TRT - How Healthy, Lean and Muscular Will Testosterone Replacement Make You? Data from Recent Meta-Analysis

TRT - How Healthy, Lean and Muscular Will Testosterone Replacement Make You? Data from Recent Meta-Analysis

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TRT - What to expect in terms of its effects on a man's body composition?

If you hear people talk about "gear" (=performance enhancing drugs | PED), you get the impression that one injection of testosterone, nandrolone and co would turn a scrawny beginner into an Olympian. Reality, however, looks much different ... in fact, the number of people who ruin their health with (often oral) designer steroids without seeing any of the results they expect has been increasing continuously over the past years (Baker. 2006a,b; Graham. 2008; Rahnema. 2014) and that despite the fact that the "Anabolic Steroid Control Act" of 2004 was originally meant to prevent exactly that from happening (Herschthal. 2012).

In spite of the fact that the introduction of today's SuppVersity article focused on PED, the purpose of the meta-analysis and thus its summary was "systematically review [...] available observational and register studies reporting data on body composition in studies" in men with low or at least suboptimal testosterone levels.

This is what most studies were lacking: Exercise to shed fat and gain muscle.

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The original meta-analysis by Corona et al. (2016) was published in the Journal of Endocrine Investigation, only a few days ago. It involved "an extensive MEDLINE, Embase, and Cochrane search [that] was performed including the following words: testosterone and body composition. And is thus not focussing exclusively on testosterone as a "new anti-obesity medication", which is how the authors refer to it in the very first sentence of the abstract, because "all observational studies comparing the effect of TS on body weight and other body composition and metabolic endpoints were considered" (Corona. 2016) in the scientists' meta-analysis. Here's an overview of the studies, their design an results, as they were summarized by Corona et al.:

• 

  Suggested Read: 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 | more

  Valdermasson et al. (1987) - no placebo group, 10 subjects, 9 months, late onset hypogonadism (LOH) w/ baseline T of 1.8 nmol/l receiving TE 250 mg/3–4 weeks
• Rebuffé-Scrive et al. - no placebo group, 11 subjects, 1.5 months, mean age 42y, overweight/obese subjects, mean baseline T 13.8nmol/l, receiving TU 120–160 mg/day
• Forbes et al. (1991) - no placebo group, 7 subjects, 4 months, healthy, normal T levels, receiving TE 42 mg/kg/week
• Marin and Krotkievski et al. (1992) - no placebo group, 11 subjects, 1.5 months, mean age 42y, obese subjects, low T at 13.8 nmol/l, receiving TU oral 160 mg/day
• Marin and Krotkievski et al. (1996) - no placebo, 8 subjects, 3 months, mean age 42y, obese, low T at 14.1 nmol/l on T gel 250 mg/day
• Brodsky et al. (1996) - no placebo, 5 subjects with late onset hypogonadism (LOH) and T-levels of only 3.7 nmol/l on TC 3 mg/kg/2 weeks
• Katznelson et al. (1996) - no placebo, 29 subjects, 13 months, mean age 57, LOH w/ testosterone levels of 6.4 nmol/L on TE or TC 100 mg/week
• Wang et al. (1996) - no placebo, 67 subjects, for 6 months, LOH w/ starting T levels of 4.1 nmol/l taking T sublingually at 15 mg/day
• Zgliczynski et al. (1996) - no placebo, 22 subjects, 12 months, mean age 58.5y, normal elderly men with very low T (4.3 nmol/l) taking TE 200 mg/2 weeks
• Bhasin et al. (1997) - no placbeo, 7 subjects, 2.5 months, mean age 34.7y, LOH at initially 2.5 nmol/l receiving TE at a dosage of 100 mg/week
• Tan et al. (1998) - no placebo, 11 subjects, 4 months, mean age 33.3y, LOH w/ initially 5.5 nmol/l receiving TE at a dosage of  250 mg/4 weeks
• Brill et al. (2002) - no placebo, 10 subjects, 1 month, mean age 68.1y, but T-levels of 15 nmol/l treated with T patches at 5 mg/day
• Minnemann et al. (2007) - no placebo 25 subjects, mean age 57y w/ LOH and initial T levels of pretty high 14.3 nmol/l receiving TU 1000 mg/12 weeks from week 6

• 

  Suggested Read: Tribulus Boosts Testosterone (+12%), IGF-1 (+20%), Sheds 2kg (7%) Body Fat and Maintains Lean Mass in 12 Wk RCT | more

  Naharci et al. (2007) - no placebo, 24 subjects, 6 months, mean age 20.7y, low T at 5.7 nmol/l treated with mixed ester at 250 mg/3 weeks
• Saad et al. (2007) - no placebo, 28 subjects, 13 months, LOH with erectile dysfunction (ED), low  T at initially 7.5 nmol/l treated with  TU at 1000 mg/12 weeks from week 6
• Saad et al. (2008) - 27 subjects, 9 months, mean age 60y LOH with ED and initial T levels of 7.5 nmol/l treated with TU 1000 mg/12 weeks from week 6 or T gel 50mg/day
• La Vignera et al. (2009) - no placebo, 7 subjects, 3 months, mean age 58y, LOH with MetS and unknown baseline T levels treated with T gel 50 mg/day
• Moon et al. (2010) - no placebo, 133 subjects, 6 months, mean age 54y baseline T of 8.6 nmol/l treated with TU at 1000 mg/12 weeks from week 6
• Permpongkosol et al. (2010) - no placebo, 161 subjects, 13.5 months, mean age of 60.4y and LOH consulting urological center w/ T at 9.4 nmol/l on TU 1000 mg/12 weeks from week 6
• Garcia et al. (2011) - no placebo, 29 subjects, treated for 25.5 months,  mean age 55.5y, LOH and diabetes, no baseline T available, treated with TU 1000 mg/12 weeks from week 6
• Schwarz &Willix (2011) - no placebo, 56 subjects, 18 months, mean age 52.3y, overweight or obese with baseline T of 15 nmol/l receiving TC 80–200 mg/week + diet + training
• Arafa et al. (2012) - no placebo, 56 subjects, 12 months, mean age 55.5y w/ T2DM and unknown baseline T treated w/ TU 1000 mg/12 weeks from week 6
• Schroeder et al. (2012) - no plaebo 29 subjects, 4 months, mean age 71y, baseline T of 13.1 nmol/l treated with T patch 5 or 10 mg/day
• Jo et al. (2013) - no placebo, 18, 26.8 months, mean age 35.9y and suffering from Klinefelter syndrome, with low T at 3.1 nmol/l at baseline treated w/ TU 1000 mg/12 weeks from week 6

What is the Klinfelter syndrome? That's a genetic disorder that affects males. Klinefelter syndrome occurs when a boy is born with one or more extra X chromosomes. Most males have one Y and one X chromosome. Having extra X chromosomes can cause a male to have some physical traits unusual for males.

• Ko et al. (2013) - no placebo, 246 subjects, 14.7 months, mean age 58.5y  treated w/ TU 1000 mg/12 weeks from week 6
• Rodriguez-Tolrà et al. (2013) - no placebo, 50 subjects, 12 months, mean age 59.1y, LOH, mean T at baseline 10.2 noml/l treated w/ T gel 25–100 mg/day

• 

  Suggested Read: Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance | more

  Saad et al. (2013) - no placebo, 255 subjects, 60 months, mean age 58y, mixed urological population, low T at 10.0 nmol/l treated with TU 1000 mg/12 weeks from week 6
• Tirabassi et al. (2013) - no placebo, 15 subjects, 18.5 months, mean age of 55.7y, LOH w/ baseline T levels of 5.2 nmol/l on TU 1000 mg/12 weeks from week 6
• Zitzmann et al. (2013) - no placebo, 1438 subjects, 10.5 months, mean age 49.2y, LOH w/ baseline T levels of 9.6 nmol/l on TU 1000 mg/12 weeks from week 6
• Francomano et al. (2014) - no placebo, 20 subjects, 60 monhts, mean age 57.5y, MetS and basline T of 8.3 nmol/l on TU 1000 mg/12 weeks from week 6
• Pexman-Fieth et al. (2014) - 669 subjects, 6 months, 53y, LOH on  T gel 50, 75 or 100 mg/day
• Yassin et al. (2014) - no placebo, 261 subjects, 54 months, mean age 59.5y, LOH w/ baseline T levels of 7.7 nmol/l treated w/ TU 1000 mg/12 weeks from week 6
• Zitzmann et al. (2014) - no placebo, 381 subjects, treated for 60 months, mean age 42.6y w/ LOH and low T at 5.2 nmol/l on TU 1000 mg/12 weeks from week 6

Figure 1: Influence of trial duration (a, b), age (c, d) and testosterone levels at enrollment (e, f) on weighted mean differences (with 95 % CI) of body weight (a, c, e) and waist circumference (b, d, f) at endpoint after testosterone supplementation. The size of the circles reflects the sample dimension (Corona. 2016).

Why did the scientists prefer observational trials over RCTs? "The peculiar study design of these RCTs might, as the authors point out justify the lack of efficacy of testosterone supplementation on weight parameters in previous meta-analyses. In fact, RCTs are performed under idealized and rigorously controlled conditions, which are different from everyday clinical practice. Hence, results of RCTs offer an indication of the efficacy of an intervention rather than its effectiveness in everyday practice. [...] In contrast, observational and register studies maintain the integrity of the context in which medical care is provided. As a result, whereas RCTs provide an indication of the minimal effect of an intervention, observational studies offer an estimate of the maximal one," Corona et al. write.

Table 1: Number and proportion (%) men reporting use of AAS, life-time, past 12 months and past 30 days, in different subgroups (Leifman. 2011).

All in all, we are talking about 32 out of 824 initially retrieved articles and 4513 patients whose mean age of 51.7 ± 6.1 years is yet far above that of the average PED (ab-)user whose age appears to be somewhere between 25 and 29, likely to have visited only "compulsory school" and a friend of alcohol and dietary supplements (Leifman. 2011 | see Table 1) and a very obvious result, i.e. that the supplementation of testosterone "was associated with a time-dependent reduction in body weight and waist circumference (WC).

To be more specific, "[t]he estimated weight loss and WC reduction at 24 months were −3.50 [−5.21; −1.80] kg and −6.23 [−7.94; −4.76] cm, respectively" (Corona. 2016). In addition, the provision of testosterone was, as you would probably have guessed based on previous SuppVersity articles, "also associated with a significant reduction in fat and with an increase in lean mass as well as with a reduction in fasting glycemia and insulin resistance" that were accompanied by reductions in fasting glycemia and insulin resistance (IR), as detected by HOMA-IR index - especially in studies enrolling a diabetic subject clientele at baseline (Corona. 2016).

Figure 2: Effects of TRT on blood pressure, lipids and glucose metabolism (Corona. 2016).

But isn't testosterone supplementation (TS) bad for your cholesterol and blood pressure? Even though nobody really appears to care about cholesterol on the interwebs, these days, the claim that testosterone would ruin your blood lipids and, maybe more importantly, one's blood pressure, is still propagated on "the boards". In the studies Corona et al. reviewed for their latest meta-analysis, however, the provision of exogenous testosterone (albeit in not necessarily superphysiological levels) triggered sign. improvements of the subjects' lipid profiles (reduction in total cholesterol as well as of triglyceride levels and an improvement in HDL cholesterol levels) and in both systolic and diastolic blood pressure was observed.

You're scratching your head, I see... Are you disappointed of the effect sizes? Well, you should take a closer look at the full spectrum of the results. Let's take the reduction in waist circumference, for example (Figure 3):

Figure 3: Effect of TS on waist circumference (cm) in the studies that were part of the meta-analysis (Corona. 2016).

As you can see, the latter ranged from ZERO in La Vignera (2009), who didn't even measure the waist circumference ;-) to HERO,... ah, I mean -19.6 cm in Zitzmann (2014), who studied the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. With a baseline waist circumference of relatively moderate 99.5 +/ - 15.25 cm, we are talking about a ~20% reduction in waist circumference, here!

Figure 4: Zitzmann et al. also found sign. improvements in mood (left) and the ability to concentrate (right) in their previously (mostly) hypogonodal subjects (Zitzmann, 2014).

Physical changes that were accompanied by significant improvements in the subjects' mood (Figure 4, right) and ability to concentrate (Figure 4, right) - results that had the authors conclude that their "study corroborates and strengthens the modern view on the desirability and efficacy of substitution therapy in men with proven hypogonadism, also in a “real-life” setting" (Zitzmann. 2014).

You to know more about superphysiological doses?

If that's not "good enough" for you, let me remind you of my previous review of a seminal paper by Bhasin et al.  who conducted (to my knowledge) the only "dose-escalation" study that comes remotely close to being a "PED"-RCT, i.e. a controlled trial that may give us some insights into the effects T at dosages that are used by performance enhancing drug users would have.

Figure 5: Dose response relationship of muscle gain (in kg) per mg of testosterone enanthate (left) , the white line indicates a dose that would probably have produce testosterone levels identical to baseline; and relative change in lean and fat mass in response to changes in serum testosterone levels (right | Bhasin. 2001)

While I've reprinted the most important data in Figure 5, I'd still suggest you take a closer look at the corresponding SuppVersity Classic article, if you want to learn more - especially about the interpretation of the graph on the right hand side that shows the relative change in lean and fat mass in response to changes in serum testosterone levels.

Overview of factors controlling muscle gains (Moussa. 2012)

If you want to know what's possible in healthier people, I suggest you go back to my articles in the "Intermittent Thoughts on Building Muscle" series. More specifically, the articles "Zoning in on "The Big T" - Does Testosterone (Alone) Build Muscle?" (read it), "Quan-tifying "The Big T" - Do Testosterone Increases Within the Physiological Range Really Matter? And How Much is too Much?" (read it) and the conclusion "Exercise, mTOR/AKT/MAPK, IGF-1, Testosterone, Estrogen, DHT, Nutrition, Supps & Sleep" (read it) from which I have copied the overview of different mechanism that contribute to / control muscle growth on the right | Comment

References:

• Baker, Julien S., Michael Graham, and Bruce Davies. "Gym users and abuse of prescription drugs." Journal of the Royal Society of Medicine 99.7 (2006a): 331-332.
• Baker, J. S., M. R. Graham, and B. Davies. "Steroid and prescription medicine abuse in the health and fitness community: A regional study." European journal of internal medicine 17.7 (2006b): 479-484.
• Bhasin, Shalender, et al. "Testosterone dose-response relationships in healthy young men." American Journal of Physiology-Endocrinology And Metabolism 281.6 (2001): E1172-E1181.
• Corona, G., et al. "Testosterone supplementation and body composition: results from a meta-analysis of observational studies." Journal of Endocrinological Investigation (2016): 1-15.
• Graham, Michael R., et al. "Anabolic steroid use." Sports medicine 38.6 (2008): 505-525.
• Herschthal, Adam. "From Rats to Riches: How the Anabolic Steroid Control Act of 2004 Unjustly Punished the Gym Rat and How a New Prescription Is the Road to Salvation." Syracuse L. Rev. 63 (2012): 437.
• La Vignera, S., et al. "Andrological characterization of the patient with diabetes mellitus." Minerva endocrinologica 34.1 (2009): 1-9.
• Rahnema, Cyrus D., et al. "Anabolic steroid–induced hypogonadism: diagnosis and treatment." Fertility and sterility 101.5 (2014): 1271-1279.
• Zitzmann, Michael, et al. "IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men." The journal of sexual medicine 10.2 (2013): 579-588.

Your Post-Workout Testosterone Levels Can Predict Your Gains - Study Takes Novel Approach to the T ↔ Muscle Link

Your Post-Workout Testosterone Levels Can Predict Your Gains - Study Takes Novel Approach to the T ↔ Muscle Link

build muscle gains gainz GH hormones IGF-1 insulin muscle gains testosterone

GainZ - Are they all about T and we just didn't do the right statistical tests in previous studies to realize that?

Only recently one of the longstanding "truths" of protein anabolism has been busted (learn why the acute muscle protein synthesis response matters more than prev. thought). And now, a new paper in the Journal of Strength and Conditioning Research (Mangine. 2016), appears to suggest that the lack of effect of exercise induced hormone elevations may have been misunderstood, too.

In the conclusion of their study, Mangine et al. point out that the previously used "[t]raditional statistical measures do not adequately assess the relationships between multiple variables that exist across time" (Mangine. 2016).

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In order to overcome this problem, their study used what the scientists call a "unique method for analyzing these types of relationships without the need for transforming data"; and - first things first - their the PLS-SEM analysis (details below) shows: "baseline muscle size and the hormonal response to resistance exercise are related to muscle hypertrophy following 8 wks of training  (Mangine. 2016).

Figure 1: The scientists ,odel for the relationship between changes in muscle size and the endocrine response to resistance exercise predicts influence of all hormones on muscle size and vice versa(!); RF_CSA = Rectus femoris cross-sectional area; RF_MT = Rectus femoris muscle thickness; VL_CSA = Vastus lateralis cross-sectional area; VL_MT = Vastus lateralis muscle thickness; WK1 = Week 1; WK8 = Week 8 (Mangine. 2016).

Moreover, the data from the Kennesaw State University, the University of Central Florida and the College of New Years appears to suggest that the often derided exercise-induced post-workout (PWO) increases in testosterone concentrations may be the most important agent in the hormone quintet of testosterone, cortisol, growth hormone, IGF-1, and insulin that is going to react to every intense resistance training study.

Figure 2: Sign. associations between PWO hormone levels and lean mass, as well as fiber size increases (West. 2012).

That's surprising in two ways: (A) the majority of previous studies refuted the existence of a practically relevant link between the amount of muscle you will gain and the change in hormone levels, altogether. And (B) you will remember that my hitherto favorite study on the "[a]sociations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training" by West and Phillips (2012) showed in a large cohort that - if there is any link between the PWO hormone response to resistance training and the changes in muscle size it would be a link to growth hormone (GH) and cortisol (see Figure 2).

Free testosterone (upper line) and cortisol (lower line) levels before and after exhaustive endurance exercise in trained young men (Anderson. 2016).

Excess cardio cannot, it will ruin your testosterone levels and (surprise) 24h post also your cortisol levels: The data in the figure on the left hand side was recorded in a recent study by Anderson et al. (2016) who observed that the full recovery of free testosterone and cortisol after an exhaustive endurance exercise session (prolonged exercise run on the treadmill until volitional fatigue, running at 100 % of ventilatory threshold (VT), within 3 % - 75 minutes) will take 48h - even in endurance trained fit, young men such as the 12 subjects (VO2max 66.3±4.8 ml/kg/min, age 22.8 ± 3.1 years, body fat 11.0 ± 1.4 %, training 7.1y) Anderson et al recruited.

That's obviously significantly different from what we see in the Magine study, at hand, where the likewise previously trained subjects completed at least 28 resistance training sessions (~90%) of an 8-wk resistance-training program (4 sessions/wk) that included six upper- and lower-body exercises during each session, under supervision of certified strength & conditioning specialists.

With the inclusion of potential influence of the initial muscle mass on the hormonal response to exercise Magine's study does now suggest what many trainees still believed, anyways: "When it comes to making gainz, the testosterone response to workouts counts." Furthermore, the scientists argue that the reason studies like McCall et al. (1999), Ahtianinen et al. (2003), and Walker et al. (2015), which used Pearson’s product moment correlation coefficients or Spearman’s rank correlation coefficients (Walker. 2014) were conflicting and not really reliable, because...

"significant amount of information [that] is lost when using either of these statistical procedures for assessing the relationships between concepts that exist across time (i.e. hypertrophy, multiple endocrine responses) because the statistics can only assess the relationship between two sets of values" (Mangine. 2016). 

With their approach, on the other hand, Mangine et al. (2016) transformed the correlation between hypertrophy and the endocrine response from baseline and post-testing into a single value (i.e. change score, average score). The method to do this is called "partial least squares structural equation modeling" (PLS-SEM) and it allows estimating complex cause-effect relationship models with latent variables. Since it is a component-based estimation approach, it differs from the covariance-based structural equation modeling you'd usually expect to be used and constitutes, as the scientists summarize

"[...] a variance based procedure that utilizes bootstrapping to statistically assess the relationships between multiple latent variables that are developed from several collected indicator variables [which has] been used to assess relationships within the biomedical sciences [already... even though] it has not yet been used to assess the relationships between the post-exercise endocrine response and muscle hypertrophy" (Mangine. 2016).

For it to work, the authors obviously have to assume that "the related variables were collected without systematic or random error" in their experiment that included pre-tests (PRE) of measures of muscle size (thickness and cross-sectional area) of the vastus lateralis and rectus femoris in 26 resistance-trained men who were randomly selected to complete a high-volume (VOL, n=13, 10–12RM, 1-min rest) or high-intensity (INT, n = 13, 3–5RM, 3-min rest) resistance training program while following a food-log controlled diet that was supplemented with a standardized supplement containing ~235 mL of chocolate milk (170 calories; 2.5g Fat; 29g Carbohydrate; 9g protein) or Lactaid® (150 calories; 2.5g Fat; 24g Carbohydrate; 8g protein) to each participant immediately following each workout.

A pre- vs post-workout salivary testosterone test could hold the clue to the perfect workout | more

Another argument that "testosterone may count" comes from a previously discussed, but in my humble opinion largely overlooked study by Beaven et al. (2008) whose study into the correlation between the individual testosterone response to a certain workout style and the subsequent gains subjects in a randomized cross-over design study made also suggests that "testosterone counts". Sounds intruiging? I know, but the corresponding SuppVersityarticle from 2013 went almost as unrecognized as the original paper that was published 5 years before in the Journal of Strength and Conditioning Research - the same journal in which Mangine et al. have now published the results of their study.

Blood samples were collected at baseline, immediately post-exercise, 30-min, and 60-min post-exercise during weeks 1 (WK1) and 8 (WK8) of training and testosterone, growth hormone [22 kD], insulin-like growth factor-1, cortisol, and insulin levels were evaluated using area-under-the-curve (AUC) analyses of the blood values, based on which the scientists were able to identify the relationships between muscle size (PRE), AUC values (WK1 + WK8) for each hormone, and muscle size (POST) "using a consistent PLS-SEM algorithm and tested for statistical significance (p<0.05) using a 1000 samples consistent bootstrapping analysis" (Mangine. 2016).

Figure 3: Actually significant was only the link between the effect of the muscle mass before the study and the testosterone response and the testosterone response on the muscle mass after the 8-wk study (Mangine. 2016).

The model the scientists developed was capable of explaining 73.4% (p<0.001) of variance in muscle size at POST and revealed "[s]ignificant pathways between testosterone and muscle size PRE (p=0.043) and muscle size at POST (p=0.032) were observed.

Table 1: In contrast to what you may have expected, there was no sign difference in the way the hormones effected the outcomes of the 8-wk resistance training study between the high intensity and volume arm (Magine. 2016).

And while the ability to explain muscle size at POST improved when the model was analyzed by group (INT: VOL: p<0.001), the data in Table 1 goes to show you that the researchers found no group differences between the intense low volume and the moderate intensity high volume training. This in turn suggests that the link between muscle size and post-exercise increases in hormone levels - especially the effects on testosterone - are universal and do not dependent on the training type (volume vs. high intensity), as previous studies that argued in favor of volume training based on its more pronounced effects on the hormone response to exercise suggested.

In view of the conflicting evidence and hitherto relatively conclusive evidence that endogenous T & co elevations do not matter, I would not begin to train "for testosterone elevations", now... you may after all still be barking up the wrong tree. Correlations and links are after all no causations | learn more

Bottom line: I would like to point out that the study at hand does not provide sufficiently reliable evidence to say that Mangine, et al. had 'proven that the post-workout testosterone increase had a mechanistic effect on your muscle gains'. What it does show, however, is, just as the scientists say, that "[e]xercise-induced testosterone elevations, independent of the training programs used in this study, appear to be related to muscle growth" (Magine. 2016, my emphasis in the quote).

This is in contrast to previous studies, where the pre-tfiraining correlation between muscle mass and thus testosterone levels had not been accounted for. The scientists' partial least squares regression structural equation modeling (PLS-SEM), however, is eventually just "statistical shenanigan". Therefore, its impressive explanatory power of 73.4% of the variance in muscle size following 8 wks of resistance training is a neat figure, but no proof of a mechanistic link.

Furthermore, one has to be careful to falsely single out testosterone among the five hormones that were assessed. After all, restricting the model to T, which was the only significant hormonal correlate of muscle gains, reduced the explanatory power of the model by only 30.8%. This leaves the rest of the hormones with an explanatory power of 42.6% (all statistics, obviously ;-). To say that GH, IGF-1, insulin and cortisol had 'no say' in skeletal muscle hypertrophy is thus just as unwarranted as the previously hinted at (false) conclusion that the study at hand would provide the long-sought definitive evidence of the muscle building effects of exercise-induced, natural testosterone surges, i.e. the temporary elevation of T-levels after a workout | Comment!

References:

• Ahtiainen, Juha P., et al. "Muscle hypertrophy, hormonal adaptations and strength development during strength training in strength-trained and untrained men." European journal of applied physiology 89.6 (2003): 555-563.
• Beaven CM, Cook CJ, Gill ND. Significant strength gains observed in rugby players after specific resistance exercise protocols based on individual salivary testosterone responses. J Strength Cond Res. 2008 Mar;22(2):419-25.
• Mangine, Gerald T., et al. "Exercise-Induced Hormone Elevations Are Related To Muscle Growth." The Journal of Strength & Conditioning Research (2016).
• McCall, Gary E., et al. "Acute and chronic hormonal responses to resistance training designed to promote muscle hypertrophy." Canadian Journal of Applied Physiology 24.1 (1999): 96-107.
• Walker, Simon, et al. "Effects of prolonged hypertrophic resistance training on acute endocrine responses in young and older men." Journal of Aging & Physical Activity 23.2 (2015).
• West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.

Tribulus Boosts Testosterone (+12%), IGF-1 (+20%), Sheds 2kg (7%) Body Fat and Maintains Lean Mass in 12 Wk RCT

Tribulus Boosts Testosterone (+12%), IGF-1 (+20%), Sheds 2kg (7%) Body Fat and Maintains Lean Mass in 12 Wk RCT

andropause build muscle gains lose fat male health testosterone testosterone booster tribulus tribulus terrestris TRT

Could a high dose of purified saponin tribulus extract as it was obviously used in the study at hand actually be a valid TRT alternative or even option? 

No, this is not the 2015 study in trained boxers that found similarly surprising, because impressive benefits from tribulus terrestris (TT) supplementation (read it). It's a new study from the Jerzy Kukuczka Academy of Physical Education in Katowice, Poland (Wilk. 2016) that has no direct link to the previously discussed study from the  Shanghai University of Sport Affiliated School of Sports in China.

And even though, the aim, i.e. to determine the effects of steriodal saponins from tribulus terrestris on the blood concentration of testosterone (T), GH and IGF-1 was similar, the overall design of the study was significantly different.

Don't forget to work out - Without exercise you're not going to get lean and jacked, bro!

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Study Indicates Cut the Volume Make the Gains!

While the previously discussed study by Ma et al. (2015) was conducted with young athletic individuals, Wilk et al. deliberately chose 14 men between the age of 45 and 60 years, i.e. exactly those years in a man's life over the course of which the natural hormone production starts to decline significantly.

Table 1: How to recognize your T-levels are declining (from Matsumoto. 2002).

Over twelve weeks, the subjects who were normal-to-overweight with a body mass index of 25–33, and body fat content between 23–30%, received either...

• experimental group: steroidal saponins (TT) - for the first six weeks three capsules (900 mg) per day in split doses (2x capsules were ingested in the morning on an empty stomach, 600 mg, and one at bedtime, 300 mg) and twice the dose, i.e. 6 capsules (1,800 mg) were ingested per day in split doses (4x capsules in the morning on an empty stomach, 1,200 mg, and 2x capsules at bedtime, 600 mg), or 

What's the use of the "front load", i.e. taking more in the AM vs. PM? That's a question I just received from Peter via Facebook. Good question, but one the scientists do not answer. So I'd have to speculate that they may have intended to mirror the natural 24h (=circadian) rhythm of testosterone which peaks in the AM and declines over the day to re-increase over night and peak again in the AM. What is particularly interesting about this rhythm, by the way, is that it - or rather the peaks in the AM, are lost as you age (see Figure on the left | Bremner. 1983).

• control group: placebo (CON) - in the form of gelatin capsules using the same supplementation protocol as it was prescribed in the experimental group 

And even though all subjects participated in a physical activity program over the 12 week study period, the workouts the scientists describe as follows,...

"Get leaner, more muscular and hornier than ever before" - That's probably the promise on the T-booster someone will release after reading this SuppVersity Classic article and sourcing an inferior Shilajit extract on Alibaba. Is that going to be a waste of time - just as the majority of the tribulus products on the market, which are lightyears away from providing grams of pure saponines on a multiple serving per day basis | learn more.

"4 training sessions per week, with 2 sessions directed at the improvemnt of anaerobic power (resistance exercise), while 2 consisted of aerobic endurance exercise. Aerobic training was performed on a stationary cycle ergometer, starting with 30 minutes of continuous exercise at an intensity of 70–75% of maximum heart rate (HR max). Every two weeks, the work volume was increased by 5 minutes in order to reach 60 minutes in the last two weeks of the experiment. Strength training had a holistic aproach, involving all major muscle groups (the back, chest, abdomen, arms and lower limbs). For the first four weeks, exercises were performed in 3 sets of 8–12 reps with the resistance equal to 60–70% of 1RM and 2 min rest periods between sets. During the experiment, the number of sets of each exercise increased from 3 to 4 sets in weeks 5–8, and respectively to 5 sets in weeks 9–12 for each exercise," (Wilk. 2016)

was of course not the same as the one in the previously discussed Chinese study. In conjunction with the standardized isocaloric (same energy content) mixed diet containing 55% carbohydrate, 20% protein, 25% fat, the workouts are still an important means of standardizing / reducing inter-group differences that could otherwise arise due to personal exercise and / or diet preferences.

Figure 1: Relative changes in blood lipids, GH, IGF-1 and testosterone (Wilk. 2016).

The results of the scientists' two series of laboratory tests (independent tests were conducted at the beginning and after 12 weeks of the intervention), revealed a statistically significant effect of the intervention on the following variables: T-Ch (η2 = 0.542), HDL-Ch (η2 = 0.522), LDL-Ch (η2 = 0.587), T (η2 = 0.603), IGF-1 (η2 = 0.512) and GH (η2 = 0.621).

Figure 2: Relative changes in body composition; effect sizes and p-values (Wilk. 2016).

Effects of which you will probably pleased to hear that they went hand in hand with significant decreases in total body fat (TBF) total body mass (BM) and borderline significant effects on the fat-free mass (muscle, organ and bone mass) of the subjects - an observation of which the scientists say that it "indicate[s] that treatment or supplementation of individual hormone deficiencies can be a successful form of counteracting the aging process" - an aging process that is evidenced by increasing body fat levels, decreasing amounts of fat-free mass and concomitant deterioration of blood lipids and blood glucose (the latter was unfortunately not measured in the study at hand).

Wtf!? What kind of tribulus was that? I wish I could tell you that, but a brand name or other specifics are not mentioned in the publicly financed study from Poland.

Make no mistake about it, the impressive increases in free T in Brown's often miscited 2001 study from which I took this figure were due to a combination of the prohormone androstenediol with tribulus and other herbs. To ascribe the T-increase to TT is idiotic.

What I can tell you is that the results are in line with a 2009 study by Milasius, et al. who used food a commercial supplement Tribulus from Optimum Nutrition, USA, and observed positive effects on the acid-base equilibrium after short-term, high intensity anaerobic exercise in competitive athletes. The study at hand apparently used a more pruified steroidal saponin supplement, however, and observed similar effects as Brown et al. (2001), who supplemented tribulus alongside 300mg of the prohormone androstenediol and found - not to anyone's surprise, probably a significant effect on serum testosterone concentration in both young and older men (see Figure to the right).

Since no such effects were observed in the often cited study by Neychev, et al.  (2005) in allegedly much younger subjects, the question future studies will have to answer is whether that's due to an (subject-)age- or dosage / otherwise supplement-related difference between the high dose of (probably) pure saponins used in the study at hand and the relatively low dose of Bulgaria TT (200mg/day) with 60% saponins that was used by Neychev, et al. in 2005 | Comment!

References:

• Bremner, William J., Michael V. Vitiello, and Patricia N. Prinz. "Loss of Circadian Rhythmicity in Blood Testosterone Levels with Aging in Normal Men*." The Journal of Clinical Endocrinology & Metabolism 56.6 (1983): 1278-1281.
• Brown, Gregory A., et al. "Endocrine and lipid responses to chronic androstenediol-herbal supplementation in 30 to 58 year old men." Journal of the American College of Nutrition 20.5 (2001): 520-528.
• Matsumoto, Alvin M. "Andropause clinical implications of the decline in serum testosterone levels with aging in men." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57.2 (2002): M76-M99.
• Milasius, K., R. Dadeliene, and Ju Skernevicius. "The influence of the Tribulus terrestris extract on the parameters of the functional preparedness and athletes’ organism homeostasis." Fiziol Zh 55.5 (2009): 89-96.
• Neychev, Vladimir Kostadinov, and Vanyo Ivano Mitev. "The aphrodisiac herb Tribulus terrestris does not influence the androgen production in young men." Journal of ethnopharmacology 101.1 (2005): 319-323.
• Wilk, Michał, et al. "Endocrine Responses to Physical Training and Tribulus Terrestris Supplememtation in Middle-Age Men." Central European Journal of Sport Sciences and Medicine 13.1 (2016): 65-71.

Shilajit: Ayurvedic Testosterone Booster that Works in Men, not Rats: ~20% Increase in Free T + Higher Total T & DHEA

Shilajit: Ayurvedic Testosterone Booster that Works in Men, not Rats: ~20% Increase in Free T + Higher Total T & DHEA

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"Get leaner, more muscular and hornier than ever before" - That's probably the promise on the T-booster someone will release after reading this SuppVersity article and sourcing an inferior Shilajit extract on Alibaba.

No, I hadn't heard of Purified Shilajit (PS), either, before I read about it in a very recent study in the peer-reviewed scientific journal Andrologia (Pandit. 2015). Actually, the study was first published in online (ahead or print), in late 2015. It took several months for it to be finally available in print and to appear on my "study radar", though.

Shilajit is traditionally used in Ayurveda, an indigenous system of Indian medicine, as a remedy for several diseases, particularly chronic diseases. It is a pale-brown to blackish-brown exudate that oozes from sedimentary rocks worldwide, largely in the Himalayas. The natives describe it as pahar-ki-pasina (sweat of mountains), paharki-khoon (mountain blood), shilaras (rock juice), asphalt, bitumen, etc.

Don't forget to work out - Without exercise you're not going to get lean and jacked, bro!

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Shilajit is said to carry the healing power of these great mountains (Frawley. 1986) and is one of the "important drug[s] of the ancient Ayurvedic materia medica and [... ] to this day used extensively by Ayurvedic physicians for a variety of diseases (Pandit. 2015). As Pandit et al. point out, ...

"[e]arly Ayurvedic writings from the Charaka Samhita (Sharma, 1998) describe Shilajit as a cure for all diseases as well as a Rasayana (rejuvenator) that promises to increase longevity. It is composed of rock humus, rock minerals and organic substances that have been compressed by layers of rock mixed with marine organisms and microbial metabolites" (Pandit. 2015).

That this is probably not exactly accurate must not hide the fact that it has in fact been used successfully to treat diabetes and diseases of the urinary tract, oedema, tumours, muscle wasting, epilepsy and even insanity in practice and that clinical research confirms many of the properties for which Shilajit has been used (Talbert. 2004).

Figure 1: A study by Biswas 2009 in infertile men is the first to show the potent effects of Shilajt in a randomized controlled human trial involving a total of 60 (active treatment + placebo) oligospermic men (Biswas. 2009).

Needless to say that, in Ayurveda, Shilajit is also used for the management of male reproductive disorders, and in particular, under the parlance of Vrisya (an aphrodisiac with special reference to spermatogenesis). In that, it has been shown to pose no toxicity issues with several studies reporting an LD50 of  >2000 mg/kg, acutely (Acharya et al., 1988; Ghosal et al., 1989), and doses of 0.2–1.0 g per kg body weight when used chronically (Kelginbaev et al., 1973; Anisimov & Shakirzyanova, 1982; Fortan & Acharya, 1984; Al-Hamaidi & Umar, 2003).

And the data from Biswas 2009 study (Figure 1) demonstrates that Shilajit is not just safe (no alterations in serum urea, uric acid, serum bilirubin, total protein, serum globulin, SGPT, SGOT and alkaline phosphatase were observed), but also effective in improving the total sperm count (+61.4%), motility (12.4–17.4% after different time intervals), normal sperm count (+18.9%) and total testosterone (+23.5%) levels with concomitant decrease in 28 patients with oligospermia and infertility when it was administered at a dosage of only 100 mg twice daily for 90 days.

Sponsored study warning: The study used a product that goes by the name PrimaVie™. It is a a patented (US 6,440,436, 6,969,612, 6,558,712, EP 1 387 614) standardized extract of native Shilajit from Natreon, Inc. of which the scientists confirmed in HPLC analysis that it contains >60% w/w of total bioactives, which include not less than 50% w/w of fulvic acids (FAs), not less than 0.3% w/w of dibenzo α-pyrones (DBPs) and not less than 10% w/w of dibenzo-α-pyrone chromoproteins (DCPs). Unfortunately, the producers didn't just sponsor the product but also supported the study. This does not mean that the results are not reliable, but we must still treat the scientists conclusions more carefully than those of independent researchers. Furthermore, the scientists recorded 21 dropouts (total from both groups) who were not included in the calculations of testosterone and co.

According to Pandit et al. the data from Biswas study is supported by their own unpublished human safety study of purified Shilajit from Natreon, Inc., New Brunswick, NJ, USA, and an unpublished animal study in rats with 100 mg/kg b.w. (equivalent to human dose of 850 mg) by Natreon showed a significant increase in testosterone levels. Based on the three studies, Pandit et al. chose a dose of 250 mg twice daily for their study.

Figure 2: Schematics of study design (Pandit. 2015).

"A schematic of the study design is shown in Fig. 2. Healthy volunteers aged between 45 and 55 years, irrelevant of religion, income status and occupation, were selected for the present purpose, and the distribution of patients was done by the method of double-blind randomised techniques. Initially, 145 volunteers were selected on the basis of primary assessment eligibility and 49 among them were excluded for various reasons (Fig. 2). A total of 96 volunteers were enrolled in the present trial and randomly divided into two equal groups as PS treated and placebo treated, each with 48 subjects. In the course of the study, 21 subjects discontinued for various reasons and 38 subjects in PS-treated group and 37 subjects in the placebo group completed the study (Fig. 2). Mean age of the volunteers was 49.44 years in the test drug group and 48.89 years in the placebo group, and thus, there is no bias due to the difference in mean ages" (Pandit. 2015).

Subjects in both groups received respective drugs in the dose of 250 mg/capsule orally, twice daily after major meals, for a total duration of 90 days. In that...

• Group – I received the active treatment PS 250 mg BID (38 subjects), while 
• Group – II was supplied w/ a Placebo 250 mg (microcrystalline cellulose 124 mg + lactose 124 mg + magnesium stearate 2 mg) BID (37 subjects)

Both the PS and placebo capsules were white opaque, Size 1, and looked identical. The same cannot be said of the study results in Figure 3.

Figure 3: Effect of PS on testosterone & its mediators w/ respect to placebo control; rel. changes over bars (Pandit. 2015).

More specifically, Pandit et al. observed that in the "PS-treated group, there was an increase in testosterone levels (ng/ml) on days 30 (6.82%), 60 (3.09%) and 90 (20.45%) with respect to day ‘0’" (Pandit. 2015). Furthermore, ...

• testosterone levels on day ‘90’ rose significantly (P < 0.05) vs. baseline in PS,
• testosterone levels decreased sign. (P < 0.05) vs. baseline in placebo,
• testosterone in PS-treated group on day 90 was sign. higher (P < 0.05) than placebo, 
• free testosterone in PS-treated group on day 90 increased sign. (19.14%), and 
• free testosterone level of PS-treated group on day 90 was also sign. higher than placebo.

In addition, the researchers recorded no difference in LH levels (which is good, because this means the testes worked more efficient, not overtime) and a significantly increased FSH level (P < 0.004) in the PS-treated group on days 30, 60 and 90 with respect to baseline. Thus, the result of FSH was significantly better in PS-treated group than placebo group on day 90.

The same goes for DHEAs, the adrenal hormone and potential (!) precursor of testosterone, which showed "interesting results" (Pandit. 2015) with PS, where the level of DHEAs gradually increased on day 30 (9.14%), 60 (9.59%) and 90 (31.35%) with respect to values on day ‘0’. The change of DHEAs in placebo group, on the other hand was "irregular" (Pandit. 2015). Eventually, the level of increase in DHEA in PS-treated group on day 90 was found to be significantly higher (P < 0.05) than baseline value of PS-treated group and 90-day value of placebo.

T-Boosters Revisited: Maca & Garcinia Cola Boost Testosterone by More Than 125% and 300% While Increasing Libido | more!

Bottom line: So what's going on, here? 20% increase in testosterone? That's huge! No? Well, it is a significant difference, but the 20% decrease in testosterone 'due to' a placebo, of which the researchers say that it "has neither stimulation nor inhibiting role on testosterone secretion or synthesis" (Pundit. 2015), should be evidence enough that a 20% change in testosterone levels can occur "randomly".

Against that background and in view of the fact that the scientists don't discuss the regular circadian variety in testosterone levels, I have to repeat my "watch out: sponsored research!"-warning | Comment on Facebook!

References:

• Biswas, Tuhin Kanti, et al. "Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia." Andrologia 42.1 (2010): 48-56.
• Frawley, David, and Vasant Lad. "The yoga of herbs." Santa Fe (NM): Lotus (1986).
• Pandit, S., et al. "Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers." Andrologia (2015).
• Talbert, Robert. "Shilajit: a materia medica monograph." California College of Ayurveda A 1117 (2004).