Effect of Carnosine or beta-Alanine Supplementation on Markers of Glycemic Control and Insulin Resistance in Humans and Animals: A Systematic Review and Meta-analysis

Author(s)

Matthews, Joseph J. ^{[1, 2]} ; Dolan, Eimear ^[3] ; Swinton, Paul A. ^[4] ; Santos, Livia ^[1] ; Artioli, Guilherme G. ^{[5, 3]} ; Turner, Mark D. ^[6] ; Elliott-Sale, Kirsty J. ^[1] ; Sale, Craig ^[1]

Affiliation

^[1] Nottingham Trent Univ, Sport Hlth & Performance Enhancement SHAPE Res Ct, Sch Sci & Technol, Musculoskeletal Physiol Res Grp, Nottingham - England

^[2] Birmingham City Univ, Res Ctr Life & Sport Sci CLaSS, Sch Hlth & Life Sci, Dept Sport & Exercise, Birmingham, W Midlands - England

^[3] Univ Sao Paulo, Sch Phys Educ & Sport, Appl Physiol & Nutr Res Grp, Sao Paulo - Brazil

^[4] Robert Gordon Univ, Sch Hlth Sci, Aberdeen - Scotland

^[5] Univ Sao Paulo, Fac Med FMUSP, Rheumatol Div, Sao Paulo - Brazil

^[6] Nottingham Trent Univ, Ctr Diabet Chron Dis & Ageing, Sch Sci & Technol, Nottingham - England

• Document type: Review article
• Source: ADVANCES IN NUTRITION; v. 12, n. 6, p. 2216-2231, NOV 2021.
• Web of Science Citations: 1

Abstract

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor beta-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or beta-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of beta-cell function (HOMA-beta) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random- effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n=4 human, n=16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-beta, and HOMA-IR). Themodel provides evidence that supplementation decreases fasting glucose {[}humans: mean difference (MD)(0.5) =-0.95 mmol . L-1 (90% CrI: -2.1, 0.08); rodent: MD0.5 =-2.26 mmol . L-1 (90% CrI: -4.03, -0.44)], HbA1c {[}humans: MD0.5 =-0.91% (90% CrI: -1.46, -0.39); rodents: MD0.5 =-1.05% (90% CrI: -1.64, -0.52)], HOMA-IR {[}humans: standardizedmean difference (SMD)(0.5) =-0.41 (90% CrI: -0.82, -0.07); rodents: SMD0.5 =-0.63 (90% CrI: -1.98, 0.65)], and fasting insulin {[}humans: SMD0.5 =-0.41 (90% CrI: -0.77, -0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or beta-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. (AU)

• FAPESP's process: 14/11948-8 - Life without carnosine: development and characterization of a KO rat model for studying the physiological role of carnosine and its implications to physical exercise and muscle metabolism
• Grantee: Guilherme Giannini Artioli
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/26899-6 - The bone response to exercise a translational research program exploring clinical and mechanistic aspects
• Grantee: Eimear Bernadette Dolan
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 19/05616-6 - The bone response to exercise: a translational research program exploring clinical and mechanistic aspects
• Grantee: Eimear Bernadette Dolan
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/25032-9 - The role of carnosine on Ca2+ handling, control of oxidative stress and protection against protein glycation: advances and applications of the study life without carnosine
• Grantee: Hamilton Augusto Roschel da Silva
• Support Opportunities: Regular Research Grants