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Safety of L-Carnitin as a dietary supplement using a multi-platform metabolomics approach
Project
Project code: MRI-OG-08-54401Metabolomics3
Contract period: 01.01.2014
- 29.02.2016
Purpose of research: Applied research
L-Carnitine is formed in the human organism and needed for lipid metabolism. L-carnitine is marketed as a dietary supplement due to its proposed fat-burning and performance-enhancing properties, although these effects could not be proved so far. However, some people take up large amount of L-carnitine. In this case, it is assumed that only part of the compound is directly absorbed in the gut while the remainder is degraded by gut bacteria leading to products like trimethylamin and trimethylamine-N-oxide. These substances may be harmful for the cardiovascular system and may also, under certain conditions, be converted to the carcinogen N-Nitrodimethylamine. In a study investigating the chronic toxicity of L-carnitine in rats, no adverse effects with respect to the cardiovasdular system or increased formation of preneoplastic lesions were observed [1]. However, effects of the supplementation on the metabolite profile were not addressed so far. The aim of this research program was to investigate the effect of a chronic supplementation with L-carnitine on the metabolite profile of rat plasma. Using targeted as well as untargeted methods (GC×GC-MS und LC-MS), a broad spectrum of endogenous compounds as well as L-carnitine metabolites will be detected in order to establish a firm basis for safety evaluation. [1] Empl MT et al., The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats. Archives of Toxicology, 2014. [2] Kulling SE, Weinert CH et al., Metabolomics: Ungerichtete Analysen in Lebensmitteln. Forschungsreport 2/2014. [3] Weinert CH, Über die Eignung der umfassenden zweidimensionalen Gaschromatografie mit Quadrupol-MS-Detektion (GC×GC-qMS) für die Durchführung von Metabolomanalysen humaner und pflanzlicher Matrizes. Dissertation, Karlsruher Institut für Technologie, 2014. [4] Weinert CH, Egert B, Kulling SE, Comprehensive two-dimensional gas chromatography combined with a fast- scanning quadrupole mass spectrometer (GC×GC-qMS): Suitable for untargeted large-scale metabolomics? Journal of Chromatography A, 2015 (eingereicht).
In a previous toxicity study performed by the University of Veterinary Medicine Hannover, rats were supplemented with up to 0.5 g/L L-carnitine in the drinking water for the duration of one year. For the present project, blood samples from this study were analyzed with targeted and untargeted LC-MS/MS and GC×GC-MS methods (metabolomics approach) in order to investigate whether supplementation with L-carnitine leads to changes in the metabolite profile or formation of new or unknown metabolites. 359 metabolites were unambiguously quantified with the applied combination of methods, and 29 metabolites from different substance classes were significantly influenced by the permanent administration of L-carnitine. The majority of metabolites (e.g. organic acids, amino acids, phospholipids, sugars) showed only a minor change of plasma concentrations (mostly decrease), and the biological relevance of these changes remains unclear. The plasma concentration of L-carnitine itself was slightly increased upon supplementation (max. 26% at highest dose). A very strong and dose-dependent change was observed for one important metabolite of L-carnitine, namely trimethylamine-N-oxide (TMAO): a tenfold higher TMAO level on average was observed in the high-dose group compared to the control group (2.5 µmol/L vs. 25.0 µmol/L). No other drastic changes in the overall plasma metabolome were detected. However, as it is still unclear whether TMAO is a risk factor for the development of cardiovascular diseases, a health risk due to chronically elevated TMAO plasma concentrations cannot be safely excluded.
Section overview
Subjects
- Physiology of Nutrition
- Food Chemistry
Framework programme
Funding programme
Excutive institution
MRI - Department of Safety and Quality of Fruit and Vegetables (MRI-OG)
