Tier 2 — strong

Choline and betaine concentrations in plasma discriminate levels of dietary choline intake in healthy adults: analysis of a double-blind randomized crossover controlled feeding study

Isis Trujillo-Gonzalez, David A Horita, Julie Stegall, Rachel Coble, Evan M Paules, Anju A Lulla, Emmanuel Baah, Teodoro Bottiglieri, Wei Sha, Martin Kohlmeier, Walter B Friday, Steven H Zeisel
The American journal of clinical nutrition 2026 123(4):101236

Bibliography

PubMed
PMID 41687879
PubMed Central
PMC13084590
DOI
10.1016/j.ajcnut.2026.101236
Funding
Reported funding/support: This work was supported by the NIH/NIDDK R01 DK115380 (SHZ), NIH/NIDDK P30 DK056350 (SHZ).
Competing interests
Reported disclosure: EVM reports financial support was provided by Balchem Corp. IT-G reports financial support was provided by Balchem Corp. SHZ reports financial support was provided by National Institutes of Health. SHZ reports a relationship with SNP Therapeutics that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Study snapshot

DesignRandomized crossover controlled feeding RCT
ModelHuman participants
Sample73-75 adults in endpoint-specific analytic samples
InterventionCholine at about 100%, 50% and 25% of adequate intake; stable-isotope testing
Duration15 days per diet
EndpointsCholine-status biomarkers; Betaine; Liver fat

What the study showed, in plain terms

Published in 2026, this source examined food sources, absorption and nutrient metabolism. Design: Randomized crossover controlled feeding RCT. Sample/model: 73-75 adults in endpoint-specific analytic samples. The exposure or intervention was Choline at about 100%, 50% and 25% of adequate intake; stable-isotope testing. Follow-up or treatment period: 15 days per diet.

Plasma choline and betaine distinguished low from adequate choline intake; the combined biomarker panel performed better than either alone.

A choline-status study rather than a TMG supplementation trial. The final peer-reviewed paper supersedes its earlier preprint.

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Key findings

  • Plasma choline and betaine distinguished low from adequate choline intake; the combined biomarker panel performed better than either alone.
  • The recorded outcome domains were Choline-status biomarkers; Betaine; Liver fat.
  • The result applies to the tested exposure: Choline at about 100%, 50% and 25% of adequate intake; stable-isotope testing; 15 days per diet.

What this study can and cannot tell us

  • A choline-status study rather than a TMG supplementation trial. The final peer-reviewed paper supersedes its earlier preprint.
  • 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: Accessible full-text extract plus indexed bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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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