LAUSR

Background Leveraging in vivo imaging and physiological studies, we previously demonstrated robust associations between skeletal muscle fat accumulation, whole-body insulin resistance and perturbed hepatic energy kinetics in young, non-diabetic males with elevated intrahepatic triglyceride (IHTG) content. In a randomised, double-blind, placebo-controlled, isocaloric trial, we have now investigated the effect of 24 weeks‘ L-carnitine supplementation on metabolic phenotype in non-alcoholic fatty liver disease (NAFLD). Methods Non-diabetic male participants with NAFL (IHTG >5.56% on proton magnetic resonance spectroscopy:1H MRS) without significant liver fibrosis (stage Results Eighteen male NAFL subjects (age 36.3 ± 9.1 yrs, BMI 32.6 ± 4.4 kg/m2) were enrolled; 9 were randomised to receive carnitine and 9 to placebo. Demographic and baseline laboratory characteristics were similar across groups. One subject was excluded due to >7% weight gain during study protocol. After 24 weeks, carnitine-treated patients had a significant absolute reduction in IHTG (-3.5% [-5.9; -1.5]) versus an increase in the placebo group (+ 6.0% [1.5;11.0], p=0.002, figure 1A), a decrease in IMCL:EMCL ratio (0.92 to 0.42 vs 1.53 to 1.47, p=0.001) and improved leg glucose uptake (11.7 to 21.3 μmol/ml/kg, p=0.02). Serum alanine aminotransferase (ALT) declined significantly in carnitine vs placebo groups (73.6 to 48.1 v 64.4 to 67.3, p=0.04). No significant change from baseline occurred between groups in whole-body insulin sensitivity (p=0.83) or adipose tissue insulin resistance indices (p = 0.72). Forward rates of hepatic ATP synthesis improved with L-carnitine vs placebo (+0.50 mM/s vs -0.09 mM/S, p=0.02, figure 1B).There was no significant change in weight (kg) from baseline between groups (p=0.67). Conclusion L-carnitine exerts favourable metabolic effects in NAFLD, independent of weight loss. Increased leg glucose uptake in tandem with the decrease in IMCL: EMCL ratio suggest that hepatic effects occur secondary to a carnitine-mediated increase in muscle lipid β-oxidation. L-Carnitine could represent a viable option for the treatment of NAFLD.