Dehydroepiandrosterone (DHEA) hormones are the most abundant steroids in the human body. Low levels of DHEA are associated with aging and disease states. Specifically, a deficiency of DHEA has been found to correlate with immune dysfunction, inflammation, greater risk of certain cancers, heart disease in men, and osteoporosis. The special interest in DHEA replacement, however, stems from its function as a prohormone, meaning a precursor to a great variety of beneficial steroids, both in the estrogenic and androgenic family, on an “as-needed” basis.
Perhaps the most exciting new finding relates to the antiatherogenic benefits of DHEA. The dramatic aging-related drop in DHEA levels is accompanied by an equally dramatic rise in cardiovascular disease. We have now come closer to elucidating the cardioprotective mechanism of DHEA. It appears that DHEA is incorporated into both high and low-density cholesterol, protecting it from oxidation. In the aged, however, cholesterol-bound DHEA becomes virtually undetectable, and the cholesterol molecules are much more susceptible to oxidation than in young individuals. But this is not the end of the story. It turns out that DHEA also increases the activity of platelet superoxide dismutase (SOD), one of our most important antioxidant enzymes. Thus, DHEA seems to play an essential role as part of the body’s antioxidant defence.
Another recent finding involves the anti-inflammatory properties of DHEA. It has been known for a long time that DHEA can lower the levels of interleukin-6 (IL-6), a pro-inflammatory cytokine (meaning a chemical messenger used by the immune system) that seriously escalates the inflammatory process, recruiting immune cells that often end up destroying healthy tissue as well. Now it has been established that DHEA can lower the production of another inflammatory cytokine as well, one called tumor necrosis factor alpha (TNF-alpha). The levels of both IL-6 and TNF-alpha rise with aging, showing an increased inflammatory state and possible immune dysfunction. The role of DHEA in regulating the immune response has been shown to include also the enhanced secretion of interferon-gamma. The decline in DHEA levels is closely tied to immunosenescence.
This is excellent news for those who suffer from chronic inflammatory diseases. However, it could be argued that aging itself is, in a sense, a chronic inflammatory state. The levels of various chemical mediators of inflammation, such as IL-6 and TNF, increase as we age. At the same time, our production of DHEA plummets with aging. Maintaining youthful levels of DHEA means less chronic inflammation. It should be pointed out that chronic inflammation is known to play a critical role in the development of the killer diseases of aging: heart disease, Alzheimer’s disease and certain types of cancer.
More good news includes also the finding that DHEA protects brain tissue under conditions simulating stroke and trauma damage, and is likely to be involved in protecting the brain against the development of Alzheimer’s disease. The neuroprotective mechanism of DHEA appears to go beyond its anti-glucocorticoid effect, that is, its ability to antagonize the harmful effects of cortisol; anti-inflammatory action is likely to be involved as well. DHEA has also been shown to lower hyperglycemia (elevated blood sugar) in diabetic rats, and protect their kidneys from the damage caused by high blood sugar. In addition, DHEA enhances the immune response and helps us fight infection; several studies have confirmed its usefulness in combating bacterial, parasitic and viral infections, including HIV. DHEA also helps protect the thymus against cortisol-induced atrophy.

Speaking of cortisol, we are beginning to understand that it is the ratio of DHEA to cortisol that is of critical importance in aging and certain diseases such as AIDS. A recent French study done at the Pasteur Institute in Paris found that the minority of patients who do not succumb to the severe side effects of highly aggressive antiretroviral therapy show a normalized DHEA/cortisol ratio. The majority of AIDS patients, however, have an abnormally low DHEA/cortisol ratio and thus suffer from symptoms usually associated with excess cortisol, even though their cortisol levels are within normal. Cardiac patients and the victims of Alzheimer’s disease also show low DHEA/cortisol ratio. The manipulation of this crucial ratio, including DHEA therapy, could prove highly significant both in the treatment of AIDS and in anti-aging medicine in general. In fact, a small pilot study has already indicated that DHEA combined with an anti-inflammatory drug such as indomethacin can moderate or even normalize the various pathological changes of AIDS-related lipodystrophy.

One surprising finding showed that an 80 mg/day dose of DHEA can help some infertile patients ovulate and become pregnant, making previously ineffective ovarian stimulation succeed at last (in one case, the result was twins!). An animal study confirmed that DHEA is important as a steroidogenic substrate (precursor of other hormones) in ovarian production of various sex steroids. Interestingly, immunomodulatory 7-hydroxy metabolites of DHEA have also been discovered in human semen, with possible further implications for fertility. In postmenopausal women, research on DHEA replacement continues to indicate improved well-being and libido, among many other benefits. We are also closer to understanding the mechanism through which DHEA enhances the sense of well-being: it significantly increases the levels of beta-endorphins.

Those readers who are considering following a ketogenic (low-carbohydrate) diet may be interested in a small study done on rheumatoid arthritis patients: the low-calorie ketogenic diet using less than 40 g of carbohydrates per day resulted in a 34% rise in DHEA within a week; the ketogenic diet was as effective as sub-total fast in raising DHEA levels. This study needs to be replicated, however, using a larger number of healthy subjects. In primates, calorie restriction has indeed been found to preserve higher DHEA levels, indicating a slower rate of aging. In humans, fasting is known to raise DHEA levels in both sexes. Anorexic and bulimic women likewise show higher serum DHEA. Exercise can also raise DHEA in some individuals, possibly due to the inverse relationship between DHEA and insulin. Finally, while meditation has long been known to increase DHEA, participation in drum circles has also been shown to increase DHEA and DHEA/cortisol ratio, confirming the hypothesis that stress reduction in general boosts DHEA production, probably through a shift of adrenal steroidogenesis from cortisol to DHEA. High insulin, high cortisol and low DHEA constitute a large part of the pathological endocrine profile of aging. Restoring the correct hormonal ratios should be one of the primary goals of any anti-aging program.