(A) Oral bioavailability of C₈-carnitine was determined by dosing n = 3 male rats with 0.5 mg/g and following C₈-carnitine levels in the blood over time. The ratio of the AUC for oral dose: i.v. dose represents bioavailability, which is 18%. (B) Data are averages of 2 male WT mice gavaged with 3 μCi of ¹⁴C-labeled C₈-carnitine. Mice were placed into boxes connected to a KOH trap to capture exhaled breath. Samples withdrawn from the trap at the indicated times were subjected to scintillation counting. The y axis is the cumulative counts over time. When the curve plateaus, it means the substrate has been completely oxidized. (C–F) Effect of feeding control diet (Ctrl) versus C₈-carnitine (C₈C) at 3% w/w for 10 days on serum and tissue acylcarnitines. (C) Serum C_14:1-carnitine is pathognomonic for human VLCAD deficiency and is recapitulated in the LCAD-KO mouse. Dietary C₈C does not alter this diagnostic long-chain acylcarnitine species. (D) Serum acylcarnitines < 8 carbons are systemically reduced in LCAD-KO mice (blue vs. gray bars); dietary C₈C increases all to normal or above normal levels (yellow bars). (E and F) Tissue levels of free carnitine and C₈-carnitine are increased in the disease-relevant tissues liver, muscle, and heart after feeding C₈-carnitine. (G and H) Single gavaged doses of 0.5 mg/g C₈-carnitine improve running capacity in LCAD-KO mice while limiting lactic acidosis. (D) *P < 0.01 LCAD-KO versus WT and ^#P < 0.01 LCAD-KO C₈C versus WT; all other panels,*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001 by Student’s t test with Bonferroni correction for multiple comparisons. Data are shown as mean ± SEM.