DHEA: The Measure of Our Youth It hardly seems fair. While human life expectancy has risen from an average of 49 years in 1900 to over 76 years today, the actual age at which one's body naturally begins to deteriorate, typically in the middle to late twenties, has increased little. Around this age, muscles begin to weaken, metabolism slows, lowering the rate at which calories are burned, hair starts to thin, and hearing begins to fade. As one's thirties roll along, laugh lines and fine furrows appear around the mouth and eyes as skin begins to lose elasticity, women notice the appearance of age spots, and extra effort is required to maintain cardiovascular fitness, an increasingly important factor for men, whose LDL count (the bad cholesterol) continues to climb. Why, by the time we have achieved (it is hoped) a measure of success in our careers and personal lives, we are already sliding down the slippery slope of physical decline, older and wiser,perhaps, but almost certainly weaker and sicker as well. However, research into promising new treatments for aging-related diseases, coupled with advances in our understanding of the actual mechanisms of aging, offers the hope that it soon may be within the means of science to preserve, or at least to recreate, the days of our youth. Perhaps the most exciting of these treatments centers on a hormone known as dehydroepiandrosterone, or, more mercifully, DHEA. DHEA is the most abundant naturally occurring steroid hormone in the body. It is produced by the adrenal gland, which secretes many other hormones, like adrenaline. DHEA is often referred to as a "motherlode" hormone because the body converts it into active hormones such as testosterone and estrogen, substances essential for, among many critical functions, regulating libido, metabolism, and forming muscle mass. A growing body of research suggests that DHEA may have a number of vital medical applications, including bolstering immunity in the elderly, inhibiting certain cancers, and combating atherosclerosis, Alzheimer's disease, lupus, diabetes, and obesity. Moreover, there is mounting evidence that the level of DHEA in a person's blood is a good predictor not only of the incidence of afflictions commonly associated with aging, such as cancer, cardiovascular disease, and memory disorders, but of aging itself. As people age, levels of DHEA decrease so that by age 65 production of the hormone is only 10 to 20 percent of that in the average 20-year old. Because one of DHEA's primary roles is to protect against bacterial and viral infections, this fall in its production has been closely correlated with a, general weakening of the immune system. At birth, the reference range for DHEA is 1.7-3.6 micrograms/milliliter for both males and females and peaks at 1.4-7.9 mcg/ml for males and 0.7-4.5 for females between age 20-29. Although many other hormones also are important in warding off disease, DHEA has been found to confer protection against a wider range of viruses and infections, several of which, such as streptococcus, are potentially lethal. Researchers are particularly excited about studies done on mice (whose response to vaccinations is similar to old humans) in which a single dose of DHEA administered with a vaccine stimulated a powerful antibody response characteristic of young mice. And though it is premature to draw definitive conclusions from these experiments alone, there is hope DHEA may stimulate a parallel immune reaction in people, which would be critical for delaying the onset of disease in the elderly. Indeed, the implications of these findings, says Richard Hodes, head of the National Institute on Aging, are "extremely interesting and potentially important." DHEA's usefulness as a factor to forecast and assess one's risk for cancer is equally exciting. Epidemiological studies suggest that the risk of developing a number of cancers strongly relates with serum or urine levels of DHEA or its chemical relative, DHEAS (DHEAS is 300-500 higher in concentration than DHEA). A low level of the hormone in the bloodstream has been linked with gastric, prostate, and bladder cancer. As of today, more research is required to ascertain the hormone's actual value in cancer treatment. To wit, there is concern among some clinicians that DHEA, which is close in composition to sex hormones, might cause enlargement of the prostate, and consequently many physicians caution against its therapeutic use in cases of prostate abnormality. Furthermore, animal studies suggest that DHEA may both promote and suppress the growth of mammary tumors, raising concerns that in women it may heighten the risk for breast cancer. DHEA also exhibits promise in treating atherosclerosis, a disease in which small deposits of fat, called plaque, accumulate on the inner walls of the arteries. One study stretching nearly 20 years showed DHEAS levels in men who died of coronary heart disease to be appreciably lower than those of men whose levels were normal. In rabbits with the disease, DHEA reduced plaque by almost 50 percent over controls whose DHEA levels were lower. And in yet another experiment, low levels of the hormone were found in 32 men (aged 26-40 years) who had suffered myocardial infarction, reinforcing the view that DHEA was a predictor, and quite possibly a cause, of atherosclerosis. These and other similar findings have the medical community abuzz regarding DHEA's value in defeating this leading killer. While a cure for Alzheimer's disease continues to elude researchers, evidence increasingly suggests that DHEA is essential in maintaining the function of brain cells. Recent studies indicate that Alzheimer's patients' DHEA levels are uniformly lower than people without the disease; further, DHEA and DHEAS sink to markedly low levels later in life, when the incidence of the disorder is much higher. In vitro studies of mice show that even minimal doses of the hormones lessen amnesia and augment long-term memory. Thus, neurologists speculate that DHEA supplementation in humans may be an important ingredient both in slowing the progression of Alzheimer's and in treating the sort of degenerative memory disorders that often arise in old age. Systemic lupus erythematosus is a chronic inflammatory disease in which the immune system causes abnormalities in blood vessels and connective tissues that can damage the kidney, nervous system, joints, and skin. Moreover, because lupus is commonly treated using large doses of steroids and cancer chemotherapy agents, the side effects of therapy are often worse than the disease itself. In a test of DHEA on 57 women with lupus, Stanford University researchers say that roughtly two-thirds of the subjects reported some alleviation of their symptoms, including a reduction in the severity and frequency of rashes, joint pain, headaches, and fatigue. According to Dr. James McGuire, one of the leaders of the study, many of the women also reported a heightened tolerance for exercise and an improvement in concentration. These encouraging results have spurred the Food and Drug Administration to facilitate further clinical trials to evaluate DHEA's efficacy as an alternative to conventional lupus therapy. In the 1980s, Dr. Arthur Schwartz of the Fells Institute for Cancer Research and Molecular Biology at Temple University discovered another effect of DHEA: It induced weight loss in laboratory animals irrespective of much food they consumed. This dramatic result has prompted researchers to study DHEA's use as a weight-loss therapy for humans. One explanation for this property of DHEA is that it increases the release of cholecytokinin (CCK), a hormone responsible for signaling the brain when the body has ingested enough food to feel satiated, or "full." Rats fed DHEA produced higher levels of CCK, lowered their intake of food, and showed a consonant decrease in body fat. It is also believed that DHEA alters metabolism by causing the body to shift glucose metabolism from the production of fat to the production of energy. In a study where DHEA was given to five normal weight males for 28 days (and where diet and physical activity were controlled), 4 of the 5 subjects experienced an average fat loss of 31 percent. Most significantly, perhaps, none of the four exhibited an aggregate change in weight, meaning that the loss in fat was balanced by a proportional gain in muscle. Because weight gain in older adults is often accompanied by mature-onset diabetes, experts suspect that this higher incidence of the disease is a function of the steep decline in DHEA levels associated with advancing age. DHEA has been found to inhibit development of diabetes in rats genetically predisposed to it, and some clinicians report that, in humans, DHEA reduces the need for insulin. A related finding suggests that the higher incidence of cardiovascular disease in diabetics is caused by elevated levels of insulin that, in turn, act to lower levels of DHEA. Anti-aging medicine specialists list the diseases mentioned in this article-cancer, atherosclerosis, diabetes-as principal benchmarks of aging, which is why many of these same experts point to DHEA as perhaps the most useful indicator of aging and longevity. Research has shown that DHEA can prolong life span in laboratory animals by 50 percent, while mice given the hormone actually appear to age slower, maintaining the glossiness and coat color of their youth. Says Dr. Ronald Klatz, president of the American Academy of Anti-Aging Medicne," DHEA is undeniably one of the most crucial predictive factors in diagnosing aging-related diseases, and it may turn out to be an effective anti-aging medication as well." Also undeniable is that the outlook for DHEA research is excellent. Once disparaged as of minor interest by the scientific establishment, this remarkable little molecule has become the subject of intense scrutiny. DHEA research currently is being underwritten by the National Institute on Aging, the National Cancer Institute, the National Institutes of Health, the American Cancer Society, and other major scientific agencies. Moreover, it is being investigated for its possible use in a host of other areas, including AIDS, osteoporosis, Epstein-Barr viral infections, chronic fatigue syndrome, menopause, depression, herpes, and even stress. Pending the results of long-term human studies of DHEA, the FDA has yet to approve the substance, while its proponents are lobbying hard to make it available at least as an experimental drug. However, what is certain is that DHEA's promise as a defense against the scourge of aging and the degenerative diseases aging engenders is, for all of us, enormous. References Bird, C.E. et al. "Dehydroepiandrosterone: Kinetics of Metabolism in Normal Men and Women." Journal of Clinical Endocrinology and Metabolism, 47:818-22 (1978). Block, Will. "DHEA Replacement Therapy." Life Extension Report, 13, no. 9 (Sept 1993). Boggs, Carl. "DHEA: The Youth Hormone Can Now be Added Back to the Body With Full Rejuvenating Potential." Journal of Longevity Research, 1, no. 1, (1994). Braverman, Eric R. "DHEA and Adrenopause: A New Sign of Aging and a New Treatment." Total Health, 16, no. 1, (Feb 1994). Dilman, Vladimir M. and Ward Dean. The Neuroendocrine Theory of Aging and Degenerative Disease. Pensacola, Florida: The Center for Bio-Gerontology, 1992. Ebeling, Pertti and Veikko A. Koivisto. "Physiological Importance of Dehydroepiandrosterone." The Lancet, 343, no. 8911, (June 11 1994). Fettner, Ann Guidici. "DHEA Gets Respect." Harvard Health Letter, 19, no. 9, (July ,1994). WHAT TREATMENTS ARE BEING TRIED USING DHEA? Abstract # 25 . DHEA AS A MARKER OF AGING AND A THERAPEUTIC PRINCIPAL Julian M. Whitaker, M.D., Medical Director, Whitaker Wellness Institute, Newport Beach, CA. Dehydrepiandrosterone (DHEA) is a steroid hormone produced by the adrenal gland. Synthesized from cholesterol, it is produced in larger amounts than any other adrenal steroid hormone. DHEA isboth a precursor to the sex hormones and functions as a "buffer" hormone. It also has recently discovered independent functions of its own. DHEA has therapeutic potential for many medical conditions including: cardiovascular disease, diabetes, hypercholesterolema, obesity, cancer, Alzheimer's disease, memory deficits, autoimmunediseases, immune disorders including AIDS, chronic fatigue, and osteoporosis. In addition, DHEA has a decided effect on mortality, with studies showing that an increase in blood levels of DHEAsulfate is associated with a 36% reduction in mortality from any cause. An individual's innate blood levels of DHEA reach a peak in his or her mid-twenties and progressively decline from that point. Blood levels of DHEA sulfate are a marker for manydegenerative diseases, including the above-mentioned conditions. Supplemental DHEA is being used clinically for these conditions, as well as for physical and psychological well-being and life extension. Doses vary but as much as 1,600 mg/day have been given for a month without side effects. A recommended initial therapeutic dose is 25 mg/day forwomen and 50 mg/day for men, with monitoring of blood levels every three months and adjusting thedose accordingly. The intent is to maintain levels in the average range for a young adult, regardless of the individual's age. John Cottingham "KNOWLEDGE is of two kinds: we know [log in to unmask] a subject, or we know where we can OR find information upon it." [log in to unmask] Dr. Samuel Johnson