Kristaps Krims-Davis

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.

Thioredoxin reductase is an essential enzyme that plays a crucial role in maintaining cellular redox homeostasis by catalyzing the reduction of thioredoxin, which is involved in several vital cellular processes. The overexpression of TrxR is often associated with cancer development. A series of 1,2-dithiolane-4-carboxylic acid analogs were obtained to verify the selectivity of 1,2-dithiolane moiety toward TrxR. Asparagusic acid analogs and their bioisoters remain inactive toward TrxR, which proves the inability of the 1,2-dithiolane moiety to serve as a pharmacophore during the interaction with TrxR. It was found that the Michael acceptor functionality-containing analogs exhibit higher inhibitory effects against TrxR compared to other compounds of the series. The most potent representatives exhibited micromolar TrxR1 inhibition activity (IC₅₀ varied from 5.3 to 186.0 μM) and were further examined with in vitro cell-based assays to assess the cytotoxic effects on various cancer cell lines and cell death mechanisms.