title: The influence of a chronic L-carnitine administration on the plasma metabolome of male Fischer 344 rats.
abstract: 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.
  
  
  
  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).
  
  
  
  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.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Weinert
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hanover, Hanover, Germany.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Empl
authors.affiliation: Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Krüger
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Frommherz
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Egert
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hanover, Hanover, Germany.
authors.forename: Pablo
authors.initials: P
authors.lastname: Steinberg
authors.affiliation: Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, Karlsruhe, Germany.
authors.forename: Sabine E
authors.initials: SE
authors.lastname: Kulling
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D002331:Carnitine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008744:Methylamines / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D053719:Tandem Mass Spectrometry
chemical_list: D002273:Carcinogens; D008744:Methylamines; C005855:trimethyloxamine; D002331:Carnitine
keywords: Fischer 344 rat; Food safety; L-carnitine; Trimethylamine-N-oxide; Untargeted multi-platform metabolomics