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

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.

Automated summary

Supplementation with carnosine or beta-alanine shows potential to improve metabolic dysregulation in diabetes and related conditions, with significant effects on markers of glycemic control and insulin resistance. The systematic review and meta-analysis reveal that these supplements can reduce fasting glucose, HbA1c, and insulin resistance in both humans and rodents, suggesting their therapeutic potential for enhancing glycemic control. However, certainty in the effects varies between human and rodent studies, with moderate certainty in human outcomes and very low certainty in rodent outcomes.