Tier 2 — strong

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

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
The Journal of clinical endocrinology and metabolism 2018 103(8):3038-3049

Bibliography

PubMed
PMID 29860335
PubMed Central
PMC6692715
DOI
10.1210/jc.2018-00507
Funding
Reported funding/support: American Diabetes Association##7-13-CE-17Bedside to Bench and Back: Cardiometabolic Effects of Betaine SupplementationAmerican Diabetes Association Mentor-Based Minority Postdoctoral Fellowship1-15-MI-05National Institutes of Health10.13039/100000002P30 DK036836R01 DK 029953R01DK1081572DK108159DK08157209Sunstar Foundation Postdoctoral FellowshipThe Harvard CatalystThe Harvard Clinical and Translational Science CenterNational Center for Research Resources10.13039/100000097National Center for Advancing Translational Sciences10.13039/100006108NIH10.13039/100000002UL1 TR001102Harvard University and its affiliated academic health care centersJoslin Clinical Research Center
Competing interests
A competing-interest declaration was not available in the indexed record or accessible disclosure metadata.

Study snapshot

DesignRandomized controlled trial
ModelHuman participants
Sample27 adults with obesity and prediabetes
InterventionBetaine 3.3 g twice daily initially, then 4.95 g twice daily versus placebo
Duration12-week trial with a 10-day initial lower-dose period
EndpointsInsulin sensitivity; Glycemia; Liver fat; Cholesterol

What the study showed, in plain terms

Published in 2018, this source examined metabolic health and liver trials. Design: Randomized controlled trial. Sample/model: 27 adults with obesity and prediabetes. The exposure or intervention was Betaine 3.3 g twice daily initially, then 4.95 g twice daily versus placebo. Follow-up or treatment period: 12-week trial with a 10-day initial lower-dose period.

Clamp-measured insulin sensitivity, liver fat and endothelial function did not improve. Total cholesterol increased, despite some changes in insulin response and metabolites.

Small study with several endpoints. The fasting-glucose trend was not statistically significant and should not be described as diabetes treatment.

Continue with TMG Data Center

Continue with TMG for Weight Loss: Body-Fat Findings and Their Limits

Key findings

  • Clamp-measured insulin sensitivity, liver fat and endothelial function did not improve.
  • Total cholesterol increased, despite some changes in insulin response and metabolites.
  • The recorded outcome domains were Insulin sensitivity; Glycemia; Liver fat; Cholesterol.
  • The result applies to the tested exposure: Betaine 3.3 g twice daily initially, then 4.95 g twice daily versus placebo; 12-week trial with a 10-day initial lower-dose period.

What this study can and cannot tell us

  • Small study with several endpoints. The fasting-glucose trend was not statistically significant and should not be described as diabetes treatment.
  • An individual controlled trial must be interpreted alongside its comparator, sample size, endpoint selection and independent replication. It does not validate a different commercial formulation or a general longevity claim.
  • Source basis: Indexed abstract and bibliographic data. Missing method details, funding information or participant denominators are not inferred.

Related papers in the corpus

Tier 4
Dietary Choline and Betaine Are Not Associated With the Risk of Type 2 Diabetes. A Systematic Review and Meta-Analysis of Observational Studies
Elham Sharifi-Zahabi et al. · Journal of diabetes research · 2026
Tier 4
High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study
Erwin Garcia et al. · Journal of clinical medicine · 2019
Tier 4
Associations between Serum Betaine, Methyl-Metabolizing Genetic Polymorphisms and Risk of Incident Type 2 Diabetes: A Prospective Cohort Study in Community-Dwelling Chinese Adults
Xiaoting Lu et al. · Nutrients · 2022
Tier 2
Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial
Manal F Abdelmalek et al. · Hepatology (Baltimore, Md.) · 2009
Tier 2
Pilot trials of oral betaine in participants with metabolic dysfunction-associated steatotic liver disease and elevated alanine aminotransferase
Andrew S Lim et al. · Hepatology (Baltimore, Md.) · 2026
Tier 4
Betaine in Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanisms of Action and Therapeutic Potential
Tatjana Radosavljevic et al. · Antioxidants (Basel, Switzerland) · 2026

Citation network

Articles citing this research paper

1 article

Biohack Blueprint analyses that reference this study in their evidence base.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology