Caffeine ingestion stimulates plasma carnitine clearance in humans

Increasing skeletal muscle carnitine content can manipulate fuel metabolism and improve exercise performance. Intravenous insulin infusion during hypercarnitinemia increases plasma carnitine clearance and Na⁺ -dependent muscle carnitine accretion, likely via stimulating Na⁺ /K⁺ ATPase pump activity. We hypothesized that the ingestion of high-dose caffeine, also known to stimulate Na⁺ /K⁺ ATPase activity, would stimulate plasma carnitine clearance during hypercarnitinemia in humans. In a randomized placebo-controlled study, six healthy young adults (aged 24 ± 5 years, height 175 ± 8 cm, and weight 70 ± 13 kg) underwent three 5-h laboratory visits involving the primed continuous intravenous infusion of l-carnitine (CARN and CARN + CAFF) or saline (CAFF) in parallel with ingestion of caffeine (CARN + CAFF and CAFF) or placebo (CARN) at 0, 2, 3, and 4 h. Regular blood samples were collected to determine concentrations of blood Na⁺ and K⁺ , and plasma carnitine and caffeine, concentrations. Caffeine ingestion (i.e., CAFF and CARN + CAFF conditions) and l-carnitine infusion (i.e., CARN and CARN + CAFF) elevated steady-state plasma caffeine (to ~7 μg·mL^-1 ) and carnitine (to ~400 μmol·L^-1 ) concentrations, respectively, throughout the 5 h infusions. Plasma carnitine concentration was ~15% lower in CARN + CAFF compared with CARN during the final 90 min of the infusion (at 210 min, 356 ± 96 vs. 412 ± 94 μmol·L^-1 ; p = 0.0080: at 240 min, 350 ± 91 vs. 406 ± 102 μmol·L^-1 ; p = 0.0079: and at 300 min, 357 ± 91 vs. 413 ± 110 μmol·L^-1 ; p = 0.0073, respectively). Blood Na⁺ concentrations were greater in CAFF and CARN + CAFF compared with CARN. Ingestion of high-dose caffeine stimulates plasma carnitine clearance during hypercarnitinemia, likely via increased Na⁺ /K⁺ ATPase activity. Carnitine co-ingestion with caffeine may represent a novel muscle carnitine loading strategy in humans, and therefore manipulate skeletal muscle fuel metabolism and improve exercise performance.