METABOLIC FATE OF ACETYLCARNITINE IN MICE AND HUMANS: INSIGHTS INTO BIOAVAILABILITY AND EXCRETION

Objectives. Acetylcarnitine, widely used in food supplements as a source of carnitine and
acetyl groups, is marketed for its potential benefits in neurological disorders. This study aimed
to clarify the bioavailability, distribution, metabolism, and elimination pathways of
acetylcarnitine through investigations in both murine models and healthy human volunteers.
Materials and Methods. In murine studies, [13C]-acetylcarnitine was administered
intravenously and orally at doses of 20 and 200 mg/kg. In the clinical study, healthy volunteers
received a single oral dose of 1500 mg acetylcarnitine. Blood and urine samples were collected
at baseline and specified intervals throughout the study. Quantification of acetylcarnitine and
L-carnitine concentrations in biological samples was conducted by ultrahigh-performance
liquid chromatography-tandem mass spectrometry (UPLC–MS/MS).
Results. Oral administration of acetylcarnitine in mice at a dose of 200 mg/kg resulted in a
bioavailability of only 8.6%. Administration of [13C]-acetylcarnitine induced the washout of
endogenous unlabeled carnitine and unlabeled acetylcarnitine from tissue stores, leading to
significant increases in plasma concentrations by 26% and 139%, respectively. Furthermore,
acetylcarnitine administration markedly increased urinary excretion of carnitine and
acetylcarnitine, accounting for up to 50% of the administered dose. Plasma levels of mediumand long-chain acylcarnitines also increased following acetylcarnitine intake. In human
subjects, acetylcarnitine exhibited even lower bioavailability than in mice. Additionally,
substantial part of the ingested dose was metabolized by gut microbiota into trimethylamine
that later was metabolised to trimethylamine N-oxide by the liver enzymes. Consistent with
murine data, acetylcarnitine supplementation in humans stimulated the renal excretion of
carnitine and its derivatives.
Conclusions. The oral bioavailability of acetylcarnitine is minimal (1-2%) in both mice and
humans. Supplementation induces the release of endogenous carnitine, acetylcarnitine, and
other acylcarnitines from tissues, promoting their subsequent urinary excretion. These findings
offer novel insights into the in vivo regulation of acetylcarnitine and carnitine homeostasis.