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Cited by 425

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Kinetics, Pharmacokinetics, and Regulation of l‐Carnitine and Acetyl‐l‐carnitine Metabolism

REBOUCHE, CHARLES J.·2004·Annals of the New York Academy of Sciences
DOI 10.1196/annals.1320.003
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Abstract

A bstract: 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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Metadata

Authors
REBOUCHE, C. J.
Venue
Annals of the New York Academy of Sciences
Publisher
Wiley
Published
2004-11
Volume
1033
Issue
1
Pages
30-41
ISSN
  • 0077-8923 (ISSN-L)
  • 1749-6632
DOI
10.1196/annals.1320.003
OpenAlex
W2166129869
Cited by
425
References
3
FWCI
4.92
Type
journal article
Language
en
Open access
closed

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