DHEA and Fat

Our circulatory system carries many hormones and their metabolites throughout our bodies. Bodybuilders tend to focus closely on hormones like insulin, testosterone, and GH because of the powerful effect they exert on muscle growth. Recent studies suggest that testosterone is a very powerful fat burning hormone. Testosterone is made from conversion of cholesterol by a number of enzymes with a few precursors along the way:

Cholesterol --> Pregnenolone --> 17-OH Pregnenolone --> DHEA --> Androstenedione --> Testosterone

Something that is very frequently overlooked is that precursors to testosterone and even metabolites of those precursors have intrinsic metabolic effects that may be of significant interest to bodybuilders. In particular, the precursor dehydroepiandrosterone (DHEA) has been marketed heavily as a fountain of youth and a testosterone booster.

DHEA is the most abundant steroid hormone in the circulatory system and it has direct biological effects on tissues by binding to cell surface and nuclear receptors (1). Even though DHEA functions mainly as a precursor for androgens like testosterone and dihydrotestosterone (DHT), DHEA has its own ability to bind to the androgen receptor (2). Unfortunately, DHEA’s intrinsic activity at the androgen receptor is quite low and thus it really just acts as an antagonist which means it could be detrimental to testosterone function. In normal conditions this is likely a very negligible effect because DHEA’s actual affinity for the receptor is also quite weak.

Since there is a gradual age related decline in DHEA that correlates with a similar decline in testosterone many studies have evaluated supplementation with DHEA in older populations (3). Low levels of DHEA have also been correlated with accumulation of fat in the abdomen of men and DHEA’s role in regulating fat stores has been supported by numerous animal studies. One particular study in rats demonstrated that DHEA actually prevented fat accumulation in rats that were fed a high fat diet (4). Clinical trials have examined the effect of DHEA on body fat in young, old, and athletic populations with mixed results. One of the most highly quoted studies is by Nester et al. in 1988 that found remarkable results of an extraordinary dosage of 1600mg/day for 28days (5). Compared to a placebo they found that the 3x increase in circulating DHEA decreased body fat by 30% without a change in bodyweight although there were no significant changes in testosterone or estrogen levels. Unfortunately other researchers have not been able to replicate this effect and the follow-up studies are variable in dose, age, sex, and fatness. Lower doses in obese subjects have been unsuccessful in improving body composition and this may be related to fat’s ability to metabolize androgens (6). Also more recent double blinded placebo controlled studies have shown benefits on insulin resistance, triglycerides, and body composition, especially in elderly men (7, 8).

Clinical studies of DHEA have been a little inconsistent which has made DHEA less popular in the supplement industry, but more recent animal and laboratory studies suggest that DHEA deserves another look. DHEA appears to exert multiple effects on fat tissue including inhibition of fat cell growth, increase resting metabolic rate, and inhibition of the actions of cortisol (9). A study in 2012 by Karbowska and Kochan examined a more interesting ability of DHEA to mobilize fat from its stores while increasing the burning of fat (9). Other studies have demonstrated that DHEA and/or its metabolites have an ability to increase resting metabolic rate (RMR) even in a calorie-restricted/dieted state where the RMR usually decreases (10).

In a future blog post I will go into more detail about DHEA and 7-Keto DHEA supplementation.

References:

1) Webb SJ, et al. "The biological actions of dehydroepiandrosterone involves multiple receptors". Drug Metabolism Reviews 2006;38 (1–2): 89–116

2) Chen F, et al. "Direct agonist/antagonist functions of dehydroepiandrosterone". Endocrinology 2005 Nov; 146 (11): 4568–76.

3) Tchernof A, Labrie F. DHEA, obesity and cardiovascular disease risk: a review of human studies. Eur J Endocrinol 2004;151:1-14

4) Hansen PA, et al. DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet. Am J Physiol 1997;273:R1704-8

5) Nester JE, et al. DHEA reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1998 Jan;66(1):57-61

6) Vogiatzi MG, et al. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism. 1996 Aug;45(8):1011-5

7) Jankowski CM, et al. Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids. Clin Endocrinol (Oxf). 2011 Oct;75(4):456-63

8) Villareal DT, et al. Effect of DHEA on abdominal fat and insulin action in elderly women and men: a randomized controlled trial. JAMA 2004;292:2243-8

9) Karbowska J, Kochan Z. Fat-reducing effects of DHEA involve upregulation of ATGL and HSL expression, and stimulation of lipolysis in adipose tissue. Steroids 2012;77:1359-1365

10) Zenk JL, et al. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007 Sep;18(9):629-34.


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