DHEA: Efficacy Supported by Testing and Model Studies

In their useful clinical study, Flynn et al. (1) found that supplementation of older men with DHEA changed a variety of hormone and other serum constituents, in a statistically significant manner. This is an important clinical observation for DHEA that has received much public hype, use, and discussion. They noted“ statistically significant blood [constituents] changes were seen” (1). Then Flynn et al. (1) concluded, without documentation in their paper, “but none was clinically meaningful…” Such far-reaching and all encompassing conclusions should be documented. Others studies should be cited to show that the magnitude of the biological changes induced by DHEA was clinically irrelevant. DHEA routinely reduces loss of antioxidant vitamins during retroviral damage (2) and old age (3) and overcomes immunosenescence (3) in old mice, in retrovirus-infected mice (4), and humans (5). DHEA helped restore physical activity in old mice (6) while dramatically increasing their survival as the oldest of the old were dying of “old age” (7). Reviews in a recently published book on DHEA supplementation summarized evidence for its role in the reduction in energy expenditure, alteration of lipid metabolism and lowering of serum lipids, reducing bone loss and others, while its effects on body weight and muscle mass remain unclear (5). When viewed in the light of a spectrum of studies, observed changes by Flynn et al. (1) in serum constituents due to DHEA replacement seem to have potential clinical significance. They support further studies with better design, possibly at higher doses, and for longer periods than 3 months, rather than being clinically and experimentally irrelevant to man or mouse. Flynn et al. (1) “found no support for claims made for DHEA replacement dosage.” Although some of the multitude of claims made for DHEA have not (5) been confirmed in experimental trials, the conclusion of Flynn et al. (1) is not justified after measuring only a small number of serum constituents, especially when their levels were changed by only 3 months of DHEA replacement. Animal (2–4, 6) and some human (5) trials support the hypothesis that DHEA supplementation has significant biological changes, as Flynn et al. (1) actually reported. Bellino (7) from the National Institutes of Health stated that many DHEA supplementation studies used a placebo-controlled cross-over design [as Flynn et al. (1) did]. Bellino (7) suggests that the design should be changed to a randomized, placebo-controlled, multiarm design to decrease the chance of biased results from subjects who know they will receive DHEA. More long-term, double-blind trials, as well as additional animal model experiments (5, 7), are needed before rejecting all claims and studies supporting the health-promoting benefits of DHEA, especially using the results from a focused, short, and incorrectly designed single study. The data of Flynn et al. (1) are exciting and encouraging. However, the conclusion of no clinical relevance when DHEA caused multiple biological changes in the subjects was unsupported and undocumented in their study.