ROCHESTER, Minn. -- The widely used anti-aging supplement DHEA (dehydroepiandrosterone) has no beneficial effect on body composition, physical performance, insulin sensitivity, or quality of life, according to Mayo Clinic researchers.
ROCHESTER, Minn., Oct. 18 -- The widely used anti-aging supplement DHEA (dehydroepiandrosterone) has no beneficial effect on body composition, physical performance, insulin sensitivity, or quality of life, according to Mayo Clinic researchers.
A two-year placebo-controlled, randomized, double-blind trial revealed no effect on aging markers, such as muscle strength, peak endurance, muscle and fat mass, glucose tolerance, or quality of life, reported K. Sreekumaran Nair, M.D., Ph.D., and colleagues, in the Oct. 19 issue of the New England Journal of Medicine.
In a separate analysis, low-dose testosterone given to older men also fell short, they found.
The DHEA findings flatly contradicted the persistent belief that the popular supplement, an adrenal sex steroid, sold in health food-stores and other shopping venues, has anti-aging properties.
In the study, increasing the level of DHEA in older men and women (at least age 60) with low androgen levels, and also giving low-dose testosterone to men with low hormone values, increased these measures to those considered normal for young people. Nevertheless, neither treatment had any detectable effect on aging markers, Dr. Nair's team wrote.
The Mayo Clinic study included 87 older men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 older women with low levels of sulfated DHEA.
Of the men, 29 received DHEA (75 mg/day), 27 received low-dose testosterone, and 31 received placebo. Twenty-seven women received DHEA (50 mg/day) and 30 were given a placebo.
Compared with baseline, participants given DHEA for two years had an increase in plasma levels of sulfated DHEA by a median of 3.4 ?g/mL (9.2 ?mol/L) in men and by 3.8 ?g/mL (10.3 ?mol/L) in women.
Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng/dL (1.1 nmol/L), compared with the change in the placebo group.
A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute (VO2), muscle strength, or insulin sensitivity.
The effect of DHEA on bone mineral density (BMD) was minimal and inconsistent, the researchers said. Men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultra distal radius. However, there was no significant increase in BMD at other sites for men or women, and the magnitude of changes was far smaller than that of established therapies for osteoporosis, they said.
Men who received testosterone had a slight increase in fat-free mass, but no significant change in thigh-muscle area or muscle strength, or improvement in any of the performance measures.
Although a pharmacologic dose of testosterone may have a marked effect on body composition and function, low-dose replacement, as in this study, had no demonstrable effect. Higher doses of testosterone, Dr. Nair warned, may increase adverse effects such as prostate enlargement or cancer, and any beneficial effects remain to be established. The men in the Mayo study did not have prostate problems.
Finally, the researchers reported, neither DHEA nor testosterone treatment improved the quality of life or had major adverse effects.
Discussing the validity of the findings, the researchers said that statistical analysis (mainly, 95% CI range) shows that the number of participants in the study was sufficient to establish that any treatment effects that might exist were not clinically meaningful.
Also, they said, it is possible that DHEA had short-term effects on measures of strength, peak VO2, quality of life, or measures of insulin sensitivity, but the current data indicate that if short-term restoration of DHEA levels has favorable biologic effects, they were not sustained.
These placebo-controlled, randomized findings contradict some of the previous DHEA reports, Dr. Nair said, but many of those studies were of short duration and included only small numbers of participants. A review of the literature indicates that most studies showing positive effects in humans were short-term, used pharmacologic doses of DHEA, or were in rodents that normally have very low or zero levels.
In all, "we found little if any beneficial effect of the restoration of DHEA levels in elderly men and women," the researchers wrote, adding that additional long-term studies of testosterone are warranted to determine the risk-benefit ratio of higher doses.
"Taken together, our data provide no evidence that either DHEA or low-dose testosterone is an effective antiaging hormone supplement and argue strongly against use of these agents for this purpose," the Mayo team concluded.
Co-author L. Joseph Melton, III, M.D., reported having received lecture fees from Amgen, Merck, Novartis, and Procter & Gamble. Ajay Nehra, M.D., has served as a consultant to Pfizer.
In an accompanying editorial Paul M. Stewart, M.D., of the University of Birmingham in England, said the results of the Mayo study are largely confirmatory. Yet another "negative" study is unlikely to have much effect on its use in Western societies. As a result of a loophole in U.S. legislation, DHEA is regarded not as a drug but as a dietary supplement, he pointed out.
Further research focusing on the action of DHEA (which is not essential for life) is certainly indicated, Dr. Stewart said. Establishing the hormone's safety or its lack thereof might lead to reclassification of DHEA as a drug, since supplements are defined as causing no harm. Although DHEA in this study caused no harm, other research, notably estrogen studies, are a reminder that reversing an age-related endocrine deficit may actually cause more harm than good.
"The search for eternal youth will continue, Dr. Stewart said. "but the reversal of age-related decreases in the secretion of DHEA and testosterone through 'physiologic' replacement regimens offered no answer and should not be attempted."
In light of the evidence, he added, "DHEA should no longer be accepted as a food supplement and should instead be treated as a regulated drug. Appropriate regulation would dispel much of the quackery associated with this elusive hormone."
Dr. Stewart reported having received consulting fees from Duocort, grants from Novo Nordisk and Novartis, and a consulting fee and grant from Pfizer. He also holds patents on an inhibitor of 11?-hydroxysteroid dehydrogenase as a treatment for glaucoma.