LIFE EXTENSION June 2007 Congress Seeks to Ban DHEA by William Faloon

LIFE EXTENSION June 2007 Congress Seeks to Ban DHEA By William Faloon

A bill has been introduced in Congress that would classify DHEA as an “anabolic steroid drug” and thus make it illegal for Americans to obtain. DHEA, however, is not an anabolic steroid drug. It is a natural hormone that declines as people mature past the age of 30. Low DHEA levels have been related with degenerative conditions associated with aging.1-28 A large volume of published scientific studies reveals that supplemental DHEA can provide unique health benefits.29-62 For more than a decade, DHEA has been sold as a dietary supplement. The availability of DHEA supplements has enabled many aging Americans to avoid the risks associated with declining DHEA levels. It is in the financial interests of pharmaceutical companies to have DHEA banned so that aging people will have to rely instead on expensive prescription drugs. If Congress is persuaded by drug lobbyists to outlaw DHEA supplements, more Americans will become vulnerable to declining DHEA levels, resulting in an economic bonanza for pharmaceutical companies. In this report, we expose shocking facts behind this new attack on DHEA so that citizens will be armed with the information they need to dissuade Congress from prohibiting this lifesaving hormone. > > >

June 2007 LIFE EXTENSION On March 5, 2007, legislation was introduced that would add dehydroepiandrosterone, or DHEA, to the list of anabolic steroids that are classified as controlled substances under the Anabolic Steroid Control Act.63 DHEA, a natural hormone, does not function like muscle-building anabolic steroid drugs. In fact, no scientific studies indicate that DHEA increases muscle mass in young men with already-adequate DHEA levels. To frighten the public into thinking that DHEA poses a danger, a blatantly false press release is now circulating in Congress. Here is an excerpt from this press release: “Like all steroids, DHEA has a number of potential long-term physical and psychological effects, including heart disease, cancer, stroke, liver damage, severe acne, baldness, dramatic mood swings, and aggression.” 64 This same study analyzed the tional profits from cardiac drugs if As you will read next, these alle- relationship of DHEA, free testoster- Congress bans DHEA supplements. gations are totally inconsistent with one, and insulin-like growth factor-1 Pharmaceutical lobbying has the scientific literature. Even more (IGF-1) to mortality in men suffering already curtailed Americans’ access disturbing is that a basis for this new from chronic heart failure. The chart to inexpensive ways to boost testos- attack on DHEA comes from those below reveals the startling results terone and IGF-1, though certain who have a huge financial interest in when these three hormones were nutrients have been shown to boost turning DHEA into an expensive pre- correlated with three-year survival: IGF-1 and testosterone in some scription drug. studies.53,68,70 Three-Year DHEA Protects Against Heart Hormone Survival Cardiac Dangers Associated Disease—It Does Not Cause It! Status Rate with Low DHEA

Drugs to prevent and treat heart High levels of Epidemiological studies show that disease generate more profit for DHEA, testosterone, low levels of DHEA in men correlate pharmaceutical companies than any and IGF-1 83% with a higher risk of cardiovascular other class of medication. The use of disease. The Massachusetts Male DHEA as a dietary supplement has Deficiency in one Aging Study followed 1,700 men been increasing as new studies reveal hormone (DHEA, between the ages of 40 and 70 for that DHEA might reduce heart attack testosterone, or IGF-1) 74% nine years. The authors found that 7-10,12,26,27,65-69 risk. Pharmaceutical com- Deficiency in two men in the lowest quartile of serum panies thus face huge economic hormones (DHEA, DHEA at baseline were 60% more losses if too many Americans use low- testosterone, or IGF-1) 55% likely to develop ischemic heart dis- cost DHEA supplements and reduce ease, suggesting a valuable role for their reliance on expensive cardiac Deficiency in all DHEA in averting the nation’s lead- drugs. three hormones (DHEA, ing cause of death.9 To give you an idea of the magni- testosterone, and IGF-1) 27% Additionally, higher DHEA levels tude of loss faced by drug companies, seem to positively affect endothe- a study published in October 2006 The doctors who conducted this lial cell signaling, which could have showed that higher DHEA levels study concluded that a deficiency in important implications for avoid- resulted in improved ejection frac- any of these hormones is “an inde- ing heart disease. In a subset of men tions (a measurement of the heart’s pendent marker of poor prognosis.” from the Baltimore Longitudinal pumping capacity) and lower levels Based on this one study alone, Study of Aging, levels of hormones of a blood marker that indicates seri- pharmaceutical companies stand (including DHEA) were measured ous congestive heart failure.26 to earn billions of dollars of addi- and correlated with arterial stiffness

LIFE EXTENSION June 2007 (using ultrasound imaging of the Another animal study simulated carotid arteries). Men with higher the depressed cardiovascular func- levels of testosterone and DHEA had tion (shock) that follows major less stiffness of the arteries, indicat- trauma.72 In response to adminis- ing a decreased risk of cardiovascular tration of a DHEA metabolite, the events such as heart attacks.65 depression of cardiovascular func- A similar link between low serum tion and organ blood flow induced by DHEA levels and greater risk for shock was reversed. The dangerous carotid artery disease was demon- inflammatory cytokine interleukin- strated last year in a study of young 6 (IL-6), which had been elevated women with polycystic ovary syn- in the state of simulated shock, was drome, a condition associated with also reduced by this DHEA metabo- an increased risk of cardiovascular lite. The investigators concluded disease and metabolic syndrome.71 that treatment with this metabolite Congress Seeks A study in animals in 2006 shed could be valuable in restoring car- further light on how DHEA promotes diovascular function and correcting To Ban DHEA: cardiovascular health.66 Researchers abnormal cytokine levels. What You Need to Know fed young and old female mice a Furthermore, investigators deter- daily DHEA supplement. After 60 mined that DHEA injected directly • A bill recently introduced in Congress days of treatment, the investigators into the coronary arteries of pigs would classify the popular supple- measured the stiffness of the test ani- produced acute dilation of the blood ment dehydroepiandroesterone (DHEA) mals’ left ventricle, the heart’s major vessels, with associated increases in as an anabolic steroid drug. If the pumping chamber. The DHEA-sup- coronary blood flow.67 proposed bill becomes law, DHEA plemented older mice had decreased would be regulated as a controlled left ventricular stiffness compared DHEA Protects Against substance and would no longer be to the non-supplemented older Atherogenic Risk Factors readily available as a nutritional animals. supplement. The scientists concluded that A number of studies indicate • DHEA is not an anabolic steroid drug, DHEA supplementation is capable that DHEA helps protect aging but rather a natural hormone that is of reversing the left ventricular stiff- adults against atherosclerosis and essential for good health. Since DHEA ness that accompanies aging, thus its life-threatening consequences, levels in the human body decline promoting youthful structure and such as coronary artery dis- after the age of 30, many people rely function in the heart’s tissues. ease.7-10,26,27,31,32,65,68,69,73-75 Several mecha- on DHEA supplements to combat nisms of action may account for these diseases associated with aging. A wealth of research demonstrates Sen. Hatch to Oppose DHEA Ban benefits. In a controlled trial, 24 older men that optimal DHEA levels can help orally ingested 50 mg of DHEA or a protect against heart disease, cogni- Sen. Orrin Hatch (R-UT), who was placebo at bedtime for two months. tive decline, and premature death. instrumental in the passage of the 1994 The researchers then measured • Those seeking to ban DHEA claim Dietary Supplement and Health Education arterial dilation and blood flow. that it causes many adverse effects Act (DSHEA) and remains one of Congress’ While the placebo-treated sub- in the body, including mood swings staunchest advocates of health freedom, jects had no changes in any of the and liver toxicity. However, no sub- told Life Extension that he opposes S. 762 parameters measured, the DHEA- stantial scientific evidence exists to and other efforts to re-classify DHEA as an treated men experienced increased support these claims; in fact, in the anabolic steroid. levels of a substance that helps blood more than 10 years that DHEA has According to Hatch, the proposed leg- vessels to dilate, as well as decreas- been available as a dietary supple- islation “specifically overturns the exemp- ing levels of a marker for blood ment, there have been no reports of tion we made for DHEA.” The senator notes clotting. They also had lower serious adverse health effects related that DHEA was exempted from the list of levels of artery-clogging low- to DHEA. banned anabolic steroids under DSHEA density lipoprotein (LDL) after • If DHEA becomes a controlled because “there is no evidence that DHEA treatment than did the controls. substance, Americans will have has posed any health problem.” Based on the beneficial effects of lost a valuable weapon for averting “In fact, [DHEA] is being used safely by short-term DHEA treatment, the the diseases of aging. To preserve many Americans who recognize its poten- researchers concluded that long- your freedom to use DHEA and other tial,” says Sen. Hatch. “I’ll be working to term DHEA supplementation may dietary supplements, contact your make certain the Senate does not pass this prevent atherosclerotic changes Senators and Representative and unwise bill.” caused by falling levels of vessel- urge them to vote against Senate bill dilating biochemicals.68 S.762 and House bill H.R.1229.

June 2007 LIFE EXTENSION Higher DHEA Levels Tied levels of these inflammatory media- to Lower Mortality Risk tors may be an important part of the neuroprotective mechanism of Of the many tactics that can be DHEA. deployed to increase one’s life span, In addition, DHEA has been shown supplementing with DHEA seems to protect against the toxicity of the particularly beneficial, as new find- amyloid-beta protein and excess glu- ings imply that higher levels of DHEA tamate.76 Treatment with glutamate are associated with a longer life produced a copious increase in the span.4 neuronal glucocorticoid receptor. Scientists recently examined data Treatment with DHEA reversed this on nearly 1,000 older Taiwanese increase, demonstrating the anti- adults to determine the relationship glucocorticoid action of DHEA. between DHEA levels and three-year A study conducted in Cambridge, mortality risk. England, compared DHEA and cor- At the study’s end three years later, tisol levels in clinically depressed the data analysis revealed that par- patients (categorized as “major ticipants with lower DHEA levels had depressives”) with a matched group a 64% greater risk of death than did of patients in remission from depres- individuals with higher DHEA levels. sion and healthy controls.21 Both The study authors concluded that morning and evening levels of DHEA lower levels of DHEA have a notable were lowest in depressed patients. Animal Study Data Misused effect in increasing mortality risk, Depressed patients showed low to Discredit DHEA’s and that optimal DHEA levels may DHEA relative to high cortisol lev- Well-Established Safety Profile help to promote longevity.4 els (similar to the ratio shift seen in The press release attacking DHEA aging). The authors point out that One way scientists evaluate for that is now circulating in Congress DHEA not only protects against toxicity is to have animals consume states that DHEA use is associated harmful effects of excess cortisol, large amounts of a compound and with heart disease. This is a blatantly but also may have mood-improving then carefully assess them for organ false allegation, as can be clearly properties and that this may have damage. However, different animal seen by examining published sci- “significant implications” for the models need to be used in differ- entific studies showing that DHEA treatment of depression.52,83-92 ent situations—a “one-size-fits-all” most likely protects against heart DHEA’s ability to protect the hip- approach makes for bad science. disease.7-9, 26,27,65-69 pocampus and enhance its activity One such example is the use of is important in regard to Alzheimer’s animal models to assess for liver tox- DHEA Protects the Brain— disease. Studies have generally found icity with compounds that are per- It Does Not Cause Stroke! increased cortisol and lower DHEA in oxisome proliferators. Peroxisome Alzheimer’s disease patients.80 Excess proliferators are potent rat carcino- DHEA is especially abundant in cortisol damages the hippocampus gens in the liver. However, this exper- the human brain. Many earlier stud- and potentiates amyloid-beta toxic- imental model is not valid to assess ies reported a protective effect of ity.80 DHEA is believed to be able to human liver toxicity for these types DHEA against the deterioration of antagonize the destructive effects of of compounds. mental function with aging.21,51,56-58,76-81 excess cortisol.83,93,94 There are significant species dif- Those stricken with Alzheimer’s and The authors of a recent study have ferences in response to peroxisome other neurodegenerative diseases, concluded that dementia is corre- proliferators. Rats and mice are very for instance, have lower levels of lated with low DHEA more so than sensitive to the toxic effects of these DHEA.79,80 A recent Canadian study with high cortisol.80 Another study compounds, but peroxisome pro- found that rats implanted with a high also showed that while normal aging liferators do not produce toxicity in dose of DHEA showed significantly results in decreased DHEA levels, species like guinea pigs, monkeys, less hippocampal damage after stroke victims of dementia have even lower and humans at dose levels that pro- was induced (88% injured neurons in levels of DHEA than do the healthy duce a dramatic toxic response in the placebo group compared to only elderly.95 rodents.99 60% in those given DHEA).81 DHEA is protective against a Scientists have published research It has been demonstrated that wide range of neurological disor- papers indicating that peroxisome DHEA markedly inhibits the inflam- ders.21,51,52,56-58,76-78,80,81,96-98 DHEA has proliferators do not pose a liver matory cytokines tumor necrosis fac- never been shown to increase stroke toxicity risk to human beings. One tor-alpha (TNF-alpha) and IL-6 in risk, as the bogus press release circu- researcher noted, “it is reasonable to glial cells.82 The ability to lower the lating in Congress alleges. conclude that the encountered levels

LIFE EXTENSION June 2007 of exposure to these non-genotoxic Even ignoring the fact that rats DHEA Can Cause agents (peroxisome proliferators) do and mice are invalid models to Acne in Women— not present a hepatocarcinogenic assess for liver toxicity risk in When the Dose Is Too High hazard to humans.”100 humans with supplements like Since DHEA is a peroxisome pro- DHEA, and ignoring the fact that Women tend to require less DHEA liferator, it comes as no surprise that appropriate animal models for than men. When a woman takes too liver damage ocurred when scien- extrapolation to humans do not much DHEA, acne can result, but tists administered huge doses of a show any evidence of liver injury this dissipates when the DHEA dose well-known carcinogen, N-nitro- risk with DHEA, the rat-mouse is lowered. somorpholine, and huge doses of DHEA studies on liver toxicity use We at Life Extension have never DHEA in the diets of lab rats, roughly enormous amounts of DHEA— heard of “severe acne” being caused the human equivalent of 6774 mg doses equivalent to 130 times the by DHEA, as the biased press of DHEA daily! Contrast this enor- average 50 mg of DHEA per day release being circulated in Congress mous amount of DHEA with the typi- used by healthy adults. asserts. If the worst that can hap- cal 15-75 mg per day of DHEA used It is ludicrous to suggest that pen to women is temporary acne by healthy aging humans.101 DHEA be banned on the basis of in response to excessive intake of Valid animal models that have invalid animal models that use DHEA, this would appear to be a been used to assess the liver toxicity human-equivalent doses of DHEA small price to pay in relation to the risk of DHEA in humans have found that are more than 100 times multiple health benefits DHEA has no evidence of liver injury or toxic- greater than those used by healthy been shown to confer. ity. For example, a study showed that adults. An important study in The potential acne effect of DHEA rats and mice given large amounts of JAMA in 2006 showed signs of liver on women has been long known, DHEA in the diet displayed increased damage in patients who consumed and women usually stay at moderate liver enzyme levels associated with 4 grams daily of Tylenol® (acet- 15-50 mg/day DHEA doses and avoid lipid accumulation in rodent liver, aminophen) for two weeks.104 This acne altogether. but no such increase was shown in means that taking two Extra Strength guinea pigs.102 Another study showed Tylenol® caplets, four times daily, can DHEA Does Not Cause Hair Loss evidence of increased liver enzyme generate evidence of liver damage. levels when DHEA was adminis- Yet the misleading press release We could find no reports that tered to mice at a human-equiva- being circulated in Congress sug- DHEA causes hair loss. While one lent dose of about 1700 mg per day gests that DHEA should be outlawed could propose a theoretical basis of DHEA. However, in guinea pigs, a because it causes “liver damage.” that somehow orally ingested DHEA valid animal species for comparison This is an egregious distortion of would increase dihydrotestosterone to humans in this context, there was the facts—especially when there are (DHT) enough to promote hair loss, no evidence of toxicity at a human- no reported human cases of liver there is no evidence to show that this equivalent dose of over 4500 mg per damage caused by DHEA in the has ever actually happened. day of DHEA.103 scientific literature. If DHEA were to increase dihydrotestosterone, the solution would be to take a 5-alpha reductase inhibi- tor (like low-dose Proscar®) or possi- bly saw palmetto extract to block this effect.

DHEA Does Not Cause “Wild Mood Swings and Aggressiveness”

DHEA’s role as an antidepressant has been rigorously examined for years. During these many trials, researchers routinely found that when taken daily, DHEA supplements effectively reduced depressive episodes and enhanced mood. In fact, according to one major study in the UK, as many as 67% of men and 82% of women reported a notice- able decrease in their depressive symptoms while taking as little as

June 2007 LIFE EXTENSION (calcitriol) is a “steroid hormone,” but no one is yet suggesting that vitamin D be banned. In fact, both vitamin D and DHEA are synthesized from cholesterol, the most common sterol found in the body. DHEA exerts very weak androgenic (testosterone-like) and estrogenic (estrogen-like) activity, and can be converted into metabolites, depending on the body’s need and hormone balance.146 Under normal conditions, the conversion of DHEA to testosterone is tightly controlled by the body. DHEA has been consistently shown to not influence testosterone levels in young men.147-149 25 mg per day of DHEA.65 In addition, tion to their anti-psychotic medica- If DHEA did function as an ana- women suffering from adrenal insuf- tions.97 The study authors attributed bolic androgenic steroid, then aging ficiency have reported an improved this specific anxiety-reducing effect men would not be seeking prescrip- sense of well-being and an associ- to DHEA’s influence on the brain’s tion testosterone drugs to reverse cer- ated increase in both sexual interest GABA receptors, which are central to tain symptoms of aging. and sexual satisfaction while taking regulating mood.97 Since medical science defines DHEA.50 To characterize DHEA as caus- DHEA as a “steroidal hormone,” Sexual function is closely linked ing “wild mood swings and aggres- some lawmakers in Congress now with emotional health and well- siveness,” as was done in the press think it should be classified as a being, and scientists now know that release circulating in Congress, is “controlled substance” and removed DHEA levels are strongly associated the exact opposite of the beneficial from the marketplace. This is quite with healthy sexual function. Two psychological effects that DHEA an allegation when one considers recent studies found that sexual exerts on the body. that DHEA has been freely sold in the function105 and overall self-reported United States for over 10 years, with health and functional status106 were DHEA and Cancer no reports of serious adverse events. better among women with relatively The problem is that members of high levels of DHEA. Even low-dose No human study in which DHEA Congress are not scientists, and they DHEA supplementation may be was administered as a supplement are unable to differentiate between effective in providing these benefits. or drug has ever shown that it causes natural steroidal substances in the For example, in a group of women cancer. Petri dish and live animal body (such as cholesterol, vitamin with systemic lupus erythematosus, studies show that DHEA may pro- D, and DHEA) and the synthetic ana- daily doses of DHEA as low as 20-30 tect against certain cancers.41-46,109-145 bolic steroid drugs that are abused by mg improved health-related quality Human studies that measure DHEA some bodybuilders. of life and sexual interest and activ- blood levels and correlate them to ity compared to placebo.61 Other future cancer risk are contradictory What Is an researchers have reported notable and not representative of the DHEA “Anabolic Steroid Drug”? improvements in libido and mood protocols used by health-conscious in women who supplemented with people today. According to the United States DHEA.107,108 government’s own Medline Medical Even more promising are stud- Why Laypeople Confuse DHEA Dictionary, an anabolic steroid is ies suggesting that, in addition to its with Synthetic Steroid Drugs defined as: positive impact on depression and sexual function, DHEA may help to DHEA is produced mainly in the “Any of a group of usually manage symptoms of schizophre- adrenal glands and serves as a natu- synthetic hormones that are nia. Based on their preliminary find- ral precursor and balancer to many derivatives of testosterone, are used ings demonstrating DHEA’s efficacy hormones in the body. While DHEA medically especially to promote in reducing symptoms of schizo- is defined as a “steroidal hormone,” tissue growth, and are sometimes phrenia,84 researchers further noted that does not equate to an “anabolic abused by athletes to increase the improvement in illness severity and steroid drug.” size and strength of their muscles anxiety in a group of schizophrenic By way of example, the bioac- and improve endurance.” 150 patients who received DHEA in addi- tive form of vitamin D in the blood (Medline-March 12, 2007)

LIFE EXTENSION June 2007 Based on the government’s own Let Your Voice Be Heard References definition of “anabolic steroid,” on Capitol Hill DHEA does not fit into this category. 1. Ravaglia G, Forti P, Maioli F, et al. The Controlled clinical trials indicate relationship of dehydroepiandrosterone There is at least one pharma- sulfate (DHEAS) to endocrine-metabolic that its use in young adults does not ceutical company lobbyist for each parameters and functional status in the result in performance-related gains, member of Congress. Drug lobbyists oldest-old. Results from an Italian study on and it is not associated with the myr- function solely to persuade Congress healthy free-living over-ninety-year-olds. J Clin Endocrinol Metab. 1996 Mar;81(3):1173-8. iad side effects that accompany ana- to enact laws that make pharmaceu- 2. Ravaglia G, Forti P, Maioli F, et al. 147-149,151-153 bolic steroid abuse. DHEA tical companies more money. They Dehydroepiandrosterone-sulfate serum is sold as a natural (not synthetic) have no interest in protecting the levels and common age-related diseases: hormone and is not a derivative of American public’s health. results from a cross-sectional Italian 154 study of a general elderly population. Exp testosterone. If DHEA is classified as a “con- Gerontol. 2002 May;37(5):701-12. Anabolic steroid drug abuse is trolled substance,” pharmaceutical 3. Celec P, Starka L. Dehydroepiandrosterone— purported to result in cardiovascu- companies stand to earn enormous is the fountain of youth drying out? Physiol lar conditions such as hypertension, Res. 2003;52(4):397-407. profits from the drugs Americans 4. Glei DA, Goldman N. atherosclerosis, and blood clotting, will need to treat disorders as Dehydroepiandrosterone sulfate liver conditions such as jaundice diverse as: (DHEAS) and risk for mortality among and hepatic carcinoma, tendon older Taiwanese. Ann Epidemiol. 2006 Jul;16(7):510-5. damage, reduced fertility and breast • Type II diabetes 5. ��Mazat L, Lafont S, Berr C, et al. Prospective�� enlargement (in males), and adverse • Hypertension measurements of dehydroepiandrosterone psychological and behavioral • Depression sulfate in a cohort of elderly subjects: effects. DHEA does not exert these • Coronary and systemic relationship to gender, subjective health, 155,156 smoking habits, and 10-year mortality. Proc effects. atherosclerosis Natl Acad Sci USA. 2001 Jul 3;98(14):8145-50. Moreover, surveys of weightlift- • Osteoporosis 6. Stahl F, Schnorr D, Pilz C, Dorner G. ers and other athletes conducted • Chronic inflammation. Dehydroepiandrosterone (DHEA) levels by Harvard University researchers in patients with prostatic cancer, heart diseases and under surgery stress. Exp Clin show that DHEA is rarely used to Members of Congress have been Endocrinol. 1992;99(2):68-70. increase muscle size or strength or victimized by a misinformation 7. Thijs L, Fagard R, Forette F, to improve endurance.157 Therefore, campaign designed to disparage Nawrot T, Staessen JA. Are low dehydroepiandrosterone sulphate levels the notion that DHEA is in any DHEA for the purpose of having it predictive for cardiovascular diseases? A way comparable to controlled ana- reclassified as an “anabolic steroid review of prospective and retrospective bolic steroid drugs is scientifically drug.” Consumers must rally to studies. Acta Cardiol. 2003 Oct;58(5):403-10. unfounded and legally invalid. 8. Herrington DM. Dehydroepiandrosterone overcome this deceptive attempt to and coronary atherosclerosis. Ann NY Acad deny Americans continued access Sci. 1995 Dec 29;774:271-80. to this scientifically validated sup- 9. Feldman HA, Johannes CB, Araujo AB, et plement safely used by millions of al. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: Americans each day. prospective results from the Massachusetts Another troublesome aspect Male Aging Study. Am J Epidemiol. 2001 Jan about this charade to discredit 1;153(1):79-89. 10. Khalil A, Fortin JP, LeHoux JG, Fulop T. Age- DHEA is that it could provide a related decrease of dehydroepiandrosterone springboard for pharmaceutical concentrations in low density lipoproteins companies to attack other supple- and its role in the susceptibility of low ments that compete against their density lipoproteins to lipid peroxidation. J Lipid Res. 2000 Oct;41(10):1552-61. drug sales. So whether you use 11. Thomas N, Morris HA, Scopacasa F, Wishart DHEA or not, the hoax being per- JM, Need AG. Relationships between age, petrated in Congress is a genuine dehydro-epiandrosterone sulphate and threat to health freedom across the plasma glucose in healthy men. Age Ageing. 1999 Mar;28(2):217-20. board. 12. Kapoor D, Malkin CJ, Channer KS, Jones TH. The Senate bill that seeks to ban Androgens, insulin resistance and vascular DHEA is S.762. The companion disease in men. Clin Endocrinol (Oxf). 2005 Sep;63(3):239-50. House bill is H.R.1229. To register 13. Haden ST, Glowacki J, Hurwitz S, Rosen your opposition to these bills log C, LeBoff MS. Effects of age on serum on to www.lef.org/lac to con- dehydroepiandrosterone sulfate, IGF-I, and veniently send a prepared let- IL-6 levels in women. Calcif Tissue Int. 2000 Jun;66(6):414-8. ter via email to your members of 14. Paolisso G, Ammendola S, Rotondi M, et al. Congress. Insulin resistance and advancing age: what role for dehydroepiandrosterone sulfate? Metabolism. 1997 Nov;46(11):1281-6.

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Osmanagaoglu MA, Okumus Dehydroepiandrosterone inhibits human androgenic structural analogs. J Cell B, Osmanagaoglu T, Bozkaya H. platelet aggregation in vitro and in vivo. Ann Biochem Suppl. 1995;22:210-7. The relationship between serum NY Acad Sci. 1995 Dec 29;774:281-90. 44. Inano H, Ishii-Ohba H, Suzuki K, et dehydroepiandrosterone sulfate 33. Casson PR, Andersen RN, Herrod HG, al. Chemoprevention by dietary concentration and bone mineral density, et al. Oral dehydroepiandrosterone in dehydroepiandrosterone against lipids, and hormone replacement therapy physiologic doses modulates immune promotion/progression phase of radiation- in premenopausal and postmenopausal function in postmenopausal women. Am J induced mammary tumorigenesis in rats. women. J Womens Health (Larchmt). 2004 Obstet Gynecol. 1993 Dec;169(6):1536-9. J Steroid Biochem Mol Biol. 1995 Jul;54(1- Nov;13(9):993-9. 34. Kawano H, Yasue H, Kitagawa A, et al. 2):47-53. 19. Szathmari M, Szucs J, Feher T, Hollo I. 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Casson PR, Faquin LC, Stentz FB, et al. initiation and modulation stages of liver Dec 20;89(2):97-106. Replacement of dehydroepiandrosterone and lung carcinogenesis induced by 21. Michael A, Jenaway A, Paykel ES, Herbert enhances T-lymphocyte insulin binding in dihydroxy-di-n-propylnitrosamine in F344 J. Altered salivary dehydroepiandrosterone postmenopausal women. Fertil Steril. 1995 rats. Carcinogenesis. 1988 Aug;9(8):1507-9. levels in major depression in adults. B�iol�� May;63(5):1027-31. 47. Osawa E, Nakajima A, Yoshida S, et al. Psychiatry. 2000 Nov 15;48(10):989-95. 37. Sun Y, Mao M, Sun L, et al. Treatment Chemoprevention of precursors to colon 22.�� Basar MM, Aydin G, Mert HC, et al. of osteoporosis in men using cancer by dehydroepiandrosterone (DHEA). Relationship between serum sex steroids dehydroepiandrosterone sulfate. Chin Med J Life Sci. 2002 Apr 19;70(22):2623-30. and Aging Male Symptoms score and (Engl). 2002 Mar;115(3):402-4. 48. Yang S, Fu Z, Wang F, Cao Y, Han International Index of Erectile Function. 38. Villareal DT, Holloszy JO, Kohrt WM. Effects R. Anti-mutagenicity activity of Urology. 2005 Sep;66(3):597-601. of DHEA replacement on bone mineral dehydroepiandrosterone. Zhonghua Zhong 23.�� Muller M, Grobbee DE, den T, I, Lamberts density and body composition in elderly Liu Za Zhi. 2002 Mar;24(2):137-40. SW, van der Schouw YT. ��Endogenous sex women and men. Clin Endocrinol (Oxf). 49.�� Yoshida S, Honda A, Matsuzaki Y, et al. hormones and metabolic syndrome in 2000 Nov;53(5):561-8. Antiproliferative action of endogenous aging men. J Clin Endocrinol Metab. 2005 39. Labrie F, Diamond P, Cusan L, et al. Effect dehydroepiandrosterone metabolites on May;90(5):2618-23. of 12-month dehydroepiandrosterone human cancer cell lines. Steroids. 2003 24. Genazzani AR, Inglese S, Lombardi replacement therapy on bone, vagina, and Jan;68(1):73-83. I, et al. Long-term low-dose endometrium in postmenopausal women. 50.�� Arlt W, Callies F, van Vlijmen JC, et al. dehydroepiandrosterone replacement J Clin Endocrinol Metab. 1997 Dehydroepiandrosterone replacement in therapy in aging males with partial Oct;82(10):3498-505. women with adrenal insufficiency.N Engl J androgen deficiency.Aging Male. 2004 Med. 1999 Sep 30;341(14):1013-20. Jun;7(2):133-43. 25. Khorram O, Vu L, Yen SS. Activation of immune function by dehydroepiandrosterone (DHEA) in age- advanced men. J Gerontol A Biol Sci Med Sci. 1997 Jan;52(1):M1-M7. 26.�� Jankowska EA, Biel B, Majda J, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):1829-37. 27. Moriyama Y, Yasue H, Yoshimura M, et al. The plasma levels of dehydroepiandrosterone sulfate are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab. 2000 May;85(5):1834-40. 28. Sacco M, Valenti G, Corvi MP, Wu FC, Ray DW. DHEA, a selective glucocorticoid receptor antagonist: its role in immune system regulation and metabolism. J Endocrinol Invest. 2002;25(10 Suppl):81-2.

10 LIFE EXTENSION June 2007 71. Vryonidou A, Papatheodorou A, Tavridou A, et al. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 May;90(5):2740-6. 72. Shimizu T, Choudhry MA, Szalay L, et al. Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage. Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2): R386-90. 73. Origlia C, Pescarmona G, Capizzi A, et al. Platelet cGMP inversely correlates with age in healthy subjects. J Endocrinol Invest. 2004 Feb;27(2):RC1-4. 74. Okamoto K. Relationship between dehydroepiandrosterone sulfate and serum lipid levels in Japanese men. J Epidemiol. 1996 Jun;6(2):63-7. 75. Shono N, Kumagai S, Higaki Y, Nishizumi M, Sasaki H. The relationships of testosterone, 51. Herbert J. Neurosteroids, brain damage, and 61. 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Relationships between 56. de B, V, Vieira MC, Rocha MN, Viana GS. dehydroepiandrosterone sulfate on dehydroepiandrosterone sulfate (DHEAS) Cortisol and dehydroepiandosterone sulfate ventricular diastolic function with young and cortisol (CRT) plasma levels and plasma levels and their relationship to aging, and aged female mice. Am J Physiol Regul everyday memory in Alzheimer’s disease cognitive function, and dementia. Brain Integr Comp Physiol. 2006 Jan;290(1):R251-6. patients compared to healthy controls. Cogn. 2002 Nov;50(2):316-23. 67. Hutchison SJ, Browne AE, Ko E, et al. Horm Behav. 1999 Jun;35(3):254-63. 57. Magri F, Terenzi F, Ricciardi T, et al. Dehydroepiandrosterone sulfate induces 80. Murialdo G, Nobili F, Rollero A, et al. Association between changes in adrenal acute vasodilation of porcine coronary Hippocampal perfusion and pituitary- secretion and cerebral morphometric arteries in vitro and in vivo. 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Eur J Neurosci. 2002 dehydroepiandrosterone sulfate, mortality, selectively inhibits production of tumor Aug;16(3):445-53. and cardiovascular disease. N Engl J Med. necrosis factor alpha and interleukin-6 59. Mills SJ, Ashworth JJ, Gilliver SC, Hardman 1986 Dec 11;315(24):1519-24. [correction of interlukin-6] in astrocytes. Int MJ, Ashcroft GS. The sex steroid precursor 70. Morales AJ, Haubrich RH, Hwang JY, J Dev Neurosci. 1999 Dec;17(8):765-75. DHEA accelerates cutaneous wound healing Asakura H, Yen SS. The effect of six months 83. Young AH, Gallagher P, Porter RJ. Elevation via the estrogen receptors. J Invest Dermatol. treatment with a 100 mg daily dose of of the cortisol-dehydroepiandrosterone 2005 Nov;125(5):1053-62. dehydroepiandrosterone (DHEA) on ratio in drug-free depressed patients. Am J 60. Ayhan S, Markal N, Siemionow K, Araneo circulating sex steroids, body composition Psychiatry. 2002 Jul;159(7):1237-9. B, Siemionow M. 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June 2007 LIFE EXTENSION 11 85. Young AH, Gallagher P, Porter RJ. Elevation of the cortisol-dehydroepiandrosterone ratio in drug-free depressed patients. Am J Psychiatry. 2002 Jul;159(7):1237-9. 86. Valtysdottir ST, Wide L, Hallgren R. Mental wellbeing and quality of sexual life in women with primary Sjogren’s syndrome are related to circulating dehydroepiandrosterone sulphate. Ann Rheum Dis. 2003 Sep;62(9):875-9. 87. Jozuka H, Jozuka E, Takeuchi S, Nishikaze O. Comparison of immunological and endocrinological markers associated with major depression. J Int Med Res. 2003 Jan;31(1):36-41. 88. Schmidt PJ, Murphy JH, Haq N, Danaceau MA, St CL. Basal plasma hormone levels in depressed perimenopausal women. Psychoneuroendocrinology. 2002 Nov;27(8):907-20. 89. Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR. Dehydroepiandrosterone 101. Metzger C, Bannasch P, Mayer 111. Lubet RA, Gordon GB, Prough RA, et al. treatment of midlife dysthymia. Biol D. Enhancement and phenotypic Modulation of methylnitrosourea-induced Psychiatry. 1999 Jun 15;45(12):1533-41. modulation of N-nitrosomorpholine- breast cancer in Sprague Dawley rats by 90. Wolkowitz OM, Reus VI. Neurotransmitters, induced hepatocarcinogenesis by dehydroepiandrosterone: dose-dependent neurosteroids and neurotrophins: new dehydroepiandrosterone. Cancer Lett. 1997 inhibition, effects of limited exposure, models of the pathophysiology and Dec 23;121(2):125-31. effects on peroxisomal enzymes, and lack treatment of depression. World J Biol 102. Imai K, Kudo N, Koyam M, of effects on levels of Ha-Ras mutations. Psychiatry. 2003 Jul;4(3):98-102. Shirahata A, Kawashim Y.Effects of Cancer Res. 1998 Mar 1;58(5):921-6. 91. van BF, Verkes RJ. Neurosteroids in dehydroepiandrosterone on oleic acid 112.�� Perkins SN, Hursting SD, Haines DC, et depression: a review. Psychopharmacology formation in the liver of rats, mice and al. 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Might DHEA be considered a beneficial abnormalities, and depression in women Dehydroepiandrosterone sulfate enhances replacement therapy in the elderly? Drugs with epilepsy treated with antiepileptic natural killer cell cytotoxicity in humans via Aging. 2007;24(3):173-85. drugs. Epilepsy Behav. 2005 May;6(3):360-5. locally generated immunoreactive insulin- 96. Wojtal K, Trojnar MK, Czuczwar SJ. 106.�� Santoro N, Torrens J, Crawford S et al. like growth factor I. J Clin Endocrinol Metab. Endogenous neuroprotective factors: Correlates of circulating androgens in mid- 1999 Sep;84(9):3260-7. neurosteroids. Pharmacol Rep. 2006 life women: the study of women’s health 117. Mei JJ, Hursting SD, Perkins SN, Phang May;58(3):335-40. across the nation. J Clin Endocrinol Metab. JM. p53-independent inhibition of nitric 97. Strous RD. Dehydroepiandrosterone 2005 Aug;90(8):4836-45. oxide generation by cancer preventive (DHEA) augmentation in the management 107. Buvat J. 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12 LIFE EXTENSION June 2007 120. Prough RA, Lei XD, Xiao GH, et al. 131. Dashtaki R, Whorton AR, Murphy TM, et 141. Schatzl G, Madersbacher S, Thurridl T, et Regulation of cytochromes P450 by DHEA al. Dehydroepiandrosterone and analogs al. High-grade prostate cancer is associated and its anticarcinogenic action. Ann NY inhibit DNA binding of AP-1 and airway with low serum testosterone levels. Prostate. Acad Sci. 1995 Dec 29;774:187-99. smooth muscle proliferation. J Pharmacol 2001 Apr;47(1):52-8. 121. Schwartz AG and Pashko LL. Cancer Exp Ther. 1998 May;285(2):876-83. 142.�� Schatzl G, Reiter WJ, Thurridl T, et al. prevention with dehydroepiandrosterone 132.�� Wang TT, Hursting SD, Perkins SN, Phang Endocrine patterns in patients with benign and non-androgenic structural analogs. J JM. Effects�� of dehydroepiandrosterone and malignant prostatic diseases. Prostate. Cell Biochem Suppl. 1995;22:210-7. and calorie restriction on the Bcl-2/ 2000 Aug 1;44(3):219-24. 122. 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June 2007 LIFE EXTENSION 13

How Congress Is Being Misled to Think That DHEA Is an “Anabolic Steroid”

No organization in the world has studied DHEA longer than the Life Extension Foundation. Since 1981, we have: 1) compiled and analyzed volumes of published DHEA studies; 2) performed and analyzed thousands of human DHEA blood tests; 3) published advanced DHEA safety-dosing protocols; 4) and in recent years have maintained a database that compiles real-world information showing what DHEA does in the human body.

We have witnessed firsthand the unique benefits that DHEA can bestow on aging humans. We know that DHEA does not cause the dramatic fat-loss and muscle-bulking effects of anabolic steroid drugs. If DHEA did contour muscular physique the way anabolic steroid drugs do, this would be truly miraculous, in as much as DHEA is virtually free of side effects. The bottom line is that DHEA does not produce the effects associated with anabolic steroids and is in fact not an anabolic steroid drug. More than 30 years of peer-reviewed published research substantiates this. How then can some members of Congress say that DHEA is now an “anabolic steroid drug”? > > >

June 2007 LIFE EXTENSION 15 Gene Expression Assays: A Little-Understood Technology When we inquired to the Congressional office leading the assault on DHEA, we were sent one study that used gene expression assays to compare the effects of DHEA to dihydrotestosterone (DHT), a potent testosterone metabolite.1 Gene expression studies assess the level of changes in response to the introduction of an external agent such as a drug, hormone, or nutrient. Comparing the status of gene activity before and after treatment provides a description of the genomic effect an external agent has on analyzed tissue. That’s right. The lead author of The Flawed Study According to this study being the DHEA-anabolic steroid study used to attack DHEA, extremely high circulating in Congress today is The study being used in efforts DHEA doses caused some of the same the inventor of patents that would to ban DHEA measured the effects gene expression changes as DHT in a enable DHEA to be used in synergis- of very high doses of DHEA that hybrid group of mice. Since few doc- tic combination with various drugs were injected into a hybrid strain tors are able to interpret gene expres- to improve their efficacy.4 of castrated mice.1 The study used sion assay studies, a technology that It would appear that Congress DNA microassays to compare the virtually no one can comprehend is may base its decision to ban DHEA genomic effects of DHEA, DHT, being used to discredit DHEA. on a study whose author stands and placebo (control) on prostate The Life Extension Foundation to make a fortune if DHEA supple- tissues. At autopsy, prostate tis- is a pioneer in the development of ments are outlawed. sues of the various groups of mice gene expression assay technology.2,3 In the gene analysis study being were weighed to assess anabolic We were the first organization to used to attack DHEA, th��e�� lead ��author�� stimulatory growth. use gene expression assays to iden- makes legal conclusions that DHEA Compared to the DHT group, tify potential anti-aging therapeutic should be removed from the OTC the prostate tissues of mice injected agents. We currently fund aggres- (over-the-counter) market and re- with very-high-dose DHEA weighed sive gene expression assay research classified as an anabolic steroid. This 33% less. Even more revealing aimed at finding calorie-restriction of course would pave the way for pat- was the finding that the prostate mimetics (such as metformin and ented DHEA prescription drugs that tissues of an intact control group resveratrol) that aging people can use offer the same benefits as low-cost that received neither DHEA or today to slow or reverse the effects of DHEA supplements do today.5 DHT weighed 24% more than the aging in their bodies. These kinds of legal interpreta- DHEA group—suggesting that DHEA Based on Life Extension’s analy- tions, by the way, are quite unusual to may have had an anti-anabolic sis and opinion, the gene expression see in peer-reviewed scientific stud- effect in the tissues weighed. study being circulated in Congress ies. Even more curious is the state- Since huge doses of DHEA were contains many serious flaws that ment at the very end of this study, injected into the mice, bypassing render its findings meaningless. where the authors declare that: normal digestive-absorption-limit- ing barriers and the liver degradation Guess Who Authored “There is no conflict of that occurs when humans swallow This Questionable Study? interest that would prejudice DHEA supplements, the genomic the impartiality of this findings—which are themselves Before we reveal the failings scientific work.” 1 highly questionable—have no rela- of the study being used to attack tionship whatsoever to what occurs DHEA, readers should understand Based on the patents issued in the in a human being taking 15-75 mg that the lead scientist who authored name of the lead author of this study, of DHEA daily. this study (stating that DHEA is an it would appear that a significant To expose some of the specific anabolic steroid) is also listed on economic “conflict of interest” exists defects in the gene analysis study in patents that could turn DHEA into as it relates to the “impartiality of this the simplest terms, we present the lucrative prescription drugs! scientific work.” following observations:

16 LIFE EXTENSION June 2007 1. In the four-week arm of the then computing the mode of admin- mouse study, the amount of istration given to the mice (i.e., DHEA injected daily was 30 injection), the human-equivalent times greater than the DHT dose DHEA dose if taken orally would (0.1 mg of DHT compared to 3 be about 15,800 mg a day. Typical mg of DHEA). In the one-week human doses of DHEA are only 15- arm of the study, the amount of 75 mg a day, a vastly smaller amount DHEA injected daily was than used in this mouse study being 62 times greater than the DHT used to discredit DHEA. dose (0.1 mg of DHT compared In other words, the mice in this to 6.25 mg of DHEA). Since the study used to attack DHEA were given dose of DHEA was 30-62 times a human-equivalent dose that was a greater than the dose of DHT, the startling 316 times greater than the effects shown on the gene expres- average 50 mg per day health-con- sion assays are not comparable. scious people are taking today to This has not stopped certain restore DHEA to youthful ranges. members of Congress from stat- To put this in perspective, if one ing that DHEA exerts the same were to evaluate the genomic effects effects as DHT—a statement of a human taking one standard that is invalidated by the grossly aspirin tablet daily (325 mg)—but higher amounts of DHEA used in the equivalent of 316 aspirin tablets this study compared to DHT. (102,700 mg) were given to lab mice to measure the gene expression 2. The mice were given extremely effects—the findings would have no high doses of DHEA that exceed meaning, since humans do not take what any human would ever take. 316 tablets of aspirin in a day. For example, in the four-week The DHEA dose was even higher portion of the DHEA-DHT study, in the one-week arm of the study, the numerical human- where the extrapolated human- comparison dose of DHEA based equivalent dose of 43,910 mg of on weight alone was 5,832 mg, DHEA was administered to mice. To DHEA: whereas in the one-week elaborate, when DHEA is injected, study, the numerical human- it bypasses normal absorption bar- What You Need to Know comparison dose was 16,200 mg. riers and degradation by the liver, thus becoming much more potent • For more than 25 years, the When calculating the correction to the organism. Life Extension Foundation has factor that extrapolates the conver- Based on the egregious over- exhaustively researched DHEA’s sion value of mice to humans, and doses of DHEA used in this mouse benefits for promoting human health study, the findings have no genomic and longevity. Currently, DHEA is relevance to the 15-75 mg a day of readily available as a low-cost dietary DHEA that humans take. Yet certain supplement. members of Congress have been • Due to the recent publication of a led to believe that this study some- flawed study, the US Congress is how changes the status of DHEA to considering whether DHEA should be that of an anabolic steroid. reclassified as an anabolic steroid. If this occurs, DHEA will no longer be 3. The experiments were per- readily available to health-conscious formed on gonadectomized consumers. (testicles removed) animals. • The study being used in this attempt The effect of DHEA on the gene to ban DHEA is full of flaws regarding expression of normal (non- dosage, route of administration, and gonadectomized) animals is not interpretation of data, rendering its described (neither by itself, nor findings practically meaningless. compared to the effect of DHT • Concerned citizens can help protect on normal animals). The use of their access to this crucial dietary this flawed animal model further supplement by alerting members of renders the findings meaning- Congress that DHEA should not be less to humans. reclassified as an anabolic steroid. 4. When comparing the prostate weight of the mice receiving DHT, DHEA, or control, the DHEA group showed smaller growth in the prostate gland and surround- ing tissues than the DHT and the intact control group, suggesting that DHEA may have impeded undesirable prostate growth in animals that were not castrated. The prostate tissues of DHT mice weighed 33% more than those of the DHEA group, whereas prostate tissues in the intact control group (receiving neither DHT nor DHEA) weighed 24% more than the DHEA group. This finding showed that DHEA did not exert anabolic steroid effects, yet this study is being used as evidence to re-classify DHEA as been made by assessing for as to favorable or unfavorable an anabolic steroid drug when cell proliferation, mRNA changes in gene expression. the only tissues weighed show expression, and quantitative Gene expression in response to DHEA administration resulted in real-time polymerase chain an agent can be up-regulated, lower prostate weight than seen reaction (PCR).8 Furthermore, down-regulated, or unchanged. in normal control animals. studies using human prostate The gene expression study being cancer cells show that DHEA has circulated in Congress describes 5. Microarray gene studies often a delayed and reduced effect on only those genes that are, per the yield a large number of differen- cancer cell proliferation authors, “commonly modulated,” tially expressed genes that may compared to testosterone or i.e., up-regulated in both DHEA require validation depending DHT.9 Researchers at NIH and DHT treatments, or down- on study design and statistical concluded that DHT promotes regulated in both treatments. methods used. Some research- prostate growth partly via The authors do not comment on ers suggest that the expression modulation of the stromal cell the numbers and identities of changes in a subset of genes IGF axis, while DHEA did not genes that are: should be confirmed by indepen- have this effect.8 These studies dent methods (such as real-time refute the notion that DHEA is an a. up-regulated in one, polymerase chain reaction, or “anabolic steroid”, but were not but not in the other RT-PCR).6,7 even mentioned in the treatment, conclusion of the one biased b. down-regulated in one, 6. The findings of the study used study being used as evidence that but not in the other to attack DHEA contradict other DHEA should be outlawed. It is treatment, recent side-by-side gene customary to mention contradic- c. up-regulated in one, but comparison studies. In fact, tory research in the conclusions down-regulated in the studies show the risk of prostate of scientific studies in order to other treatment. cancer in men is clearly provide the reader with a glimpse associated with increases in gene of other research findings that It is our opinion that, without the expression involving insulin-like show different outcomes. data above, it is impossible to com- growth factor-1 (IGF-1). Rigorous pare the effects of DHEA to those scientific studies recently 7. The DHEA-DHT study showed of DHT. Simply noting the “common conducted at the National that several genes were modulation” of a certain number of Institutes of Health (NIH) with modulated by both DHEA and genes does not establish a “genetic human prostate cells (in con- DHT in the mouse prostate and signature,” or “proof of androgenic trast to the aforementioned seminal vesicles.1 However, anabolic activity.” Such a study would mouse study) show that unlike simply because a number of require verification using qualitative DHT, DHEA does not stimulate mouse genes are modulated by genomic analysis of commonly and IGF-1 in human prostate cells, both DHEA and DHT does not separately affected genes to assess a and this determination has in any way provide information genomic relationship between DHEA

18 LIFE EXTENSION June 2007 and DHT. Their relationship to bio- valuable if DHEA became a prescrip- logical anabolic activity needs to be tion-only drug. further investigated using sophis- Since members of Congress are ticated molecular biological tech- unlikely to see the blatant flaws niques like quantitative real-time that exist in this study, but are likely PCR. Furthermore, due to known to be besieged by pharmaceutical species-specific responses exhibited lobbyists, it is critical for concerned by DHEA, interspecies extrapolation citizens to alert their Congressional to humans (with an experimental members today to the fact that DHEA species of mice that was used in this is not an anabolic steroid. study) needs to be cautioned. The Senate bill that seeks to ban DHEA is S.762. The companion House bill is H.R.1229. To register Don’t Let Congress Be Fooled your opposition to these bills log Despite these serious flaws that on to www.lef.org/lac to con- invalidate the findings and conveniently send a prepared let- clusions of this DHEA-DHT study, ter via email to your members of Congress may unwittingly use this Congress. biased DHEA-DHT gene expression study to outlaw DHEA. References: The reason Congress may be misled is that gene expression 1. J Steroid Biochem Mol Biol. 2006 Jul;100(1-3) technology is incomprehensible to 52:8. Dehydoepiandrosterone�� (DHEA) is an those who are not directly involved anabolic steroid like dihydrotestosterone in the field. We doubt that anyone (DHT), the most potent natural androgen, in Congress will figure out that the and tetrahdyogestrinone (THG). author of this study is listed on pat- 2. Life Extension. January, 1999. Genomics: ents that could become enormously The key to new treatments?

3. Life Extension. November, 1999. How We Calculated Human-Equivalent Dosing Implications of the new biology of aging. 4. US Patent 7,005,428. February 28, 2006. The amount of DHEA (3-6.25 mg, or 83.3-231.5 mg/kg) injected daily into these hybrid, 5. Endocr Relat Cancer. 2006 Jun;13(2):335-55. castrated mice might appear to be small by human standards. Future perspectives of selective estrogen When one considers, however, that the mean weight of these mice was 1.26 ounces, then receptor modulators used alone and in the magnitude of the high dose of DHEA used becomes apparent. The average person weighs combination with DHEA. 2,464 ounces—about 1900 times more than the average mouse in this study. 6. Reproduction. 2005 Jul:130(1):1-13. A guide When extrapolating doses used in animal studies to what the human-equivalent dose to issues in microarray analysis: application (HDE) would be, factors in addition to weight have to be considered (such as the body surface to endometrial biology. area of lab mice compared to humans). We considered this and used recognized scientific 7. J Mol Diagn. 2001 Feb;3(1):26-31. Validation tables to reduce the human equivalent dose by 12.3 times. Even with this large percentage of array-based gene expression profiles by reduction, the human-equivalent dose of DHEA was still very high compared to what humans real-time (kinetic) RT-PCR. supplement with. 8. Am J Physiol Endocrinol Metab. 2006 When we saw that the mice were injected with the DHEA instead of having it added to May;290(5):E952-60. DHT and testosterone, their food, we had to adjust the human equivalent dose much higher, since the natural but not DHEA or E2, differentially modulate limitations relating to digestion-absorption and liver degradation in response to oral ingestion IGF-I, IGFBP-2, and IGFBP-3 in human would not occur. prostatic stromal cells. We found a study showing that relative to subcutaneous dosing of DHEA, oral dosing of DHEA 9. Am J Physiol Endocrinol Metab. 2005 10 is only approximately 3% as potent. Since the mice were injected with DHEA, we calculated an Mar;288(3):E573-84.Comparative effects of equivalent potency dose for oral ingestion. DHEA vs. testosterone, dihydrotestosterone, The numbers came in showing that the human-equivalent dose of DHEA used in this gene and estradiol on proliferation and gene expression study was 15,800 mg in the four-week arm, and an astounding 43,910 mg in the expression in human LNCaP prostate one-week arm. cancer cells. Since typical human doses of DHEA are 15-75 mg a day, with an average daily dose of 50 10. J Endocrinol. 1996 Sep;150 Suppl: mg, the outlandish doses of DHEA (316-878 times more) used in the one- and four-week arms S107-18. High bioavailability of of this mouse study discredit its application to humans. dehydroepiandrosterone administered percutaneously in the rat.

June 2007 LIFE EXTENSION 19 How You Can Prevent DHEA from Becoming an “Illegal Drug”

It has been a while since a specific dietary supplement has been threatened to be turned into an illegal drug by an act of Congress.

In the past, we have advised people to stock up on a large supply of the endan- gered supplement in the event of its abrupt removal from the marketplace.

This time, we have to caution that if Senate bill 762 (S.762) and House Resolution 1249 (H.R. 1249) are enacted into law, DHEA would be classified as a “controlled substance” under the Anabolic Steroid Control Act. This would mean that mere possession of DHEA could subject you to criminal sanctions, including jail time.

If the thought of federal agents raiding the homes of elderly Americans to seize their DHEA sickens you as much as it does us, we urge you to email and call your two Senators and House Representative and tell them to vote against any legislation seeking to restrict DHEA.

Those without computer access can tear out the next page, photocopy it, and mail it to their Representative and Senators. If you have the time, please use this letter as a basis from which to write your own personal letter to your elected officials. Personal letters are taken very seriously by those in government. We also ask that you phone your Representative and Senators at 1-202-224-3121 to let them know how disgusted you are that Congress would even contemplate turning a safe dietary supplement like DHEA into a controlled substance—especially when the apparent motive to remove DHEA as a low-cost supplement is so that it can be sold as an expensive prescription drug.

To make it very convenient, we have set up a special website that enables you to send our form letter and/or any other communications to your members of Congress. You can log on directly to this website at www.lef.org/lac

We suggest that email be used as much as possible. For those who want to mail a printed letter, it should be sent to the legislator’s home office and not to Washington, DC. To find the name and home office address of your members of Congress, call 1-202-224-3121 and provide your zip code, and you will be connected to your Representative’s office. You can call back to be connected to your Senators. This not only enables you to obtain the home office address, but also gives you a chance to make your views known about this bill that would ban consumer access to DHEA.

It is crucial that all Life Extension members let their Senators and Representatives know that DHEA is not an anabolic steroid, despite the misleading information that appears to be disseminated by pharmaceutical interests. You can reach your members of Congress during daytime hours by calling 1-202-224-3121, and you can email them 24 hours a day by logging on to www.lef.org/lac Congress Threatens to Ban DHEA

Dear Member,

A bill has been introduced in Congress that would reclassify DHEA as an anabolic steroid drug, thus making it illegal for Americans to even possess.

Life Extension has reviewed these unfounded attacks and has prepared the attached rebuttal that explains why DHEA is not an anabolic steroid drug and how pharmaceutical influence appears to be behind this deceptive scheme to turn DHEA into an expensive prescription drug.

We invite you to review the attached rebuttals, which will appear in the next (June 2007) issue of Life Extension magazine you receive.

To conveniently notify your two Senators and Representative to vote NO on this bill that would ban DHEA, click here to enter our legislative action website that enables you to send an email to your members of Congress in just a few minutes.

Please know that most members of Congress prefer their constituents notify them via email, rather than writing paper letters. One reason is the anthrax scare and other threats that cause congressional aides to be nervous about opening regular mail.

If DHEA were to be removed from the marketplace, Life Extension believes this would result in an epidemic of age-related disorders associated with low levels of DHEA. Please don’t let drug lobbyists take away this natural, safe, and low-cost dietary supplement that is helping so many aging adults.

Click here to instantly and conveniently notify your members of Congress that they should vote NO on any legislation that bans citizens’ free access to DHEA.

For longer life,

William Faloon The Flawed DHEA Study

A study being circulated in Congress human doses of DHEA are only 15-75 mg a day, purports that DHEA (dehydroepiandrosterone) a vastly smaller amount than used in this mouse is an anabolic steroid. The study measured the study being used to discredit DHEA. In other effects of very high doses of DHEA that were words, the mice in this study were given a human- injected into a hybrid strain of castrated mice. equivalent dose that was a startling 316 times The study used DNA microassays to compare greater than what the average dose health- the genomic effects of DHEA, DHT (dihydro- conscious people are taking today to restore DHEA testosterone), and placebo (control) on prostate to youthful ranges. tissues. At autopsy, prostate tissues of the various groups of mice were weighed to assess anabolic The DHEA dose was even higher in the one- stimulatory growth. week arm of the study, where the extrapolated human-equivalent dose of 43,910 mg of DHEA Compared to the DHT group, the prostate was administered to mice. To elaborate, when tissues of mice injected with very-high-dose DHEA is injected, it bypasses normal absorption DHEA weighed 33% less. Even more revealing barriers and degradation by the liver, thus was the finding that prostate tissues of an intact becoming much more potent to the organism. control group that received neither DHEA or DHT weighed 24% more than the DHEA group— Based on the egregious overdoses of DHEA suggesting that DHEA may have had an used in this mouse study, the findings have no anti-anabolic effect in the tissues weighed. genomic relevance to the 15-75 mg a day of DHEA that humans take. Yet certain members of In the four-week arm of the mouse study, Congress have been led to believe that this study the amount of DHEA injected daily was somehow changes the status of DHEA to that of an 30 times greater than the DHT dose (0.1 mg of anabolic steroid. DHT compared to 3 mg of DHEA). In the one- week arm of the study, the amount of DHEA The findings of the study used to attack injected daily was 62 times greater than the DHT DHEA contradict other recent side-by-side gene dose (0.1 mg of DHT compared to 6.25 mg of comparison studies. These studies refute the DHEA). Since the dose of DHEA was 30-62 times notion that DHEA is an “anabolic steroid,” but higher than the dose of DHT, the effects shown on were not even mentioned in the conclusion of the gene expression assays are not comparable. the one biased study being used as evidence that DHEA should be outlawed. It is custom- The mice were given extremely high doses ary to mention contradictory research in the of DHEA that exceed what any human would ever conclusions of scientific studies in order to take. For example, in the four-week portion of provide the reader with a glimpse of other research the DHEA-DHT study, the numerical human- findings that show different outcomes. comparison dose of DHEA based on weight alone was 5,832 mg, whereas in the one-week The flawed DHEA-DHT study showed that study, the numerical human-comparison dose several genes were modulated by both DHEA and was 16,200 mg. DHT in the mouse prostate and seminal vesicles. However, simply because a number of mouse When calculating the correction factor that genes are modulated by both DHEA and DHT does extrapolates the conversion value of mice to not in any way provide information as to favorable humans, and then computing the mode of or unfavorable changes in gene expression. For a administration given to the mice (i.e., injection), complete report about why DHEA should not be the human-equivalent DHEA dose if taken orally reclassified as an anabolic steroid drug, log on to would represent about 15,800 mg a day. Typical www.lef.org/featured-articles/dheafact