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Why DHEA May Be the Best-Validated Anti-Aging Supplement

November 2006

By Julius Goepp, MD

A review of the published scientific literature reveals that DHEA (dehydroepiandrosterone) may be the best-validated anti-aging supplement currently available. Brand-new studies indicate that DHEA is even more effective than previously demonstrated.

DHEA was introduced to Americans by the Life Extension Foundation in 1981. For nearly two decades, a battle raged between health freedom activists who wanted free access to DHEA and government bureaucrats who wanted to ban it.

The tide turned in 1996, after two Life Extension members were arrested for importing DHEA for personal use. Attorneys hired by the Life Extension Foundation proved that DHEA was not a controlled substance and was indeed perfectly legal to buy and sell.

The last two years have produced a torrent of positive research findings concerning DHEA. As most members know, DHEA is abundantly produced in healthy young adults, but its levels decline dramatically with advancing age,1,2 coinciding with the onset of numerous diseases of aging.2-7

While DHEA’s demonstrated anti-aging benefits have made it a popular supplement, powerful new evidence supports DHEA’s critical role in alleviating depression,8,9 enhancing endothelial function,10-12 preventing atherosclerosis,13-15 increasing bone mass,16-18 slowing osteoporosis,16-18 improving insulin resistance,19,20 and even hastening wound healing.21,22

Despite its ever-growing list of health benefits, however, DHEA remains under political attack. Its frequent mischaracterization as an “anabolic steroid” has led some in Congress to call for outlawing DHEA.

Fortunately, thanks to the concerted efforts of key lawmakers and champions of health freedom, DHEA remains readily available to all health-conscious adults who seek to reap its far-ranging, multifaceted benefits.

DHEA Supports Mood and Sexual Function

In just the last two years, researchers have published exciting new findings that underscore DHEA’s value in alleviating depression, improving sexual function, and managing the symptoms of schizophrenia.

Building on earlier results pointing to DHEA’s promise in treating major depression,9 in 2005 researchers conducted a double-blind, placebo-controlled trial of 46 men and women with major or minor depression.8 The subjects received 90 mg of DHEA per day for three weeks and 450 mg per day for an additional three weeks. Treatment with DHEA produced dramatic gains on standard depression rating scales, with half the subjects showing a 50% or greater improvement. The DHEA-supplemented subjects also recorded significant improvements on a score of sexual function. The researchers concluded that DHEA is effective in treating depression when used in the absence of prescription antidepressants.8

DHEA’s effects in combating depression were further confirmed in a study published in early 2006. Scientists treated 145 HIV-positive patients showing signs of depression with either DHEA at a dose of 100-400 mg per day or a placebo.23 Outcomes were measured using standard depression rating scales. DHEA proved superior to placebo in alleviating depression, with 56% of the DHEA-treated patients showing improvement compared to 31% in the placebo group.


DHEA is the most abundant steroid in the human body.31 Although primarily produced in the endocrine glands, DHEA technically is not a hormone, but rather a “prohormone,” or hormone precursor.32 In many organ systems, it is converted to the so-called “sex hormones”—the androgens and estrogens—by enzymes located in the tissues.33 DHEA is synthesized from cholesterol in a series of enzymatic reactions that occur in the adrenal glands, liver, and small intestine. Most DHEA in the body is bound to a sulfate molecule, and thus referred to in this form as dehydroepiandrosterone-sulfate, or DHEA-S. When a person orally ingests DHEA supplements, a sulfate molecule is added as it passes through the liver. The sulfate attachment appears to be necessary to keep the entire molecule inactive until it reaches its target tissues. Both DHEA and DHEA-S were used in studies cited in this article.

Unfortunately, DHEA levels decline with advancing age,1,2 and this falloff is more pronounced in men than in women.1 Some scientists believe that the drop in levels of DHEA and DHEA-S—and the consequent decline in levels of testosterone and estrogen—may be related to many common age-related conditions, including diseases of the nervous, cardiovascular, and immune systems.2-4 Other conditions now believed to be related to diminished levels of DHEA and its end products include cancer, osteoporosis, and type II diabetes.2,5-7

A common thread running through some of these various conditions is the so-called “metabolic syndrome,” which appears to underlie deleterious alterations to the blood vessel linings and the way in which the body metabolizes many vital nutrients, including glucose and calcium.5-7

Sexual function is closely linked with emotional health and well-being, and scientists now know that DHEA levels are strongly associated with healthy sexual function. Two notable studies from 2005 found that sexual function24 and overall self-reported health and functional status25 were better among women with relatively high levels of DHEA-sulfate (DHEA-S). Even low-dose DHEA supplementation may be effective in providing these benefits. For example, in a group of women with systemic lupus erythematosus, daily doses of DHEA as low as 20-30 mg improved health-related quality of life and sexual interest and activity compared to placebo.26 Other researchers have reported notable improvements in libido and mood in women who supplemented with DHEA.27,28

Even more promising are several recent studies from 2005 suggesting that, in addition to its positive impact on depression and sexual function, DHEA may help to manage symptoms of schizophrenia. Based on their preliminary findings demonstrating DHEA’s efficacy in reducing symptoms of schizophrenia,29 researchers further noted improvement in illness severity and anxiety in a group of schizophrenic patients who received DHEA in addition to their anti-psychotic medications.30 The study authors attributed this specific anxiety-reducing effect to DHEA’s influence on the brain’s GABA receptors, which are central to regulating mood.30

DHEA Protects Arteries, Promotes Cardiovascular Health

Extremely positive findings about the cardiovascular benefits of DHEA were reported in the Massachusetts Male Aging study. Researchers confirmed that men with higher DHEA-S levels were less likely to have heart disease,13 suggesting a valuable role for DHEA in averting the nation’s leading cause of death.

Additionally, higher DHEA levels seem to positively affect endothelial cell signaling, which could have important implications for avoiding heart disease. In a subset of men from the Baltimore Longitudinal Study of Aging,14 levels of hormones (including DHEA-S) were measured and correlated with arterial stiffness, as measured using ultrasound imaging of the carotid arteries. Men with higher levels of total and free testosterone and DHEA-S had less stiffness of the arteries, indicating a decreased risk of cardiovascular events such as heart attacks.

A similar link between low serum DHEA-S levels and greater risk for carotid artery disease was demonstrated last year in a study of young women with polycystic ovary syndrome, a condition associated with an increased risk of cardiovascular disease and metabolic syndrome.15

A study in animals in 2006 shed further light on how DHEA promotes cardiovascular health.34 Researchers fed young and old female mice a daily DHEA-S supplement. After 60 days of treatment, the investigators measured the stiffness of the test animals’ left ventricle, the heart’s major pumping chamber. The DHEA-S-supplemented older mice had decreased left ventricular stiffness compared to the non-supplemented older animals. The scientists concluded that DHEA-S supplementation is capable of reversing the left ventricular stiffness that accompanies aging, thus promoting youthful structure and function in the heart’s tissues.

Another animal study simulated the depressed cardiovascular function (shock) that follows major trauma.35 Researchers gave male rats doses of a DHEA metabolite. This treatment reversed the depression of cardiovascular function and organ blood flow induced by shock. Scientists were able to measure that plasma levels of the inflammatory cytokine interleukin-6, which had been elevated in the state of simulated shock, were promptly reduced by treatment with the DHEA metabolite. The investigators concluded that treatment with a DHEA metabolite could be valuable in restoring cardiovascular function and correcting abnormal cytokine levels.

Furthermore, investigators determined that DHEA-S injected directly into the coronary arteries of pigs produced acute dilation of the blood vessels, with associated increases in coronary blood flow.36

DHEA Improves Blood Flow and Endothelial Function

Strong new evidence indicates that DHEA and DHEA-S help protect aging adults against atherosclerosis and its life-threatening consequences such as coronary artery disease.10,11,37 Several mechanisms of action may account for these benefits.

In one blind, placebo-controlled trial, 24 older men orally ingested 50 mg of DHEA or a placebo at bedtime for two months. The researchers then measured arterial dilation and increased blood flow. While the placebo-treated subjects had no changes in any of the parameters measured, the DHEA-treated men experienced increased levels of a substance that helps blood vessels to dilate, as well as decreasing levels of a marker for blood clotting. They also had lower levels of artery-clogging low-density lipoprotein (LDL) after treatment than did the controls. The researchers concluded, based on the beneficial effects of short-term DHEA treatment, that long-term DHEA supplementation may prevent atherosclerotic changes caused by falling levels of vessel-dilating biochemicals.37

Higher DHEA-S Levels Tied to Lower Mortality Risk

Of the many tactics that can be deployed to increase one’s life span, supplementing with DHEA seems to be one of the most beneficial, as new findings imply that higher levels of DHEA are associated with a longer life span.38

Scientists recently examined data on nearly 1,000 older Taiwanese adults to determine the relationship between DHEAS levels and three-year mortality risk.

At the study’s end three years later, the data analysis revealed that participants with lower DHEA-S levels had a 64% greater risk of death than did individuals with higher DHEA-S levels. The study authors concluded that lower levels of DHEA-S have a notable effect in increasing mortality risk, and that optimal DHEA-S levels may help to promote longevity.38

Previous studies have shown that platelet levels of an important vasodilating agent decrease with age, apparently due to the diminished efficiency of enzyme systems that are involved in their production.10 These changes may also influence platelet “stickiness,” which tends to increase with age. These tendencies toward decreased vasodilation and increased platelet aggregation over time may be defining features of the relationship between impaired endothelial function and atherosclerosis.12

A study in 2003 investigated the effect of DHEA supplementation (25 mg per day) on endothelial function, an instigating factor in the development of atherosclerosis.11 The investigators examined how the diameter of the large artery in the upper arm known as the brachial artery responded to blood-flow demands in DHEA-treated and placebo-treated men. Significantly, researchers found increases in blood vessel dilation—and therefore increased blood flow—in the DHEA-supplemented group. As in the study just described, investigators also found decreased plasma levels of a clotting agent in the treatment group. Finally, plasma glucose levels decreased significantly and safely in the treated group compared to controls. According to the authors, low-dose DHEA supplementation improved endothelial function, increased insulin sensitivity, and decreased blood-clotting tendency11—all factors that may slow the development of numerous age-related disorders, including heart disease and metabolic syndrome.