Carnitine facilitates the transport of long chain fatty acyl CoA esters across the inner mitochondrial membrane, facilitating beta-oxidation of fatty acids and acting as an intracellular energy reservoir of acetyl groups. In conditions of ischemia and carnitine deficiency, these acyl esters accumulate and cause deleterious effects, including inhibition of adenine nucleotide translocase, causing inhibition of ATP production (5). Carnitine modulates the ratio of CoA to CoA-SH, is involved in trapping acyl residues from peroxisomes and mitochondria, and stabilizes cellular membranes (6). Carnitine is a free radical scavenger and may take part in nuclear transcription.
High serum carnitine levels generally correlate with better functional capacity in clinical trials. Exogenous carnitine enhances mitochondrial function in several studies, thought due to an increase in fatty acid oxidation and conservation of glycogen or a decrease in levels of acetyl-CoA, which inhibits pyruvate dehydrogenase (1). In ischemic animal models, carnitine reduces loss of high-energy phosphates, enhances glucose oxidation, preserves myocardial carnitine stores, reduces accumulation of fatty acid esters, and enhances lactate extraction. Numerous studies report that carnitine supplementation improves cardiac performance in animal models of cardiomyopathy or ischemic insult, including improved myocardial metabolic patterns, reduced necrosis, diminished enzymatic infarct size, and preserved left ventricular function (8). L-carnitine has been shown to inhibit cisplatin-induced injury of the kidney and small intestine in animal models (13). One study suggested that L-carnitine inhibits caspases and decreases levels of TNF-alpha (14).
A few mechanisms that result in the anti-catabolic effects and the improvement of fatigue following l-carnitine supplementation include affecting improved nitrogen balance either due to increased protein synthesis or reduced protein degradation, inhibition of apoptosis and abrogation of inflammatory processes. Animal studies indicate that carnitine supplementation prevents oxidative stress and ameliorates mitochondrial function (29).
In a study of mice metabolism of dietary l-carnitine by intestinal microbiota produced trimethylamine-N-oxide (TMAO), a proatherogenic species, which accelerated atherosclerosis (30). Clinical trials are needed to determine the implications of this study in humans.
Long-term carnitine supplementation in humans is correlated with improved myocardial mechanical performance, reduction in ventricular arrhythmias, and increased exercise tolerance (7). In one study carnitine was shown effective in reversing hyperthyroidism by acting as a peripheral antagonist of thyroid hormone action (3).