Wednesday, July 21, 2010

DHEA: Overlooked or Overrated?

With DHEA (structure of DHEA-S, see image on the right; HMDB. V2.5) having been mentioned in a few of the last posts as a precursor to other androgens, I thought it might be interesting to have a brief look at the effect of DHEA supplementation on mood, body composition, sex life and human endocrine balance.

Lately, a 1988 study by Nestler (Nestler. 1988) has caught my attention. The researchers investigated the effect of 28 days of 1600mg/day (no, this is no typo) orally supplemented DHEA in 5 normal men (+5 men on placebo). The results were simply amazing. Apart from a 2.5x-3.5x increase in DHEA-levels, the researchers found:
"In the DHEA group the mean percent body fat decreased by 31%, with no change in weight. This suggests that the reduction in fat mass was coupled with an increase in muscle mass." (Nestler. 1988)
In addition mean serum low density lipoprotein cholesterol decreased by 7.5% (3.21 +/- 0.11 vs. 2.97 +/- 0.14 nmol/L; P less than 0.01) in the DHEA group, only. Other than the researchers had hoped, insulin sensitivity was yet not augmented. And, surprisingly, other than androstenedione, which rose from 4.3 +/- 0.6 to 8.6 +/- 1.2 nmol/L, the concentrations of all major androgens, i.e. serum total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and estrone levels, did not change.

In view of these results the question is: "Why don't we just give huge amounts of DHEA to the obese and soon everybody will be slim and healthy? "

Well, a  follow up study done by Usiskin in 1990 could not replicate these promising results, although the used the same, from a contemporary perspective ridiculously high amount of DHEA, i.e. 1600mg/day (Usiskin. 1990). Other than Nestler, two years before, Usiskin found a body fat mass was reduction in only two of the six men following DHEA administration.
It is, however, worth mentioning that there was one significant difference as far as the group of subjects is concerned: While Nestler had used "normal", i.e. healthy normal-weighed subjects, Usiskin, probably hoping to identify DHEA as a fat-loss panacea, selected overweight subjects, whose fat-depots have lately been found to be a major contributor to androgen metabolism (eg. Poulus. 2010). It is thus possible that the peripheral substrate metabolism prevented substantial weight loss in subjects with a) especially high body fat percentage or b) an endrocinologically unfavorable body fat distribution. In view of contemporary knowledge about the endocrinological significance of adipose tissue, Usiskin's neglect of measuring the serum levels of at least the most prominent DHEA metabolits in their subjects renders the results of their pretty useless.

In the following, the ineffectiveness of DHEA as a weight-loss supplement in obese or morbidly obese patients (e.g. mean weight > 260pounds; BMI > 50) has been confirmed in several other studies. Such as Vogiatzi 1996 all these studies employed significantly lower doses of DHEA (2x40mg/day in Vogiatzi. 1996). Further investigations using healthy male subjects are wanting.

And while, in a 1999 review on DHEA luridly labeled "DHEA: panacea or snake oil?" Sirrs and Bebb (Sirrs & Bebb. 1999) correctly state:
"Current enthusiasm for using DHEA as a panacea for aging, heart disease, and cancer is not supported by scientific evidence in the literature. Given the potentially serious adverse effects, using DHEA in the clinical setting should be restricted to well-designed clinical trials only." (Sirrs & Bebb. 1999)
The authors must yet admit that DHEA
might be beneficial for improving someone's sense of well-being; minor improvements in body composition have been noted for men only.
An interesting side not to the debate on DHEA is that in 1995 and in view of the craze about DHEA it was Dr. John Nestler, whose study was among the cornerstones of the hype around DHEA (s. above), was the first to speak of DHEA as "Snake Oil" in the course of the New York Academy of Sciences Conference on the benefits and pitfalls of DHEA supplementation.

After being unavailable as an over-the-counter supplement for some years, DHEA has been revived by the anti-aging industry (I insist most of those doctors are entrepreneurs, not medical practitioners) most studies (cf. The DAWN Study. 2007) investigate the beneficial effects of DHEA-supplementation, when natural levels are decreasing with age.

Focussing on the influence of DHEA on  body composition and improvements of athletic performance the International Society of Sports Nutrition (ISSN) summarizes the research results on DHEA as follows:
"The decline in DHEA levels with aging has been associated with increased fat accumulation and risk to heart disease [344]. Since DHEA is a naturally occurring compound, it has been suggested that dietary supplementation of DHEA may help maintain DHEA availability, maintain and/or increase testosterone levels, reduce body fat accumulation, and/or reduce risk to heart disease as one ages [342,344]. Although animal studies have generally supported this theory, the effects of DHEA supplementation on body composition in human trials have been mixed. For example, Nestler and coworkers [345] reported that DHEA supplementation (1,600 mg/d for 28-d) in untrained healthy males promoted a 31% reduction in percentage of body fat. However, Vogiatzi and associates [346] reported that DHEA supplementation (40 mg/d for 8 wks) had no effect on body weight, percent body fat, or serum lipid levels in obese adolescents. More recent work has supported these findings suggesting that one year of DHEA supplementation had no effect on body composition when taken at 50 mg per day [347]."
The ISSN also mentions 7-Keto-DHEA as a possible, yet not thoroughly researched alternative to DHEA. I will look into that in another blog-item as soon as I get the chance - Promise! In the mean time, you better not experiment with doses of DHEA > 100mg/day! Chances of over-aromatization (high estrogen) are too high, even if you are relatively slim, already.

 A dubious appeal to participate in a DHEA + ATD study purportedly financed by
Anabolic Xtreme and Patrick Arnold former head of ErgoPharm (now E-Pharm) 

On a side note: A post on the Anabolic Xtreme (AX is now obviously "AthleticXtreme") message board indicates, that Patrick Arnold (PA), founder of ErgoPharm (PA's new company is called E-Pharm) and inventor of the "first" prohormone 1-AD, and the guys of AX must have been financing a study investigating the effect of 1,000mg/day DHEA + 50mg/day ATD (an aromatization inhibitor, preventing the conversion of downstream testosterone to estrogen) on body composition and athletic performance. Unfortunately, the study that should have been conducted in 2007 has never been publicly released. So, either it was a haox in the first place, or the study did not deliver the results PA and the guys from AX expected.
From the distinct mechanism of actions of those compounds, a more reasonable stack starting with 100mg DHEA (with weekly increases of 25-50mg) + 50mg ATD (later maybe 75mg) per day would make sense, though. But as always: DO NOT TAKE THIS AS A MEDICAL ADVICE!