10%(+) Reduction in Testosterone After Glucose and Whey Protein Shakes - Is the Classic #BB Shake Anti-Anabolic?

We're talking about a cross-over study in adolescent subjects and acute changes but that's neither the only nor the most relevant reason you don't have to be afraid of the bodybuilding staple, now. In fact, a closer look at the data seems to suggest that we're talking about a 'protein-anabolic decrease in testosterone'... sounds odd? Well, here's how it may relate to your #androgenReceptors (AR) and eventually your gainz, irrespective of your age, by the way.

I have previously addressed the possible ill effects of very high protein intakes on your testosterone levels - in particular, when those intakes are combined with a caloric deficit and, accordingly, reduced intakes of glucose and fat (re-read "True or False - High or Low Protein Intakes Have Profound Influence on Testosterone, SHBG, Estrogen, Cortisol & Co?" | here)... Now, a new study in Clinical Endocrinology (Schwartz 2019) shows that testosterone ⇆ protein/carbohydrate interactions trigger significant acute decreases in serum testosterone levels in those whose testosterone levels should be soaring: adolescent males.

Read more about studies involving TRT/HRT & co on suppversity.com:

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Needless to say that this raises the question: Does that mean that a classic #bodybuilding staple, the high carb, high protein post-workout shake, will ruin your 'muscle building hormone' (learn more)?

The study Schwartz et al. conducted in twenty‐three adolescent males (12‐18 years old; only those with testosterone levels indicating mid-late puberty were included in the analysis) measured the levels testosterone, as well as luteinizing hormone (LH), GLP‐1 (active), ghrelin (acylated), glucose, insulin and subjective appetite prior (0) and at 20, 35 and 65 minutes after the consumption of a test-beverage; a test beverage that contained...

"...either 1 g of glucose monohydrate (BioShop Canada Inc, Burlington, Ontario, Canada) or 1 g of protein (plain whey protein isolate; BiPro USA) per kg of body weight [...] A noncalorie drink was used as control" (Schwartz 2019).

With a protein content of 90.4% (5.7% moisture, 2.2% ash, 1.18% fat and 0.6% carbohydrates), these test beverages were eventually only 'almost' isocaloric, though: 3.74 kcal/kg body weight for the protein and 4 kcal/kg body weight for the sugar shake is yet not far enough apart to invalidate the study results and the flavor was standardized:

"All beverages were flavoured with 1.5 mL of chocolate extract (Vanilla Food Company) to account for the flavour differences and mixed with 500 mL of water, similar to previous protocols.The whey protein and control beverages were sweetened with 0.2 g sucralose (Tate & Lyle) in order to match sweetness with the glucose beverage. Sucralose was chosen as it has been shown to have no effect on postprandial plasma glucose or insulin. Test beverages were prepared the evening before the study and refrigerated in order to be served chilled the following morning. Participants were served the drink in a large covered opaque cup through a straw" (Schwartz 2019).

In the 3xAM sessions that took place, each after a 12h fast, all participants of this cross over trial had to consume the randomly selected beverages (protein, glucose, control) within 5 minutes. In order to wash away any potential aftertaste, they topped that off with 50 mL of plain water.

Testosterone level changes from baseline to 60 min after ingesting the glucose/protein beverage in pre-early puberty (n = 8) and mid-late puberty (n = 13) | results of a previous study by Schwartz (2015).

Where does the idea of reduced T in adolescents even come from, anyway? Schwartz et al. actually did the study under review as a follow-up to their 2015 study in which they observed an acute decrease in serum testosterone after the consumption of a mixed glucose and protein beverage in order to identify whether glucose and protein, each on its own would have similar or the same ill effects on male adolescents postprandial testosterone levels as the researchers observed them in 2015. Reductions as high as -20% in male adolescents in the mid-late phase of puberty (see Figure on the left).

Since the scientists also speculated that these liquid snacks would have different effects on the subjects appetite and, more importantly, ad-libitum food intake, the boys/young men were fed an ad libitum pizza meal after the final blood draw. In that, the "[p]articipants were instructed to eat [pizza] during the next 20 minutes until comfortably full. Based on prescreening participant preferences" (Schwartz 2019 | Pepperoni pizza (87 g) contained 9 g protein, 6 g fat and 23 g carbohydrates for a total energy content of 180 kcal); three‐cheese pizza (81 g) contained 10 g protein, 6 g fat and 23 g carbohydrate for a total energy content of 180 kcal).

Significant differences in terms of the number of slices of pepperoni and/or three-cheese pizza were not observed. Neither in form of treatment nor baseline body weight. 

In other words, with ~1,300 kcal the pizza love (or rather food intake) of the boys was not influenced by either the beverage or the boys' weight status (F = 2.23, P = 0.14). That's in contrast to the testosterone levels which differed significantly when the scientists compared the testosterone response of overweight and normal-weight adolescents (Figure 1.B).

Figure 1: Differential effects of treatments by weight status (A), overall effect of weight status on plasma testosterone (B).

In that, Figure 1.B seems to suggest that lean individuals (mean BMI = 21.1 ± 0.9 kg/m²) are more susceptible to the detrimental effects of protein/carbohydrate shakes than overweight/obese ones (mean BMI = 29.8 ± 1.2 kg/m²). In fact, though, the differential effects of treatments by weight status that are plotted in Figure 1.A, as well as the lack of an asterisk below the open "normal weight" bar in Figure 1.B tell you that the ostensibly large changes in testosterone the scientists observed in the 12 normal-weight subjects were overall non-significant.

So, being overweight or obese seems in fact to modulate the effects of glucose and protein beverages on adolescents' ... as it is common for every extra pound you carry, negatively.

Table 1:  Baseline levels of appetite‐ and sex‐related hormones (Schwartz 2019); interestingly enough, the level of these metabolically relevant measures didn't change differently for normal- vs. overweight subjects in response to either PRO or GLU.

Does that mean that being fat sucks? Well, let's check if any of the metabolic parameters can explain the difference: At least based on the changes that were reported in the FT, that was not the case - while insulin, GLP1, and ghrelin increased, increased and decreased in response to the beverages, they did so to a similar extent in all adolescents. More importantly, though, ...

...there were no differences in the insulin, GLP1 and/or ghrelin response when comparing the protein vs. glucose beverages.

In the absence of treatment effects on the satiety and hunger hormones, it is no longer that surprising that the scientists didn't observe measurable (and significant) effects on the subjects' pizza intake (reported further towards the beginning of this article) - and that despite the fact that all participants' subjective appetite was decreased after the glucose (no, not the protein) beverage (p = 0.0198 for control and p = 0.0247 for protein).

So what's the main takeaway message, then? Is it "Boys love pizza, no matter what?" 

Well, that could be one takeaway, but I think that Schwartz et al. are right to point towards three other results when it comes to the takeaway messages:

• both, glucose and protein shakes acutely lower the testosterone levels of adolescent males, 
• but the effect is not mediated by the macronutrient composition of the liquid meals, 

Moreover, the levels of testosterone the scientists measured in their young subjects' blood or, rather, the changes that were induced by the protein and glucose beverages did not correlate with the regulation of appetite or food intake. The latter was, however, what the scientists had expected when they planned this follow-up to their previously mentioned 2015 study.

This is not an outlier study and similar effects can be expected in older men: The study at hand has by no means produced revolutionary new evidence. In fact, it rather adds to the results of previous research and the testosterone decline(s) that were observed in Caronia et al. 2013 in men who consumed 75g of glucose and Schwartz' previously referenced study in overweight/obese adolescents from 2015, for example (see previous infobox).

The underlying mechanisms of these effects, however, are still not clear. As the scientists from the University of Toronto point out, the changes may be initiated ....

Table 2: Relationships between testosterone and luteinizing hormone with dependent measures (Δ from baseline means).

"by the intake of glucose or amino acids, particularly leucine, which stimulates rapamycin (mTOR) signalling and subsequent protein synthesis" and/or their "inhibitory effect on adenosine monophosphate‐activated protein kinase (AMPK)," (Schwartz 2019)... 

which should - theoretically - have increased the androgen receptor (AR) mRNA expression (Shen et al. 2014 observed the opposite effect, i.e. AMPK up = AR down in prostate cancer cells and it's likely similar effects will occur in skeletal muscle).

Your androgen receptor status may not just determine how much muscle you gain - the data from Morton et al. seems to suggest that it even determines if you make visible muscle gains, at all (learn more in my August 2018 article with the title "If the Androgen Receptor Response to Training Determines Your Gainz, the Question is: How Can You Optimize 'ur AR Density? Training-, Diet-, and Supplement-Effects Reviewed".

So, does it all come back to androgen receptors? Unlike acute changes in testosterone, the androgen receptor density on your muscles has recently been shown to significantly affect the gains of resistance trained men. I discussed the corresponding study at length in a SuppVersity article from August 2018. What I may or may not have highlighted enough in that context is that...

...any increase in androgen receptor (AR) expression leads to greater testosterone uptake by the muscle tissue which lowers plasma testosterone levels... and that probably to an extent similar to what was observed in the study at hand!

This may also explain why neither glucose nor protein has ever been shown to have anti-anabolic effects. In fact, if their isolated and combined consumption in form of a beverage does indeed increase the AR receptor expression and lower the levels of circulating testosterone only by increasing the amount of T that's bound to receptors, that's even more evidence that, on the endocrine level, both nutrients exert pro- not anti-anabolic effects. Accordingly, the notion that the study at hand would support low-carb keto- vs. classic high protein + low-fat-diets for bodybuilders and anyone else striving for a muscular physique would be fundamentally flawed... but let's not jump to conclusions, here! It will be up to other, long(er)-term studies that include resistance training regimen and more relevant outcomes (=changes in body composition) to say which dietary pattern is best for your gainz - as of now, it seems to make less of a difference than people on either side of the nutritional divide want to make you believe - that is, assuming that the dietary protein and energy intake are equal in a low vs. high carb diet | Comment!

References:

• Caronia, Lisa M., et al. "Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism." Clinical Endocrinology 78.2 (2013): 291-296.
• Schwartz, Alexander, et al. "Acute decrease in serum testosterone after a mixed glucose and protein beverage in obese peripubertal boys." Clinical Endocrinology 83.3 (2015): 332-338.
• Schwartz, Alexander, et al. "Acute decrease in plasma testosterone and appetite after either glucose or protein beverages in adolescent males." Clinical Endocrinology (2019).
• Shen, Min, et al. "The interplay of AMP‐activated protein kinase and androgen receptor in prostate cancer cells." Journal of cellular physiology 229.6 (2014): 688-695.