Empl Michael T, Kammeyer Patricia, Ulrich Reiner, Joseph Jan F, Parr Maria K, Willenberg Ina, Schebb Nils H, Baumgärtner Wolfgang, Röhrdanz Elke, Steffen Christian, Steinberg Pablo
Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173, Hannover, Germany.
Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559, Hannover, Germany.
Arch Toxicol. 2015 Nov;89(11):2079-87. doi: 10.1007/s00204-014-1341-4. Epub 2014 Aug 28.
L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.
左旋肉碱是脂肪酸氧化的关键成分,如今作为一种营养补充剂被广泛使用,据称具有“燃烧脂肪”和增强体能的特性,尽管迄今为止尚无确凿数据支持这些说法。此外,外源性补充与生物利用度之间存在反比关系,即口服相当高剂量时不能被完全吸收,因此大量肉碱会留在肠道内。人和大鼠的肠道细菌可将未吸收的左旋肉碱降解为三甲胺或氧化三甲胺,在某些条件下,它们可能转化为已知的致癌物N-亚硝基二甲胺。最近的研究结果表明,氧化三甲胺可能也与动脉粥样硬化病变的发展有关。因此,我们研究了通过饮用水给Fischer 344大鼠连续一年施用不同浓度(0、1、2和5克/升)的左旋肉碱,是否会导致其结肠中癌前病变(所谓的异常隐窝病灶)的发生率增加,以及这些动物主动脉中动脉粥样硬化病变的出现。在大鼠结肠和主动脉病变形成方面,各试验组之间未观察到显著差异,这表明在给定的实验条件下,饮用水中浓度高达5克/升的左旋肉碱对Fischer 344大鼠的胃肠道和血管系统没有不良影响。