Kirsti Tiihonen, Markku T Saarinen, Esa Alhoniemi, Nobuaki Mitsuya and Goro Yamaki
Objective: Betaine (trimethylglycine) is a naturally-occurring osmolyte and methyl donor with reported effects on liver metabolism. The aim of this study was to evaluate the safety and the effects of betaine administration to metabolic risk factors in Asian males. Methodology: Twenty Japanese males (30-59 years) with mild fatty liver were enrolled in this blinded, placebocontrolled, randomized, parallel trial to assess the effects of 3 g of daily betaine for 12 weeks on safety and metabolic biomarkers. Selection criteria included fatty liver disease, as assessed by an abdominal ultrasonogram (US), the practice of moderate alcohol consumption, liver performance status and body mass index (≤27). Abdominal computed tomography (CT) as well as blood and urine sampling were performed before and after the intervention period. Results: No differences in the degree of hepatic steatosis or in the occurrence of adverse events were observed between the groups. Compared to the placebo group, the betaine group showed a significant increase in plasma betaine (P<0.0001) and high-density lipoprotein (HDL)-cholesterol (P<0.05) concentrations. Conclusion: Low-dose betaine supplementation to subjects with mild fatty liver disease is safe and well tolerated. Betaine increased plasma HDL which may reflect the favorable effects of betaine on liver function-related metabolic metabolism in Asian population.