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In mammals, the carnitine pool consists of nonesterified l-carnitine and many acylcarnitine esters. Of these esters, acetyl-l-carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary l-carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary l-carnitine is 54-87% and is dependent on the amount of l-carnitine in the meal. Absorption of l-carnitine dietary supplements (0.5-6 g) is primarily passive; bioavailability is 14-18% of dose. Unabsorbed l-carnitine is mostly degraded by microorganisms in the large intestine. Circulating l-carnitine is distributed to two kinetically defined compartments: one large and slow-turnover (presumably muscle), and another relatively small and rapid-turnover (presumably liver, kidney, and other tissues). At normal dietary l-carnitine intake, whole-body turnover time in humans is 38-119 h. In vitro experiments suggest that acetyl-l-carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl-l-carnitine concentration was increased 43% after oral acetyl-l-carnitine supplements of 2 g/day, indicating that acetyl-l-carnitine is absorbed at least partially without hydrolysis. After single-dose intravenous administration (0.5 g), acetyl-l-carnitine is rapidly, but not completely hydrolyzed, and acetyl-l-carnitine and l-carnitine concentrations return to baseline within 12 h. At normal circulating l-carnitine concentrations, renal l-carnitine reabsorption is highly efficient (90-99% of filtered load; clearance, 1-3 mL/min), but displays saturation kinetics. Thus, as circulating l-carnitine concentration increases (as after high-dose intravenous or oral administration of l-carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating l-carnitine concentration to baseline. Elimination kinetics for acetyl-l-carnitine are similar to those for l-carnitine. There is evidence for renal tubular secretion of both l-carnitine and acetyl-l-carnitine. Future research should address the correlation of supplement dosage, changes and maintenance of tissue l-carnitine and acetyl-l-carnitine concentrations, and metabolic and functional changes and outcomes.

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