Machin D (2020). Investigating the optimisation of the ergogenic effects of L-carnitine supplementation in humans.
Abstract: Investigating the optimisation of the ergogenic effects of L-carnitine supplementation in humans
L-carnitine, when consumed alongside high dose oral carbohydrates or infused under insulin clamp conditions increases muscle total carnitine. This is likely via increased insulin augmented Na+/K+ -ATPase pump activity via Na+ dependent OCTN2 carnitine transport. Increased muscle total carnitine is associated with numerous physiological effects including increased fatty acid metabolism and improved exercise time trial performance. However, significant practical and health issues including weight gain exist with the current mechanism of carbohydrate/ insulin augmented carnitine uptake. The purpose of this thesis therefore was to investigate an alternative methodology that could stimulate increased muscle carnitine uptake in humans without the calorific load required via oral carbohydrates. This was investigated by using caffeine to stimulate Na+/K+ -ATPase pump activity similarly to that of the previously identified action of insulin. The effects of caffeine ingestion during hypercarnitinemia on Na+, K+ and plasma carnitine amongst other measures were investigated. Experimental group participants consumed 9mg/kg/bw caffeine over a period of 5 hours intravenous infusion of L-carnitine (C&C), with carnitine only (CARN) and caffeine only (CAFF) placebo groups also investigated. Combined hypercarnitinemia and caffeine decreased steady state plasma carnitine by 10.2% (~30 μmol.L-1) compared to carnitine infusion alone. Rate of carnitine clearance from plasma increased by 9.2% (C&C 205.1 μmol.L-1 vs 187.9 μmol.L-1 CARN) and rate of tissue uptake also increased proportionately (C&C 36.9 μmol.L-1vs 33.7 μmol.L-1CARN). Caffeine ingestion increased steady state whole blood Na+ (C&C 138.1 mmol/L, CAFF 138.2 mmol/L vs CARN 137.6mmol/L) whilst simultaneously decreasing K+ (C&C 4.1mmol/L, CAFF 4.1mmol/L vs CARN 4.3 mmol/L). Consequently, the changes in carnitine clearance were likely stimulated by caffeine’s actions influencing Na+/K+ kinetics, due to increased Na+/K+ -ATPase pump activity. Further pilot data appears to indicate that caffeine ingestion acetylated the muscle carnitine pool with free carnitine decreasing between baseline and post infusion (-1.8mmol/kg CAFF vs -0.5mmol/kg CARN) with the caffeine mediated decrease being largely attenuated when caffeine was consumed in a state of hypercarnitinemia (-0.9mmol/kg C&C). After ~14 hours post infusion CAFF continued to acetylate the carnitine pool, whilst CARN was unchanged and C&C returned towards baseline (CAFF -2.3mmol/kg, CARN +0.6mmol/kg, C&C -0.3mmol/kg) with pre-exercise muscle free carnitine obtained the absolute highest value in the C&C group (CARN 10.7mmol/kg, CAFF 10.7mmol/kg vs C&C 12.5mmol/kg). Neither carnitine, caffeine nor a combination of the two appeared to significantly alter any markers of metabolism or exercise performance in the pilot data (n=2) regardless of condition. Collectively these novel findings indicate that it is likely that caffeine is able to augment human skeletal muscle carnitine uptake but may lead to increased acetylation of the muscle carnitine pool. The direct effects of these findings on muscle total carnitine, metabolism and exercise performance are yet to be identified. However, a novel mechanism for increasing plasma carnitine clearance and thus likely increased skeletal muscle carnitine uptake appears to have been discovered.