Evidence mapPaperPMID 40758380Full record

Trial reportHepatology (Baltimore, Md.)2026

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 and 3 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Hepatology (Baltimore, Md.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Andrew S LimResearch Healthcare Group, Veterans Administration Healthcare System, Long Beach, California, USA.
Sheena N CruzHCA Healthcare Program, Riverside Community Hospital, Riverside, California, USA.
Aliya Asghar UddinResearch Healthcare Group, Veterans Administration Healthcare System, Long Beach, California, USA.
Olga MalyshevaDivision of Nutritional Sciences, Cornell University, Ithaca, New York, USA.ORCID 0009-0004-9114-1657
Marie A CaudillDivision of Nutritional Sciences, Cornell University, Ithaca, New York, USA.ORCID 0000-0002-7192-5743
Cristina AlonsoRubió Metabolomics, Derio, Bizkaia, Spain.
Alejandro MontillaRubió Metabolomics, Derio, Bizkaia, Spain.
Morten A KarsdalNordic Bioscience A/S, Herlev Hovedgarde, Herlev, Denmark.
Diana Julie LeemingNordic Bioscience A/S, Herlev Hovedgarde, Herlev, Denmark.
Alejandro E Mayorca-GuilianiNordic Bioscience A/S, Herlev Hovedgarde, Herlev, Denmark.
Frederik Høbjerg SvejsøNordic Bioscience A/S, Herlev Hovedgarde, Herlev, Denmark.
Craig J McClainDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, Kentucky, USA.ORCID 0000-0002-7219-8939
Timothy R MorganResearch Healthcare Group, Veterans Administration Healthcare System, Long Beach, California, USA.ORCID 0000-0003-1328-0307

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsBetaine, 20 g/day for 12 months, reduced liver injury in several trials in non-alcoholic steatohepatitis (NASH). Our aim was to determine the safety and efficacy of lower doses of betaine in clinically diagnosed metabolic dysfunction-associated steatotic liver disease (MASLD) and an elevated ALT. APPROACH AND

resultsWe performed 3 pilot trials in participants with clinically diagnosed non-cirrhotic MASLD and ALT ≥50 U/L. In the first trial, 44 participants were randomized to 4 or 8 g daily for 12 weeks. In the second trial, 10 participants received 1 g/day for 24 weeks, while 16 participants received 2 g/day for 24 weeks in the third trial. The primary outcome was the percent decline in the abnormal component of ALT (ie, ALT >30 for males or >25 for females). Other outcomes included improvement in absolute ALT and AST, and other serologic tests of liver injury, including metabolomics-advanced steatohepatitis fibrosis (MASEF) score, cytokeratin 18, and pro-C3. Baseline and end-of-treatment data were compared with a paired t test. At baseline, more than 75% of participants had NASH when tested by the MASEF score. ALT, AST, cytokeratin 18, pro-C3, and MASEF score decreased significantly among participants receiving 8, 4​​​​​, and 2 g, but not 1 g. High-density lipoprotein increased in the 4 and 2 g cohorts; low-density lipoprotein did not change. Approximately 35% reported mild, transient gastrointestinal symptoms.

conclusionsBetaine 8, 4​​​​​​, and 2 g/day for 12-24 weeks significantly reduced ALT and other serologic markers of liver injury among participants with clinically defined MASLD and an elevated ALT.

Indexed as

Alanine TransaminaseBetaineNon-alcoholic Fatty Liver DiseaseAdministration, OralAdultAgedFemaleHumansMaleMiddle AgedPilot ProjectsTreatment OutcomeAlanine TransaminaseBetainebetaineclinical trialmetabolic dysfunction–associated steatotic liver disease

Identifiers

PMID40758380
PMCPMC13178775

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.