trade. ment is possible. In our modern day and age, it may seem Other motivations include the defense of stand up to scrutiny.” anachronistic that medicine would be ideological positions (expert opinions) taken regulated by this same social institution. by authorities. Good examples of this Modern doctors must endure a long (and include investigations for 1) the prescrip- somewhat cruel) apprenticeship (medical tion of vitamins instead of drugs, 2) the school and residency) to learn to be a doctor. prescription of drugs for unapproved uses, “Such `investigations’ Doctors’ conduct is regulated by 3) failing to use an approved therapy (i.e., are quite common and somewhat-vague references to “generally chemotherapy or vaccinations), and are often defined by a accepted” medical practices, in other words, 4) prescription of drugs that the FDA has not whatever other doctors think should or yet determined to be safe or effective (even conspicuous absence of should not be done. As you might imagine, if they are completely safe and effective). patient complaints and this system rewards orthodoxy and This is “political correctness” applied to a lack of specific victimizes innovation. medicine. Although orthodox medical rhetoric So before you expect your doctor to allegations of harm states that there is a direct connection prescribe piracetam to you, or before you or endangerment.” between generally accepted medical get upset that your doctor won’t do it, practices and patient welfare, such an recognize that they are effectively caught argument does not stand up to scrutiny. between a rock and a hard place. Consider Some innovations may put patients at greater the wisdom of obtaining the drugs without risk, but others are more likely to provide a prescription and ask your doctor for added benefits. To determine the relative medical supervision. This minimizes the “Support pending risks and benefits, one might think that a likelihood that your doctor will get legislation in your state risk-benefit analysis would be the standard disciplined and/or lose his or her license to protect alternative of judgment, but it isn’t. A bene- ficial for providing you with the innovative treatment is automatically condemned just medical services you want. practitioners. With such because it is not yet recognized by other In the meanwhile, support pending legis- legislation, doctors may be doctors. lation in your state to protect alternative able to afford to practice Regulation of doctors by the generally- practitioners from this kind of harassment. accepted-practices standard not only ends With such legislation, doctors may be able to their best medicine.” up denying patients effective treatments, it afford to practice their best medicine. ¤ Smart Drug News [v3n9] 30 January 1995 9 Trisomy 21 News Update: Down’s Syndrome Symposium by Dixie Lawrence Scientists from the United States, at this approach to improving the lives of Canada and France who are involved in persons with Down’s syndrome. At this researching Down’s syndrome will gather in time, it is estimated that more than 5,000 US San Diego, California to attend a three-day patients are on MSBP, with an equal number symposium November 7-9. This scattered among some 14 other countries symposium will be attended by researchers including Great Britain, Saudi Arabia, Dixie and Madison and biochemists involved in metabolic Australia, New Zealand and South Africa. studies of Down syndrome, including Marie Well-designed, double-blind studies are “Scientists from the Peeters of the Institut De Progense — now in progress in several countries United States, Canada founded by Jerome Lejuene, the scientist including the US and New Zealand. who originally discovered that trisomy 21 is Trisomy 21 supplies parents with and France will gather caused by the presence of an extra 21st pertinent documentation and abstracts for in San Diego, California chromosome. Marie Peeters and I will be their physician’s information and review. to attend a three-day addressing the conference on Thursday, Generally, once a physician has ordered and November 9th, and a panel discussion will reviewed metabolic profiling of both blood symposium” follow at 6PM. Panel participants will and urine, they have little difficulty include Steven Fowkes (CERI), Dr. Paul assisting parents with this protocol. Results Spurlock (Tulane University), Dr. Alex of tests consistently show dangerous low “At this time, it is Bralley and/or Dr. Richard Lord levels of antioxidants and certain amino estimated that more than (MetaMetrix Medical Testing Laboratory), acids necessary for neurotransmission, Kent McLeod (NutriChem Laboratory), Dr. among other metabolic abnormalities. 5,000 US patients are on Charles Thomas (Pantox Laboratory), and As of this time, the National Down MSBP, with an equal Dr. Marie Peeters. Syndrome Associations have not addressed number scattered among the merits of the MSBP program, other than News Update to advise their readers to disregard it. While some 14 other countries.” National media exposure over the past this is the official line, it is interesting that year has enabled Trisomy 21 Research, Inc. persons involved with the management of to provide thousands of parents and various parent groups have placed their own physicians with information regarding the children on the protocol. potential manipulation of gene We hope that the upcoming symposium over-expression as a viable therapeutic in San Diego will add to the momentum of “Best results are obtained approach to managing Down’s syndrome. our efforts and will move us closer to the by modifying the formula A standard formula is now available (called day when caring for the diverse nutritional MSBP) from NutriChem Labs in Ottawa, needs of patients with Down’s syndrome to each child’s individual Ontario, Canada, however, best results are and the use of nootropics to enhance metabolic needs as obtained by modifying the formula to each memory and learning will become a identified through blood child’s individual metabolic needs as standard of care for our children. ¤ identified through blood and urine analysis. and urine analysis.” Growing acceptance in the medical community has prompted even persons who Coming to a Theater Near You were initially skeptical to take a second look We will be covering the proceedings of the Down’s syndrome symposium in New Source the next few issues of Smart Drug News. Euro Care Mailorder Pharmacy 011-31-320-257-639 We will have a feature article on P.O. Box 75; 8200 AB Lelystad; THE NETHERLANDS intelligence by David Bezanson, Ph.D. Euro Care is a source for nootropics and more than 2000 other European All the wild speculation in the national prescription drugs. They carry DHEA, melatonin, acetyl-L-carnitine, media about the absence of the Q&A in piracetam, oxiracetam, vasopressin, levamisol, adrafinil, biostim, deprenyl, this issue are merely rumors. ;-) Pay centrophenoxine and growth hormone. The phone and fax numbers are them no heed. It will return. dedicated to US customers. They accept VISA credit-card payments. Their stated delivery time is 2-3 weeks after order is received. Faster UPS shipments And, yes, Virginia, we are in the process are available. Fax: 011-31-320-257-931. of reviewing another melatonin book.

12 Smart Drug News [v4n6] 6 November 1995 Nutrition Arts: cantly enhanced in diseases which involve phan deficiency. A future SDN article will The Art of immunological responses [for an in-depth describe newer diagnostic approaches to discussion of these relationships, see identify causes of secondary tryptophan Nutritional Forefront 7(2): 1-6, July 1992]. deficiency. Therapeutics In such cases, diminished serotonin To our knowledge, the concept of a levels and depression could be viewed as a secondary nutritional deficiency of trypto- continued from previous page natural consequence of excessive catab- phan as a public health risk has not been olism of the essential nutrient tryptophan. adequately advanced in the medical litera- “The concept of a From the standpoint of nutritional bio- ture. Perhaps this is related to the medico- secondary nutritional chemistry, the concept of serotoninergic- pharmaceutical paradigm that would have deficiency of tryptophan related depression as a symptom of primary us rely upon patentable and profitable drug or secondary deficiencies of tryptophan treatments rather than nutritionally as a public health risk seems hard to assail. It is a general principle oriented self-care. And perhaps we should has not been adequately of nutritional science that the restoration of also acknowledge that the average physician advanced in the a nutrient-dependent function by the probably doesn’t have the time, diagnostic medical literature.” administration of a nutrient is prima facie technology and economic incentive to evidence of nutritional deficiency. unravel the complex array of lifestyle and Restoration of brain serotonin levels can metabolic factors which induce secondary be achieved through drug intervention or by deficiencies of tryptophan, low serotonin correcting the primary or secondary trypto- states and depression. ¤

Question: I was recently privy to a Answer: There is no credible evidence that conversation between several doctors who this is a significant concern. The calcium were discussing a theoretical problem with buildup that everybody is talking about piracetam and possible calcium metabolism results from excitotoxicity, a technical term problems in the brain. Have you heard for the overstimulation of excitatory anything about this? My 6-year-old daughter neurons. The best example of an excito- has Down’s syndrome and has been taking toxin is glutamate (better known as mono- piracetam for two years. She is doing very well sodium glutamate, or MSG). Glutamate is on it, but now I’m a little worried about also a natural excitatory neurotransmitter. long-term piracetam use. OTP In normal amounts, it is used by neurons to transmit messages from one part of the “Doctors were discussing Answer: See next question and answer. brain to another. In higher amounts, it a theoretical problem with causes marked stimulation (an increased uestion: Hello Steve! I am the mom of a flux or flow of calcium into the cells). In piracetam and possible Q 26-month-old boy with Down syndrome (DS). even higher amounts, it causes overstimu- calcium metabolism He has been taking MSP Plus with piracetam lation (excitotoxicity) which results in too problems in the brain. for the past eight months and we are much calcium entering the cells and extreme Have you heard anything impressed with the results. During an on-line cellular stress from trying to pump out all about this?” DS chat session, one father announced that he the excess calcium. If the cell cannot keep had taken his child off piracetam because a up with the influx of calcium by pumping doctor at the National Down Syndrome it out, it can die. Congress convention had mentioned that Glutamate (also called glutamic acid) piracetam has been linked to exacerbating and its related amino acid cousin asparate calcification of the brain in persons with DS. (aspartic acid) are common components of When I pressed him for the information the the protein found in our food. Other diet- doctor used to draw this conclusion, I got no ary substances are also known to stimulate clear response. Obviously, if there is any truth excitatory receptors, but to a lesser degree. to this statement at all, which at this point I These include glutamine, aspartame, pyro- seriously doubt, then it would behoove me to glutamate and piracetam. Pyroglutamate is be certain that I am giving my son the proper much weaker than aspartame, and glutamine amount of piracetam. I suspect that his and piracetam are much weaker than intake of dairy products would be more of a pyroglutamate. concern (as it relates to calcification of the Given the prevalence of powerful excita- cells) than his intake of piracetam. I would tory substances like glutamate and aspartate appreciate your comments greatly. Thanks in in our natural diets and in commercially advance! TR processed foods (which contain MSG, Smart Drug News [v4n9] 29 February 1996 9 Questions & protein hydrolysates and soup broths — all received are any indication, MSB+ [a Answers: high in free glutamate), and the ready nutritional formula developed specifically availability of glutamine, aspartame for DS children] treatment seems to (continued from previous page) (NutraSweet), and pyroglutamate (one of normalize immune function and resolve the the primary natural skin humectants chronic infections which plague untreated [moisturizers] of the human body), it is DS children. In that case, the risks from highly doubtful that piracetam poses a consumption of dairy products should be “Given the known significant excitatory risk to the central similar to kids without DS. SWF benefits of piracetam in nervous system of free-living human beings. the treatment of various I’d also like to point out the suscepti- Question: I have tried a few small doses (1/8 neurological conditions, it bility to excitotoxicity is increased in infants, to 1/4 of a 5 mg tablet once a week) of deprenyl children, the elderly, people who’ve suffered and have noticed useful effects similar to those would seem inappropriate to head traumas, and individuals exposed to described in your book Smart Drugs II. avoid it for that reason.” certain toxins (through food poisoning and However, I am concerned about possible bacterial/fungal infections). In the large detrimental long-term effects. For example, number of clinical studies of piracetam in since deprenyl inhibits the degradation of the elderly, excitotoxicity and calcium- neurotransmitters and boosts the release of channel side effects have not been reported. dopamine, I am curious if any studies have When I last reviewed the literature, there been done to determine if the brain can acquire were no reports of piracetam antagonizing a dependence on the deprenyl for generating the activity of calcium-channel blocking dopamine or for other aspects of drugs, which are now popularly prescribed neurotransmitter activity. More bluntly, can I for elderly individuals. And piracetam get Parkinson’s or some other disorder by seems to provide substantial clinical benefit getting used to deprenyl and then ceasing its in the post-trauma recovery phase following use? If so, what is the minimum period of time head injuries. necessary to establish a dependence? Although the above discussion does Have there been other kinds of studies on present a theoretical basis for activation of the long-term effects of deprenyl use? If so, “Can I get Parkinson’s calcium channels by piracetam, the evidence what were the results? If such studies were or some other disorder by for would seem to indicate that it is not carried out on an elderly population or on getting used to deprenyl clinically significant. Given the known groups with Parkinson’s, what inferences and then ceasing its use?” benefits of piracetam in the treatment of can reasonably be made regarding possible various neurological conditions, it would effects on healthy persons from such seen inappropriate to avoid it for that reason. studies? I wouldn’t worry about dietary calcium I would like to continue to use deprenyl from food (i.e., dairy products) as a risk now that I have settled on a comfortable factor either. It is excessive neurologic ac- dosage (1 mg every 5 days with about 150 mg tivity or hormone imbalances, not excessive dl-phenylalanine). However, I am consid- calcium, which is the primary cause of ering delaying further use until I can get calcium overload in neurons. Unless there is reliable data on long-term effects. I would a magnesium deficiency (which is needed to greatly appreciate any relevant information balance calcium), dietary calcium is not which may help me make this decision. likely to pose special risks for DS children. HAP I think that DS kids have a harder time Answer: We all suffer from slight degrada- with dairy products than kids without DS tion of the substantia nigra of the brain due to excessivbe mucous formation that as we get older (severe degradation results in provides a growth media for respiratory and Parkinson’s disease). One prominent inner-ear infections. But if the reports I’ve neuroscientist told me that “if we lived long enough, we’d all suffer from Parkinson’s disease.” No long-term studies that I know New Source of have been conducted using normal human subjects — as with most potential United Prescription Center 305-987-4441 800-421-7455 life-extending agents — nor are any studies 4517 Hollywood Blvd., Hollywood, FL 33021 likely to be performed. If we wait for long- UPC carries DHEA and many other pharmaceuticals. They formulate term human studies to be conducted before custom medications to your doctor’sprescription. They ship all over North we attempt anti-aging intervention, the America. Fax: 305-987-8049. US/Canada toll free: 1-800-421-7455. information gained will be of no use to those Worldwide toll free: 800-700-5769. of us now living. The best we can do is to

10 Smart Drug News [v4n9] 29 February 1996 Smart Drug News THE NEWSLETTER OF COGNITIVE ENHANCEMENT & LONGEVITY

Smart Drugs & Down’s Syndrome: Part 2 Smart Drug News ISSN 1060-8427 Antioxidant Intervention in Down’s Syndrome Published 10 times annually by the by Steven Wm. Fowkes Cognitive Enhancement Research Institute Two years ago, we published our first the mother’s egg and the other from the P. O. Box 4029 article about smart drugs and Down’s syn- father’s sperm). Every time a cell divides, Menlo Park, CA 94026. 415-321-CERI drome which focused primarily on clinical each of the 46 chromosomes must be (415-321-2374) approaches. This article will begin an duplicated and separated, one copy of Copyright © 1996 extensive discussion of metabolic and bio- each chromosome ending up in each All rights reserved. chemical mechanisms underlying Down’s daughter cell. Sometimes the process of Subscription $44/year syndrome — and proposed nutritional pulling apart the duplicated chromosomes Canadian $46/year Overseas $55/year interventions which may mitigate these malfunctions, and both copies of one of Single issue $6 metabolic disturbances. the 21st chromosomes end up in the same Vol. 4, No. 10 daughter cell. In other words, one cell has April 15, 1996 Genetic Over-Expression only one 21st chromosome (which fails to Unlike most other genetic conditions replicate) and the other has three 21st Editor which are characterized by a deficiency chromosomes. This is why Down’s syn- Steven Wm. Fowkes (deletion) or change (mutation) of the drome is referred to as trisomy 21 (tri Medical Editor genetic material, Down’s syndrome is means three, somy refers to chromosome). Ward Dean, M.D. characterized by a duplication of all or This extra genetic material causes over- Subscription Services part of the 21st chromosome. Normally, expression of the duplicated genes. In J. R. Richards each cell in the body is supposed to have other words, genes make both enzymes two 21st chromosomes (one derived from and proteins, and too many genes lead to continued on next page Also In This Issue Melatonin Update: What are Free Radicals page 2 Is Melatonin a Sex-Enhancing Hormone? Figure 1: by Steven Wm. Fowkes H2O2 Flow Diagram Since the recent publication of The Mel- sex throughout their entire extended page 2 atonin Miracle: Nature’s Age-Reversing, lifetimes.” Figure 2: Disease-Fighting, Sex-Enhancing Hor- Although the mechanism of this pro- H2O2 Flow in Down’s Syndrome mone, written by Drs. Walter Pierpaoli and sexual effect in mice is not clear, Pierpaoli page 2 William Regelson, interest in melatonin’s and Regelson suggest that this may be Figure 3: sex-enhancing properties has become a partly due to the ability of melatonin to The Recycling of Glutathione media issue. In their chapter on “Mela- preserve ovaries and testes against age- page 3 tonin and Sex,” Pierpaoli and Regelson associated shrinkage. They state, “We FDA Retaliation Getting Noticed argue that the age-associated decline in believe that there is a direct connection page 4 sex drive may be ameliorated by mela- between the youthful state of the sex tonin supplementation. In mice experi- organs and the level of sexual activity.” GATT (and the World Trade Organization) ments, they observed that melatonin “had They suggest that this may be extrapo- vs Vitamin Supplements a profoundly rejuvenating effect” on aged latable to humans, and that melatonin page 5 mice. “Their coats grew thick and supplementation may enhance fertility, lustrous, their eyes remained clear and delay menopause, enhance erotic dreams Q&A cataract-free, their digestion improved, and sexual pleasure, boost libido and page 6 and their strength and muscle tone was encourage intimacy. New Doctors enhanced.” Regarding sex, they state, The appeal of such claims is obvious. page 7 “Both males and females displayed [...] the But are these effects real in humans? Calendar of Upcoming Events sexual fortitude of much younger mice, At the Fourth Annual Antiaging and page 12 and they appeared to preserve interest in continued on page 11 Smart Drugs & too many enzymes and proteins. This, in Figure 1: Down’s Syndrome: turn, distorts normal metabolism and H2O2 Flow Diagram development. Antioxidant - Intervention Nutritional Intervention O2* HO2 2 superoxide hydrogen peroxide anion radical in Down’s The key concept underlying nutritional g l c u

intervention in Down’s syndrome is meta- a t a Syndrome e t t

a

g h l

bolic correction of genetic overexpression. a i

a o

(continued from previous page) m s n Although the extent of the metabolic dis- a e e

d p

turbances in trisomy 21 is not fully known, l e

a r

c o i 2

several of the more significant distur- O x

d i oxygen d

a

r a

bances are now becoming well charac- s e e

e

terized. Effective metabolic management r of these disturbances offers the hope of f HO2 ameliorating the disability typically associ- water ated with untreated Down’s syndrome. The degree of amelioration must depend Figure 2: on 1) the metabolic effectiveness of the H2O2 Flow in Down’s Syndrome intervention, and 2) the age at which it was begun. Early clinical reports by physi- -* O2 2 2 cians and anecdotal reports by parents superoxide HO anion radical hydrogen peroxide

e g g l a c u a t

a

t

m t a

What are Free Radicals? h a l

i a

d o

s n Molecules are composed of atoms bonded together. This bonding l e a e c p

process is accomplished by the sharing of electrons. When two atoms i e r

d 2 o

come together and their electrons pair up, a bond is created. O x

a i oxygen d

r

a

It is a general principle of quantum chemistry that only two s e e

e

electrons can exist in one bond. Specifically, each electron must have r opposite “spin” from the other. Like male and female animals, “up” f HO2 electrons pair up with “down” electrons, and bonds are created. water Paired electrons are quite stable; almost 100% of all electrons in the human body exist in a paired state. When a bond is broken (by radiation, for example), the electrons utilizing some of the approaches that will can stay together (i.e., both go to one of the atoms and the other atom be discussed in this article suggest that gets none) or they can split up (one electron goes to each atom). If functional normalization of growth rate they stay together, the molecular fragments are called ions, and they and cognitive development is likely if are electrically charged (the atom with the electrons is negatively intervention is begun early in life. This charged and the one without the electrons is positively charged). A possibility is at complete odds with the good example of this is sodium chloride (salt) which splits up into a orthodox view that Down’s syndrome chloride anion (Cl–) and a sodium cation (Na+). infants are born retarded and that If the electrons split up, the atoms are free radicals (molecules with treatment is fundamentally futile. an unpaired electron). The unpaired electrons are highly energetic Several of the major metabolic path- and seek out other electrons with which to pair—and stealing them in ways known to be disturbed in trisomy 21 the process. This electron “rip off” is what makes free radicals both are directly attributable to genetic over- useful and dangerous. expression. Perhaps the most important Since most electrons exist in a paired state, free radicals often end example of this is destabilization of the up reacting with paired electrons. When they do so, one of the antioxidant defense system by over- electrons pairs with the (former) free radical and the “odd electron expression of the enzyme superoxide out” becomes another free radical (odd plus even equals odd). Only dismutase (SOD), which is located on the when a free radical pairs up with another free radical is the free radical 21st chromosome. Overexpression of the terminated (odd plus odd equals even). enzyme cystathionine β-synthase seems Antioxidants (also known as free radical scavengers) function by to be significantly responsible for the offering easy electron targets for free radicals. In absorbing a free metabolic disruption of “active” methyla- radical, antioxidants “trap” (de-energize or stabilize) the lone free- tion pathways (the SAM cycle). And radical electron and make it stable enough to be transported to an connective tissue problems appear to be enzyme which combines two stabilized free radicals together to directly attributable to overexpression of neutralize both. SWF collagen genes on the 21st chromosome. Other metabolic disturbances have not 2 Smart Drug News [v4n10] 15 April 1996 Smart Drugs & been tied to specific genes. As examples, there are three copies of the SOD gene Down’s Syndrome: tryptophan deficiency and ammonia instead of the normal two. With over- accumulation are common features of production of SOD, catalase and gluta- Antioxidant Down’s syndrome. Fortunately, these thione peroxidase are challenged to keep Intervention metabolic disturbances are just as amen- up with the accelerated production of in Down’s able to nutritional intervention as those hydrogen peroxide. When they don’t, Syndrome tied to genes. The remainder of this article excess hydrogen peroxide accumulates in will be devoted to discussing the anti- the cells and tissues (see Figure 2) causing (continued from previous page) oxidant disturbances associated with increased oxidative stress, free-radical overexpression of SOD. The rest of the proliferation and accelerated aging. examples will be discussed in the When endogenous (internally manu- following article. factured) antioxidant enzymes (catalase and glutathione peroxidase) are over- Superoxide Dismutase whelmed with hydrogen peroxide, exog- Superoxide dismutase (SOD) is a vital enous (dietary) antioxidants are forced to free-radical scavenger. Its job is to “mop take up the slack. This greater-than- up” stray superoxide ion radicals (O2–) normal burden on exogenous antioxi- and convert them to hydrogen peroxide dants is evidenced by depleted levels of (see Figure 1). Hydrogen peroxide is then vitamins A, E and/or C, zinc, selenium, detoxified by other enzymes (catalase and and/or glutathione in untreated Down’s Figure 3: glutathione peroxidase). Normally, SOD syndrome individuals. The Recycling is in balance with catalase and glutathione of Glutathione peroxidase. But in Down’s syndrome, Glutathione Glutathione (GSH) is a central player in the antioxidant defense system (see Figure HO2 2 OxidizedOxidized State State GSSG 3). It is a tripeptide (3-amino-acid protein) GSSG made from glutamate, cysteine and free glycine. The active site on the glutathione radicals SOD Se glutathione NADP molecule is the sulfhydryl (SH) group on peroxidase the cysteine part of the glutathione (which H2O glutathione is where the “SH” comes from in the “GSH” reductase B cellular 2 B3 energy abbreviation for glutathione). The sulf- hydryl group (sometimes called a thiol group) interacts with a free radical to form GSH ReducedReduced State State NADPH aglutathione radical, which dimerizes (pairs up with another glutathione radical) Reduced (anti-oxidized) glutathione (GSH) is used by glutathione peroxi- to form oxidized glutathione (GSSG) (see dase (a selenium-dependent enzyme) to detoxify hydrogen peroxide (H2O2). Figure 3). Oxidized glutathione is then In this process, the oxidation power of hydrogen peroxide is transferred to recycled (reduced) back to glutathione for oxidized glutathione (GSSG). In other words, H2O2 moves down while GSH reuse. moves up. While GSSG still has oxidizing power, it is significantly less than The maintenance of reduced gluta- that of H2O2. GSSG is recycled by glutathione reductase using NADPH. In the thione appears to be especially critical for + process, NADPH is converted into NADP (the oxidized form of NADPH). The overall health maintenance; Down’s regenerated GSH is then ready to detoxify more hydrogen peroxide. syndrome children appear to be more When the antioxidant defense system is functioning properly, most of it’s susceptible to infection when glutathione components are present in their reduced form (H O, GSH, and NAHPH). If 2 levels are low, even when other deficien- there is a malfunction, then the oxidized components (H2O2, GSSG and/or NADP) tend to accumulate — with adverse effects. The entire process is cies are milder than expected [MacLeod, driven by energy production at the cellular level, which involves proper 1996]. Down’s syndrome children with thyroid hormone levels, healthy mitochondrial function, and an active high glutathione levels appear to be more pentose-phosphate metabolic pathway. The pentose-phosphate pathway is healthy, even if they are suffering from especially important for providing NADPH for red blood cells and hepatocytes additional deficiencies that are quantita- (liver cells). In some populations, one of the key enzymes in the pentose- tively more severe than usual. phosphate pathway (glucose-6-phosphate dehydrogenase, or G6PD) is Although glutathione levels do tend to frequently deficient due to mutations. Over 300 variants of G6PD have increase when other antioxidant deficien- been identified! With diminished G6PD activity, the supply of NADPH is cies are corrected, they generally do not impaired, GSSG levels tend to accumulate, and control of hydrogen peroxide fully normalize. We do not know why. (and superoxide) is impaired. This results in formation of methemoglobin (an Given that cysteine is a component of oxidized and inactive form of hemoglobin), and if severe enough, hemolytic glutathione, it is somewhat paradoxical anemia (wholesale destruction of red blood cells). SWF that Down’s syndrome is characterized by Smart Drug News [v4n10] 15 April 1996 3 Smart Drugs & abun- dant cysteine and deficient glutathi- some degree of balance with the over- Down’s Syndrome: one. The dynamics of this relationship are expressed SOD. In areas of the world not yet fully understood, but it may be where selenium deficiency is severe (i.e., Antioxidant wholly or partly the direct result of New Zealand and China), selenium Intervention oxidative stress. supplementation has been found to in Down’s readily reverse selenium-deficiency Syndrome Glutathione Peroxidase diseases in animals (e.g.,white-muscle Glutathione peroxidase (GSHpx) is a disease in sheep) and man (Keshan’s (continued from previous page) endogenous antioxidant enzyme that disease). detoxifies hydrogen peroxide (H2O2,or Food sources of selenium can be prob- HOOH) and fatty acid hydroperoxides lematic. Selenium is not an essential (fatty-OOH). It is constructed from four nutrient in plants as it is in animals. Wheat identical subunits, each of which contains grown in selenium-rich soil (i.e., South “Functional normaliza- one atom of selenium (Se), a fairly rare Dakota) contains respectable levels of tion of growth rate and element in the oxygen and sulfur family. selenium, but wheat grown in selenium- Glutathione peroxidase uses reduced poor soil (i.e., Oregon) does not. Does cognitive development glutathione to detoxify peroxides, anybody really know where their wheat is a reasonable expec- releasing oxidized glutathione in the was grown? tation if intervention is process. Oxidized glutathione is recycled In one trial of Down’s syndrome indi- by glutathione reductase back to reduced viduals, selenium supplementation was begun early in life.” glutathione (see Figure 3) using riboflavin found to increase the levels of glutathione (vitamin B2) as a cofactor and NADPH as a peroxidase. Thus, selenium supplemen- reducing agent (an anti-oxidizing sub- tation appears to be a viable strategy for stance, like vitamin C). compensating for SOD overexpression. The central role of selenium in gluta- thione peroxidase activity provides a The Antioxidant focus for intervention. Selenium supple- Defense System mentation may be able to up-regulate The control of free radicals and oxi- glutathione peroxidase activity to restore dizing agents is central to the life process. While the atmosphere is dominated by oxygen (20%) and free radicals (billions FDA Retaliation Getting Noticed per cubic foot), the chemical environment We’ve been suggesting that the FDA is a vindictive agency for years, within our cells is reduced (the opposite of but now Congress and the media are beginning to ask questions. With oxidized). A good way to think of oxida- the Republican takeover of key Congressional committees last year, tion and reduction (redox for short) is in some corrageous industry insiders have testified that fear of FDA terms of electrons. The atmosphere and retaliation keeps industry personnel from making honest criticisms of oxidizing agents (like bleach) are poor in the agency. Although FDA spokespersons have denied that retaliation electrons, and the reduced chemicals of exists,severalegregiousexampleshavepromptedseveralkey cellular metabolism (fatty acids, carbo- committee members to notify FDA Commissioner David kessler in hydrates and amino acids) are rich in elec- writing that any intimidation of committee witnesses would not be trons. We tap into the electron tug-of-war tolerated. Although the issue has not received much media attention, between oxidants and reductants to drive a November 1995 survey of health care business executives conducted our biochemical machinery, much like by Citizens for a Sound Economy (CSE) found that 46% of the 500 how a battery drives an electric motor. By executives surveyed believe that the FDA has retaliated against carefully transporting oxygen (safely companies that have criticised the FDA by “slowing down the approval bound to hemoglobin) to the cells where process or more closely scrutinizing the companies’ records and it can be combined with carbohydrate factories.” Almost two-thirds of the executives thought “the FDA has (acetate) under enzymatically controlled become more concerned with expanding its jurisdiction and power conditions, a host of electron-rich chemi- than with facilitating approval of new drugs and medical products.” cals essential to life can be generated The extent of FDA retaliation may never be fully appreciated due to (NADH, NADPH, FADH2, and ATP). the fundamentally subjective nature of the drug-approval process [see The fundamental antagonism between “The Efficacy Standard Reconsidered” in SDN v4n8p1]. However, the the oxidized atmosphere and reduced CSE survey did report that 4 of 10 companies stated that “they did not living systems makes control of oxidation pursue new product development because of FDA regulations and the (and oxidizing free radicals) essential. approval process.” The gasoline-air explosion in a car engine Citizens for a Sound Economy Foundation, Washington, DC, 202-783-3870. or a raging forest fire are graphic examples Special thanks to John Hammell, Political Coordinator for the Life Extension Foundation, of the power of oxidation in action. By for bringing this survey to our attention. comparison, the bio-oxidation of fats and 4 Smart Drug News [v4n10] 15 April 1996 Smart Drugs & carbohydrates is a severely constrained terol, triglycerides, and lipid peroxides. Down’s Syndrome: process. Even so, significant quantities of One company is even measuring oxidative oxidizing free radicals (several percent of damage to DNA. These assessments will Antioxidant the total energy flux) escape from bio- undoubtedly get much more sophisticated Intervention logical control. The antioxidant defense in the near future. in Down’s system is necessary to “mop up” these While quantitative assessment of Syndrome stray free radicals to maintain the reduced antioxidants measures the pieces and conditions necessary for life. parts of the antioxidant defense system, (continued from previous page) Loss of control of oxidation and free there is an oxidative stress test which radicals has been implicated in such measures the ability of living blood cells to diverse conditions as bruising, cataracts, resist an oxidative challenge. Although sunburn, radiation poisoning, cancer, this approach is relatively new, it promises heart disease, and sudden infant death to provide information about how well the syndrome. parts of the antioxidant defense system operate in concert. Antioxidant Assessment Although vitamin and trace-mineral “Loss of control of oxi- In the last decade, several new testing assessments will be discussed in more dation and free radicals technologies have been developed for detail in the next article, it is important to assessing antioxidant requirements. The mention that vitamins B2, B3, B6, B12 and has been implicated in use of these testing systems offers the folic acid, and the minerals copper, zinc, such diverse conditions potential of identifying both oxidative manganese, iron and selenium, play a vital as bruising, cataracts, stresses and antioxidant deficiencies. The role in the antioxidant defense system. most well established approach is direct Furthermore, heavy metals have a dele- sunburn, radiation quantitative measurement of antioxidants terious effect on antioxidant defenses poisoning, cancer, heart in blood. These might include vitamin C, which must be taken into account. All of disease, and sudden vitamin A, vitamin E (varied tocopherols), this will be discussed in the next issue. coenzyme Q10, b-carotene (and other Although these tests require consider- infant death syndrome.” carotenoids), glutathione, uric acid and able sophistication for interpretation, they bilirubin, Quantitative measurement of are powerful tools for identifying blood is currently expanding to include nutritional status and guiding antioxidant measurements of oxidants and oxidation intervention. by-products, like iron, lipoprotein choles-

GATT (and the World Trade Organization) vs Vitamin Supplements Although GATT and NAFTA were promoted as proposals will force the US to accept regulations free-trade agreements, they do far more than attempt to fundamentally identical to those proposed by the FDA lower trade barriers. In order to determine which laws are and repeatedly rejected by Congress. fair and which are anti-competitive trade barriers, there Congressional acceptance of the GATT agreement must be a “standard” with which to make a comparison. has made CODEX regulations binding on the US Many standards are currently being established by economy. In other words, Congress has already international committees set uyp by these agreements, and surrendered US sovereignty on this issue to the all countries are bound to conform — or else. Through the CODEX Commission. If the German CODEX proposal Wold Trade Organization (WTO), the “or else” can include is approved as it stands, US voters will have three sanctions and heavy fines, which continue until the tough options to consider: 1) vote every Senator and “problems” (local laws) are corrected (repealed). Representative out of office that voted for GATT (and Under the GATT/WTO agreement, the status of dietary see that their replacements repeal it), 2) accept supplements is under review by the Codex Alimentarious international criticism and financial penalties, or 3) Commission. In response to a proposal from the German accept decimation of the nutritional industry in delegation, the commission is now considering accordance with the wishes of some international international GATT/WTO standards that would: 1) prevent special interests. any supplements from being sold for preventive or Although free trade is the Washington buzz word therapeutic use, 2) prevent supplements from having about GATT, it appears that no country will be allowed potencies higher than amounts set by Codex, 3) prevent to have freer trade than that sanctioned by any country from developing alternative standards GATT/WTO. Since the US has the freest supplement regarding supplements, and 4) require all new dietary industry in the world, it appears that our freedom is to supplements to obtain some kind of Codex approval be sacrificed in the interests of “international before they could be marketed. In other words, the Codex harmony” and a “kinder, gentler” new world order. ¤

Smart Drug News [v4n10] 15 April 1996 5 Smart Drugs & Additional Metabolic Issues Antila E, Norberg U-R, Syvaoja E-L and Wetermarck T. Selenium therapy in Downs Syndrome (DS): a Down’s Syndrome: Part 3 of this series will continue in the theory and a clinical trial. In: Antioxidants in Antioxidant next issue with discussion of metabolic Therapy and Preventative Medicine, pp. 183-86, Plenum Press, New York, 1990. Intervention disturbances relating to methylation metabolism, collagen synthesis, trypto- Daumer-Haus C, Schuffenhaurer S, Walther JU, in Down’s Schipper RD, Porstmann T and Korenberg JR. phan metabolism and ammonia detoxifi- Tetrasomy 21 pter—>q22.1 and Down syndrome: Syndrome cation. molecular definition of the region. American Journal of Medical Genetics 53(4): 359-65, 1 (continued from previous page) References: December 1994. Anneren G and Edman B, Down syndrome—a gene Epstein CJ. Models for Downs syndrome: Chromo- dosage disease caused by trisomy of genes within a some 21-specific genes in mice. Prog Clin Biol Res small segment of the long arm of chromosome 21, 360: 215-32, 1990. exemplified by the study of effects from the MacLeod, K. Personal communication, Down’s Syn- superoxide type-1 (SOD-1) gene. AMPIS Suppl 40: drome Conference, Los Angeles, 24 February 1996. 71-9, 1993.

Question: I am renewing my subscrip- typically varies from 99% to 99.9% purity. tion one more time. I am very frustrated Get only the 99.9% purity. when I read your answers. To many of Some companies produce a GHB the questions require a doctorate in chem- version of cough syrup by dissolving istry in order to understand what it is all NaGHB in sugar water. Although this is about. Is it possible to simplify the an- frequently referred to as liquid GHB, it is swers so it is clear to us non-PhDs? EF not the same thing as free-acid GHB. GHB can be called γ-hydroxybutyrate, Answer: Thanks for renewing. I am γ-hydroxybutyric acid, sodium γ-hydroxy- sorry that answers are too technical or butyrate, 4-hydroxybutyric acid, 4-hy- “Too many of the obscure. I, for one, would be happy to droxybutyrate, and sodium 4-hydroxy- questions require a work harder to make them easier to butyrate. Hopefully, somebody will understand. I enjoy getting simple, basic eventually figure out that it is a bright idea doctorate in chemistry questions for the Q&A column. We get so to make potassium GHB (KGHB), or other in order to understand few, I give them a high priority. mineral salts of GHB (MgGHB or CaGHB). what they are about.” Can I suggest that when you are SWF reading the next issue of Smart Drug News Question: On page 96 of Smart Drugs & that you keep a pen and piece of paper Nutrients, there is a chart showing typical handy to write down questions as you are DHEA levels for men of various ages. The reading? I’d appreciate the help, and a lot chart is presented in ng/ml units. I have of other subscribers would probably recently received a lab report that stated thank you as well. SWF my level as 700 ug/dl (I am a 72-year-old male). Could you please convert this to Question: I contacted two of the non-US the units used in your chart. suppliers on your list for GHB. They both As page 2 of this fax, I am sending a had “sodium 4-HB” which, from the sug- chart of the same type which was sent to gested doses, is much weaker than the me by the Life Extension Foundation. The GHB I read about in Better Sex Through units are mcg/dl. Would you please give Chemistry. This makes their prices seem me the conversion factor to go from your “Would you please rather expensive. What different kinds/ chart to theirs so that I may compare the give me the conversion strengths of GHB are there, and do you two charts. RHG know who supplies “pure” GHB? (net) factor to go from Answer: The “ug” units are probably your chart to theirs Answer: Almost all the available GHB is micrograms (which should be abbreviated µ so that I may compare sodium GHB (NaGHB). The free acid is as g or mcg by convention). But I guess liquid, quite acidic, and somewhat un- ug looks enough like µg.... the DHEA charts.” stable; I don’t know anybody who sells it. There are 1000 ug in 1 mg, and 1000 mg It’s difficult to ship and would be much in 1 g. The “ng” units are nanograms. more likely to be discovered by Customs There are 1000 ng in 1 ug (mcg). So to when imported. convert nanograms (ng) to micrograms NaGHB and GHB are used inter- (ug), divide by 1000. To convert micro- changeably. NaGHB is about 18% sodium grams to nanograms, multiply by 1000. and 82% hydroxybutyrate. NaGHB The “dl” units are deciliters (one tenth 6 Smart Drug News [v4n10] 15 April 1996 Smart Drug News THE NEWSLETTER OF COGNITIVE ENHANCEMENT & LONGEVITY

Smart Drugs & Down’s Syndrome: Part 3 Smart Drug News ISSN 1060-8427 Nutritional Intervention in Down’s Syndrome Published 10 times annually by the by Steven Wm. Fowkes Cognitive Enhancement Research Institute The previous article of this series (Part 2) systemic depletion of serine reserves. P. O. Box 4029 discussed genetic overexpression and the Indeed, the vast majority of untreated Menlo Park, CA 94026. 415-321-CERI antioxidant disturbances associated with the Down’s individuals show serum serine levels (415-321-2374) superoxide dismutase (SOD) gene. This at the low end or below the low end of the Copyright © 1996 article will cover additional metabolic normal range. All rights reserved. disturbances, and nutritional interventions Serine is also used to fuel the folic acid Subscription $44/year targeted to ameliorate those disturbances. cycle (Figure 1, cycle B). The shortage of Canadian $46/year Overseas $55/year serine impairs the production of methyl Single issue $6 Methylation Pathways tetrahydrofolate (Me-THF), which is required Vol. 5, No. 1 Down’s syndrome individuals exhibit to recycle homocysteine to methionine (re- June 3, 1996 significant disturbances in methylation action 1). With an insufficiency of Me-THF, pathways (see Figure 1, page 2). The over- more homocysteine goes down the cystathi- Editor expression of cystathionine β-synthase onine pathway to be converted into cysteine Steven Wm. Fowkes (located on the 21st chromosome) causes instead of being recycled into methionine. Medical Editor homocysteine to be converted into cysteine This undercuts methylation metabolism. Ward Dean, M.D. (reaction 2) at an accelerated rate Methionine is required for the produc- Subscription Services [Chadefaux, 1985]. This conversion requires tion of S-adenosylmethionine (SAM), the J. R. Richards serine. One of the signs of increased “active methyl donor” that is a vital part of cystathionine β-synthase enzyme activity is a countless metabolic reactions throughout continued on next page Also In This Issue Smart Drug Update: The SAM Cycle page 2 Recent Developments with Deprenyl Flow Diagrams of by Ward Dean, M.D., and Steven Wm. Fowkes the SAM Cycle Over the last year, we have been inves- sive evaluation that is being prepared. We page 3 tigating several controversial matters con- had intended to incorporate personal com- New Practitioners cerning L-deprenyl (selegiline), one of which munications from the authors of the study in page 3 is creating a mini-controversy on the Inter- question, as well as from other prominent net. The question being discussed on the Parkinson/deprenyl researchers and clini- New Source Internet arose from last year’s publication of cians. However, because of the furor being page 4 a long-term study of Parkinson’s disease generated on the Internet, we believed that Parkinson’s Disease which evaluated three therapeutic regimens: this preliminary (and necessarily incom- Survival Data 1) L-dopa; 2) L-dopa plus deprenyl; and 3) plete) report should be made at this time. page 6 Parlodel (bromocriptine). The results of the study raised some serious concerns about Dopa/Deprenyl Send Us Your Old Deprenyl! Combination Therapy page 6 the use of deprenyl/dopa combination therapy for Parkinson’s disease, and some The focus of the controversy regards the A Death Window? have questioned the value of deprenyl alone long-term findings of the Parkinson’s page 7 for Parkinson’s disease and, of broader con- Disease Research Group (PDRG) of the Testing Services cern to many readers of Smart Drug News, United Kingdom [Lees et al., 1995]. The page 9 it’s use as a potential life-extending, anti- results of this study indicated that the aging and cognition-enhancing substance in combination of deprenyl plus L-dopa (also Q&A normal, healthy people. known as levodopa, or just dopa for short) page 10 Thisarticleshouldbeconsideredan resulted in a increased incidence of mortality interim report, pending a more comprehen- continued on page 6 Smart Drugs & the body. The under-activity of the folate and/or irritability when given 20 mg folic Down’s Syndrome: cycle coupled with overactivity of the cysta- acid (50 times the adult RDA). In a recent thionine pathway diverts the homocysteine version of MSB Plus compounded by Nutri- Nutritional from the SAM cycle (see Figure 2, page 3). In chem Pharmacy (which normally includes 45 Intervention other words, the almost-closed cycle is mg vitamin B6, 45 mcg B12, 1 mg folic acid, in Down’s opened and homocysteine drains into the 200 mg serine, 75 mg methionine and 75 mg Syndrome cysteine pool. cysteine), an increase of folate to 3 mg (7.5 Many parents have reported cognitive times RDA) and methionine to 275 mg (continued from previous page) and behavioral improvements after supple- (approximately the RDA) resulted in a mentation with methyl donors (DMAE, substantial number of children exhibiting choline, DMG and betaine) and methylation extreme irritability and hyperactivity catalysts (folic acid and vitamins B6 and B12). behaviors. The symptoms reversed in days “This experience should SAM itself has also been used to treat with discontinuation of the additional folate encourage moderation children with attention-deficit disorder. and methionine, but this experience should Although methylation pathways are encourage moderation when supplementing when supplementing usually deficient in Down’s syndrome, some methyl donors and methylation co-factors. methyl donors and degree of moderation is required not to It is not known whether the disturbances methylation co-factors.” overdrive the folic acid cycle (Figure 1, Cycle in serine, folate and methylation metabo- B). In Dr. Peters study of folic acid in Down’s lism are fundamentally due to cystathionine syndrome, approximately ten percent of the β-synthase overactivity or whether they may children exhibited excessive hyperactivity also be due to impaired digestion and mal-

Figure 1: One of the essential metabolic functions of the body is active methyl donation (cycle The SAM Cycle A). The active methylation donor is S-adenosylmethionine (SAM), which is produced from methionine by the addition of ATP (adenosine triphosphate). After the methyl group has been donated (reaction 3), homocysteine remains. Because homocysteine has pro-oxidant properties (elevated levels are associated with cardiovascular disease), it must be detoxified. Two separate mechanisms exist — both of which are serine dependent. In the Methyl Acceptor first (reaction 1), homocysteine is re-methylated by methyltetrahydrofolate (Me-THF, or “activated” folic acid) back to methionine, and Methyl S-Adenosylmethionine ATP the SAM cycle is closed. Under most circum- Donation (SAM) stances, this should be the dominant pathway. In the second mechanism (reaction 2), homo- 3 cysteine is combined with serine to form Methionine cystathionine which is split back apart (slightly differently) THF Serine to yield cysteine and S-Adenosylhomocysteine AA homoserine. (SAH) (reversible) B12 B6 This reaction BB depends on 1 Glycine the enzyme cystathionine Homocysteine NADH β Adenosine Me-THF (irreversible) -synthase 2 which opens up the SAM cycle and Serine results in loss of methionine (and accumulation Sulfite B6 of cysteine). Cystathionine The restoration of the SAM cycle is not solely 4 Molybdenum dependent on increasing serine levels. The B6 folate cycle (cycle B) is essential to close the Cysteine SAM cycle and keep methionine available for Sulfate producing SAM. The folate cycle not only requires folic acid, but also vitamins B6 and B12,andNADH(avitamin a-Ketobutyrate Homoserine B3-containing reducing agent). NADH is now available as a dietary supplement in the US.

2 Smart Drug News [v5n1] 3 June 1996 Smart Drugs & absorption of associated vitamins, minerals impaired by a host of conditions. For Down’s Syndrome: and amino acids. An experiment is being example, the hydroxylation of collagen is designed using trisomy-16 mice to investi- dependent on vitamin C, which also serves Nutritional gate the influence of digestive stimulation on as an antioxidant. Also, the final cross- Intervention metabolic imbalances that might give us linking of collagen depends on the enzyme in Down’s some clues. lysyl oxidase, which uses copper as a co- Syndrome factor. Copper is also a component of the Collagen Expression over-expressed superoxide dismutase. It is (continued from previous page) Collagen is a major constituent of con- not known to what degree collagen mis- nective tissue, skin, cartilage, tendon and metabolism may be due to induced bone. It comprises approximately 30% of all deficiencies (e.g., vitamin C), or the direct the protein in the human body. Collagen over-expression of the two collagen genes proteins are fibrous (linear, or branched) on the 21st chromosome. and they are responsible for the “toughness” These two mechanisms may not be easily “The collagen of tissues. Without collagen, tissue would separable. The competitive effects between connection to Down’s have the consistency of Jell-O. overactive and underactive collagen Collagen proteins have an unusual amino pathways may induce secondary proline or syndrome is fairly acid profile. They are 1) devoid of trypto- vitamin C deficiencies. In other words, the obvious. Newborn phan and cysteine, and 2) rich in glycine, overactive collagen pathways may squander infants and children lysine, proline, hydroxyproline and hydroxy- scarceresourcesleavingtheunderactive lysine. The latter two are rare amino acids. pathways starved for raw materials. exhibit extreme joint The collagen connection to Down’s syn- It is this latter observation that led Dixie laxity. In addition, drome is fairly obvious. Newborn infants Tafoya to try feeding the collagen pathways structural defects in and children exhibit extreme joint laxity. In as a nutritional intervention strategy for her addition, structural defects in the formation daughter. When she added vitamin C, bio- the formation of the of the heart affect roughly half of all Down’s flavonoids, α-ketoglutarate and proline, her heart affect roughly syndrome individuals. Of the dozen-plus daughter’s connective tissue and ligaments half of all Down’s collagen genes that have been discovered, improved markedly. This strategy appears two of them reside near the tip of the 21st to be universally successful. syndrome individuals.” chromosome. Collagen synthesis is extremely com- Tryptophan, Serotonin, Melatonin plicated. Collagen is initially made as a Down’s syndrome individuals frequently preprocollagen, which is transported and show low serum tryptophan levels. Whether converted to procollagen, which is then this deficiency is primary (poor tryptophan hydroxylated, glycosylated, wound into a absorption) or secondary (increased trypto- helix and transported again, after which it is phan catabolism) is not known. Regardless clipped into collagen molecules, assembled of the cause, low tryptophan levels impair Figure 2: into collagen fibers, and cross-linked into protein synthesis (tryptophan is usually a Flow Diagrams final form. Each of these steps could be rate-limiting amino acid) and decrease serotonin levels (tryptophan is the precursor of the SAM Cycle to serotonin). Serotonin is the brain neuro- M transmitter that not only regulates emotional AM e th control and sleep quality, but helps influence S i o carbohydrate feeding behavior. People with M M n A e i

S th n low serotonin levels tend to have carbo-

e e e i e o Trisomy hydrate cravings. n H i o Metabolism n Serotonin is also the precursor for mela-

m

e e e e e e e Normal e o tonin, an important neurohormone that H c o Metabolism y plays a role in the synchronization of m ste 1 o ine circadian (daily) biorhythms, the regulation cy dietary of aspects of immune function, and protec- st 1 methioninmethioninee eine 2 tion from hydroxyl radicals (an especially dietary dangerous kind of free radical that can be methionine easily produced from hydrogen peroxide). 2 cysteine Although newborn infants produce mini- pool mal melatonin, production dramatically cysteine increases during the first two years of life. pool Melatonin peaks in early childhood, and begins a steep decline just before puberty. Smart Drug News [v5n1] 3 June 1996 3 Smart Drugs & Ammonia Detoxification clinically to increase the release of growth Down’s Syndrome: Ammonia is a byproduct of many meta- hormone. Typically, relatively large doses bolic reactions. When protein is burned for are required to produce this effect. How- Nutritional energy, ammonia is released (from the ever, there might be some degree of growth- Intervention amino part of amino acids). Ammonia is hormone effect from smaller doses in in Down’s absorbed by key molecules and transported children who are slower growing and/or Syndrome through the body to be dumped in urine in metabolically challenged in varying ways. the form of urea (an ammonia-rich chemi- More research will be needed to determine (continued from previous page) cal). whether this effect is significant in Down’s syndrome. Glutamine and Arginine One of the key ammonia-carrying molecules Testing and Customization in the brain is glutamine, an amino acid Although antioxidant disturbances, and which tends to accumulate in Down’s syn- serine and tryptophan deficiencies, are “Zinc deficiency may drome. Glutamine is made from glutamate almost universal concomitants of Down’s have serious manifes- (glutamic acid) by the addition of one am- syndrome, there are other metabolic monia molecule, and from α-ketoglutarate problems that commonly show up. Zinc tations in Down’s by the addition of two ammonia molecules. deficiency, for example, may have serious syndrome infants. Due to the general overabundance of am- manifestations in Down’s syndrome infants. α Zinc is not only a monia in Down’s syndrome, -ketoglutar- Zinc is not only a component of superoxide ate is the ideal precursor to supplement the dismutase, it is required for proper growth, component of SOD, it glutamate/glutamine pathways without healing and immune function. Perhaps is required for proper increasing the ammonia burden. more importantly, zinc is required to growth, healing and The primary urea-carrying molecule in produce insulin-like growth factor type 1 the body is the amino acid arginine. When (IGF-1), which is specifically deficient in immune function.” arginine reaches the kidneys, it is split into Down’s syndrome children after about one urea and ornithine by the enzyme arginase. year of age. Zinc supplementation has been Theureaisdumpedintheurineand shown to significantly increases IGF-1 levels ornithine is recycled to pick up more urea. in non-Down’s syndrome children. In an Due to the over-abundance of ammonia, earlier Down’s syndrome study, 15 of 22 ornithine is the preferred supplement to individuals receiving zinc sulfate increase urea-carrying capacity in Down’s experienced increased growth [Napolitano et syndrome. al., 1990]. This suggests that zinc deficiency Arginine and ornithine are also used may be a common problem in Down’s syndrome. Another problem that has been reported New Practitioners to be somewhat common is hypothyroidism, Randy V. Smith, M.D. 770-991-0933 which is usually treated with thyroid Smith Psychiatric Clinic; 1631 Phoenix Blvd., Suite 8; Atlanta, GA 30349 supplements. Although overexpression of Psychiatrist with focus on AAMI, Alzheimer’s disease, ADD, and SOD may be directly responsible for the associated affective or depressive components. diminished levels of rT3 [Lejeune, 1990], this hormone has minimal biological activity and Julian M. Whitaker, M.D. 714-851-1550 this mechanism cannot account for lowered Whitaker Wellness Institute T3 or T4. Some other nutritional factors may 4321 Birch Street, Suite 100; Newport Beach, CA 92660 directly influence thyroid hormone General practice and preventive medicine, with emphasis on nutrition, regulation. Iodine is necessary for the supplementation, hormone replacement and IV therapies, including EDTA chelation. The institute also offers week-long residence programs production of thyroxine (T4), and selenium (medical testing, treatment and education) for heart disease, diabetes, is a component of the enzyme that converts arthritis and other degenerative diseases. T4 into T3, the most potent and active form of thyroid hormone. Eric R. Braverman, M.D. 609-921-1842 Some doctors suggest that thyroid should PATH, 212 Commons Way, Building 2; Princeton, NJ 08540 be in the top half of the “normal” range for Dr. Braverman is the Director of Princeton Associates for Total Health best health, but many doctors unfamiliar and has expertise in “DHEA and all of the smart drugs and nutritional with hypothyroidism and Down’s syndrome therapies.” He is an instructor at New York University Medical School and has authored more than sixty medical research papers. PATH de-emphasize thyroid medications because services include: brain electrical activity mapping, cranial electrical of a widespread professional prejudice stimulation, ultrasound vascular screening, and computerized against supplementing thyroid when blood neurological and psychometric assessment. Fax: 609-921-6092. tests indicate that thyroid hormones are in the “low-normal” range. 4 Smart Drug News [v5n1] 3 June 1996 Smart Drugs & Nutritional Assessment in future articles. Down’s Syndrome: In the last decade, several new testing References technologies have been developed for Nutritional Anneren G and Edman B, Down syndrome—a gene assessing nutritional requirements. The use dosage disease caused by trisomy of genes within a Intervention of these testing systems offers the potential small segment of the long arm of chromosome 21, exem- of identifying the specific nutritional defi- plified by the study of effects from the superoxide type-1 in Down’s (SOD-1) gene. AMPIS Suppl 40: 71-9, 1993. ciencies of each individual — whether they Syndrome Antila E, Norberg U-R, Syvaoja E-L and Wetermarck T. have Down’s syndrome or not. Red-blood- Selenium therapy in Downs Syndrome (DS): a theory (continued from previous page) cell mineral analysis is good for determining and a clinical trial. In: Antioxidants in Therapy and nutritional trace mineral deficiencies (and Preventative Medicine, pp. 183-86, Plenum Press, New York, 1990. excesses) for less than $200. Hair mineral Chadefaux B, Rethor MO, Raoul O, Ceballos I, Poisson- analysis of trace minerals is also a valuable nier M, Gilgenkrantx S and Allard D. Cystathionine beta nutritional assessment, but it is especially synthase: Gene dosage effect in trisomy 21. Biochem “In the last decade, valuable for testing heavy metals (lead, Biophys Res Commun 128: 1-10, 1985. mercury, cadmium, bismuth, arsenic, etc.). Daumer-Haas C, Schuffenhauer S, Walther JU, Schipper several new testing RD, Porstmann T and Korenberg JR. Tetrasomy of 21 Although it may be more difficult to inter- pter—q22.1 and Down syndrome: molecular definition technologies have pret, it costs only about $50. of the region. Amer J Med Genetics Supplement 53(4): been developed for Two different kinds of antioxidant tests 359-65, 1 December 1994. are now available. An antioxidant profile Epstein CJ. Models for Downs syndrome: Chromo- assessing nutritional some 21-specific genes in mice. Prog Clin Biol Res 360: measures the levels of specific antioxidants 215-32, 1990. requirements.” (ascorbate, carotenoids, tocopherols, bili- Licastro F, Mocchegiani E, Zannotti M, Arena G and rubin, ubiquinone, urate, etc.) and oxidants Masi M. Zinc affects the metabolism of thyroid (iron, TIBC, ferritin, etc.). This is probably hormones in children with Down’s syndrome: normalization of thyroid stimulating hormone and of one of the most useful tests for nutritional reversal triiodothyronine plasmic levels by dietary zinc assessment in Down’s syndrome. The supplementation. International Journal of oxidant stress test measures the ability of Neuroscience 65(1-4): 259-68, Jul-Aug 1992. “Before zinc supplementation, plasmic levels of zinc and living cells to resist oxidative stress in an ex thymulin, a zinc dependent thymic hormone, were “Although all these tests vivo assay. The latter test is an exciting new significantly decreased in DS children. After four develop- ment. months of dietary supplementation with zinc sulphate, require considerble a normalization of plasma zinc, thymulin and TSH levels Organic acid testing measures the many was observed. Plasmic levels of rT3 significantly sophistication for chemicals that are found in urine. This test increased, and after zinc treatment no difference was may be one of the most useful tests for fine- detectable between DS children and normal children. meaningful interpreta- Clinical evaluation of the health status of DS children tion, they are powerful tuning a nutritional program. By quanti- showed that zinc supplementation decreased the fying the waste acids in urine, signs of over- incidence of infectious diseases and improved school tools for identifying active or underactive enzyme systems can be attendance.” identified. Murphy M, Insoft RM, Pike-Nobile L, Derbin KS, Epstein metabolic problems and LB. Overexpression of LFA-1 and ICAM-1 in Down guiding nutritional Although all these tests require con- syndrome thymus. Implications for abnormal thymo- siderable sophistication for meaningful cyte maturation. Journal of Immunology 150(12): (and pharmacological) interpretation, they are powerful tools for 5696-703, 15 June 1993. “Given our recent observation that DS thymuses overexpress mRNA for IFN-gamma intervention.” identifying metabolic problems and guiding and TNF...” TNF induces indoleamine-2,3-dioxygenase nutritional (and pharmacological) inter- (IDO), the peripheral enzyme which catabolizes vention. These tests are in no way limited to tryptophan in response to immune activation. individuals with Down’s syndrome. They Napolitano G, Palka G, Grimaldi S, Giuliani C, Laglia G, Calabreese G, Satta MA, Neri G and Monaco F. Growth can be used to identify nutritional defi- delay in Downs syndrome and zinc sulphate supple- ciencies in anybody and everybody. We will mentation. Amer J Med Genetics Supplement 7: 63, describe these testing systems in more detail 1990. Peters M. Personal communication, Down’s Syndrome Parent Conference, San Diego, 1995. Stabile A, Pesaresi MA, Stabile AM, Pastore M, Sopo SM, New Source Ricci R, Celestini E and Segni G. Immunodeficiency and International Nutrition, Inc. 1-800-899-3413 plasma zinc levels in children with Down’s syndrome: a long-term follow-up of oral zinc supplementation. 9510 Hallhurst Road, Baltimore, MD 21236. Clinical Immunology & Immunopathology 58(2): International Nutrition has recently introduced Nutrivene-D, a high 207-16, February 1991. “63.2% of DS children had quality nutritional formula designed for metabolic management of plasma Zn levels below 0.7 mcg/dl” “DS children Down’s syndrome. It has received an endorsement by Trisomy 21 showed significantly lower proliferative response to phytohemagglutinin” “A significant increase in DNA Research Inc. Nutrivene-D does not require a prescription. Interna- synthesis was obtained after oral administration of zinc tional Nutrition’s compounding pharmacists can add piracetam to the sulfate (20 mg/kg/day), for 2 months)” “The lumpho- formula with a doctor’s prescription. Additional compounding services cyte response to PHA appeared to be normal in all are available. Local phone: 410-581-8042. Fax: 410-581-8070. patients up to six months after the end of zinc supple- mentation and it became low in half of the patients 22 months after therapy.” Smart Drug News [v5n1] 3 June 1996 5 Questions & Not everybody gets identical antidepres- rupted when I’m engrossed in an editing job sant effect from tryptophan that they do from on my computer, which was related to me by Answers Prozac and other SSRIs. SWF my wife and co-workers. Such effects are (continued from previous page) quite subtle and I think that scientists would Report: This report is more anecdotal veri- have a degree of difficulty in quantifying the fication of what you already know, that effect so that they could measure and study deprenyl, piracetam and Hydergine exhibit it. Furthermore, I kind of doubt that this is synergy. The satisfactory level of the afore- the kind of personality changes that you are mentioned for me is: 1.25 mg deprenyl (sub- worried about. Compared to the kind of lingual, 2X daily), 1.25 mg Hydergine personality changes that might be experi- (sublingual, 2X daily), 266 mg piracetam enced with use of deprenyl, Prozac, Buspar, (oral, 3X daily), 250 mg choline (oral, 3X etc., piracetam isn’t in the same league. daily, with B5 as needed). The 266 mg doses In my opinion, children with Down’s syn- are an 800 mg piracetam tablet chopped into drome may show much bigger personality thirds. Very simply, much less is better. changes from the nutrient part of their Coffee is not recommended. DRH program than piracetam. Untreated, they “Will piracetam tend to be gregarious and beneficient. negatively affect my Question: Thanks for your e-mail message Treated, they tend to be like every other kid about Down’s syndrome. I suppose one of on the planet. Unfortunately, that can mean daughter’s lipid my questions which you will not be able to stubbornness, acting out, rebelion, disobedi- metabolism?” answer is whether or not piracetam would ence, and all the other behaviors that are the negatively affect my daughter’s lipid bane of parenthood. But that might also metabolism. KM include independence, curiosity, assertive- ness, intellect, self directedness, and other Answer: Piracetam does require a func- qualities for which parents hope dearly. The tional steroid hormone system (sex and good with the bad; it’s a mixed blessing. adrenals) for it to provide benefits, but I am At very high doses, piracetam can cause unaware of any effect of piracetam in overstimulation. But insomnia and fussiness altering steroid metabolism. I do not know are not so much personality changes as they of any effect of piracetam on triglycerides or are reactions. The symptoms reverse quick- cholesterol lipoproteins either. Personally, I ly with reduction of dose or discontinuation doubt that piracetam influences lipids in any of the piracetam. Personality can definitely gross, obvious way. The only subtle effects be altered by changes in serotonin or that I might speculate as being possible is dopamine levels, but piracetam has minimal prostaglandin production, which piracetam effects on those neurotransmitter systems. might possibly lessen. SWF Piracetam is more likely to influence general “Is there any particular level of attentiveness or verbal expression. I area in which you Question: How much cognitive improve- don’t necessarily think of those as person- ment have you personally experienced from ality issues. SWF think you have seen piracetam? Are there are any side-effects cognitive improvements (such as insomnia or personality changes) Question: Is there any particular area in from piracetam?” in children with Down’s syndrome? Mostly which you think you have seen cognitive I’m worried about a personality change for improvements from piracetam? KM the worse as my daughter Megan, despite her extensive disabilities, is a happy and Answer: Organizational skills, verbal and charming child. KM speech skills, memory, motor and coordina- tion abilities, and cognitive integration. In Answer: Improvements from piracetam can Down’s syndrome, the improvement seem to vary from subtle to dramatic. The degree of be quite similar, except that verbalization impairment seems to be the most significant and speech gains are conspicuous and variable. Those with severe impairment exceptional. SWF tend to get the more dramatic benefits and “normal, healthy” individuals tend to get Question: As a Smart Drug News subscriber more subtle benefits. This has been true for and Life Enhancement products purchaser, me. I hope you can respond to this inquiry. I I don’t think personality changes from e-mailed it to Will Block back in February, piracetam have been carefully researched. but received no response and on 3/18 I sent The only anecdote that I’ve heard is a reduc- the following message to you and also got no tion in my own irritability at being inter- response. The last message to you was Smart Drug News [v5n1] 3 June 1996 11 Editorial and extinct. Those that survived were relegated phosphorylation,whichmeansoxygen- Opinion: to minor anaerobic niches like bogs and driven attachment of phosphate to produce mid-ocean hydrothermal vents. ATP (adenosine triphosphate). Oxidative The Biological As reduced-carbon chemicals (methane, phosphorylation was as great an advance as Evolution of ethane, “natural” gas) became scarce, plants photosynthesis. It allowed the subsequent Energy Systems had to develop better carbon-scavenging development of all animal life forms, abilities. Eventually they were nearly including man. (continued from previous page) depleted and carbon dioxide became the The increased quantity and efficiency of only appreciable carbon source. Plants energy production allowed animals to be became quite efficient at absorbing it. The more active, to run faster, jump higher and “Oxidative modern atmosphere contains only about a heal faster than their predecessors. They phosphorylation was third of a percent CO2. Much of the carbon even had enough energy to “waste” on that is not buried in rock or dissolved in the maintaining an elevated body temperature, as great an advance ocean has been incorporated into living and warm blooded animals began to as photosynthesis. It structures. dominate the earth. allowed the subsequent The relative wealth of energy could also Adaptation to Crisis be devoted to increased neural processing of development of all As the atmosphere became increasingly information. Central nervous systems animal life forms, oxidized, living systems adapted. They became more complex and brains got bigger. including man.” developed antioxidants and ways of directly Ever increasing neural complexity has led to harnessing the oxidizing power of the consciousness, an emergent property of atmosphere to drive metabolic reactions. mind that has extended the anti-entropic Organisms developed ways of recycling nature of life into a new realm. antioxidants to better keep oxidizing free radicals under control. Scientific Myths to Live By One of these emerging life forms Through our understanding of the developed a way to use atmospheric oxygen underlying mechanisms of life, we are now for the direct production of chemical energy. able to more finely tune our minds to the Thisprocessisnowcalledrespiration business of living and surviving as (derived from “breathing” oxygen from the anti-entropic beings in an entropic universe. air). Technically, it’s referred to as oxidative

Question: I just received 400 mg piracetam doubt. The best method for establishing capsules from England yesterday. My cause and effect in a single individual is the daughter with Down’s syndrome is 2.5 A-B-A-B process. In other words, if adding years, 24.5 lbs and I will begin dosing at 30 something (A) causes an effect and mg/kg/day. That works out to about 3/4 of withdrawing it (B) causes the effect to go one capsule per day, which I will split it into away, and then adding it back (A) causes the 3 doses of 1/4 cap at a time. She has been on effect to return and withdrawing it again (B) Nutrivene for one week. Already her speech causes it to disappear again, then you can be and signing have improved significantly. relatively assured that the effect is caused by How do I know which improvements relate the intervention. Is this knowledge worth “How do I know which to Nutrivene and which to piracetam? What putting your daughter through the A-B-A-B improvements relate to do you think about attack doses for process? If not, then you may be forced to children? Do you think that piracetam accept the fact that you may never know for Nutrivene and which wouldbeanyhelptoa12-year-oldboy sure. to piracetam?” diagnosed with ADD? I took one cap myself Idonot recommend standard loading and didn’t notice much difference except I doses for children, especially when they was much faster and more coordinated on cannot effectively communicate their the keyboard. PS subjective internal state. But an escalating dose regimen that gradually ramps up the “What do you think Answer: When you make two changes at dose over time (i.e., 10 mg/kg, 20 mg/kg, 30 about attack doses of the same time, you can’t know which is mg/kg, 40 mg/kg — or 15 mg/kg, 25 mg/kg, responsible for any observed effect, or if it is 30 mg/kg, 35 mg/kg, 40 mg/kg, etc.) will piracetam for children?” the combination that is responsible. But if allow you to titrate the piracetam dose to you allow one intervention to stabilize your child’s needs and tolerance without before making the second, you can separate risking acute overstimulation. But now that the effects. But even then there is room for your daughter is already on 30 mg/kg, you 6 Smart Drug News [v5n3] 2 September 1996 Questions & could try increasing the dose to 35 or 40 disabilities. Nutritional deficiencies are also mg/kg and see if she does any better. If not, known to impair cognitive abilities, intellec- Answers then cut back to 30 mg/kg and try 20 or 25 tual development, non-verbal intelligence (continued from previous page) mg/kg at a later time. and academic performance. A hair mineral When I first tried piracetam, I started at 5 analysis, red blood cell mineral analysis, and mg/kg for a week, then increased to 10 a urine organic acid analysis costs about mg/kg and 15 mg/kg before I ran out. I $500. never noticed anything. The second time, I Piracetam is a subtle drug. It is not sub- got a much larger supply and started a jectively intrusive like amphetamine, Ritalin loading dose of 70 mg/kg. I got beneficial or caffeine. It is easy to seamlessly integrate effects the first day. After a week at 70 it into one’s “normal” reality and not notice mg/kg, it was starting to get to be too much. beneficial effects. Improved typing skills is After 9 days, I cut back to 50 mg/kg, and then probably only the tip of the iceberg. If you a few days later, to 35 mg/kg (my present take a higher dose for a longer period of regular daily dose). On special occasions time, I wonder if you or anybody else in your (TV appearances, oral presentations, etc.) I life would notice other benefits. My co- will up my dose to 50 mg/kg for the day. I workers here at CERI noticed that I was more know a few people who get good results interruptible when taking piracetam. I don’t “When would be a good with 15 and 20 mg/kg, and two large men think that I would have noticed that by age to start children who take close to 100 mg/kg (when they can myself. SWF afford it!). So you can see that there is a on piracetam?” broad range of potential doses to consider. Question: Hello Steve. Thanks for talking Piracetam might easily help a 12-year-old with Jacquelin from Homelink down in San boy with ADD. There may not be many Diego about our request for piracetam. She studies of piracetam in Down’s syndrome, was quite concerned about our giving it to a but there are plenty of piracetam studies of baby. Nice lady. attention deficit/hyperactivity syndromes. It We have looked on the Internet re is also true that the testing procedures used research papers on piracetam. The places to assess the nutritional status of Down’s that mentioned it didn’t come through on children are equally applicable to ADD, our network. Anyway, has CERI done an ADHD or NDA kids (not diagnosed with article on it before? We would like to know anything). Exposure to toxic heavy metals more about it. Also, has there been any (lead, cadmium, mercury, etc.) is a known thought with regards to other drugs similar risk factor for hyperactivity and learning to piracetam and what their affect might be to Down syndrome children? N New Sources Answer: Piracetam is one of the most Key Pharmacy & Home Health Care 1-800-878-1322 popular smart drugs. Annual international Puget Sound Drug Corp.; 23422 Pacific Highway South; Kent, WA 98032 sales exceed a billion dollars. We’ve covered They carry DHEA, natural estrogens, progesterone, testosterone, it extensively in the newsletter, and both piracetam, L-tryptophan and 5-hydroxytryptophan, and formulate on a smart-drug books contain chapters on dye- and preservative-free basis. They support natural and alternative piracetam. There are a half-dozen piracetam medical philosophies and carry a large selection of vitamins, minerals analogs that might be usable, but no and botanicals. Local phone: 206-878-3900. controlled testing in DS has been completed Tierra Marketing International (TMI) 1-800-736-6253 yet. Piracetam has the largest amount of 223 N. Guadalupe, Suite 285; Santa Fe, NM 87501 research, especially with children subjects. TMI is a world-wide source for original-formula, procaine-based Gerovital (GH3). They are the only US-based wholesale/retail supplier of Question: Have you heard anything as to true GH3 that we know. They also carry 5-hydroxy-L-tryptophan, NADH, when would be a good age to start children pregnenolone, and DHEA. Visa, MC, Amex accepted. Contact Tierra for on piracetam? As you know, ours is four prices, as well as details of their 1994 court victory defending GH3 months old and so far he acts quite normal against the FDA. Fax: 505-982-0698. E-mail: [email protected]. Web: and has even surpassed normal children. www.rt66.com/vitaman/. We are wondering whether we should wait Quality Health, Inc. Fax: 011-44-171-580-2043 until we notice problems, or, go ahead before 401 Langham House; 29-30 Margaret Street; London W1N 7LB, ENGLAND the crucial first six month brain cell building Quality Health offers most of the popular smart drugs, including time is over. Any thoughts? piracetam, hydergine, vasopressin and deprenyl (Jumex). They accept Visa and MasterCard and claim a 3-week delivery time. Faster delivery Answer: The brain does not stop building is available. Web: www.qhi.co.uk. in six months. It is a long gradual process Smart Drug News [v5n3] 2 September 1996 7 Questions & that continues through childhood. The tam to your child’s individual needs. SWF metabolic toxicity of untreated DS adversely Answers affects brain development to such an extent Report: Dear Steve: I spoke to you over 2 (continued from previous page) that by two years it is conspicuous. The months ago about my son who has Leigh’s nutrient part of the therapy controls that Disease, a mitochondrial disorder. Any- toxicity to a significant degree, but it is way, I took a month Family Leave to spend probably never too early to start. There are with my son and I am very very happy to a few reported cases where in utero nutrition report that he is doing wonderfully and/or piracetam therapy was started after A big ‘thank you’ for your help and infor- amniocentesis-based diagnosis of Down’s mation. Marc got the Pantox antioxidant syndrome. Although only a few cases, they profile and it was good that he did. appeared to be quite successful. Although most of his values were good (I We do not have much data on what have been giving him all those vitamins), the “I started him on piracetam specifically does to brain develop- carotenoids (α-carotene, β-carotene and additional supplements ment. The absence of adverse reports in lycopene) were practically zero. He was animals and humans does not indicate that under oxidative stress because of this. I right away and people there are no effects. Several anecdotal started him on additional supplements right have already noticed a reports suggest that piracetam may enhance away and people have already noticed a big big difference. The brain development, but we do not know for difference. As a matter of fact, the doctors sure. Treatment of infants with myoclonic now want all the kids with mitochondrial doctors now want all seizure disorders does not provide quality disorders to get the Pantox profile. Thank the kids with mito- information about piracetam’s effect in you again! JM chondrial disorders to healthy DS babies. It does not appear to offer any significant risks, and dozens of DS Comment from Internet: The ketogenic get the Pantox infants have been started on piracetam diet is a diet in which 80 to 90% of all antioxidant profile.” before three months of age (including calories are derived from fat instead of “Rosebud” Spurlock, the youngest daughter carbohydrates and proteins. This forces the of Beverly and Paul Spurlock). body to convert to a fat-burning pathway, In general, I recommend that you start the creating ketone bodies as a by-product. The nutrition formula first to establish tolerance, ketone bodies act as anti-convulsants; how is dosage and benefits before adding pirace- not known. The diet is used on children who tam. That way you can assess the added do not respond to usual drug therapy for effect of the piracetam independently of the seizure control. And the diet is terrible. effects of the nutrients and titrate the pirace- Poor little guy can’t have cookies, pancakes, bread, pasta, etc... LL Calendar of Upcoming Events Response: The factor that is responsible Sept Steven Fowkes, Dixie Tafoya & Dr. Paul Spurlock will be speaking for inducing the fat-burning pathways is 14 at a Down’s syndrome parent conference in Pittsburgh, Pennsyl- carbohydrate restriction, not fat consump- vania. Call Sandy Prince at 412-531-1733 for more information. tion per se. Diets high in protein, moderate Sept Steven Fowkes, Dixie Tafoya, Paul Spurlock and Julee Bramson in fat, and low in carbohydrate will also 28 will be speaking at a Down’s syndrome parent conference in induce ketosis. Huntsville, Utah (near Ogden). Call Janet Hoffman at 801-745- Carbohydrate restriction in children is 1339 or Julee Bramson at 801-472-8778 for registration info. not only unnatural for them (they usually Oct Steven Fowkes, Dixie Tafoya and Paul Spurlock will be speaking burn sugar fuels like gangbusters), but it may 12-13 at a Down’s syndrome parent conference in Windsor, Canada on have other systemic stresses as well. The the 12th and South Bend, Indiana on the 13th. Several members process by which individual cells differen- of the Trisomy 21 scientific advisory board will be joining them in tiate into specific functions appears to be South Bend. Call Tamera Ragan at 616-684-2349 for more associated with a decrease in cellular glucose information. utilization. In other words, the growth and Oct Steven Fowkes will be speaking about “Nutrition for Healthy Kids” maturation process is characterized by a shift 27 at Health 2000, an all-day fund-raising event in support of from carbohydrate metabolism to fat metab- California medical freedom sponsored by California Citizens for olism. The effect of carbohydrate restriction Health, Hiatt Rickeys, Palo Alto. Call Cathleen Springer 415-367- on children is largely unstudied. But then 6763 for additional information. again, the same can be said of carbohydrate 1996- The MindPOWER Adventure Series featuring speakers Ward Dean, restriction in adults. 1997 Michael Hutchison, Ray Sahelian and Win Wenger will be taking In pregnant women, the placenta place throughout 1996 and 1997 at locations across the country. produces hormones that increase maternal insulin resistance (decreasing maternal 8 Smart Drug News [v5n3] 2 September 1996 Questions & glucose utilization). This results in a major being scavenged by vitamin C, vitamin E, diversion of maternal blood glucose to the vitamin A, glutathione, and many other anti- Answers fetus which sustains it’s phenomenal growth oxidants. These antioxidants become (continued from previous page) rate. Fats are primarily used for structural oxidized when they detoxify free radicals, purposes (construction of membranes), not and it is the reducing power produced by the for energy. mitochondria which recycle them back to In adults, carbohydrate restriction diets their reduced (active) forms so that they can “Although it may may actually be preferred. Such diets tend to be used again and again. These antioxidants seem counter-intuitive, reduce insulin resistance (a major problem are depleted in Down’s syndrome. in middle-aged and older individuals) that Mitochondrial ATP (the major chemical high-carbohydrate diets turns on fat neogenesis (the conversion of energy-transfer molecule) is also responsible (even high-complex carbohydrate into fat) which makes people for powering the electrical potential of the carbohydrate diets) obese (despite eating a low-fat diet). nervous system. Is it possible that seizures Interestingly, the paleolithic diet (what our are more likely in a state of depleted ATP? promote fat accumu- ancestors supposedly ate) is low in But that’s another question, and this is long lation and obesity in carbohydrate,exceptduringthesummer enough already. I think I’d better stop here. anybody that does not and fall (exactly when we want to put on fat ;-) SWF for the coming winter season). Although it exercise sufficiently.” may be counter-intuitive, high-carbohydrate Question: I am a friend of Dixie’s and diets (even high-complex carbohydrate have a 3 year old with Down’s syndrome. I diets) promote fat accumulation and obesity am a premed student and spend a lot of time in anybody that does not exercise sufficient- researching this condition. ly. Carbohydrate-restriction causes weight In 1978, LeJeune found a 0.58 correla- loss without any need for exercise. tion between serum glutathione peroxidase There is another mechanism that may be levels and IQ in Down’s kids. I have done “Interestingly, responsible for the anti-epileptic properties Medline searches like a year ago looking for the paleolithic diet of ketogenic diets — increased production of glutathione peroxidase stimulants, and only ATP (the energy “currency” of the cell) and found aloe vera juice. A few days ago, I (what our ancestors reducing power (resistance to oxidation). found that melatonin doubled the gluta- supposedly ate) is More than 90% of the energy consumed by thione peroxidase levels in mice brains. low in carbohydrate, our cells is produced in tiny organelles called What do you think of that? Do you know mitochondria, which are like little blast fur- what neurotransmitters melatonin is except during the naces or mini-power plants. The efficiency involved in? We bought the slow release summer and fall of these mitochondria is dependent on many tablets. Any idea of its half life? KW (exactly when we want factors, nutritional and enzymatic. Nutri- tional factors include lipoic acid, NADH, Answer: Since melatonin in present in very to put on fat for the coenzyme Q, and carnitine, all of which are small amounts in childhood, I would be very coming winter season).” available in foods or supplements. One of careful about supplementing it. Melatonin is the most essential enzymatic factors is the made from serotonin, a brain neurotrans- function of the citric acid cycle, which can be mitter involved in sleep and emotional fed by carbohydrate fuels (glucose, acetate, control which is made from the essential etc.) or fat fuels (fatty acids, ketones, etc.). amino acid tryptophan. Both melatonin and Dependence on glucose alone may not allow tryptophan are deficient in Down’s syn- the citric acid cycle to function adequately. drome. I presume that serotonin is as well. The induction of ketosis provides an addi- I think that tryptophan supplementation is tional energy-fuel input into the citric acid probably safer, and then the body can make cycle which may compensate for impairment melatonin the way it is supposed to. In other of glucose utilization. With up-regulation of words, I think that it is premature to consider the citric acid cycle comes increased melatonin deficiency before correcting a “A few days ago, I mitochondrial efficiency, increased energy known tryptophan deficiency. found that melatonin production in the form of ATP, and increased Glutathione peroxidase production reducing power (NADH) for fighting oxida- requires selenium (four atoms per enzyme). doubled the glutathione tive stress. Selenium is often depleted under conditions peroxidase levels in The over-expression of superoxide dis- of high oxidative stress. Make sure you mice brains. What do mutase (SOD) in Down’s syndrome results in assess the status of this critical micronutrient. increased conversion of superoxide anion Glutathione (the substrate for glutathione you think of that?” radicals into hydrogen peroxide, a powerful peroxidase) also tends to be low in Down’s oxidizing agent. Hydrogen peroxide can individuals. Glutathione can be supple- form numerous free radicals which end up mented directly (both MSBplus and Smart Drug News [v5n3] 2 September 1996 9 Questions & Nutrivene have it). Although the precursor is probably also a good idea to read the labels (cysteine) and related N-acetylcysteine on other liquid pediatric medications (cough Answers (NAC) can increase glutathione production a syrups, antibiotics, etc.) and watch for (continued from previous page) little bit under some circumstances, these similar adverse reactions. SWF should probably not be supplemented in Down’s syndrome. Due to over-expression Question from Internet: I am new on line of cystathionine β-synthase, which is coded and have no idea what you are talking on the 21st chromosome, cysteine levels about when you say “visit the web site at tend to be well above normal. signature below.” What the heck are you Ray Sahelian and I discussed melatonin talking about? DK@AOL half-lives in “A Consumers Guide to Using Melatonin” [SDN v4n9p1]. If you or any other Answer: Your internet vendor (America parents of children with Down’s syndrome On Line) has a service that you can access try melatonin with them, please report your that will allow you to “surf the web” all over experiences to us. SWF the world. The web (short for the World Wide Web) is a collection of electronic docu- “I am new on line Question: Dixie Tafoya told me to contact ments in a specific format (HTML) that is and have no idea what you regarding the proper dosage of pirace- highly compact for efficient transport over tam for my 5-month-old daughter. I have phone lines. The files can exist anywhere in you are talking about finally received (after 2 months of trying) the world on any computer that is connected when you say visit 300 ml of piracetam liquid. There were no to the Internet. Once these HTML (hypertext your web site.” dosage instructions. She weighs about 12- markup language) files get to your computer, 15 lbs. Could you please recommend her your AOL software (or any other web- dosage. R browser program) will expand them to be presented to you on your screen with Answer: At the standard 12-15 mg of different size fonts and color pictures. piracetam per pound of body weight, her There are also “search engines” that are dosage calculates to be 144-225 mg per day, provided by various companies that allow or 50-75 mg three times per day. you to browse their indexes of web materi- The liquid piracetam must have the con- als. So if you search for “smart drugs,” they centration listed on the label. It would say will likely send you to us. some number of milligrams per milliliter Since I am not familiar with AOL’s inter- (mg/ml), or some such equivalent in the face, I cannot tell you how to access their labeling. Or it would state the total amount web browser. You will have to look it up in (weight) of piracetam in the entire bottle, your manual, or ask their on-line help. They which you could divide by 300 ml to get the are heavily promoting this service, so it Conversion Equations mg/ml figure. should be easy to find. The top formula in the margin is a general Every web site has an internet address (mgs to teaspoons) formula for converting a mg dosage into a code, called a URL (universal resource loca- teaspoon (tsp) equivalent. The Glaxo-brand tor). These codes begin with dosage in mg liquid piracetam sold in Mexico http:// = dosage in tsp mg ml (Nootropil) has a concentration of (which specifies the use of hypertext transfer ? x 5 20 mg/ml, which calculates (see protocol) and end with an internet location ml tsp the bottom equation) to a half-teaspoon daily like dose (one-sixth teaspoon three times per http://www.ceri.com 50 mg day) at a 50 mg dosage. In a small child, the The “www” means it is a world-wide-web = 1/2 tsp mg x ml volume of liquid piracetam may be so small site, “ceri” is our registered internet domain 20 ml 5 tsp as to require an eighth-teaspoon to measure name, and “com” means we are a commer- the dose sufficiently accurately. cial company (just like AOL.com refers to One last comment: liquid medications America On Line). There are many other sometimes contain antifungal preservatives categories that you might run into in a URL: (like methylparaben and/or propylparaben) “edu” means an educational organization, to protect the product from molding (espe- “org” refers to a non-profit organization, cially alcohol-free formulas). Some children “gov” means a governmental agency, “ca” do not tolerate these chemicals well. If your means Canada, “fl” means Florida, “net” daughter has a bad reaction to the liquid means internet service, etc.). The “.” piracetam, you might want to try piracetam (periods) separate all the items of the tablets or capsules at a later time before internet address from each other. abandoning piracetam therapy altogether. It URL codes can also have additional 10 Smart Drug News [v5n3] 2 September 1996 was thinking the personal-use issue might you might want to consider these issues care- come up since my work is part of the medical fully. If you are an “anonymous” practitioner care system. anon with no particular political visibility, then continued from previous page EuroCare has ceased business, and ALP is you may not. When I edited STOP the FDA: closing down. IAS, InHome and Era-Bond Save Your Health Freedom, I stopped prac- “Should I receive the (newly listed in this issue) carry GHB and ticing as a nutritional consultant, even shipment at my home tryptophan. Although InHome is on import though it was an unlicensed profession. I alert and IAS and Era-Bond are not (as far as figured that the book would give me political (since it is for personal I know), I don’t think that import alert really visibility with people who might be inclined use) or would my work makes that much difference regarding to want to hassle me. So far, nothing has (at a downtown Customs detentions. Both GHB and trypto- happened (other than some undercover sur- phan are politically hot (i.e., on the govern- veillance and possibly some phone tapping). physical rehabilitation ment’s “hit list”), so if you are unlucky Many of my smart-drug shipments have clinic) be better?” enough to have your shipment detained, come directly to my office. I have yet to your chances of a hassle are high regardless experience a single detention. SWF of which company ships it to you. Basically, it’s 99.44% politics and 0.56% content. SWF Down with Down’s? IAS has told me that they will not ship I have been reading your Smart Drug controlled drugs to states in which their use News newsletter with much intrest, as my is restricted. They will probably be adding granddaughter has Down syndrome. Per- GHB to their controlled-drug list soon. WD haps your newsletter should refer to Down “One of the things that One of the things that the FDA likes to do syndrome instead of Down’s syndrome, as the FDA likes to do is is jump to the conclusion that anything and this is the proper name for the syndrome. I everything being imported is intended for think it would add validity to your news- jump to the conclusion commercial use, regardless of whether or letter by using the proper name. LC that anything and not you have stated otherwise. This is part of Down’s syndrome is the proper name, everything being their standard detention form letter. If your with a capital D and a small s. Some people shipment is being delivered to a work are pushing to have the possessive dropped, imported is intended address, they might be more inclined to get but there is hardly a consensus on the for commercial use, stuck on that assumption. Maybe, maybe change. I’ve heard the arguments about the regardless of whether not. So much depends on the individual that inappropriateness of diseases being posses- you end up dealing with, and which side of sive, but I’m not impressed with the reason- or not you have the bed they got out of that morning. ing. Since Professor John Langden Down did stated otherwise.” As far as legal consequences are con- the seminal work in characterizing Down’s cerned, there are two ways to look at your syndrome, it was his “academic risks. In criminal court, there would be a contribution” or “intellectual property.” burden of proof placed on the prosecution to That makes it possessive. Therefore, it is establish that you were, in fact, using the both grammatically correct and traditional to imported items commercially (i.e., within call it Down’s syndrome. your professional practice with your clients). When we name something after some- You would be considered innocent until body as a memorial, we do not use the “Under administrative proven guilty. Since you are not using the posessive. For example, if somebody were law the burden of imported items for anything but your per- to breed a new variety of cherry whose tree sonal use, it would be near-to-impossible for trunk had horizontal striations which looked proof lies with you to a prosecutor to make any charges stick like hatchet chops, it would be appropriate establish that you were (solicitation of perjury would be the only to name it a George Washington cherry tree. not using the imported way). However, under administrative law But if one is referring to the actual mythical the burden of proof lies with you to establish tree that George Washington cut down, then items for commercial that you were not using the imported items it would have to be called George Washing- purposes. In other for commercial purposes. In other words, ton’s cherry tree. Chopping down a cherry words, you are you are considered guilty until you prove tree imparts possession, having a tree named yourself innocent. Medical licensure is part after one’s self does not. considered guilty until of administrative law. So the bottom line, for me, is whether or you prove yourself It is highly unlikely that personal use of not professor Down’s relationship to the innocent. Medical imported smart drugs would lead to a court syndrome is more possessive or more case under any circumstances, but it would honorarial — especially since the good licensure is part of depend on whether or not anybody had doctor is no longer with us. Since this administrative law.” something to gain by your demise. If you are evaluation is significantly subjective in important enough to be a special target, then nature, I accept both uses as valid. 8 Smart Drug News [v5n8] 21 April 1997 One reason I prefer Down’s syndrome is no change in the legal status of herbs. She that it mitigates the pejorative confusion with was quite emphatic that herbs were still legal down (the direction). Down has a negative in the over-the-counter market. continued from previous page connotation with earthiness, baseness, The herbs that were supposedly affected depression and purgatory, as opposed to include: bayberry, betel nut, boldo, up’s connotation of liveliness, inspiration, rhamnus, calamus, capsicum/cayenne morality and heaven. I think saying “he’s pepper, cascara, chaparral, coltsfoot, Down’s” or “I am Down’s” or “she is using comfrey, ephedra, eyebright, feverfew, “There’s a rumor on TNI for her Down’s” makes a subtle distinc- gelsemium, germander, ginkgo, goldenseal, the Internet that tion that diffuses some of this connotation. gotu cola, hawthorn, horsetail, kava kava, In situations where there is some ambi- lily of the valley, lobelia, poke root, psyllium Canada has banned guity about English, popular use usually seed, black radish seed, blood root, senna, DHEA and is in the establishes the convention. Of seven books squill, pau d’arco (taheebo), tea tree oil and process of reclassifying that I currently have on my desk that valerian. mention Down’s syndrome (including both a Although they may not yet be banned in all herbs as drugs regular and medical dictionary) not one Canada, these herbs are being targetted by in accordance with refers to it as “Down syndrome.” All seven new Codex regulations that are being formed pending Codex use Down’s syndrome exclusively. SWF under the auspices of the World Trade Organization, sanctioned by the NAFTA and regulations.” Codex in Canada? US next? GATT agreements. These “free trade” agree- There’sarumorontheInternetthat ments (see SDN v4n10p5) will classify herbs Canada has banned DHEA and is in the (and many nutrient-based dietary supple- process of reclassifying all herbs as drugs in ments) as drugs and force signatory nations accordance with pending Codex regula- (e.g., the US and Canada) to remove them tions. Is this true? (net) from the over-the-counter market. In this According to Internet reports, both items case, NAFTA and GATT have nothing to do Communicate your are already fact. with free trade and everything to do with thoughts and suggestions We were able to confirm that Canada has restraint of trade by vested interests (i.e., about Codex to: classified DHEA as an anabolic steroid and a pharmaceutical companies) who will profit Mr. Robert McMaster controlled substance. One Canadian phar- handsomely from decreased competition. Canadian Coalition for macist told us that it has even been banned Although the proposed Codex regulations Health Freedom from any prescription medical use. Another are not finalized, when they are, they will Suite 937 - 6021 Yonge Street source stated that DHEA remains available directly conflict with the US Constitution and North York, Ontario through “some compounding pharmacists.” existing health-freedom laws. The US Con- M2M 3W2 CANADA Two sources told us that DHEA is obtainable stitution reserves unenumerated powers to phone: 416-207-0887 by doctor’s prescription through the govern- the individual States and people (the Ninth fax: 416-207-0727 ment’s Emergency Drug Release Program in and Tenth Amendments), and Federal law email: [email protected] Ottawa—if you’ve got the stamina to fill out currently prohibits the FDA from removing all the requisite paperwork and the time to herbs and nutrients from the over-the- Dr. Mary Cheney waste waiting for approval! counter market for reasons other than public (Canadian Codex Delegate) Verifying the herbal matter turned out not health, and then only with specified rule- Nutrition Evaluation Division to be so easy. According to Keith Stelling, a making procedures (i.e., public hearings, Food Directorate member of the Board of Directors of the open testimony, public comment, published Health Protection Branch Ontario Herbalists Association, Canada now proceedings, etc.). Whether these inter- Tunney’s Pasture classifies therapeutic herbs as drugs. He was national agreements (NAFTA and GATT) will (Postal Locator: 2203A) quoted as saying, “Effective 1 January 1997, prevail, or the US Constitution and law will Ottawa, Ontario K1A 0L2 most herbalists and many naturopaths, prevail, nobody knows. But given the power CANADA health food store proprietors and their staff, and influence that was exercised by well- phone: 613-957-0352 importers, growers and even restaurant placed special interests to 1) misrepresent fax: 613-941-6636 owners are now liable to conviction for drug the NAFTA and GATT agreements to the Dr. Elizabeth Yetley trafficking [italics ours]. In a sudden about- public, and 2) jam NAFTA and GATT through (US Codex Delegate) turn in policy, the [Health Protection Branch] Congress with minimal debate in the face of Special Nutritionals, HFS-45 has reclassified a whole list of traditional serious questions, I am deeply concerned. Food & Drug Administration herbal medicines as drugs because they have I believe that the only workable solution 200 “C” Street S.W. a pharmacological effect.” However, accor- to the Codex problem is for the US to Washington, DC 20204 ding to Micheline Ho, the only representative abandon its involvement in the “new world phone: 202-205-4168 of the Health Protection Branch that seemed order” and repeal NAFTA and GATT. These fax: 202-205-5295 to know anything about herbs or govern- international agreements do not include any ment regulations about herbs, there has been guarantees of personal freedom or human Smart Drug News [v5n8] 21 April 1997 9 rights. They are designed only to further the disorders. Despite this hypothetical caution, economic interests of their sponsors. The US piracetam has not been found to exhibit any Constitution and Bill of Rights are an incon- significant excitotoxic activity, and is continued from previous page venient impediment to their plans. clinically used to decrease seizure incidence. The economic interests being served by We discussed some of these issues in a “The economic interests Codex are clearly those of the multinational previous answer, which is posted on our drug and chemical corporations. These DS-only web site: http://www.win.net/ceri. being served by Codex companies will profit from 1) removal of There are significant disagreements are clearly those of the local government-imposed trade barriers about what mechanisms underly seizure dis- multinational drug and (the free-trade side of NAFTA and GATT), orders. One of them has to do with deficient and 2) establishment of international trade energy (ATP) production at the cellular level chemical corporations.” barriers (anti-competitive regulations) by mitochondria (tiny energy powerplants against non-patentable, generic health within cells). ATP energy from mitochondria technologies (the restraint-of-trade side of is required to pump ions across nerve cell NAFTA and GATT). While consumers may membranes. Sodium, potassium and calcium be likely to benefit from removal of local flow across these membranse when they fire trade barriers, they are going to pay dearly electrically. Excitotoxins cause extra calcium for loss of affordable, over-the-counter to flow into the cells. This burdens the ion- nutrients and herbs. Only the international pumping system and drains ATP energy pharmaceutical companies will profit hand- reserves. The possible involvement of this “I find it telling that the somely from both. It shouldn’t come as a mechanism is supported by the efficacy of new governing bodies surprise that Codex delegates are primarily ketogenic diets which not only induce fat- pharmaceutical company representatives burning enzymes in the mitochondria but of the new world order and governmental regulators of the pharma- also control seizures. Furthermore, genetic are unaccountable ceutical industries. mitochondrial disorders and syndromes are to either voters I find it telling that the new governing often associated with seizure activity. SWF bodies of the new world order are unac- or consumers.” countable to either voters or consumers. It’s Down’s Syndrome Surgery a neatly efficient piece of work, indeed. SWF and Nutritional Therapy (TNI) Iamapediatriciancaringfora Piracetam and Seizures? 3-months-old boy who may soon be starting Are there any precautions that should be targeted nutritional therapy for Down’s taken in administering piracetam to a child syndrome. He is currently taking digoxin with seizures? TR and hydrochlorothiazide. He also may be One should watch closely when giving undergoing heart surgery with its attendant anything to a child with seizures! This may anesthesia etc. in the next few months. I was include piracetam, although there are no wondering if there is any information “Are there any precau- special contraindications with piracetam and available about potential drug interactions tions that should be seizures. In fact, piracetam is considered a between these compounds. DZ treatment of choice for myoclonic seizures in Nutritional therapy is intended to normal- taken in administering many parts of the world. In clinical tests, ize biological functions which are disturbed piracetam to a child piracetam was found not to interfere with by the overexpression of genes on the extra with seizures?” any of the anti-epileptic medications tested, 21st chromosome. There may be many yet it was effective in ameliorating the functions normalized that we do not even cognitive dysfunction side effects of the know were disturbed, including effects on medications. This was reviewed in Smart blood clotting (which is sensitive to oxidative Drugs II (page 110). stress), vascular diameter (which is influ- I think that the concerns being expressed enced by prostaglandins), healing rate about piracetam and seizures is based on (which we know is influenced by zinc and theoretical issues that have no basis in vitamin A), and susceptibility to anesthesia clinical data. Since piracetam has been (which may be influenced by higher-than- reported to increase cellular calcium influx normal levels of nitric oxide). I do know that in tissue culture (an effect which is common DS children are more easily anesthesized to excitotoxins like glutamate (MSG), than non-DS children and that most anes- aspartate, pyroglutamate, and aspartame thesiologists are generally unaware of this (NutraSweet) and glutamine), and excito- problem (one DS child in southern California toxins can aggravate seizure disorders, died from minor elective surgery last year). somebody has reasoned that piracetam In my opinion, the biggest concern is the should not be given to people with seizure risk from the surgery itself, which is 10 Smart Drug News [v5n8] 21 April 1997 aggravated by the chronic oxidative stress of piracetam? OTP untreated DS and ameliorated by nutrient- The ice cube method will work great. To and-antioxidant therapy. More than two get 600 mg (3/4 of a capsule), dissolve 3 continued from previous page decades ago, pre-operative use of vitamin E capsules of piracetam into approximately 2 was shown to decrease surgical mortality in ounces of water and pour into 4 wells of a adults. I think this applies in spades to DS plactic ice cube tray. Take care to fill each individuals who may have abnormally low well to the same level (use a dropper to levels of vitamin E, vitamin A, glutathione, redistribute liquid from overfilled wells to selenium, zinc, and/or S-adenosylmethio- underfilled wells). Freeze. Each ice cube nine. Although you did not specifically will have 600 mg of piracetam. If you want a mention piracetam, it has a marked ability to 500 mg dose (5/8ths of a capsule), you can “Although you did not mitigate hypoxia. This provides a mechan- use 5 capsules to make 8 ice cubes. If you specifically mention istic justification for it’s use prior to surgery want a 700 mg dosage (7/8ths of a capsule), (to compensate for reduced blood oxygena- use 7 capsules to make 8 cubes. The exact piracetam, it has a tion due to blood flow between sides of the amount of water is not critical. It should be marked ability to heart) and during surgery (to diminish enough to dissolve the piracetam but not so mitigate hypoxia. This possible brain damage from ischemic much as to overfill the requisite number of complications from the surgery). ice cube wells. provides a mechanistic The lack of statistical data make any If you are using tablets, there will be a justification for it’s use decision to start, continue or stop TNI residual powder in the water that will not prior to surgery (to therapy in the face of specific conditions or dissolve (i.e., it will be milky white instead of complications problematic. However, clear). This cloudiness in the solution is compensate for reduced biochemically speaking, ceasing therapy has from the binders in the tablets, not undis- blood oxygenation) no specific theoretical justification. solved piracetam. You can ignore it. and during surgery As with any drug treatment of a condition, For measuring much smaller dosages, use one should be ready to lower the dosage of the same process. Just use fewer capsules or (to diminish ischemic medication or cease it altogether when one tablets and more water. If you want to complications).” addresses the biochemical causes of the measure 133 mg doses (approximately 1/6th condition. In other words, the use of drugs of a capsule) dissolve 1 capsule in water and is usually compensatory, and when the con- fill 6 ice cube wells. If you want to measure dition requiring compensation is eliminated, 25 mg doses (1/32nd of a capsule), dissolve so is the need for the drug. SWF 1 capsule and make 32 ice cubes. If the milligram dose does not come out Titrating GHB Dosage? to an even fraction of a capsule, use more I plan on purchasing GHB in the pow- than 1 capsule at a time (as we did in the first dered form. In order to titrate the dosage, I example) or leave the last ice cube only would like to know if it is soluble in water or partially filled. In other words, if the desired alcohol? SB dosage comes out to 3.5 doses per capsule, GHB is very soluble in water and some- you can either fill three cube wells to full and “I am puzzled by the what soluble in alcohol. This makes water a fourth to halfway, or use 2 capsules to make recent touting of dietary the ideal vehicle for dosing and alcohol a 7 cubes. SWF good solvent for recrystalization. The thing 5-hydroxytryptophan you have to be careful about with water is 5-HTP and Carbohydrate as an alternative that GHB solutions are a growth media for I am puzzled by the recent touting of to typtophan.” fungi and bacteria. It helps if you can keep dietary 5-hydroxytryptophan (5-HTP) as an the concentration of GHB as high as alternative to typtophan, with no apparent possible, or only mix what you are going to mention of the Wurtman’s Rule requiring a use in a short period of time. Another high-carbohydrate meal. Is this simply approach is to freeze the GHB solution to because the carbohydrate meal is required prevent the growth of microorganisms. If for typtophan transport across the you dilute 10 grams of GHB in a pint of water blood-brain barrier, but not 5-HTP? PVS and fill two trays of ice cubs (20 cubes), then Tryptophan and 5-HTP use the same “I have 800 mg capsules each frozen ice cube will contain 500 mg of amino acid transport enzyme to get through of piracetam. How can GHB. It’s very convenient. SWF the blood-brain barrier. Transport of both are inhibited by competing large, neutral I accurately measure Splitting Piracetam Capsules? amino acids. High-carbohydrate meals a 600 mg dose?” I have 800 mg capsules of piracetam lower competing amino acids and therefore from a compounding pharmacy. How can I enhance both tryptophan and 5-HTP trans- accurately measure a 600 mg dose of port into the brain. The carbohydrate- Smart Drug News [v5n8] 21 April 1997 11 The Newsletter of Cognitive Enhancement, Health and Longevity

Smart Drug Update: Smart Drug News ISSN 1060-8427 The Case for Piracetam in Down's Syndrome Published 10 times annually by the by Steven Wm. Fowkes Cognitive Enhancement Research Institute One of the current focal points for the that political and ideological considerations P. O. Box 4029 Menlo Park, CA 94026. emergence of smart drugs into popular con- are the sole basis of these anti-piracetam 415-321-CERI sciousness and mainstream use is the appli- policy positions. Indeed, the increasing use Copyright © 1997 cation of piracetam to Down’s syndrome of piracetam and targetted nutritional inter- All rights reserved. (DS). This application has generated lots of vention (TNI) is putting these matters to the Subscription $44/year Canadian $46/year controversy within DS circles for several test. This article will specifically focus on the Overseas $55/year reasons: 1) piracetam is not FDA approved, use of piracetam in DS-related conditions Single issue $6 2) US physicians are generally unfamiliar [see v2n10, v3n4, v4n10, v5n1 for previous Vol. 5, No. 965 with its use, and 3) major establishment DS articles]. DecemberJanuaryJune 4, 13, 199713, 1997 1996 organizations have a policy that DS is A Brief History Editor fundamentally untreatable. Steven Wm. Fowkes US physicians and scientists associated Piracetam’s earliest use in Down’s syn- Medical Editor with these DS organizations are actively drome (DS) was in Spain and Portugal in Ward Dean, M.D. discouraging piracetam’s use. Allegations of 1974 in a comparative study (using historic Assistant Editor elevated seizure risks and possible long-term case controls) of Dromia (a 5-hydroxytrypto- Anne Fowkes side effects from piractam are being made. phan-containing product) and Noostan (a Subscription Services However, the complete lack of such effects brand of piracetam) in 26 children from age J. R. Richards during more than two decades of worldwide 3 months to 12 years of age [Fialmo, 1976]. clinical experience with piracetam suggest This study was obscurely published, not continued at top of next page The adaptogen article on Eleuthero- Book Review: coccus senticosus, by Gavin Lee, was still being peer reviewed at deadline. It will appear next issue. Brain Longevity Also In This Issue review by Anne M. Fowkes Figure 1: Brain Longevity: The Breakthrough Medical messages of allopathic disinterest and insti- The Fiona Study Program that Improves Your Mind and tutional complacency, and to reclaim the page 2 Memory, by Dharma Singh Khalsa, M.D. mystic “old age” which meant wisdom and Senility Prescription Practices with Cameron Stauth (ISBN: 0-446-52067-5). power rather than an inexorable slide into page 4 I see Brain Longevity as a quintessential the pre-death death of will and conscious- Piracetam and book of the 90s. It blends many disparate ness. Sickle Cell Anemia elements of our current culture, such as The evil genie in this story is cortisol, the page 6 Eastern and Western medical traditions, into product of a primitive stress response run a program that is somewhat mysterious yet amoc. Cortisol and adrenaline (also called Q&A Rumors About GHB 8 eminently practical. It is touched by the wis- norepinephrine) are major adrenal hor- GHB in Italy 9 dom of the ages, sculpted with double-blind mones of the fight-or-flight syndrome, which Stable Vitamin C in Water? 9 placebo-controlled studies, and tempered by evolvedtoallowustoescapedanger. KGHB vs NaGHB? 10 Dr. Khalsa’s own clinical experience. Ordinarily, surges of cortisol are followed by Are GHB Kits going to be Legal? 10 It is in some ways a romance — a tale of periods of calmness, during which we can Dupuytren’s Contractures 11 a maverick young doctor scouring many recover. However, the chronic stress of our Letter to Customs paths to find the answers to questions that current lives keeps us constantly in an page 9 were raised during his work as an anesthe- activated state, in which cortisol is spewed New Sources siologist, questions about why the stress out in quantities our bodies were never page 10 surrounding surgery seemed to take a heavy designed to handle. New Practitioner toll on patients’ cognitive abilities. His dis- Dr. Khalsa presents a compelling picture page 11 course is often couched in seduction, luring of just what all that unabated cortisol does to the reader to join the quest, to lay aside the continued at bottom of back cover Smart Drug Update: indexed in any computer database, and In 1995, Dr. Fialmo’s study of Dromia and The Case for remained largely unknown in the US. piracetam was rediscovered in the US. It In the early 90s, Dixie Tafoya, the mother showed universal benefits in motor develop- Piracetam in of a child with DS, read Smart Drugs & ment, mental development, speech, affec- Down’s Syndrome Nutrients and realized that piracetam’s bene- tivesocial (emotional) development, scholas- ficial effects on various learning disabilities tic achievement, and EEG changes indicating (continued from previous page) might address some of her daughter’s devel- improved hemispheric synchronization (see opmental problems [see SDN v3n4]. Pirace- Figure 1). The gains in speech were especi- tam’s almost complete lack of toxicity ally dramatic. [Reynolds, 1996; Dukes, 1996] coupled with its ability to 1) enhance the higher (telen- Toxicity and Pharmacology “Gains in speech were cephalic) functions of the brain, 2) enhance One of piracetam’s most unique and especially dramatic.” interhemispheric communication through conspicuous features is its extremely low the corpus calosum, 3) enhance memory and toxicity. The classical measure of drug learning in both animals and humans, and toxicity, the LD50 (the dose causing death for 4) prevent memory loss and learning diffi- 50% of test animals), is not applicable; culties induced by drugs, stress and trauma standard dosing methods (oral, intravenous [reviewed by Vernon and Sorkin, 1991] made injection, intraperitoneal injection) cannot it seem an ideal prospect for DS therapy. Her deliver enough piracetam to kill laboratory daughter responded dramatically, and animals. Doses of greater than 20 g/day have piracetam use has been spreading through been given to people suffering from myo- the DS community ever since. clonic seizure disorders, without serious side

Figure 1: The Fiona study compared two groups of 26 children between the ages of 3 months and The Fiona Study 12 years. The first group received only Dromia (5-hydroxytryptophan plus “pyriglutine”) during a two year period between 1972 and 1974. The second group received Dromia plus Piracetam and Noostan (a brand of piracetam) for a two year period between 1974 and 1976. There was 5-hydroxytryptophan no no-treatment group, presumably because the Dromia-only therapy (described as “very in the treatment of encouraging” and a “considerable success”) was Down’s syndrome. Evaluation of Improvement considered a standard of care by the clinical team. (number of patients showing indicated improvement) The Dromia was administered at 1 mg/kg/day for 24681013162024 periods of 3 months, with breaks between periods. Dromia The Noostan was administered at 30 mg/kg/day on a Motor only continuous basis. Development Dromia plus Noostan 50% Improvement in all subjects was evaluated as modest (light gray), marked (medium gray), Dromia Mental only or dramatic (dark gray) in each of 6 categories. Scholastic evaluation was possible only in the Development Dromia plus 35% Noostan 12 patients older than 5 years of age. Net Improvement was calculated by Dromia only scoring 1 for modest, 2 for marked and 3 for Speech Dromia plus 142% dramatic improvement, subtracting the Noostan Dromia-only total from the Dromia-plus- Dromia Noostan total in each category, and then Affective-Social only dividing by the number of subjects. A Net Development Dromia plus Improvement score of 100% is equivalent to Noostan 92% all children advancing to the next better evaluation (i.e., from modest to marked, or Dromia only 12 of 26 patients Scholastic only were in the 5-12 year marked to dramatic). The Speech Net Improve- Achievement Dromia plus age range suitable for Noostan scholastic evaluation 67% ment score of 142% indicates the equivalent of 100% jumping one level of improvement plus Dromia 42% jumping two levels. only A positive Net Improvement score does EEG Dromia plus Noostan 58% not imply that all children achieved that positive improvement. It means that children Evaluation Key with less-than-indicated improvement would Modest improvement Marked improvement Net Improvement be balanced by children with greater-than- Dramatic improvement (patients achieving equivalent indicated improvement. SWF of next higher evaluation) 2 Smart Drug News [v5n9] 4 June 1997 Smart Drug Update: effects [Karacostas et al., 1993]. The recom- deficit, depression, gait ataxia (incoordina- The Case for mended dose of piracetam for infants with tion), and convulsions, but not to dysarthria myoclonic seizures is 10-20 g/day (approxi- (articulation difficulty). This latter finding is Piracetam in mately 1-2 rounded tablespoons), a phenom- somewhat paradoxical, given that enhance- Down’s Syndrome enally high dose by normal drug standards. ment of speech and language skills is Piracetam is absorbed rapidly and generally the rule rather than the exception. (continued from previous page) completely following oral intake, and it is Therewasalso“nopositivecorrelation excreted predominantly unchanged in the between clinical and electrophysiological “One of piracetam’s urine. Peak plasma levels are reached in less [EEG] improvement,” suggesting that pirace- most unique and than an hour. However, brain concentra- tam works through a different mechanism tions rise more slowly. It may take days for than standard anticonvulsant drugs. conspicuous features piracetam to reach peak levels in the brain, In an earlier study, myoclonic patients is its extremely and days for it to fall after discontinuation. with positive clinical responses to piracetam low toxicity.” Additional information about piracetam can (2.4 to 16.8 g/day) were studied in a placebo- be obtained by reading the Smart Drug controlled, double-blind, two-week, cross- Update on piracetam [see SDN v1n10] and the over trial. Of 21 patients with “disabling piracetam chapters in Smart Drugs & spontaneous, reflex or action myoclonus Nutrients and Smart Drugs II. due to various causes,” 10 had to be rescued from the placebo phase of the study due to Piracetam and Seizures severe exacerbations of their myoclonus “Of 21 patients with Allegations of increased seizure risk from [Brown et al., 1993]. No patients required disabling myoclonus piracetam have been made by a few US rescuing from the piracetam arm. Piracetam physicians associated with establishment DS improved motor function scores, writing due to various causes, organizations. This is of special concern due ability, functional disability scores, global 10 had to be rescued to a higher-than-normal incidence of assessment scores, and visual tests. The from the placebo phase seizures in DS individuals. The basis of these authors concluded, “Piracetam, usually in allegations of seizure risk is enhanced combinationwithotherantimyoclonic of the study due to cellular calcium influx from piracetam, an in drugs, is a useful treatment for myoclonus of severe exacerbations vitro (test-tube) finding whose applicability cortical origin.” of their myoclonus.” to real life must be seriously questioned in The dose of piracetam may be quite large the face of decades of clinical experience to in some circumstances and still be well toler- the contrary [see SDN v5n8p10]. In fact, ated. In one case of accidental electrocution, piracetam has mild anti-seizure activity, and spastic tetraparesis (limb paralysis) and it protects against memory and cognitive spontaneous myoclonus (muscle twitching) deficits caused by seizures. in both arms were successfully controlled by Piracetam is used as an adjunctive 24 g/day piracetam, administered intra- therapy for epilepsy. Although its effects on venously [Karacostas et al., 1993]. The epilepsy are not considered sufficiently sub- myoclonic movements returned three days “Piracetam is stantive when used alone, piracetam does after the piracetam was discontinued six recognized throughout potentiate the antiepileptic activity of other weeks into therapy, and were almost drugs. Some newer “racetam” analog drugs abolished when the piracetam was resumed. most of the world as appear to have stronger anticonvulsant A review of the treatment of myoclonus a treatment of choice activity. with piracetam covering “62 case reports, 3 for myoclonus, a Piracetam is recognized throughout most open trials and 2 double-blind trials, of the world as a treatment of choice for covering 171 patients” has been published seizure-like condition myoclonus, a seizure-like condition charac- [Van Vleymen and Van Zandijcke, 1996]. A characterized by terized by uncontrolled muscle twitching or clinical review of the symptoms and diag- uncontrolled muscle jerking. This application of piracetam has nosis of myoclonus, progressive myoclonus been thoroughly researched from a clinical epilepsy and other epilepsies, and the use of twitching or jerking.” perspective. Piracetam has orphan drug piracetam and 5-hydroxytryptophan in status in the US for treatment of myoclonus. recent clinical trials, has also been published In a recent study of 60 patients, piracetam in Nurse Practitioner [Tate, 1995]. was found to be “effective in myoclonus, especially that of cortical origin” when used Membrane Fluidization either singly and with other drugs [Ikeda et One of the effects common to many anti- al., 1996]. Although this study was open- seizure medications and therapies is fluidi- label, a blinded video inspection was zation of brain membranes. Membrane employed. Piracetam was of positive benefit fluidity is influenced by many factors, some to handwriting, feeding, sleep, attention of which are cholesterol content, fatty acid Smart Drug News [v5n9] 4 June 1997 3 Smart Drug Update: profile, and degree of lipid peroxidation. infants may make them more at risk from this The Case for The higher the cholesterol content, the more problem. rigid and impermeable membranes become. Piracetam mitigates oxidative stress and Piracetam in Themorepolyunsaturatedthefattyacid fluidizes brain membranes. The membrane Down’s Syndrome profile, the more fluid they become. And fluidizing effects of piracetam have been peroxidization, a potential risk factor in DS, reported in both rodents and man. The age- (continued from previous page) decreases membrane fluidity. related decrease in brain fluidity seen in aged Brain membranes may be especially rats is partially corrected by administration sensitive to changes in membrane fluidity. of piracetam. However, in young rats, pir- They have an especially high degree of poly- acetam caused no measurable fluidization unsaturation, containing high levels of EPA [Mueller et al., 1997]. This suggests that (eicosapentaenoic acid) and DHA (docosa- piracetam has a normalizing or self-limiting “Piracetam may have hexaenoic acid), which have 5 and 6 double effect on brain membrane fluidity. In other special application to bonds respectively. These highly unsatu- words, if fluidity is normal, nothing happens, rated fatty acids increase the fluidity of brain if fluidity is abnormal, it is normalized. This Down’s syndrome due membranes, but they also make them especi- finding may be of particular interest in DS to developmental delays ally sensitive to free radicals and oxidative due to the possibility of abnormal fluidity in the closing of the stress, a putative risk factor resulting from changes in early infancy and childhood. overexpression of superoxide dismutase Although this has yet to be measured direct- heart muscle wall (SOD), an antioxidant enzyme which is ly, various signs of decreased membrane between the right and encoded on the 21st chromosome. The over- fluidity are evident (seizure risks are high in left sides of the heart.” expression of SOD increases production of infants, and they have been observed to hydrogen peroxide {see SDN v4n10]. increase over time). The latter fatty acid, DHA, is found in relatively high levels in human breast milk, Piracetam and Hypoxia but not in soy or cow’s milk. Infant formulas Hypoxia is a condition of low oxygen manufactured in the US do not contain DHA, levels in the tissues. Hypoxia can be caused but many in other parts of the world do. The by lack of oxygen in the air (hypobaric or lack of DHA in early infancy, and/or its high-altitude conditions), decreased oxygen- peroxidation, may have deleterious effects carrying capacity of the blood (anemia or on cognitive development. The higher-than- carbon monoxide toxicity), by impaired normal incidence of nursing difficulties in DS circulation (ischemia, heart attacks, blood clots, etc.), or other causes. For decades, piracetam has been studied Senility Prescription Practices as an anti-hypoxia agent. This may have Clinical prescription practices may vary dramatically between countries. special application to DS due to develop- Regional differences in practice often reflect political and regulatory mental delays in the closing of the heart issues. In a recent survey of family physicians and neuropsychiatrists in muscle wall between the right and left sides Lower Saxony, Germany, physicians were asked what they would of the heart. This results in the mixing of prescribe based on a written case description of a 70-year-old widow with blood from the right side of the heart (which moderate dementia and vascular risk factors. The doctors were randomly pumps oxygen-depleted blood to the lungs) assigned one of two different case descriptions, one whose history was with blood on the left (which pumps typical of vascular dementia, and the other which was typical of senile oxygenated blood to the rest of the body). dementia of the Alzheimer’s type (SDAT). The following top responses This effectively diminishes oxygen delivery were received: capacity and exposes affected individuals to Drug Vascular dementia Alzheimer’s (SDAT) some degree of chronic hypoxia. Piracetam 25.6% 30.9% Hypoxia has an adverse effect on cogni- Ginkgo biloba 24.4% 28.4% tive functioning, which piracetam effectively Nimodipine 14.1% 25.9% prevents [see SDN v1n10]. Hypoxia is also Aspirin 29.5% 17.3% associated with increased lipid peroxidation, Overall, there were only minor treatment differences based on the type of which is inhibited by piracetam and antioxi- dementia or the medical specialty. The exceptions were co-dergocrine dants [Nagornev et al., 1996]. This effectively (ergoloid mesylates, or generic Hydergine), which was favored for SDAT increases human resistance to high altitude. over vascular dementia, and ginkgo, which was favored by family physi- In aged patients with ischemic heart disease, cians over co-dercrine and nimodepine (which may reflect an emphasis the combination of piracetam and tocopher- of family physicians on cost and safety factors). ol acetate (vitamin E) provides better control Stoppe G, Sandholzer H, Staedt J et al. Prescribing practice with cognition enhancers in outpatient of angina pain, increases exercise tolerance, care: Are there differences regarding type of dementia? Results of a representative survey in Lower and positively influences hemodynamic Saxony, Germany. Pharmacopsychiatry 29(4): 150-55, 1996. measurements [Pimenov et al., 1997]. These 4 Smart Drug News [v5n9] 4 June 1997 Smart Drug Update: observations confirmed earlier work [Pime- Piracetam’s hypoxia-protective effects The Case for nov et al., 1992]. may be maximized under more extreme Hypobaric hypoxia of pregnant rats conditions. In a rat study of experimentally Piracetam in causes memory impairment and learning induced heart attacks, piracetam (400 Down’s Syndrome delays (in both passive and active tasks) in mg/kg) and sodium oxybutyrate (GHB) (200 newborn pups. Postnatal piracetam (200 mg/kg) normalized aortic blood flow (continued from previous page) mg/kg/day) in the second and third weeks of acceleration during exercise and increased life partially corrected behavioral distur- overall survivability [Tsorin et al., 1993]. Yet bances and physical development, but not neither piracetam nor GHB had any signifi- adaptive behavior, caused by this prenatal cant effect on cardiac contractility at rest. “Postnatal piracetam hypoxia [Trofimov et al., 1993]. Piracetam may also be of benefit to other in the second and third The adverse role that oxidative stress can hypoxia-related conditions. In a Russian play in cognitive functioning can also be clinical study of 155 patients with destructive weeks of life partially blocked by piracetam. Craniocerebral pulmonary tuberculosis, the effectiveness of corrected behavioral trauma in rabbits causes 1) increased free conventional antibacterial therapy disturbances and radical activity, 2) decreased antioxidant (isoniazid, rifampicin, streptomycin) was function, and 3) increased lipid peroxidation enhanced by the addition of chemothera- physical development throughout the brain. These effects are pre- peutic drugs (pirazinamid or ethambutol) caused by prenatal vented by piracetam or amphetamine (which and vitamin therapy. There was additional hypoxia in rats.” are stimulants), but not by phenobarbitol (a enhancement of efficacy from the addition of CNS depressant) [Promyslov and Demchuk, antioxidant therapy (tocopherol acetate or 1995]. The lack of any direct antioxidant galascorbin) with anti-hypoxants (pirace- effect of piracetam or amphetamine in an in tam, calcium pangamate and piriditol) vitro model suggests that the antioxidant [Savula et al., 1993]. effect is entirely mediated by secondary metabolic effects of these compounds. Piracetam and Inflammation The regulation of biological responses to “These clinical Piracetam and Heart Disease improvements were oxygen free radicals, whether due to low or Although piracetam has obvious theoret- high oxygen levels, is mediated by tissue statistically significant ical applications to the hypoxic conditions hormones called prostaglandins.These and continued for typical of heart disease, Russian doctors and powerful hormones are created by the several months after scientists appear to be the only researchers interaction of oxygen free radicals and poly- pursuing this application. unsaturated fatty acids (PUFAs). In a series discontinuation of In 1995, Dasaeva published the results of of complicated metabolic transformations, the piracetam.” a study of hypertensive subjects under job- the oxidized PUFAs are converted stepwise related stress (i.e., “nervous and emotional into various prostaglandins which mediate stress” in their work environment). Pirace- such injury-related biological responses as tam “appeared to improve psychic state, platelet aggregation (to maximize clotting in mental performance and the occupationally bleeding areas and minimize it in others), important function of memory” without any vasoconstriction (to minimize blood loss), adverse effect on attention. A follow-up immune cell activation (to absorb necrotized report on the use of piracetam with reserpine tissue and prevent infection), vasorelaxation (an antihypertensive medication that is also (to maximize blood flow during repair) and used as an antipsychotic agent) found that blood pressure. The proper coordination of piracetam reversed the adverse effects of these events is necessary for proper reserpine on activity, memory and cognitive response to traumatic injury and for effective “The prostaglandin function [Dasaeva and Vermel, 1996]. The healing. cascade often results authors stated that the combination of The prostaglandin cascade often results piracetam and reserpine “is thought effective in collateral damage to otherwise healthy in collateral damage for inpatient treatment of hypertensive sub- tissues immediately adjacent to damaged to otherwise healthy jects exposed to psychoemotional stress.” tissue. Piracetam has been shown to moder- tissues immediately Inelderlypatientswithstableeffort ate this damage. In a study of animal burn angina, piracetam (2.4-5.2 g/day) improved wounds, piracetam (200 mg/kg IM) or adjacent to damaged several metabolic and hormonal indices. hyperbaric oxygen were both found to tissue. Piracetam Low-density lipoprotein cholesterol in protect the basal epidermal cells (the “living” moderates this serum decreased, as did triglycerides. There skin layer) from necrosis (death) were also improvements in glucose toler- [Germonpre et al., 1996]. damage.” ance (reduced hyperglycemia and hyper- insulinemia) [Pimenov et al., 1995]. Smart Drug News [v5n9] 4 June 1997 5 Smart Drug Update: antagonist) [Moriau et al., 1995]. This effect Piracetam and Heart Surgery The Case for is partially attributed to an anti-platelet effect The high incidence of heart defects in DS characterized by 1) inhibition of thrombox- Piracetam in infants has raised questions about how ane (a prostaglandin), and 2) reduction in Down’s Syndrome concurrent piracetam use may affect surgical fibrinogen and plasma factor VIII (von risks. The standard response of US cardio- Willebrand’s factor) [Moriau et al. 1993]. It (continued from previous page) vascular surgeons (and hospitals) is to insist was also attributed to various rheological that piracetam be discontinued prior to (blood flow) effects due to increased surgery. There are obvious legal and liability deformability of cell membranes (red cell, justifications for this policy, but are there white cell and platelet). Increased deforma- medical reasons for this recommendation? bility allows red blood cells to better squeeze “The anti-hypoxic, In other words, would piracetam increase or through through microcapilaries throughout neuroprotective and decrease survivability in open heart surgery? the tissues of the body. The anti-hypoxic, neuroprotective and In healthy adults, these rheological anti-inflammatory anti-inflammatory effects of piracetam effects are observed at single doses of 9.6 g effects of piracetam would seem to offer significant potential and 4.8 g, but not at 3.2 g and 1.6 g. Since the would seem to offer benefits to persons facing surgical trauma, standard dose of piracetam is 0.8 to 1.6 g especially when it is heart surgery which three times daily, standard use may be below potential benefits might entail periods of interruption of blood a rheological threshold. These effects peak to persons facing flow to the brain. Several research teams about 1-4 hours after dosage and gradually surgical trauma.” across the world have been investigating disappear over 8-12 hours [Moriau et al. aspects of this issue. 1993]. This suggests that frequent dosing (at In a randomized study of patients with least three times daily) is a requirement for severe or recurrent venous thrombosis, pir- high-dose piracetam use. It is appropriate to acetam has shown a beneficial potentiating reiterate that additional caution may be antithrombotic effect when administered warranted with any combination of high- with anticoagulants (heparin or vitamin K dose piracetam with anticoagulants (i.e., warfarin) [Pan and Ng, 1983], high-dose Piracetam and Sickle Cell Anemia anti-myoclonic drugs [Ikeda et al., 1996], or blood-thinning agents (PUFA-rich fish oils, Piracetam’s fundamental lack of toxicity has prompted numerous BHT food preservative, aspirin, etc.). pediatric uses over more than two decades of clinical use. One of the Piracetam (400 mg/kg) has also been latest appears to be sickle cell anemia and β-thalassemia. Piracetam reported to have beneficial effects on the shows a strong anti-sickling influence in vitro and in vivo, and a Saudi maturation of blood cells in rats [Nyagolov et Arabian double-blinded clinical study found a significant reduction in “the al., 1993]. Increased iron incorporation into clinical severity of the disease, the number of crises, the extent of hospital- newlyformedredbloodcells,increased ization and the blood transfusion requirements” in children in the 3-12- reticulocytes (a red cell precursor), and year age range [El-Hazmi et al., 1996]. Although these clinical improve- increased maturation of erythroblasts (a red ments were highly statistically significant (P<0.001) and continued for cell progenitor cell line located in bone several months after discontinuation of the piracetam, there were no marrow) were all indications of piracetam- corresponding changes in haematological or biochemical parameters induced erythropoiesis (the generation of associated with sickle cell disease. new red blood cells). A similar pro- El-Hazmi MAF, Warsy AS, Al-Fawaz I et al. Piracetam is useful in the treatment of children with sickle cell disease. Acta Haematologica (Basel) 96(4): 221-26, 1996. maturation effect was seen in white blood cells (small lymphocytes and granulocytes). Piracetam in Angelman Syndrome Angelman syndrome is a genetic condition characterized by a deletion Learning Disabilities of part of maternal chromosome 15 (15q11-13), which is associated with Piracetam’s ability to enhance learning severe mental retardation, ataxic (uncoordinated) gait, tremulousness, abilities may be directly related to its effect and jerky movements. Although not yet fully studied, the critical region on membrane fluidity. In rat studies, 300 of the 15th chromosome contains several genes that code for GABA-A mg/kg of piracetam administered once daily receptor subunits. The GABA-A receptor is the most common GABA enhanced brain fluidity and active avoidance receptor in the brain. GABA-A receptors regulate the flow of chloride ions learning only in old animals [Mueller et al., (Cl-) across neuron membranes, which decreases neuron excitability. In 1997]. There was no measurable effect on Angelman syndrome, the lack of adequate GABA-A influence increases either parameter in young animals. neuronal (CNS) excitability and results in myoclonic (muscle twitching) Piracetam is quite effective in reducing activity, which was reported to be significantly reduced in 5 patients by memory loss and learning deficits in rats treatment with piracetam [Guerrini et al., 1966]. caused by kindling (induction of epileptic- Guerrini R, De Lorey TM, Bonanni P et al. Cortical myoclonus in Angelman syndrome. Annals of like seizures by toxic chemicals). Kindled Neurology 40(1): 39-48, 1996. rats show decreased active avoidance 6 Smart Drug News [v5n9] 4 June 1997 Smart Drug Update: learning. Of vinpocetine (0.1 and 1.0 mg/ In a 12-week, randomized, double-blind, The Case for kg), methylclucamine orotate (225 and 450 placebo-controlled pilot study of 158 adult mg/kg), meclofenoxate [centrophenoxine] stroke patients undergoing rehabilitation, Piracetam in (100 mg/kg) and piracetam (100 mg/kg), recovery was significantly enhanced by Down’s Syndrome only piracetam was effective in preventing piracetam. Recovery in a subset of aphasic kindling-induced learning deficits regardless individuals was also significantly enhanced (continued from previous page) of the timing of administration (i.e., either (P=0.02) [Enderby et al., 1994]. before or after kindling) [Becker and Summary “Learning deficits in Grecksch, 1995]. None of these drugs had rats caused by prenatal any significant effect on the severity of Piracetam offers the potential of induced seizures. Piracetam also prevents addressing a host of DS-related conditions alcohol exposure are amnesia in kindled rats [Genkova-Papazova without imposing any significant toxicity. partially corrected by and Lazarova-Bakarova, 1996]. It has been demonstrated to augment post-natal piracetam Learning deficits in rats caused by cognitive, learning and memory abilities, to prenatal alcohol exposure are partially decrease oxidative and hypoxic stress, and to administration.” corrected by post-natal piracetam adminis- stabilize cells in the blood and central tration [Trofimov et al., 1996]. nervous system. The degree to which these The possibility of synergy between benefits may accrue to DS individuals needs biologically based therapies (i.e., nutrition to be thoroughly investigated. and/or drugs) and cognitive therapies (e.g., References training, physiotherapy, speech therapy, Becker A and Grecksch G. Nootropic drugs have different memory exercises, etc.) deserves close con- effects on kindling-induced learning deficits in rats. sideration. The standard early intervention Pharmacological Research 32(3): 115-122, 1995. “Only piracetam was Brown P, Steiger MJ, Thompson PD et al. Effectiveness of effective in preventing therapy for DS children is a form of piracetam in cortical myoclonus. Movement Disorders 8(1): educational training which can augment 63-8, 1993. kindling-induced environmental influences on development Dasaeva LA. Influence of piracetam on occupationally im- portant functions of hypertensive patients facing psycho- learning deficits and enhance cognitive potential. Synergy emotional strain at work. Meditsina Truda i Promyshlen- naya Ekologiya 10: 26-28, 1995. regardless of the timing between Ginkgo biloba and memory training [see SDN v1n10p7] has now been confirmed Dasaeva LA and Vermel AE. Antihypertensive and noo- tropic drugs in the treatment of hypertensive subjects of administration.” with ginkgo (160 mg/day) and piracetam (2.4 exposed to occupational stress. Terapevticheskii Arkhiv or 4.8 g/day) [Deberdt, 1994]. These studies 68(12): 60-3, 1996. Deberdt W. Interaction between psychological and suggest that nootropic drugs and memory pharmacological treatment in cognitive impairment. Life training enhance different cognitive Sciences 55(25-26): 2057-66, 1994. functions and act complementarily. Deberdt Dukes MNG (Editor), Meyler’s Side Effects of Drugs (13th Edition), Elsevier Science, Amsterdam, 1996. writes, “This potentiation is very clear in the Enderby P, Broeckx J, Hospers W, Schildermans F and treatment of dyslexic children.” While the Deberdt W. Effect of piracetam on recovery and rehabilita- dyslexic placebo group achieved only half tion after stroke: A double-blind, placebo-controlled study. Clinical Neuropharmacology 17(4): 320-31, 1994). the normal progress in reading accuracy and Genkova-Papazova MG and Lazarova-Bakarova MB. comprehension during a normal school year, Piracetam and fipexide prevent PTZ-kindling-provoked the piracetam group (3.3 g/day) achieved a amnesia in rats. European Neuropsychopharmacology “Early intervention 6(4): 285-90, November 1996. is a form of training full year of progress. Germonpre P, Reper P and Vanderkelen A. Hyperbaric oxygen therapy and piracetam decrease the early extension which can augment Piracetam and Language Skills of deep partial-thickness burns. Burns 22(6): 468-73, Sep- tember 1996. environmental Piracetam has a specific language- Huber W, Willmes K, Poeck K, Van Vleymen B and Deberdt enhancing effect. This effect has been W. Piracetam as an adjuvant to language therapy for influences on aphasia: A randomized double-blind placebo-controlled observed in studies of adults and children pilot study. Archives of Physical Medicine and Rehabili- development and with learning disabilities, and it has recently tation 78(3): 245-50, 1997. been confirmed in a double-blind, placebo- Ikeda A, Shibasaki H, Tashiro K, Mizuno Y and Kimura J. enhance cognitive Clinical trial of piracetam in patients with myoclonus: potential.” controlled study of aphasic infants and nationwide multiinstitution study in Japan. The young children (of up to three years of age) Myoclonus/Piracetam Study Group. Movement Disorders [Huber et al., 1997]. Aphasia involves im- 11(6): 691-700, November 1996. Karacostas D, Giannopoulos S, Artemis N and Milonas I. pairment of communication skills (speech, Effect of piracetam on myoclonus secondary to electro- written or signing) due to neurological dys- cution: A case report. Acta Therapeutica 19(4): 401-4, 1993. Krapivin SV and Sopyev ZhA. [The effect of preparations function in the dominant speech centers of with nootropic action when used long-term on the brain the brain. Huber and colleagues studied the bioelectrical activity in rats]. Eksperimentalnaia i Kliniches- effect of piracetam and placebo on 6 weeks kaia Farmakologiia 56(1): 6-9, Jan-Feb 1993. “...prolonged injection of piracetam (2 months)... increased and stabilized of intensive language therapy and found the predominant peak of EEC spectra power by the Fourier statistically significant enhancement of lan- method. Discontinuation (24 hours) of piracetam failed to impair EEG spectra and bioelectrical activity.” guage reaquisition in the piracetam group. Moriau M, Lavenne-Pardonge E, Crasborn L et al. The treat- Smart Drug News [v5n9] 4 June 1997 7 Smart Drug Update: ment of severe or recurrent deep venous thrombosis: Bene- Promyslov MS and Demchuk ML. Interrelationship ficial effect of the co-administration of antiplatelet agents between the functional state of the central nervous system The Case for with or without rheological effects, and anticoagulants. and lipid peroxidation level in brain following cranio- Thrombosis Research 78(6): 469-82, 1995. cerebral trauma. Molecular and Chemical Neuropathology Piracetam in Moriau M et al. Platelet-anti-aggregant and rheological 25(1): 69-80, May 1995. properties of piracetam: A pharmacodynamic study in nor- Reynolds JEF (Editor), Martindale: The Extra Pharmaco- Down’s Syndrome mal subjects. Arzneimittel-Forschung 43(2): 110-18, 1993. poeia (31st Edition), Royal Pharmaceutical Society of Great Mueller WE, Koch S, Scheuer K, Rostock A and Bartsch R. Britain, London, 1996. (continued from previous page) Effects of piracetam on membrane fluidity in the aged Savula MM, Kravchenko NS and Poznanskii AI. [Chemo- mouse, rat, and human brain. Biochemical Pharmacology therapy of destructive pulmonary tuberculosis with anti- 53(2): 135-40, 1997. oxidants and antihypoxic agents]. Problemy Tuberkuleza “Piracetam offers the Nagornev SN et al. [Pharmacological correction of lipid (5): 18-20, 1993. peroxidation during hypoxia and possibility to enhance Tate E. The clinical challenge of progressive myoclonus potential of addressing human resistance to high altitude by using preparations of epilepsy. Nurse Practitioner 18(5): 25-8, May 1993. the metabolic type of action]. Vestnik Rossiiskoi Akademii Trofimov SS et al. [Piracetam as a corrector of long-term a host of Down’s Meditsinskikh Nauk 7(7): 53-60, 1996. learning disorders caused by prenatal alcohol exposure: the Nyagolov Y, Dyankov E and Ganchev T. Effects of pirace- significance of the length of therapy]. Biulleten Eksperi- syndrome-related tam on erythropoiesis and leukopoiesis in rats. Acta Physio- mentalnoi Biologii i Meditsiny 121(4): 435-7, April 1996. logica et Pharmacologica Bulgarica 19(4): 97-100, 1993. Trofimov SS et al. [Behavior disorders in rats exposed to conditions without Pan HYM and Ng RP, The effect of Nootropil in a patient on intrauterine hypoxia, and their correction by postnatal treat- imposing any warfarin. European Journal of Clinical Pharmacology 24: ment with piracetam]. Biulleten Eksperimentalnoi Biologii 711, 1983. i Meditsiny 115(1): 43-5, January 1993. significant toxicity.” Pimenov LT, Kalinina SA and Churshin AD. Clinical and Tsorin IB, Kazanova GV and Chichkanov GG. [The long- hemodynamic efficiency of piracetam (Nootropil) in elderly term use of antihypoxants in myocardial infarct in rats: their and senile patients with coronary heart disease in the out- effect on the hemodynamics and contractile function of the patient rehabilitative period. Kardiologiya 32(5):35-7, 1992. heart]. Eksperimentalnaia i Klinicheskaia Farmakologiia Pimenov LT, Churshin AD and Ezhov AV. Clinical efficacy 56(3): 25-7, May-June 1993. and hormonal and metabolic reactions in elderly patients Van Vleymen B and Van Zandijcke M. Piracetam in the with angina treated by piracetam. Kardiologiya 35(11): treatment of myoclonus: an overview. Acta Neurologica 30-34, 1995. Belgica 96(4): 270-80, December 1996. Pimenov LT, Churshin AD and Ezhov AV. [Piracetam and Vernon MW and Sorkin EM. Piracetam: An overview of its tocopherol acetate ability to potentiate clinical effect of pharmacological properties and a review of its therapeutic antianginal drugs in presenile and senile patients with use in senile cognitive disorders. Drugs & Aging 1(1): 17-35, ischemic heart disease (unstable angina)]. Klinicheskaia 1991. Meditsina 75(1): 32-5, 1997.

Rumors about GHB? testimony that the “facts” being offered in AsaEuropeanphysician,Iwasdis- support of the bill were highly questionable, mayed to read an article (I do not know its the committee was not interested in hearing source) which made ludicrous, alarmist anything more than token opposition to the statements about GHB. Do you know any- bill. It passed overwhelmingly. thing about these terrorist allegations about Interestingly, the California Senate (SB#) comas, deaths, date rapes, respiratory shut and Assembly (AB6) bills to criminalize GHB downs, etc.? GHB is approved here as a were temporarily derailed, not because they prescription medication. We are having no would be bad social policy, but because they problems with it at all! anon, M.D. would cost money. California law now As you may have just read in our recent requires that the fiscal costs of all bills be editorial, elements in the US government considered in an appropriations committee “As a European have decided that GHB is the new demon before they are moved to the floor for final physician, I was drug to be prohibited at all costs. It may be vote. The authors had asserted that the bills a coincidence, and it may not, that the would have negligible fiscal impact (i.e., less dismayed to read an governmental myths about marijuana than $150,000 per year), but the article which made (which is Schedule I; no allowed medical appropriations committees found that arrest ludicrous, alarmist uses) are unraveling as several states are and incarceration of only 6 persons on GHB attempting to decriminalize its medical use. charges based on the bill would result in statements about GHB.” I prepared a 17-page report to the California exceeding that limit. Legislature (which is now posted on our web The Senate bill (SB3) has now passed the site: http://www.ceri.com) in an attempt to Senate Appropriations Committee and will counteract the anti-GHB propaganda, and I probably pass on the floor of the Senate as made arrangements to have Dr. Ward Dean this issue goes to press. It now looks like “In May, three bills fly out to California to testify before the possession of GHB is about to become a were introduced California Senate Committee on Criminal felony crime in California. The law will Procedures. But for some undisclosed become effective immediately; there will be into the House of reason, the hearing was moved up a week no grace period. SWF Representatives that without notice to me, and Dr. Dean’s Attempts are now underway to would control GHB at testimony concerning the safety of GHB and criminalize GHB nationally. In May, three the inaccuracy of alleged GHB-related deaths bills were introduced into the House of the Federal level.” was never heard. Despite my overt Representatives that would control GHB at 8 Smart Drug News [v5n9] 4 June 1997 Consumer’s Guide to Using Melatonin” in may result is 1) your disappointment in the SDN v4n9p1-4). In general, if you go to bed face of high expectations, 2) financial loss late, you might want to use a quick release (piracetam costs from 25 cents to several continued from previous page melatonin product (sublingual liquid, dollars per day depending on age and sublingual tablet, or capsule). If you go to dosage), and 3) rare temporary symptoms of bed early, you might want to use a timed- headache, nausea, diarrhea, constipation, “We’d be interested release product. Most timed-release tablets irritability, hyperactivity, spaciness, or other in hearing a report are put together in layers and consequently symptoms which may happen when you do not function in a timed-release manner give anything to anybody. SWF from you about your when broken into pieces for purposes of He has agreed to prescribe the testing, but experiences with reducing the dosage. Timed-release tablets only after we visit a geneticist. However, he melatonin and require use “as is.” SWF is reluctant to allow any supplementation We’d be interested in hearing a report beyond the USRDAs. BH meditation.” from you about your experiences with Find a new physician!! WD melatonin and meditation. Please consider I have to agree with Dr. Dean. The US writing them up for us. WD & SWF RDAs are minimal levels of nutrition that are designed only to prevent deficiency QHI Gets Vote conditions (a gross sign of unmet need) in I would just like to report that I received the average “normal” person, which also very good service from Quality Health, Inc., means that they are not designed to supply and would recommend them. Products the total nutrition needs of the majority of arrived 10 days from faxing order, and came people. The safe level is usually 2-10 times with all original packaging and inserts. DA higher for minerals, 5-30 times higher for fat-soluble vitamins, and 100-1000 times Down’s Syndrome higher for water-soluble vitamins. The toxic and Doctors level is higher still. Your physician’s I have an almost-5-year-old daughter prejudice lacks scientific justification. with Down’s syndrome and have been A typical physician regularly prescribes reading with interest the information on TNI drugs with safety margins of less than 10 (i.e., “Speech enhancement and piracetam provided by both you and Dr. ten times more than the prescribed dose will is one reason why Paul Spurlock on your respective web sites. cause serious adverse side effects). Medical Without medication, my daughter has tested opinions about megavitamins have arisen piracetam is being low normal in IQ, but her expressive speech from anticompetitive rhetoric against ortho- used so frequently with is still significantly delayed (although her molecular physicians who use nutrients (and Down’s syndrome.” speech teacher recently told me that she is drugs when necessary) to restore the proper ahead of most Down’s children her age). It molecular functioning of the body, as advo- sounds to me like piracetam may be just cated by the late Nobel laureate Dr. Linus what she needs. BH Pauling. But Professor Pauling had the un- You may be right. Speech enhancement pardonable gall to tell physicians things that is one reason why piracetam is being used so they knew to be false, namely 1) that vitamin frequently with Down’s syndrome. It specif- C was effective against the common cold, ically addresses a significant prenatal 2) that the RDA for vitamin C should be 200 element (diminished corpus callosal mg, and 3) that 2000-10,000 mg daily was development) that is common in Down’s probably healthier still. It was pure heresy! children (and to males in general). It can act But recently, Dr. Mark Levine and colleagues as a specific enhancer of linguistic skills that at NIH have scientifically verified the correct depend on interhemispheric coordination RDA of vitamin C in a detailed, painstaking for effective function. See “The Case for study of young healthy men in a totally “I have discussed Piracetam in Down’s Syndrome” in the last controlled environment [see SDN v5n2p1]. the use of TNI and issue. SWF You guessed it, it’s 200 mg daily! Pauling was IhavediscussedtheuseofTNIand right on target. But like Cassandra, he had to piracetam with our piracetam with our pediatrician, but he is be persecuted for his prescience. pediatrician, but he invoking the “first do no harm” rule. BH The sad thing is that the levels of nutrients is invoking the ‘first What does that have to do with pirace- in TNI formulas for DS are tens to hundreds tam? Piracetam is essentially non-toxic and of times lower than over-the-counter supple- do no harm’ rule.” no reports of permanent damage have ever ments in widespread use within the US. been made, unlike many drugs that your Check out the labels on MSB-plus and Nutri- pediatrician has probably already prescribed vene-D and see for yourself. Your physician to your daughter. The primary harm that probably hasn’t even examined either 8 Smart Drug News [v5n10] 4 July 1997 formula to see if there are any real long-term Fortunately for you and your daughter, risks from high levels of nutrients. There you do not need a prescription to obtain and aren’t. The risks of using the formula are far use piracetam. The FDA’s personal-use continued from previous page less than those of not using it. And the risks import policy specifies that importation of are probably far less than an agile adult piracetam is allowed for the treatment of crossing a street during rush hour to buy debilitating or life-threatening conditions. groceries at the local market. SWF Untreated DS is definitely debilitating, so you My physician said that regardless of what are covered. The personal-use import policy “If your doctor is the geneticist says, he will not support also specifies that patients must be under unwilling to provide piracetam, due to the lack of research in the “medical supervision” for the imported use of piracetam specifically in Down’s item(s). This does require your daughter’s medical supervision, patients. BH physician’s participation. If he’s unwilling to then you really need Does he prescribed antibiotics to your provide medical supervision, then you really to find another daughter? If so, ask him if he knows of any need to find another physician! SWF studies testing that antibiotic in DS patients. Correspondence physician!” Most have not been tested specifically in DS Please mail your questions to: CERI Q&A, P. O. populations. If he then falls back to “years of Box 4029, Menlo Park, CA 94026. Or you can fax general clinical experience” with antibiotics your questions to 415-323-3864, or e-mail them in DS, ask why 20+ years of general clinical to [email protected]. Initials of the author experience with piracetam is insufficient. follow each question. If you want us to use your full name, or if you want us to omit your initials, I think they call such double standards please state so in your correspondence. hypocrisy outside of the medical profession.

Nutrition Update: aspects of our relationship to the external the balance between serotonin and dop- Designer Brain environment, including emotional tone and amine is through selective neurotransmitter motivational level. precursor loading. This approach is based (continued from page 1) While the cerebral cortex is a recent evo- on feeding the metabolic pathways that lutionary adaptation of higher mammals, the produce the different neurotransmitters. Dopamine Biosynthesis brain’s limbic structures are an age-old system common to mammals, reptiles, birds Dopamine Biosynthesis O and amphibians. This has led to the limbic The catecholamine neurotransmitters OH system being described as the “reptilian” (dopamine, norepinephrine and epineph- phenylalanine NH2 brain. However, this term may be more a rine) are synthesized from phenylalanine, phenylalanine reflection of a general cultural prejudice tyrosine or dopa (see margin illustration). hydroxylase against “primitive” emotions and “animalis- The rate-limiting step in this pathway is the (or tyrosine hydroxylase) O tic” motivations by researchers interested in conversion of tyrosine to dopa by tyrosine compartmentalizing (and denigrating) our hydroxylase (which can also convert phenyl- OH tyrosine less-than-spiritual characteristics. As we will alanine to tyrosine). NH2 HO see later in this article, the limbic system is a There are fairly large differences in how ++ . tyrosine hydroxylase Fe,O,H2 4 biopterin necessary and essential aspect of being the choice of precursors affects dopamine O human. synthesis. The most obvious one is that dopa HO OH Two of the dominant neurotransmitters is the only precursor which bypasses the rate dopa NH2 of the limbic system are serotonin and limiting step in the pathway. Indeed, dopa HO dopamine. Serotonin promotes calmness, supplementation raises dopamine synthesis dopa decarboxylase B6 emotional stability, and passivity, while to a much larger degree than phenylalanine dopamine promotes arousal, emotional or tyrosine. There is also a major difference HO dopamine volatility and activity. These opposing in the degree to which different precursors NH2 actions can be considered complementary enhance the different catecholamine neuro- HO regulators of our behavioral responses. transmitters. I have observed that phenyl- dopamineβ -oxidase Cu, ascorbate This emotional and motivational regula- alanine and tyrosine enhance norepineph- OH tion is enhanced by active interaction with rine more than dopamine, and dopa HO environmental influences. Serotonin levels enhances dopamine more than norepin- norepinephrine NH2 are readily influenced by dietary composi- ephrine. HO tion, while dopamine levels are not. Thus, Epinephrine, also known as adrenaline, S-adenosylmethionine the active dynamic between these two is normally only found in trace amounts in OH neurotransmitters allows for the central the brain. It is primarily a peripheral (body) HO nervous system to adapt quite effectively to neurotransmitter produced by the adrenal epinephrine NH basic external conditions. gland for the “fight or flight” response to HO One of the simplest ways to investigate stressful (i.e., “emergency”) situations. Smart Drug News [v5n10] 4 July 1997 9 Special Report: significantly increasing it. Tryptophan and Manders DW. The FDA Ban of L-Tryptophan: Politics, 5-HTP appear to offer the potential for better Profits and Prozac. Social Policy 26(2): Winter 1995. Serotonin Precursors Pöldinger W, Calanchini B and Schwarz W. A functional- therapeutic results, decreased side effects, dimensinal approach to depression: serotonin deficiency as & Reuptake Inhibitors and lowered health-care costs. ¤ a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 24: 53-81, 1991. Blundell J. Pharmacological approaches to appetite (continued from previous page) Takahashi S, Kondo H and Kato N. Effect of L-5-hydroxy- suppression. Trends Pharmacol 12: 147-57, 1991. tryptophan on brain monoamine metabolism and evalua- Cangiano C, Ceci F, Cascino A, et al. Eating behavior and tion of its clinical effect in depressed patients. J Psychiat Res adherence to dietary prescriptions in obese subjects treated 12: 177-87, 1975. with 5-hydroxytryptophan. Am J Clin Nutr 56: 863-68. 1992. Additional references available by request.

effects through professional and Down’s Syndrome governmental channels. Piracetam is an old and Doctors drug that has been tested in people and My physician said that he will not animals for three decades. During this time, support piracetam due to the lack of no serious problems have ever surfaced. research in the use of piracetam specifically None. in Down’s patients. BH Regarding efficacy, the issue is different. The Barcelona study (conducted by Dr. One can certainly question the efficacy of Fiona and associates) tested piracetam with piracetam in treating DS if the Fiona study is and without 5-hydroxytryptophan in a DS the only evidence offered. But is this, in population [see summary in SDN v5n8p2]. itself, a good reason not to try it? Such The study was open (unblinded), used decisions involve weighing known benefits, historical controls, and has never been known risks, unknown benefits and un- replicated. known risks — a process that is necessarily “Our pediatrician’s There are two concerns regarding pirace- value dependent. Your physician has his main concern is that tam: safety and efficacy. If one focusses values and you have yours. Personally, I only on safety concerns, whether or not the think the benefits clearly outweigh the risks, we don’t know what is Fiona study has been replicated is of minimal which is why I take piracetam. But, bottom going to show up five concern. The treatment was well tolerated line, it’s only your family’s values that matter to seven years from and produced no clinically significant where therapy for your daughter is con- adverse effects — just like in every other cerned. now; his example was study of piracetam ever conducted in non-DS The harm and cost of not using TNI L-tryptophan and the populations (blinded and non-blinded and/or piracetam are: 1) brain damage problems that it ended alike). It is exceedingly rare that studies are (mental retardation), 2) inhibition of growth, ever done for narrow specialty populations 3) immune suppression (chronic infections), up causing.” for drugs in common use in the general 4) enhancement of degenerative diseases population — let alone the long-term studies (early senility, premature death), and 5) all of that we might all like to see done. Physicians the emotional and social consequences of all use drugs in practice and report adverse of the above. I think your physician is comparing real apples to immaginary New Practitioners oranges. Please consider these issues carefully before agreeing with him. SWF Robert Dozor, M.D. 707-942-4276 Our pediatrician’s main concern is that Napa Valley Family Medical Group we don’t know what is going to show up five 1705 Washington Street, Calistoga, CA 94515-1598 to seven years from now; his example was Complementary and alternative medicine integrating conventional and the wonder-drug L-tryptophan and the holistic approaches, meditation, nutrition and herbs. Fax: 707-942-4421. problems that it ended up causing. BH E-mail: [email protected]. Internet: http://wholemedicine.com. I don’t know which is worse, your David A. Nicoletti, C.C.N., R.Ph. 520-886-1035 physician’s ignorance or his arrogance. 6550 E. Carondelet Drive, Bldg. F, Tocson, AZ 85710 L-Tryptophan did not cause problems — Clinical nutrition and assessment. Cognitive enhancement and natural contamination did.Thecomplicityof hormone assessment/replacement consultations. Compounding tryptophan is an FDA-engineered myth, pharmacist. Fax: 520-886-3548. perpetuated by ignorant doctors unwilling to look into the matter for themselves. Every Philip Lee Miller, M.D. 408-358-8855 expert that hasn’t been “bought and paid for” Los Gatos Longevity Institute by Showa Denko (the company that contam- 15215 National Avenue, Suite 103, Los Gatos, CA 95032 inated its tryptophan) or the FDA knows that Longevity and anti-aging medicine, natural hormone replacement contaminants were responsible for the therapy (including human growth hormone), menopausal/andropausal medicine, complex lipid disorders (cholesterol). Fax: 408-358-8857. eosinophilia myalgia (EMS) epidemic. If your physician had bothered to look up the Smart Drug News [v6n1] 1 August 1997 5 facts, he would have found that Showa apparent problems. Logically, the sudden, Denko1)introducedanew strain of dramatic increase in EMS could only be genetically engineered bacteria into their caused by a contaminant. This same logic continued from previous page tryptophan fermentation process, 2) reduced was effectively applied to solving Tylenol the amount of activated charcoal (an poisonings, which turned out to be cyanide impurity-adsorbing agent) used in a primary contamination. No one ever suggested that purification process, and 3) partially by- Tylenol shouldn’t be let back into the market. “Physicians do have passed a reverse-osmosis filtration process Tryptophan is a ludicrous example to justify serious liability, both (another purification step) — all at the same your physician’s point. I’d bet good money time! Why would anybody make multiple, that your physician still uses Tylenol in his civil and regulatory, simultaneous changes in an industrial practice. I’d also bet that he does not for prescribing TNI process? They did it to make more consider cyanide poisoning symptoms to be and/or piracetam.” tryptophan — cheaper! Showa Denko was a sign of Tylenol toxicity. systematically driving everybody out of the One cruel fact in this tryptophan fiasco tryptophan-manufacturing business by was that uncontaminated tryptophan was undercuting their competitors prices. The found to be an effective treatment for the price for tryptophan had fallen from more contaminant-induced EMS (US patent than $400 per kilogram (2.2 pounds) to less #5,185,157). By using the contamination as “Contaminated than $200, and Showa Denko showed no a political football to ban tryptophan from tryptophan was not sign of letting up. Their problem at the time the US market, the FDA denied EMS victims was that they could not keep up with the a viable therapy and condemned them to Showa Denko’s first demand they were creating with their low- continued suffering. industrial experiment priced tryptophan. So they needed a miracle But the biggest flaw in your pediatrician’s gone wrong.” — and they thought they had one with their logic is his contention that we don’t know genetically engineered tryptophan- what will happen in 5-7 years. In fact, we fermenting bacteria that might double or know we will see mental retardation, sub- quadruple their tryptophan yields. standard growth and chronic infections if Of course, there was a catch. The new TNI and/or piracetam are not used. Your impurities introduced into Showa Denko’s physician may be comfortable using tiny “new-and-improved” tryptophan were never unknown risks to justify acceptance of major characterized or adequately tested before known risks, but you should not be fooled Figure 1: marketing. Within months of its introduc- into thinking that his position is medically The Oxidation tion, customers began to experience a host of responsible, scientifically based or ethically and Catabolism complaints that were later identified as sound. q of Vitamin C eosinophilia myalgia syndrome (EMS). Physicians do have serious liability, both Eosinophils are small white blood cells that civil and regulatory, for prescribing TNI and/ OH are produced when the body is exposed to or piracetam. Reluctance to prescribe TNI O parasites or toxins. Showa Denko’s trypto- and piracetam based on 1) fear of being sued O H H phan contaminants were systematically in the face of a negative or random outcome, ascorbate OH stimulating eosinophil production. In a or 2) fear of being disciplined or losing ones HO OH small percentage of people taking it, this license by practicing medicine differently production was so great than one’s peers, is entirely understandable. O OH as to literally fill up body Blaming it on imaginary medical concerns is O HN O H tissues with eosino- not. SWF H O NH phils, causing great What is the proper pronunciation of dehydroascorbate OH alloxan pain in more than a piracetam? BH OO OOthousand people. More I say per-ASS-ih-tam because I think HO2 than a hundred died. acetate (ASS-ih-tate) is a root word — and OH OH OH Contaminated tryptophan was not Showa because that’s how Dr. Dean says to pro- H Denko’s first industrial experiment gone nounce it. A fair minority of people say O H wrong. Twenty years earlier, Showa PEER-ah-SEE-tam. SWF diketo-L-gulonate OH Denko was found to be responsible for OO mercury-contaminated seafood, created Dehydroascorbate Toxicity HO2 by massive industrial dumping of mercury In the last issue you talked about vitamin into one of Japan’s bays. C stability in water. Is dehydroascorbate OH OH OH H Tryptophan was in widespread use really that toxic? I’ve heard that it is found O + H for two decades prior to the contam- in Ester-C. I’ve also seen plenty of liquid OH oxalate OH OH ination incident, and 14 million vitamin C products in my local health food L-threonate OOpeople were taking it without stores. How do they stabilize them? OTP 6 Smart Drug News [v6n1] 1 August 1997 Such decisions involve deep values. Some Down’s Syndrome are easily influenced by rational processes, I am a new father of a Down’s baby. My and some are overwhelmingly emotional. continued from previous page son is now six weeks old. He was born at 34 You and she can read “The Case for Pirace- weeks with some fluid in his chest cavity and tam in Down’s Syndrome” [SDN v5n9p1] and two small holes in his heart. The fluid was get a rational perspective, but I have ob- drainedimmediatelyandtheholesare served that the emotional content of values already showing signs of closing. He is are not so easily or quickly swayed. Take eating, sleeping and generally thriving whatever time is necessary to make the nicely. MM decision right the first time. Too much Collagen nutrients may possibly speed up pressure to change values too quickly can closure. These include vitamin C, bioflavo- produce upset and emotional backlash. This noids, proline and lysine (see Q&A last can be a real problem in a relationship if one “I believe that it is issue). Both Nutrivene-D and MSB-Plus are party is emotionally dominant and the other necessary to perform formulated to enhance collagen production. is rationally dominant, especially if there is See SDN v4n1p3 for more information about not enough reciprocity and/or respect for blood tests to obtain the overexpression of collagen genes on the the opposite orientation. reliable results for 21st chromosome and SDN v6n2p7 for If your wife is rationally oriented, just the sex steroids.” information about collagen applications to have her read our materials on piracetam vascular strength, strokes, heart disease and and ask her to call me call me on a Tuesday ease of bruising. SWF afternoon. I reserve from noon to 5 PM Since he was born, my wife and I have Pacific Standard Time for subscribers to ask visited and read most of the information on questions about personal matters that are the Internet on Down’s (including CERI). either 1) too private for the newsletter, or We have also read a couple of excellent 2) too individual-specific for a general books, received the parent information answer to suffice. If your wife is emotionally packet from TRI and have spoken to many oriented, I suggest you take the time to sensi- parents (some of whom have their children tively explore the emotional side of the “Although my wife on TNI). decision to her satisfaction with a let’s-sleep- and I have done My family and I moved to London three on-it attitude (i.e., a low pressure approach). months ago. We would like to start him on The answers in the Q&A column provide considerable research, Nutrivene-D and possibly, eventually, on pir- general information which should be applic- my wife is still acetam. Since we have been unable to locate able to a wider variety of situations than the uncomfortable about a London doctor who is optimistic about TNI literal question asked. However, there will and with whom we are comfortable, I was always be situations where personal circum- the use of piracetam wondering if you know any London doctors stances are too involved to adequately in our infant son.” who are advocates of TNI? MM explain in writing. That’s when its ideal to No. Sorry. But do you really need an call with your question. If you call when I’m optimistic doctor? You can import Nutrivene on the line with another subscriber, we can and piracetam with or without a prescription set up an appointment from 15 minutes later (at least I think that you can in England). to an hour later, at your convenience, at If the English authorities hassle you, which time you will have first priority. SWF consider hiring Dr. Lawrence Leichtman, I am concerned about waiting because of M.D. as your consulting physician and have the studies that I have read which discuss him prescribe Nutrivene-D and piracetam. the damage to the brain after (here I have “The answers in the With his prescription, you should be able to seen different opinions) four to twelve Q&A column provide minimize any difficulties. Most countries months of age. We have spoken to a few allow medical treatments that are begun in parents who wished that they had started general information another country to be continued in their their children on piracetam much sooner. which should be country. You just need to provide the neces- Would you mind responding with your applicable to a wider sary documentation. If a US prescription for stance on piracetam, administering to an piracetam is not honored in a British infant, safety issues, and any studies on variety of situations pharmacy, you can use it to import piracetam long-term effects? Additionally, although I than the literal fromaUScompoundingpharmacyinto have searched the Web, I have found very question asked.” England. SWF little written negatively about piracetam. I Although my wife and I have done know it must exist somewhere. Do you know considerableresearch,mywifeisstill of any of these type of sites? MM uncomfortable about the use of piracetam in Sorry, the information you are asking for our infant son. MM does not exist. Piracetam has no LD50,itis Smart Drug News [v6n3] 27 October 1997 9 essentially non-toxic and it is universally despite what rationalizations we may heap well tolerated [Vernon and Sorkin, 1991]. on it. It is fundamentally emotional. We feel Doses from 12-24 grams(!) per day are given that, somehow, we should have known continued from previous page to infants and children with myoclonic anyway. seizure disorders [Dukes, 1996; Reynolds. The process of making a decision actually 1996]. At these very high doses, piracetam alters our values. Before the decision, we “We have spoken can cause rheological (blood) effects that can weigh things differently than after the to a few parents who potentiate anticoagulant therapy with decision. When deciding between the blue warfarin (documented), aspirin (undocu- Mercedes or red Porche, the decision may be wished that they had mented), or fish-oil therapy (also undocu- neck and neck. But after the decision, the started their children mented). However, this blood-thinning blue Mercedes is definitely better. My apolo- on piracetam much effect is not observed at the 30 mg/kg dose gies to the red Porsche owners out there, but that is used for cognitive enhancement this story illustrates the emotional invest- sooner.” purposes [Moriau et al., 1993; Van Vleymen ment we make in our decisions. It really and Van Zandijcke, 1996]. doesn’t matter whether we are talking about Starting early is a good idea. Oxidative blue Mercedes, red Porsches, TNI, staying up stress associated with the overexpression of late, or age of dating. They all involve a the SOD gene on the 21st chromosome [see decision-making process that re-prioritizes “Regret is not SDN v4n10] begins at birth with the loss of our values. Worrying too much about regret fundamentally based maternal antioxidant support through the prior to the fact is itself regrettable. Take placenta. Since you have already decided on some advice: 1) take your child’s welfare to on rationality, despite TNI (targetted nutritional intervention), you heart, 2) forgive yourself in advance for the what rationalizations are not really waiting where issues of brain decision you are about to make, and 3) make we may heap on it. damage or retardation are concerned. In my your decision. SWF opinion, most of the brain damage which Dukes MNG (Editor), Meyler’s Side Effects of Drugs (13th It is fundamentally occurs in the first two years of life is due to Edition), Elsevier Science, Amsterdam, 1996. Moriau M et al. Platelet-anti-aggregant and rheological emotional. We feel that, elevated levels of superoxide dismutase and properties of piracetam: A pharmacodynamic study in normal subjects. Arzneimittel-Forschung 43(2): 110-18, somehow, we should its acceleration of apoptosis (cell suicide) of neurons in the developing brain. I think that 1993. Reynolds JEF (Editor), Martindale: The Extra have known anyway.” this oxidation-related pathology is most Pharmacopoeia (31st Edition), Royal Pharmaceutical effectively countered by the TNI component Society of Great Britain, London, 1996. Van Vleymen B and Van Zandijcke M. Piracetam in the of the program. Piracetam may help, but treatment of myoclonus: an overview. Acta Neurologica piracetam without TNI is probably not very Belgica 96(4): 270-80, December 1996. effective. I don’t have good data to back up Vernon MW and Sorkin EM. Piracetam: An overview of its pharmacological properties and a review of its therapeutic this opinion, but there is also a lack of good use in senile cognitive disorders. Drugs & Aging 1(1): 17-35, data showing enhancement of neural 1991. development or mental abilities in the 0-2 year age range. We have positive anecdotal Vitamin C and Iron Toxicity reports, but no clinical studies. Dr. Andrew Weil says not to take vitamin Any parent can regret any decision. It is Cwhenyouhaveirontoxicitybecause inherent in being a parent, not in the nature vitamin C increases iron absorption from “In my opinion, most of how you reached a specific decision. The the diet. However, excess iron stimulates of the brain damage decision to start TNI or piracetam is not free radicals and vitamin C is an fundamentally different from deciding when antioxidant. Why wouldn’t vitamin C help which occurs in the your child is ready to cross the street detoxify these free radicals? What do you first two years of life is unaccompanied, to try riding a bicycle, to say? due to elevated levels of stay up past 9 PM, or to date. All such We agree with Dr. Weil. While vitamin C decisions involve a weighing of values, is an important scavenger of oxidative free superoxide dismutase which, in 20-20 hindsight, can be reassessed radicals, it is also a catalyst in the iron- and its acceleration of at a later time. For example, Dixie Lawrence mediated Fenton reaction, which produces apoptosis (cell suicide) Tafoya regrets not putting her daughter on the dangerous hydroxyl radical.Inthe TNI and piracetam earlier. But that regret is Fenton reaction, iron in the +2 state reacts of neurons in the based on knowledge that she didn’t have at with hydrogen peroxide to form a hydroxyl developing brain.” the time of the decision, knowledge learned radical and iron in the +3 state. Vitamin C after making the decision. Rationally, there converts the iron back to the +2 state where is no way that anybody should expect it can react with hydrogen peroxide again. themselves to have considered evidence that Excess iron combined with excess vitamin C they did not have at the time. But regret is is potentially dangerous for this reason. not fundamentally based on rationality, Dr. Weil’s comment about vitamin C 10 Smart Drug News [v6n3] 27 October 1997 to compensate for this acidification, we the emotional rewards we get from life. really don’t have enough experience to Serotonin is made from tryptophan, an predict what problems might arise and how essential amino acid which serves multiple continued from previous page they can be effectively dealt with. Such independent uses in the human body (see experimentation should not be conducted Figure A below). Its largest use is for protein casually. An acidification effect from butyro- synthesis (see the top of Figure A in the lactone in a person with an acidic constitu- margin). Proteins are made from long chains tion might produce strong effects quite of about 20 different amino acids, of which quickly. Acidification in somebody with an tryptophan is one. When we say that trypto- alkaline constitution might be initially phan is essential, we mean that it cannot be helpful and therefore discounted or ignored. made in our bodies and must be obtained If you try butyrolactone, please pay close from the foods in our diet. Without trypto- attention and report your experiences to us. phan, we cannot make most of the enzymes We’ll update everybody as the information and structural proteins necessary to maintain comes in. SWF metabolism. “What I want to know Tryptophan’s minor uses (minor by Prozac for Down’s Syndrome is how exactly does volume, not by importance) are to make After listening to recent anecdotal reports serotonin (a vitally important brain neuro- Prozac work, and could that low-dose Prozac (5 mg per day) is transmitter) and nicotinamide adenine di- similar results could producinggoodresultsinchildrenwith nucleotide. NAD (also known as coenzyme be obtained through Down’s syndrome, I reluctantly put my son 1) is an essential hydrogen transfer agent on Prozac. While I don’t like the idea of that carries “reducing power” in the body in the use of nutrients using drugs, I have seen great results over the form of NADH (the H stands for hydro- or St. John’s wort?” the last few days. His behavior is much gen). Hydrogen and oxygen are necessary better, he is verbalizing much more, he is for energy production [see v5n2 for a com- trying harder to communicate, and he is plete explanation of this process]. Suffice it much more affectionate. What I want to to say here that hydrogen is the electron-rich know is how exactly does Prozac work, and pole of the biochemical “battery” that could similar results could be obtained powers our biochemistry, and oxygen is the through the use of nutrients or St. John’s electron-poor pole. This electrochemical wort? TR battery drives the production of ATP (the Prozac increases serotonin activity in the energy currency of the human body). brain. Dixie Tafoya has long argued that Although the amount of tryptophan that goes Figure 1: there is a significant serotonin deficiency in into making NADH and serotonin is small in Serotonon Down’s syndrome, despite the fact that absolute amount, the role that these Schematics tryptophan deficiency is not a universal substances play in our health is no less aspect of serum amino acid profiles. I think essential than protein synthesis. that these recent observations with Prozac There are times, however, when trypto- Dietary Tryptophan support her view. phan’s availability for protein synthesis The serotonin situation is a difficult one becomes a liability. Protein synthesis is also

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8 Smart Life News [v6n7] 29 June 1998 inhibits the growth of invading bacteria and influence the pool of released serotonin parasites and enhances our immune system’s which is stimulating the target neuron. Each effectiveness. The tryptophan-destroying of these pathways have different and inde- continued from previous page enzyme IDO is triggered by the general acti- pendent influences on both stored serotonin vation of the immune system by chemicals and released serotonin. Serotonin bio- called cytokines. These cytokines are synthesis (pathway 1) increases stored secreted by macrophages, lymphocytes and serotonin. This may also increase released “Dixie Tafoya has other immune cells. They serve as cell- serotonin. However, this pathway is limited long argued that signaling factors to coordinate the activities by the possible complicating effects of IDO of the many cell populations of the immune (see gray dashed outline in Figure A). The there is a significant system. These cytokines can also be acti- inhibition of reuptake (pathway 2) by SRI serotonin deficiency vated by allergic responses and elevated drugs like Prozac, Zoloft and Paxil increases in Down’s syndrome, corticosteroids as well. The oxidative stress released serotonin at the expense of stored associated with over-expression of SOD serotonin (see Figure B). The inhibition of despite the fact that (superoxide dismutase) may be responsible MAO (pathway 3) by strong MAO-inhibiting tryptophan deficiency for overactivating IDO in Down’s syndrome. drugs or weak inhibiting substances like St. is not a universal It is possible that some other factor is John’s wort (which contains hypericin) and responsible as well. GH-3 (which contains procaine) increases aspect of serum amino The consequences of limiting tryptophan released serotonin and thereby stored acid profiles.” availability is not restricted to protein serotonin (see Figure C). synthesis. As far as I know, nobody has yet The use of serotonin precursors (pathway measured what happens to NAD. However, 1) with reuptake inhibitors (pathway 2) tryptophan’s conversion to serotonin is counteracts the depletion of serotonin stores inhibited, as is serotonin’s conversion to by SRIs. Dr. Ward Dean and I discussed this melatonin. This is where Prozac and other strategy in depth in our Special Report on “When we speak serotonin reuptake inhibitors (SRIs) come in. “Serotonin Precursors and Reuptake Inhib- of serotonin levels, When we speak of serotonin levels, it is itors in Depressive Illness” in SDN v6n1. This important to distinguish between stored report would be good background material it is important to serotonin, which is manufactured by for your doctor. distinguish between neurons for release to stimulate target cells, The use of all three approaches simul- stored serotonin, and released serotonin, which is actively taneously (Figure D) can cause much greater stimulating the target cells in the synaptic increases of released serotonin than any which is manufactured gap between the “sending” neuron and the alone. This is because these approaches by neurons for release “target” neuron (see Figure A). From a exhibit positive synergy with each other. In to stimulate target strictly functional point of view, it is only the other words, they add or multiply together. released serotonin that matters. Stored The advantage of such a multi-faceted cells, and released serotonin is only important if it becomes approach is not in the potential for over- serotonin, which is sufficiently depleted to decrease serotonin loading serotonin, but in being able to actively stimulating release. reduce the dose of any of the three agents to So if we narrow our focus to released minimize side effects without sacrificing the target cells.” serotonin, we can see three pathways which efficacy. influence the level of serotonin stimulation Just exactly how these agents will syner- of target neurons (see Figure A). Pathway 1 gize together is not yet well studied under is the biosynthesis of serotonin that serves to either scientific or clinical circumstances. build serotonin stores and thereby promote Caution is indicated. There are likely to be serotonin release. Pathway 2 is the reuptake strong differences in how different people “It is the balance of released serotonin by presynaptic respond to different combinations due to the between 1) feeding, serotonin receptors on the surface of the influence of biochemical individuality on “sending” cell. This is a recycling mechan- this synergy. The confounding influence of 2) recycling, and ism for serotonin which serves to replenish IDO induction is another variable that can 3) elimination serotonin stores. This is also the pathway introduce unpredictable responses. There processes that inhibitedbyProzac.Pathway3isthe are potential advantages to be obtained catabolism (elimination, or destruction) of through combination therapies, but there are influence the pool serotonin. The major enzyme for this is significant unknowns at play that need to be of released serotonin monoamine oxidase (MAO), which oxidizes assessed. which is stimulating the serotonin so that it no longer has One of the unknowns is the mechanism serotonin activity and can be easily removed. of action of St. John’s wort. Although its the target neuron.” It is the balance between 1) feeding, 2) ability to inhibit MAO has been documented, recycling, and 3) elimination processes that it appears that it is not hypericin that is doing Smart Life News [v6n7] 29 June 1998 9 the inhibiting, but rather some other Figure E: flavonoid substance in the plant that is not Oxygen Representations yet characterized [Bladt and Wagner, 1994]. Triplet †‡Singlet continued from previous page St. John’s wort also appears to inhibit COMT (catechol-o-methyl-transterase), an enzyme a that parallels MAO in metabolizing neuro- O O O O O O Figure 1: transmitters [Thiede and Walper, 1994]. The Structure Some of the active chemicals in St. John’s b O O O O O O of Hypericin wort may also inhibit serotonin reuptake [Staffeldt et al., 1994], modify serotonin receptors [Muller and Rossol, 1994], and alter c OOOOOO HOO OH cytokine expression [Thiele et al., 1994]. † Triplet oxygen is a free radical. While there’s lots we do not know about the ‡ Singlet oxygen isnot a free radical. exact mechanisms of how St. John’s wort works, we do know it’s a potent anti- of light without hypericin [Martinez et al., HO depressant with approximately the same 1994]. activity as the tricyclic antidepressants but The hypericin molecule absorbs light HO with a lower side-effect profile. We also energy through its extremely large inter- know it has antidepressant activity against linked series of double bonds (see Figure F SAD (seasonal affective disorder). below). The electrons in these interlinked HO O OH This last point deserves elaboration. The double bonds fuse into an electron cloud that hypericin and pseudohypericin in St. John’s floats just above and just below the plane of wort are photoactive (light-absorbing) atomsinthehypericinmolecule.The chemicals. They absorb light in the green- electrons in this cloud absorb photons of blue-violet portion of the spectrum, which light energy. The absorbed energy is then “We know St. John’s makes hypericin and pseudohypericin transferred to other molecules in the body in wort is a potent briliantly red in color. When range animals a way that is not yet fully understood. (except goats) overgraze on St. John’s wort One of the molecules that receives this antidepressant with (also know as “goat weed” by ranchers in the energy is oxygen. Somehow, regular oxygen approximately the same Western United States), this photoactive or (O2) interacts with the energized hypericin activity as tricyclic photosensitizing property of hypericin leads molecule to convert from its normal triplet to red-blood-cell hemolysis (rupture of red state to a high-energy singlet state. antidepressants but blood cells). It has also caused photosensi- Normally, ground-state oxygen (the lowest with a lower side-effect tivity in humans in clinical studies of high- energy state) exists as a di-radical with two profile. We also know it potency Hypericum extracts and intraven- unpaired (free-radical) electrons, one on ous hypericin solutions. Some people taking each oxygen atom (see Figure E). In has antidepressant large amounts of low-potency extracts have interacting with hypericin, these electrons activity against seasonal noted increased sensitivity to sunburn, a become paired up (see Figures E and F). The affective disorder.” manifestation of photosensitivity. However, energy of the photon is transferred to the this effect is quite rare at the low doses that oxygen molecule, which is kicked off in a are typically used in treating depression. paired up (singlet) state. Because singlet The ability of hypericin to absorb light oxygen has no unpaired electrons (see may be an important mechanism of its anti- Figure E), it is not a free radical. depressant action. One of the standard However, singlet oxygen is still an Figure F: therapies for SAD is phototherapy, the oxidizing agent. In other words, it is still Oxygen Interactions exposure of the depressed person to high reactive towards electrons. The difference is with Hypericin levels of light. However, one study found that singlet oxygen prefers to react with two- that low levels of light electron targets while triplet oxygen (the free with hypericin work radical) tends to react with only one electron light oxygen O O phot just as well as at a time. The biological consequences of on high levels this shift in reactivity are not well understood e- e- or easily predictable. However, it may energy involve a decrease in general free radical oxygen radical orbitals e- hypericin double-bond orbitals e- transfer activity (one-electron reactions) with an HO increase in oxidation of the double bonds of O OH HO O polyunsaturated fatty acids (a two-electron OH hypericin OH system). HO Whether a slight increase in singlet oxygen due to traces of hypericin from St. 10 Smart Life News [v6n7] 29 June 1998 John’s wort might pose an oxidative risk or want to trim a rosebush, then the pruner is offer some degree of protection in Down’s better than the shovel. Similar contexts are syndrome is unknown. We know there is a necessary in picking smart drugs. If you continued from previous page specific oxidative stress associated with want to enhance cerebrovascular circulation, over-expression of superoxide dismutase. then ginkgo or vinpocetine are better than What we don’t know is whether this phenytoin or DMAE. If you are on a strict “Whether a slight oxidative stress would interact positively or budget, maybe ginkgo is better than increase in singlet negatively with a shift in the ratio of singlet vinpocetine. to triplet oxygen. This should be examined. Initially, you may not have much of a oxygen due to traces Analysis of fatty acid oxidation and peroxi- context to base such decisions. You aren’t of hypericin from St. dation patterns might be useful, as might likely to know whether you have a cerebral John’s wort might pose general systemic measurement of antioxi- circulatory problem or not until you try dants and oxidative byproducts (i.e.,the ginkgo or vinpocetine and it works to an oxidative risk or Pantox and Genox profiles). enhance your mental performance or relieve offer some degree of Certainly, if you try St. Johns wort, please some cognitive complaint. Likewise, it is protection in Down’s relate your experiences to us. If you have difficult to know which neurotransmitter any questions that I have not addressed here, system you might want to enhance before syndrome is unknown.” please feel free to ask. I have concerns that you begin the process of altering your there could be consequences of long-term neurotransmitter levels. Even if you know Prozac use in developing infants and children you are depressed, you don’t automatically that might not be anticipated from its clinical know whether to start with the serotonin use in adults. Such concerns may also apply system (using tryptophan or 5-hydroxy- to St. John’s wort. However, an alternative to tryptophan), the norepinephrine system Prozac, or a synergist which might allow the (using phenylalanine or tyrosine), or the dose of Prozac to be cut in half or more, dopamine system (using deprenyl). “Until such time as we might be an important discovery. At our present state of knowledge, we do develop the equivalent If you wish to bring your doctor up to not have a magic window into the inner speed on St. John’s wort, you might suggest workings of the brain and mind. Until such of the Star Trek medical Dr. Shari Lieberman’s recent short review in time as we develop the equivalent of the Star tricorder, we will have Alternative & Complementary Therapies Trek medical tricorder, we will have to to approach cognitive [4(3): 163-8, June 1998]. It is accessible, approach cognitive enhancement with some concise, and directed exclusively towards degree of experimentation. enhancement with human clinical trials. SWF If you feel awkward or uncomfortable some degree of Bladt S and Wagner H. Inhibition of MAO by fractions and with experimentation, hire a medical profes- constituents of Hypericum extract. J Geriatr Psychiatry sional to supervise your program. SWF experimentalism.” Neurol 7: (Supplement 1); S57-59, 1994. Martinez B, Kasper S, Ruhrmann S and Moller HJ. Hypericum in the treatment of seasonal affective disorders. Alzheimer’s Treatments J Geriatr Psychiatry Neurol 7: (Supplement 1); S29-33, 1994. My mother has been getting more forget- Muller WEG and Rossol R. Effects of Hypericum extract on the expression of serotonin receptors. J Geriatr Psychiatry ful for the last few years and has just been Neurol 7: (Supplement 1); S63-4, 1994. diagnosed with Alzheimer’s disease. How Staffeldt B, Kerb R, Brockmoller J, Ploch M and Roots I. Pharmacokinetics of hypericin and pseudohypericin after effective are smart drugs for treating oral intake of the Hypericum perforatum extract LI 160 in Alzheimer’s? How can I convince her doctor healthy volunteers. JGeriatrPsychiatryNeurol 7: that smart drugs should be considered? And (Supplement 1); S47-53, 1994. Thiede MH and Walper A. Inhibition of MAO and COMT by lastly, which smart drugs should we use Hypericum extracts and hypericin. J Geriatr Psychiatry first? OTP Neurol 7: (Supplement 1); S54-6, 1994. Before you begin to treat your mother, “Before you begin Thiele B, Brink I and Ploch M. Modulation of cytokine to treat your mother, expression by Hypericum extract. J Geriatr Psychiatry you should question the Alzheimer’s Neurol 7: (Supplement 1); S60-2, 1994. diagnosis. It is very easy for clinicians to you should question the misdiagnose some kinds of senility syn- Alzheimer’s diagnosis. What are the Best dromes as Alzheimer’s disease. It is also easy Smart Drugs? It is very easy for to misdiagnose some kinds of drug-drug I’m a new subscriber and would like your interactions as Alzheimer’s disease. These clinicians to misdiag- opinion about which smart drugs are best non-Alzheimer’s conditions are generally nose some kinds of for starting a smart-drug program? OTP much easier to treat than Alzheimer’s senility syndromes as Asking “What’s the best smart drug?” is disease. Sometimes, with these conditions, a like asking “What’s the best garden tool?” complete reversal of symptoms is possible. Alzheimer’s disease.” You really have to have a context to answer This is generally not a reasonable expec- the question. If you want to move dirt, then tation with Alzheimer’s disease. Effective a shovel is better than a pruner. But if you therapy for Alzheimer’s disease provides a Smart Life News [v6n7] 29 June 1998 11 quite deficient) levels. with. In men, estrogen levels increase with Transdermal testosterone delivery (via age as testosterone and DHEA levels patches, creams and lotions) has recently decrease with age. It is possible, and maybe continued from previous page become a popular alternative to injections. even likely, that some aspects of aging are Transdermal testosterone can be applied on directly due to the increasing influence of and absorbed through the skin to provide a estrogen with advancing age. It is also possi- smoother, less volatile testosterone profile ble that rising estrogen levels play a major which 1) reduces negative feedback to the role in prostate enlargement, and prostate hypothalamus, and 2) can more closely and testicular cancers. Androstenedione is Figure 1: follow the natural circadian rhythm for more closely linked to the estrogen branches Androstenedione testosterone. Testosterone creams are far of the steroid tree than DHEA, which also has Steroid Pathways less painful than injections and often much potential estrogen-related risks. more convenient for people to use. Androstenediol, a close cousin of andro- Androstenedione offers a stenedione, is able to be directly metabolized fast-acting, over-the-counter into testosterone but only indirectly into alternative to prescription- estradiol and estrone (see Figure 1). It is only testosterone patches, reportedly more efficient at producing creams and lotions. It is sold testosterone than androstenedione. It is pos- in capsules or pills for oral use, sible that it produces less estrogen as well. and it has recently become avail- As far as I know, the estrogen-enhancing able in a liquid spray for sublingual effect of all these compounds has not been use. The sublingual spray raises systematically evaluated or compared. Even testosterone levels in less than 30 if we knew the comparative risks, testing minutes. would still be needed. Clinicians report The problem with androstene- large differences among their patients in dione is that it is quickly metabolized how steroids are metabolized into estrogens. into estrogens. Estrogens have strong Test and be sure. anti-testosterone-like metabolic Androstenedione is available through effects that last for a long time Smart Basics, Vitamin Research Products and (days as opposed to hours). Olympia Nutrition, all on our Resources Androstenedione produces Listing. Androstenediol is available through estrogens through two Olympia, and Anabol Power Dist. (011-31- separate pathways. First, it 26-381-0668, in The Netherlands). Olympia can be directly metabolized into estrone also has a combination formula. SWF (see Figure 1). Second, it can be metab- olized to testosterone and then to New Liquid Deprenyl Sources? estradiol. Both estradiol and estrone Please advise as to current status of B&B are “strong” estrogens which Freight and other sources for Discovery- suppress the anabolic, metabolism- brand liquid deprenyl citrate, or alternatives enhancing, fat-loss and tissue-healing that might be available. Thank you. SK properties of testosterone. I believe that B&B Freight has folded. International many people will suffer estrogen-related side Antiaging Systems (IAS) is still shipping. A effects from androstenedione that will have new source, Professional Compounding far more negative impact on their health than Pharmacy (1-800-934-6337), just started the positive effects from androstenedione or making DEDI (Discovery) liquid deprenyl testosterone. available by prescription. Details can be The estrogen problem can be clinically found in the Sources Update on page 12 of “The problem with managed by measuring before-and-after this issue. SWF androstenedione is that estrogen levels. This can be done with blood tests that are available through a physician, Prozac vs Constipation? it is quickly metabolized or with saliva tests that are available over the Thank you for your response to my last into estrogens.” counter (call Vitamin Research Products or question about the use of Prozac in Down’s Smart Basics). Such tests can give you some syndrome. One of the changes that I have idea of the magnitude of the estrogen risks noted is that my son is no longer constipated. that may be associated with your use of Dr. [Lawrence] Leichtman has told me that androstenedione (or its immediate precursor this phenomenon is common. He thinks that DHEA, which can also be metabolized into Down’s children may not be suffering from estrogens). Hirschsprungs’s disease, but from a sero- Estrogen is not something to be trifled tonin deficiency. TR Smart Life News [v6n8] 20 August 1998 5 Constipation can be caused by a lack of v5n9], used 5-HTP doses of 1 mg/kg body peristalsis (rhythmic contractions of intes- weight. But you might want to start with tinal smooth muscles). Peristalsis is under only 5 mg and see if there is any effect for a continued from previous page the influence of the cholinergic and seroton- few days before going to 10, 25 or maybe inergic nervous systems. Cholinergic even 50 mg doses. Currently, 5-HTP is sold neurons use acetylcholine as a neuro- most commonly in 25, 50 and 100 mg sizes. transmitter, which is why choline, DMAE and These larger sizes are likely to be too large vitamin B5 increase peristalsis and stimulate for young children. However, they can be bowel movements. Although I have divided up into smaller doses and mixed into “You might want to suggested cholinergic stimulation to mothers beverages or solid foods. investigate the effects with constipated children, it has not seemed To maximize the brain’s absorption of to work as well in children with Down’s 5-HTP, it is best to take 5-HTP on an empty of 5-hydroxytryptophan syndrome as it does in the general popu- stomach (i.e., without protein-containing (5-HTP) on peristalsis lation. It is possible that the constipation foods). However, for maximizing gastro- and constipation.” problem in Down’s syndrome is due to sero- intestinal stimulation, I think it might be toninergic deficit, rather than a cholinergic better to take it with food. Plus, giving 5-HTP deficit as I had first assumed. In retrospect, with meals is probably much more conven- it makes perfect sense. ient for parents with young children and If true, then you might want to investigate busy schedules. the effects of 5-hydroxytryptophan (5-HTP) LifeLink mentioned to me that they have on peristalsis and constipation. Unlike just produced a mint flavored 25 mg 5-HTP tryptophan, whose conversion to serotonin losenge that might be a convenient strategy in the gut is limited by feedback control for giving 5-HTP to children, especially Figure 2: mechanisms (see step 1 in Figures 2 and 3), between meals. Interested readers can call Serotonin 5-HTP bypasses the bottleneck (step 2) and LifeLink at 1-888-433-5266. SWF can raise serotonin activity beyond the level Biosynthesis Tobacco vs Carbohydrates Schematic established by the body’s normal feedback control. Indeed, the most common side In your last newsletter you compared the effect from 5-HTP is gastrointestinal motility addicting properties of carbohydrates with (i.e., gut-muscle stimulation) from the con- those of tobacco. This is unfair. Carbo- version of 5-HTP into serotonin in the lining hydrates don’t cause cancer. They don’t kill Dietary of the intestine, where 5-HTP is first thousands of people every year before their Tryptophan absorbed. It seems likely that 5-HTP time. Aren’t you stretching an analogy to the supplementation would achieve the same breaking point? anon Rate serotoninergic effect in the gut as Prozac. In I actually chose that example to be 1Limiting addition, the 5-HTP that escapes gut metab- deliberately inflammatory. We (most of us, tryptophan hydroxylase olism can be absorbed by the brain and at least) have a double standard about converted into serotonin producing central addiction that blinds us to the debilitating behavioral effects similar to Prozac (refer to effects of carbohydrate addiction or wheat- the answer in the last issue for more allergy addiction in comparison to, say, 5-HTP explanation). heroin or tobacco addiction. However, from 2 Although tryptophan supplementation a biological point of view, there is very little decarboxylase can increase serotonin in the central nervous difference between tobacco addiction and system when it is taken without protein carbohydrate addiction. negative feedback and/or with carbohydrate, it does not raise Your suggestion that carbohydrates don’t control serotonin very effectively in the peripheral cause cancer is not accurate. Carbohydrates Serotonin nervous system that controls intestinal can induce hyperinsulinemia (an age- and smooth muscles. The conversion of obesity-associated state of insulin resis- tryptophan to serotonin is strongly tance), which is associated with significantly

ke regulated in the gut. The conversion of increased risks of cancer. The late Professor reupta 5-HTP to serotonin is not. Vladimir Dilman, M.D., Ph.D., D.M.Sc. even 3 MAO 5-HTP is about ten times more potent coined the name “cancerophilia” to describe than tryptophan, gram for gram, at this state of enhanced susceptibility to increasing brain serotonin. I can’t say I have cancer. Just because we praise carbo- much idea about how efficient 5-HTP may be hydrates and wheat and vilify tobacco and in stimulating peristalsis in serotoniner- heroin doesn’t change the fact that carbo- gically deprived Down’s syndrome children. hydrate-induced neuroendocrine dysregula- Some experimentation may be needed. The tion can strongly increase cancer risks. Fiona study of piracetam and 5-HTP [see SDN It is my opinion that the political pro- 6 Smart Life News [v6n8] 20 August 1998 Smart Life Update: disease (diarrhea, gut discomfort, maldiges- days followed by reintroduction of very Food Allergy and tion) and interfere with nutrient absorption small amounts of grain can produce strong in the small intestine. There may also be objective and subjective symptoms in grain- Neurodegenerative adverse health consequences from grains intolerant individuals. Intolerance can be Disease that do not act through or require immune indicated by 1) increased body temperature, sensitization (antibody production). The 2) increases in pulse rate, 3) intestinal com- (continued from previous page) quest for answers to such questions is still plaints (cramps, gas and/or diarrhea), hampered by both social and economic 4) bloating and/or puffiness (i.e., changes in “For people without imperatives that make grains a necessary and tissue hydration), 5) increased mental acuity cooperative doctors essential element of our modern diet. The initially, possibly followed by mental fuzzi- ideological defense of such imperatives is ness and “zoning out,” 6) emotional volatility or the financial means grounded in conventional wisdom that (anger, irritability, depression), and 7) food to afford blood tests, grains are one of the healthiest components cravings for more grain. Due to the possibil- dietary restriction and of a modern balanced diet. ity of extreme emotional and cognitive changes upon reintroduction of grain in an food reintroduction can Testing and Evaluation intolerant individual, the process should be provide an indication Blood tests for gluten-related antibodies conducted under controlled and supervised of food intolerance.” are available through physicians. For people conditions. Having a trusted friend or family without cooperative doctors or the financial member present is essential, not only to means to afford blood tests, dietary restric- provide an interactive stimulus from which tion and food reintroduction can provide an to judge cognitive and emotional responses, indication of food intolerance. Complete but to provide an independent observer. elimination of grain for a period of 10-14 This person can coordinate temperature

Oxidative Stress in Children during Heart Surgery Plasma Antioxidant Capacity ( mol/ ml plasma) One of the issues that we have raised on a couple of occasions is the advis- ability of continuing TNI therapy during heart surgery to correct for congenital heart defects associated with Down’s syndrome. Our position has been that the .75 standard rationale to discontinue TNI based on a lack of knowledge about how TNI might influence surgery has no documented scientific basis. Furthermore, the metabolic and antioxidant assistance that TNI offers should be of value for .50 (n=4) (n=6) (n=20) children facing the many well known and potentially extreme stresses of surgery. Direct scientific evidence documenting the extreme oxidative stress of heart surgery has been published. This research confirms that congenital heart surgery .25 in children causes massive depletion of antioxidant reserves, especially in those children less than one year of age. Antioxidant status was measured by two methods: 1) plasma antioxidant capacity (the ability of the children’s blood to <1 Month <1 Year >1 Year prevent in vitro oxidation of the polyunsaturated fatty acid linoleic acid) and Age Groups 2) malondialdehyde inhibition (the ability of the children’s blood to prevent lipid Malondialdehyde Inhibition peroxidation in beef brain homogenates). These two measurements were made (% inhibition ) at three different times (see adjacent illustrations): 1) before surgery (light gray bars), 2) after the heart bypass (mid-surgery, medium gray bars), and 3) after surgery (after transfer to intensive-care facility, dark gray bars). 75 (n=4) (n=6) (n=20) The results of this study show a drastic depletion of antioxidant reserves caused by the surgery in children of all ages. This depletion was most severe in the younger children, who showed almost complete elimination of all plasma 50 antioxidant capacity. The severity of this antioxidant depletion should give pause to physicians and surgeons recommending discontinuation of TNI prior to heart surgery, and to parents faced with such recommendations. 25 It is critical to keep in mind that the data of this study were obtained from surgeries in non-DS children, who do not have the additional antioxidant burden of a genetic disruption of their antioxidant defense systems by the overexpression <1 Month <1 Year >1 Year of SOD (superoxide dismutase) from the triplicated 21st chromosome. This Age Groups would suggest that these results, as severe as they are, would be worse in children Key with trisomy 21. SWF Baseline (pre-surgery) LA Pyles, JE Fortney, JJ Kudlak, RA Gustafson and S Einzig. Plasma antioxidant depletion after cardio- After bypass (mid-surgery) pulmonary bypass in operations for congenital heart disease. The Journal of Thoracic and Cardiovascular At recovery (post-surgery) Surgery 110: 165-71, July 1995.

Smart Life News [v6n9] 1 October 1998 3 tive protection system. The preventive effect of an antioxi- (i.e., upregulated or downregulated) by dant and the therapeutical effect of an antihypoxant were recorded in the prevention of murine death due to influ- changing conditions in the body. They enza. The mechanisms of the protective effect of the anti- adapt. Often, when exogenous antioxidants continued from previous page hypoxant is due both to its immediate antihypoxant func- are increased, endogenous antioxidants tion and its correcting influence on lipid peroxidation.” EC Pirtle, JM Sacks and RJ Nachman. Antiviral effectiveness decrease. This is due to the fact that SOD, of butylated hydroxytoluene against pseudorabies catalase and glutathione peroxidase are (Aujesky’s disease) virus in cell culture, mice and swine. American Journal of Veterinary Research 47(9): 1892-95, produced in response to specific types of September 1986. oxidative stress. If one decreases that oxida- AV Pokhil’ko, TA Kramskaia and RIa Poliak. [Stress and viral tive stress by supplementing antioxidants, infection: dynamics of expression of influenza A viral anti- gens during immobilization stress]. Voprosy Virusologii, the body’s response to oxidative stress 40(2): 76-9, Mar-Apr 1995. “The level of expression of decreases. influenza virus antigens in the target organ is an important The implications of how these two characteristic of the severity of a viral process, as was shown on a model of experimental influenza A. Stress exposure systems interact is critical to understanding augmenting the severity of the infection stimulates the how to optimize antioxidant defenses in expression of viral polypeptides in the acute period of the disease. Injection of an antioxidant ionol which may both Down’s syndrome individuals (where prevent stress-enhanced synthesis of viral proteins. there is a genetically determined imbalance Stress-induced disorder of the mechanisms of formation of in endogenous antioxidant defenses) and in “The endogenous immunological memory is paralleled by accumulation of antioxidants (catalase, high levels of virus-specific proteins in the lungs after non-DS individuals (who might want to repeated exposure of an animal to a homologous virus. optimize antioxidant defenses for general glutathione peroxidase, Hence, the level of viral antigens synthesized in the course of reinfection also helps assess the degree of body health and life-extension purposes). SOD, glutathione, etc.) protection from this agent. The second thing to understand about the are under metabolic antioxidant defense system is that anti- Antioxidant Supplements? oxidants work with each other. This means and genetic control, Some of the information I recently down- that synergy (enhanced antioxidant func- and are therefore not loaded off the Internet (CERI’s and Dr. tion) is often noted with combinations of easily manipulated.” Swenson’s sites) suggests that antioxidant antioxidants that is not noted with single supplementation is the primary answer to antioxidants. Antioxidants are like the rungs the increased oxidative stress of SOD over- of a ladder; when one rung is weak or expression in Down’s syndrome. Is it really missing, it is hard to use the ladder effectively that simple? P or safely. Yes and no. Yes, antioxidant supplemen- Another useful analogy is the old-time tation is currently our best therapeutic bucket brigade for putting out fires. Free- approach. However, it is not just a matter of radical stress is like a fire, and the antioxidant increasing all antioxidants equally. A full defensesystemcarriesbucketsofwater understanding of how the antioxidant (reducing power) to the sites of the stress to defense system works and how SOD quench the fire. If everybody in the bucket (superoxide dismutase) overexpression brigade from the water supply to the fire disturbs that function is necessary to specify hands off buckets equally quickly, then the which antioxidants and which cofactors chances of putting out fires are maximized. should be supplemented, and which should If one person is unable to keep up, then the “A full understanding not. line is slowed down. This causes buckets to of how the antioxidant The first thing to understand about the accumulate at certain points along the way, antioxidant defense system is that it is and depletion of buckets at other points. If defense system works composed of two different parts: 1) the an extra person can be added “in parallel” to and how superoxide exogenous antioxidants, which can be assist the slowest person, then efficiency dismutase over- obtained from outside the body (through the goes up and the backlog of buckets is diet), and 2) the endogenous antioxidants, returned to the chain. This is what happens expression disturbs which are made within the body. The exog- when you supplement a deficient antioxi- that function is enous antioxidants (vitamins A, C and E, dant. If the extra person assists somebody necessary to specify carotenoids, cysteine, Co-Q10,thiamine, who is keeping up and who does not have a lipoate, etc.) and cofactors (iron, zinc, backlog of buckets, there will be minimal which antioxidants and copper, manganese, selenium, B-vitamins, improvement, if any. This is what happens which cofactors should etc.) are easily manipulated through diet and when you over-supplement a robust anti- be supplemented, and supplements. The endogenous antioxidants oxidant. (catalase, glutathione peroxidase, SOD, I like the bucket brigade analogy for which should not.” glutathione, etc.) are under metabolic and another reason: it works by timing and genetic control, and are therefore not easily rhythm. Each person has to be ready to manipulated. accept the next bucket when it is handed. If Endogenous antioxidants are induced somebody hands buckets too fast, they can Smart Life News [v6n9] 1 October 1998 5 upset the rhythm of the next person and Dealing with increased hydrogen perox- overload the chain. The speed and rhythm ide is more straightforward. We feed the of the human bucket brigade is analogous to nutrients which maximize the body’s ability continued from previous page the “balance” between antioxidants in the to induce (produce) catalase and glutathione antioxidant defense system. peroxidase, which keep hydrogen peroxide In normal antioxidant metabolism (see under control. The nutritional cofactor for “The question as to Figure 1, below), the production of SOD and catalase is iron. However, excess iron can what to do about the catalase are optimized to maintain the “ideal” aggravate hydrogen peroxide toxicity (via amount of superoxide anion (an “activated” the Fenton reaction) (see SDN v4n10). So we decreased levels of form of oxygen necessary for various supplement iron only when there is a superoxide in trisomy metabolic reactions) and hydrogen peroxide demonstrated state of iron-deficiency 21 is not one that has (also necessary for metabolism). In Down’s anemia. syndrome, the extra 21st chromosome The nutritional cofactor for glutathione yet been answered.” produces 50% more SOD (see Figure 2). This peroxidase is selenium, four atoms of which decreases superoxide (which is upstream are needed to make one glutathione peroxi- from SOD) and increases hydrogen peroxide dase enzyme. Selenium supplementation (which is downstream from SOD). (In a poses no significant toxicity and is therefore Figures 1-4: genetic disorder characterized by deletion a universal element of targeted nutritional Flow Diagrams instead of duplication of genetic material, intervention (TNI) formulas for Down’s of the Antioxidant the opposite change occurs: the upstream syndrome. Defense System substances are increased and the down- The constant induction of glutathione stream substances are diminished.) peroxidase by elevated hydrogen peroxide The question as to what to do about the (see Figure 2) can deplete selenium levels. decreased levels of super- In the face of a selenium deficiency (see O catalase 2 HO22 oxide in trisomy 21 is not Figure 3), glutathione peroxidase production superoxide SOD hydrogen anion peroxide onethathasyetbeen may become seriously compromised, further radical GSH-px answered. Supplementa- increasing the hydrogen peroxide pool. Figure 1: Normal tion of superoxide anions (also The metabolic consequences of selenium Genetically balanced antioxidant enzymes known as “negative ions”) may deficiency go beyond hydrogen peroxide. correct for metabolic impair- Selenium is also necessary for the produc- O 2 HO22 catalase ment of oxygen metab- tion of thyroid hormone in the thyroid gland, superoxide SOD hydrogen olism due to superoxide and for the conversion of T (low-potency anion peroxide 4 radical GSH-px deficiency, but it also thyroid hormone) into T3 (high-potency Figure 2: Trisomy 21Down’s syndrome: would increase hydro- thyroid hormone) in the non-thyroid tissues Overexpressed SOD, induced catalase & glutathione peroxidase gen peroxide burdens of the body. Indeed, thyroid insufficiency in the bargain. The problems have been noted as a clinically O current “conventional wis- significant feature of Down’s syndrome. 2 HO22 catalase superoxide SOD hydrogen dom” of the Trisomy 21 Selenium supplementation in Down’s anion peroxide radical GSH-px Research Scientific Advis- syndrome removes possible impairment of Figure 3: Trisomy, Se deficient ory Committee is that an glutathione peroxidase synthesis, optimizes 50% more SOD, impaired glutathione peroxidase induction increase in hydrogen the body’s ability to reduce elevated hydro- peroxide may pose an gen peroxide levels (see Figure 4), and unacceptable risk, so we do prevents “secondary” (induced) selenium O catalase 2 HO22 not try to ameliorate the deficiency problems in other systems of the superoxide SOD hydrogen anion peroxide deficiency of superoxide body (i.e., thyroid regulation of protein radical GSH-px caused by SOD over- synthesis, mitochondrial function and basal Figure 4: Trisomy, Se supplemented expression. metabolic rate). For an article discussing 50% more SOD, enhanced glutathione peroxidase induction secondary nutrient deficiencies, see “The Art of Nutritional Therapeutics” (SDN v4n9). Table 1: Antioxidant Enzymes in Down’s Syndrome The critical importance of selenium and Control DS Variance glutathione peroxidase in Down’s syndrome Enzyme ActivityEnzyme Activity Increase ControlDS Diff. may have been revealed recently by a study of endogenous antioxidants in 72 patients SOD-1476 ±67U/g Hb 635 ±70U/g Hb 133%±14% ±11% -3% [Pastor et al., 1998]. The researchers CAT1482 ± 250 U/g Hb 1843 ± 250 U/g Hb 124%±17% ±14% -3% measured levels of superoxide dismutase GSHpx21.5 ± 3.6 U/g Hb 23.2 ± 5.3 U/g Hb 108%±17% ±23% +6% (SOD-1), glutathione peroxidase (GSHpx), GSHr6.9 ± 1.3 U/g Hb 9.32 ± 1.4 U/g Hb 135%±19% ±15% -4% catalase (CAT), and glutathione reductase (GSHr) enzymes in red blood cells (see Table Adapted from M C Pastor, C Sierra, W Dolade et al. Clinical Chemistry 44(5): 924-9, May, 1998. 1 at left). The activity of SOD-1 was 33% 6 Smart Life News [v6n9] 1 October 1998 higher than normal controls, which was consistent with its overexpression from the triplicated 21st chromosome. The activity of continued from previous page the “downstream” enzymes CAT and GSHpx were also increased, presumably induced (upregulated) by the increased hydrogen peroxide from the extra SOD. However, the induction of these enzymes was not proportional to the increase of SOD. While CAT activity was increased 24%, a value close to the 33% increase for SOD, GSHpx activity “This shortfall of was only increased by 8%. This shortfall of glutathione peroxidase GSHpx may be a focal point for maladapta- tion to oxidative stress in Down’s may be a focal point syndrome. This hypothesis is supported for maladaptation to by the slightly higher activity of GSHr, oxidative stress in which recycles glutathione and assists the activity of the stressed-out GSHpx. Down’s syndrome.” Further evidence for GSHpx stress can be found in the variance in values for the different enzymes. The variance in enzyme levels in the DS group was less than controls, except for GSHpx activity, O DHEAS which was higher. Convergence O S O (lessening) of variance is what we O would expect in a stressed system that is adapting adequately, which is what we The see with SOD, CAT and GSHr. However, Steroid Tree “Selenium supple- GSHpx values diverge with the oxidative Copyright 1997, 1998 by Steven Wm. Fowkes mentation also has the stress of Down’s syndrome, suggesting the possibility of maladaptation. potential for decreasing Selenium supplementation also has the overall cancer risks.” potential for decreasing overall cancer risks. In epidemiological studies, selenium levels are strongly correlated with both cancer incidence and cancer mortality. SWF M C Pastor, C Sierra, W Dolade et al. Antioxidant enzymes (steps 1 and 2) increases testosterone while and fatty acid status in erythrocytes of Down’s syndrome catabolism (steps 2, 3 and 4) decreases patients. Clinical Chemistry 44(5): 924-9, May, 1998. “The aim of this study was to evaluate the cellular antioxidant testosterone. It is the balance between bio- system by determining the catalytic activity of the SOD1, synthesis and catabolism that ultimately glutathione peroxidase, catalase, and glutathione reductase enzymes and the concentrations of alpha-tocopherol in red determines testosterone levels. Supple- blood cells (RBCs) in a group of 72 DS patients.” “No menting testosterone, androstenediol, differences were observed in RBC alpha-tocopherol androstenedione, DHEA, pregnenolone concentrations between the two groups studied. Long-chain ω6 PUFA (C20:3n6, C20:4n6) concentrations were increased and/or progesterone may increase the bio- in DS patients, suggesting enhanced delta-6-desaturase synthetic pathways, but they cannot guaran- activity. The long-chain ω3 PUFA (docosahexenoic acid) “What’s the best way to does not appear to be affected by increased oxidative stress, tee increased testosterone levels. One must raise testosterone levels probably because of the existence of compensatory also consider the catabolic pathways which antioxidant mechanisms.” turn testosterone into dihydrotestosterone in a 58-year-old man? and estradiol (estrogen). 5-α-Reductase Androstenediol? DHEA? Raising Testosterone? (step 3) converts testosterone into dihydro- What’s the best way to raise testosterone Testosterone itself?” testosterone. Aromatase (step 4) converts levels in a 58-year-old man? Androstenediol? testosterone into estradiol (and androstene- DHEA? Testosterone itself? MD dione into estrone). When considering testosterone, we need Although biosynthesis of testosterone to step back one level to consider the two decreases with age, I think that most men’s opposing influences of 1) biosynthesis testosterone levels are not as strongly limited (testosterone production) and 2) catabolism by the availability of precursors (biosynthe- (testosterone conversion to other hormones) sis) as they are by age-associated increases in (see Steroid Tree illustration). Biosynthesis the activity of 5-α-reductase and aromatase. Smart Life News [v6n9] 1 October 1998 7 lower temperature, because MCT oil is more temporary? That is, if she were to be taken volatile and therefore more flammable than off, would the tone return? If I do take her off long-chain fats). the GABA, should it be backed down slowly, continued from previous page A strategy for enhancing fat burning that or can I do it at one time? works for me is to take a little bit of MCT oil I think phasing GABA out over several (1/2 a tsp for instance) before doing some days to a week should be the least stressful sort of extended exercise. AMF waytoproceed.Iwouldexpecttosee increased muscle tone in just days after “I understand that GABA GABA and Muscle Tone in DS? lowering the dose. may have a deleterious Hi Steve. I don’t know if you remember I, as many parents, value your opinion. I me or not, but we met at a few of the TNI know no one has all the answers, but we are effect on muscle tone.” seminars. I have have been following the all looking. What are your thoughts about recent discussion regarding use of GABA the homeopathic remedy, “serotonium”? and muscle tone. I have given it to my I don’t think there is much risk in trying a 2-year-old daughter (DS) on two different homeopathic serotonin formulation in sero- occasions. The first was from lab results toninergically deficient children. done at 6 months of age through Munroe I have been following the Prozac trials, Labs (George Miroff). Miroff suggested I add but have not tried it with my daughter. We it to her protocol. I added it for a few months don’t have a major constipation issue with and then remembered Dixie’s warning her as long as she eats many fruits and people about changing the protocol, etc. So veggies. But now that she’s getting older and I stopped. Just about 3 wks ago, started eating only what she wants, fruits and vege- “It is possible that a using it again. I understand that GABA may tables are getting harder to push all the time. combination of GABA have a deleterious effect on muscle tone. Your thoughts on 5-HTP? Yes. Skeletal muscles use the neurotrans- LifeLink has just formulated a sweetened with DMAE or choline mitter acetylcholine to stimulate tone, and 5-HTP lozenge that might be convenient for would allow the GABA to relax muscle tone. Acetylcholine dosing children. Their first formulation is beneficial effects of can be increased by taking precursors really intended for older children and adults (DMAE, choline, phosphatidylcholine, with 25 mg 5-HTP, minimal sweetness, and GABA on speech lecithin) and cofactors (vitamin B5). GABA mint flavoring. I think that a sweeter, grape-, without excessive can be increased by supplementing GABA or cherry-, lemon-lime- or orange-flavored loss of muscle tone.” GHB. lozenge with maybe 10 mg of 5-HTP would Maybe I’m being ultra paranoid, but can have great potential for young children, but changes in muscle tone be noticed in as short it needs some experience in the trenches to a time as 2-3 weeks? get a better idea about doses, frequency of Changes in muscle tone from GABA can dosing, threshold effects, combining with take place quickly. They may take days to food, and possible synergy with Prozac or St. weeks to reach maximum potential, but they John’s wort. I’d very much like to hear any are subjectively noticeable in maybe 30 observations you have about these issues. minutes to possibly two hours. Try it your- self so that you can know how it works from 5-HTP Contamination? a personal perspective. GABA is rather A recent paper makes the claim that pleasant. It is a good after-work destresser 5-HTP products are contaminated with for many people. “peak X.” Is this true? What is peak X? And “A recent paper Mydaughterseemsmorelike“dead is there cause for concern? makes the claim that weight” to me these last couple of days. I did It is true. A recent letter to the editor notice a positive change in her concentra- claims that at least some of the 5-HTP 5-HTP products are tion and an increase in her speech (new products currently in the market contain contaminated with words were the rule, instead of the excep- very small amounts of an unknown sub- ‘peak X.’ Is this true? tion), but her speech and articulation have stance which may be associated with cases of fortunately always been quite good. At the EMS (eosinophilia myalgia syndrome). I say What is peak X? Is there age of 2, she uses about 20 different words “may” because we do not know that peak X cause for concern?” and is just starting to put two words together is causally related to EMS. Although a tenta- occasionally. tive structure for peak X has been proposed, It is possible that a combination of GABA it has yet to be confirmed by an independent with DMAE or choline would allow the laboratory. We really are not yet sure just beneficial effects of GABA on speech without what peak X is. excessive loss of muscle tone. Since all substances sold in the market Is this possible decline in muscle tone have impurities, “peaks” are the rule rather Smart Life News [v6n9] 1 October 1998 9 Angeles. Inquiring at all possible Customs Deprenyl Delay? offices is a large amount of work — and IAS in England said they shipped my probably a semi-futile proposition. SWF order of liquid deprenyl, but it has not yet arrived. I don’t know if it is being held by Dr. Warner on Piracetam customs or not. I have received no com- The following is an e-mail from a lady on munications from them. I assume the ship- the official NACD list: “A friend just returned ment has been routed through Chicago, as yesterday from the Warner Clinic in Califor- this is our closest point of entry. Is there nia with her 4 year DS son. She came home anything I can do? Thanks. Anon loaded with info and a giant-sized warning There’s not much you can do. Assuming from Dr. Warner about the use of piracetam. that IAS really did ship your order, it could be She knows I have both my kids on it and was sitting in a Customs or FDA office some- concerned about their taking it. Apparently, “Unfortunately, there’s where waiting for someone to take action she said Dr. Warner told her he is seeing no way to know which (i.e., send you a letter). Sometimes FDA clients now who have been on piracetam for agents wait 2-3 months before sending a some time and they are showing major signs port of entry your letter notifying the citizen of the detention. of regression in their speech. She said he shipment might have Who would know if they never sent you a attributed this to piracetam thinning or gone through.” letter? It would take an audit by Customs to destroying the myelin sheath covering the cross check detained shipments with FDA nerves.” Can you address this? N letters. I doubt that anybody in the govern- There is no evidence that piracetam thins ment is willing to do that for two reasons: 1) or destroys myelin or myelin nerve sheaths it is expensive to investigate such matters, in anybody, despite 30 years of clinical use. and 2) they might find that dereliction of duty The two most authoritative texts summa- “A friend came home is common practice among FDA personnel. rizing piracetam’s medical uses and side loaded with info and Unfortunately, there’s no way to know effects are probably Martindale: The Extra which port of entry your shipment might Pharmacopoeia (published by the Royal a giant-sized warning have gone through. Chicago may be closest Pharmaceutical Society of Great Britain), and from Dr. Warner about to you, but the first Customs port that your Meyler’s Side Effects of Drugs (published by the use of piracetam.” shipment passes through handles the inspec- Elsevier Publishing, one of the largest and tion. Mail from Europe is just as likely to most prestigious scientific/medical pub- have been routed through Baltimore, New lishers in the world). Neither of these York or Atlanta. It could even have gone sources (nor any of the published review through Dallas/Fort Worth, Denver or Los articles on piracetam) mention any myelin-

The Genetics Promoter I.1 Promoter I.4 Promoter I.3 Promoter II CYP19 Gene Exon I.1 Exon I.4 Exon I.3 Exon II Exon III Exon IV... of Aromatase 5’ terminus Introns 3’ The CYP19 gene provides the genetic transcription sequence for aromatase (also called P450arom). Placenta Trans I.1 Trans II Trans III Trans IV... It consists of nine exons Trans I.4 Trans II Trans III Trans IV... Adapted from (genetic sequences that are Adipose/skin Bulun et al., 1997. preserved during the transcription Adipose Trans I.3 Trans II Trans III Trans IV... process), a number of introns (genetic sequences that are “edited out” and lost during the transcription Gonads/adipose Trans II Trans III Trans IV... process), and four promoters (genetic sequences that trigger gene transcription). Transcription is the biological process of translating DNA sequences (genes) into RNA (ribonucleic acid) sequences, and then into amino acid sequences (otherwise known as peptides, proteins and/or enzymes). Transcription is the mechanism underlying protein synthesis. Of the nine exons (II-X), only exons II, III and IV are shown in the above illustration. Transcription of the aromatase protein begins at the 5’ terminus (end), just after the promoter, and continues towards the 3’ terminus, from exon II through exon X. The intron-derived segments are snipped out during the transcription process so that the exon-derived protein segments end up connected end to end. Finally, the exon I protein segment is removed, leaving the finished protein product, aromatase. Despite multiple promoters and different exon I segments during transcription, the finished aromatase enzymes end up identical, consisting only of protein segments transcribed from exons II through X. The multiplicity of promoters allows a variety of agents to independently influence and/or regulate the production of aromatase. SWF

Smart Life News [v7n1] 4 January 1999 7 related effects from piracetam. Yet all of homeostasis mechanisms, which attempt to these sources conspicuously mention the restore “balance” in response to pretty much rheological (blood-thinning) effects of any metabolic shift. Piracetam produces a continued from previous page piracetam at the higher doses typically used pharmacological effect, to which the body to treat myoclonic seizure disorders (usually partially compensates. This is in no way a 4-10 times higher than doses than are sign of degenerating myelin. SWF commonly used to treat Down’s syndrome). “There have been no These rheological effects are not seen at the Calcium Pantothenate? studies on long-term 30 mg/kg doses used for cognitive-enhance- Are cheap calcium pantothenate tablets ment purposes. good sources for pantothenic acid (vitamin speech enhancement I have searched Medline (the US Library B5)? DM in Down’s syndrome of Medicine), EMbase (Excerpta Medica, the Yes, if they dissolve appropriately. individuals.” European medical database), and Biosis Calcium pantothenate is simply the calcium (Biological Sciences database) and there is salt of pantothenic acid. It is, overall, the no reference for demyelinating effects from best commercial source of vitamin B5 avail- piracetam. However, there may be such a able. report published somewhere in the world, in You can test your cheap calcium panto- some language, that discusses such a hypo- thenate tablets by dropping one or more of thesis. I rely extensively upon Medline, them into a small glass or glass bottle filled because it is inexpensive and easy to access. with about half an inch of white vinegar. However, Medline only covers about 5% of Any vinegar is OK if it is transparent enough the world’s total published medical litera- to clearly see the tablets. The vinegar (5% ture. EMbase is better, being less provincial acetic acid) approximates the hydrochloric “Piracetam produces a and covering maybe 15% of the world’s acid in the stomach. If the tablet(s) dissolve, pharmacological effect, literature. But it is is expensive to access. disperse or disintegrate in 15 minutes or less, The point to understand is that there is a lot they are OK. to which the body of published research out there which is not If they don’t spontaneously disintegrate, partially compensates. accessible through electronic databases. there may be a problem. Pick up the glass This is in no way a sign As to speech regression, that is possible. and tilt the glass back and forth to gently There have been no studies on long-term swirl the vinegar around the tablet. If they of degenerating myelin.” speech enhancement in Down’s syndrome remain intact, try poking them with a knife individuals. However, I am inclined to or fork and see if they are softened. If not, discount Dr. Warner’s observations for the they are not worth any price. Ask for your following reasons: 1) the studies of speech money back — or throw them away. enhancement in non-DS populations do not This test does not work with timed- show a regression effect, 2) such an effect release tablets, which are designed not to has not been noted by other practitioners disintegrate quickly. However, timed- treating DS with piracetam, 3) Dr. Warner’s release tablets are usually substantially more attitude towards piracetam is, in my opinion, expensive to manufacture, so it is unlikely highly prejudiced and un-scientific, and that your “cheap” tablets would be of the 4) parents using piracetam with their DS timed-release type. SWF “These two abstracts children are reporting long-term sustained Nasal Bromocriptine Better? on Medline regard enhancement of verbal abilities. This latter point needs some clarification. Man, I love your articles in the CERI the use of a nasal Some parents have commented that the newsletter! It seems that you are answering form of bromocriptine, initial quite-beneficial effects of piracetam a question I just found myself asking, or you which seems to offer were not sustainable, more specifically, that are anticipating a question I haven’t part of the benefit wore off in a matter of days formulated yet. Thanks... and keep up the several advantages.” to weeks, maybe months. However, they good work! generally thought that their child was still I found these two abstracts on Medline. doing much better on piracetam than before They regard the use of a nasal form of piracetam. Some parents tried stopping bromocriptine, which seems to offer several piracetam and noted a drop in verbalization, advantages, 1) it raises drug levels higher which was reversed when they resumed it. and faster than oral dosing, and 2) it This type of response — an initially strong bypasses liver metabolism so that less drug reaction which moderates with longer-term does more. Have you heard anything about use — is common with smart drugs in people this? Since the active ingredient in Parlodel of all ages and conditions. I think that part is in a salt form, shouldn’t it be soluble in of this response is attributable to the body’s water or saline? Might I be able to make a 8 Smart Life News [v7n1] 4 January 1999 have it (a false negative result). The antigen much as we’ve had time to, and are learning test is much more likely to detect it than a so much about the disorder. We are very stool culture. encouraged about the TNI protocol and continued from previous page Not all parasites are sensitive to the above would like to start our daughter on it as soon drugs. You have to figure out which one you as she’s born. But we want to know if there have to make sure you take the right drug. anything I can take while I’m still pregnant Those ones do most of them, however. that could help her physical and/or mental Chronically high levels of cortisol can development? DS sometimes be reduced by taking phospha- There are definitely things you can do tidylserine (OTC, expensive) and more often during the pregnancy. A minimalist (con- by taking carbamazepine (Rx, inexpensive, servative) approach would be to take pre- potentially toxic at doses near those natal vitamins. There are no scientific data “My unborn baby girl required). Carbamazepine is a standard backing it up, but women taking collagen has just been diagnosed antiepilepsy drug and is used for many other precursors may have DS children with less things, so most physicians will be familiar chance of heart defects and less joint laxity at with Down syndrome. with it but will not have heard of this use. It birth. That’s my hypothesis, based on a Is there anything I can reducesbaselinecortisolandmakesthe theoretical understanding of the conse- take while I’m still response to stress sharper, with higher spikes quences of over-expression of the two for acute stress events (and makes these collagen genes on the 21st chromosome, and pregnant that could spikes happen properly if you have trouble a few anecdotal reports. Post-natal collagen help her physical with that). It doesn’t do anything until you precursor therapy works wonders in the and/or mental get up to a therapeutic level similar to that children. used to control epilepsy. At this level it may It is my belief that antioxidant therapy is development?” impair coordination like alcohol does. By not needed during pregnancy unless you the way, one good indicator of cortisol ex- have an outright deficiency in your antioxi- cess is a weight problem. Dr. Andrew Cutler dant defense system. Your body does a good I should also add that vitamin A doses job of protecting your baby from oxidative above 10,000 IU may pose risks of birth stress, so you can wait until immediately defects (terratogenicity) during the earlierst before or after birth for antioxidants. SWF stages of pregnancy. Women capable of I was surprised that that issue of prenatal getting pregnant should not take high doses therapy was not covered in the TNI informa- of vitamin A. tional pages. DS The product MGN-3 is another enhancer I think that most organizations with “Women taking collagen of natural killer cells. “deep pockets” are leery of possible civil and precursors may have Herpes and other lipid enveloped viruses regulatory liability were they to say some- (hepatitis virus, influenza virus, cytomegalo- thing that is not approved of or sanctioned children with less virus, Epstein-Barr virus, varicella zoster by governmental and medical “experts.” The chance of heart defects virus, Newcastle disease virus, pseudorabies general rule is: if you don’t know for sure, and less joint laxity virus) seem to respond quite well to BHT (the don’t say anything. This rule especially food preservative) and hypericin (a applies to anybody that sells products at birth.” substance concentrated from St. John’s regulated by FDA. Since we do not, our wort). See SLN v6n9p4 for a report of BHT information is protected by the First Amend- and hypericin in a case of hepatitis C, and see ment to the US Constitution. We can provide Wipe Out Herpes with BHT and the BHT you information, speculations, theory and Toxicology Report for detailed information beliefs, and as long as we correctly identify it about BHT therapy. as such, we do not violate any laws. We For subscribers interested in mercury leave it up to you to integrate the information toxicity from dental fillings, Dr. Cutler has we provide into your personal values. produced an extensive book titled Amalgam So far, with four cases reported to us, no Illness: Diagnosis and Treatment which is woman taking collagen precursors has given available from the author for $35 (US funds birth to a DS infant with a heart defect. That’s drawn on US banks, sent to 10 Thunder Run not a very solid finding from a scientific per- #28-C, Irvine, CA 92614-7034 USA. Or write spective, but only you can make a judgement to [email protected]). SWF as to whether such potential benefits are worth the potential risks of taking collagen In Utero DS Therapy? precursors (which, I think, are minimal). The I am about 5 months pregnant. My unborn FDA won’t let any product-selling company baby girl has just been diagnosed with Down make that claim, even with disclaimers. A syndrome. My husband and I have read as recent Appeals Court decision may change 10 Smart Life News [v7n5] 15 September 1999 that, but I’ll believe it when it happens. have three choices for collagen amino acids: There is no reason why you cannot get 1) liquid predigested collagen protein (made yourself tested with the Metametrix ION test from hydrolyzed animal connective tissues continued from previous page panel while you are pregnant. If you have a and sold in health food stores), 2) purified selenium or zinc deficiency, the earlier you lysine and proline (proline is expensive), know about it the better for your pregnancy. and 3) Knox unflavored, unsweetened “There is no reason A deficiency of either one can have a serious gelatin (also made from connective tissues, why you cannot get impact on your baby’s antioxidant defense but sold in grocery stores). system after birth, and both are relatively If my baby already has a heart defect, yourself tested while easy and inexpensive to correct through would/could it still help her? you are pregnant. dietary supplements. In my opinion, yes! Heart development If you have a selenium In my opinion, the use of piracetam is a accelerates in the last trimester. Good luck separate question. If you haven’t already and best wishes. SWF or zinc deficiency, done so, please read the “The Case for Pir- the earlier you know acetam in Down’s Syndrome” article [SDN Metallic Urine from GHB? about it the better for v4n9p1 and on our web site]. I think that Could GHB cause a metallic smell in urine? piracetam is very useful during labor. It is I know that sounds a bit odd, but in my case your pregnancy.” fairly efficiently excreted in breast milk, it is a genuine question. Please answer. which makes dosing your baby easy if you I believe that pretty much anything can are willing to take it yourself. SWF causeanything.IfyoudoanA-B-A-B What are collagen precursors and how process on it and every time you take GHB can I tell if they are in my supplements? DS you get the metallic smell in your urine, and A precursor is a molecule or substance every time you stop it goes away, I would from which something else is made — like conclude that the answer to your question is sand is a precursor for a glass bottle. yes. It is, however, not a typical symptom. Proteins are made from amino acids. There- There may be something unique in your “If my baby already has fore amino acids are the precursors to metabolism. There is no reason that you a heart defect, could proteins. cannot investigate this possibility. Urine When you string amino acids together, organic acids is a test that might show high it still help her?” like beads on a string, you get proteins. The levels of succinic acid (a metal chelating collagen protein is made from a long string agent that would be produced if you were of amino acids, every third of which is not metabolizing GHB all the way) or other glycine, and almost every third of which is water-soluble metabolic byproducts of proline. A significant percentage of the other abnormal metabolism. Urine minerals is a third is lysine. Since 30% of the protein in the test that will identify the actual metals human body is collagen, and 30% of the content of your urine. Ask your doctor to do collagen is glycine and 30% is proline, that’s these tests, and see. SWF a lot of glycine and proline in absolute terms. So the precursors to look for on your Microhydrin? “Could GHB cause a supplement labels are: lysine, proline and I’m wondering if Microhydrin is something I metallic smell in urine?” glycine. Actually, glycine is so plentiful in should consider adding to my supplement the human diet that it rarely needs supple- intake. I’m 36 yrs old, in good health, and mentation. It doens’t hurt to take it and it is looking to stay young and in optimum quite inexpensive in comparison to the other health. Does this stuff live up to the hype I’m amino acids, but it is unnecessary. Lysine hearing? WL and proline are the important ones. Maybe. Microhydrin is a potent reducing There are also cofactors required for agent, and if you are deficient in reducing collagen maturation. These are vitamin C (or power (i.e., over-oxidized), you might see mineral ascorbates), bioflavonoids (there are some results. I know of only two reasons a wide variety that might be used), and the why you shouldn’t try it: 1) you are overly “I’m wondering trace minerals copper and iron (which reduced already (a rare phenomenon if Microhydrin is should not be supplemented if they are indeed), and 2) you can’t afford the price (it’s already present in ample amounts). These fairly expensive). something I should cofactors are necessary to convert procolla- Those people who respond dramatically consider adding to my gen to collagen. to Microhydrin may be able to reduce their supplement intake?” If they are not present in your supple- costs over the long run by purchasing an ments, you can take them separately. electrical “microwater” machine. These Vitamin C and bioflavonoid combination devices (expensive) use electricity (cheap) to products are plentiful in the market. You separate water into cation-rich alkaline Smart Life News [v7n5] 15 September 1999 11 drugs your father was taking at the hospital Generally no. The doses of substances in were more responsible for his side effects Nutrivene are purposefully low so that the than the Eldepryl. Since most authorities chance of overdosing at the recommended continued from previous page (medical, legislative and regulatory) believe dose is nearly zero. If anything, you may that all deprenyls are equivalent, only have to add more of some ingredients if your graphic clinical contrary experience is going son has above-average nutritional needs. to convince anybody that Eldepryl is Furthermore, blood tests are not infallible “If you are going to inappropriate and that Discovery’s deprenyl technology. They are actually quite limited. build a case, with the is essential to your father’s treatment. You They are a one-dimensional view of a three- may believe it, and I may believe it, but most dimensional body. They usually have little media or politicians, people do not. It took me years to fully bearing on potential bad reactions or “harm” you will nead clear and appreciate the differences. If you are going per se. Hopefully, testing guides you to one unequivocal evidence to build a case, with the media or politicians, or more needs of the person, that if you will nead clear and unequivocal evi- addressed, will enhance their health and that Discovery’s dence that Discovery’s deprenyl is clinically wellbeing. deprenyl is clinically different from Eldepryl in your father’s case. For example, if your son has a severe zinc different from Eldepryl Under normal circumstances, it might be deficiency, the Nutrivene may not be suffi- considered unethical to subject your father to cient to correct it. But the less-than-adequate in your father’s case.” Eldepryl. But since the choice of using zinc level won’t make him sick, it will likely Discovery’s liquid deprenyl citrate has been make him better—but not as good as a forcibly removed from you by the FDA, the greater amount would. In other words, a two remaining options—using Eldepryl or mild zinc deficiency is much better than a doing without any deprenyl—are both simi- severe zinc deficiency, but no deficiency is larly disadvantageous. Since you and your better still. family are responsible for your father care, I A good way to think about the blood tests suggest you weigh these options and choose is that they are about “tuning” the program. what you consider to be the best of a bad lot. If you have lots of money, then testing before My third suggestion is to build a support starting TNI can give you some information system of people who are as fully informed that might be of value. But testing after “Is it harmful to start as possible about what is happening with starting TNI is much more likely to give you TNI without having your father’s care. This may involve friends useful information. In other words, before- and relatives, but it may also involve home- and-after testing is best, but after-only testing his blood tested first?” care specialists, localreporters,elected is almost as good. Plus, if the after testing representatives and maybe even your local finds something significant, then you might police. If you have strong community rela- want to repeat the after testing a second time tionships, it is more difficult for FDA agents to verify that the change in TNI is actually to harrass you. accomplishing what you want it to. Testing Such community ties also may allow you is not a trivial cost. Make it count. to have greater political influence. A Con- Safety and tolerance are not absolutely gressional aide is probably more likely to ask correlated among people. That’s why you tougher questions of the FDA and Justice pay attention when you give anything to Department if they know that you are talking your child, even puree of banana or cream of “If you have lots of to local reporters and writing letters to local wheat. Some people may react badly to money, then testing papers. The squeeky wheel gets the greese. things on which most of us thrive. Reporters may be more likely to talk with Bad reactions to TNI are rare, and they are before starting TNI you if your story involves frustration with minimized by gradual dosing (i.e., first 25%, can give you some elected officials. SWF then50%,then100%).Thisisbecause information that might gastrointestinal flora are an important part of Starting TNI Therapy? health, and TNI (and anything else you be of value. But testing My two-week-old son has Down syndrome. I ingest) can disturb the biological balance in after starting TNI have done a lot of reading about TNI and I the intestine. SWF is much more likely think it would be benefit him in many ways. Do you think it is too soon to start my son Yet I am nervous about starting my son on on NuTriVene-D? KA to give you useful NuTriVene-D, mostly because I do not know My opinion is that it is never too early to information.” much (yet) about vitamins, minerals, amino start. Ultimately, I think that prenatal TNI acids, how they combine, if the levels are therapy will eventually become the standard safe, and what my son’s metabolic make-up of care. SWF is at this point. Is it harmful to start TNI At what age would piracetam be recom- without having his blood tested first? KA mended? KA 8 Smart Life News [v7n6] 17 November 1999 This is a tougher question. Piracetam is Pyruvate for considered the treatment of choice for Down’s Syndrome? newborn infants with myoclonic seizure dis- While reading up on pyruvate recently, I continued from previous page orders, at extremely high doses (up to 12-24 read that it “can actually help to inhibit free grams!). It is surprisingly well tolerated. So radical production and that it also helps to the sub 1-gram doses are not likely to be a reduce DNA injury resulting from oxidative “Long-chain significant toxic risk. But there is much more stress...and that studies indicated that DNA polyunsaturated to life than toxicity. breaks were reduced 40% by it.” NS A huge amount of brain development The glycolysis pathway splits glucose (a fatty acids are an takes place in the first two years of infancy. six-carbon carbohydrate) into two pyruvates essential structural It is possible that piracetam may have (three-carbon carbohydrates), which feed element of human negative, positive, or negative and positive into the energy cycle (the Krebs citric acid effects on brain growth, differentiation and cycle) [see Figure A]. So pyruvate is a major brain membranes and apoptosis (programmed cell death) that are player in energy production. Usually, pyru- absolutely necessary too subtle to be seen in a clinical therapeutic vate deficiency is not a problem. If anything, for normal, healthy context. It just hasn’t been researched pyruvate tends to accumulate. Excess pyru- sufficiently. vate is temporarily converted into lactate brain development.” Brain growth is an extremely complicated (lactic acid), which is converted back to process and difficult to view non-invasively. pyruvate when the Krebs cycle “catches up” Most people do not know that a huge with glycolysis and the pyruvate/lactate number of brain cells die during normal excess can finally be burned. SWF brain growth from birth to 2 years of age. In Do you think that pyruvate may be useful “Do you think that DS, more than the normal number die, in helping to stop the free radical damage pyruvate may be useful presumably from increased oxidative stress. in DS, or is pyruvate’s molecular make up It is my opinion that this increased brain cell something that would exacerbate the situ- in helping to stop the mortality causes the mental retardation that ation? NS free radical damage in is associated with untreated DS. I think that The energy produced by pyruvate has Down’s Syndrome?” piracetam may assist TNI in preventing that. potential uses to assist the antioxidant Maybe it doesn’t. We’re just not sure. SWF defense system and other potential risks to What about Efalex and DHA? Should produce free radicals. This is because these be taken with NuTriVene-D? KA energy production 1) causes free radicals, Long-chain polyunsaturated fatty acids and 2) powers the antioxidant defense (PUFAs) are an essential structural element system. All fuels, whether carbohydrate, of human brain membranes and absolutely lipid or amino acid have this potential. It is necessary for normal, healthy brain devel- difficult to pre-judge the net effect when you opment. We know that PUFA deficiencies have opposite processes taking place. I Figure A: cause impairment of brain development and would think (assume) that normalization of decreased mental capabilities later in life. energy production would be beneficial (i.e., Role of Pyruvate in That’s why DHA is added to infant formulas increasing sub-normal energy production) Energy Production in Europe. The USA, led by the FDA, has yet and that over-revving the energy production to get with the program. But this is not too system would tend to aggravate the free- surprising, given their 20-40 year lag on the radical problem. folic-acid-causes-birth-defects issue. There is one more issue that I should Glucose PUFAs are not without risk. They oxidize mention, given our recent focus on meta- (peroxidize) rapidly and become rancid. bolic types and pH balance. There are two glycolysis Rancid fat is immunosuppres- separate input paths for pyruvate into the sive. So DHA and related Krebs cycle [see Figure B, next page]. One Lactate PUFAs must be fresh, stored pathway adds carbon dioxide (CO2)to carefully (protected from heat, pyruvate to form oxaloacetate [see pathway moisture, light and oxygen), pre- 1]. Another pathway removes CO2 to form Pyruvate served whenever possible, and dis- acetyl-CoA (coenzyme A) [see pathway 2]. carded immediately after becoming rancid. Pathway 1 is catalyzed by pyruvate If you can taste the rancidity (on the back carboxylase, an enzyme which converts the center of your tongue), throw it out. threecarbon pyruvate into a four-carbon energy Citric There are some blood tests for fatty acids oxaloacetate. Pathway 2 is catalyzed by the production Acid that can give you a clue as to the correct pyruvate dehydrogenase enzyme complex, Cycle amount to use. However, blood lipid levels which converts the three-carbon pyruvate are not necessarily linearly correlated with into a two-carbon acetate (commonly called brain lipid levels. SWF acetic acid, or vinegar). Smart Life News [v7n6] 17 November 1999 9 This pyruvate dehydrogenase complex is powerful free radical neutralizer. Their web similar to the alpha-ketoglutarate dehydro- site talks about negatively charged electrons genase complex on the other side of the and the element “hydrogen.” Not being a continued from previous page Krebs cycle [see Figure B below]. They are biochemist, I don’t know if using this sub- both composed of three closely associated stancewouldexacerbatethe“hydrogen” enzymes that use 1) thiamine diphosphate peroxide problem or not. Is this marketing (vitamin B1 coenzyme), 2) lipoamide (lipoic hype, or would it be helpful? I wish I’d have “The balance acid coenzyme), and 3) FAD (vitamin B2 taken more chemistry courses so I could between oxaloacetate coenzyme). evaluate such statements as, “Silica hydride, The balance between oxaloacetate and when combined with an additional, loosely and acetate is also acetate is important because these two wrapped, negatively charged ion, is the most important because molecules condense to form citric acid [see powerful antioxidant available. It is a free it directly affects Figure B]. This reaction is catalyzed by the radical neutralizer which has many enzyme citrate synthase, which joins the thousands of times more antioxidant power pH balance in the four-carbon oxaloacetate with the two- than any form of vitamin, mineral or food mitochondrion.” carbon acetate to form a six-carbon citrate. supplement.” NS This is a one-way reaction, like the dehydro- Hydrogen and hydride carry reducing genase complex reactions, and unlike the power,theoppositeofoxidizing power. rest of the reactions of the Krebs cycle. This can be trapped in a silica matrix, or it The balance between oxaloacetate and can be carried by “microwater” (alkaline acetate is also important because it directly reduced water). Reducing power is also affects pH balance in the mitochondrion. carried by vitamin C. The carboxylation of pyruvate (pathway 1) Reducing power is necessary to life. So is absorbs CO2 from the mitochondrial matrix oxidizing power. Too much oxidation or too Figure B: and thereby raises (alkalinizes) pH [see much reduction interferes with the body’s pH and Pyruvate Figure B]. Another way to say it is that CO2 energy and homeostatic systems. Hydrogen Metabolism is acidic, so removing acidity produces alka- is like the negative pole of a battery while linity. On the other hand, the dehydrogena- oxygen is like the positive pole of the battery. tion/decarboxylation of pyruvate (pathway You need both poles to have power. glucose 2) produces CO2, which lowers (acidifies) The product you are talking about is pH. So pathway 1 drives pH up and probably Microhydrin. The reducing power glycolysis pathway 2 drives it down. it carries is in direct opposition to both The balance between oxalo- hydrogen peroxide (which is excessive in pyruvate lactate acetate and acetyl-CoA is DS) and superoxide (which is deficient in regulated locally (in the DS). I wouldn’t hazard to guess the net effect pyruvate mitochondrion) by acetyl- because I could see it working both ways, but dehydrogenase pH CO2 CoA-induced activation of I would not be surprised if it would be a great pyruvate carboxylase. When benefit in DS. One of the major effects of CO2 pH acetyl-CoA levels rise, pyru- reducing power is to keep glutathione in its Acetyl-CoA vate carboxylase activity reduced state, and this becomes increasingly increases to augment the pool important as oxidative stress increases and citrate of oxaloacetate. However, both glutathione levels decline. oxaloacetate synthase citrate oxaloacetate and acetyl-CoA are There is a testing machine called the BTA produced from many other (Biological Terrain Assessment) which can pathways, and not just from measure redox (a contraction of reduction pyruvate. These other reac- and oxidation) potential in blood, urine and tions may skew the balance saliva. You might be able to use that Krebs between oxaloacetate and machine to see if the overall oxidative stress Citric Acid acetyl-CoA, which then has to in DS can be measured in redox potential, be adjusted locally. This can and then if the redox potential can be Cycle lead to mitochondrial pH “normalized” by Microhydrin or microwater. stress and metabolic ineffi- Furthermore, you might be able to use such ciency. a test to quantify how much Microhydrin or CO2 CO2 For these reasons, it may be a microwater is sufficient (without over- good idea to examine the role reducing the redox potential). I think micro- of metabolic types in Down’s water and Microhydrin have their strongest α-ketoglutarate syndrome therapy. SWF effect in the blood stream, where the dehydrogenase complex What can you tell me about ingested water first absorbs across the silica hydride. It is touted as a digestive tract. The saliva is more a measure 10 Smart Life News [v7n6] 17 November 1999 of the cellular redox environment. The oxidativestressinDown’ssyndromeis New GHB Legislation? probably greatest at the cellular level where What’s happening with the legal battle continued from previous page hydrogen peroxide is produced. over GHB? Technically, these products should be The federal law is pending. California thought of as reducing agents, not anti- has passed its new law which is worded “Technically, oxidants. Although reducing agents usually similarly to Georgia’s. It will criminalize all these products support the antioxidant defense system, GHB-related compounds including salts, most antioxidants are not reducing agents in ethers, esters, isomers and precursors of should be thought of the biological redox environment. GHB as of January 1, 2000. This includes as reducing agents, There is a similar confusion between GHB, butyrolactone, butyleneglycols, alpha- not antioxidants.” oxidizing agents and free radicals. Although hydroxy butyrates (“alpha-hydroxy” skin- most free radicals are oxidizing agents in care products), beta-hydroxy acids (also in biological systems, the reverse is not true. cosmetics), GABA, certain polymers (n-butyl For example, ground-state (singlet) ozone polyesters/polyethers, nylon-4, and some and singlet oxygen are not free radicals, but harder-than-steel automotive plastics), they are strong oxidizing agents. acetone-free nail polish remover, industrial Reducing agents are not something to be cleaning solvents, and some medical handled carelessly, but they can be very products (blood plasma extenders). SWF beneficial when applied correctly. SWF (to be continued in next issue)

Metabolic Balancing: to crash as it does with fast oxidizers. Fruit, complementary arms of the autonomic Oxidative and starchy vegetables (like yams, squash and (involunary) nervous system. Sympathetic Autonomic Nutrition potatoes) and sweet vegetables (carrots, dominant types are “activated” by increased onions, and beets) are included. Beta-oxida- activity of the adrenal, thyroid and pituitary (continued from page 1) tion does not need proactive cultivation. glands. They are often described as having Fat-rich foods like red and dark meats, fatty “Type A” personality (strong drives, hyper fish, vegetable oils and nuts are minimized or behaviors and goal-orientation). But they “Metabolic balancing avoided. may also exhibit poor digestion, headache, is accomplished high blood pressure and depressed appetite Autonomic Types from their sympathetic dominance. by counteracting Autonomic types come in sympathetic Parasympathetic dominant types are blood pH stress.” and parasympathetic types. These are often described by their “Type B” behaviors defined by the relative dominance of the two (more relaxed, laid back, socially oriented, and more likely to procrastinate). The para- sympathetic nervous system drives the Autonomic and Oxidative Positive Influences digestive organs. These includes the liver, Type I Type II intestine, stomach, salivary glands and Oxidative Metabolic Types pancreas (excluding insulin secretion, which Slow Oxidizers Fast Oxidizers is sympathetically driven). Parasympathetic Autonomic Metabolic Types types are more likely to develop hypo- Sympathetic Parasympathetic thyroidism and acid indigestion. Minerals Metabolic Classifications magnesium, potassium, iron calcium, sodium, phosphorus The categorizations of nutritional ele- copper, manganese, chromium, vanadium zinc, iodine, boron ments into groups with specific metabolic Vitamins activity (e.g., sympathetic, or catabolic) are beta-carotene vitamin A (palmitate) not necessarily consistent between meta- vitamin C (ascorbic acid) vitamin C (calcium, sodium ascorbates) bolic types. However, the groupings for vitamins D and K vitamin E 3 autonomic and oxidative influences are vitamins B (thiamine) & B (riboflavin) choline, inositol 1 2 almost identical, which is why we discuss vitamin B3 (niacin) vitamin B3 (niacinamide) them together. These are listed in the vitamin B6 (pyridoxine) vitamin B5 (pantothenate) adjacent sidebar (arbitrarily labeled Type I folic acid (folate), biotin, PABA vitamin B12 on the left and Type II on the right). This Amino Acids congruence in classifications for oxidative aspartic & glutamic acids phenylalanine, tyrosine, methionine and autonomic types is not shared with other glutamine, histidine, proline leucine, isoleucine, carnitine metabolic types (which will be discussed in Miscellaneous Other later articles). bioflavonoids, nucleotides (RNA, DNA) Although the similarity in groupings for Smart Life News [v7n6] 17 November 1999 11 shake for quick disolution. Get at least two Allergy to Piracetam? vials so you can wash one while the other is My 2-year-old child with Down’s syndrome in use. If you put a piece of clear tape on the started piracetam on December 7th and outside of the vial and mark it with a broke out in hives on the 11th. I think its an permanent marker at the three or six allergic reaction to the piracetam because teaspoon level, you can save time by filling it there were no other changes involved, no with distilled water to the mark instead of change in Nutrivene-D or diet, and I’ve seen having to carefully measure out three or six this allergic reaction before. The piracetam teaspoons of water each time. You can even isliquid,prescribedbyourdoctor,and put additional marks at each teaspoon level, made by a compounding pharmacy. I if that would make dosing easier. thought I should tell you. K The measure of volume that you use is Piracetam allergy is extremely rare. It is basically arbitrary. I mentioned teaspoons “Unlike piracetam, much more likely that the allergic reaction because they are likely to be in every kitchen, methylparaben and was caused by the preservatives used in but you could just as easily use milliliters, stabilizing liquid piracetam preparations cubic centimeters, fluid ounces, or drops. propylparaben are not against fungal contamination. Unlike pirace- The only limitation is that the water volume uncommon triggers tam, methylparaben and propylparaben are be sufficient to dissolve the piracetam com- of allergic and not uncommon triggers of allergic and pletely. This is not really a problem because intollerance reactions. You can check this piracetam is highly water soluble. One gram intollerance reactions.” out by having your physician change the of piracetam (1000 mg) will readily dissolve prescription to capsules (or powder) and in only two cubic centimeters of water (less dissolving it into liquid as you use it (on an than a half teaspoon). ongoing basis). There is no need for preser- Another technique that can be a big con- vatives in dry piracetam preparations, or venience is piracetam-sicles. You can take a “Piracetam-sicles can freshly prepared solutions. However, with- plastic ice-cube tray with ten (or twelve) ice- allow gradual taste out preservatives, you should dissolve only cube compartments and fill it with piracetam the amount that can be used in a day — or solution containing ten (or twelve) doses of desensitization in two with refrigeration. piracetam. You can find out exactly how children who would This may not be as convenient as pre- much water to use if you fill the tray with otherwise object to a prepared liquid piracetam, but there are a plain water first, and then carefully pour it few suggestions that I can offer that might be into a graduated kitchen measuring cup. The sudden bitter flavor.” helpful. Assuming that you give piracetam only trick to piracetam-sicles is having to fill three times per day, you can get the new each compartment in the ice-cube tray to piracetam capsules with three doses per approximately the same level to keep the Add capsule (a full days dosage) or six doses doses even. A little practice may be needed. er 2 per capsule (two days worth). This Once the piracetam solution has frozen at Fill will save you money over single- into ice cubes, a cube can be added to a w water to line d dose capsules (encapsulization is beverage for dosing. Because the piracetam- le t il en labor-intensive, especially in the sicles melt slowly, the bitter taste of t m is e g small batches made by hand by piracetam is lowest with the first sip and d r la compounding pharmacists). gradually gets stonger. This can allow n This can also save you gradual taste desensitization in children who E time. You can dump the would otherwise object to a sudden bitter contents of a three- or flavor. Piracetam can also be dissolved in six-dose capsule into fruit juices and frozen into piracetam-sicles three or six teaspoons of to make taste more acceptable. Generally, distilled water, and then citrus juices are best for masking bitter measure out one teaspoon flavors. When children are old enough, they of the piracetam solution at may appreciate an after-school piracetam- a time for dosing. In other sicle on a stick. Just insert the popsicle sticks words, mix once a day (or every into piracetam-juice mixture in the ice-cube other day) and dose three times per day. trays before it freezes. After it freezes, grab It might be helpful to ask the pharmacist the stick and the piracetam-sickle will pop for a few small glass vials with screw caps out in your hand. SWF into which you can dump the capsule’s 3 contents (throwing away Metabolic Independence? Replace cap and the empty capsule), In your introduction to metabolic balanc- shake until dissolved fill with water, and ing, you say that autonomic and oxidative Smart Life News [v7n7] 23 February 2000 9 types are truly independent but in the later regulated by anabolic/catabolic systems. I article you say that the categories are the think of the anabolic/catabolic balance as a same. Doesn’t this mean that they are tied “deep” or “primitive” aspect of metabolic bal- continued from previous page together and not truly independent? OTP ance, primarily operating at the subcellular, I see what you mean. Metabolic types are cellular and maybe tissue levels. I regard the truly independent in that all possible combi- oxidative and autonomic metabolic controls nations of types are found in people. There as “higher order” systems that evolved after “The oxidative and are sympathetic fast oxidizers, parasympa- the anabolic/catabolic systems and which autonomic systems thetic fast oxidizers, parasympathetic slow operate at the tissue and organism levels. It oxidizers and sympathetic slow oxidizers. makes sense to me that new homeostatic independently regulate This was my meaning. But your statement control mechanisms had to evolve as life overlapping metabolic that they must be tied together is also correct evolved from single cell organisms to multi- systems. In other in a different context. The oxidative and cellular organisms to complex multicellular autonomic systems independently regulate organisms. Each new layer of complexity words, it is a situation overlapping metabolic systems. In other would need to be stabilized against stresses of dual control.” words, it is a situation of dual control. The from the external environment. autonomic system has its control mechan- We’ll be reviewing William Wolcott’s new isms for maintaining blood pH homeostasis, book, The Metabolic Typing Diet, in the next and the oxidative system has its control sys- newsletter. Get it. It’s out in hardback. It’s tems. However, they are wired oppositely. excellent. SWF Nutrients which produce acidification through the oxidative system produce alka- Cell Therapy? linization through the autonomic system, From my investigations, cell therapy seems and vice versa. to have merit as a Down’s syndrome “What do you think Imagine a sandwich. The oxidative bread therapy. Although I wouldn’t trust the live about cell therapy?” is on the bottom, the blood pH metabolic cells in Mexico or France, I do have more system “fixings” are in the middle, and the trust in the frozen cells made in Germany autonomic bread is on the top. Just as the through Bio-Pharm. The live cells scare me sandwich fixings are contained by both and I do indeed think that viruses can be pieces of bread, the blood pH is influenced transmitted. From what I have researched, by the oxidative and autonomic systems. the cells from BioPharm have not had any And the bottom-up regulatory systems are viral transmissions in its 60 years of pro- not necessarily the same as the top-down ducing cells. What do you think about cell systems. The fact that they are wired oppo- therapy? NS sitely probably has survival value in allowing I think cell therapy has immense humans to survive better under highly potential—if you can get the right cells. skewed diets. It may also allow these That’s the problem in medically over- systems to check and balance each other to regulated countries like the US, and in “In the US, the some extent. countries in which corrupt business prac- political suppression of Another analogy could be the control of tices are condoned. corporations. The President or CEO runs the In the US, the political suppression of ‘alternative’ therapies corporation on one level and the Board of “alternative” therapies by medical regulators by medical regulators Directors runs the corporation on another and “unapproved” therapies by the FDA and ‘unapproved’ level. They can have different ideas of what drives the would-be-legitimate players out of is “best” for the corporation. A business the market and leaves charlatans and therapies by the FDA proposal going through the president’s office crusaders to fill consumer need. Some of the drives the would-be- might be accepted whereas the Board might crusaders are providing good product, but legitimate players reject it. The relative dominance between on the surface, it is very difficult to tell the the Board and CEO can make a big difference crusaders from the charlatans. In Germany out of the market in what happens to the corporation. The and Switzerland, where 1) medical regula- and leaves charlatans Board and CEO are independent, but tied tion is less oppressive, 2) the costs of the and crusaders to together. drug-approval process for biological thera- I suspect that the reason that oxidative pies is vastly lower, and 3) anti-fraud law is fill consumer need.” and autonomic types have almost identical strongly enforced, cell therapy has thrived. nutritional groupings while anabolic/ By the way, BioPharm has no way of catabolic groupings are totally different has knowing whether or not viruses have been to do with the fact that the oxidative and transmitted in their cells. They can know autonomic systems regulate the same whether or not there have been any reported biological “level” which is different from that cases of viral disease. They can know 10 Smart Life News [v7n7] 23 February 2000 whether or not specific viruses can be memory is very weak (2 minutes to 4 hours). detected or cultured. But that is far from Depression and low energy are also a definitive evidence. First of all, there are a lot problem. Local doctors tell us this is all we continued from previous page of viruses around, and most of the time we can hope for, though we may see minor im- fight them off without dramatic symptoms. provement in the months ahead. We are Secondly, there is no easy or affordable way looking for information about memory to assay for “unknown” viruses that might be rehabilitation. Any help would be greatly present. appreciated. LB In my opinion, prions are a much more There are many therapies that might be of serious but less likely risk than viruses. use that are not necessarily recognized by Prions cause bovine spongiform encephalo- “local” doctors. For example, B-complex “Piracetam is a pathy (mad-cow disease), scrapie (in sheep), vitamins and trace minerals are so “low tech” standard therapy in and Kreutzfeld-Jacob disease (in humans). that they are virtually ignored in cardiac and My last comment has to do with a possi- stroke rehabilitation. Without professional Europe for cognitive ble presumption about “frozen cells.” The support, the patient and/or caregiver must and speech rehabili- process of freezing cells is a reliable way to assume the primary responsibility of investi- tation following stroke, keep cells alive, which is an important aspect gating these therapeutic options. of cell-therapy efficacy. The freezing of Piracetam is a standard therapy in Europe but it would be highly sperm, eggs and embryos is routine in for cognitive and speech rehabilitation unusual for a stroke animal husbandry and fertility medicine. So following stroke, but it would be highly patient to receive frozen cells are not necessarily dead. In unusual for a stroke patient to receive pirace- addition, even if the cells were frozen in a tam in the US without specifically asking for piracetam in the US lethal manner, or freeze dried, viruses (or demanding) it. If you can’t get your without specifically wouldn’t necessarily be killed. Viruses do medical professionals or insurance company asking for (or not have a metabolism that can be stopped to cooperate, you can opt to pay for pir- to “kill” them. They have a static structure acetam out of your own pocket and initiate demanding) it.” that must be disrupted, disassembled or therapy despite your doctor’s objections or broken for them to become non-infectious. discomfort. With a doctor’s prescription, Freezing is not a reliable way to kill viruses. you can get piracetam from a US com- Prions are even more stable than viruses. pounding pharmacy in a day or two. They are known to be able to “survive” Without a physician’s prescription, you will boiling water. SWF have to import it for “personal use,” which takes weeks. The FDA’s policy on this is “Following a heart Anoxia and Coma Therapies? covered in back issues and on our web site attack, my wife Following a heart attack, my wife (49 years (www.ceri.com). young) had eight minutes of anoxia. She You might also want to consider 1) (49 years young) was revived, a blood clot in the left anterior methylation cofactors (vitamin B12, folate, had eight minutes coronary artery was chemically dissolved trimethylglycine), 2) oxygen therapy (intra- of anoxia.” and she remained in a coma, on life support, venous hydrogen peroxide, hyperbaric oxy- for four days. After regaining conscious- gen, superoxide negative ions, aerobic exer- ness, she has started to recover. She is now cise), 3) circulation enhancement (chelation home with me, receiving physical, occupa- therapy, niacin, vinpocetine, arginine, tional and speech therpy. She gets around ginkgo), 4) metabolic balancing (diet and the house well on good days. Her long-term supplements), 5) metabolic enhancement memory is fragmented and short-term (acetyl-L-carnitine, Hydergine, vinpocetine, coQ10), and 6) collagen support (lysine, Metabolic Rate Schematic proline, ascorbate, bioflavonoids). Ideally, it would be a good idea to have a health-care normal basal rate full recovery professional to assist you with prioritizing sleep incomplete recovery these options. w/GHB partial recovery Another factor that should be considered consciousness is basal metabolism (overall cellular energy threshold production). Coma involves profound sup- anesthesia pression of basal metabolism which may not coma fully resolve spontaneously (see margin illustration). A similar condition can occur deep coma following anesthesia, a medical procedure death Time which purposefully induces the same kind of metabolic suppression as a coma, but under Smart Life News [v7n7] 23 February 2000 11 energy pathways. SWF finding is completely dependent on the quality of the investigation. It would be easy No Piracetam for to see the bias of scientists claiming that continued from previous page Down’s Syndrome? trumpetting elephants are neither big nor The Canadian Down Syndrome Society has loud if you could see that they had put brown taken a position against piracetam in the paper grocery bags over their heads and “The Canadian Down treatment of Down’s syndrome. What do beans in their ears. Most scientists engaged Syndrome Society has you think of their research study? DS in obfuscation (the obscuring of the truth) It was a classic, well designed, blinded, are too clever to qualify their findings by taken a position crossover study, but incompetently executed openly disclosing their study’s limitations. against piracetam due to the choice of dose. The children were As you might expect, they purposefully hide in the treatment of given 80-100 mg/kg of piracetam, which is the details to make it difficult to evaluate approximately three times the amount what they did and didn’t do. Down’s syndrome. usually recommended for treatment of How many people reading the Canadian What do you think of learning disabilities in children. Not sur- Down’s Syndrome Society’s quarterly publi- their research study?” prisingly, they saw a clear spectrum of cation would know that the generally stimulatory side effects (four cases of aggres- accepted dose of piracetam recommended siveness, three of agitation, two of sexual for treatment of learning disabilities was only arousal, and one each of irritability and poor 30 mg/kg and not 100 mg/kg? Only a few, sleep). The researchers were unable to see would be my guess. any “significant” changes in cognitive Let’s look at the article written about the “The children were abilities. study’s findings. Dr. Robert Haslam explains given 80-100 mg/kg This last point needs elaboration. “No piracetam as, “a cyclic derivative of gamma- significant changes” does not mean that amino butyric acid, a central nervous system of piracetam, which is there were no cognitive improvements from inhibitor.” Such a statement is truthful, but at approximately three piracetam. It means that the technique used the same time quite misleading. Piracetam is times the amount to measure cognitive function were not able not a GABAergic drug, nor does it inhibit the to generate a statistically significant differ- central nervous system. As a matter of fact, usually recommended ence between the piracetam and placebo it tends to accomplish the opposite effect. for treatment of groups. Based on scientific reports and He then states, “piracetam has been reported learning disabilities previous research with piracetam and DS to improve dementia, particularly in indi- children, the most likely cognitive ability to viduals with Alzheimer’s disease.” The first in children.” be expected to be enhanced by piracetam part is right, the latter is wrong. Piracetam would be verbal ability, which was not tested actually works better in non-Alzheimer’s by the researchers. It is also possible that the dementias than it does in Alzheimer’s disease overt bias of the researchers may have (see SDN v3n1p3). Then he states that influenced how they looked for results (i.e., piracetam “has also been used to treat myo- not too closely). In addition, cognitive clonic epilepsy, autism, aphasia, dyslexia, benefits could easily have been missed and learning disorders.” Although this is a “Cognitive benefits because of the small size of the study (25 fair summary, he immediately qualifies it could easily have been children, only 18 of which completed the with, “Unfortunately, there have been few study). scientifically well-designed studies to test the missed because of the A similar bias problem cropped up when efficacy of piracetam in the above condi- small size of the study.” the sugar industry set out to prove that tions.” Not only is that not true, that’s the vitamins did not increase IQ in children [see kettle calling the pot black. Piracetam is one the interview with Dr. Stephen Schoenthaler of the most thoroughly studied drugs on the in SDN v1n7p1]. The researchers designed planet. It is recognized as the treatment of their study to fail by using assessment tests choice for myoclonic seizure disorders by which were so crude that they would miss an the world’s medical communities (excepting “The most serious IQ enhancement of less than 10 points, the US and Canadian medical authorities, of problem with the study which was three times the IQ enhancement course). The evidence is so strong, it it con- found by Schoenthaler, and Benton and sidered medical negligence to fail to treat is that it ignored Roberts in more conscientious studies. Sure myoclonus with piracetam (again, except in TNI completely.” enough, the industry-funded researchers the US and Canada). were able to confirm their preconceived Dr. Haslam’s criticism of the quality of notion that IQ was not statistically enhanced other piracetam research studies in the face by vitamins. This is the political side of of his own fundamentally flawed study is a science. good example of the political hypocrisy prin- The importance of a negative scientific ciple in action: attack your opposition for 8 Smart Life News [v7n8] 14 May 2000 your own failings and their honest criticisms If you haven’t received it, simply refuse to appear to be “sour grapes” retaliation. accept it when it arrives. One procedure The most serious problem with the study used for Schedule I and II substances is for a continued from previous page is that it ignored TNI completely. In Down’s narcoticsofficerdressedinaUSPostal syndrome therapy, TNI is essential, Service uniform to attempt delivery in piracetam is elective. The many metabolic person. They knock on your door, hand you imbalances created by trisomy 21 are not the package, and then arrest you — then, or addressed by piracetam. So the efficacy of a few minutes later. If you have a post office piracetam in an untreated DS population box, they might put it in the box and wait for would not be indicative of its efficacy in a you to pick it up, or they might put a yellow “The order I placed is TNI-supplemented population. slip in the box for pick-up at the counter. If a Schedule-IV drug, Bottom line: its good politics, not good you refuse to accept it, the DEA has a much science. SWF harder time proving possession. They may and I am wondering still try to charge you with “intent” or what kind of punish- Ordering Scheduled Drugs? “conspiracy” to violate the Controlled ment I may face.” I now see that the order I placed is a Substances Act. Schedule-IV drug, and I am wondering what In the future, to avoid this problem, don’t kind of punishment I may face. Also, what order any controlled substances! SWF are the chances my package will not be intercepted? anon NADH Source? It is my understanding that possession of In the Parkinson’s Report Q&A you sug- “The chance of small amounts of a schedule IV drugs with- gested trying a sublingual form of NADH. a package being out a prescription is a misdemeanor crime, as My dad has taken NADH for a number of long as there is absolutely no question of years and has had a profound effect from it. intercepted is intent to sell. A lawyer can confirm that for He has been able to stay off of other Parkin- approximately one you. Whether or not there may be an addi- son’s medications so far. However, our in ten. In certain tional charge of violating import laws, I do problem has been finding a good source of not know. Talk to a lawyer. NADH. The only one currently available areas, interception Although it might be unreasonable for the that we are aware of is manufactured by may be as low as government to assume that you would have Enada, which does not work for my Dad at one in a hundred.” advance knowledge of every drug’s sched- all. If you have information on a sublingual uling status, the law does require you to form, we would be very interested in who the know this. “Ignorance of the law is no manufacturer is, and how we could order excuse” is the standard line, although there some. JB are exemptions (precedents) that have been The enteric-coated Enada NADH can be made by the courts from time to time — taken sublingually by thoroughly chewing especially when lawmakers break the law. up the tablets and refraining from We ordinary citizens are held to a higher swallowing for a while. It also helps to move standard than politicians. the NADH-rich saliva around the cheeks and The worst scenario will probably be gums with the tongue. somebody at DEA wanting a promotion who We have had a few other complaints by “Our problem has may try to make an example of you. I don’t subscribers that the “new” Enada is not as been finding a good really see what a Schedule-IV example is good as the “old” Enada, but this is entirely worth, but they might try a bit of intimidation anecdotal. You can order grams of pow- source of NADH.” anyway and see how you react. Playing dered NADH from BIOS Biochemicals dumb may be a good strategy. (1-800-404-8185) and then use it sub- In general, the chance of a package being lingually. It’s a lot less expensive on a intercepted is approximately one in ten. mg-to-mg basis, but it’s much more difficult That is a crude approximation. In certain to measure out the extremely tiny doses of areas, interception may be as low as one in a powder. I’d be interested to know if you “We have had a few hundred. It also depends on the size and develop other ways of taking it. SWF other complaints by weight of the package. Small, lightweight flats are the least likely to get inspected. Alcohol Remedy? subscribers that the Heavy, bulky boxes are much more likely to I was fascinated by your article “Alcohol, ‘new’ Enada is not as get inspected. Reducing Power and Oxidative Stress.” I good as the ‘old’ Enada.” If you haven’t yet taken possession of the had to read it several times to follow it (no schedule-IV substance in question, you are fault of yours). It is amazing what compli- not yet “in possession” of anything, cated systems we have, how intricate the regardless of whether or not you ordered it. reactions are. Thank you for this great piece Smart Life News [v7n8] 14 May 2000 9 expiration date of the product. A solution: Liquid Deprenyl Citrate? pour half of the contents of the Citr-A-Sol Anywordonthecourtcaseandwhen bottle into an old, empty, smaller, scrupu- Discovery’s liquid deprenyl might or might lously cleaned DEDI bottle (with the plastic not become available? many seal under the cap if you’ve still got it) and James Kimball, President of Discovery freeze it for later use. SWF Experimental & Development (DEDI), has been convicted of multiple counts, from Antioxidants vs Reductants? misbranding (a misdemeanor) to defrauding In several newsletters, you have written the FDA (a felony). From what I witnessed, about reducing agents and reducing power and heard from lawyers and participants, I being useful for fighting oxidative stress. can only regard the court case as a travesty of These sound to me like antioxidants. Are justice. Witnesses described to me 1) sub- they? If not, how are they different? OTP “Any word on mission of falsified evidence (forged docu- Reducing agents are a subcategory of the court case and ments) by the prosecutor, 2) perjury by antioxidants. Generally, reducing agents act government witnesses, 3) arbitrary dismissal as antioxidants, but antioxidants do not when Discovery’s liquid of relevant laws by the court, 4) court refusal necessarily act as reducing agents. For deprenyl might or might to allow defense witness testimony, and examples: Vitamin A and vitamin E are good not become available?” 5) misinstruction of the jury by the judge. antioxidants, but their role as reducing Sentencing is scheduled for August. agents in biological systems is minor. Then As a result of this case, DEDI has ceased there is vitamin C, which has important business. Assets have been sold to another antioxidant and reducing functions. And company, Strictly Supplements, which states finally, there are NADH, NADPH and FADH2, “Reducing agents sound that they are now producing an over-the- which rarely act as antioxidants, but play a to me like antioxidants. counter, dietary-supplement version of central role as reducing agents. SWF DEDI’s liquid deprenyl product. They are I’d like a basic conceptual explanation so Are they? If not, how calling it Citr-A-Sol. Anne and I have that I can intuitively understand what you are they different?” switched to it, and it seems identical to the are talking about. OTP old DEDI liquid deprenyl citrate. We are Temperature is a good analogy. Oxida- tracking ongoing developments and will tion and reduction are like hot and cold. have more detailed things to say in a future Oxidizing free radicals are extremely hot, issue. At this time, we can provide their like the sun’s rays on a hot Summer day. address and phone number: Reducing agents are cold. Antioxidants “Antioxidants protect Strictly Supplements protect against oxidizing free radicals like an against oxidizing 2920 N. Greenvalley Parkway, Suite 321 umbrella protects against the hot rays of the Henderson, Nevada, 89014 USA sun. Reducing agents protect against oxi- free radicals like Phone: 702-547-9009 dizing stress like a block of ice or a cold drink an umbrella protects Citr-A-Sol comes in a one-ounce bottle (600 protect against overheating. against the hot rays drops), which is twice the size of the old An umbrella works by intercepting the DEDI bottles (300 drops). This may be an sun’s rays and converting them to warmth of the sun. Reducing excellentpackagesizeforParkinson’s (the umbrella surface and the air in the vicin- agents protect against patients using 10 mg per day (a two-month ity of the umbrella surface are hotter than the oxidizing stress like supply), but it poses a technical problem for ambient air). In an analogous manner, anti- people (like me) taking deprenyl in extreme- oxidants intercept oxidizing free radicals to a cold drink protects ly low doses (one drop every other day), create oxidized antioxidants, which are far against overheating.” where the 600-drop bottle would last 40 less oxidizing than the original free radical. months (3.3 years). This is well past the So the umbrella converts heat to warmth, like antioxidants convert strong oxidants to mild Redox Term Temperature-Analogous Term oxidants. Just as the umbrella casts a redox potential temperature shadow of safety from the suns rays, so do oxidation warming, heating antioxidants create a zone of protection from oxidative stress. reduction cooling, refrigeration What an umbrella does not do is cool you oxidizing agent (oxidant) sunlight, fire, hot water, steam off. If it is 101°F [38°C] in the shade, you are reducing agent (reductant) cold water, an ice cube, snow, dry ice still uncomfortably hot under the umbrella. oxidized hot, heated, warmed, cooked But a block of ice, a cold drink or a air reduced cool, cold, cooled, iced, refrigerated conditioner will cool you off. That is what oxidizing power a furnace, heater or other heat source reducing agents do. reducing power an air conditioner or cooling influence In this analogy, temperature represents 6 Smart Life News [v7n9] 22 August 2000 redox potential. (The term “redox” is a con- dizing agents) are electron poor and have traction of reduction and oxidation.) Hot strong affinity for gaining electrons (oxi- and cold are extremes of temperature like dizing power). Other substances (reducing (continued from previous page) oxidation and reduction are extremes of agents and biological molecules) are redox potential. electron rich, some of which have an easy “Redox potentials for The concept of reduction is difficult for time giving up electrons (reducing power). biological systems are most people. Not only does reduction have Examples of these substances are qualita- absolutely nothing to do with the common tively ranked in Figure 1. The oxidizing not in the middle of meaning — to lessen or decrease in amount agents are towards the top and reducing the redox range.” — but there is no common experience of agents towards the bottom. reduction in the real world to which we can The first thing to notice about Figure 1 is easily relate. Iron does not un-rust, wood that the redox potentials for biological Figure 1: does not un-burn, and apples do not un- systems are not in the middle of the redox Redox Schematic brown. range for chemicals. They are, in fact, rather Yet if you look closely, these examples of far off center, being entirely located in the oxidation are also reduced end of the redox range (towards the Chemically Oxidized Fluorine radical hidden examples of bottom of Figure 1). This is a graphic way to Hydroxyl radical Antioxidation reduction! In each, the describe the fundamental polarity between Hydrogen peroxide air (atmospheric oxy- living biological systems (electron-rich, gen) is being reduced. reduced environments) and their non-living Superoxide Antioxidation Because we do not see external environments (electron-poor, Oxygen the air, or see the air oxygen-rich, oxidizing environments). To change from one form say it poetically, life is an oasis of electrons Nitrite to another, we tend to in an electron-poor desert. Nitrate ignore it, but oxygen is Getting back to the original question: the being reduced to oxide function of antioxidants is to mitigate the Selenite (or hydroxide)when destructive effects of powerful oxidizing Potential Selenate iron rusts, wood burns agents (those close to the top of Figure 1). and apples brown. Antioxidants do this by interacting with Ascorbyl radical Though transparent, oxidizing (electron-grabbing) substances Tocopheryl radical the oxygen in air is an and lowering (de-energizing, reducing, or GSSG

Redox Potential essential participant in antioxidizing) them to levels close to the bio- Biologically Oxidized Vitamin A rusting, browning and logical redox range (see downward-pointing Optimal Biological Vitamin E combustion. white arrows). Antioxidation (reduction) of Redox Range Vitamin C, glutathione On a physical level, oxidants can happen in a single step (left- Biologically Reduced NADH, NADPH, FADH2 oxidation involves the most white arrow) or in multiple steps (right- Microhydrin & Microwater loss of electrons and most, overlapping white arrows). reduction involves the The function of reducing agents is differ- Chemically Reduced Hydride gaining of electrons. ent than antioxidants. Reducing agents have The reciprosity of these processes is redox potentials below the dashed line (the Biologically acriticalconceptforunder- one in the middle of the “optimal biological Over-oxidized standing reduction. For one redox range” in Figure 1). In this way, Biologically molecule to gain electrons, reducing agents can lower the general redox Oxidized another molecule must potential of the living system, to prevent it lose them. When electrons from getting too warm and to keep it within Optimal A BC travel from one substance the optimal biological redox range. Said sim- BiologicalBiologically to another, from one ply, antioxidants specialize in “hot spots,” molecule to another, one while reducing agents specialize in the regu- ViableRedox Range D E F substance or molecule is lation of ambient temperature. SWF Redox being oxidized at the So how does one take advantage of Biologically same time that the other is reducing agents to optimize health or extend Reduced being reduced. Oxidation lifespan? OTP and reduction are comple- The magnified inset in Figure 1 shows the Biologically mentary processes. potential benefits (and potential harm) of Over-reduced Every substance has electrons. reducing influences. Reducing influences A, However, substances differ in the B and C all normalize redox potential based number of electrons they contain, and in the on different starting redox potentials. How- strength or weakness with which they hold ever, reducing influences D, E and F over- on to those electrons. Some substances (oxi- reduce the biological system, which can have Smart Life News [v7n9] 22 August 2000 7 adverse influences on redox reactions neces- gray arrow), which starts out steep (when sary for biosynthesis and respiration (energy antioxidants are involved) and ends up production). Since people exist with a wide approaching horizontal (when reducing (continued from previous page) variety of starting redox potentials, some agents take over). care must be taken to ensure that reducing In step 1, the antioxidant (e.g., vitamin E therapy is not taken too far. The same strong or tocopherol) interacts with the oxidizing reducing influence can be beneficial (in free radical (a byproduct of rancid fat) to “The redox potential of situation C) or deleterious (in situation F). dramatically lower the radical’s redox poten- a blood sample starts Even subtle reducing influences may be tial towards the biological redox range (the to drift immediately harmful in those rare individuals who are light gray area at the bottom of Figure 2). This over-reduced to begin with (situation D). takes place in cell membranes. Step 2 takes after it is drawn.” However, the vast majority of individuals, place at the membrane surface, where particularly those middle-aged and older, the oxidized antioxidant (the tocopheryl tend to be overly oxidized. This means that radical) interacts with a cellular antioxidant/ moderate use of reducing agents is very reducing agent (in this case glutathione) to much more likely to be beneficial than become recycled (reduced) back to toco- harmful, at least at the beginning of therapy. pherol. In step 3, the oxidized glutathione “Since people exist Children and infants — and possibly fetuses then interacts with a reducing angent with a wide variety — tend to be more reduced than adults. (NADPH), to become reduced glutathione Reducing therapies based on substances again. In step 4, the oxidized reducing agent of starting redox whose redox potentials are within the opti- (NADP) is reduced back to NADPH by the potentials, some care mal biological range (vitamins A, E and C, pentose phosphate pathway (or by NADH). must be taken to ensure glutathione, NADH, etc.) are self-limiting in Through these steps, the oxidizing potential their potential to reduce the cellular redox of the free radical is reduced (both meanings that reducing therapy environment. They cannot lower redox intended) to the biological redox range (see is not taken too far.” potential below their own redox potential. the curved gray arrow). Stronger reducing agents like microwater There is lots of attention being paid to the (alkaline-reduced water), Microhydrin, and preventive and therapeutic value of antioxi- alkali hydrides have redox potentials below dants. Perhaps we should be spending equal the optimal biological redox range. Used time addressing the value of reducing agents? indiscrimiately and to excess, these stronger One way to do this is to measure reducing Figure 2: reducing agents have the power to over- potential directly. I am aware of one com- Antioxidation reduce biological systems. mercial device, the Biological Terrain Assess- and Reduction How do reducing agents and antioxi- ment (BTA) system, which is capable of dants work together? Are there any strategies measuring redox potential of urine, saliva for optimizing synergy between them? What and blood in a clinical environment. The testing methods are available? BTA is not yet in widespread use, so it may Antioxidants and reducing agents defi- be difficult to locate a practitioner who Fatty acid nitely work together. In dealing with employs it. A BTA test usually costs between peroxide radical oxidizing free radicals, antioxidants are the $100 and $200 to perform. first line of defense, and reducing agents mop Unlike most standard blood tests, redox up the pieces after antioxidants have done potential cannot be easily measured at a their job. In the adjacent time-sequence dia- remote laboratory. The redox potential of a gram (Figure 2), the redox potential of a free blood sample starts to drift immediately after radical (arbitrarily chosen to be a fatty per- it is drawn. Oxygen from the air and oxide radical), is gradually reduced in dissolved oxygen in the blood shift the redox Tocopheryl a multi-step process. This follows potential of blood samples within minutes to radical a sweeping curve (see the wide hours. Samples must be measured immedi- biological reduction ately after collection. SWF of free radicals Glutathione Testosterone Patch Problem? radical in cellular lipid For six weeks I have been using Androderm Redox Potential 1 membranes patches (1 patch per day). The results from testosterone are excellent, but the testoster- NADP g 2 ly HO2 n one patches cause unpleasant skin irrita- io c

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o o biological GSH o 4 pharmacist know the makeup of testosterone redox range NADPH cream. Do you have this information? DCA 8 Smart Life News [v7n9] 22 August 2000 years, most people feel that they have better vascular system is already over-relaxed in things to do than fight with the FDA. DS. The vascular smooth muscle relaxing If there’s something in your life that you factor that controls blood flow is nitric oxide (continued from previous page) can exploit, you do not necessarily need a (NO) [see the sidebar in SLN v6n10p4 for the lawyer. Intimidation can be based on internal mechanism]. It is believed that publicity (your cousin’s inlaw is an assistant vinpocetine works, at least partially, by producer on Oprah, or the editor of the local enhancing the action of NO. The precursor “If there’s something community newspaper) or politics (your for NO is the amino acid arginine, which in your life that you husband’s Best Man is on Senator Boxer’s tends to be high in DS. Furthermore, NO campaign re-election committee, or you levels are reduced by reaction with – can exploit, you do were a volunteer for George Bush’s [your superoxide (O2 ), which is low in DS. not necessarily need a state] campaign committee). But it is my Let me go through this another way. The lawyer. Intimidation opinion that such tactics are best reserved for superoxide dismutase (SOD) gene is on the the second letter. If your first letter is mild triplicated 21st chromosome and gets over- can be based on and polite yet direct to each and every point expressed in Down’s syndrome (trisomy 21). publicity or politics.” in the FDA’s personal use import policy, then Overexpression of SOD means underrepre- you become an “average citizen victimized sentation of superoxide, which is SOD’s sub- by a FDA bureaucrat” instead of a “radical strate. By analogy, the more dogs you have, troublemaker out to circumvent the law.” the faster you go through dog food (which Publicity and politics are 93% perception and is the substrate for dogs). Low superoxide “Every citizen can 7% content [And I’m an optimist ;-) ]. means increased NO (they are antagonistic to benefit from knowing I also agree with Ward in that I think that each other). So I am left with the question: every citizen can benefit from knowing the do we want to risk increasing something that the technical details technical details of governmental authority. is already elevated? of governmental With this knowledge, you can be better able It is possible that vinpocetine has non-NO authority.” to make the right statements and ask the mechanisms of action that might prove more right questions to get a government agent to valuable than any overdriving of vascular 1) engage in unauthorized action, 2) extend relaxation. It is also possible that there is that into an overtly illegal act, and then 3) some kind of adaptation, resistance or habit- incriminate themselves in a way that cannot uation to increased NO that would respond be denied, without them necessarily positively to vinpocetine, ginkgo or arginine. realizing what you are doing. SWF There is no fundamental incompatibility between piracetam and vinpocetine. If you “The benefits of Vinpocetine in try it, please share your observations. Down’s Syndrome? vinpocetine seem oddly These concerns about vinpocetine apply I know I said I don’t usually pester much, but only to Down’s syndrome. Non-DS individ- similar to problems I’ve got one question here that is bugging me uals do not have the elevated arginine and that our DS children ;-), so may I impose on you just one more low superoxide that might constitute a experience. Might time? I was reading VRP’s newsletter re contraindication for vinpocetine. SWF vinpocetine and apparently it is an excerpt it be helpful?” from the first smart-drug book. It states that Basal Metabolism? vinpocetine facilitates cerebral metabolism, I am recent subscriber to your newsletter. I by improving the blood microcirculation, ordered all the back issues and I am slowly stepping up brain cell ATP production, and working my way through them. My first im- “The metabolic and increasing utilization of glucose and pression is WOW! You guys are way ahead anti-ischemic effects of oxygen. It also has been used for memory of the curve. problems, heart problems, aphasia, apraxia, The November 2000 feature on basal vinpocetine might be motor disorders, inner ear problems and eye metabolism convinced me to start taking my of significant value in problems. This list seems oddly similar to temperature. I had all the symptoms of an treating DS. However, problems that our DS children experience. underactive thyroid and sure enough, my Might vinpocetine be helpful? Or does temperature is consistently 1.5 to 2 degrees I have been reluctant piracetam address these things in the same below normal. It is usually around 97 to suggest vinpocetine way? Or can vinpocetine be used along side degrees or slightly lower upon waking, and because the vascular piracetam? N often below 98 degrees throughout the day. The metabolic-enhancing and anti- Three months ago, my former doctor had system is already ischemic effects of vinpocetine might be of told me my thyroid was “basically normal,” over-relaxed in DS.” significant value in treating Down’s syn- but now I have an appointment with a drome. However, I have been reluctant to doctor that is a subscriber to your newsletter. suggest vinpocetine because I think that the I feel that thanks to you, I am getting more 10 Smart Life News [v8n1] 21 January 2001