Recent studies have implicated
trimethylamine N-oxide (
TMAO) in
atherosclerosis, raising concern about
L-carnitine, a common supplement for patients with
inborn errors of metabolism (IEMs) and a
TMAO precursor metabolized, in part, by intestinal microbes. Dietary meat restriction attenuates
carnitine-to-
TMAO conversion, suggesting that
TMAO production may not occur in meat-restricted individuals taking supplemental
L-carnitine, but this has not been tested. Here, we mine a metabolomic dataset to assess
TMAO levels in patients with diverse IEMs, including organic acidemias. These data were correlated with clinical information and confirmed using a quantitative
TMAO assay. Marked plasma
TMAO elevations were detected in patients treated with supplemental
L-carnitine, including those on a meat-free diet. On average, patients with an organic acidemia had ~45-fold elevated [
TMAO], as compared to the reference population. This effect was mitigated by
metronidazole therapy lasting 7 days each month. Collectively, our data show that
TMAO production occurs at high levels in patients with IEMs receiving oral
L-carnitine. Further studies are needed to determine the long-term safety and efficacy of chronic oral
L-carnitine supplementation and whether suppression or circumvention of intestinal bacteria may improve
L-carnitine therapy.