Journal of Orthomolecular Medicine Official Journal of the International Society for Orthomolecular Medicine International Standard Serial Number 0317-0209

Volume 24 Second Quarter, 2009 Number 2 Table of Contents

Editorial ...... 59

My Paranoid Patients Are Now My Friends A. HOFFER, M.D., Ph.D.; F. FULLER, RNCP (Cand) ...... 61

Antioxidant Vitamins Reduce the Risk for Cancer: Part Two M.J. GLADE, Ph.D., FACN, CNS ...... 65

Case from the Center–Vitamin D (25-OH-D3) Status of 200 Chronically Ill Outpatients Treated at The Center J.A. JACKSON, MT(ASCP), CLS, Ph.D., BCLD(AAB); R.K. KIRBY, R.D., M.S., M.D.; M. BRAUD, M.D.; K. MOORE, B.S., MT ...... 88

Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases Examined from Both Perspectives C. QUATTRO, P.A., DAOM, L.Ac...... 91

ISOM News –2009 Orthomolecular Medicine Hall of Fame; 2009 Orthomolecular Doctor of the Year; 2009 Orthomolecular Medicine Today Conference Report ...... 100

Information for Manuscript Contributors ...... 110

Orthomolecular Medicine © 2009 by the International Schizophrenia Foundation. Publication Office: 16 Florence Avenue, Toronto, ON Canada M2N 1E9. Printed in Canada. Published quarterly. Reproduction without permission is prohibited. 06/09 Editors Interim Editor-in-Chief Harold D. Foster , Ph.D.

Assistant Editor Andrew W. Saul, Ph.D.

Managing Editor Steven J. Carter

Production Editor Gregory Schilhab

Contributing Editors

Richard P. Huemer, M.D. Erik T. Paterson, M.B. Palmdale, California Creston, British Columbia

James A. Jackson, Ph.D. Jonathan Prousky, N.D. Wichita, Kansas Toronto, Ontario Editorial Review Board

Michael Gonzalez, D.Sc., Ph.D. Karin Munsterhjelm-Ahumada, M.D. San Juan, Puerto Rico Enekas, Finland

Masatoshi Kaneko, Ph.D. Alexander G. Schauss, Ph.D. Tokyo, Japan Tacoma, Washington

Steve Hickey, Ph.D. Gert Schuitemaker, Ph.D. Manchester, UK Gendringen, The Netherlands

L. John Hoffer, M.D., Ph.D. Garry M. Vickar, M.D. Montreal, Quebec St. Louis, Missouri

Editorial Offices

16 Florence Avenue, Toronto, ON Canada M2N 1E9 Telephone: 416-733-2117 Facsimile: 416-733-2352

website: www.orthomed.org e-mail: [email protected] Editorial

In this issue of the Journal of Orthomolecular Medicine, the editorial pages have been left empty as a symbol of Dr. Abram Hoffer’s passing. For 40 years he populated these pages with his inspiring opinions, ideas and hopes.

59 Editorial

60

Editorial Hoffer blank.indd 2 7/24/09 4:29:20 PM My Paranoid Patients Are Now My Friends

Abram Hoffer, M.D., Ph.D; Frances Fuller, RNCP (Cand)1

Introduction hospital under a Provincial Act. In Ontario Just before Christmas in 1960, I it is against the law to force medication. received a handwritten two-page letter Not so in the rest of Canada. from Dr. Ted Robie of New Jersey. Ted had been practising psychiatry for about What is Paranoia? forty years. He was compelled to write to Paranoid ideas are delusions that are me because, for first time in his career, his held firmly against known facts. It is there- paranoid patients had become his friends. fore a value judgement that has to balance I think that in this very brief statement he the probability that the facts used by the demonstrated the fundamental difference paranoid patient to support his delusion between standard psychiatry as practised are real. There is no doubt that many then and even now, and orthomolecular paranoids are not really paranoid but are medicine, practised by a few. responding to their altered perceptions, as You have to understand paranoid Dr. John Conolly pointed out many years patients to grasp what Ted wrote. Para- ago. A common example was the belief noid patients are fearful because of their that one’s spouse was putting poison into delusional beliefs and they do not trust one’s food. However, this could be traced very many people. Even patients who to the bitter taste that food may develop have had loving relationships with their when patients are deficient in zinc. When partners for many years will doubt them I explained to some of these patients that and, in the past, it was not unusual for the bitter taste arose from a deficiency of paranoid patients to believe their mates zinc, they were no longer paranoid. were poisoning their food. Since most There is no limit to the number of paranoid patients do not believe they are paranoid delusions patients will develop. sick and it’s the rest of the world that is Here is an example of a paranoid delusion out of order, it becomes very difficult to that forced a prisoner from Prince Albert treat them. They have had to be forced or prison to flee and kidnap several police in committed into hospital, where treatment their car. After being returned to prison he was forced upon them, and since most of told me he had to escape in order to save them did not recover, they never had a his life. He was convinced that poison gas chance to establish positive relationships was being piped into his cell. His evidence with their doctors. was that he could smell it coming from A paranoid patient in one of Ontario’s the vents. He tried to stop this by plugging mental hospitals refused to accept treat- the air vents. (Kahan, 1973). ment. He said that he preferred to deal In her second report, Kahan described with his ideas free of the drugs with their the history of a young man who killed terrible side effects. This issue was taken almost the entire Hoffman family in to the Supreme Court of Canada, which northern Saskatchewan because he had found that forcing anyone to submit to been ordered to do so by the Devil, and treatment against his or her will was this command was not countered by the against Canada’s constitution. Of course, usual advice he would get from his guard- governments have immense power to have ian angel not to do so. He died psychotic their own way. He was therefore kept in in a mental hospital. Recently in Canada, another schizo- 1. 3A-2727 Quadra Street, Victoria, BC V8T 4E5 phrenic patient was found not guilty by

61 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 reason of insanity because he too believed perhaps we would not be in our present he was ordered by God to kill a fellow financial situation. I think also it can be bus passenger, which he did by cutting helpful to believe when driving that other off his head. drivers may actually want to hurt you, Conolly described a woman in his as long as you know this is seldom true. hospital who was very depressed because Interestingly, paranoid patients, no matter she knew her husband was dead. She how delusional and paranoid they can be, could see his ghost perched in a tree out- are gullible when it comes to other ideas, side her window. Her doctor told her hus- like falling for the billion dollar scams that band about this delusion, but would not flood the Internet. let him go into the room lest it frighten her too much. However, when no one was Why So Few Paranoid Patients Become looking, he went in anyway. She looked Friendly With Their Psychiatrists at him, fainted, and when she came to The main reason is that most of these said, “Let’s go home, John.” Confronted patients do not recognize they are sick, with reality she no longer believed that and therefore cannot be persuaded that her hallucination was his ghost. treatment will do any good. ‘In vino veri- An example of the tenacity with tas’ refers to men or women who, under which patients can hold onto their delu- the influence of alcohol, will blurt out sions was the patient who had concluded paranoid and other socially unacceptable he was dead, and could not be argued out ideas. The alcohol reduced some of their of this. When his doctor asked him, “Do social controls. Paranoid patients are very dead men bleed?” He replied, “Of course pleased when they are no longer bothered not! What a ridiculous question.” The by these repetitive intrusive ideas, and doctor followed up, “Will you allow me the odds they will become friendly with to prick your finger to see if you bleed?” the doctors who treated them increased. “Of course,” he replied and held up his Otherwise, they cannot be persuaded that forefinger. The doctor pricked the finger to get well they need correct treatment, and it bled. The patient was astounded. nor that it would be smarter on their part He exclaimed, “I did not realize dead men not to talk about their paranoid ideas. could bleed.” This delusion reminds me of In Hoffer reported by Challem (2007), the delusions held by modern psychiatry I summarized the major change that that their toxic, poisonous drugs are more has occurred from psychiatry of 1950 helpful than harmful to patients. and orthomolecular psychiatry today. In Paranoid ideas are not always in- June, 2007, a forty-year-old man came to jurious. For some occupations, being see me, accompanied by his sister. He paranoid can be very useful. I think be- had been a very busy and skilful artisan. ing paranoid is very helpful for police He told me that he had suffered from officers, for detectives, for the military, anxiety and depression most of his life, as this will prolong their lives. I think and latterly from what he described as a paranoia is advantageous evolutionally if delusional disorder, meaning he became it is not excessive, or else it would have extremely suspicious of any girlfriend, disappeared long ago. The Trojan horse believing she is unfaithful. This always tactic succeeded because of insufficient broke up the relationship. Five years ago paranoia. Even for many business affairs he had been diagnosed schizophrenia, it may be very helpful. Had the govern- but more recently had been given a more ment controllers of the world’s banking esoteric diagnosis, “Othello’s Syndrome”, system displayed a little more paranoia, by his current psychiatrist. For this he

62 My Paranoid Patients Are Now My Friends was prescribed Risperidone, 3 mg per did not need psychotherapy. He was given day. Risperidone made him more anxious, the information doctors must give to and he was depressed most of the time. their patients. He did not have “Othello’s He denied having experienced visions or syndrome”, whatever that is. It is another voices. He had been in a psychiatric ward example of psychiatrists attempting to twice, the last time for five days at the end develop fancy diagnoses by describing of April, 2007. He had been abstinent from the symptoms of the illness in more and pot and cigarettes for two months prior more detail, and by attaching a name to to seeing me. it that gives it more cachet. This man was There was clear evidence that he was another example of a pellagra psychosis, allergic to dairy products. He was advised the vitamin B3 dependency, which can to follow the following nutrient program: take almost any clinical form. When mod- niacin 1 gram TID, ascorbic acid 1 g ern psychiatry becomes better informed, it TID, B-complex 100 mg OD, pyridoxine will depend upon simple laboratory tests 250 mg OD, vitamin D 6000 IU during and the response to vitamins to make winter, 4000 IU in summer, zinc citrate the diagnosis. No one diagnoses syphilis 50 mg OD, salmon oil 1 g TID, selenium anymore by describing the clinical symp- 200 mcg OD, and apple cider vinegar 1-2 toms. It is diagnosed by laboratory tests. tbsp with meals. In brief, in 1950 there was no treatment; Two months later he was normal. today there is. What a difference! “Othello” had vanished, driven away by a The schizophrenic psychosis charac- few simple vitamins. Had he gone for help teristic of late stage pellagra cannot be in 1950 he would have been offered deep distinguished from schizophrenia unless psychotherapy, preferably psychoanalysis, the typical nutritional history associated and if he could afford it, weekly sessions with it is present. The discovery that nia- or more often for up to ten years, because cin and niacinamide cured pellagra made it was believed that paranoid ideas arose it possible to use a very simple diagnostic from unexpressed homosexuality. At test that in my opinion turned out to one of our conferences the presenting harmful to schizophrenics. In the 1930s psychiatrist described a similar case and pellagra psychotics were distinguished by then told us he was homosexual. I asked giving them the vitamin. If they recovered what the evidence was. Had he, in fact, quickly, in a matter of weeks, they were ever been or even expressed any inter- called pellagra, but if they did not they est in men? The doctor replied that of were allowed to remain schizophrenic. course he was homosexual, since Freud The gross error in this reasoning was had shown this in a book he had written that it did not take into account the fact about one paranoid psychotic judge. He that individuals’ needs do differ, and was paranoid and that was enough to optimum doses are not invariant. As has prove to this doctor he was a latent ho- been pointed out repeatedly, whether the mosexual. The odds are that this patient deficiency is low dose or high dose, the would eventually have wound up in some condition is the same except that high chronic mental hospital ward and later, doses were not continued long enough if he survived, he would have been driven to make any difference. Paranoid ideas into the streets, as is the case with so were common amongst pellagrins; not many of these patients today, surprisingly, they vanished when patients This recovery from “Othello’s syn- were given the correct doses of vitamin. drome” shows that in this man no psy- This is recently referred to by Prakash, chological complexes were involved; he Gandotra, Singh et al (2008).

63 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009

Brief Case History of a Very Sick Para- What Helped Him Become So Much noid Schizophrenic Patient Who is on Better? the Road to Recovery Fortunately, he was always able to Several decades ago a young man find living quarters with which he was was referred to me. After having seen able to cope. Physically he was well; he more than five thousand schizophrenic did not show the typical appearance of patients over fifty years, I think I have seen a chronic tranquilized patient. My of- nearly every form it can manifest. He was fice always treated him with respect and the only one who made me fearful by his consideration, and when he was abused manner, which sizzled with the intensity by the system I became his advocate, writ- of his anger at the whole world, and by ing letters and making calls on his behalf. the tenacity with which he adhered to his And of course, he never stopped taking fantastic delusional ideas. He frightened niacin every day, 1 gram after each of three his social workers, who refused to see meals. I did not treat his paranoid ideas. him alone, and also alienated most of I did not try to persuade him they were the doctors at the clinic he attended. He wrong, and no matter how bizarre they never threatened my staff, or me, nor was were, I still listened. He would have made he paranoid about us. an excellent science fiction writer on the I never argue with paranoid patients, morbid side. His paranoid delusions are nor do I try to convince them they are playing a much lesser role because his wrong. After each visit he may have felt schizophrenia is coming under control. better, but I felt very much worse, tired One does not treat the paranoid delusions; from listening to all those psychotic ideas one treats the basic disease present in the pouring out of him. I immediately started human being. him on niacin, 1 gram after each of three meals, plus 5 mg of Haldol, one of the Literature Cited safest antipsychotics, until its patent ran Kahan, FH, Skafte: A “symptom-free” murderer, out, when it suddenly became very dan- Part 1. J Orthomol Psychiat, 1973; 2: 169–181. Kahan, FH: Schizophrenia, mass murder and the gerous, especially as the new ‘atypicals’ law. J Orthomol Psychiat, 1973; 2: 127-146. were developed. Hoffer A: Guest Commentary. A Case of “othellos’s His visits went on year after year. syndrome.” Nutritonal Reporter Extra (Jack I measured the degree of improvement Challem) 2007;18. by the amount of time he gave to his Prakash R, Gandotta S, Singh LK, Das B, Lakra A. paranoid ideas compared to the time Rapid resolution of delusional parasitosis in pellagra with niacin augmentation of therapy. given to reality-based problems. After I Gen Hosp Psychiat, 2008; 30: 581-584. changed my status from psychiatrist to consultant, there was a subtle shift. Over the past year, almost 90 percent of the content of his conversation was reality based. We speak about vitamins, whether he needs any more, and so on. He is no longer frighteningly hostile and, amaz- ingly, he now has a job. The last interview he told me how much he liked me, and that I was the best doctor he had ever had; this, from an originally very hostile paranoid patient.

64 Antioxidant Vitamins Reduce the Risk for Cancer: Part Two

Michael J. Glade, Ph.D., FACN, CNS1

Part One (JOM 24.1) presented the evidence tocopherol intake > 10.4 mg vs < 6.4 mg: for vitamin C in reducing cancer risk. 0.5; 95% C.I.: 0.2, 1.0; OR, postmenopausal women with daily a-tocopherol intake Vitamin E Reduces the Risk for Breast > 10.4 mg vs < 6.4 mg: 0.5; 95% C.I.: 0.3, Cancer 1.0; both adjusted for age, education, age The scientific evidence indicates that at menarche, age at first pregnancy and increased consumption of vitamin E re- BMI).11 These protective effects was not duces the risk for breast cancer. The results enjoyed by similar premenopausal women of several retrospective observational stud- who had a positive family history of breast ies support the conclusion that increased cancer, indicating that chronic vitamin E consumption of vitamin E reduces the deficiency cannot overcome factors that risk for breast cancer.10,11,16-18,21,37-39,43,98 In predispose a woman of any age to breast a case-control study conducted in New cancer.11 York state, the multivariate-adjusted In a case-control study conducted in odds of developing breast cancer were re- China (the Shanghai Breast Cancer Study), duced significantly among premenopausal the odds of women developing breast women by any daily intakes of a-tocopherol cancer were reduced significantly among equal to or greater than 2/3 of the RDA women who consumed more than the RDA (OR, daily vitamin E intakes > 10 mg vs for vitamin E, compared to vitamin E defi- < 7 mg: 0.55; 95% C.I.: 0.34, 0.88; adjusted cient women (OR, vitamin E intake > 19.9 for age, education, age at first birth, age mg/day vs < 9.4 mg/day: 0.72; 95% C.I.: 0.54, at menarche, history of first-degree rela- 0.96).37 In an extension of this study, the tives with breast cancer, personal history multivariate-adjusted odds of developing of benign breast disease, BMI and total breast cancer were reduced significantly daily energy intake).10 This significant among women with diets deficient in reduction in risk was independent of the vitamin E and who consumed dietary intakes of other dietary antioxidants and supplements of vitamin E (OR, vitamin E did not require but was not attenuated deficient diet plus vitamin E supplement by dietary supplementation with vitamin vs vitamin E deficient diet alone: 0.8; 95% E, although it became less important with C.I.: 0.6, 1.0; adjusted for age, education, increasing consumption of vegetables. In a age at menarche, parity, BMI, menopausal case-control study of women conducted in status, level of recreational exercise, his- western New York state, the multivariate- tory of fibroadenoma, history of breast adjusted odds of developing breast cancer cancer in first-degree relatives and phase were reduced significantly in both pre- of study).38 In addition, in a case-control menopausal and postmenopausal women study nested within the Danish Diet, Can- without a family history of breast cancer cer and Health Study of postmenopausal and who consumed the most a-tocopherol, women, the odds of developing breast despite the almost universal prevalence of cancer were reduced significantly by the vitamin E deficiency among these women daily consumption of at least 25 mg of (OR, premenopausal women with daily a- vitamin E, compared to the odds associ- ated with the daily consumption of 10 to 1. PO Box 4997, Skokie IL 60076 15 mg (Incidence Rate Ratio: 0.59; 95% C.I.:

65 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009

0.37, 0.95; adjusted for vitamin C intake, a-tocopherol intake, plasma a-tocopherol vitamin A intake, number of childbirths, concentration increases 10%).23,99 age at first childbirth, history of surgery In contrast to this large body of for benign breast disease, education, years evidence demonstrating that increased of hormone replacement therapy, alcohol consumption of vitamin E reduces the risk consumption and BMI).43 for breast cancer, the prospective obser- From the data obtained in a case- vational data collected during the 8-year control study conducted in Italy it was prospective observational Nurses’ Health determined that 8.6% of the risk of devel- Study II of 90,655 premenopausal women oping breast cancer is attributable to daily aged 26 to 46 years indicated that the mul- vitamin E intake less than 8.5 mg.98 The tivariate-adjusted risk of developing breast impact of poor vitamin E nutrition on risk cancer was not affected by differences in for breast cancer was confirmed further by the daily intakes of vitamin E from foods the results of another case-control study or from foods plus supplements (adjusted conducted in Italy, in which the energy- for age, smoking status, height, parity, adjusted odds of developing breast cancer age at first full-term birth, BMI, age at were reduced significantly by increased menarche, family history of breast cancer, vitamin E consumption (OR, 5th quintile personal history of benign breast disease, of daily vitamin E intake vs 1st quintile: oral contraceptive use, menopausal status, 0.75; p < 0.05)39 and in another, the odds alcohol consumption, daily energy intake of developing breast cancer were inversely and daily intake of animal fat).27 Similarly, correlated with daily intakes of vitamin in the 14-year prospective Nurses’ Health E.21 Furthermore, in a case-control study Study of 83,234 women in the US, the mul- conducted in Uruguay, the multivariate- tivariate-adjusted risk of developing breast adjusted odds of developing breast cancer cancer was not affected by differences in were reduced significantly by even mod- daily intakes of vitamin E from foods alone erately increased daily vitamin E intakes or from foods and dietary supplements (OR, 2nd quartile of vitamin E intake vs 1st (adjusted for age, length of follow-up, daily quartile: 0.53; 95% C.I.: 0.35, 0.83; adjusted energy intake, parity, age at first birth, age for adjusted for age, residence, urban or at menarche, history of breast cancer in a rural status, family history of breast can- mother or sister, history of benign breast cer in a first-degree relative, BMI, age at disease, alcohol consumption, BMI at age menarche, parity, menopausal status and 18 years, change in body weight since age total energy intake)17 and in a more recent 18 years, height, age at menopause and case-control study conducted in Uruguay, postmenopausal hormone therapy).28 The the likelihood of breast cancer in premeno- results of a prospective observational study pausal women was inversely correlated of 34,387 postmenopausal women in the with vitamin E intake.18 In addition, in a state of Iowa in the US (the Iowa Women’s case-control study of women conducted Health Study) also indicated that the in western India, the odds of developing multivariate-adjusted risk of developing breast cancer were significantly lower breast cancer was not affected by differ- among women with the highest plasma ences in vitamin E intakes (adjusted for a-tocopherol concentrations, compared to age, daily energy intake, age at menarche, the odds among women with the lowest age at menopause, age at first live birth, (OR: 0.37; 95% C.I.: 0.21, 0.67).16 (Circulating parity, BMI at entry into study, BMI at age concentrations of vitamin E can be used 18 years, family history of breast cancer, as biomarkers of exposure to dietary vita- personal history of benign breast disease, min E; for example, for every doubling of alcohol consumption and education).29

66 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two

Three other prospective observational US,103 the odds of developing breast cancer studies also failed to reveal a relationship were not affected by differences in serum between vitamin C consumption and the a-tocopherol concentrations. incidence of breast cancer.9,30,31 For ex- Similarly, in a case-control study nest- ample, data obtained from 4,697 women, ed within the Canadian National Breast initially cancer-free and aged 15 years or Screening Study of 56,837 women, the older, after 25 years of observation failed multivariate-adjusted odds of developing to reveal a significant relationship between breast cancer were not affected by differ- differences in daily vitamin E intakes and ences in the daily intakes of vitamin E or the occurrence of breast cancer.30 After the a-tocopherol from either foods or dietary first 4.3 years of the prospective observa- supplements (adjusted for adjusted for age, tional study of 62,573 women aged 55 to daily energy intake, age at menarche, surgi- 69 years (the Netherlands Cohort Study), cal menopause, age at first live birth, educa- the risk of developing breast cancer was tion, family history of breast cancer, and not affected by differences in vitamin E personal history of benign breast disease).34 intakes.31 Interestingly the results of an In case-control studies conducted in China 8-year prospective observational study of (the Shanghai Nutrition and Breast Disease 59,036 women aged 40 to 76 years in Swe- Study,35 the Shanghai Breast Cancer Study36 den (the Swedish Mammography Cohort), and studies conducted in Shanghai and among women with BMI >25, differences in Tianjin20), differences in vitamin E intakes vitamin E intakes were unable to overcome had no effects on the age-adjusted odds of the established procarcinogenic influence developing nonproliferative benign breast of excess body weight on the risk of devel- disease, proliferative benign breast disease oping breast cancer.9 without atypia or proliferative benign The results of retrospective observa- breast disease with atypical hypertrophy. In tional studies conducted in the US32,33,100-103 several European case-control studies con- also failed to demonstrate the protective ducted in Sweden,104 Italy,40 Greece41 and effect of increased vitamin C consumption the UK105 and in a similar study conducted against breast cancer. In a case-control in western India,16 the odds of developing study conducted in western New York breast cancer were not affected by differ- state, the odds of developing breast can- ences in daily intakes of vitamin E. cer were not affected by differences in In case-control studies conducted in vitamin E intakes33 and in a more recent Germany12 and Seoul, Korea,13 the odds of case-control study of women conducted in developing breast cancer were not affected North Carolina, the multivariate-adjusted by differences in vitamin E intakes; howev- odds of developing breast cancer were not er, over 80% of the subjects in these studies affected by dietary supplementation with were chronically vitamin E deficient. any amount of vitamin E (adjusted for One double-blind, randomized, pla- age, age at menarche, age at first full-term cebo-controlled clinical trial directly ad- pregnancy, menopausal status, lactation dressed the effects of dietary supplemen- history, family history, BMI, waist-to-hip tation with vitamin E in the prevention circumference ratio, education, alcohol of breast cancer. In the 10-year Women’s consumption, smoking history and daily Health Study, in which 39,876 apparently intakes of fruits and vegetables).32 In case- healthy women over 45 years old consumed control studies nested within prospective either placebo or 600 IU of vitamin E ev- studies conducted in Missouri,100 Wash- ery other day, this amount and pattern of ington County, MD,101,102 and within the vitamin E supplementation did not affect prospective Nurses’ Health Study in the the age-adjusted risk for breast cancer (RR,

67 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 vitamin E vs placebo: 1.00; 95% C.I.: 0.90, In addition, the results of retrospec- 1.12).106 However, the extent to which sepa- tive observational studies support the rating episodes of vitamin E consumption conclusion that increased consumption by 48 hours prevents the establishment of vitamin E reduces the risk for colon of an elevated steady-state of circulating cancer.99,108-113 In the case-control North a-tocopherol concentration is not known; Carolina Colon Cancer Study, a group of a-tocopherol concentrations were not African-American men and women with measured during this study. “high” vitamin E intakes (median: 140 The scientific evidence indicates that mg/day) experienced significantly less risk increased consumption of vitamin E reduc- for colon cancer than was experienced by es the risk for breast cancer. The evidence another otherwise similar group of Afri- documented by 11 retrospective observa- can-American men and women with “low” tional studies10,11,16-18,21,37-39,43,98 supports this vitamin E intakes (median: 6 mg/day; OR: conclusion and there is no evidence that 0.3; 95% C.I.: 0.1, 0.6).108 In contrast, the increased consumption of vitamin E may odds of developing colon cancer were not increase the risk for breast cancer. In addi- affected by differences in vitamin E intakes tion, the results of two studies12,13 confirm among white men and women, over half that vitamin E deficiency does not protect of whom were vitamin E deficient.108 On against breast cancer. average, individuals with colon cancer consumed significantly less vitamin E but Vitamin E Reduces the Risk for Colon vitamin intakes appeared to have no effect Cancer on the relative incidence of microsatellite The scientific evidence indicates that instability (a biomarker for risk for colon increased consumption of vitamin E re- cancer).109 duces the risk for colon cancer. The results In a case-control study conducted in of a prospective observational study of the Seattle, Washington area, the age- and 35,215 women aged 50 to 69 years in Iowa sex-adjusted odds of developing colon (the Iowa Women’s Health Study), largely cancer were reduced significantly in men as a result of the protective effect of supple- and women who supplemented their diets mental vitamin E intakes greater than 30 with vitamin E (OR, daily supplemental mg/day (age-adjusted RR, supplemental vitamin E intake > 15 mg vs none: 0.61; vitamin E intake > 30 mg/day vs none: 0.44; 95% C.I.: 0.42, 0.87)110 and in a case-control 95% C.I.: 0.28, 0.71), women consuming the study conducted in Montreal, Quebec, most vitamin E experienced significantly Canada, the multivariate-adjusted odds of less risk for colon cancer (age-adjusted RR, developing colon carcinoma were reduced total vitamin E intake > 35 mg/day vs < 6 significantly by increased consumption of mg/day: 0.32; 95% C.I.: 0.19, 0.54).107 These vitamin E (OR, 2nd quartile of vitamin E protective effects remained significant after intake vs 1st quartile: 0.54; 95% C.I.: 0.37, further adjustment of the calculated risk 0.80; adjusted for sex, age, marital status, ratios for age, daily total energy intake, history of colon carcinoma in first-degree height, parity, vitamin A supplementation relatives and total daily energy intake).111 In and daily intakes of seafood and skinless a case-control study conducted in Shang- chicken (multivariate-adjusted RR, supple- hai, China, the odds of men developing mental vitamin E intake > 30 mg/day vs colon cancer were reduced significantly none: 0.50; 95% C.I.: 0.28, 0.87; multivari- by greater daily intake of vitamin E (OR, ate-adjusted RR, total vitamin E intake > vitamin E intake > 32 mg/day vs < 26 35 mg/day vs < 6 mg/day: 0.42; 95% C.I.: mg/day: 0.6; 95% C.I.: 0.4, 0.9), although the 0.22, 0.78).107 odds of women developing colon cancer

68 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two were not affected by differences in vitamin measured during this study. E intakes.99 The scientific evidence indicates In a case-control study conducted in that increased consumption of vitamin New York City, NY, the odds of adenoma- E reduces the risk for colon cancer. The tous polyp recurrence were reduced signifi- evidence documented by a prospective cantly among patients who supplemented observational study107 and 7 retrospective their diets with vitamin E (OR, vitamin E observational studies99,108-113 supports this supplementation vs none: 0.62; 95 % C.I.: conclusion and there is no evidence hat 0.39, 0.98).112 Similarly, in Denmark, the increased consumption of vitamin E may odds of adenomatous polyp recurrence increase the risk for colon cancer. were inversely correlated with daily intakes of vitamin E.113 Vitamin E Reduces the Risk for Colorec- In contrast to these reports, when the tal Cancer data from 87,998 women in the prospective The scientific evidence indicates Nurses’ Health Study were combined with that increased consumption of vitamin the data from 47,344 men in the prospec- E reduces the risk for colorectal cancer. tive Health Professionals Follow-Up Study, The results of several retrospective obser- the risk for developing colon cancer was vational studies support the conclusion found to be unaffected by differences in that increased consumption of vitamin E vitamin E consumption.114 In addition, reduces the risk for colorectal cancer.53,55,63 in a case-control study conducted in Salt In a case-control study conducted in North Lake City, Utah, the odds of developing Carolina, the multivariate-adjusted odds colon cancer did not reflect differences in of developing colorectal adenoma were daily intakes of a-tocopherol.115 In a 17-year reduced significantly in men by intakes prospective study of 2,974 men in Basel, of vitamin E greater than the RDA (OR, Switzerland,86,87 and in a case-control study vitamin E intake > 15.3 mg vs < 0.3 mg: nested within a prospective study in Wash- 0.22; 95% C.I.: 0.07, 0.77; adjusted for age, ington County, MD,101 differences in serum BMI, daily energy intake, smoking status, vitamin E concentrations had no effect on use of dietary supplements, family history the risks of developing colon cancer. of colon cancer and daily intakes of fat, di- One double-blind, randomized, pla- etary fiber and alcohol).63 In a case-control cebo-controlled clinical trial directly ad- study conducted in Italy, the multivariate- dressed the effects of dietary supplemen- adjusted odds of developing colorectal can- tation with vitamin E in the prevention cer were reduced significantly by increased of colon cancer. In the 10-year Women’s vitamin E intakes (OR, vitamin E intake > Health Study, in which 39,876 apparently 12.3 mg/day vs < 12.3 mg/day: 0.72; 95% healthy women over 45 years old consumed C.I.: 0.6, 0.9; adjusted for age, study center, either placebo or 600 IU of vitamin E ev- sex, education, level of physical activity ery other day, this amount and pattern of and daily intakes of energy and dietary vitamin E supplementation did not affect fiber).53 In another case-control study the age-adjusted risk for colon cancer (RR, conducted in northern Italy, the odds of vitamin E vs placebo: 1.00; 95% C.I.: 0.77, developing colorectal cancer were reduced 1.31).106 However, the extent to which sepa- significantly by vitamin E consumption rating episodes of vitamin E consumption (OR, 5th quintile of daily vitamin E intake by 48 hours prevents the establishment vs 1st quintile: 0.60; p < 0.05).55 of an elevated steady-state of circulating In contrast, the results of several other a-tocopherol concentration is not known; retrospective observational studies failed a-tocopherol concentrations were not to reveal a relationship between increased

69 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 consumption of vitamin E and reduced risk odds of developing colorectal adenoma for colorectal cancer.52,63,116 In a case-control were not affected by differences in plasma study conducted in North Carolina, the a-tocopherol concentration (adjusted for multivariate-adjusted odds of developing location, sex, age, date examined, ethnic- colorectal adenoma were not affected by ity, serum total cholesterol concentration, differences in vitamin E intakes in women serum triglyceride concentration, BMI, ex- (adjusted for age, BMI, daily energy intake, ercise, smoking, alcohol consumption, daily smoking status, use of dietary supplements, caloric intake, daily intakes of saturated fat, family history of colon cancer and daily in- fruits, vegetables, folate and calcium, use takes of fat, dietary fiber and alcohol).63 In a of nonsteroidal anti-inflammatory drugs case-control cross-sectional observational and plasma Ferritin concentration).117 study of men and women in California, Similarly, in three case-control studies differences in vitamin E intakes, with or conducted in Japan, no relationship was without supplements, had no effect on the observed between colorectal adenoma or odds of developing colorectal adenomatous cancer and circulating vitamin E concen- polyps.116 In a case-control study conducted trations.118-120 in France, the multivariate-adjusted odds The results of a double-blind, ran- of developing colorectal adenoma were not domized placebo-controlled clinical trial affected by differences in the consumption in which men and women supplemented of vitamin E.52 their diets with either placebo, β-carotene In a case-control study conducted in (25 mg/day), vitamin C (1000 mg/day) plus Los Angeles, CA, the multivariate-adjusted vitamin E (400 mg/day) or all three antioxi- odds of developing colorectal adenoma dants for 4 years indicated that combined were not affected by differences in vitamin dietary supplementation with this amount E intakes from foods or from supplements of vitamin E did not affect the incidence among a study population that was almost of colorectal adenoma (RR: 1.08; 95% C.I.: entirely vitamin E deficient, even with vita- 0.91, 1.29; adjusted for age, sex, number min E supplementation (adjusted for daily of prior adenomas, actual length of time intakes of calories, saturated fat, folate between clinical evaluations and study and fiber, alcohol consumption, current center).58 This finding was confirmed in smoking status, BMI, race, level; of daily another 2-year double-blind, randomized, physical activity and use of nonsteroidal placebo-controlled human clinical trial, anti-inflammatory drugs).62 In this study, patients who were thought to be free of varying the degree of vitamin E deficiency colorectal polyps after polyp removal and did not reduce the risk for colorectal ad- who added either placebo or a supplement enoma. Similarly, in a case-control study containing 400 mg of vitamin C and 400 conducted in the Canton of Vaud, Swit- mg of vitamin E to their diets exhibited no zerland, the multivariate-adjusted odds difference in the multivariate-adjusted risk of developing colorectal cancer were not of developing new polyps (adjusted for age affected by differences in daily intakes of and the usual frequency of consumption of vitamin E in another population that was meats and fish).59 However, the placebo- largely vitamin E deficient (adjusted for controlled trials were of inadequate dura- age, sex, education, smoking status, alco- tion to measure accurately the incidence hol consumption, BMI, level of physical of new polyps or tumors; even in patients activity and daily intakes of energy and who have undergone polypectomy, the dietary fiber).54 minimum time before re-examination In a case-control study conducted in recommended by the 2006 Consensus Los Angeles, CA, the multivariate-adjusted Update on Guidelines for Colonoscopy

70 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two after Polypectomy of the US Multi-Society odds of developing adenocarcinoma of Task Force on Colorectal Cancer and the the esophagus were reduced significantly American Cancer Society is 5 years.61 in men who consumed more than 13 mg The results of secondary endpoint of vitamin E daily (RR, adenocarcinoma, analyses of the data obtained during the daily vitamin E intake > 13 mg vs < 13 prospective, double-blind, randomized mg: 0.13; 95% C.I.: 0.09, 0.54; adjusted and placebo-controlled Alpha-Tocopherol, for unspecified “known risk factors”).70 Beta-Carotene Cancer Prevention study of In a case-control study in Uruguay, the 29,133 middle-aged male cigarette smokers multivariate-adjusted odds of developing in Finland who supplemented their diets esophageal cancer were reduced signifi- with 50 mg of vitamin E, 20 mg of -carotene cantly by daily vitamin E intakes greater or placebo for 5 to 8 years indicated that than the lowest quartile of intake (OR: supplementation with 50 mg of vitamin E 0.41; 95% C.I.: 0.22, 0.76; adjusted for age, was associated with a significant increase gender, residence, urban or rural status, in the incidence of colorectal polyps,121 education, BMI, smoking status, alcohol although the incidence of colorectal cancer consumption, total energy intake and was not affected.60,122 This report is hardly daily intakes of β-carotene, -carotene , credible; the incidence of new colorectal lutein, lycopene, β-cryptoxanthin, vitamin adenoma reported in the subjects who did E, glutathione, quercetin, kaempferol, total not receive supplemental vitamin E was flavonoids, β-sitosterol, campesterol and over 10 times the projected incidence of stigmasterol).128 In a case-control study such cancers among the general US male conducted in China (the General Popula- population in 2008123 and an additional tion Trial in Linxian, China), although the 2- to 10-fold increase would be expected to mean serum concentration of a-tocopherol dominate the findings of every clinical trial did not differ between men and women that employed at least 50 mg of vitamin E. with esophageal cancer and cancer-free This has not happened.3,106,124-127 men and women, for every 25% increase The scientific evidence indicates that in serum a-tocopherol concentration above increased consumption of vitamin E re- the mean, the risk for esophageal cancer duces the risk for colorectal cancer. The decreased significantly by 10%.129 evidence documented by three retrospec- On the other hand, a secondary end- tive observational studies53,55,63 supports this point analysis of the data obtained during conclusion and there is no evidence that the prospective, double-blind, randomized, increased consumption of vitamin E may placebo-controlled Alpha-Tocopherol, increase the risk for colorectal cancer. Beta-Carotene Cancer Prevention study of 29,133 middle-aged male cigarette smokers Vitamin E Reduces the Risk for Adeno- in Finland who supplemented their diets carcinoma of the Esophagus with 50 mg of vitamin E, 20 mg of -caro- The scientific evidence indicates that tene or placebo for 5 to 8 years, determined increased consumption of vitamin E re- that 5 to 8 years of daily supplementation duces the risk for adenocarcinoma of the with 50 mg of vitamin E was unable to over- esophagus. The results of several retrospec- come the procarcinogenic effects of lifelong tive observational studies70,128,129 support cigarette smoking on the incidence of the conclusion that the consumption of esophageal cancer.130 However, the results increased amounts of vitamin E reduces of this epidemiologic analysis is relevant the risk for adenocarcinoma of the esopha- only to populations that match the parent gus. In a case-control study conducted experiment’s subjects – middle-aged male in Germany, the multivariate-adjusted life-long cigarette smokers.

71 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009

The results of three retrospective ing esophageal squamous cell carcinoma observational studies71,73,131 failed to reveal (OR: 0.37; 95% C.I.: 0.27, 0.60; adjusted for a protective effect of increased vitamin E sex, state of residence, age, race, income intakes against adenocarcinoma of the bracket, education, BMI, cigarette smok- esophagus. In a case-control study con- ing, alcoholic beverage consumption and ducted in New York state, the odds of de- total daily energy intake).69 Similarly, in a veloping adenocarcinoma of the esophagus case-control study conducted in France, were not affected by differences in vitamin the multivariate-adjusted odds of devel- E intakes.71 In a case-control study of the oping squamous cell carcinoma of the impact of vitamin E deficiency on adeno- esophagus were reduced significantly by carcinoma of the esophagus conducted in less-deficient intakes of vitamin E (OR, Sweden, the multivariate-adjusted odds of daily vitamin E intake > 7 mg vs < 7: 0.49; developing squamous cell carcinoma of the 95% C.I.: 0.28, 0.87; adjusted for interviewer, esophagus were not affected by differences age smoking status and daily consumption in vitamin E intakes in a vitamin E deficient of beer aniseed aperitives, hot Cakvados, population (adjusted for age, sex, BMI whisky, total alcohol and total energy).132 and smoking status).73 In a case-control This protection was strongest among the study conducted in the state of Hawaii, heaviest consumers of alcoholic bever- mean serum a-tocopherol concentrations ages. In a case-control study conducted in of subjects with and without esophageal Germany, the multivariate-adjusted odds cancer were not different.131 of developing squamous cell carcinoma of The scientific evidence indicates that the esophagus were reduced significantly increased consumption of vitamin E reduces in men who consumed more than 13 mg the risk for adenocarcinoma of the esopha- of vitamin E daily (RR, daily vitamin E gus. The evidence documented by three intake > 13 mg vs < 13 mg: 0.17; 95% C.I.: retrospective observational studies70,128,129 0.09, 0.48; adjusted for unspecified “known supports this conclusion and there is no risk factors”).70 evidence that increased consumption of In a case-control study in Uruguay, vitamin E may increase the risk for adeno- the multivariate-adjusted odds of devel- carcinoma of the esophagus. oping esophageal cancer were reduced significantly by daily vitamin E intakes Vitamin E Reduces the Risk for Squa- greater than the lowest quartile of intake mous Cell Carcinoma of the Esophagus (OR: 0.41; 95% C.I.: 0.22, 0.76; adjusted The scientific evidence indicates that for age, gender, residence, urban or rural increased consumption of vitamin E re- status, education, BMI, smoking status, duces the risk for squamous cell carcinoma alcohol consumption, total energy intake of the esophagus. The results of several ret- and daily intakes of β-carotene , lutein, rospective observational studies69,70,128,129,132 lycopene, β-cryptoxanthin, vitamin E, support the conclusion that the consump- glutathione, quercetin, kaempferol, total tion of increased amounts of vitamin E flavonoids, β-sitosterol, campesterol and reduces the risk for squamous cell carci- stigmasterol).128 In a case-control study noma of the esophagus. In a case-control conducted in China (the General Popula- study conducted in the US, compared to tion Trial in Linxian, China), although the men and women with daily vitamin E mean serum concentration of a-tocopherol intakes less than the 25th percentile, men did not differ between men and women and women with daily vitamin E intakes with esophageal cancer and cancer-free greater than the 75th percentile exhibited men and women, for every 25% increase significantly reduced odds of develop- in serum a-tocopherol concentration above

72 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two the mean, the risk for esophageal cancer mean serum a-tocopherol concentrations decreased significantly by 10%.129 of subjects with and without esophageal In contrast, a secondary end-point cancer were not different.131 analysis of the data obtained during the The scientific evidence indicates that prospective, double-blind, randomized, increased consumption of vitamin E reduc- placebo-controlled Alpha-Tocopherol, es the risk for squamous cell carcinoma of Beta-Carotene Cancer Prevention study of the esophagus. The evidence documented 29,133 middle-aged male cigarette smokers by five retrospective observational stud- in Finland who supplemented their diets ies69,70,128,129,132 supports this conclusion with 50 mg of vitamin E, 20 mg of β-caro- and there is no evidence that increased tene or placebo for 5 to 8 years, determined consumption of vitamin E may increase that 5 to 8 years of daily supplementation the risk for squamous cell carcinoma of with 50 mg of vitamin E was unable to over- the esophagus. In addition, the evidence come the procarcinogenic effects of lifelong documented by a retrospective observa- cigarette smoking on the incidence of tional study73 demonstrates that squamous esophageal cancer.130 However, the results cell carcinoma of the esophagus is not of this epidemiologic analysis is relevant prevented by vitamin E deficiency. only to populations that match the parent experiment’s subjects – middle-aged male Vitamin E may Reduce the Risk for life-long cigarette smokers. Laryngeal Cancer Data obtained during four retrospec- The scientific evidence suggests that tive observational studies73,82,131,133 failed increased consumption of vitamin E may to reveal a protective effect of increased reduce the risk for laryngeal cancer. The vitamin E intakes against squamous cell results of a retrospective observational carcinoma of the esophagus. In two case- study134 support the conclusion that the control studies conducted in Uruguay, the consumption of increased amounts of multivariate-adjusted odds of developing vitamin E reduces the risk for laryngeal squamous cell carcinoma of the esophagus cancer. In a case-control study conducted were not affected by differences in vitamin in Uruguay, the multivariate-adjusted E intakes (adjusted for age, sex, residence, odds of developing laryngeal cancer were urban or rural status, birthplace, educa- inversely correlated with vitamin E intake tion, BMI, smoking status, years since quit (adjusted for age, sex, residence, urban smoking, number of cigarettes smoked per or rural status, education, BMI, smoking day, alcohol consumption, mate tea con- status, years since quit smoking, number sumption and total daily energy intake;133 of cigarettes smoked per day by current adjusted for age, residence, urban or rural smokers, age at start of smoking and total status, education, family history of prostate daily energy intake).134 Increased vitamin cancer, BMI and total daily energy intake).82 E intake was most effective in the preven- In a case-control study of the impact of tion of cancer of the superglottis and less vitamin E deficiency on squamous cell effective in the prevention of cancer of the carcinoma of the esophagus conducted in glottis. Risk reduction was weakened by Sweden, the multivariate-adjusted odds of continuation of cigarette smoking. developing squamous cell carcinoma of the In contrast, a post hoc secondary end- esophagus were not affected by differences point analysis of the data obtained during in vitamin E intakes in a vitamin E deficient the prospective, double-blind, randomized, population (adjusted for age, sex, BMI placebo-controlled Alpha-Tocopherol, and smoking status).73 In a case-control Beta-Carotene Cancer Prevention study of study conducted in the state of Hawaii, 29,133 middle-aged male cigarette smokers

73 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 in Finland who supplemented their diets takes.136 Although the odds of men in the with 50 mg of vitamin E, 20 mg of -caro- US developing malignant melanoma were tene or placebo for 5 to 8 years, determined not affected by differences in the intakes that 5 to 8 years of daily supplementation of vitamin E from foods and supplements, with 50 mg of vitamin E was unable to the odds of women developing malignant overcome the procarcinogenic effects of melanoma were halved when daily total lifelong cigarette smoking on the incidence vitamin E intakes from foods and supple- of laryngeal cancer.130 However, the results ments exceeded the RDA (OR: 0.41; 95% of this epidemiologic analysis is relevant C.I.: 0.21, 0.81).137 Consistent with these only to populations that match the parent reports, the results of observing the 39,268 experiment’s subjects – middle-aged male male and female participants in the Finnish life-long cigarette smokers. Social Insurance Institution’s Mobile Clinic On the other hand, the results of two Health Survey, aged 15-99 and initially retrospective observational studies131,135 free from cancer, prospectively for 8 years failed to reveal a protective effect of in- indicated that serum a-tocopherol concen- creased vitamin E intakes against laryngeal trations were inversely correlated with the cancer. In a case-control study conducted risk of developing melanoma.138 in Japan, the multivariate-adjusted odds In contrast, the results of combining of developing laryngeal cancer were not the data obtained from 73,525 female par- affected by differences in vitamin E intakes ticipants in the prospective observational (adjusted for age, sex, smoking status, Nurses’ Health Study and from 88,553 alcohol consumption, use of multivitamin prospective observational Nurses’ Health supplements, total daily energy intake, Study II indicated that the multivariate- dental hygiene and year of first hospital adjusted risk of developing melanoma was visit)135 and in a case-control study con- not affected by differences in vitamin E ducted in the state of Hawaii, mean serum intakes from foods or dietary supplements a-tocopherol concentrations of subjects (adjusted for age, skin reaction after 2 with and without laryngeal cancer were hours of sun exposure during childhood, not different.131 number of sunburns over lifetime, number The scientific evidence suggests that of sunburns during adolescence, number increased consumption of vitamin E may of moles on left arm, number of moles reduce the risk for laryngeal cancer. The on lower legs, hair color, family history of evidence documented by a retrospective melanoma, state of residence, menopausal observational study134 supports this conclu- status, use of oral contraceptives, use of sion and there is no evidence that increased postmenopausal hormone therapies, par- consumption of vitamin E may increase ity, height and BMI).139 In a case-control the risk for laryngeal cancer. study conducted in Boston, MA, the multivariate-adjusted odds of developing Vitamin E Reduces the Risk for malignant melanoma were not affected Melanoma by differences in plasma a-tocopherol con- The scientific evidence indicates centrations or vitamin E intakes (adjusted that increased consumption of vitamin E for age, sex, plasma lipid concentrations, reduces the risk for melanoma. The results hair color and the ability to suntan).140 of a case-control study conducted in Wash- In a series of case-control studies nested ington County, MD, indicated that the odds within a prospective study in Washington of developing malignant melanoma were County, MD, prediagnostic serum vitamin inversely correlated with age, education, E concentrations were not associated with and energy intake-adjusted vitamin E in- the odds of developing melanoma.101,141

74 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two

The scientific evidence indicates that smoking and drinking habits and non- increased consumption of vitamin E re- alcohol energy intake).144 duces the risk for melanoma. The evidence However, the results of four retro- documented by a prospective observational spective observational studies131,145-147 study138 and 2 retrospective observational failed to document a relationship between studies136,137 supports this conclusion and vitamin E and cancer of the oral cav- there is no evidence that increased con- ity. For example, in a case-control study sumption of vitamin E may increase the conducted in Melbourne, Australia, the risk for melanoma. odds of developing squamous cell cancer of the oral cavity were not affected by dif- Vitamin E Reduces the Risk for Cancer ferences in dietary vitamin E intakes.145 In of the Oral Cavity a case-control study conducted in Japan, The scientific evidence indicates the odds of developing oral leukoplakia, that increased consumption of vitamin a precursor of cancer of the oral cavity, E reduces the risk for cancer of the oral were not affected by differences in serum cavity. The results of four retrospective a-tocopherol concentrations.146 In a case- observational studies135,142-144 support the control study conducted in the state of conclusion that increased consumption Hawaii, mean serum a-tocopherol con- of vitamin E reduces the risk for cancer centrations of subjects with and without of the oral cavity. In a case-control study any upper aerodigestive tract cancer were conducted in New York City, the odds not different.131 In a case-control study of developing cancer of the oral cavity conducted in Washington County, MD, were inversely correlated with dietary the odds of developing cancer of the oral supplementation with vitamin E.142 In cavity were not affected by prediagnostic another case-control study conducted serum a-tocopherol concentration.147 in the US, the odds of developing cancer In addition, in the prospective, double- of the oral cavity were inversely corre- blind, randomized and placebo-controlled lated with vitamin E supplementation Alpha-Tocopherol, Beta-Carotene Cancer (OR, supplementation vs none: 0.5; 95% Prevention study of 29,133 middle-aged C.I.: 0.4, 0.6).143 In a case-control study male cigarette smokers in Finland who conducted in Japan, the multivariate- supplemented their diets with 50 mg of vi- adjusted odds of developing cancer of tamin E, 20 mg of -carotene or placebo for the oral cavity were reduced significantly 5 to 8 years, supplementation with 50 mg in men and women by greater intakes of of vitamin E daily did not appear to affect vitamin E (OR, daily vitamin E intake > the prevalence of either oral leukoplakia or 7.7 mg vs < 4.0 mg: 0.54; 95% C.I.: 0.33, dysplastic lesions of the buccal epithelium 0.88; adjusted for age, sex, smoking sta- or the incidence of upper aerodigestive tus, alcohol consumption, use of multi- tract cancers (cancers of the oral cavity, vitamin supplements, total daily energy pharynx, esophagus or larynx).130,148 intake, dental hygiene and year of first The scientific evidence indicates hospital visit).135 In a case-control study that increased consumption of vitamin conducted in Italy and Switzerland, the E reduces the risk for cancer of the oral multivariate-adjusted odds of developing cavity. The evidence documented by four either pharyngeal cancer or cancer of the retrospective observational studies135,142-144 oral cavity were reduced significantly by supports this conclusion and there is no increased intake of vitamin E (OR: 0.74; evidence that increased consumption of p < 0.05; adjusted for age, sex, center, vitamin E may increase the risk for cancer education, occupation, body mass index, of the oral cavity.

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Vitamin E Reduces the Risk for cancer-free women participating in the Ovarian Cancer 16-year prospective Nurses’ Health Study,75 The scientific evidence indicates the risks of developing ovarian cancer were that increased consumption of vitamin E not affected by differences in vitamin E reduces the risk for ovarian cancer. The intakes. In a case-control study conducted results of retrospective observational stud- in Hawaii and Los Angeles, CA, differences ies support the conclusion that increased in vitamin E intakes did not affect the consumption of vitamin E reduces the risk odds of premenopausal or postmenopausal for ovarian cancer.74,79,149 In a case-control women developing ovarian cancer.78 In a study of women conducted in North case-control study nested within a pro- Carolina, total daily intakes of vitamin E spective study conducted in Washington in excess of 75 mg reduced significantly County, MD, the odds of developing ovar- the odds of developing epithelial ovarian ian cancer were not affected by differences cancer (OR: 0.44; 95% C.I.: 0.21, 0.94) and in cholesterol-adjusted serum a-tocopherol dietary supplementation with any amount concentrations.150 In a case-control study of vitamin E also reduced significantly conducted in New Hampshire and eastern the odds of developing epithelial ovarian Massachusetts, differences in daily intakes cancer (OR: 0.33; 95% C.I.: 0.18, 0.60).74 Con- of vitamin E had no effect on the odds of sistent with this report, in a case-control premenopausal or postmenopausal women study conducted in Canada, any amount of developing ovarian cancer.80 supplementation with vitamin E for more The scientific evidence indicates that than 10 years halved the adjusted odds of increased consumption of vitamin E re- developing ovarian cancer (OR: 0.49; 95% duces the risk for ovarian cancer. The evi- C.I.: 0.30, 0.81; adjusted for age, residence, dence documented by three retrospective education, alcohol consumption, cigarette observational studies74,79,149 supports this smoking, BMI, daily energy intake, recre- conclusion and there is no evidence that ational physical activity, parity, years of increased consumption of vitamin E may menstruation and menopausal status).79 increase the risk for ovarian cancer. In a case-control study conducted in Italy, the risk of developing epithelial ovarian Vitamin E Reduces the Risk for cancer was reduced significantly among Pancreatic Cancer women who regularly consumed more The scientific evidence indicates than the median amount of vitamin E that increased consumption of vitamin daily, compared to the risk of women who E reduces the risk for pancreatic cancer. regularly consumed less than the median The results of retrospective observational amount of vitamin E daily (RR: 0.6; 95% studies conducted in Shanghai, China, C.I.: 0.4. 0.7; adjusted for age, study center, support the conclusion that increased year of entry into study, BMI, parity, use of consumption of vitamin C reduces the oral contraceptives, occupational physical risk for pancreatic cancer.151,152 In one activity and daily energy intake).149 study, the multivariate-adjusted odds In contrast, the results two prospec- of developing pancreatic cancer were tive75,77 and three retrospective obser- reduced significantly in men (but not vational studies78,80,150 failed to discern women) consuming “high” amounts a relationship between vitamin C and of vitamin E (OR, daily vitamin E con- ovarian cancer. Among 97,275 initially sumption > 41 mg vs < 26 mg: 0.57; cancer-free women participating in the 8- 95% C.I.: 0.35, 0.93; adjusted for age, year prospective California Teachers Study income, smoking, green tea drinking of women,77 and among 80,326 initially and daily caloric intake).151 In the other,

76 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two the multivariate-adjusted odds of devel- Vitamin E Reduces the Risk for oping pancreatic cancer were reduced Pharyngeal Cancer significantly in both men and women The scientific evidence indicates that consuming “high” amounts of vitamin E increased consumption of vitamin E re- (OR, men, 4th quartile of daily vitamin duces the risk for pharyngeal cancer. The E consumption vs 1st quartile: 0.5; 95% results of a case-control study conducted C.I.: 0.3, 0.7; women, 4th quartile of daily in Italy and Switzerland indicated that the vitamin E consumption vs 1st quartile: multivariate-adjusted odds of developing 0.5; 95% C.I.: 0.3, 0.8; both adjusted for either cancer of the oral cavity or pharyn- age, income, smoking, green tea drinking geal cancer were reduced significantly by and daily caloric intake).152 increased intake of vitamin E (OR: 0.74; p However, in a case-control study < 0.05; adjusted for age, sex, center, educa- nested within a prospective study in tion, occupation, body mass index, smok- Washington County, MD, prediagnostic ing and drinking habits and non-alcohol serum vitamin E concentrations were energy intake).144 not associated with the odds of develop- However, in the prospective, double- ing pancreatic cancer.101 In addition, the blind, randomized and placebo-controlled results of a secondary endpoint analysis Alpha-Tocopherol, Beta-Carotene Cancer of the data obtained in the prospective, Prevention study of 29,133 middle-aged double-blind, randomized and placebo- male cigarette smokers in Finland who controlled Alpha-Tocopherol, Beta-Caro- supplemented their diets with 50 mg of tene Cancer Prevention study of 29,133 vitamin E, 20 mg of β-carotene or placebo middle-aged male cigarette smokers in for 5 to 8 years, supplementation with 50 Finland who supplemented their diets mg of vitamin E daily had no effect on with 50 mg of vitamin E, 20 mg of β- the incidence of upper aerodigestive tract carotene or placebo for 5 to 8 years cancers (cancers of the oral cavity, phar- indicated that supplementation with 50 ynx, esophagus or larynx).130 Consistent mg of vitamin E daily had no effect on with this report, in a case-control study the incidence of pancreatic carcinoma.153 conducted in Japan, the multivariate- In addition, an epidemiologic analysis of adjusted odds of developing pharyngeal that data indicated that the risk of devel- cancer were not affected by differences in oping pancreatic cancer was not affected vitamin E intakes (adjusted for age, sex, by differences in the intake of vitamin smoking status, alcohol consumption, use E.154 Similarly, the results of observing of multivitamin supplements, total daily a cohort of 13,979 initially cancer-free energy intake, dental hygiene and year of residents of a retirement community for first hospital visit).135 Similarly, in a case- 9 years indicated that the risk of develop- control study conducted in Melbourne, ing pancreatic cancer was not affected Australia, the odds of developing either by differences in the daily consumption squamous cell cancer of the oral cavity or of vitamin E.155 pharyngeal cancer were not affected by The scientific evidence indicates that differences in dietary vitamin E intakes.145 increased consumption of vitamin E re- In addition, the results of a case-control duces the risk for pancreatic cancer. The study conducted in the state of Hawaii evidence documented by two retrospective indicated that the mean serum a-tocoph- observational studies151,152 supports this erol concentrations of subjects with and conclusion and there is no evidence that without upper aerodigestive tract cancer increased consumption of vitamin E may were not different.131 increase the risk for pancreatic cancer. The scientific evidence indicates that

77 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 increased consumption of vitamin E re- that even though differences in serum a- duces the risk for pharyngeal cancer. The tocopherol concentrations had no effect evidence documented by a retrospective on the odds of developing prostate cancer observational study144 supports this conclu- during the study,161 19 years later the risks sion and there is no evidence that increased for any prostate cancer and for advanced consumption of vitamin E may increase prostate cancer were inversely correlated the risk for pharyngeal cancer. with prestudy serum a-tocopherol con- centrations (risk estimates were adjusted Vitamin E Reduces the Risk for for age at blood sample collection, trial Prostate Cancer intervention arm, serum total cholesterol The scientific evidence suggests that concentration, body weight, urban resi- the consumption of increased amounts dence and education).162 These findings are of vitamin E reduces the risk for prostate even more remarkable given the continued cancer. In a secondary endpoint analysis of cigarette smoking by the subjects during the data obtained during the prospective, and after the study and the data from a double-blind, randomized and placebo- 20-year prospective observational study controlled Alpha-Tocopherol, Beta-Caro- of 17,633 white males aged 35 years and tene Cancer Prevention study of 29,133 older (the Lutheran Brotherhood Cohort middle-aged male cigarette smokers in Study) that confirm that the use of tobacco Finland who supplemented their diets with products increases the risk of developing 50 mg of vitamin E, 20 mg of β-carotene prostate cancer.163 or placebo, it was determined that 5 to 8 The results of prospective observa- years of daily dietary supplementation with tional studies also support the conclusion 50 mg of vitamin E produced a significant that increased consumption of vitamin decrease in the incidence of new prostate E reduces the risk for prostate cancer.86- cancer (RR: 0.52; 95% C.I.: 0.29, 0.95; ad- 88,164,165 For example, although the results of justed for age, presence of benign pros- an 8-year prospective observational study tatic hyperplasia, living in an urban area, (the Prostate, Lung, Colorectal and Ovar- presence or absence of concurrent dietary ian Cancer Screening Trial) suggest that supplementation with β-carotene and se- among all men, differences in vitamin E or rum total cholesterol concentration).122,156- a-tocopherol intakes from foods or dietary 158 Consistent with this result, two groups of supplements do not affect the multivariate- analysts performing systematic reviews of adjusted risk of developing prostate cancer human clinical trials concluded that daily (adjusted for age, daily energy intake, race, supplementation with 50 mg of vitamin E study center, family history of prostate can- significantly reduces the risk for developing cer, BMI, smoking status, physical activity, prostate cancer.159,160 daily consumption of fats and red meats, In addition, an analysis of the effects history of diabetes and aspirin use) among of prestudy serum a-tocopherol concen- current smokers and nonsmokers who had trations on the development of prostate quit smoking within 10 years, daily dietary cancer 19 years later in participants in supplementation with more than 400 IU of the prospective, double-blind, randomized vitamin E reduces significantly the risk of and placebo-controlled Alpha-Tocopherol, developing advanced prostate cancer (OR, Beta-Carotene Cancer Prevention study of daily dietary supplementation with more 29,133 middle-aged male cigarette smok- than 400 IU of vitamin E vs none: 0.29; ers in Finland who supplemented their 95% C.I.: 0.12, 0.68; adjusted for age, daily diets with 50 mg of vitamin E, 20 mg of energy intake, race, study center, family -carotene or placebo for 5 to 8 years found history of prostate cancer, BMI, smoking

78 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two status, physical activity, daily consumption In a case-control study conducted in Ser- of fats and red meats, history of diabetes bia, the odds of developing prostate cancer and aspirin use).88 Similarly, among cur- were reduced significantly by greater daily rent smokers and nonsmokers who had intakes of a-tocopherol (OR: 0.15, 95% C.I.: quit smoking within 10 years and who 0.05, 0.53)95 and in a case-control study had consumed any amount of supplemen- conducted in Athens, Greece, the odds of tal vitamin E for at least 10 years, daily developing prostate cancer were inversely dietary supplementation with vitamin E correlated with vitamin E intakes.166 reduces significantly the risk of developing In a case-control study nested within a advanced prostate cancer (OR, supplemen- prospective study conducted in Washing- tation with any amount of vitamin E for at ton County, MD, the multivariate-adjusted least 10 years vs none: 0.30; 95% C.I.: 0.09, odds of developing prostate cancer were 0.96; adjusted for age, daily energy intake, reduced significantly when serum a-to- race, study center, family history of pros- copherol concentration was greater than tate cancer, BMI, smoking status, physical 1.31 mg/dl, serum gamma-tocopherol con- activity, daily consumption of fats and red centration was greater than 0.28 mg/dl and meats, history of diabetes and aspirin use). serum selenium concentrations was either Consistent with this report, in a 17-year less than 0.79 ppm (OR: 0.34; 95% C.I.: 0.12, prospective study of 2,974 men in Basel, 0.99; adjusted for age, education and hours Switzerland, serum vitamin E concentra- since last meal when blood was obtained) tions < 30.02 uM increased significantly the or greater than 0.79 ppm (OR: 0.27; 95% risk of developing prostate cancer among C.I.: 0.10, 0.72; adjusted for age, education cigarette smokers (RR: 19.89; 95% C.I.: 3.60, and hours since last meal when blood was 109.80).86,87 On the other hand, the results obtained).167 Consistent with this report, of the double-blind, randomized placebo- in a case-control study conducted in India, controlled Prevention Research Veteran mean erythrocyte ascorbic acid content Affairs E-vitamin Nutrition Trial indicated and mean plasma vitamin E concentration that daily supplementation with 400 IU of were significantly lower among patients vitamin E produced a significant increase with prostate cancer.168 in mean serum a-tocopherol concentration In contrast to this body of supportive without affecting mean serum prostate evidence, the results of prospective85,89,169,170 specific antigen concentration164 and the and retrospective91,94,96,97,101,171-174 observa- results of a 10-year prospective observa- tional studies did not provide support for tional study of 35,242 men conducted in the conclusion that increased consumption Washington State indicated that the risk of vitamin C reduces the risk for prostate for advanced (regionally invasive or distant cancer. After 10 years of observation, metastatic) prostate cancer was reduced those among the 47,780 men participat- significantly by daily supplementation ing in the prospective US Health Profes- with at least 400 IU of vitamin E (HR: sionals Follow-Up Study who consumed 0.43; 95% C.I.: 0.19, 1.0; adjusted for age, dietary supplements containing vitamin family history of prostate cancer, history E exhibited no change in their multivari- of benign prostatic hyperplasia, income, ate-adjusted risk of developing prostate use of multivitamins and serum prostate cancer (adjusted for period of study, age, specific antigen concentration).165 family history of prostate cancer, vasec- The results of retrospective observa- tomy status, smoking status, current BMI, tional studies also support the conclusion BMI at age 21 years, physical activity level that increased consumption of vitamin E at entry into study, daily energy intake reduces the risk for prostate cancer.95,166-168 and daily intakes of calcium, lycopene,

79 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 fructose and total fat).169 Similarly, among odds of developing prostate cancer were not the 72,704 men of the American Can- affected by differences in prestudy serum cer Society Cancer Prevention Study II a-tocopherol concentrations (adjusted for Nutrition Cohort, the risk of developing study center, asbestos exposure, age, sex, prostate cancer was not affected by the smoking status during study, year of entry intakes of vitamin E from either foods or into study and cigarette smoking history supplements,170 among the 475,726 men prior to the study).171 Similarly, in a case- participating in the 18-year prospective control study nested within the 8-country observational American Cancer Society European Prospective Investigation into Cancer Prevention Study II, daily dietary Cancer and Nutrition (EPIC), the multi- supplementation with vitamin E did not variate-adjusted odds of developing prostate affect the multivariate-adjusted rate of cancer were not affected by differences in death from prostate cancer (adjusted for prestudy plasma a-tocopherol concentra- age, race, education, smoking status, family tions (adjusted for BMI, smoking status, history or prostate cancer, exercise, BMI, alcohol consumption, level of physical alcohol consumption, vegetable consump- activity, marital status and education).172 tion and dietary supplementation with In individual case-control studies nested multivitamins, vitamin A and vitamin C)85 within a prospective study in Washington and the results of a 6.3-year prospective County, MD, prediagnostic serum vitamin observational study of 58,279 men aged 55 E concentrations were not associated with to 69 years (the Netherlands Cohort Study) the odds of developing prostate cancer101,173 indicated that the age- and sex-adjusted and when the data from 2 case-control risk of developing prostate cancer was not studies conducted in Washington County, affected by differences in vitamin E intakes MD were combined, the odds of developing in that study population.89 prostate cancer were found to be unaffected In case-control studies conducted in by differences in serum concentrations Sweden94 and Montreal, Quebec, Canada,96 of a-tocopherol.97 In a case-control study the odds of developing either any form conducted in Hawaii, the multivariate-ad- of prostate cancer or advanced prostate justed odds of developing prostate cancer cancer were not affected by differences in were not affected by differences in serum daily intakes of vitamin E (adjusted for age a-tocopherol concentrations.174 and daily energy intake). In a case-control The scientific evidence indicates that study conducted in the state of Washington increased consumption of vitamin E reduces in the US, the multivariate-adjusted odds the risk for prostate cancer. The evidence of developing prostate cancer were not documented by a secondary endpoint analy- affected by the use of any dietary supple- sis of the data obtained during a prospective ments of vitamin E (adjusted for dietary trial,122,156-158 the results of two systematic intakes of fat and total energy, race, age, reviews,159,160 6 prospective observational family history of prostate cancer, BMI, se- studies86-88,163,165,166 and 4 retrospective obser- rum prostate specific antigen concentration vational studies95,166-168 supports this conclu- and education).91 sion and there is no evidence that increased In a case-control study nested within consumption of vitamin E increases the risk the prospective Beta-Carotene and Retinol for prostate cancer. Efficacy Trial (CARET) of dietary supple- mentation of 18,314 high-risk subjects Conclusions (heavy smokers and workers exposed to The foregoing credible scientific evi- asbestos) with placebo, beta-carotene or dence establishes that adequate intakes of retinyl palmitate, the multivariate-adjusted vitamin C and vitamin E safely reduce the

80 Antioxidant Vitamins Reduce the Risk for Cancer, Part Two

risk for cancer in general. Individually, Control, 2005; 16: 1135-1145. vitamin C reduces the risk for bladder 7. Jacobs EJ, Henion AK, Briggs PJ, et al: Vitamin cancer, breast cancer, cervical cancer, co- C and vitamin E supplement use and bladder lon cancer, colorectal cancer, endometrial cancer mortality in a large cohort of US men cancer, adenocarcinoma of the esophagus, and women. Am J Epidemiol, 2002b; 156: 1002- 1010. squamous cell carcinoma of the esophagus, 8. Zeegers MP, Goldbohm RA, van den Brandt gastric carcinoma, lung cancer, cancer of PA: Are retinol, vitamin C, vitamin E, folate the oral cavity, ovarian cancer, pancreatic and carotenoids intake associated with blad- cancer, pharyngeal cancer, prostate cancer, der cancer risk? Results from the Netherlands renal cell cancer, and cancer of the salivary Cohort Study. Br J Cancer, 2001; 85: 977-983. 9. Michels KB, Holmberg L, Bergkvist L, et al: Di- glands. Vitamin C also may reduce the risk etary antioxidant vitamins, retinol, and breast of laryngeal cancer. Individually, vitamin E cancer incidence in a cohort of Swedish women. reduces the risk for bladder cancer, brain Int J Cancer, 2001; 91: 563-567. cancer, breast cancer, cervical cancer, colon 10. Freudenheim JL, Marshall JR, Vena JE, et al: cancer, colorectal cancer, adenocarcinoma Premenopausal breast cancer risk and intake of the esophagus, squamous cell carcinoma of vegetables, fruits, and related nutrients. J Natl Cancer Inst, 1996; 88: 340-348. of the esophagus, gastric carcinoma, lung 11. Ambrosone CB, Marshall JR, Vena JE, et al: cancer, melanoma, cancer of the oral Interaction of family history of breast cancer cavity, ovarian cancer, pancreatic cancer, and dietary antioxidants with breast cancer pharyngeal cancer, prostate cancer, and risk (New York, United States). Cancer Causes renal cell cancer. Vitamin E also may Control, 1995; 6: 407-415. 12. Adzersen KH, Jess P, Freivogel KW, Gerhard I, reduce the risk of laryngeal cancer and Bastert G: Raw and cooked vegetables, fruits, rectal cancer. selected micronutrients, and breast cancer risk: A case-control study in Germany. Nutr Cancer, References 2003; 46: 131-137. 1. Castelao JE, Yuan JM, Gago-Dominguez M, et 13. Do MH, Lee SS, Jung PJ, Lee MH: Intake of di- al: Carotenoids/vitamin C and smoking-related etary fat and vitamin in relation to breast cancer bladder cancer. Int J Cancer, 2004; 110: 417- risk in Korean women: A case-control study. J 423. Korean Med Sci, 2003; 18: 534-540. 2. Bruemmer B, White E, Vaughan TL, Cheney CL: 14. Zaridze D, Lifanova Y, Maximovitch D, Day Nutrient intake in relation to bladder cancer NE, Duffy SW: Diet, alcohol consumption and among middle-aged men and women. Am J reproductive factors in a case-control study of Epidemiol, 1996; 144: 485-495. breast cancer in Moscow. Int J Cancer, 1991; 48: 3. Yalcin O, Karata F, Erula FA, Ozdemir E: The 493-501. levels of glutathione peroxidase, vitamin A, E, 15. Landa MC, Frago N, Tres A: Diet and the risk of C and lipid peroxidation in patients with tran- breast cancer in Spain. Eur J Cancer Prev, 1994; sitional cell carcinoma of the bladder. BJU Int, 3: 313-320. 2004; 93: 863-866. 16. Bala DV, Patel DD, Duffy SW, et al: Role of 4. Michaud DS, Pietinen P, Taylor PR, et al: In- dietary intake and biomarkers in risk of breast takes of fruits and vegetables, carotenoids and cancer: A case control study. Asian Pac J Cancer vitamins A, E, C in relation to the risk of bladder Prev, 2001; 2: 123-130. cancer in the ATBC cohort study. Br J Cancer, 17. Ronco A, De Stefani E, Boffetta P, et al: Veg- 2002; 87: 960-965. etables, fruits, and related nutrients and risk of 5. Michaud DS, Spiegelman D, Clinton SK, et al: breast cancer: A case-control study in Uruguay. Prospective study of dietary supplements, mac- Nutr Cancer, 1999; 35: 111-119. ronutrients, micronutrients, and risk of bladder 18. Ronco AL, De Stefani E, Boffetta P, et al: Food cancer in US men. Am J Epidemiol, 2000; 152: patterns and risk of breast cancer: A factor 1145-1153. analysis study in Uruguay. Int J Cancer, 2006; 6. Holick CN, De Vivo I, Feskanich D, et al: Intake 119: 1672-1678. of fruits and vegetables, carotenoids, folate, 19. Guo WD, Chow WH, Zheng W, Li JY, Blot WJ. and vitamins A, C, E and risk of bladder cancer Diet, serum markers and breast cancer mortality among women (United States). Cancer Causes in China. Jpn J Cancer Res, 1994; 85: 572-577.

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study in Italy. Ann Oncol, 2001; 12: 1589-1593. rum and dietary vitamin E in relation to prostate 150.Helzlsouer KJ, Alberg AJ, Norkus EP, et al: cancer risk. Cancer Epidemiol Biomarkers Prev, Prospective study of serum micronutrients 2007; 16: 1253-1259. and ovarian cancer. J Natl Cancer Inst, 1996; 163.Hsing AW, McLaughlin JK, Schuman LM, et 88: 32-37. al: Diet, tobacco use, and fatal prostate cancer: 151.Ji BT, Chow WH, Gridley G, et al: Dietary Results from the Lutheran Brotherhood Cohort factors and the risk of pancreatic cancer: A Study. Cancer Res, 1990a; 50: 6836-6840. case-control study in Shanghai China. Cancer 164.Hernáandez J, Syed S, Weiss G, et al: The Epidemiol Biomarkers Prev, 1995; 4: 885-893. modulation of prostate cancer risk with alpha- 152.Ji BT, Chow WH, Yang G, et al: Dietary habits tocopherol: A pilot randomized, controlled and stomach cancer in Shanghai, China. Int J clinical trial. J Urol, 2005; 174: 519-522. Cancer, 1998; 76: 659-664. 165.Peters U, Littman AJ, Kristal AR, et al: Vitamin 153.Rautalahti MT, Virtamo JR, Taylor PR, et al: E and selenium supplementation and risk of The effects of supplementation with alpha- prostate cancer in the Vitamins and lifestyle tocopherol and beta-carotene on the incidence (VITAL) study cohort. Cancer Causes Control, and mortality of carcinoma of the pancreas in 2008; 19: 75-87. a randomized, controlled trial. Cancer, 1999; 166.Tzonou A, Signorello LB, Lagiou P, et al: Diet 86: 37-42. and cancer of the prostate: A case-control study 154.Stolzenberg-Solomon RZ, Pietinen P, Taylor in Greece. Int J Cancer, 1999; 80: 704-708. PR, Virtamo J, Albanes D: Prospective study of 167.Helzlsouer KJ, Huang HY, Alberg AJ, et al: As- diet and pancreatic cancer in male smokers. sociation between alpha-tocopherol, gamma- Am J Epidemiol, 2002; 155: 783-792. tocopherol, selenium, and subsequent prostate 155.Shibata A, Mack TM, Paganini-Hill A, Ross cancer. J Natl Cancer Inst, 2000; 92: 2018-2023. RK, Henderson BE: A prospective study of 168.Surapaneni KM, Ramana V: Erythrocyte pancreatic cancer in the elderly. Int J Cancer, ascorbic acid and plasma vitamin E status 1994; 58: 46-49. in patients with carcinoma of prostate. Ind J 156.Albanes D, Heinonen OP, Huttunen JK, et al. Physiol Pharmacol, 2007; 51: 199-202. Effects of alpha-tocopherol and beta-carotene 169.Chan JM, Stampfer MJ, Ma J, et al: Supplemen- supplements on cancer incidence in the Alpha- tal vitamin E intake and prostate cancer risk Tocopherol Beta-Carotene Cancer Prevention in a large cohort of men in the United States. Study. Am J Clin Nutr, 1995; 62(Suppl.): 1427S- Cancer Epidemiol Biomarkers Prev, 1999; 8: 1430S. 893-899. 157.Heinonen OP, Albanes D, Virtamo J, et al: 170.Rodriguez C, Jacobs EJ, Mondul AM, et al: Vita- Prostate cancer and supplementation with min E supplements and risk of prostate cancer alpha-tocopherol and beta-carotene: Incidence in U.S. men. Cancer Epidemiol Biomarkers Prev, and mortality in a controlled trial. J Natl Cancer 2004; 13: 378-382. Inst, 1998; 90: 440-446. 171.Goodman GE, Schaffer S, Omenn GS, Chen 158.Hartman TJ, Albanes D, Pietinen P, et al: The as- C, King I: The association between lung and sociation between baseline vitamin E, selenium, prostate cancer risk, and serum micronutrients: and prostate cancer in the alpha-tocopherol, Results and lessons learned from beta-carotene beta-carotene cancer prevention study. Cancer and retinol efficacy trial. Cancer Epidemiol Epidemiol Biomarkers Prev, 1998; 7: 335-340. Biomarkers Prev, 2003; 12: 518-526. 159.Shekelle P, Hardy ML, Coulter I, et al: Effect of 172. Key TJ, Appleby PN, Allen NE, et al: Plasma ca- the supplemental use of antioxidants vitamin C, rotenoids, retinol, and tocopherols and the risk vitamin E, and coenzyme Q10 for the prevention of prostate cancer in the European Prospective and treatment of cancer. Evid Rep Technol Assess Investigation into Cancer and Nutrition study. (Summ). 2003 Oct; (75): 1-3. Am J Clin Nutr, 2007; 86: 672-681. 160.Coulter ID, Hardy ML, Morton SC, et al: Antioxi- 173. Hsing AW, Comstock GW, Abbey H, Polk BF: dants vitamin C and vitamin E for the prevention Serologic precursors of cancer. Retinol, carot- and treatment of cancer. J Gen Intern Med, 2006; enoids, and tocopherol and risk of prostate 21: 735-744. cancer. J Natl Cancer Inst, 1990b; 82: 941-946. 161.Weinstein SJ, Wright ME, Pietinen P, et al:Serum 174. Nomura AM, Stemmermann GN, Lee J, Craft alpha-tocopherol and gamma-tocopherol in NE: Serum micronutrients and prostate cancer relation to prostate cancer risk in a prospective in Japanese Americans in Hawaii. Cancer Epide- study. J Natl Cancer Inst, 2005; 97: 396-399. miol Biomarkers Prev, 1997; 6: 487-491. 162.Weinstein SJ, Wright ME, Lawson KA, et al: Se-

87 Case From the Center

Vitamin D (25-OH-D3) Status of 200 Chronically Ill Outpatients Treated at The Center

James A. Jackson, MT(ASCP), CLS, Ph.D., BCLD(AAB); Rebecca K. Kirby, R.D., M.S., M.D.; Mary Braud, M.D.; Karen Moore, B.S., MT1

There have been many studies re- were ordered on 200 patients seen at The cently concerning the proper amount Center over the past four months. The of Vitamin D (25-OH-D3) that is neces- test was performed in our own BioCenter sary to combat the many diseases that Laboratory (www.biocenterlab.com) using are now being associated with vitamin the DiaSorin® R.I.A. method. Reference D deficiencies. Two studies examined ranges were established from data col- the vitamin D status of hospitalized lected from our patient population and patients, general population and those cross checked with other laboratories. admitted to a rehabilitation hospital.1,2 Table 1 (p.89) shows some of the de- The study of hospitalized patients found mographic data and preliminary results. the vitamin D status of sub-optimal to Sixty-six percent of the patients were overt deficiency levels to be a common female and the ages of all patients ranged finding. The same findings were found from 6 to 91 years of age with a mean age in 51 non-hospitalized volunteers. It also of 55 years. Results of the vitamin D tests found that sub-optimal levels of vitamin ranged from 5.0 ng/mL (overt deficiency) D increased the length of stay (LOS) in to 96 ng/mL. The mean range of the 200 hospitalized patients.1 tests was 32.5 ng/mL (sub-optimal). The A study of 100 patients, men and optimal range of The BioCenter Labora- women with various diagnoses (mean age tory is 40 to 80 ng/mL. of 70 years) admitted to a rehabilitation Table 2 (p.89) shows the results of hospital found that 11% of the patients patients based on four different classifi- to be overtly vitamin D deficient (<8.0 cations. Considering that the minimum ng/mL) and “ninety-four percent” of the optimal range is 40 ng/mL, 152 patients patients had sub-optimal levels (<32 ng/ (76%) had less than optimal vitamin D mL) of vitamin D. A simple, inexpensive levels. It does appear that the older the treatment with vitamin D (25-OH-D3) patient, the lower the level. One 78-year could improve the patient’s functional old female had a value of 5.0 ng/mL; 3 ability, decrease the LOS and dramatically females age 60 and one male age 66 had reduce the cost of health care.2 levels of 6.0 mg/dL. Only 48 patients The Center only treats chronically ill (24%) had optimal levels of vitamin D. patients with various diseases on an out- These data tends to confirm that pa- patient basis. Based on geography, most tients suffering from different disease and of our patients come from the mid-West. older patients have low or sub-optimal However, patients have come from every levels of vitamin D. It has been shown in state in the U.S. as well as from over 40 many studies that vitamin D deficiency foreign countries. To check the finding is a contributing factor for hypertension, of sub-optimal or deficient vitamin D in diabetes, multiple sclerosis, rheumatoid patients with various illnesses, we exam- arthritis, insulin-resistance, early age mac- ined the vitamin D (25-OH-D3) levels that ular degeneration, bone health, depression and cancer.3,4,5 Most of the patients in this 1.The Center for the Improvement of Human Function- ing International, Inc, 3100 N. Hillside Ave, Wichita, KS study had one or more of these diseases. 67206 USA How can this international finding of

88 Case from the Center deficient or sub-optimal vitamin D levels interesting finding in this study is that be corrected? Plenty of sunshine (UVB) in some patients with sub-optimal vi- without layers of sunscreen, eating foods tamin D levels, Co-Q10 enzyme levels high in vitamin D, supplementation with were also in the low range. Not every vitamin D, to name a few. The RDA is patient that had vitamin D test ordered designed to prevent deficiency diseases had Co-Q10 ordered. The Co-Q10 test such as osteomalacia or rickets, not to was also performed in our laboratory maintain good health. The RDA in the and the reference ranges are 0.3 to 1.5 U.S. of 400 IU/day is entirely too low to ug/mL. Table 3 (below) There were 41 prevent the diseases shown above. The patients in the sub-optimal vitamin D RDA should be at raised to maintain a range. The Co-Q10 tests on these patients level of 2000-4000 IU/day.6,7 This is the ranged from 0.1 to 0.6 - very low. We will amount routinely prescribed by The examine these data on future patients to Center’s physicians. determine if there is any physiological Although the data is too limited and/or biochemical connection between to be statistically significant, one other the two tests.

Table 1. Data on number, age and vitamin D (25-OH-D3) results on 200 chronically ill out patients.

Number = 200 Age- Years Results, ng/mL Vitamin D (25-OH-D3)

Females = 132 (66%) Range = 6 to 91 Range = 5 to 96 Males = 68 (34%) Mean = 55 Mean = 32.5

Table 2. Vitamin D (ug/dL) ranges based on classification of results and gender on 200 patients. Deficient Insufficient Expected Range Optimal Range

1 to 5.0 ng/mL 6 to 14 ng/dL 15 to 40 ng/mL > 40 ng/mL Male = 1 (0.5%) Male = 5 (2.5%) Male = 50 (25%) Male = 12 (6%) Female= 0 Female = 10 (5.0%) Female= 86 (43%) Females = 36 (18%) Totals= 1 (0.5%) 15 (7.5%) 136 (68%) 48 (24%)

Table 3. Comparison of limited numbers of Co-Q10 to sub-optimal vitamin D levels.

Number 12 23 6 Vitamin D Range 12-20 ng/mL 21-30 ng/mL 31-40 ng/mL Range Co-Q10 *0.1-0.8 ug/mL .1-1.0 ug/mL 0.1-0.6 ug/mL Mean Co-Q10 0.3 ug/mL 0.4 ug/mL 0.3 ug/mL

*= reference range for Co-Q10 at our laboratory = 0.3 to 1.5 ug/mL

89 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009

References in the U.S. due to inadequate doses of solar 1. Moore NL, Kiebzak GM: Sub-optimal vitamin ultraviolet-B radiation. Cancer, 2002; 94: 1867- D status is a highly prevalent but treatable 1875. condition in both hospitalized patients and 5. Vieth R, Ladaky Y, Walfish PE: Age related the general population. J Am Acad Nurse Pract, changes in the 25-hydroxy vitamin D versus 2007; 19(12): 642-651. parathyroid hormone relationship suggest s 2. Kiebzak GM, Moore NL, Margolis S, et. al: different reason why older adults require more Vitamin D status of patients admitted to a vitamin D. J Clin Endocrinol Metab, 2003; 88(1): hospital rehabilitation unit; relationship to 85-91. function and progress. Am J Phys Med Rehabil, 6. Ashton FE: Vitamin D supplementation in 2007; 86(6): 435-445. the fight against multiple sclerosis. J Orthomol 3. Lappe J, Tavera-Gustafson D, Davis K, et. Med, 2004; 17(1): 27-38. al: Vitamin D and calcium supplementation 7. Vieth R, Bischoff-Ferrari H, Borcher BJ, et. al: reduces cancer risk: results of a randomized The urgent need to recommend an intake of trail. Am J Clin Nutr, 2007; 85(6): 1586-1591. vitamin D that is effective. Am J Clin Nutr, 2007; 4. Grant B: An estimation of premature mortality 85(3): 649-650.

90 Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases Examined from Both Perspectives

Cynthia Quattro, P.A., DAOM, L.Ac.1

Abstract associated traditions resulted in what is Interconnection and cross-cultural learning now termed Oriental Medicine (OM). is as important in modern medicine as it is in OM practices date back as far as 2000 the rest of contemporary life. This case study B.C., but the West has imported and de- documents six chronic Lyme disease cases as veloped these therapeutic principles and observed through both Orthomolecular and techniques only in the past 30 years. OM Oriental Medicine approaches. These two is not standardized, either within Asia or medical paradigms were cross-referenced the West, and styles of acupuncture and and both found disorders of microcirculation its application vary as much as any other with blood coagulopathy. A cross-cultural medical specialty. review demonstrates that Oriental Medi- In the United States, although there cine provides a more specific treatment to are no standardized care protocols, there address blood coagulopathy than does are national standardized credentialing Orthomolecular Medicine. requirements for licensed acupuncturists. There are 36 accredited educational pro- Introduction grams, which demand from 2,500 to 3,000 The Chinese have taken most of the hours of training, extended over three to credit for the development of acupuncture four years of full-time study. In California, and herbal therapies. After the Cultural acupuncturists are required to undergo Revolution in 1959, acupuncture and its 3,000 hours of training because they are related therapies were modernized and classified as primary-care providers. named Traditional Chinese Medicine or There are approximately 20,000 TCM. Many of the more ancient principles, licensed acupuncturists in the United which were associated with alchemical States with licensure in all but two elements and religious disciplines, were states.1 There is a national board exam then banned in China, with dire conse- and Continuing Education Units (CEUs) quences for those who made any attempt required biannually to maintain licensure. to preserve these philosophies. However, In certain states, a state board exam is also in adjacent regions such as the Japan, Ko- required. A Doctor of Acupuncture and rea, India, and Taiwan, acupuncture and Oriental Medicine (DAOM) is the high- its related therapies continued to flourish est formal education credential available and were not affected by the restrictive in the field of acupuncture in the United political and intellectual climate of China. States. There are currently three nation- Acupuncture and its related therapies in ally-accredited DAOM programs; these these countries maintained a combina- require 1,200 hours of graduate didactic tion of ancient techniques and modern and clinical training beyond an existing methods of application. Recognition in state acupuncture license. these countries outside China of this Additionally, the American Medi- combination of old and new acupuncture- cal Acupuncture Association offers a 1. PO Box 1635, Capitola CA 95010 300-hour Continuing Medical Education [email protected] (CME) program offered only to medical

91 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 doctors who are interested in studying to the other. The goal of these investigative acupuncture. This program does not re- studies that cross-reference practices of sult in a special license or a required board OM with diagnostic imaging is to reveal exam. Also, it is not required to accrue after thousands of years of clinical use ongoing continuing education in order to how OM actually works. practice acupuncture. There are approxi- The application of state-of-the-art mately 5,000 medical doctors in the U.S. medical technology to the low-tech, mil- who have completed this program.2 lennia-old practice of acupuncture seems at first to represent scientific overkill, but Validating OM with Western Measurement several preliminary explorations in this With the growth of acupuncture as “West meets East” field of inquiry have an increasingly mainstream medical spe- yielded extremely promising results. Just cialty in the United States it not surpris- as brain imaging is used on acute isch- ing that the National Institute of Health emic stroke patients to assess the need (NIH) has taken considerable interest in for administering so-called clot busting this medical specialty. drugs, research is being conducted to look As long ago as 1999, the NIH and more closely at how diagnostic imaging its Complementary and Alternative can elucidate where acupuncture impacts Medicine (CAM) division allotted ninety the brain. million dollars to perform acupuncture A collaborative study between the research.3 University of California-Irvine and univer- Investigational studies have continued sity medical centers in Seoul, Korea used to be funded by the NIH. Billions of dollars fMRI to observe the correlation between have been spent researching OM in an effort traditional acupuncture points for the to verify that the ancient healing principles treatment of eye disorders and the cor- of the East have statistical validity. Scien- responding brain localization for vision. tific studies have cross-referenced Western This was a small study of 12 volunteers.4 medical findings with those indicated by Stimulation of the prescribed acu- acupuncture. Functional MRI (fMRI) brain puncture point activated the occipital imaging has demonstrated cortical tissue lobes seen in the center of this fMRI (Fig- response that maps one medical tradition ure 1, below). On the left is a depiction of

Figure 1. MRI showing stimulation of prescribed acupuncture point activating the occipital lobes.

92 Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases

Figure 2. Cortical-activation map shows the result of acupuncture stimulation on another vision-related acupuncture point on the Gall Bladder channel (GB.37).

the occipital lobes when the eye had been vision-related acupuncture points and the stimulated by an eight-Hz flash stimula- light stimulator. tor. The results showed similar activation The acupuncture points used in this in both occipital lobes regardless of the study were located on the Urinary Bladder source of stimulation. channel. They were named here as VA1 As a control, acupuncture points thru VA8. The Urinary Bladder is unique were stimulated 2-5 cm away from the because it is the longest meridian of the vision-related acupuncture points. These body and includes 67 specific points. This control acupuncture points did not acti- meridian follows the vertebral column. vate the occipital lobes, as shown on the There, it connects to each of the intra-tho- fMRI on the far right; compare to the racic body organs, enters the intrathecal visual-cortex activation as initiated by the space and brain, then doubles back and

93 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 extends more superficially down the leg to distinctly different languages used by the the outer foot and 5th toe metatarsal where two medical paradigms. Bearing essentially the points in this study were stimulated. the same message, both medical paradigms A separate cortical-activation map support ideal regulatory function or bal- (Figure 2, p. 93) shows the result of acu- anced homeodynamic physiology. In OM, puncture stimulation on another vision- this same healing philosophy is articulated related acupuncture point on the Gall Blad- as the intent to enhance and maintain der channel (GB.37). The observations from uninterrupted Qi flow and promote micro- this fMRI showed visual-cortical activation circulation to the central nervous system from both direct retinal stimulation from and all organ tissues. a flashing light (shown in column a) and The best description of Qi (pro- acupuncture application to another vision- nounced “chee” by the Chinese, or “key” by related point GB.37 (shown in column b). the Japanese) is that it is the vital impulse Cortical stimulation looks comparatively that keeps the heart beating. It might be the same in both groups. understood as the life force itself. Similar This research shows that physi- concepts in other cultures would be “spiri- ological effects initiated by the ancient tus” in Roman mythology or Christianity, modalities of acupuncture can be docu- or “mana” in Polynesian mythology. It is mented by modern Western technology. measured only in its detriment–otherwise Despite these physiological parallels, the it is taken for granted that it is present in medical terminology used to describe adequate amounts. Put in Western medical functions within each of these medical terms, the Qi function keeps mitochondria paradigms is not so neatly equivalent. The healthy enough to manufacture adequate lack of common descriptive terminology ATP for life-sustaining activities. prevents cross-referencing of common Both OMM and OM see illness as medical findings and hinders coherent an opportunity to change and improve communication between these medical health. Both emphasize prevention and paradigms. early intervention.

Translating between OM and OMM Treatment Goals in OMM Figure 3 (below) shows a correlation Improve detoxification pathways of OM therapeutic language with the physi- Support the immune function ological goals as described by Orthomo- Reduce inflammation lecular Medicine (OMM) terminology. Balance hormones These descriptions demonstrate the Correct nutrition

Figure 3. Oriental Medicine therapeutic language with the physiological goals as described by Orthomolecular Medicine terminology.

OMM deals with the body’s regulatory functions OM deals with the body’s innate qi status

Serious illness can be prevented by good regula- Serious illness can be prevented by reinforc- tory system functioning ing adequate measurements of qi flow

Goal: Sound cellular metabolism and mitochon- Goal: Uninterrupted qi and blood flow to all drial respiration body tissues and organs

94 Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases

Treatment Goals in OM treats multiple systems and includes herbal Regulate and circulate the flow of Qi therapy as a whole foods approach. Warm and remove cold from the body Enhance microcirculation Comparison between OM and OMM in Control the regulation of the interior and Lyme Disease (Figure 4, p. 96) exterior Bearing these complementary medical paradigms in mind, I conducted a small OMM and OM may appear to have retrospective clinical study in my medical different treatment goals, given the differ- practice with six Lyme disease patients. ences in language. As a brief review, Lyme disease is In OMM, treatment goals focus on known as the fastest-growing vector-borne methods of detoxification and, for example, disease in the United States today. By look to the enhancement of methylation, 2006, the Centers for Disease Control has glycation, and glucoronidation pathways. reported more than 19,000 cases annually.5 The treatment goals of OM, however, These are primarily acute cases, with vast focus on a process of regulating the flow numbers of chronic disease cases remain- of vital life force or Qi, removing the con- ing uncounted. Lyme disease is recorded in strictive effects of cold, and enhancing ef- almost every state, with highest concentra- fective microcirculation. Controlling both tions on the two coasts and in the Great the body’s interior and exterior implies the Lakes region. importance of its largest organ, the skin. Although standardized treatment The skin’s multifunctional structures and protocols are designed either for prophy- layers, along with its enormous protec- laxis or for early recognition of acute Lyme tive and regulatory function of blood and disease, Johns Hopkins University online lymph circulation, is all but ignored in the patient-education pages list Lyme disease Western biomedical paradigm but is of in three stages:6 paramount importance in OM. Early localized disease: skin inflamma- tion. Treatment Modalities of OMM Early disseminated disease: heart and Laboratory testing nervous system involvement, including Physical exam palsies and meningitis. Kinesiology Late disease: motor and sensory nerve dam- Nutrient Therapy age, brain inflammation and arthritis. Accumulated resources summarize Treatment Modalities of OM common symptoms and observations Abdominal and body palpation which include: Pulse analysis Erythema migrans–less than 50% Tongue analysis Fever–30-40% Acupuncture techniques Fatigue–60% Herbal therapies Flu-like symptoms–50% Headache–40-50% Obviously, OMM and OM use dis- Stiff neck–30-40% similar diagnostic and treatment methods. Myalgias–40-50% OMM relies primarily on a reductionist Polyarthralgias–40-50% approach that analyzes objective findings and treats with countering replacement Complications in the disease progression nutrients. OM relies on more of a holistic include: dynamic that simultaneously observes and Peripheral Neuropathy

95 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009

Radiculoneuropathy mutually exclusive although each symp- Atrioventricular nodal block tom category constituted a primary set Pericarditis of complaints. Eye symptoms–Optic neuritis Meningitis Biomedical Laboratory Markers Encephalopathy Several laboratory markers were Treatment protocols initiated by tracked throughout the course of treat- Lyme experts consist of multiple rotating ment. Most observable were contribut- antibiotics and symptomatic treatment. able factors to blood coagulopathy or Periodic laboratory and diagnostic test- haemorheology. The clinical intent was ing monitors the treatment course, which to monitor coagulation markers and ge- may last from months to years. netic influences that change the course OMM strategies target nutritional of optimal blood fluidity. Research has deficiencies and the disorders of various shown that changes in the blood and its detoxification pathways that interfere constituents (for example, blood viscosity, with eradication of the Lyme bacteria and blood viscoelasticity, blood plasma viscos- its related pathogens. ity, erythrocyte and platelet aggregation OM’s holistic approach offers re- and adhesion) all play a very important storative treatments that target the core role in the appearance and development constitutional imbalance. of many dangerous and chronic diseases Clinical observations of Lyme disease associated with microcirculation.7 Bio- patients in my practice showed three medical conditions such as cardiovas- subtypes of symptom complaints. These cular disease, diabetes, renal failure, and groups included: apoplexy are more obvious conditions Dizziness and Disequilibrium (D): Symp- stemming from coagulopathy. There ap- toms of vertigo, unsteady gait, woozy pears to be a direct connection between feeling, depth perception disorder the scope of haemorheologic changes and Arthralgias (A): Large and small joints the gravity of most critical conditions and unilateral or bilateral their prognosis. Fatigue (F): Leading to cognitive decline More recently, evaluation of chronic and disability diseases like Lyme disease, fibromyalgia, These symptom categories were not and chronic fatigue, have shown evidence

Figure 4. Summary of a retrospective analysis comparing six patients with chronic lyme disease.

Background: Current treatment protocols of Lyme disease are standardized regardless of each patient’s health status

Objective: Observe for subtypes in symptom patterns Observe course of illness using OM; Compare biomedical and OM markers

Results and Conclusion: Integrated medicine shortens the course of treatment and prevents illness progression Microcirculation disorders are a common finding in both the OM and OMM.

96 Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases of abnormal blood coagulopathy indica- A model which looks to the influence tors. In a cohort study of 54 patients of coagulation defects in the presence of with Chronic Fatigue Syndrome and 23 chronic pathogens predicts that fibrin will controls, 92% of the patients had a demon- be deposited and blood viscosity increased. strable hypercoagulable state or low-level In this model, chronic disease such as activation of coagulation.8 Lyme disease can become exacerbated and In this retrospective study of six Lyme resistant to treatment. 13 disease patients, the following coagula- tion markers were measured periodically Patient Laboratory Results throughout the course of treatment. Over the course of five years, as I treated six patients diagnosed with Lyme Fibrinogen: Although it is a variable disease, I followed their contributory co- marker, fibrinogen is a major contributor agulation markers. The results revealed to the accumulation of fibrin by the action (Figure 5, below): and influence of thrombin production. Patients with disequilibrium (D) Fibrinogen was repeatedly measured and showed elevated fibrinogen and LpA. averaged throughout the course of treat- Patients with arthritis (A) showed ment. consistently elevated fibrinogen and a heterozygous MTHFR. Lipoprotein A (LpA): A highly heritable Patients with fatigue and cognitive marker, Lipoprotein A is related to an in- decline (F) showed less coagulation defects crease risk of atherosclerosis and thrombo- but showed one homozygous positive sis. Its structure is similar to plasiminogen MTHFR mutation. and tPA (tissue plasminogen activator) Patient summary of coagulation and competes for binding sites leading indicators suggest a strong link between to reduced fibrinolysis.9 LpA additionally hypercoagulopathy and the chronicity of stimulates PAI-1, which is a contributing Lyme disease. factor to thrombogenesis.10,11 OM Diagnosis MTHFR (methylenetetrahydrofolate In OM, a diagnosis is based upon reductase): MTHFR is considered one a combination of physical signs and of the many polymorphisms that can be symptoms unique to its medical meth- measured and expressed as a heterozy- odology. Although each individual’s gous or homozygous heritable mutation. clinical presentation may vary from visit This mutation prevents a crucial link in to visit, the core constitutional diagnosis converting homocysteine to methionine. remains the same. This constitutional Elevated homocysteine is a leading cause diagnosis is what long-term treatment is of increased risks of blood clotting and based upon. thrombosis.12 The medical term “blood stasis” is

Figure 5. Patient summary of coagulation factors.

D1 D2 A1 A2 F1 F2 Fibrinogen High High High High Low normal MTHFR Negative +/- Negative +/- Negative positive LpA High High High Normal Normal normal

97 Journal of Orthomolecular Medicine Vol. 24, No. 2, 2009 commonly used in OM and implies biomed- Hundreds of herbs have been observed, ical pathology described as agglutination of researched and studied for every condi- RBCs, increased intracellular viscosity, or tion imaginable. In the past 25 years, these decreased plasticity of erythrocytes. In ad- herbs have been imported into the Western vanced blood stasis there may be increased hemisphere, where they have been used fibrinogen, thombogenesis, or increased according to ancient principles. There are hematocrit.13 The accumulative effect of now strict growing and manufacturing these leading pathologies contributes to processes that make Chinese herbs a safer and results in symptoms of blood stasis. alternative than in earlier days of their Notable physical signs related to blood importation. Various sources of organic stasis (or, in OMM terms, hypercoagulopa- herbs are now also available. American and thy), include a radial pulse that is consid- European collaborations with the Chinese ered “choppy” or has a feeling of disconti- have been instrumental in ensuring that nuity. The pulse may also feel deep or hard herb quality now meets standards of good as though the blood flow is impeded. The manufacture and processing. tongue may appear with a darker color or The category of Chinese herbs classi- be slightly purple. The abdomen may feel fied as blood vitalizing or blood circulating tight and mildly tender, especially in the herbs are of interest in the treatment of mid-epigastric area. blood hypercoagulopathy. The primary and secondary diagnosis One of the most commonly-known pattern for each of the six Lyme disease herbs in this category is Salvia miltorrhizae. patients is outlined in Figure 6 (below). The root of this common sage plant by Based on these OM diagnoses, there chance is a deep red color. Its primary me- is evidence of pathology related to the tabolite is a diterpene, most notably studied insufficiency of core organ systems. These in the Pacific yew tree. The yew tree is best core imbalances directly influence blood known for its extract originally developed circulation and regulate its coagulation by Bristol-Meyers Squibb to manufacture pathways. Paclitaxel or taxol. It is used as one of the most commonly prescribed chemotherapy OM and the Use of Chinese Herbs to agents in the treatment of breast cancer, Treat Blood Stasis classified as an anti-angiogenesis agent. For millennia, Chinese herbs provided Additional blood anticoagulants found the basis for most treatment modalities in Salvia miltorrhizae, also known as dan practiced in China. This held true un- shen in Chinese pinyin terms, is salvianolic til Western medicine was introduced. acid. In research studies salviol (or salviano-

Figure 6. Oriental Medicine diagnosis based on system patterns.

Primary Diagnosis Secondary Diagnosis

D1 Spleen qi deficiency Damp heat in the gallbladder D2 Stomach and kidney yin deficiency Deficient heat rising A1 Spleen qi deficiency Damp bi and blood stasis A2 Spleen qi deficiency Stomach and gallbladder heat with shen disturbance F1 Yin and yang deficiency Damp heat toxin F2 Spleen and kidney deficiency Liver qi stagnation with wind symptoms

98 Oriental Medicine and Orthomolecular Medicine: Six Lyme Disease Cases

lic acid) has been demonstrated to inhibit puncture: What’s the difference? http://www. platelet aggregation as a thromboxane in- pulsemed.org/medicalacupuncture.htm hibitor. Salviol increases cerebral blood flow 3. Horowitz S: Alternative and Complementary Therapies. February 2003, 9(1): 11-15. doi: after ischemia and has shown to increase 10.1089/10762800360. MMWR, Oct 3,2008/ the production of a potent vasodilator, 57(SS10);1-9 nitric oxide (NO).14 Additional chemical 4. Cho ZH, Chung SC, Jones JP, et al: New find- constituents such as tanshinones, also de- ings of the correlation between acupoints and rived from dan shen, are protective against corresponding brain cortices using functional myocardial ischemia and reperfusion. MRI. PNAS, 1998; 95/5: 2670-2673. 5. Schwartz B: Johns Hopkins Arthritis Center Tanshinones have been found to increase www.hopkins-arthritis.org/arthritis-info/lyme- the proteolysis of fibrinogen to fibrinogen disease”www.hopkins-arthritis.org/arthritis- degradation products.15 There are also info/lyme-disease anti-inflammatory effects associated with 6. Neeb G: Blood Stasis. New York, NY: Churchill its pharmacological activity.16 Livingston; 2007. 7. Berg DE, Berg LH, Harrison HH, et al: Low Level Numerous clinical trials have been Activation of Coagulation with Coagulopa- performed in China using the herb dan shen thies in the etiology of CFS/FM and Chronic orally and intravenously. Although some Illnesses, An Exploratory Model Revisited. HE- of these research studies would not match MEX Laboratories Publications. www.hemex. the standards of research methodology in com/publications/cfs_model.php the West, taken as a whole, these multiple 8. Dahlén GH, Ekstedt B: The importance of the relation between lipoprotein(a) and lipids for clinical trials make compelling evidence of development of atherosclerosis and cardiovas- its beneficial effects as an anti-coagulant. cular disease. J Intern Med, 250 (3): 265–7. 9. Caplice NM, Panetta C, Peterson, et al: Lipo- Conclusion protein (a) binds and inactivates tissue fac- The parallels between different medi- tor pathway inhibitor: a novel link between cal paradigms are evidence of conjoined lipoproteins and thrombosis. Blood, 1998; 98 (10): 2980–7. practice principles. While Eastern and 10. Schreiner PJ, Morrisett JD, Sharrett AR, Western medical traditions demonstrate et al: http://atvb.ahajournals.org/cgi/re- disparate cultures, language, and modali- print/13/6/826.pdf” \o “http://atvb.ahajour- ties, it is significant that blood stasis or nals.org/cgi/reprint/13/6/826.pdf hypercoagulopathy is becoming better 11. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Arterioscler Thromb, 1993; 13 known as a condition in the West but is an (6): 826–33. ancient remedied treatment in the East. 12. National Library of Medicine,National Institute of Recognizing subtypes in Lyme disease Health.http://ghr.nlm.nih.gov/gene=mthfr”http:// can help to identify more difficult-to-di- ghr.nlm.nih.gov/gene=mthfr. agnose cases in the absence of definitive 13. Neeb G: Blood Stasis. New York, NY: Churchill findings. These subtypes may assist in Livingston; 2007. 14. Tang MK, Ren DC, Zhang JT: Effect of salvi- a more precisely guided, quickly imple- anolidc acid from Radix Salviae miltiorrhizae mented treatment protocol. on regional cerebral blood flow and platelet The evaluation of the pathophysiolgi- aggregation in rats. Phytomed, 2002, 9: 405-9. cal and therapeutic implications of blood 15. Wang CS, Chen CS, Yang TT: In vitro root of coagulopathy can influence a better prog- salvia miltiorrhiza action on blood antico- nosis and outcome of chronic disease. agulation and fibrinogenolysis. Chin Med J, 1978 4:123-6. 16. Jia WK, Fan JP: Observation of the therapeutic References effects of different doses of fufang danshen in 1. Kaptchuk T: Acupuncture: Theory Efficacy and 95 patients with stroke. Hunan J Chin Med, Practice. Ann Intern Med, 2002;136:374-383 1994 10: 36-37. 2. Adam B: Medical Acupuncture vs Licensed Acu-

99 ISOM News

2009 Orthomolecular Medicine Hall of Fame

The following is excerpted from introductory remarks by Andrew Saul. For the full text of his presentation, please visit www.doctoryourself. com/2009HOF.html

“Welcome to the Sixth Annual Orthomolecular Ilya Metchnikov, Ph.D. T. L. Cleave, M.R.C.P. Medicine Hall of Fame inductions. I am representative of the tors and practitioners understand this all malnourished generation. Typically, our too well. Acceptance of nutrient-based mothers consumed too little folic acid therapeutics has been decades-long in while they were carrying us. We were coming. Tonight’s honorees have been bottle-fed on formula containing no biotin. criticized, even ridiculed, in their time. Vitamin E wasn’t even listed as an RDA These five very important gentlemen are item until 1968. We chowed down on being enrolled in our Hall of Fame not “Wonder Bread,” which supposedly, some- just because they were unappreciated, but how built strong bodies 12 ways. We ate because they were right. a lot of frankfurters. For dinner, our mom Perhaps we are what we eat after all. Dr. opened canned vegetables and then cooked Abram Hoffer and I, in our new book Ortho- them. On the other hand, my mother was molecular Medicine for Everyone, note that at least partly orthomolecular. Having the average age of Orthomolecular Medicine opened the cans, she drank the juice the Hall of Fame inductees is about 80 years of vegetables were packed in, or put it into age. Nobel Laureate Dr. Albert Schweitzer homemade soups. We were compelled to was right: “Not only is example the best way eat liver. My brothers and I each had to to teach, it is the only way.” Tonight we offer take a multivitamin every day, long before five outstandingly good examples. it was popular. We never had a day without orange juice, nor a day without whole grain Ilya Metchnikov cereals at breakfast. “Death begins in the colon.” And, we rarely went to the doctor; Born in 1845 in Ukraine, Ilya Metch- at five dollars a visit, it was “too damned nikov studied natural sciences at the Uni- expensive.” When we did go, it usually had versity of Kharkov and pioneered research to be for a condition serious enough to in immunology. In 1904, he became the require a tetanus shot, or an antibiotic. deputy director at the Pasteur Institute Speaking of antibiotics, not everyone laboratory in Paris from where he discov- knows that Alexander Fleming, M.D., ered the process of phagocytosis which wrote, “Penicillin sat on my shelf for 12 demonstrated how specific white blood cells years while I was called a quack. I can can engulf and destroy harmful bacteria in only think of the thousands who died the body. His theories were radical and the needlessly because my peers would not “sophisticated” microbe hunters in the West use my discovery.” –Pasteur, Behring and others–scorned the Orthomolecular researchers, educa- Russian and his humble theory. 100 ISOM News

Hugh MacDonald Sinclair, Ch.B. Archie Kalokerinos, M.D. Jeffrey Bland, Ph.D. Nevertheless, history vindicated Metch- to replace the harmful microbes by useful nikov’s brilliant theory and he was awarded microbes.” He wrote two more books: Im- the Nobel Prize for medicine in 1908. Al- munity in Infectious Diseases (1905) and though references to the nutritional power The Nature of Man (1938). of fermented foods date back thousands of In recognition of Metchnikov’s place in years, Metchnikov is regarded as the father the probiotic realm, the International Dairy of modern probiotics. He made a landmark Federation (IDF) created, in 2007, “The observation that the regular consumption IDF Ilya Metchnikov Prize” to recognize of lactic acid bacteria in fermented dairy outstanding scientific discoveries in the products, such as yogurt, was associated fields of microbiology, biotechnology, nutri- with enhanced health and longevity in tion and health with regard to fermented Bulgarian peasant populations. He linked milk products. this to the “Bulgarian bacillus” and he later demonstrated how healthy bacteria T. L. Cleave in yogurt helped digestion and improved “Cleave saw that many of the diseases of civili- the immune system. The reduction of the zation could be explained as the consequences harmful bacteria coupled with the increase of eating refined carbohydrate, pointing out in good bacteria in the intestines appear to the crucial fact that refined foods are an improve the immune system and reduce artefact of technological civilization.” the burden on the cleansing organs such –Kenneth Heaton as the kidneys and liver. The scientific rationale for the health Thomas Latimer Cleave was born in benefit of lactic acid bacteria was provided Exeter and entered the Bristol Medical in his book The Prolongation of Life pub- School at the age of sixteen, finished his lished in 1907, in which he asserted that training at St. Mary’s Hospital and went some of the bacterial organisms present straight into the Royal Navy. There he was in the large intestine were a source of a medical specialist in various hospitals at toxic substances that contributed to ill- home and abroad, ending up as surgeon ness and aging. This book also delved into captain and director of medical research the potential life-lengthening properties of until he retired in 1962. lactic acid bacteria. He suggested that “The After working in obscurity for many dependence of the intestinal microbes on years, in the 1970s Cleave received interna- the food makes it possible to adopt mea- tional acclaim as the father of the dietary sures to modify the flora in our bodies and fibre hypothesis. His great vision was to see 101 ISOM News that the human body was maladapted to perts in human nutrition. He was born in the refined foods of civilization, primarily Duddington House, Edinburgh, Scotland, carbohydrates, sugar and white flour. He and went to Oriel College, Oxford to study reasoned that if man avoided unnatural Animal Physiology. He was appointed De- foods he would avoid unnatural diseases partmental Demonstrator in Biochemistry, which were generally absent in wild ani- before going on to study Clinical Medicine mals or primitive communities. He spent at University College Hospital Medical his life gathering evidence and developing School, London. Sinclair spent most of his arguments to support this view, which working life as a Fellow of Magdalen Col- culminated in his grand hypothesis that a lege, Oxford, though he made many forays range of diseases –from obesity, to diabetes, into a wider world, notably during the coronary heart disease, ulcers, dental car- Second World War when he was involved ies, constipation and appendicitis–were in planning how the British could be prop- caused by maladaptation to foods con- erly nourished and in famine relief in the taining refined carbohydrates. Since they Netherlands and Rhineland. all had a common cause he viewed them Sinclair is most widely known for as a single master disease, he called “the claiming that “bad fats” worsened what saccharine disease.” His book of the same he called “diseases of civilization”, such as name, published in 1974, sold thousands coronary heart disease, cancer, diabetes, of copies and was written in laymen’s lan- strokes and skin disease. He believed that guage that the public could readily grasp. diets deficient in essential fatty acids are In 1986, the British Medical Association the cause of most degenerative illnesses. finally answered Cleave’s voice in the wil- Sinclair’s forceful arguments on this matter derness in its report Food, Nutrition and preceded firm scientific evidence, however. Health, which recommended an increase in His self-experimentation, including the in- consumption of fresh food and vegetables famous 100 day seal-meat diet, dramatically and whole grains. demonstrated the importance of long-chain One of Cleave’s most effective advo- fatty acids of fish oils in decreasing the cates was Dr. Denis Burkitt, the legendary aggregation of platelets and thus the inci- cancer researcher, and their collaboration dence of thrombosis. Sinclair recognized was turning point in the fortunes of Cleave’s the central importance of nutrition to hu- hypothesis. Burkitt’s connections with man life and, at a time when it had become 150 third world hospitals enabled him to unfashionable, he constantly emphasized confirm many of Cleave’s epidemiological the importance of the right food for proper observations. Burkitt acknowledged his health. In a famous letter to the Lancet in debt to his friend, stating “Cleave was one 1956, he made a particular contribution in of the most revolutionary and far-sighted identifying the crucial role of essential fatty medical thinkers of the twentieth century, acids in health, which readers classed as seeing far beyond the small vision of intri- either visionary or lunatic, depending on cate details of individual diseases.” their point of view. His letter foreshadowed half a century of research on a nutritional Hugh Macdonald Sinclair topic which is steadily increasing in im- “He may prove to be one of those people whose portance. long term influence is far greater than ever Sinclair’s greatest dream was to estab- seemed likely while he was alive” lish an international centre for the study of –David Horrobin human nutrition. He argued that nutrition is an important area of science in its own Hugh Macdonald Sinclair, was one of right, and that new insights into the rela- the twentieth century’s outstanding ex- tionships between food and human health 102 ISOM News should guide developments in medicine, Nobel prize winner Linus Pauling, (who agriculture, and food technology. Many of wrote the foreword to Every Second Child) his ideas have relevance for us today. endorsed his views. Kalokerinos is a Life Fellow of the Archie Kalokerinos Royal Society for the Promotion of Health, “Any attempt to adequately write about of the International Academy of Preventive Archie Kalokerinos would need a thousand Medicine, of the Australasian College of pages and would incorporate many such ad- Biomedical Scientists, of the Hong Kong jectives as: far-sighted, intelligent, sensible, Medical Technology Association, and a observant, honest, caring, altruistic, conge- Member of the New York Academy of Sci- nial, meticulous, brave, dogged, intrepid, and ences. In 1978 he was awarded the AMM last but not least, the trite, but well-deserved, (Australian Medal of Merit) for outstanding ‘great.’ ” –Oscar Falconi scientific research. He is an author of 28 papers listed in PubMed. He retired from Archie Kalokerinos was born in Glenn full time practice in 1993 and spends most Innes, Australia, in 1927 and took his MD of his time doing private research. degree from Sydney University in 1951. He was appointed Medical Superintendent Jeffrey Bland of the hospital at Collarenebri, Australia, “Jeff is the most important innovator and where he served until 1975. His practice is educator in natural medicine in North based on Linus Pauling’s theory that many America.” –Abram Hoffer diseases result from excessive free radicals and can accordingly be prevented or cured Jeffrey Bland was born in 1946 in Il- by vitamin C. linois, and grew up in Southern California, Kalokerinos is well known worldwide where he graduated from the University of as the doctor who spent much of his time California, Irvine, in 1967 with degrees in fighting for the well-being of the Aboriginal biology and chemistry. In 1971, he com- inhabitants of Australia. He became very pleted his doctorate degree in synthetic concerned about the high death rate of organic chemistry and began his career as Aboriginal children in New South Wales a university professor and researcher at the and came to the conclusion that the infants University of Puget Sound with a dual ap- had symptoms of scurvy, a deficiency of pointment in Chemistry and Environmen- vitamin C. In his ground-breaking book, tal Sciences. From 1976-1995, he served as Every Second Child, he discovered that the a prominent educator for the natural foods an acute vitamin C deficiency provoked by and nutritional supplement industries and the vaccinations was the reason why, at a was involved in the founding of Bastyr certain point, up to half of the vaccinated University of Natural Health Sciences in Aboriginal infants died. Instead of being Seattle, the first accredited university of rewarded for this lifesaving observation, naturopathic medicine in North America. Kalokerinos was harassed and his meth- In 1981, Bland was invited by Linus Paul- ods were disregarded by the authorities, ing to become the Director of Nutritional probably because they were too simple, Supplement Analysis at the Linus Pauling too cheap and too efficacious to be ac- Institute in Palo Alto, California. cepted by the vested interests of modern In 1984, he started HealthComm, a medicine. Besides, they were meant to company dedicated to teaching physicians protect a population which, in its own and other licensed health care providers native county, is regarded by some as not how to successfully implement nutrition worth taking the trouble for anyway. Dr. intervention into their practices. Since Kalokerinos, thought differently, and the 1978, Dr. Bland has authored four books on 103 ISOM News nutrition and health for the general public as the Chief Science Officer of Metagen- and six books for health professionals. He is ics and the President of Metaproteomics, also the principal author of over 100 peer- a nutrigenomic research and develop- reviewed research papers on nutritional ment company employing more than 40 biochemistry. With his establishment of the scientists and physicians at its research Institute for Functional Medicine in 1991, centers. Dr. Bland merged his company, Jeffrey Bland conceptualized functional HealthComm International, with Meta- medicine as a patient-centered systems genics, the combined Metagenics has biology approach to medicine. Utilizing become the largest global nutraceutical his Textbook of Functional Medicine, first and medical food company serving the published by the Institute in 2005, Dr. fields of functional and integrative medi- Bland introduced the concept of functional cine. In 2006, Jeffrey Bland established medicine to Europe, Asia, Mexico, Brazil, “Synthesis” on his website to serve as a Australia, and New Zealand. repository for his functional medicine Since 2000, Jeffrey Bland has served educational materials.

2009 Orthomolecular Doctor of the Year Aileen Burford-Mason, Ph.D.

Aileen Burford-Mason receives the award from 2008 recipient, Jim Jackson, PhD,, the lab director and senior research consultant at the Bio-Center Laboratory, Wichita, KS. The award is inscribed: “For Your Dedication as an Educator, Researcher, Practitioner and Spokesperson in the Advance- ment of Orthomolecular Medicine”

The recipient of the 2009 Orthomo- Medicine Today Conferences on the ortho- lecular Doctor of the Year Award, Aileen molecular approach to candida, insomnia, Burford Mason, is a nutritionist and im- and addiction. Dr. Burford-Mason main- munologist with a deep interest in the evi- tains a private practice as a biochemical dence base for orthomolecular medicine. nutrition consultant in Toronto. Her long- Dr. Burford-Mason has authored articles time advocacy and tireless promotion of in many fields including gastroenterology, orthomolecular medicine to the public and pathology, cancer, and infectious diseases. to practitioners has made her an invalu- She has presented at Orthomolecular able leader in our cause.

104 ISOM News

The CenterOrthomolecular for the Improvement of HumanMedicine Functioning Today InternationalConference Celebrates Report: its 30th Montreal, Anniversary May 1–3, 2009

Jack Challem eating fresh, minimally processed foods, Dysglycemia–The Common Factor in smaller and smaller fibre portions he lost Mental Disorders 20 pounds and reversed the physiological Jack Challem’s talk focused on the dy- biomarkers of his own prediabetes. glycemia, the syndrome of clinical features which often progress to diabetes, heart Doron Gothelf, MD disease, obesity and negative cognitive Pediatric Psychiatry effects. Prediabetes is of vital interest be- Doron Gothelf, MD, is a professor cause it can be reversed through relatively of psychiatry at Sackler Faculty of Medi- simple dietary strategies. Prediabetes is cine, Tel Aviv University, director of the intertwined with obesity, and is an often Child Psychiatry Outpatient Clinics at overlooked problem in diet failures Schneider Children’s Medical Center of The early signs of prediabetes, accord- Israel. He has published more than 70 ing to Jack, are hyperinsulinemia, insulin peer-reviewed articles in the field of child resistance, reactive hypoglycemia and ab- psychiatry, psychopharmacology, genetics dominal obesity. Dietary causes include too and neuroscience. many refined carbohydrates, trans fats and Dr Gothelf outlined two current chal- junk oils and too many calories-Americans lenges of psychiatry i.e. current medica- eat 3,900 calories a day, but they only need tions do not treat causes or mechanisms 2,000 for health maintainence. of psychiatric disorders, which remain Jack cited useful laboratory tests for largely unknown, and approved medica- assessing prediabetes including fasting tions are less effective in children but have glucose, fasting insulin and glycated he- more serious adverse effects. Dr Gothelf moglobin. Interventions include a focus recommended the following: shifting to protein rich Mediterranean and Personalized medicine includes phar- paleo diet models and using the glycemic macogenetics, and medication that targets index. He ended his talk with his own ex- causes or deficits of disorders This approach, periences in the grip of prediabetes. After he states, will bring psychiatric treatment instituting his own recommendations out of the ‘50s to the present time.

Jack Challem Doron Gothelf, MD Natash Campbell-McBride, MD James Greenblatt, MD

105 ISOM News

Natasha Campbell-McBride, MD University Medical School, Department of Gut and Psychology Syndrome Psychiatry.Dr. Greenblatt explained that, Natasha Campbell-McBride, MD, although genetics plays a role, nutritional practiced in Russia as a neurologist and a deficiencies during puberty may affect gene neurosurgeon and then moved to the UK. expression in the onset/maintenance of After her son was diagnosed with autism she anorexia nervosa. A SAD diet, stress, excess developed her theories on the relationship estrogen, vegetarianism can all contribute between neurological disorders and nutri- to a depletion of key nutrients, particularly tion, competing a second degree in Human zinc, that can trigger the onset of AN. Nutrition. She opened the Cambridge Nutri- Dr. Greenblatt highlighted preven- tion Clinic and has written several books. tion strategies for AN based on better Dr Campbell-McBride introduced the understanding of risk factors and trig- Gut and Psychology (GAP) Syndrome, a gers. Although risk factors may not all be combination of digestive problems, asthma, reversible, environmental and nutritional eczema, bed wetting, chronic cystitis, aller- modulators can be. gies, malnutrition and thrush. In children the syndrome is connected to autism, Aileen Burford-Mason, PhD ADHD, dyslexia as well as learning, behav- Orthomolecular Treatment for Insomnia ioural and social problems. In adults, it is Aileen Burford-Mason, PhD, is an im- often present with substance abuse, depres- munologist, cell biologist and nutritionist sion and mental disorders. with a focus on orthomolecular medicine. Dr. Campbell McBride stressed the She co-founded the Holistic Health Re- critical need to re-establish normal gut-flora search Foundation Canada. in GAP patients. The key supplements are Dr. Burford-Mason presented evidence vitamin A, EFAs, mineral amino-acids and of the significant effect of sleep deprivation digestive enzymes. With these treatment on cognitive function, immunity, weight recommendations, a major component of gain and mood. Recommended prophy- psychological disorders can be addressed. laxis included lifestyle changes such as sleeping in complete darkness and an opti- James Greenblatt, MD mal diet rich in nutrients for the brain, Key Orthomolecular Treatment for Eating supplements for insomnia are l-theanine, Disorders 5-HTP, melatonin and magnesium. Dr. James Greenblatt, MD, is the Chief Burford-Mason recommended the amino- Medical Officer of Walden Behavioral acid or protein chelated forms for oral Care in Waltham, Massachusetts. He ingestion, magnesium gel for use topically has been treating patients with complex and Epsom salts for the bath. With these eating disorders since 1988. He is also nutrients considered a deep, healthy and an Assistant Clinical Professor at Tufts regenerating sleep can be assured.

Aileen Burford-Mason, PhD Gary Ginsberg, DrPH Alexander Schauss, PhD Maret Traber, PhD

106 ISOM News

Gary Ginsberg, PhD on Acai, a type of Amazon palm fruit which Prioritizing Mainstream and Non-main- is one of the most powerful antioxidants stream Interventions discovered. The Acai palm, said Schauss, Dr, Ginsberg’s presentation applied can produce up to 1,000 kilos of fruit in a statistical cost-benefit analysis to compare 7-10 year period, but because of its volatility orthomolecular and conventional medicine and distance from western markets, it can for the benefit of governments and health only be handled by vacuum freeze drying. care insurers-in short those who hold the It is the freeze dried plant which is used in purse strings of our health-care system. studies because only this form preserves the A concept in the health industry, termed phytochemical content, enzymatic activi- QALY, or “quality adjusted life year” is a new ties, nutritional value, antioxidant activity measure for cost-benefit analysis. A QALY and taste. Schauss also detailed the mineral, measures a disease burden, including both amino acid, lipid, fiber and phytochemical the quality and the quantity of life lived and content and antioxidant capacity of Acai. is based on the number of years of life that Schauss spoke of brain health and oxi- would be added by the intervention. As it dative stress and presented some studies on turns out, this metric makes orthomolecular how Acai can be used to quench excessive therapies score quite favorably. free radicals which are implicated in many Nutritional therapies can cause huge brain health issues such as Alzheimer’s, reductions in mortality and morbidity, but Parkinson’s, stroke and dementia. to demonstrate this through the QALY measure, high level studies are needed. The Maret Traber, PhD highest levels are randomized clinical trials, Vitamin E Revisited while the lowest are studies of before/after; Dr. Traber’s presentation attempted or expert opinion. Orthomolecular medi- to make sense of the years of equivocal cine in its current state languishes in the studies on the efficacy of vitamin E in evidence basement-very few of the studies preventing chronic disease. The signs of are at the highest level. Ginsberg appealed vitamin E deficiency were discussed and to his colleagues to produce higher quality despite the fact that 90% of men and orthomolecular studies which would surely 96% of women do not consume adequate demonstrate a better way to care for the Vitamin E, she noted that deficiencies are overall health of the population. almost never due to low intake but rather poor fat absorption or impaired lipopro- Alexander G. Schauss, PhD tein synthesis in the liver. The deficiency Acai: The World’s Richest Antioxidant symptoms can be as diverse as peripheral Alexander Schauss, is senior director of neuropathy and muscle weakness natural and medicinal products research for Maret went into the possible reasons AIBMR Life Sciences. He gave a presentation the legacy of inconsistent conclusions

Michael Schacter, MD John Hoffer, MD, PhD Ron Hunninghake, MD Jeffrey Bland, PhD

107 ISOM News in vitamin E research. She ventured that voice in the wilderness by any means. It is some negative studies may be due to insuf- estimated, he said, that 64-82% of cancer ficient dose, type of participants and the patients use nutritional supplements of use of the synthetic form of vitamin E. their own, 14-32% start after diagnosis, and 68% of their physicians are unaware of this Michael Schachter, MD adjunctive therapy. Mainstream oncology’s Making Decisions about Cancer Treatment bias against vitamin C seems to be cen- Dr. Schachter has been the medi- tered on conjecture that it may reduce the cal director of the Schachter Center for effectiveness of standard chemotherapy. To Complementary Medicine in Suffern NY. address this issue, Dr. Hoffer put forward His presentation focused on what patients a hypothesis that vitamin C may amplify need to consider before making decisions the cytotoxicity of chemotherapy for cancer on conventional or orthomolecular cancer cells while quenching it for normal cells. treatments, treatment course. Whether antioxidants are beneficial or Integrative medicine evaluation is harmful is now a critical question, but one about treating the patient as a person, as- without a clear scientific answer at this sesses strengths and weaknesses and evalu- time. When the evidence is inconclusive, ates their support systems, with a full clinical Dr. Hoffer suggested that patient values, history and physical exam, assessment of preferences and circumstances will loom lifestyle factors and a nutritional and labo- larger than when the evidence is strong. ratory testing. Schachter’s Integrative lab Future evidence should focus on polished testing checks for particular vitamins and case histories, disseminated statistics. any immune-supressive heavy metal bur- dens such as lead or mercury. Schachter’s Ronald Hunninghake, MD integrative cancer therapies use organic Oral vs Intravenous Vitamin C food, exercise, stress management, sun- Dr. Hunninghake, current chair of the light, sleep, supplements, detoxification and ISF and director of the Kansas’ Center for energy treatments. His advice to patients the Improvement of Human Functioning was simple: we are all entitled to make our presented a talk which weighed the dif- own decisions about health, and we should ferences in oncology paradigms-what he be empowered not bullied by the medical termed allopathic vs orthopathic cancer establishment. therapies. Allopathic oncology represents establishment medicine and falls into a John Hoffer, MD, PhD predictable pattern of treating the disease High Dose Ascorbic Acid and Cancer by determine the grade, killing cancer cells, Dr. John Hoffer has long been involved and creating more oxidative stress with the in investigating the effects of high-dose quality of survival rather ignored. vitamin C in cancer therapy. He is not a The orthopathic approach, by com- parison, is a path which Dr. Hunninghake follows and first and foremost concerns itself with treating the patient as a per- son, correcting the underlying causes of disease, strengthen healthy cells, lessen- ing oxidative stress and improving the overall quality of life. Dr. Hunninghake also described the orthopathic approach created by his late colleague, Dr. Hugh David Quig, PhD Patrick Holford Riordan. This is the “RECNAC” approach

108 ISOM News which first developed the doctor-co- of treating heavy metal overload in the body. learner relationship and created a goal Some ways are not generally known, such as for the patient to heal themselves through boosting the body’s endogenous chelating learning and using the healing power of molecule, glutathione by supplementing nature and food as medicine. Vitamin C with its precursors vitamin C, NAC, lipoic is the main biological response modifier acid and glycine. Another of Quig’s strategies in cancer treatment which is known to is to increase dietary protein which helps boost immunity, stimulate collagen, in- to excrete metals, and use IV chelation for hibit hyaluronidase and relieve the general heavier metal burdens. Assessment is done scurvy of cancer. in two basic ways. Hair analysis because met- als irreversibly bind to hair and blood tests Jeffrey Bland, PhD which can be used to assess recent acute The Past, Present and Future of Orthomo- exposures which is the gold standard, but lecular Medicine not indicative of the body burden. Dr. Quig Jeffrey Bland has been teaching func- explained that particular metal burdens tional medicine to physicians, health may respond to specific chelating strategies care practitioners, students, and audi- and provided the example of the amino ences around the world for over 20 years. acid, glycine, which if taken orally has the Bland’s presentation, laid out an historical advantage of going right into cell, bringing overview of the early progenitors of or- metals to the extracellular surface, and pull- thomolecular medicine, the emergence of ing toxins out of cells. Glycine is best used orthomolecular medicine per se, 40 years in conjunction with other agents to remove ago, and the issues practitioners will face toxins from the body. in the future and ideas on how we may overcome them. In the present we are Patrick Holford faced with a curious stand-off in assessing Dysglycemia–The Common Factor in the efficacy of orthomolecular medicine. Mental Disorders There often seems to be a discrepancy In 1984 Patrick Holford founded the between the positive effects of orthomo- Institute of Optimum Nutrition, the Food lecular therapy in observational studies for the Brain Foundation and has also which often fails to be confirmed in large written a total of 29 best-selling books. randomized trials. Mr. Holford presented studies linking Bland then speculated on the future of high sugar diets and insulin resistance to orthomolecular medicine and he believes depression, aggressive behaviour, dementia, epigenetics will factor strongly in future memory loss and heart disease. Other studies studies of human diseases. Epigenetics showed an inextricable link between depres- may help explain the relationship between sive disorders and metabolic syndrome, the genome and the environment and may indicating that either condition often follows provide clues for modifying these effects the other. This is consistent with an ortho- in disease prevention and therapy. molecular approach to treating disease. In his book “The GL Revolution” Mr David Quig, PhD Holford recommends simple rules such as Safe and Efficacious Metal Detoxification eating no more than 40/60 GLs a day; eat- Metal detoxification an oft-overlooked ing protein with carbohydrates; and graz- health optimizer, according to Dr. Quig. His ing rather than gorge. These three simple talk covered hair and blood analysis, the steps can stabilize blood sugar levels, best ways of assessing chemical and metal support weight loss and treat a plethora toxicity and also outlined the various ways of physical and mental illnesses.

109 Information for Manuscript Contributors

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For journal references cited: 1. Pauling L, Itano HA, Singer SJ, et al: Sickle cell anemia: a molecular disease. Science, 1949; 110: 543–548.

For books cited: 2. Williams RJ: Biochemical Individuality. New York. John Wiley & Sons. 1973; 32–36.

For papers cited from books: 3. Cameron, E: Vitamin C, Carnitine and cancer. In. eds. Bland J. A Year in Nutritional Medicine. New Canaan, CT, Keats Publ. 1986; 115-123. Tables and illustrations. Placement in manuscripts should be indicated with a line break and the entry:

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