Betaine as a regulator of metabolism, epigenetics, and cellular osmoprotection: therapeutic implications in cardiometabolic and renal diseases
Abstract
Betaine, a glycine derivative found in spinach, beets, and whole grains, offers significant pharmacological and nutritional benefits. Researchers are focusing on betaine due to its therapeutic properties and ease of dietary incorporation. The zwitterion betaine is a derivative of N,N,N-trimethylglycine, which is produced during choline metabolism. However, endogenous synthesis of betaine may not always meet the health requirements, and dietary supplementation is needed. Betaine also acts as a methyl donor and an osmolyte and has proven beneficial in treating conditions such as hyper homocysteinemia, inflammation, cardiovascular disorders, and metabolic disorders. Pre-clinical and clinical studies demonstrate its therapeutic effectiveness, supported by safety reports confirming its role in enhancing human health. This review aims to summarize the biochemical, molecular, and therapeutic roles of betaine across multiple disease conditions, with a particular focus on its role in metabolic liver diseases (ALD/MASLD/MASH), cardiovascular dysfunction, diabetes, and renal disorders. Additionally, it highlights betaine's emerging role as an epigenetic regulator and assesses its safety and toxicity profile. Betaine primarily acts as a methyl donor in the one-carbon metabolism pathway, reducing hyperhomocysteinemia and attenuating cardiovascular risk. In hepatic metabolism, betaine modulates lipid homeostasis by regulating key lipogenic transcription factors, contributing to its…
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