Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes
What this study found
Betaine produced little clinically meaningful metabolic benefit overall. It did not improve clamp-based insulin sensitivity, intrahepatic fat, or endothelial function, and fasting glucose only showed a non-significant downward trend at 12 weeks. Some intermediate measures favored betaine, including lower OGTT insulin AUC and a better Matsuda index, but total cholesterol increased by 21 mg/dL (95% CI, 3 to 40; P = 0.032). The authors concluded that these findings do not support betaine supplementation to treat prediabetes or reduce cardiometabolic risk in obesity and prediabetes.
- Study & population
- Single-center, randomized, placebo-controlled trial in adults 21 to 70 years old with prediabetes and overweight or obesity (BMI 25 to 45 kg/m2) at Brigham and Women’s Hospital in the United States.
- Intervention
- Oral betaine supplementation was given as 3300 mg twice daily for 10 days, then increased to 4950 mg twice daily through 12 weeks.
- Key limitation
- Small single-center trial with a short 12-week duration limits generalizability and power for clinical endpoints.
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Open PDFOriginal abstract
Context Plasma betaine correlates with insulin sensitivity in humans. Betaine supplementation improves metabolic effects in mice fed a high-fat diet. Objective To assess metabolic effects of oral betaine in obese participants with prediabetes. Design A 12-week, parallel arm, randomized, double-masked, placebo-controlled trial. Setting University-affiliated hospital. Participants and Interventions Persons with obesity and prediabetes (N = 27) were randomly assigned to receive betaine 3300 mg orally twice daily for 10 days, then 4950 mg twice daily for 12 weeks, or placebo. Main Outcome Measures Changes from baseline in insulin sensitivity, glycemia, hepatic fat, and endothelial function. Results There was a 16.5-fold increase in plasma dimethylglycine [dimethylglycine (DMG); P < 0.0001] levels, but modest 1.3- and 1.5-fold increases in downstream serine and methionine levels, respectively, in the betaine vs placebo arm. Betaine tended to reduce fasting glucose levels (P = 0.08 vs placebo) but had no other effect on glycemia. Insulin area under curve after oral glucose was reduced for betaine treatment compared with placebo (P = 0.038). Insulin sensitivity, assessed by euglycemic hyperinsulinemic clamp, was not improved. Serum total cholesterol levels increased after betaine treatment compared with placebo (P = 0.032). There were no differences in change in intrahepatic triglyceride or endothelial function between groups. Conclusion DMG accumulation supports DMG dehydrogenase as rate limiting for betaine metabolism in persons with prediabetes. Betaine had little metabolic effect. Additional studies may elucidate mechanisms contributing to differences between preclinical and human responses to betaine, and whether supplementation of metabolites downstream of DMG improves metabolism.