Saturday, September 26, 2015

Testosterone Gel Augments Increases in Lean Mass Gains (+3.9kg in 6 Months) in Older Intensely Training Men, but Testim Blocks Decrease in Marker of Heart Disease Risk

Building muscle becomes increasingly harder, the older you get. While there's no evidence that any of the overpriced natty T-boosters can solve this problem, Testim(R) can. That's at least what a recent Danish study shows.
If you believe in what you read in the ads for testosterone boosters, all you'd have to do to get jacked was to increase your testosterone levels by a few percentages.

In view of the fact that it took transdermal testosterone gels and a 100% increase in bioavailable testosterone (most T-boosters boast of boosting total testosterone by 20-40%) in a recent study from the Odense University Hospital and the University of Southern Denmark (Glintborg. 2015) to trigger - albeit significantly - muscle gains of +3.5 kg in older subjects on a high intensity resistance training regimen, it is highly questionable how capable the average "natural muscle builder" really is ... but let's not rant and rather take a look at what really works (for the elderly, at least).
If you want to build muscle forget T-booster and optimize your protein intake 

Protein Timing DOES Matter!

5x More Than the FDA Allows!

Protein requ. of athletes

High EAA protein for fat loss

Fast vs. slow protein

Whey vs. Pea Protein
So, the study at hand was actually not designed to elucidate the effects of testosterone on lean mass gains or fat loss, but rather to investigate testosterone's ability to augment or block the exercise-induced reductions in soluble CD36 a protein. CD36??? Well, I have to admit this is not exactly the best known inflammatory protein, but in view of the fact that it has been associated with the obesity induced increase in atherosclerosis risk (Handberg. 2006), it is an important one.

To quantify said effects, a group of Danish scientists measured the changes in soluble CD36 (sCD36) and body composition in response to a testosterone treatment (TT) and/or strength training (ST) in men with low-normal testosterone levels (Glintborg. 2015).
Table 1: Baseline characteristics of the subjects | TT, testosterone treatment; (ST) strength training. Data presented as median (interquartile range); No significant differences, Mann-Whitney test between groups. Bio T, Bioavailable testosterone; LEFM, lower extremity fat mass; SAT, subc. adipose tissue; VAT, visc. adipose tissue (Glintborg. 2015).
All in all, the researchers recruited 54 men aged 60–78 years with testosterone levels below 7.3 nmol/L (that's the usual cut-off for hypogonadism differential diagnosis) and waist circumferences above 94 cm for a randomized double-blinded, placebo-controlled study in which the subjects were assigned to four different groups:
  • the testosterone aka TT group in which the subjects were treated with 50–100 mg/day of testosterone from Testim per day (n= 20),
  • the placebo aka PLA group in which the subjects were treated in which the subjects received an identically looking placebo supplement (n= 18),
  • the strength training aka ST group in which the subjects followed a standardized progressive heavy strength training program (n= 16), and
  • the combined groups with ST + TT or ST + PLA
To determine the success of the interventions, the scientists used both, the levels of soluble CD36 (sCD36) and determined the total and regional fat mass by Dual X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) after three (half-way) and six months (end of the intervention).
Figure 1: Changes in body composition (left) and bioavailable testosterone levels (right | Glintborg. 2015).
As you can see in Figure 1, the testosterone treatment augmented the increases in lean mass in response to the standardized high intensity resistance training protocol that involved 3 supervised resistance training workouts per week (minimum two workouts) consisting of 5-min bicycling for warm-up (approximately 100 W) plus a standardized full body workouts (6-10 reps at the respective RMs, weights were increased progressively) with leg presses, knee extensions, leg curls, chest presses, latissimus pull downs, back extensions, and crunches.

And the effect was not just statistically, but also practically significant: Instead of the meager 0.6 kg without testosterone treatment, the subjects on T-gel gained a whopping 4.5 kg (that's +650%). That's truly impressive.
Dose response relationship of muscle gain (in kg) per mg of testosterone enanthate from previous SV article; the white line indicates a dose that would probably have produce testosterone levels identical to baseline (calculated based on Bhasin. 2001 | learn more!)
Beware of jumping to conclusions! In view of the age and the low baseline testosterone levels of the subjects it is unwarranted to assume that you or anyone else in the prime of his year (and testosterone production ;-) will see the same, or even similar increases in size gains as the 60y+ agers in the study at hand. Addition due to user question: It is also not necessarily certain that the same results will be seen with any other form of administering T. If you achieve stable high-normal T levels with injectables, though, it is pretty sure that people with initially low T-levels will benefit. I highly suggest you read my article "Quantifying the Big T" if you want to know more about the dose-response ratio (also in young men) | read it!
What was less impressive were the changes in body fat: While both TT and ST had beneficial effects on the total amount of body fat (-1.4kg in the TT group vs. +1.2 kg, -0.8kg and -0.7kg in the PLA, ST and ST + TT groups, respectively), there were no significant decreases in waist circumference a primary marker of metabolic disease risk and indicative of the amount of "bad" visceral fat you're carrying around - a result of which we are going to see that it is in line with the lack of effect on the previously mentioned artherosclerosis risk marker CD36.
Figure 2: In spite of the fact that the atherosclerosis risk factor sCD36 usually correlates with obesity, its reduction by exercise was blunted by the provision of exogenous testosterone even though the fat loss in the ST + TT group did not differ significantly from that in the ST + PLA (testosterone-free) training group (Glintborg. 2015).
While the latter, i.e. CD36 and thus the putative artherosclerosis risk, improved significantly in the resistance training group (without T-gel), the addition of 50-100mg of transdermal testosterone appears to reverse or impair the exercise-induced improvements in artherosclerosis risk and entail the risk of an unwanted increase in this allegedly important CVD risk marker. The obvious question is thus: How significant is the increase in sCD36 in the testosterone treated "best+ agers"?
Figure 3: Scientists believe that the association between CD36, atherosclerosis, diabetes and CVD is mediated by its effects on macrophage foam cell formation (Febbraio. 2001).
So, is TRT dangerous? Well, atherosclerosis is only one out of several diseases in which sCD36 is elevated. Increased CD36 has also been associated with the development of metabolic diseases such as type 2 diabetes, and overall cardiovascular disease (Febbraio. 2001). In view of the fact that this correlation appears to have a mechanistic background that relates to the way CD36 stimulates macrophage foam cell formation, it is hard to discount the ill effects of testosterone on CD36 as irrelevant. Against that background, we would yet have to expect that studies investigating the long-term effects of testosterone treatment on atherosclerosis and CVD risk show distinct risk increases. This, however, is not the case - at least not consistently.

Rather than being associated with a distinct increase in CVD risk, the available data on the effects of testosterone treatment on heart health shows both positive, as well as negative effects (Haddad. 2007). Along with the publication of several very recent studies, an updated meta-analysis by Morgentaler et al. (2015) even suggests that the tides, which have long been "anti-TRT" are now turning so that the "[c]urrently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects" (Morgentaler. 2015).

Eventually, we or rather patients and clinicians will yet need more and larger randomized trials of TRT being used in men at risk for cardiovascular disease to better inform the safety of long-term testosterone use. Studies that measure only the short-term response of alleged markers of CVD risk, such as CD36 in the study at hand, are eventually of little use, when it comes to finding a definitive answers to the question whether TRT increases CVD risk. What they can tell us, though, is that TRT is a powerful tool to alleviate and reverse the age-related decline in muscle mass - in isolation and, even more so, in conjunction with high intensity resistance training | Comment!
References:
  • Bhasin, Shalender, et al. "Testosterone dose-response relationships in healthy young men." American Journal of Physiology-Endocrinology And Metabolism 281.6 (2001): E1172-E1181.
  • Febbraio, Maria, David P. Hajjar, and Roy L. Silverstein. "CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism." Journal of Clinical Investigation 108.6 (2001): 785.
  • Glintborg, Dorte, et al. "Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition." Scandinavian journal of clinical and laboratory investigation ahead-of-print (2015): 1-8.
  • Haddad, Rudy M., et al. "Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials." Mayo Clinic Proceedings. Vol. 82. No. 1. Elsevier, 2007.
  • Handberg, Aase, et al. "Identification of the Oxidized Low-Density Lipoprotein Scavenger Receptor CD36 in Plasma A Novel Marker of Insulin Resistance." Circulation 114.11 (2006): 1169-1176.
  • Kvorning, Thue, et al. "Mechanical Muscle Function and Lean Body Mass During Supervised Strength Training and Testosterone Therapy in Aging Men with Low‐Normal Testosterone Levels." Journal of the American Geriatrics Society 61.6 (2013): 957-962.
  • Morgentaler, Abraham, et al. "Testosterone therapy and cardiovascular risk: advances and controversies." Mayo Clinic Proceedings. Vol. 90. No. 2. Elsevier, 2015.