ACCEPTED. Changes in body composition and performance with supplemental HMB FA+ATP

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Journal of Strength and Conditioning Research Publish Ahead of Print DOI: 10.1519/JSC.0000000000001760 Manuscript Clarification Changes in body composition and performance with supplemental HMB FA+ATP Stuart M. Phillips, Ph.D., McMaster University Alan A. Aragon, M.S., California State University, Northridge Paul J. Arciero, Ph.D., Skidmore College Shawn M. Arent, Ph.D., Rutgers University Graeme L. Close, Ph.D., Liverpool John Moores University D. Lee Hamilton, Ph.D., University of Stirling Eric R. Helms, M.S., M.Phil, Sports Performance Research Institute New Zealand Menno Henselmans, M.Sc., Bayesian Bodybuilding Research and Development Jeremy P. Loenneke, Ph.D., The University of Mississippi Layne E. Norton, Ph.D., BioLayne LLC Michael J. Ormsbee, Ph.D., Florida State University Craig Sale, Ph.D., Nottingham Trent University Brad J. Schoenfeld, Ph.D., Lehman College Abbie E. Smith Ryan Ph.D., University of North Carolina Kevin D. Tipton, Ph.D., University of Stirling Matthew D. Vukovich, Ph.D., South Dakota State University

Colin Wilborn, Ph.D., University of Mary Hardin Baylor Darryn S. Willoughby, Ph.D. Baylor University ---------------------------------------------------------------------------------- Response from the Authors In response 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+AP supplemented (n=8) versus a 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 calcium HMB showing improved muscle protein turnover (9). We are unaware of any similar data for FA HMB despite greater bioavailability and uptake (into what tissue is unknown) (3). Do the authors know of any data showing that HMB FA affects human muscle protein turnover (9)? We note that leucine had the same anabolic effects as calcium 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/leucine intake, did not appear 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 (400mg/d) resulted in a positive effect on muscle mass, strength, and power gains. The authors state (4) that a previously reported increase in post exercise 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 6min post exercise (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? Reference List 1. Cermak NM, Res PT, de Groot LC, Saris WH and 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 and 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 and 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 and 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 and 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 and 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 and 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 and 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 and 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 and 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. 11. Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM, Stout JR, Duncan N, Fuller JC, Baier SM, Naimo MA and Rathmacher J. The effects of 12 weeks of beta hydroxy beta methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance trained individuals: a randomized, double blind, placebo controlled study. Eur J Appl Physiol 114: 1217 1227, 2014.