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Carnosine metabolism in skeletal muscle: a multi-approach study


Carnosine is a cytoplasmic dipeptide found in high concentrations in the skeletal muscle of both vertebrates and non-vertebrates, and is associated with muscle buffering, sensitivity of calcium release channels and/or calcium sensitivity of the contractile apparatus and scavenging of reactive oxygen species. It has been shown that the elevation of muscle carnosine concentrations through the dietary intake of carnosine or supplementation with ²-alanine can lead to improved high-intensity exercise performance and capacity, although the mechanism underpinning these improvements remains to be elucidated. Furthermore, whilst there is some suggestion that prolonged high-intensity exercise training can result in increased muscle buffering capacity, it is unknown whether this is due to increased muscle carnosine content. Several important questions relating to carnosine and ²-alanine supplementation remain. Firstly, the upper limit to carnosine concentration in muscle, and concomitant exercise benefits, are currently unknown. Prolonged supplementation with ²-alanine will allow us to provide some answers to these questions, whilst also providing information on the effects of long term supplementation on carnosine related genes. Secondly, the mechanisms contributing to the performance effects of increased muscle carnosine are currently debated within the literature; providing an analysis of the carnosine content of various compartments within the muscle cell (e.g., mitochondria, cytosol, nucleus) would provide evidence to suggest the most likely mechanism contributing to increased exercise performance and capacity. Thirdly, no studies have examined the effects of long-term high-intensity exercise training on increases in muscle carnosine and muscle buffering capacity. As such, we propose here a comprehensive programme of work, comprising three experimental investigations, aimed at gaining some insight into these vitally important questions. Study 1 will investigate the effect of long-term ²-alanine supplementation on peak muscle carnosine concentrations, as well as the associated changes in exercise capacity, carnosine related genes and any potential side effects. The effects of prolonged high-intensity training on muscle buffering capacity and muscle carnosine concentrations, both in whole muscle and single muscle fibres, will be determined in study 2. Study 3 will utilise a comparative physiology design in order to examine the muscle carnosine content of the humming bird, pheasant and human, and will also determine the compartmentalisation of carnosine in the cell. (AU)

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Scientific publications (24)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SAUNDERS, BRYAN; ELLIOTT-SALE, KIRSTY; ARTIOLI, GUILHERME G.; SWINTON, PAUL A.; DOLAN, EIMEAR; ROSCHEL, HAMILTON; SALE, CRAIG; GUALANO, BRUNO. beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. BRITISH JOURNAL OF SPORTS MEDICINE, v. 51, n. 8, p. 658+, . (14/11948-8, 15/11328-2, 13/14746-4)
KRATZ, CAROLINE DE ANDRADE; PAINELLI, VITOR DE SALLES; DE ANDRADE NEMEZIO, KLEINER MARCIO; DA SILVA, RAFAEL PIRES; FRANCHINI, EMERSON; ZAGATTO, ALESSANDRO MOURA; GUALANO, BRUNO; ARTIOLI, GUILHERME GIANNINI. Beta-alanine supplementation enhances judo-related performance in highly-trained athletes. JOURNAL OF SCIENCE AND MEDICINE IN SPORT, v. 20, n. 4, p. 403-408, . (14/11948-8, 13/04806-0, 13/14746-4)
SAUNDERS, B.; DE OLIVEIRA, L. F.; DA SILVA, R. P.; DE SALLES PAINELLI, V.; GONCALVES, L. S.; YAMAGUCHI, G.; MUTTI, T.; MACIEL, E.; ROSCHEL, H.; ARTIOLI, G. G.; et al. Placebo in sports nutrition: a proof-of-principle study involving caffeine supplementation. SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS, v. 27, n. 11, p. 1240-1247, . (14/11948-8, 11/19513-2, 13/14746-4, 13/04806-0)
DOLAN, EIMEAR; GUALANO, BRUNO; RAWSON, ERIC S.. Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury. European Journal of Sport Science, v. 19, n. 1, SI, p. 1-14, . (15/11328-2, 13/14746-4)
BASSINELLO, DIOGO; PAINELLI, VITOR DE SALLES; DOLAN, EIMEAR; LIXANDRAO, MANOEL; CAJUEIRO, MONIQUE; DE CAPITANI, MARIANA; SAUNDERS, BRYAN; SALE, CRAIG; ARTIOLI, GUILHERME G.; GUALANO, BRUNO; et al. Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men. Amino Acids, v. 51, n. 1, p. 27-37, . (13/14746-4, 17/04973-4, 16/50438-0, 16/10993-5, 15/23072-2, 13/04806-0, 15/11328-2)
DA SILVA, RAFAEL PIRES; DE OLIVEIRA, LUANA FARIAS; SAUNDERS, BRYAN; KRATZ, CAROLINE DE ANDRADE; PAINELLI, VITOR DE SALLES; SILVA, VINICIUS DA EIRA; BOUZAS MARINS, JOAO CARLOS; FRANCHINI, EMERSON; GUALANO, BRUNO; ARTIOLI, GUILHERME GIANNINI. Effects of -alanine and sodium bicarbonate supplementation on the estimated energy system contribution during high-intensity intermittent exercise. Amino Acids, v. 51, n. 1, p. 83-96, . (13/14746-4, 16/50438-0, 12/13026-5, 14/11948-8, 13/04806-0)
DOLAN, E.; SAUNDERS, B.; DANTAS, W. S.; MURAI, I. H.; ROSCHEL, H.; ARTIOLI, G. G.; HARRIS, R.; BICUDO, J. E. P. W.; SALE, C.; GUALANO, B.. A Comparative Study of Hummingbirds and Chickens Provides Mechanistic Insight on the Histidine Containing Dipeptide Role in Skeletal Muscle Metabolism. SCIENTIFIC REPORTS, v. 8, . (13/14746-4, 16/10993-5, 17/09635-0, 15/11328-2, 16/50438-0, 17/04973-4)
GONCALVES, LIVIA DE SOUZA; SALES, LUCAS PEIXOTO; SAITO, TIEMI RAQUEL; CAMPOS, JULIANE CRUZ; FERNANDES, ALAN LINS; NATALI, JOSE; JENSEN, LEONARDO; ARNOLD, ALEXANDRE; RAMALHO, LISLEY; BECHARA, LUIZ ROBERTO GRASSMANN; et al. Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model. REDOX BIOLOGY, v. 44, . (17/16540-5, 13/14746-4, 17/11142-1, 13/07937-8, 17/13552-2, 19/24899-9, 18/14544-6, 19/25032-9, 14/11948-8, 20/04006-7)
PAINELLI, VITOR DE SALLES; NEMEZIO, KLEINER MARCIO; PINTO, ANA JESSICA; FRANCHI, MARIANA; ANDRADE, ISABEL; RIANI, LUIZ AUGUSTO; SAUNDERS, BRYAN; SALE, CRAIG; HARRIS, ROGER CHARLES; GUALANO, BRUNO; et al. High-Intensity Interval Training Augments Muscle Carnosine in the Absence of Dietary Beta-alanine Intake. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 50, n. 11, p. 2242-2252, . (14/11948-8, 13/04806-0, 13/14746-4, 16/50438-0)
CARVALHO, VICTOR H.; OLIVEIRA, ANA H. S.; DE OLIVEIRA, LUANA F.; DA SILVA, RAFAEL P.; DI MASCIO, PAOLO; GUALANO, BRUNO; ARTIOLI, GUILHERME G.; MEDEIROS, MARISA H. G.. Exercise and beta-alanine supplementation on carnosine-acrolein adduct in skeletal muscle. REDOX BIOLOGY, v. 18, p. 222-228, . (14/11948-8, 16/24761-9, 13/14746-4, 13/07937-8)
SILVA, VINICIUS DA EIRA; PAINELLI, VITOR DE SALLES; SHINJO, SAMUEL KATSUYUKI; PEREIRA, WAGNER RIBEIRO; CILLI, EDUARDO MAFFUD; SALE, CRAIG; GUALANO, BRUNO; OTADUY, MARIA CONCEPCION; ARTIOLI, GUILHERME GIANNINI. Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment. SCIENTIFIC REPORTS, v. 10, n. 1, . (14/11948-8, 13/04806-0, 13/14746-4)
GONCALVES, LIVIA DE SOUZA; PAINELLI, VITOR DE SALLES; YAMAGUCHI, GUILHERME; DE OLIVEIRA, LUANA FARIAS; SAUNDERS, BRYAN; DA SILVA, RAFAEL PIRES; MACIEL, ERIKA; ARTIOLI, GUILHERME GIANNINI; ROSCHEL, HAMILTON; GUALANO, BRUNO. Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation. Journal of Applied Physiology, v. 123, n. 1, p. 213-220, . (11/19513-2, 13/14746-4, 12/13026-5, 13/04806-0)
REZENDE, NATHALIA SAFFIOTI; SWINTON, PAUL; DE OLIVEIRA, LUANA FARIAS; DA SILVA, RAFAEL PIRES; DA EIRA SILVA, VINICIUS; NEMEZIO, KLEINER; YAMAGUCHI, GUILHERME; ARTIOLI, GUILHERME GIANNINI; GUALANO, BRUNO; SAUNDERS, BRYAN; et al. 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, v. 11, . (13/14746-4, 17/04973-4, 17/09635-0, 15/23176-2, 19/27758-7, 19/05616-6, 17/23688-9, 14/11948-8)
SAUNDERS, BRYAN; FRANCHI, MARIANA; DE OLIVEIRA, LUANA FARIAS; SILVA, VINICIUS DA EIRA; DA SILVA, RAFAEL PIRES; PAINELLI, VITOR DE SALLES; RIANI COSTA, LUIZ AUGUSTO; SALE, CRAIG; HARRIS, ROGER CHARLES; ROSCHEL, HAMILTON; et al. 24-Week beta-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males. EUROPEAN JOURNAL OF NUTRITION, v. 59, n. 1, p. 57-65, . (13/14746-4, 17/04973-4, 16/50438-0, 12/13026-5, 14/11948-8, 13/04806-0, 15/22686-7)
SWINTON, PAUL A.; HEMINGWAY, BEN STEPHENS; SAUNDERS, BRYAN; GUALANO, BRUNO; DOLAN, EIMEAR. A Statistical Framework to Interpret Individual Response to Intervention : Paving the Way for Personalized Nutrition and Exercise Prescription. FRONTIERS IN NUTRITION, v. 5, . (13/14746-4, 17/04973-4, 16/50438-0, 17/09635-0, 15/11328-2)
OLIVEIRA, L. F.; DE SALLES PAINELLI, V.; NEMEZIO, K.; GONCALVES, L. S.; YAMAGUCHI, G.; SAUNDERS, B.; GUALANO, B.; ARTIOLI, G. G.. Chronic lactate supplementation does not improve blood buffering capacity and repeated high-intensity exercise. SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS, v. 27, n. 11, p. 1231-1239, . (14/11948-8, 13/04806-0, 13/14746-4)
YAMAGUCHI, GUILHERME CARVALHO; NEMEZIO, KLEINER; SCHULZ, MARIANE LEICHSENRING; NATALI, JOSE; CESAR, JONATAS EDUARDO; RIANI, LUIZ AUGUSTO; GONCALVES, LIVIA DE SOUZA; MOLLER, GABRIELLA BERWIG; SALE, CRAIG; GENNARI DE MEDEIROS, MARISA HELENA; et al. Kinetics of Muscle Carnosine Decay after beta-Alanine Supplementation: A 16-wk Washout Study. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 53, n. 5, p. 1079-1088, . (13/07937-8, 17/13552-2, 19/25032-9, 14/11948-8, 13/14746-4)
NEMEZIO, KLEINER; YAMAGUCHI, GUILHERME DE CARVALHO; BOITO RAMKRAPES, ANA PAULA; SCHULZ, MARIANE LEICHSENRING; BAPTISTA, IGOR LUCHINI; RIANI, LUIZ AUGUSTO; GONCALVES, LIVIA DE SOUZA; SALE, CRAIG; GENNARI DE MEDEIROS, MARISA HELENA; GUALANO, BRUNO; et al. The role of chronic muscle (in)activity on carnosine homeostasis: a study with spinal cord-injured athletes. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, v. 320, n. 6, p. R824-R832, . (14/11948-8, 19/25032-9, 17/13552-2, 13/07937-8, 15/23176-2, 13/14746-4, 19/12236-5)
DOLAN, EIMEAR; SAUNDERS, BRYAN; HARRIS, ROGER CHARLES; BICUDO, JOSE EDUARDO PEREIRA WILKEN; BISHOP, DAVID JOHN; SALE, CRAIG; GUALANO, BRUNO. Comparative physiology investigations support a role for histidine-containing dipeptides in intracellular acid base regulation of skeletal muscle. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY, v. 234, p. 77-86, . (13/14746-4, 17/04973-4, 16/50438-0, 17/09635-0, 15/11328-2)
DOLAN, EIMEAR; SWINTON, PAUL A.; PAINELLI, VITOR DE SALLES; HEMINGWAY, BENEDICT STEPHENS; MAZZOLANI, BRUNA; SMAIRA, FABIANA INFANTE; SAUNDERS, BRYAN; ARTIOLI, GUILHERME G.; GUALANO, BRUNO. A Systematic Risk Assessment and Meta-Analysis on the Use of Oral beta-Alanine Supplementation. ADVANCES IN NUTRITION, v. 10, n. 3, p. 452-463, . (13/14746-4, 17/04973-4, 16/50438-0, 17/09635-0, 14/11948-8, 13/04806-0, 15/11328-2)
HANNAH, RICCI; STANNARD, REBECCA LOUISE; MINSHULL, CLAIRE; ARTIOLI, GUILHERME GIANNINI; HARRIS, ROGER CHARLES; SALE, CRAIG. beta-Alanine supplementation enhances human skeletal muscle relaxation speed but not force production capacity. Journal of Applied Physiology, v. 118, n. 5, p. 604-612, . (13/14746-4)
SAUNDERS, BRYAN; PAINELLI, VITOR DE SALLES; DE OLIVEIRA, LUANA FARIAS; SILVA, VINICIUS DA EIRA; DA SILVA, RAFAEL PIRES; RIANI, LUIZ; FRANCHI, MARIANA; GONCALVES, LIVIA DE SOUZA; HARRIS, ROGER CHARLES; ROSCHEL, HAMILTON; et al. Twenty-four Weeks of beta-Alanine Supplementation on Carnosine Content, Related Genes, and Exercise. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 49, n. 5, p. 896-906, . (13/14746-4, 14/11948-8, 12/13026-5, 11/19513-2, 13/04806-0, 15/22686-7)
DE ARAUJO DIAS, GABRIELA FROIO; SILVA, VINICIUS DA EIRA; PAINELLI, VITOR DE SALLES; SALE, CRAIG; ARTIOLI, GUILHERME GIANNINI; GUALANO, BRUNO; SAUNDERS, BRYAN. (In) Consistencies in Responses to Sodium Bicarbonate Supplementation: A Randomised, Repeated Measures, Counterbalanced and Double-Blind Study. PLoS One, v. 10, n. 11, . (14/11948-8, 11/19513-2, 13/14746-4, 13/04806-0)

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