DHEA - The Hormone of Youth?
By Dr. Edward R. Rosick
The quest for immortality is as old as human history. The Spanish explorer Juan Ponce de León searched for the fountain of youth in Florida; today scientists are probing the secrets of our genetic code to find the key to staying young. We know we can slow the aging process through healthy living - good diet, plenty of exercise, no smoking, and, of course, supplementation with vital nutrients - and thus live longer, healthier lives. In the end, though, age will still take its inevitable toll. Whether rich or poor, black or white, powerful or powerless, aging is the great equalizer of us all.
But why do we age? It's obvious that all living organisms change and eventually die as time passes. Gerontologists (scientists who study aging) generally agree that the aging process, and the way some people "age well," is probably due to complex interactions among three factors: heredity, environment, and lifestyle.
Is Aging Caused by Errors?
A current debate among gerontologists concerns two major theories on how aging occurs. The first is called the error theory, in which aging is thought to be caused primarily by external or environmental factors that cause cellular damage, ultimately leading to organ damage and death. The errors may be ours, due to unwise lifestyle choices, or they may be inflicted on us by factors beyond our control.
The error theory is further divided into four subtheories: (1) The wear-and-tear theory holds that cells in the body eventually wear out and malfunction, in much the same way that parts do in cars and other machinery. (2) The cross-linking theory is based on the idea that aging is caused by the accumulation of cross-linked (malformed) proteins that damage cells and eventually lead to organ failure. (3) The free radical theory states that the body sustains continuous cellular damage throughout life through the actions of harmful molecules called free radicals; these molecules are formed when cells turn food and oxygen into energy, and they also arise from outside sources, such as smoking, radiation, and air pollution. (4) The error catastrophe theory postulates that damage to the mechanisms of protein synthesis leads to damage of cells, tissues, and organs, which manifest as the many physical declines of aging.
Or Is Aging Programmed?
Most people remember biblical stories of patriarchs living 900+ years, but the actual maximum human lifespan has long been known to be about 120 years. A few animals, such as the giant tortoise, live longer - up to 150 years or so - than we do. (No mammals outlive us; the supposedly exceptional longevity of elephants has been greatly exaggerated). At the other end of the spectrum, dogs generally live about 10-20 years, depending on the breed, and most small rodents live only 2-3 years. Butterflies (adult phase) live about 3 months. The simple observation that some species live longer than others gives credence to the idea that heredity, or genetic makeup, plays a key role in aging.
The idea that the functioning (or nonfunctioning) of certain genes contributes to the aging process is derived from the other major category of aging theories, calledprogrammed theories, which hold that aging follows a more or less fixed biological timetable, starting at birth and continuing until death. One such theory, theimmunological theory, states that aging is predominantly the result of a progressive decline in the immune system, leading to multiple infectious and noninfectious diseases. By contrast, the endocrine theory states that a person's biological clock is regulated through the production of certain hormones that control the pace of aging.
DHEA - The Body's Most Abundant Steroid Hormone
A hormone that has attracted the attention of many gerontologists isdehydroepiandrosterone, or DHEA. This steroid, first isolated in 1934, is secreted by the adrenal glands, which sit atop the kidneys (ad renal means "by the kidney"). DHEA is secreted into the bloodstream in humans and primates and is converted by the liver to DHEA sulfate, or DHEAS, which is the predominant form (about 90%) of DHEA in the body.* Thousands of scientific articles have been published on the wide-ranging effects of DHEA, yet many questions remain regarding its specific effects and benefits for human health.
*It should be understood that when we speak of DHEA levels in the body, it is really DHEAS that is meant.
One thing scientists do know about DHEA is that it's a precursor to testosterone and estrogen. Testosterone is the hormone that gives men their masculine traits, such as low voices, beards, and large muscles, while estrogen is the hormone (three related hormones, actually) that makes women, well, women. We also know that DHEA is produced abundantly after puberty and peaks in our early to middle twenties. After that, there is a steady decline in the production and secretion of DHEA, by about 10% per decade of life. Some intriguing early studies have correlated the decline in DHEA production with many of the degenerative changes seen in aging, such as heart disease, cancer, and osteoporosis.1
Bad Things Happen When DHEA Is Too Low
Although it's normal (though perhaps not desirable) for DHEA to decline as we age, certain diseases cause DHEA levels to plummet. Addison's disease, or primary adrenal failure, occurs in about 1 in every 25,000 people. Without functioning adrenal glands, the body cannot produce many important steroid hormones, including DHEA. Standard treatment for this condition has been to replace the missing hormones. Until recently, however, most mainstream physicians did not replace DHEA. Furthermore, it was observed that patients with Addison's disease - even those who received standard hormone replacement therapy - consistently reported a reduced quality of life, with symptoms such as persistent fatigue and depression.
A recent study looked at the effects of DHEA supplementation in patients with Addison's disease.1 In this randomized, double-blind trial, 39 patients (15 men and 24 women, aged 25-69) were given either 50 mg of DHEA daily for 12 weeks, followed by a 4-week washout period and then 12 weeks of placebo, or the opposite regimen (placebo/washout/DHEA). After DHEA supplementation, the patients' blood levels of DHEA rose from subnormal to the normal range for young adults. More importantly, the patients taking DHEA showed positive psychological changes, including enhancements in self-esteem and mood, and a decrease in fatigue.
On a side note, the researchers discovered that, while the increase in DHEA levels was followed by an increase in testosterone levels in the women (all women have some testosterone, just as all men have some estrogen), this effect was not seen in the men. This led the authors to speculate that, in men, the beneficial effects of DHEA, which are apparently independent of testosterone levels, may be due to a direct action of the hormone on the central nervous system.
Other conditions besides Addison's disease can cause a significant decrease in DHEA levels. In adrenal insufficiency, e.g., the adrenal glands secrete some hormones, but at subnormal levels. In a double-blind study of 24 women with this condition, DHEA supplementation (50 mg daily for 4 months) raised DHEA levels to normal.2 It also increased the women's sense of well-being, frequency of sexual thoughts, and sexual interest, as well as decreasing depression and anxiety.
DHEA May Slow Down Aging
Because DHEA is known to peak at high levels in young adults and then decline with increasing age, there has been a high level of interest in using DHEA as an antiaging hormone. A recent study in Italy looked for a correlation between DHEA levels and quality of life in people over 90 years of age; the subjects were 36 men aged 90-103 and 39 women aged 90-106.3 The study evaluated functional ability and quality of life by dividing the subjects into high-, medium-, and low-functioning groups based on their "activities of daily living" (ADL) scores. This is a measure of a person's ability to perform basic daily tasks, such as getting dressed, answering the phone, and maintaining normal hygiene.
The study found a direct relationship between DHEA levels and functional independence in men. No such statistically significant result was seen in women, however, leading the authors to suggest that "DHEAS influences different physiological mechanisms in elderly males and females." This reaffirmed the results of many other studies on DHEA showing marked differences between the sexes in their responses to this hormone.
DHEA in Monkeys and Men
The correlations between longevity and three factors - body temperature, insulin levels, and DHEAS levels - discussed in the accompanying article have been found both in the monkey studies and in the Baltimore Longitudinal Study of Aging (BLSA). The figure shown here summarizes these findings. For male rhesus monkeys, it graphs the effects of caloric restriction versus control monkeys who were not calorically restricted (parts A, B, and C). And for men in the BLSA, it shows the effects of the same three factors on natural longevity, expressed in terms of survival time (parts D, E, and F).
Men who had lower body temperatures andlower insulin levels - even though they were not calorically restricted, as the rhesus monkeys were - lived longer (top survival curves in the graphs) than those who had higher values in those parameters (bottom survival curves). And men who had higherDHEAS levels had significantly greater longevity (top curve) than men with lower levels (bottom curve).
DHEA Correlates with Longevity in Men
One of the most ambitious studies on the aging process was begun in 1958 in Baltimore, and it continues to this day. Called the Baltimore Longitudinal Study of Aging (BLSA), it has been carefully examining the aging process in more then 1000 people from ages 20 to 90. Among the many physiological factors that have been recorded in this study is the level of DHEAS in the blood - and it has been found that men with higher levels of DHEAS tend to live longer than men with lower levels.
This observation jibes with the results of recent studies on caloric restriction (a severely limited diet) in male rhesus monkeys. Caloric restriction (CR) is well known to extend the lifespan of rodents, and it appears to do so for monkeys as well, although the evidence for that is not conclusive. If it really does so, then it would probably do the same for humans - if they were willing to endure the hardship of such a diet.* (Not surprisingly, there have been very few volunteers to test this theory.)
*It is believed that one way in which caloric restriction slows aging is by facilitating a process called gene silencing, in which certain genes that extend lifespan "silence," or suppress, the activity of other genes that shorten it. This process depends critically on a molecule called NAD, which is derived from the vitamin niacin. CR reduces the cells' need for NAD in energy metabolism, thus making more of it available to participate in gene silencing.
Monkeys, Too, Live Longer with Higher DHEA
But what does caloric restriction in rhesus monkeys have to do with DHEAS levels in men? Well, it turns out that DHEAS levels decline with age in the monkeys just as they do in humans, and CR slows the rate of decline. Thus, these healthier, longer-lived monkeys have higher DHEAS levels than normal monkeys.
It has been found that men with
higher levels of DHEAS tend to live
longer than men with lower levels.
A paper published recently in the journal Science discusses all this.4 The authors' research on caloric restriction in monkeys prompted them to look at the BLSA data, and they found striking correlations between CR-induced longevity in their monkeys and natural longevity in some men, i.e., those men who just live longer than most, for whatever reasons. The crucial question, of course, is: what are those reasons?
Increasing DHEA Levels Is Easy
Quite possibly, one reason that some men live longer is above-average DHEAS levels - some men just naturally have more than others. Other possible reasons are below-average insulin levels and below-average body temperature. The monkey studies have shown definite correlations between longevity and these factors too - not surprisingly, because caloric restriction reduces the body's food intake and, therefore, its rate of energy metabolism. This, in turn, reduces the need for insulin and tends to lower body temperature.
Although we cannot necessarily conclude that high levels of DHEAS mean an increased lifespan, the authors of the Science paper did state that "DHEAS, which declines in both rhesus monkeys and humans during normal aging, may be important in health maintenance and may serve as another potential longevity marker." What they didn't point out, but it's worth mentioning, is that it's much easier to raise your DHEAS levels through supplementation than to lower your insulin levels or your body temperature (unless you live in Antarctica).
Is DHEA in the Fountain of Youth?
There is no magic elixir of youth on the market today, but supplementation with hormones such as DHEA to maintain youthful levels may very well help one live a longer, healthier life. Ponce de León's fountain of youth has still eluded explorers, but if they ever do find it, it may turn out to have some DHEA in its waters.
Supplemental DHEA is obtained not from human beings or primates, but from wild yams of the genus Dioscorea, found in abundance in the southern United States and Mexico. The yams contain a compound called diosgenin, which is converted to DHEA in the laboratory. Our bodies are unable to duplicate this chemical process, so certain products containing unprocessed extracts of yams and sold as "natural DHEA" or "DHEA precursor complexes" are worthless for their intended purpose. Caveat emptor.
- Hunt PA, Gurnell EM, Huppert FA, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trail. J Clin Endocrin Metab 2000;85(12):4650-6.
- Wiebke A, Callies F, Vlijmen JC, et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 1999;341(14):1013-20.
- Ravaglia G, Forti P, Maioli F, et al. The relationship of dehydroepiandrosterone sulfate (DHEAS) to endocrine-metabolic parameters and functional status in the oldest-old. Results from an Italian study on healthy free-living over-ninety-year olds. J Clin Endocrin Metab 1996;81(3):1173-8.
- Roth GS, Lane MA, Ingram DK, Mattison JA, Elahi D, Tobin JD, Muller D, Metter EJ. Biomarkers of caloric restriction may predict longevity in humans. Science2002 Aug 2;297(5582):811.
Dr. Rosick is an attending physician and clinical assistant professor of medicine at Pennsylvania State University, where he specializes in preventive and alternative medicine. He also holds a master's degree in healthcare administration.