Longterm DHEA Supplementation Improves Suboptimal Insulin Sensitivity and Induces Beneficial Changes in Body Composition and Inflammatory Markers TNF-Alpha & IL-6 in Elderly Subjects

It has long been established that after peaking at the end of puberty, the production of dehydroepiandrosterone (DHEA) steadily declines with age and approaches levels of approximately 80% in the elderly (>75y). In the late 20th century, initial studies investigating the "anti-aging" effect of the adrenal hormone DHEA provided results that appeared to confirm the hypothesis that the restauration of DHEA to youthful levels would have beneficial cognitive and metabolic effects. Many of the findings could yet not be reproduced in follow-up studies and the pharmaceutical industry soon lost interest in spending money into research on a naturally occurring and thus non-patentable compound. Consequently, expensive long-term studies such as the one (Weiss. 2011) recently been published in the medical journal AGING are scarce and thus well-worth being mentioned on the SuppVersity.

Figure 1: Changes in Body Weight and Body Composition Before and After 12 months of DHEA
(data adapted from Weiss. 2011)

In 2004, already, Villareal, Weiss et al. had published the encouraging results of a short term intervention with DHEA on abdominal fat and insulin action in elderly women and me. The study at hand is a follow up on these results intended to evaluate the longterm efficacy and safety of 50mg supplemental DHEA in a study cohort of 136 men and women who were randomized to either DHEA or placebo treatment for 12 months. The outcomes of the first 12 month (114 subjects decided to either begin or continue treatment with DHEA for a second year) showed minor, but statistically improvements in body composition in the male subjects (cf. figure 1) and a normalization of insulin sensitivity in patients with previously impaired glucose metabolism.

The DHEA replacement resulted in small but significant decreases in body fat percentage and total fat mass in the male participants, while the men in the placebo group had small but significant increases. Trunk and appendicular fat masses showed a similar reduction. Abdominal visceral fat, evaluated using MRI, underwent a very small, but statistically significant, decrease in the men in the DHEA group; however, the difference between the changes in visceral fat between the DHEA and placebo groups was not significant. There were no significant changes in body weight in the women in either the DHEA or placebo group. The only significant change in body composition in the women was a small increase in fat free mass in the DHEA group. 
[...] improvements in glucose tolerance in response to DHEA occurred only in those participants who had abnormal glucose tolerance.

These results, along with the finding that other than minor increments in both testosterone and estradiol in the male subjects, would suggest that the bodies of the subjects "used" the supplemental DHEA to replenish their age-relatedly low DHEA-sulfate levels and the ensuing effects on previously impaired glucose tolerance and the reduction of inflammatory cytokines TNF-Alpha (-30%) and IL-6 (-31%) could be directly related to the restauration(!) of youthful DHEA levels in the 65 to 75 year-old study participants. The improvements in body composition, which were observed exclusively in the male participants, on the other hand, could be intricately related to the downstream metabolism of DHEA into testosterone. At least, this would explain the lack of significant effects in women, who, nevertheless, gained a small, yet measurable amount of lean body mass in the course of the first 12 month on DHEA (cf. figure 1).