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Dr. Bernard Presser D.C.
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"DHEA Breakthrough! Look younger, live longer, feel better! Reduce body fat and build lean muscle mass. Restore sexual vigor. Boost your immune system, and protect against major diseases." i This promotion from one book reflects the type of media exposure given to DHEA supplement, a so-called "superhormone" which had recently exploded on the retail scene. Learn everything about dheas and dhea hormone.
After being available only by prescription for 10 or more years, the U.S. Dietary Supplement Health and Education Act of 1994 made it possible for DHEA to be sold directly to consumers. This law allows for many substances to be sold for human consumption without approval from the Food and Drug Administration (FDA), placing the burden of proving the substances unsafe on the government agency rather than the burden of safety on the manufacturers.
Aggrandized as a "fountain of youth," DHEA is offered as a "supplement" that can help burn fat, build muscle mass, boost libido, strengthen the immune system, prevent heart disease, cancer, non-insulin-dependent diabetes; retard memory loss, assist in treating lupus erythematosus, and prevent or slow the progression of Alzheimer's and Parkinson's disease. "All this, despite the fact that not one of these benefits has yet been demonstrated in a large randomized placebo-controlled clinical trial." And, there are possible adverse effects and dangers. ii Of the many scientific studies conducted with DHEA, most have been animal and laboratory studies, or human studies with inconclusive or contradictory results. "What doctors know about DHEA's effects on the body could practically fit on the back of an envelope." Thus consumers are guinea pigs for an unproven drug. As one of the foremost DHEA researchers, endocrinologist John Nestler, said, "...we can't go recommending something we know so little about. The Hippocratic Oath says, ‘First, do no harm.'" iii
DHEA (dehydroepiandrosterone) is a steroid hormone produced primarily by the adrenal glands (minute amounts by the gonads) ONLY in humans, primates (monkeys), and a few nonprimate species. It is formed from cholesterol.
Most all (95%) the DHEA in the body is in sulfated form, dehydroepiandrosterone sulfate (DHEAS), which enhances the water solubility of the hormone, thereby decreasing its biological activity and increasing its excretion. Only a small fraction of DHEA is needed or used for regulation while the rest is degraded.
DHEAS, though having its own biologic role(s), may serve as a transport form for the steroid since DHEA's main function is as a precursor for other steroid hormones: androgens or estrogens. Yet, "[h]ow DHEA exerts its biologic actions remains an enigma." Laboratory animals such as rats, mice, and rabbits -- usually employed in studies -- have little or no circulating DHEA or DHEAS, in contrast to human biochemistry.iv
DHEAS secretion from the adrenals shows a dramatic cycle of high and low points over the lifespan of most humans. Secretion is very high in the fetus, drops sharply after birth to very low levels in childhood, rises before puberty, and again reaches high levels in young adulthood. Thereafter, levels progressively decline (about 2% per year), often reaching very low levels after age 70. Researchers do not know why these fluctuations occur. Neither do they know if the decline in older humans is due to deprivation of an essential hormone or if it is a natural and normal consequence of aging.v
Further, at all ages, the individual variability is very high and the normal range of serum DHEAS is therefore very wide. Also, important genetic differences appear to exist. (For example, Japanese men have significantly lower levels than American white men.) Though by age 80, usually levels of DHEA are only about 20% of those at age 25, and generally men have levels 10 to 30% higher than women, individual differences are immense. Some 80-year old people have very high levels, particularly those with certain illnesses or diseases, while others have only negligible levels. So, couldn't the physical and mental condition of human subjects used in research lead to misinformation or erroneous conclusions, especially since most elderly subjects are sick, taken from hospitals or clinics?vi
"The interpretation of studies relating to DHEAS levels to physiological aging, general health condition, or life expectancy is complicated by the fact that during illness, mental depression, or other stress factors, there is a dissociation between DHEAS and cortisol [another adrenal steroid hormone] levels, the former [DHEAS] being decreased during stress situations," and cortisol is increased. (Emphasis added) vii
When changes in the "immune response potential" are pronounced (i.e., with immune system compromise or stress) plasma levels of DHEAS are "markedly reduced..." Levels are known to fall during such illnesses as rheumatoid arthritis, polymyalgia rheumatica, the skin conditions pemphigus and pemphigoid, lupus, and major depressive disorders -- conditions in which the adrenal glands are highly stressed.
So another question arises: Do DHEAS levels fall when the adrenal glands are weakened or for some reason underfunctioning? If so, is it wise to administer a hormone which could further disrupt endocrine equilibrium or, rather, to support the function and health of the glands as well as reduce or eliminate some stresses to allow for adrenal repair and thus hormonal balance? viii
A hormone is a chemical messenger that has specific regulatory effects on physiological processes. It is NOT a dietary nutrient. Attempting to manipulate a hormone in the body "is tricky, far too tricky for most mortals." One problem is the natural feedback mechanism for hormone production, a system so far not understood for DHEA. When a hormone is taken, the gland normally producing it is signaled that there are adequate or excess hormone levels in circulation, and thus no need to produce or secrete the hormone. In time, the glandular functions lessen, eventually ceasing any hormone synthesis. A dependency for the outside (imitation) hormone develops, often accompanied by biochemical disruption.
What effects the added hormone will have on various and seemingly unrelated biologic functions can't be predetermined. Nothing works independently, especially in the endocrine system: one altered area can affect many other areas. It is known that DHEA is involved in a wide variety of functions. Taking the hormone may have a multiplicity of adverse and long-term effects. Such data are not yet available.
Another hormone, cortisone, was also once reputed to be a miracle drug or "cure-all," but was found to be much more complex than initially thought. Serious side effects and multiple injuries occurred. High dosages must be quickly tapered; or the adrenals quit producing cortisol.ix
In most cases, DHEA "supplements" are synthetic (artificially prepared) steroid hormones. Synthetic forms are used in scientific studies and in tests by drug companies. The same drug "in pharmacologically adequate doses" is available from health food stores and supplement companies. Often DHEA is sold as an extract of wild yam labeled as "natural DHEA" or "DHEA precursor complexes." But, there is NO DHEA in Mexican wild yam and there are NO precursors in the yam which can be converted into DHEA or any other steroid hormone in the body. This can only be achieved by a series of 6 to 8 chemical reactions in the laboratory used to convert plant extracts into DHEA precursors or other steroid hormone precursors.
A leading expert in the field, Seymour Lieberman, explains: "A comparable series of reactions is not known to exist in nature and certainly not in humans. Consequently, it is highly unlikely, perhaps impossible is a better word, that the ingestion of extracts of the Dioscorea plant [wild yam] will lead to the formation, by metabolic transformation of the relevant plant constituent, to either pregnenolone or DHEA."
Additionally, it is not known if the commercial DHEA pills, whether synthetic or chemically altered ("semisynthetic") wild yam, can be naturally sulphated and thus safely neutralized in the body. In either form, it is a drug, something foreign to the body, actually foreign to nature.x
STUDIES AND CLAIMS
So far, the claims made for DHEA supplementation "lack sufficient clinical evidence to back them up." Most claims are based on rodent studies, certainly not conclusive or applicable to humans since mice and rats do not produce DHEA.
One small study at the University of California showed that older people felt better on DHEA -- the majority reporting an increase in physical and psychological well being. This is a far cry from the "fountain of youth" reference. Many drugs and synthetic hormones produce the same euphoric feeling, usually due to the xenobiotic (foreign substance) reaction of being rushed through the circulation for maximum excretion in the urine.xi
In the follow-up study, as Arlene Morales of the University of California, relates: "We didn't get the same positive reports of wellbeing. So it's not clear what effect, if any, DHEA has on energy or mood."xii
The claim that experimental mice do better and live longer on DHEA than those not on the hormone is "not true," according to Richard Weindruch, University of Wisconsin. "DHEA does not prolong the lives of my laboratory mice, and may even shorten their life span."xiii
As for heart disease, a study in 1986 showed that men with high blood levels of DHEAS had about half the incidence of heart disease as those with low levels. Conversely, women with high DHEAS levels had higher risk. Follow-up studies of the SAME patients over longer periods of time did not produce the same results.
Tissue culture, animal studies, and epidemiologic studies "suggest" that DHEA may inhibit atherosclerosis via its powerful antiproliferative effects. Findings of a clinical study "suggest" DHEA inhibits platelet aggregation. Nevertheless, many clinical investigations will be needed to "convincingly establish" that DHEA will have "beneficial" drug reactions.xiv
There are reports indicating that DHEA boosts the immune system and may be beneficial in autoimmune disorders. For instance, low DHEA levels in the blood have been associated with breast cancer. "As far as I am aware, says Dennis Wang, who helped direct the Guernsey study which discovered low DHEA blood levels in women who developed breast cancer, "there's no good evidence that DHEA affects the development or prognosis of breast cancer." Three other studies found that women who got breast cancer were no more likely to have had lower DHEA levels than comparable women who remained free of cancer.xv
Two other studies -- one with women who developed ovarian cancer and one with postmenopausal women with breast cancer -- revealed there were higher DHEA levels years before the development of disease.xvi
Persons with systemic lupus who were given 200 milligrams (mg) DHEA daily experienced symptom improvements. A study of people with multiple sclerosis reported increased feelings of strength, stamina, and well-being, but no reduction in disability. Postmenopausal women on a 50 mg daily dose appeared to experience increases in the activity of natural-killer cells (white blood cells). Allusions to other immune system "responses" have been made or tested. But so far, either the studies have been performed on laboratory animals, the effects have been symptom-masking only (a pharmaceutical, NOT nutritional, effect) or the results have been controversial.xvii
Studies of DHEA as a vaccine adjuvant for elderly patients have been made. The tetanus study showed the hormone had no significant effect. In the influenza vaccine study, more volunteers given DHEAS had "influenza hemaglutination inhibition (HAI) titers" -- an antigen response seen under the microscope, but not yet seen in preventing flu.xviii
The claim that, no matter what a person eats, he/she will still lose weight by taking DHEA is "totally false." Arthur Schwartz of the Fels Institute for Cancer Research and Molecular Biology, states: "No human data exist whatsoever that show that DHEA can help a person lose weight."xix
One small study did show that eight older men taking DHEA for six months lost fat and gained muscle. Yet six other studies with men and women found no change in body fat.xx
Does DHEA stimulate the libido? Only one study so far asked the question. Volunteers reported no change in sexual desire while taking DHEA. No well designed study has looked at sexual activity and DHEA.xxi
Some researchers believe that DHEA might protect against non-insulin dependent diabetes. In one small study, 15 postmenopausal women were found to have enhanced insulin sensitivity when given 50 mg a day. "Whether this effect is reproducible in larger studies remains to be determined..." Additionally, "the role of insulin in regulating adrenal androgen secretion is controversial."xxii
The claim that DHEA prevents osteoporosis is "not proven," says Elizabeth Barrett-Connor, University of California. In her 1993 study, more DHEA in the blood did not mean denser bones even after 16 years.xxiii
A clinical trial is now testing DHEA on Alzheimer's patients, but the researchers are not optimistic since "there is no evidence that it helps." Most studies have not found lower levels of DHEA in such patients.xxiv
In short, there is too much not known or understood about DHEA. No one knows whether the effects of the naturally produced DHEA come from the hormone (including sex hormones) it is converted into. It is not certain which organs it affects and how it does so. "Human hormones are powerful chemicals," and administering a synthetic hormone can be risky, often dangerous.
In one experiment, 14 out of 16 rats given DHEA developed liver cancer. Of course, this does not necessarily mean the results are applicable to humans. However, "if this were an experimental drug, it would be banned by the FDA on this basis." When taken as a pill, DHEA first must be broken down in the liver - normal detoxification for any drug. Excessive amounts may stress or damage the liver.
Adverse effects can and do occur, such as increased insulin resistance, a drop in HDL (the so-called "good" cholesterol), mood swings, fatigue, transient hepatitis, elevations in liver function tests. In women, there can be hair loss, acne, hirsutism (excessive body and facial hair), breast tenderness and swelling, irritability, menstrual changes, deepening of the voice, etc. In men, acne and gynecomastia (breast enlargement) have been reported.
Concern is growing regarding the possibility of increased risk of ovarian and breast cancer in women as well as prostate cancer in men. Taken by younger people, DHEA supplements might suppress the body's natural production of the hormone. Many doctors and researchers recommend that a DHEA serum level be measured before anyone starts taking a supplement and that the level be checked periodically. xxv
Arlene Morales, co-author of the two largest DHEA trials, says: "It's crazy that people can walk into a store and buy DHEA without a prescription." At the levels given in the studies (50 to 100 mg a day), higher-than-normal levels of male hormones were produced in women, "and we don't know what that does to women over long periods of time."xxvi
Alan R. Gaby, M.D., notes that women whose adrenal glands do not produce sufficient cortisol could create more adrenal insufficiency problems using DHEA. "DHEA is an anabolic steroid. Remember all the fuss about male bodybuilders who damaged their livers by taking anabolic steroids? There are no long-term studies to show what DHEA could lead to..." xxvii
Extremely important questions remain unanswered. "No one has yet tracked a large group of people over time to determine whether individual changes in DHEA concentrations can be used to predict subsequent disease. There have been no large clinical trials to determine whether taking DHEA is effective in staving off degenerative diseases or whether it is safe for long-term use." xxviii
A physician publication, The Medical Letter, states: "There is no convincing evidence that DHEA has any beneficial effect on aging or any disease. Patients would be well advised not to take it." xxix
Since DHEA made by the body appears to be a precursor to some childhood growth hormones and sex hormones prior to the full maturation of the ovaries or testes, it would make sense that growing and developing children have a much greater need (and production) of it than mature individuals whose growth and development have essentially ceased. To "replace" a hormone that the body itself may reduce at a certain age is at least questionable if not hazardous. xxx
If DHEA/DHEAS levels are lower than normal (although there is wide variance) for a person's age, the reasonable and safe approach would be to support the health and function of the adrenal glands as well as endocrine balance - to reinforce biochemical equilibrium rather than perhaps further disrupting it. Nutritionally, a supplement schedule could include a multi-glandular support, adrenal B complex, wheat germ oil, essential fatty acids, and alkaline-ash minerals. As is true with all steroids, DHEA is made from cholesterol, so some whole food sources in the diet can only be supportive. Years ago, Dr. Royal Lee presented an appropriate principle: "All synthetic drugs [and DHEA is a drug] have had the same unfortunate history as a general rule. Thyroxin [thyroid hormone] was made synthetically, put on the market, vast quantities sold on prescription, and its toxic properties discovered the hard way, simply because the unwarranted conclusion was drawn that it was identical in action with the natural hormone." Is it déjà vu all over again? xxxi
i Stephen Cherniske, M.S., The DHEA Breakthrough, Ballantine Books, 1996.
ii A. Skolnick, JAMA, Vol.276, No.17, 6 Nov. 1996, pp.1365-1367.
iii University of California at Berkeley Wellness Letter, Vol.12, Is. 4, Jan. 1996, pp.1-2; B. Carey, Health, Vol.9, No.7, Nov./Dec. 1995, pp.69-74.
iv C. N. Falany, et al., Dehydroepiandrosterone (DHEA) and Aging, Annal, NY Academy of Sciences, Vol.774, 1995, pp.59-72; J. E. Nestler, Ibid., pp.ix-xi.
v P. J. Hornsby, Ibid., pp.29-46.
vi A. Vermeulen, Ibid., pp.121-127; T. Valentine, True Health, Fall 1996, pp.1-10.
vii A. Vermeulen, Dehydroepiandrosterone (DHEA) and Aging, p.124.
viii Ibid., p.124; B. Araneo, et al., Ibid., p.232; D. Williams, Alternatives, Vol.5, No.20, Feb. 1995, pp.158; F. DelaTorre, et al., Clinical Experimentia in Rheumatology, Vol.13, 1995, p.345.
ix D. Howe, The ANMA & AANC Journal, Vol.1, No.3, June/July 1996, pp.21-22; Williams, Alternatives, Feb. 1995, pp.158-159
x Wellness Letter, Jan. 1996, p.2; Valentine, True Health, Fall 1996, pp.5-6; E. L. Knight, Ph.D., Medical Update on Vitamins and Herbs,Vol.1, No.4, Oct. 1996, pp.1-4; Wm. Douglass, Second Opinion, Vol.VI, No.10, Oct. 1996, pp.1-6; R. Sahelian, Health Freedom News, Vol.15, No.4, Sept./Oct. 1996, pp.44-45.
xi A. Morales, et al., Journal of Clinical Endocrinology & Metabolism, Vol.78, 1994, p.1360.. xii D. Schardt and S. Schmidt, Nutrition Action Healthletter, Vol.24, No.2, March 1997, p.5. xiii Ibid., p.3.
xiv Wellness Letter, Jan. 1996, p.1; Skolnick, JAMA, 6 Nov. 1996, pp.1366-1367; Nestler, Dehydroepiandrosterone (DHEA) and Aging, p.x; E. Barrett-Connor, et al., Ibid., pp.259-270.
xv Schardt and Schmidt, Nutrition Action Healthletter, March 1997, p.4.
xvi Cancer Research, Vol.52, 1992, p.1; JAMA, Vol.274, 1995, p.1926.
xvii Douglass, 5; Health Facts, Vol.XXI, No.210, Nov. 1996, p.3; Harvard Women's Health Watch, Vol.III, No.7, Dec. 1996, p.6.
xviii Skolnick, JAMA, 6 Nov. 1996, p.1366.
xix Schardt and Schmidt, Nutrition Action Healthletter, March 1997, p.4.
xx Ibid., p.4; E. Barrett-Connor, et al., Dehydroepiandrosterone (DHEA) and Aging, pp.259-270.
xxi Schardt and Schmidt, Nutrition Action Healthletter, March 1997, p.4-5.
xxii Skolnick, JAMA, 6 Nov. 1996, p.1367;
Vermeulen, Dehydroepiandrosterone (DHEA) and Aging, p.123.
xxiii American Journal of Epidemiology, Vol.137, 1993, p.201.
xxiv Schardt and Schmidt, Nutrition Action Health letter, March 1997, p.5.
xxv Wellness Letter, Jan. 1996, p.2; Valentine, True Health, Fall 1996, p.6; Health Facts, Nov. 1996, p.3; J. Challem, Natural Health, Vol.26, No.6, Nov./Dec. 1996, p.130; Skolnick, JAMA, 6 Nov. 1996, p.1367; B. Bilger, The Sciences, Vol.35, No.5, Sept./ Oct. 1995, pp.26-30; K. Ullis, K. Patel, The Sciences, Vol.36, No.3, May/June 1996, p.3; Knight, Medical Update on Vitamins & Herbs, Oct. 1996, p.3; L. Milewich, Dehydroepiandroserone (DHEA) and Aging, pp.149-170.
xxvi Schardt and Schmidt, Nutrition Action Healthletter, March 1997, p.4.
xxvii Women's Health Letter, Vol.VI, No.2, Feb. 1997, p.7.
xxviii Harvard Women's Health Watch, Vol.III, No.7, Dec. 1996, p.6.
xxix Health Facts, Nov. 1996, p.3.
xxx Valentine, True Health, Fall 1996, p.7.
xxxi Royal Lee, Lecture, International Association of Liberal Physicians, New York, NY, Oct.23, 1943.
Originally published as an issue of Nutrition News and Views, reproduced with permission by the author, Judith A. DeCava, CNC, LNC.