Request for Clarification:
The authors are satisfied that their original responses to the prior Manuscript Clarification address the issues raised here.
Lowery et al. (6) reported, in contrast to an often‐observed heterogeneity in training‐induced hypertrophy, remarkably consistent between‐group changes in muscle mass to find statistical significance between an HMB‐FA+ATP (beta-hydroxy beta-methyl butyrate-free acid and adenosine triphosphate) supplemented (n = 8) versus placebo (n = 9) groups. The difference divergence between the supplemented and placebo groups occurred despite optimal training and optimal nutritional support. We note that HMB has been shown to result in a trivial training‐induced adaptive advantage (8) and that the gain in lean body mass was in previously resistance‐trained subjects who would have had less propensity to gain lean body mass (7). For absolute clarity, could the authors please present the absolute body weight and body composition (lean body mass and fat mass) as opposed to % change data? We believe this would be helpful for readers.
There are data for FA-HMB showing improved muscle protein turnover (9). However, we note that leucine had the same anabolic effects as FA‐HMB (9) and that dietary protein can exert a positive effect on gains in muscle mass with resistance training (1). The placebo group, recipients of optimal protein and leucine intake, did not seem to respond at all to the overreaching phase. Can the authors speculate why?
Lowery et al. (6) supplemented with ATP, which has undetectable bioavailability (2). Wilson et al. (10), reported that ATP (400 mg·d) resulted in a positive effect on muscle mass, strength, and power gains. The authors' state (4) that a previously reported increase in postexercise blood flow induced by the ATP (5) in the supplemented group could be responsible. The magnitude of that flow increase was only about 100–150 ml·min, was not consistently observed across weeks of supplementation, and lasted no more than 3–6 min postexercise (5). How do the authors think a small, inconsistent, and short‐lasting increase in blood flow could affect performance?
In the response to Hyde et al. (4), Lowery et al. (6) stated that they selected “…a responsive population who possess a quantity of lean mass indicative of previous responses to resistance training…” What was the screening process to pick the participants? The authors state their subjects had muscle “…an order of magnitude [an order of magnitude is defined as 10‐times greater, so this cannot be the case] higher than average lean mass…” Could the authors please state the exact criteria for inclusion as a participant? It would be useful for the authors to describe how many participants were recruited and screened, the final number entered into the study, and the number of dropouts. Were participants randomized to treatment and placebo groups, pair matched based on body mass, lean body mass, strength, or another variable?
1. Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: A meta-analysis. Am J Clin Nutr 96: 1454–1464, 2012.
2. Coolen EJ, Arts IC, Bekers O, Vervaet C, Bast A, Dagnelie PC. Oral bioavailability of ATP after prolonged administration. Br J Nutr 105: 357–366, 2011.
3. Fuller JC Jr, Sharp RL, Angus HF, Baier SM, Rathmacher JA. Free acid gel form of betahydroxy- beta-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt. Br J Nutr 105: 367–372, 2011.
4. Hyde PN, Kendall KL, LaFountain RA. Interaction of beta-hydroxy-betmethylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power, in resistance trained invidividuals. J Strength Cond Res 30: e10–e14, 2016.
5. Jager R, Roberts MD, Lowery RP, Joy JM, Cruthirds CL, Lockwood CM, Rathmacher JA, Purpura M, Wilson JM. Oral adenosine-5′-triphosphate (ATP) administration increases blood flow following exercise in animals and humans. J Int Soc Sports Nutr 11: 28, 2014.
6. Lowery RP, Joy JM, Rathmacher JA, Baier SM, Fuller JC Jr, Shelley MC, Jager R, Purpura M, Wilson SM, Wilson JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30: 1843–1854, 2016.
7. Morton RW, Oikawa SY, Wavell CG, Mazara N, McGlory C, Quadrilatero J, Baechler BL, Baker SK, Phillips SM. Neither load nor systemic hormones determine resistance training-mediated hypertrophy or strength gains in resistance-trained young men. J Appl Physiol (1985) 121: 129–138, 2016.
8. Rowlands DS, Thomson JS. Effects of beta-hydroxy-beta-methylbutyrate supplementation during resistance training on strength, body composition, and muscle damage in trained and untrained young men: A meta-analysis. J Strength Cond Res 23: 836–846, 2009.
9. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Etheridge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 591: 2911–2923, 2013.
10. Wilson JM, Joy JM, Lowery RP, Roberts MD, Lockwood CM, Manninen AH, Fuller JC, De Souza EO, Baier SM, Wilson SM, Rathmacher JA. Effects of oral adenosine-5′-triphosphate supplementation on athletic performance, skeletal muscle hypertrophy and recovery in resistance-trained men. Nutr Metab (Lond) 10: 57, 2013.