Individual Participant Data Meta-Analysis Provides No Evidence of Intervention Response Variation in Individuals Supplementing With Beta-Alanine

in International Journal of Sport Nutrition and Exercise Metabolism
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  • 1 University of São Paulo
  • | 2 Robert Gordon University
  • | 3 Nottingham Trent University
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Currently, little is known about the extent of interindividual variability in response to beta-alanine (BA) supplementation, nor what proportion of said variability can be attributed to external factors or to the intervention itself (intervention response). To investigate this, individual participant data on the effect of BA supplementation on a high-intensity cycling capacity test (CCT110%) were meta-analyzed. Changes in time to exhaustion (TTE) and muscle carnosine were the primary and secondary outcomes. Multilevel distributional Bayesian models were used to estimate the mean and SD of BA and placebo group change scores. The relative sizes of group SDs were used to infer whether observed variation in change scores were due to intervention or non-intervention-related effects. Six eligible studies were identified, and individual data were obtained from four of these. Analyses showed a group effect of BA supplementation on TTE (7.7, 95% credible interval [CrI] [1.3, 14.3] s) and muscle carnosine (18.1, 95% CrI [14.5, 21.9] mmol/kg DM). A large intervention response variation was identified for muscle carnosine (σIR = 5.8, 95% CrI [4.2, 7.4] mmol/kg DM) while equivalent change score SDs were shown for TTE in both the placebo (16.1, 95% CrI [13.0, 21.3] s) and BA (15.9, 95% CrI [13.0, 20.0] s) conditions, with the probability that SD was greater in placebo being 0.64. In conclusion, the similarity in observed change score SDs between groups for TTE indicates the source of variation is common to both groups, and therefore unrelated to the supplement itself, likely originating instead from external factors such as nutritional intake, sleep patterns, or training status.

Esteves, Artioli, Roschel, Gualano, Saunders, and Dolan are with the Applied Physiology & Nutrition Research Group, School of Physical Education and Sport, Rheumatology Division, Faculdade de Medicina FMUSP, University of São Paulo, São Paulo, Brazil. Swinton is with the School of Health Sciences, Robert Gordon University, Aberdeen, United Kingdom. Sale and James are with the Musculoskeletal Physiology Research Group, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom. Gualano is also with the Food Research Centre, University of São Paulo, São Paulo, Brazil. Saunders is also with the Institute of Orthopaedics and Traumatology, Faculty of Medicine FMUSP, University of São Paulo, São Paulo, Brazil.

Dolan (eimeardolan@usp.br and eimeardol@gmail.com) is corresponding author.

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  • Atkinson, G., & Batterham, A. (2015). True and false interindividual differences in the physiological response to an intervention. Experimental Physiology, 100(6), 577588. PubMed ID: 25823596 doi:10.1113/EP085070

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Atkinson, G., Williamson, P., & Batterham, A. (2019). Issues in the determination of “responders” and “non-responders” in physiological research. Experimental Physiology, 104(8), 12151225. PubMed ID: 31116468 doi:10.1113/EP087712

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Baguet, A., Reyngoudt, H., Pottier, A., Everaert, I., Callens, S., Achten, E., & Derave, W. (2009). Carnosine loading and washout in human skeletal muscles. Journal of Applied Physiology, 106(3), 837842. PubMed ID: 19131472 doi:10.1152/japplphysiol.91357.2008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bassinello, D., de Salles Painelli, V., Dolan, E., Lixandrão, M., Cajueiro, M., de Capitani, M., . . . Roschel, H. (2019). Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men. Amino Acids, 51(1), 2737. PubMed ID: 29905904 doi:10.1007/s00726-018-2593-8

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Betts, J.A., Gonzalez, J.T., Burke, L.M., Close, G.L., Garthe, I., James, L.J., . . . Atkinson, G. (2020). PRESENT 2020: Text expanding on the checklist for proper reporting of evidence in sport and exercise nutrition trials. International Journal of Sport Nutrition and Exercise Metabolism, 30(1), 213. PubMed ID: 31945740 doi:10.1123/ijsnem.2019-0326

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bishop, D., Edge, J., Mendez-Villanueva, A., Thomas, C., & Schneiker, K. (2009). High-intensity exercise decreases muscle buffer capacity via a decrease in protein buffering in human skeletal muscle. Pflugers Archiv European Journal of Physiology, 458(5), 929936. PubMed ID: 19415322 doi:10.1007/s00424-009-0673-z

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Blancquaert, L., Everaert, I., & Derave, W. (2015). Beta-alanine supplementation, muscle carnosine and exercise performance. Current Opinion in Clinical Nutrition and Metabolic Care, 18, 6370. doi:10.1097/MCO.0000000000000127

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bonafiglia, J., Brennan, A., Ross, R., & Gurd, B. (2019). An appraisal of the SD IR as an estimate of true individual differences in training responsiveness in parallel-arm exercise randomized controlled trials. Physiological Reports, 7(14), 14163. doi:10.14814/phy2.14163

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Burke, L.M., & Peeling, P. (2018). Methodologies for investigating performance changes with supplement use. International Journal of Sport Nutrition and Exercise Metabolism, 28(2), 159169. PubMed ID: 29468949 doi:10.1123/ijsnem.2017-0325

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bürkner, P.-C. (2017). brms: An R package for Bayesian multilevel models using stan. Journal of Statistical Software, 80(1), 128. doi:10.18637/jss.v080.i01

    • Crossref
    • Search Google Scholar
    • Export Citation
  • da Eira Silva, V., de Salles Painelli, V., Katsuyuki Shinjo, S., Pereira, W., Cilli, E., Sale, C., . . . Artioli, G. (2020). Magnetic resonance spectroscopy as a non-invasive method to quantify muscle carnosine in humans: A comprehensive validity assessment. Scientific Reports, 10(1), 4908. PubMed ID: 32184463 doi:10.1038/s41598-020-61587-x

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Danaher, J., Gerber, T., Wellard, R.M., & Stathis, C.G. (2014). The effect of β-alanine and NaHCO3 co-ingestion on buffering capacity and exercise performance with high-intensity exercise in healthy males. European Journal of Applied Physiology, 114(8), 17151724. PubMed ID: 24832191 doi:10.1007/s00421-014-2895-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dankel, S.J., Bell, Z.W., Spitz, R.W., Wong, V., Viana, R.B., Chatakondi, R.N., . . . Loenneke, J.P. (2020). Assessing differential responders and mean changes in muscle size, strength, and the crossover effect to 2 distinct resistance training protocols. Applied Physiology, Nutrition, and Metabolism, 45(5), 463470. PubMed ID: 31553889 doi:10.1139/apnm-2019-0470

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Derave, W., Ozdemir, M.S., Harris, R.C., Pottier, A., Reyngoudt, H., Koppo, K., . . . Achten, E. (2007). Beta-Alanine supplementation augments muscle carnosine content and attenuates fatigue during repeated isokinetic contraction bouts in trained sprinters. Journal of Applied Physiology, 103(5), 17361743. doi:10.1152/japplphysiol.00397.2007

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Dolan, E., Saunders, B., Harris, R., Bicudo, E., Bishop, D., Sale, C., & Gualano, B. (2019). Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid-base regulation of skeletal muscle. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology, 234, 7786. doi:10.1016/j.cbpa.2019.04.017

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gelman, A., Carlin, J.B., Stern, H.S., Dunson, D.B., Vehtari, A., & Rubin, D.B. (2013). Bayesian Data Analysis (3rd ed.). Boca Raton, FL: CRC Press.

  • Guyatt, G., Oxman, A., Vist, G., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., . . . GRADE Working Group. (2008). GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. British Medical Journal, 336(7650), 924926. doi:10.1136/bmj.39489.470347.AD

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Harris, R., Tallon, M., Dunnett, M., Boobis, L., Coakley, J., Kim, H., . . . Wise, J. (2006). The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids, 30(3), 279289. PubMed ID: 16554972 doi:10.1007/s00726-006-0299-9

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Hecksteden, A., Kraushaar, J., Scharhag-Rosenberger, F., Theisen, D., Senn, S., & Meyer, T. (2015). Individual response to exercise training – a statistical perspective. Journal of Applied Physiology, 118(12), 14501459. PubMed ID: 25663672 doi:10.1152/japplphysiol.00714.2014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Hill, C., Harris, R., Kim, H., Harris, B., Sale, C., Boobis, L., . . . Wise, J. (2007). Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino Acids, 32(2), 225233. PubMed ID: 16868650 doi:10.1007/s00726-006-0364-4

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Islam, H., & Gurd, B. (2020). Exercise response variability: Random error or true differences in exercise response? Experimental Physiology, 105(12), 20222024. PubMed ID: 33372724 doi:10.1113/EP089015

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Jones, R.L., Barnett, C.T., Davidson, J., Maritza, B., Fraser, W.D., Harris, R., & Sale, C. (2017). β-alanine supplementation improves in-vivo fresh and fatigued skeletal muscle relaxation speed. European Journal of Applied Physiology, 117(5), 867879. PubMed ID: 28349262 doi:10.1007/s00421-017-3569-1

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kelley, G., & Kelley, K. (2019). Systematic reviews and meta-analysis in nutrition research. British Journal of Nutrition, 122(11), 12791294. doi:10.1017/S0007114519002241

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Mann, T.N., Lamberts, R.P., & Lambert, M.I. (2014). High responders and low responders: factors associated with individual variation in response to standardized training. Sports Medicine, 44(8), 11131124. PubMed ID: 24807838 doi:10.1007/s40279-014-0197-3

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Marticorena, F., Carvalho, A., de Oliveira, L., Dolan, E., Gualano, B., Swinton, P., & Saunders, B. (2021). Nonplacebo controls to determine the magnitude of ergogenic interventions: A systematic review and meta-analysis. Medicine & Science in Sports & Exercise. doi:10.1249/mss.0000000000002635

    • Search Google Scholar
    • Export Citation
  • McGuinness, L.A., & Higgins, J.P.T. (2021). Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing risk-of-bias assessments. Research Synthesis Methods, 12(1), 5561. PubMed ID: 32336025 doi:10.1002/jrsm.1411

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Morris, S., & DeShon, R. (2002). Combining effect size estimates in meta-analysis with repeated measures and independent-group designs. Psychological Methods, 7(1), 105125. PubMed ID: 11928886 doi:10.1037/1082-989X.7.1.105

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., . . . Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. British Medical Journal, 71. doi:10.1136/bmj.n71

    • Search Google Scholar
    • Export Citation
  • Patel, K.A., Farias de Oliveira, L., Sale, C., & James, R.M. (2021). The effect of β-alanine supplementation on high intensity cycling capacity in normoxia and hypoxia. Journal of Sports Sciences, 17. doi:10.1080/02640414.2020.1867416

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Rezende, N.S., Swinton, P., de Oliveira, L.F., da Silva, R.P., da Eira Silva, V., Nemezio, K., . . . Dolan, E. (2020). The muscle carnosine response to beta-alanine supplementation: A systematic review with bayesian individual and aggregate data E-Max model and meta-analysis. Frontiers in Physiology, 11, 913. PubMed ID: 32922303 doi:10.3389/fphys.2020.00913

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Sale, C., Hill, C.A., Ponte, J., & Harris, R.C. (2012). β-alanine supplementation improves isometric endurance of the knee extensor muscles. Journal of the International Society of Sports Nutrition, 9(1), 26. PubMed ID: 22697405 doi:10.1186/1550-2783-9-26

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Sale, C., Saunders, B., Hudson, S., Wise, J.A., Harris, R.C., & Sunderland, C.D. (2011). Effect of β-alanine plus sodium bicarbonate on high-intensity cycling capacity. Medicine & Science in Sports & Exercise, 43(10), 19721978. doi:10.1249/mss.0b013e3182188501

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Saunders, B., de Salles Painelli, V., de Oliveira, L.F., da Eira Silva, V., da Silva, R.P., Riani, L., . . . Gualano, B. (2017a). Twenty-four weeks of β-alanine supplementation on carnosine content, related genes, and exercise. Medicine & Science in Sports & Exercise, 49(5), 896906. PubMed ID: 28157726 doi:10.1249/MSS.0000000000001173

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Saunders, B., Elliott-Sale, K., Artioli, G.G., Swinton, P.A., Dolan, E., Roschel, H., . . . Gualano, B. (2017b). β-alanine supplementation to improve exercise capacity and performance: A systematic review and meta-analysis. British Journal of Sports Medicine, 51(8), 658669. PubMed ID: 27797728 doi:10.1136/bjsports-2016-096396

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Saunders, B., Sale, C., Harris, R.C., Morris, J.G., & Sunderland, C. (2013). Reliability of a high-intensity cycling capacity test. Journal of Science and Medicine in Sport, 16(3), 286289. PubMed ID: 22884738 doi:10.1016/j.jsams.2012.07.004

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Senn, S. (2004). Individual response to treatment: Is it a valid assumption? British Medical Journal, 329(7472), 966968. PubMed ID: 15499115 doi:10.1136/bmj.329.7472.966

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Sterne, J.A.C., Savović, J., Page, M.J., Elbers, R.G., Blencowe, N.S., Boutron, I., . . . Higgins, J.P.T. (2019). RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 366, l4898. doi:10.1136/bmj.l4898

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Swinton, P.A., Hemingway, B.S., Saunders, B., Gualano, B., & Dolan, E. (2018). A statistical framework to interpret individual response to intervention: Paving the way for personalized nutrition and exercise prescription. Frontiers in Nutrition, 5, 41. PubMed ID: 29892599 doi:10.3389/fnut.2018.00041

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Trexler, E.T., Smith-Ryan, A.E., Stout, J.R., Hoffman, J.R., Wilborn, C.D., Sale, C., . . . Antonio, J. (2015). International society of sports nutrition position stand: Beta-Alanine. Journal of the International Society of Sports Nutrition, 12(1), 30. doi:10.1186/s12970-015-0090-y

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Watson, J.A., Ryan, C.G., Atkinson, G., Williamson, P., Ellington, D., Whittle, R., . . . Martin, D.J. (2021). Inter-individual differences in the responses to pain neuroscience education in adults with chronic musculoskeletal pain: A systematic review and meta-analysis of randomized controlled trials. The Journal of Pain, 22(1), 920. PubMed ID: 32585363 doi:10.1016/j.jpain.2020.03.006

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Williamson, P.J., Atkinson, G., & Batterham, A.M. (2017). Inter-individual responses of maximal oxygen uptake to exercise training: A critical review. Sports Medicine, 47(8), 15011513. PubMed ID: 28097487 doi:10.1007/s40279-017-0680-8

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Williamson, P.J., Atkinson, G., & Batterham, A.M. (2018). Inter-individual differences in weight change following exercise interventions: A systematic review and meta-analysis of randomized controlled trials. Obesity Reviews, 19(7), 960975. PubMed ID: 29701297 doi:10.1111/obr.12682

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Yamaguchi, G.C., Nemezio, K., Schulz, M.L., Natali, J., Cesar, J.E., Riani, L. A., . . . Artioli, G.G. (2021). Kinetics of muscle carnosine decay after β-alanine supplementation: A 16-wk Washout Study. Medicine & Science in Sports & Exercise, 53(5), 10791088.

    • Crossref
    • Search Google Scholar
    • Export Citation
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