Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment

Abstract

The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite N-acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of Helicobacter pylori eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.

Keywords: beta-alanine; carnosine; health benefits; human diseases; supplementation; zinc-carnosine.

Figure 1

Chemical structure of carnosine, zinc-L-carnosine and beta-alanine.

Figure 2

Biological activities of carnosine, simplified. ALE: advanced lipoxidation end products; AGE: advanced glycation end products; mTOR: mammalian target of rapamycin; NO: nitric oxide; RNS: reactive nitrogen species; ROS: reactive oxygen species. Additional information on carnosine’s molecular functions can be found in Supplementary Table S1.

Figure 3

Metabolism of carnosine and beta-alanine. Carnosine (Car) enters the enterocyte by a peptide transporter (PepT1); beta-alanine (b-Ala) enters by a specific transporter for beta-amino acids, a proton-assisted amino acid transporter (PAT1) and a taurine transporter (TauT); and histidine (His) enters by a sodium-dependent neutral amino acid transporter (NAT). Proton-coupled peptide-histidine transporter 2 (PepT2) carnosine transporting is expressed in the membrane on majority extraintestinal tissue. b-Ala is transported from the circulation by beta-amino acid specific transporter (ßAAT) and His by PHT1. In the extraintestinal tissues, carnosine is cleaved by carnosinases CN1 or CN2 into b-Ala and His, respectively, and formed from these two amino acids through carnosine synthetase (CS).