Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes.

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.

• Authors: Ana Maria Grizales, Mary-Elizabeth Patti, Alexander P Lin, Joshua A Beckman, V Anik Sahni, Emilie Cloutier, Kristen M Fowler, Jonathan M Dreyfuss, Hui Pan, Chisayo Kozuka, Adrienne Lee, Rita Basu, David M Pober, Robert E Gerszten, Allison B Goldfine
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 8 Pg. 3038-3049 (08 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 29860335 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Placebos
• Betaine

Topics

• Aged
• Betaine (administration & dosage, pharmacology)
• Blood Glucose (drug effects, metabolism)
• Dietary Supplements
• Double-Blind Method
• Energy Metabolism (drug effects)
• Female
• Humans
• Insulin Resistance
• Male
• Middle Aged
• Obesity (complications, drug therapy, metabolism)
• Placebos
• Prediabetic State (complications, drug therapy, metabolism)
• Proof of Concept Study