Bioavailability and Distribution of Acetylcarnitine in Mice and Healthy Volunteers

Objectives*
Acetylcarnitine, commonly used in food supplements as a source of carnitine and acetyl groups, is promoted
as a food supplement for improving neurological disorders. This study aimed to investigate the bioavailability,
distribution, metabolism, and elimination pathways of acetylcarnitine using both mouse models and healthy
human volunteers.
Materials and Methods
In mice, [13C]-acetylcarnitine was administered intravenously and orally at doses of 20 and 200 mg/kg. In a
clinical study, healthy volunteers received a single oral dose of 1500 mg acetylcarnitine. In both mice and
human studies, blood and urine samples were collected at baseline and during the study period. Concentrations of acetylcarnitine and L-carnitine in the samples were analysed using ultrahigh-performance liquid
chromatography-tandem mass spectrometry (UPLC–MS/MS).
Results
The oral bioavailability of acetylcarnitine in mice, after administration at a dose of 200 mg/kg, was only 8.6%.
Administration of [13C]-acetylcarnitine caused the efflux of endogenous carnitine and acetylcarnitine from tissues, significantly increasing their plasma concentrations for 26% and 139%, respectively. Acetylcarnitine administration also enhanced urinary excretion of carnitine and acetylcarnitine, amounting to up to 50% of the
administered dose. In response to acetylcarnitine administration, plasma levels of medium- and long-chain
acylcarnitines were also elevated. In humans, intake of acetylcarnitine resulted in even lower bioavailability
than in mice, and 25% part of the supplement were metabolized into trimethylamine N-oxide. Similar to results
in mice, acetylcarnitine intake in humans stimulated urinary excretion of carnitine and its derivatives.
Conclusions
The oral bioavailability of acetylcarnitine in both mice and humans is very low. Supplementation triggers the
release of endogenous carnitine, acetylcarnitine, and other acylcarnitines from tissues, and further excretion
into urine. These findings provide new insights into the regulation of acetylcarnitine and carnitine turnover in
vivo.