Trial reportJournal of the American Heart Association2017
Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study.
Trial report in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
79 citing papers in PubMed, 4 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Significant correlation between the gut microbiota-derived metabolite trimethylamine-N-oxide and the risk of stroke: evidence based on 23 observational studies.European journal of clinical nutrition · 2023Pooled it
- SGLT2 Inhibition, Choline Metabolites, and Cardiometabolic Diseases: A Mediation Mendelian Randomization Study.Diabetes care · 2022Pooled it
- Gut microbiota-derived metabolite trimethylamine-N-oxide and multiple health outcomes: an umbrella review and updated meta-analysis.The American journal of clinical nutrition · 2022Pooled it
- Gut microbiota-associated metabolite trimethylamine N-Oxide and the risk of stroke: a systematic review and dose-response meta-analysis.Nutrition journal · 2020Pooled it
- Plasma choline and betaine and neurological function trajectory after acute ischemic stroke.BMC neurology · 2026Trial
- Preliminary evidence of effects of potassium chloride on a metabolomic path to diabetes and cardiovascular disease.Metabolomics : Official journal of the Metabolomic Society · 2020Trial
- Rosuvastatin alters the genetic composition of the human gut microbiome.Scientific reports · 2020Trial
- Comparative insights into the gut-heart axis: cross-species and cross-population perspectives.Gut microbes · 2026Review
- Trimethylamine N-oxide and major adverse cardiac and cerebrovascular events: results of umbrella review and meta-analysis.Nutrition & metabolism · 2026Article
- Choline status and related health outcomes in humans: A scoping review.Nutrition and health · 2026Article
- The role of choline in neurodevelopment.Pediatric research · 2026Review
- The Mediterranean Diet and Cardiovascular Protection: Biochemical Mechanisms with Emphasis on Platelet-Activating Factor.Nutrients · 2026Review
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Betaine: A Promising Natural Product for Neurological and Psychiatric Diseases.Current neuropharmacology · 2026Review
- The Mediterranean diet and cardiovascular disease.Cardiovascular research · 2025Review
- Metabolomic profiles of an atherogenic TMAO-dietary pattern among postmenopausal women.European journal of nutrition · 2025Article
- Dysregulation of the FGF21-Adiponectin Axis in a Large Cohort of Patients with Severe Obesity and Liver Disease.International journal of molecular sciences · 2025Article
- Recent advances in precision nutrition and cardiometabolic diseases.Revista espanola de cardiologia (English ed.) · 2025Review
- The gut microbiota in thrombosis.Nature reviews. Cardiology · 2025Review
- Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 13 institutions in 2 countries.
Funding
Abstract
backgroundThe relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. METHODS AND
resultsWe designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and α-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and α-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59;
conclusionsA metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk. CLINICAL
trial registrationURL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
Indexed as
Identifiers
What Socratic holds
Registered trials
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.