Description
ObjectivesAcetylcarnitine, a common dietary supplement and mitochondrial metabolite, may influence cardiac energy metabolism. Given the role of disrupted acylcarnitine profiles in heart failure, this study aimed to investigate the bioavailability, distribution, metabolism, and elimination of acetylcarnitine in mice and healthy human volunteers to better understand the relevance of its supplementation.
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 their 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 medium- and long-chain acylcarnitines also increased following acetylcarnitine intake. In human subjects, acetylcarnitine exhibited even lower bioavailability than in mice (1-2%). Additionally, substantial part of the ingested dose was metabolized into trimethylamine N-oxide. 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 in mice and humans. Its supplementation promotes tissue release and urinary excretion of carnitine, acetylcarnitine, and other acylcarnitines. To target metabolic dysregulation in heart failure by acetylcarnitine, innovative formulations might be needed to increase its bioavailability.
| Period | 16 Sept 2025 → 18 Sept 2025 |
|---|---|
| Event title | COST Action - EU-METAHEART 2nd International Conference |
| Event type | Conference |
| Location | Jurmala, LatviaShow on map |
| Degree of Recognition | International |