Low Bioavailability and High TMAO Production: Novel Insights Into Acetylcarnitine and Carnitine Metabolism

The food supplement acetylcarnitine is marketed for use in neurological support; however, research on its bioavailability and metabolic fate has been limited. This study investigated the absorption, metabolism, and excretion of acetylcarnitine compared with those of carnitine. Healthy volunteers received either carnitine or an acetylcarnitine supplement (0.5 or 1.5 g). Plasma and urine samples were collected at baseline and at multiple time points (1-48 h) post intake and analyzed using LC‒MS/MS. Both carnitine and acetylcarnitine exhibited low intestinal absorption and renal reabsorption. The peak plasma concentrations increased over the baseline values by 48% (acetylcarnitine) and 43% (carnitine) following a 1.5 g dose. However, the increase in area under the curve (ΔAUC) from acetylcarnitine was 7.7-fold lower than that from carnitine. Elevated plasma levels of carnitine and acetylcarnitine led to a 5-fold increase in clearance, and a substantial portion of the supplements were excreted via urine. The acetylcarnitine supplement was mostly eliminated in the form of carnitine. Approximately 90% of both supplements were metabolized to TMAO, reaching 50 µM in plasma-levels previously found to be associated with adverse health outcomes. Acetylcarnitine has significantly lower bioavailability than carnitine. The intake of both supplements resulted in substantial TMAO production, raising potential health concerns.