Tier 2 — strong

Pilot trials of oral betaine in participants with metabolic dysfunction-associated steatotic liver disease and elevated alanine aminotransferase

Andrew S Lim, Sheena N Cruz, Aliya Asghar Uddin, Olga Malysheva, Marie A Caudill, Cristina Alonso, Alejandro Montilla, Morten A Karsdal, Diana Julie Leeming, Alejandro E Mayorca-Guiliani, Frederik Høbjerg Svejsø, Craig J McClain, Timothy R Morgan
Hepatology (Baltimore, Md.) 2026 83(6):1515-1528

Bibliography

PubMed
PMID 40758380
PubMed Central
PMC13178775
DOI
10.1097/HEP.0000000000001477
Funding
Funding was not specified in the indexed record or accessible funding metadata.
Competing interests
Reported disclosure: Cristina Alonso is employed by Rubió Metabolomics. Alejandro Montilla is employed by Rubió Metabolomics. Mortel A. Karsdal owns stock in and is employed by Nordic Bioscience. Diana Julie Leeming owns stock in and is employed by Nordic Bioscience. Alejandro E. Mayorca-Guiliani is employed by Nordic Bioscience. Frederik Høbjerg Svejsø is employed by Nordic Bioscience. The remaining authors have no conflicts to report.

Study snapshot

DesignDose-comparison and uncontrolled pilot trials
ModelHuman participants
Sample70 participants across three cohorts: 44, 10 and 16
InterventionBetaine 4 versus 8 g/day; separate 1 and 2 g/day cohorts
Duration12 weeks at 4-8 g; 24 weeks at 1-2 g
EndpointsALT and AST; Liver-injury biomarkers; Tolerability

What the study showed, in plain terms

Published in 2026, this source examined metabolic health and liver trials. Design: Dose-comparison and uncontrolled pilot trials. Sample/model: 70 participants across three cohorts: 44, 10 and 16. The exposure or intervention was Betaine 4 versus 8 g/day; separate 1 and 2 g/day cohorts. Follow-up or treatment period: 12 weeks at 4-8 g; 24 weeks at 1-2 g.

Liver enzymes and several injury markers decreased at 2, 4 and 8 g/day but not 1 g/day. Mild transient gastrointestinal symptoms affected approximately 35%.

The randomized portion compared active doses rather than placebo; the other cohorts were uncontrolled. Biomarker improvement does not confirm reversal of fibrosis.

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Key findings

  • Liver enzymes and several injury markers decreased at 2, 4 and 8 g/day but not 1 g/day.
  • Mild transient gastrointestinal symptoms affected approximately 35%.
  • The recorded outcome domains were ALT and AST; Liver-injury biomarkers; Tolerability.
  • The result applies to the tested exposure: Betaine 4 versus 8 g/day; separate 1 and 2 g/day cohorts; 12 weeks at 4-8 g; 24 weeks at 1-2 g.

What this study can and cannot tell us

  • The randomized portion compared active doses rather than placebo; the other cohorts were uncontrolled. Biomarker improvement does not confirm reversal of fibrosis.
  • Without a sufficiently blinded concurrent control, time effects, expectations, co-interventions and regression toward the mean can explain part of an apparent improvement.
  • Source basis: Indexed abstract and bibliographic data. Missing method details, funding information or participant denominators are not inferred.

Related papers in the corpus

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 4
Betaine in Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanisms of Action and Therapeutic Potential
Tatjana Radosavljevic et al. · Antioxidants (Basel, Switzerland) · 2026
Tier 2
Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes
Ana Maria Grizales et al. · The Journal of clinical endocrinology and metabolism · 2018
Tier 2
Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects
Ursula Schwab et al. · The American journal of clinical nutrition · 2002

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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