1. Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes
- Author
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Sahni Va, Grizales Am, Alexander P. Lin, Rita Basu, Chisayo Kozuka, Mary-Elizabeth Patti, Jonathan M. Dreyfuss, Cloutier E, Robert E. Gerszten, Joshua A. Beckman, Allison B. Goldfine, Lee A, David Pober, Hui Pan, and Fowler Km
- Subjects
Blood Glucose ,Male ,0301 basic medicine ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Context (language use) ,Placebo ,Proof of Concept Study ,Biochemistry ,Placebos ,Prediabetic State ,Dimethylglycine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Insulin resistance ,Betaine ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,Obesity ,Prediabetes ,Clinical Research Articles ,Aged ,Triglyceride ,business.industry ,Insulin ,Biochemistry (medical) ,Middle Aged ,medicine.disease ,030104 developmental biology ,chemistry ,Dietary Supplements ,Female ,Insulin Resistance ,Energy Metabolism ,business - Abstract
ContextPlasma betaine correlates with insulin sensitivity in humans. Betaine supplementation improves metabolic effects in mice fed a high-fat diet.ObjectiveTo assess metabolic effects of oral betaine in obese participants with prediabetes.DesignA 12-week, parallel arm, randomized, double-masked, placebo-controlled trial.SettingUniversity-affiliated hospital.Participants and InterventionsPersons 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 MeasuresChanges from baseline in insulin sensitivity, glycemia, hepatic fat, and endothelial function.ResultsThere 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.ConclusionDMG 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.
- Published
- 2018