title: Chronic Oral L-Carnitine Supplementation Drives Marked Plasma TMAO Elevations in Patients with Organic Acidemias Despite Dietary Meat Restrictions.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Miller
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Bret L
authors.initials: BL
authors.lastname: Bostwick
authors.affiliation: Metabolon Inc., Durham, NC, 27713, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kennedy
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Taraka R
authors.initials: TR
authors.lastname: Donti
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: V Reid
authors.initials: VR
authors.lastname: Sutton
authors.affiliation: Department of Molecular and Human Genetics, Medical Genetics Laboratory, Baylor College of Medicine, Houston, TX, 77030, USA. elsea@bcm.edu.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Elsea