Tier 4 — mechanistic

Plasma trimethylamine N-oxide, carnitine, choline, and betaine distinguish cognition impairment in Parkinson's disease

Zhaohan Xu, Hucheng Chen, Guoyan Zheng, Wei Zhang, Jing Wang, Jian Zhang, Qing Gao, Jun Wu, Xue Xue
Parkinsonism & related disorders 2025 135:107844

Bibliography

PubMed
PMID 40286463
DOI
10.1016/j.parkreldis.2025.107844
Funding
Funding was not specified in the indexed record or accessible funding metadata.
Competing interests
Reported disclosure: The authors 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

DesignCase-control diagnostic biomarker study
ModelHuman participants
Sample234 Parkinson patients and 220 healthy controls
InterventionMeasured betaine status and related metabolites; no randomized TMG treatment
DurationSingle cognitive and blood assessment
EndpointsParkinson disease; Cognitive biomarkers

What the study showed, in plain terms

Published in 2025, this source examined human observational and biomarker research. Design: Case-control diagnostic biomarker study. Sample/model: 234 Parkinson patients and 220 healthy controls. The exposure or intervention was Measured betaine status and related metabolites; no randomized TMG treatment. Follow-up or treatment period: Single cognitive and blood assessment.

TMAO-pathway metabolite patterns, including higher betaine in some patient comparisons, helped distinguish groups with Parkinson disease and cognitive impairment.

Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.

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Key findings

  • TMAO-pathway metabolite patterns, including higher betaine in some patient comparisons, helped distinguish groups with Parkinson disease and cognitive impairment.
  • The recorded outcome domains were Parkinson disease; Cognitive biomarkers.
  • The exposure was observed rather than assigned as an isolated supplement treatment.

What this study can and cannot tell us

  • Observational exposure analysis: residual confounding and reverse causation remain possible. Associations do not establish that betaine supplementation causes the same outcome. Diet recall, case selection or illness-related metabolite changes may introduce bias.
  • Confounding, dietary patterns, illness, medication use and reverse causation can influence an association. Blood or dietary concentrations do not identify the effect of starting a capsule.
  • Source basis: Indexed abstract and bibliographic data. Missing method details, funding information or participant denominators are not inferred.

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Editorial review

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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