Oral supplementation with L-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of L-carnitine, trimethylamine oxide (TMAO), is an independent and dose-dependent risk factor for cardiovascular disease (CVD). Given the limited data demonstrating efficacy with oral L-carnitine therapy and the newly raised questions of potential harm, we assessed plasma TMAO levels in patients with mitochondrial disease with and without oral L-carnitine supplementation. Nine subjects were recruited and completed the study. Eight out of 9 subjects at baseline had plasma TMAO concentrations <97.5th percentile (<15.5 μM). One subject with stage 3 renal disease, had marked elevation in plasma TMAO (pre 33.98 μm versus post 101.6 μm). Following at least 3 months of L-carnitine supplementation (1000 mg per day), plasma TMAO levels were markedly increased in 7out of 9 subjects; overall, plasma TMAO significantly increased 11.8-fold (p < 0.001) from a baseline median level of 3.54 μm (interquartile range (IQR) 2.55–8.72) to 43.26 (IQR 23.99–56.04) post supplementation. The results of this study demonstrate that chronic oral L-carnitine supplementation markedly increases plasma TMAO levels in subjects with mitochondrial disorders. Further studies to evaluate both the efficacy and long term safety of oral L-carnitine supplementation for the treatment of mitochondrial disorders are warranted.
Vallance, H. D., Koochin, A., Branov, J., Rosen-Heath, A., Bosdet, T., Wang, Z., … Horvath, G. (2018). Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral L-carnitine. Molecular Genetics and Metabolism Reports, 15, 130–133. https://doi.org/10.1016/j.ymgmr.2018.04.005