Saturday, March 17, 2012

DHEA Inhibits Fat Gain More Effectively Than Testosterone. Both Work by Reducing PPAR-γ and Thusly Lipid Storage

Image 1: This is the "Fountain of Youth" in Karlsruhe, Germany. I have never been there, but I guess I should take the next train and check whether water contains 0.4% or 0.8% DHEA ;-)
Outside of the medical practices of some anti-aging docs nobody appears to care about the "good old" dehydroepiandrosterone (DHEA), these days. As a diligent student of the SuppVersity, you are yet well aware of the reviving effects DHEA has on the liver (cf. August, 26, 2011), pancreas & insulin sensitivity (cf. May, 15, 2011) and adipocyte metabolism (cf. April, 8, 2011) in "older" people or everyone with suboptimal DHEA levels. You will also be aware that the adrenal steroid hormone which can be converted to testosterone (and thusly DHT or estrogen) at the target tissue exerted pretty astonishing effects on body composition in a handful of initial (very) high-dose trials. Follow up studies in the late 1990s were yet mostly unable to reproduce these encouraging results and with the increasing concerns about potential side-effects and the lack of funding from the pharmaceutical industry, who did not have an interest in finding out that a non-patentable substance would ameliorate or even cure some of of the ailments they were and still are making a fortune on.

DHEA a Weapon in the War Against Diabesity?

The most widespread of these ailments certainly is diabetes; a pathology the management of which (not it's treatment!) has generated a $42 billion dollar market (data from 2010) that is estimated to grow to $114.3 billion dollar by 2016 (inverstorplace.com). It is thusly no wonder that the recently published study by Kei Fujioka and his colleagues from the Departments of General Internal Medicine and Parasitology at the Gifu University Graduate School of Medicine in Gifu, Japan, was not funded by a Japanese (let alone US ;-) pharmaceutical company, but by a research grant from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Fujioka. 2012).
Figure 1: Simplified illustration of the adrenal hormone production cascade
Based on the scattered conglomerate of previous results the researchers speculated that feeding Otsuka Long-Evans Tokushima fatty rats chow with 0.4% dehydroepiandrosterone (DHEA) in it would ameliorate if not totally prevent the development of type II diabetes and / or related pathologies to which this rodent strain, which is also one of the standard models for type II diabetes, is particularly prone.
Figure 2: Relative differences in epdidymal fat pad weights, serum glucose, triglyceride, total cholesterol and free fatty acid levels in LETO and OLETF rats after 52weeks on chow with 0.4% DHEA (=100mg/day; human equivalent: 16mg/day); data expressed relative to rats on control diet (data adapted from Fujioka. 2012)
As you can see in figure 1 rodents don't have to be genetically disposed to get type II diabetes to benefit from a human equivalent of ~16mg/day. The ever-hungry (=polyphagic) LETO rats, the scientists put on the same 0.4% DHEA diet for 52 weeks has similarly reduced visceral fat depots (epididymal fat - LETO: -50%; OLETF: -33% vs. control), triglycerides and free fatty acids. The improved glucose levels were yet only statistically significant in the otherwise diabetic OLETF rats and the increase in total cholesterol in the LETO group is difficult to judge without at least some additional data on the ratio of "good" HDL to "bad" LDL.

DHEA vs. Testostosterone - Who is the "King" of Metabolic Hormones

Luckily, the Fujioka et al. were not satisfied with these results and conducted another experiment. This time with normal rats (Wistar strain) and with a second group which received 0.4% testosterone in their chow.
Figure 3: Fat weight, triglyceride content of liver and gastrocnemius muscle, body temperature and adipocyte diameter in male wistar rats after 4 weeks on DHEA (0.4%) or testosterone (0.4%) containing chow; data expressed relative to control on standard chow (data adapted from Fujioka. 2012)
Compared to the poor critters in the control group, who had to content themselves with the "non-anabolic" standard chow, both the rats in the DHEA and the testosterone groups had reduced body fat levels (remember the control rats were "normal", not fat!), reduced triglyceride deposition in both liver and muscle tissue, an increased body temperature and a statistically highly significantly decreased adipocyte size (cf. figure 3) - and believe it or not, all these beneficial effects were more pronounced in the DHEA group.
Figure 4: DHEA-S (µg/dL), testosterone (ng/dL) and PPAR-γ expression in control, DHEA and testosterone group at the end of the study period (data adapted from Fujioka. 2012)
In view of the initially mentioned role of dehydroepiandrosterone as a precursor to testosterone (cf. figure 1) and its own yet negligible ability to interact with the androgen receptor (Tan. 1997), it should not surprise you that the purported mechanism behind their beneficial effects on "all things fatty" is identical: a reduced expression of the "triglyceride storage receptor" PPAR-γ, the same receptor the smart business men from the pharmaceutical industry target with their lipid and blood glucose lowering drugs to treat high blood glucose and/or lipid levels for increased obesity, and subsequently another increase in glucose and lipid levels which will "unfortunately" require either more of the old or even better less of the more expensive "next generation" drugs... *clever, right?*

Similar Effects in Healthy, Young Human Beings are Highly Questionable

Image 2: Neither Drogba (l) nor Ronaldo (r) are candidates for DHEA supplementation (img VanityFair WC special edition).
Assuming that you are not already on your way to your local supp store to make sure you get the last bottles of DHEA before the FDA comes up with another horror story based on which this "dangerous supplement" has to be added to the banlist, I want to caution you that a 2010 study from the PA University of Novi Sad (Ostojic. 2010), in Serbia did not find any beneficial effects on body composition in 20 young soccer players who received an oral DHEA supplement (100mg/day) for 4 weeks - and that, despite +40% increases in total testosterone (free testosterone unchanged), +27% increases in estrogen and 197% increases in DHEA. As an active non-sedentary, non-obese, non-metabolically deranged individual, like the 19-22 year old soccer players in the Ostojic study, it is unlikely that your six-pack will show overnight, just by popping grams of DHEA per day.

Before we do not know why in some trials (rodents and humans) oral DHEA supplements yield phenomenal results (in the study at hand, both the lower dosage, as well as the "chronic" administration in very low doses spread across the day could be decisive factors), while they totally suck in others, the "specificity rule" from the Three Simple Rules of Sensible Supplementation would preclude anyone under the age of 35+ (DHEA levels begin to decline ~30y) from supplementing with DHEA, unless this someone knows (not just guesses!) from bloodwork that his/her DHEA levels are at least borderline low. And don't forget, even then DHEA or rather its downstream metabolites (estrogen in particular) can be similar suppressive on your own natural hormone production as "real gear" or the reputed OTC "pro-hormones" 90% of which are active steroids, anyway.