Trial reportThe Journal of clinical investigation2019
l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.
Trial report in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 190 papers, 6 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.
CARNIVAL Study: Gut Flora Dependent Metabolism of Dietary CARNItine and Phosphatidylcholine and cardioVAscuLar Disease
Plant-Based Meat vs Animal "Red" Meat: a Randomized Cross-over Trial
Who cites it
190 citing papers in PubMed, 6 syntheses or guidelines pooled it, 320 citations in OpenAlex.
- A systematic review of TMAO, microRNAs, and the oral/gut microbiomes in atherosclerosis and myocardial infarction: mechanistic insights and translational opportunities.Journal of translational medicine · 2025Pooled it
- The Effect of Red Meat Consumption on Circulating, Urinary, and Fecal Trimethylamine-N-Oxide: A Systematic Review and Narrative Synthesis of Randomized Controlled Trials.Advances in nutrition (Bethesda, Md.) · 2025Pooled it
- Gut microbiota regulate atherosclerosis via the gut-vascular axis: a scoping review of mechanisms and therapeutic interventions.Frontiers in microbiology · 2025Pooled it
- Association between trimethylamine N-oxide and prognosis of patients with myocardial infarction: a meta-analysis.Frontiers in cardiovascular medicine · 2024Pooled it
- Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- The relationship between trimethylamine-N-oxide and the risk of acute ischemic stroke: A dose‒response meta-analysis.PloS one · 2023Pooled it
- Effect of a polyphenol-rich pomegranate extract on plasma trimethylamine N-oxide levels following an oral carnitine challenge: a randomized controlled crossover trial in healthy adults.Frontiers in nutrition · 2026Trial
- Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism.Molecular nutrition & food research · 2025Trial
- Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial.JAMA network open · 2023Trial
- Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.Journal of the American Heart Association · 2021Trial
- Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial.The American journal of medicine · 2021Trial
- Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery.Microbiome · 2020Trial
- A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT).The American journal of clinical nutrition · 2020Trial
- Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study.Journal of the American Heart Association · 2020Trial
- Trial
- Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women.European heart journal · 2019Trial
- Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction.The Journal of clinical investigation · 2026Article
- The gut microbiome and allograft outcomes: implications for heart transplantation.The Journal of clinical investigation · 2026Review
- Divergent skeletal muscle metabolite exchange in insulin-like growth factor-1-stimulated myotubes and resistance-exercised human muscle.Experimental physiology · 2026Article
- Design and Therapeutic Applications of Hydrogel Dressings in Diverse Wound Management.ACS omega · 2026Review
130 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
19 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundl-Carnitine, an abundant nutrient in red meat, accelerates atherosclerosis in mice via gut microbiota-dependent formation of trimethylamine (TMA) and trimethylamine N-oxide (TMAO) via a multistep pathway involving an atherogenic intermediate, γ-butyrobetaine (γBB). The contribution of γBB in gut microbiota-dependent l-carnitine metabolism in humans is unknown.
methodsOmnivores and vegans/vegetarians ingested deuterium-labeled l-carnitine (d3-l-carnitine) or γBB (d9-γBB), and both plasma metabolites and fecal polymicrobial transformations were examined at baseline, following oral antibiotics, or following chronic (≥2 months) l-carnitine supplementation. Human fecal commensals capable of performing each step of the l-carnitine→γBB→TMA transformation were identified.
resultsStudies with oral d3-l-carnitine or d9-γBB before versus after antibiotic exposure revealed gut microbiota contribution to the initial 2 steps in a metaorganismal l-carnitine→γBB→TMA→TMAO pathway in subjects. Moreover, a striking increase in d3-TMAO generation was observed in omnivores over vegans/vegetarians (>20-fold; P = 0.001) following oral d3-l-carnitine ingestion, whereas fasting endogenous plasma l-carnitine and γBB levels were similar in vegans/vegetarians (n = 32) versus omnivores (n = 40). Fecal metabolic transformation studies, and oral isotope tracer studies before versus after chronic l-carnitine supplementation, revealed that omnivores and vegans/vegetarians alike rapidly converted carnitine to γBB, whereas the second gut microbial transformation, γBB→TMA, was diet inducible (l-carnitine, omnivorous). Extensive anaerobic subculturing of human feces identified no single commensal capable of l-carnitine→TMA transformation, multiple community members that converted l-carnitine to γBB, and only 1 Clostridiales bacterium, Emergencia timonensis, that converted γBB to TMA. In coculture, E. timonensis promoted the complete l-carnitine→TMA transformation.
conclusionIn humans, dietary l-carnitine is converted into the atherosclerosis- and thrombosis-promoting metabolite TMAO via 2 sequential gut microbiota-dependent transformations: (a) initial rapid generation of the atherogenic intermediate γBB, followed by (b) transformation into TMA via low-abundance microbiota in omnivores, and to a markedly lower extent, in vegans/vegetarians. Gut microbiota γBB→TMA/TMAO transformation is induced by omnivorous dietary patterns and chronic l-carnitine exposure.
trial registrationClinicalTrials.gov NCT01731236.
fundingNIH and Office of Dietary Supplements grants HL103866, HL126827, and DK106000, and the Leducq Foundation.
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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 OpenQuestion graph.