Christoph H Weinert1, Michael T Empl2, Ralf Krüger3, Lara Frommherz1, Björn Egert1, Pablo Steinberg2, Sabine E Kulling1. 1. Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany. 2. Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hanover, Hanover, Germany. 3. Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
Abstract
SCOPE: L-carnitine has been advertised as a fat-lowering and performance-enhancing supplement, although scientific evidence for its effectiveness is lacking. The uptake of about 1-2 g of L-carnitine per day may result in the formation of metabolites like trimethylamine-N-oxide (TMAO), which in turn may be converted to potential carcinogens or promote the development of cardiovascular diseases. METHODS AND RESULTS: To assess whether an L-carnitine supplementation changes overall metabolism or causes the formation of previously unknown metabolites, we analyzed plasma samples from Fischer 344 rats originating from a previous study using a multi-platform metabolomics approach comprising LC-MS/MS and GC×GC-MS methods. Despite an intake of up to 352 mg L-carnitine/kg body weight/day for 1 year, plasma concentrations of only 29 out of 359 metabolites were significantly influenced, the induced concentration changes being often comparatively small. Nevertheless, a clear dose-response relationship and a substantial concentration increase were observed for TMAO, i.e. a tenfold higher TMAO level was measured in the high-dose group when compared to the control (2.5 versus 25.0 μM). CONCLUSION: Although L-carnitine supplementation did not cause large changes in the plasma metabolome, a higher risk for cardiovascular disease due to chronically elevated TMAO plasma concentrations cannot be excluded.
SCOPE: L-carnitine has been advertised as a fat-lowering and performance-enhancing supplement, although scientific evidence for its effectiveness is lacking. The uptake of about 1-2 g of L-carnitine per day may result in the formation of metabolites like trimethylamine-N-oxide (TMAO), which in turn may be converted to potential carcinogens or promote the development of cardiovascular diseases. METHODS AND RESULTS: To assess whether an L-carnitine supplementation changes overall metabolism or causes the formation of previously unknown metabolites, we analyzed plasma samples from Fischer 344 rats originating from a previous study using a multi-platform metabolomics approach comprising LC-MS/MS and GC×GC-MS methods. Despite an intake of up to 352 mg L-carnitine/kg body weight/day for 1 year, plasma concentrations of only 29 out of 359 metabolites were significantly influenced, the induced concentration changes being often comparatively small. Nevertheless, a clear dose-response relationship and a substantial concentration increase were observed for TMAO, i.e. a tenfold higher TMAO level was measured in the high-dose group when compared to the control (2.5 versus 25.0 μM). CONCLUSION: Although L-carnitine supplementation did not cause large changes in the plasma metabolome, a higher risk for cardiovascular disease due to chronically elevated TMAO plasma concentrations cannot be excluded.
Authors: Manuela J Rist; Alexander Roth; Lara Frommherz; Christoph H Weinert; Ralf Krüger; Benedikt Merz; Diana Bunzel; Carina Mack; Björn Egert; Achim Bub; Benjamin Görling; Pavleta Tzvetkova; Burkhard Luy; Ingrid Hoffmann; Sabine E Kulling; Bernhard Watzl Journal: PLoS One Date: 2017-08-16 Impact factor: 3.240