Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.
Level 3 - non-randomized controlled study
Prospective and cross-sectional observational clinical cohort combined with mechanistic animal and human challenge models
PubMed 23563705 · doi:10.1038/nm.3145
What was done
Researchers examined the relationship between dietary L-carnitine, gut microbiota metabolism, and atherosclerosis using human cohorts and animal models. They evaluated plasma L-carnitine and trimethylamine-N-oxide (TMAO) levels in 2,595 subjects undergoing cardiac evaluation to assess risks for prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke, or death). They also compared TMAO production in omnivorous versus vegan or vegetarian humans after L-carnitine ingestion and examined associated fecal bacterial taxa. In mice, they tested the effects of chronic dietary L-carnitine supplementation on cecal microbiota, TMA/TMAO synthesis, reverse cholesterol transport, and atherosclerosis, with and without gut microbiota suppression.
What was found
Omnivorous humans produced more TMAO than vegans or vegetarians after L-carnitine ingestion. In the human cohort (n = 2,595), plasma L-carnitine predicted increased risk for prevalent CVD and incident major adverse cardiac events only in subjects with concurrently high TMAO levels (exact effect sizes and hazard ratios were not provided in the abstract). In mice, L-carnitine supplementation altered cecal microbial composition, enhanced TMA and TMAO synthesis, reduced in vivo reverse cholesterol transport, and increased atherosclerosis; these effects were prevented when intestinal microbiota were suppressed.
Why it matters
This study identifies a microbial pathway linking red meat intake to cardiovascular disease, showing that gut microbiota-dependent conversion of L-carnitine to TMAO accelerates atherosclerosis.
Limits
The abstract provides no numerical effect estimates, odds ratios, or confidence intervals for the clinical associations. The clinical cohort was restricted to patients undergoing cardiac evaluation rather than a general population sample, and the causal link between carnitine metabolism and atherogenesis was established primarily in animal models.
Cited by
- supports Oral L-carnitine has low absorption bioavailability and oral supplementation increases trimethylamine N-oxide (TMAO).
- supports Gut bacteria determine whether dietary L-carnitine and choline are converted into TMAO.