Study Says "BCCAs, Don't Build Muscle!" I Say "True, But They Seem to Create an Anabolic Potential." Plus: Potential ≠ Growth ➲ You're Still Better Off With Complete Protein

The above is a question way too many trainees ask: "Who the f*** needs BCAA supplements?" Ok, the industry, but who else does?

They are not sold as the "next best thing", they are sold as "the best thing"any ambitious trainee may be taking. As a regular, here at the SuppVersity, you will yet know that despite all their advantages, the BCAAs, leucine, iso-leucine and valine, also have their downsides ("The Neurotransmitter Depleting Effects of Branched Chain Amino Acids (BCAAs) and Their Potential Ergolytic, Anxiogenic & Depressive Downstream Effects" | read more) and should not be all too surprised by the "news" that "BCAAs don't build muscle".

A news I gathered from a study by scientist from the Wayne, the Northeastern, the Victoria and the Texas A&M Universities; a study that says that the provision of 120mg/kg body weight of BCAAs did not augment the protein synthetic effect of resistance training in 27 active men (18-30 years), when it was added to a baseline peri-workout supplement that contained 1.5g/kg carbohydrates.
I guess some of you may be interested in a slightly less comprehensive overview of the supplementation regimen, so here are the facts again:

• 27 active men, 18-30y of age, no history of regular resistance training in the past year | Q: Why did the scientists select these participants? A: Because there is no chance that they will suffer from m-TOR resistance (learn more), therefore the increase in muscle protein synthesis (MPS) should be large and statistically different, if the supplementation regimen works | Q2: What about advanced / professional trainees? A2: If there is no response in someone with a normal baseline intake and little training experience, the chance that there is one in advances trainees borders zero.
• Comparison of (a) BCAA + CHO vs. (b) CHO (c) PLA, peri workout | By comparing BCAA + CHO vs. CHO alone to a calorie, CHO and amino acid free placebo, the scientists wanted to isolate the individual "impact of peri-exercise supplementation of BCAA [...] on markers indicative of muscle protein  synthesis within the PI3K/Akt-mTOR signaling pathway in human skeletal muscle following a single bout of RE [resistance exercise]." (Ferreira. 2013)
• Dosing - 120mg/kg BCAAs (~9-10g of BCAAs), 1.5g/kg carbohydrate | The supplements were dissolved in regular Chrystal Light(R). The placebo was Chrystal Light(R).

• Figure 1: Schematic presentation of the experimental protocol (Ferreira. 2013)

  Timing - 1/3 of the total amount of BCCA+CHO / CHO 2xPRE, 1xPOST | You can see the "exact" timing in Figure 1 to the right - don't forget that the whole dosage of ~9.6g of BCAAs and 120g carbs was spread equally!
• Exercise regimen - 4 sets of leg presses and -extensions | Warm-up with 2 sets of 10-12 reps of angled leg press and knee extension exercise, each (10-12 reps at 50% of 1-RM) + 4 sets of 8-12 repetitions at 75%-80% of 1-RM leg presses + extensions; 2.5 min of rest between sets.
• Hypothesis: The BCAAs will have a greater anabolic effect | In particular, Ferreira et al. expected the signaling markers IRS-1, Akt, mTOR, and p70S6K to be elevated in response to the addition of BCAAs to the CHO baseline.

By now you should be in the know, as far as the study design is concerned. The most important question, i.e. "What were the results", does yet still have to be answered. So let's take a look at the data in Figure 1 and see if it's correct that "peri-exercise co-ingestion of CHO and BCAA did
not augment RE-induced increases in skeletal muscle signaling markers indicative of MPS
when compared to CHO. " (Ferreira. 2013)

Figure 2: Post-workout changes in insulin, insulin recepter 1 expression, Akt, mTOR, p70S6k and 4E-BP1 (Ferreira. 2013)

I have to admit, the researchers almost tricked me to believe them... well, at least until I plotted Figure 2, where even a blind man can see that there were differences. Ok, they were not statistally significant- the 6h post value for p70S6k, for example has a standard deviation that's 41% larger than the mean (!), but that is exactly what is interesting, here. Why? Well,  if we don't measure either the fractional protein synthesis or at least the disappearance of amino acids from the blood, this protein is our best indicator of how much protein is pumped into the cells (Kawasome. 1998)

Can't disprove the researchers' conclusion, but have my doubts

Obviously a statistically non-significant, but for some study participants obviously exorbitant difference in p70S6k and Akt in the late post-workout period (remember the SD being 141% of the mean for p70S6k at T = 6h post exercise) does obviously not suffice to disprove Ferreira et al.'s conclusion that their initial hypotheses that the BCAAs would "optimize cell signaling markers indicative of MPS [muscle protein synthesis]" (Ferreira. 2013) has to be rejected. It is correct, that they 

"[...] failed to demonstrate an augmented insulogenic response from the co-ingestion of CHO and BCAA and that the effects of signaling markers of the PI3K/Akt-mTOR pathway were not preferentially affected compared to CHO." (Ferreira. 2013)

At least for the latter this is yet a failure on statistical terms and one that raises the question, how likely it is to observe such pronounced increases in otherwise reliable markers of acute protein synthesis in some of the study participants in the absence of a (late) increase in protein synthesis 2h-4h after the exercise stimulus and the ingestion of the last serving of the supplement.

Still, even if this was significant.  What does it tell us? And why does it occur 2-4h after both the effects of the nutritional stimulus should already have abated ("The Anabolic Barndoor" | learn more). In the absence of adequate protein nutrition (there is no information on a meal or fourth supplement with a complete protein source being provide to the subjects 2h after the workout in the study) the increase must yet be considered an "anabolic potential", but not as an increase in protein synthesis, which would obviously require the "raw materials", BCAAs alone don't provide.
References: 

• Biolo, G., RY Declan Fleming, and R. R. Wolfe. "Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle." Journal of Clinical investigation 95.2 (1995): 811. 
• Ferreira, Maria Pontes, et al. "Peri-exercise co-ingestion of branched-chain amino acids and carbohydrate in men does not preferentially augment resistance exercise-induced increases in PI3K/Akt-mTOR pathway markers indicative of muscle protein synthesis." Nutrition Research (2014).
• Gelfand, Robert A., and Eugene J. Barrett. "Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man." Journal of Clinical Investigation 80.1 (1987): 1. 
• Hulmi, Juha J., Christopher M. Lockwood, and Jeffrey R. Stout. "Review Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein." Nutrition & metabolism 7 (2010): 51. 
• Kawasome, Hideki, et al. "Targeted disruption of p70s6k defines its role in protein synthesis and rapamycin sensitivity." Proceedings of the National Academy of Sciences 95.9 (1998): 5033-5038.