L-carnitine supplementation in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) dominates the landscape of modern hepatology. Affecting 25% of the general population, there is critical unmet need to identify broadly available, safe and cost-effective treatments. Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD, such that lipid accretion is not matched by efficient utilisation. L-carnitine is a crucial mediator of fatty acid metabolism in vivo, promoting mitochondrial lipid β-oxidation and enhancing tissue metabolic flexibility. These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry, liver fat and insulin sensitivity in NAFLD.METHODS Search strategies, eligibility criteria and analytic methods were specified a priori(PROSPERO reference: CRD42018107063). Ovid MEDLINE, Ovid EMBASE,Pub Med, Web of Science and the Cochrane Library were searched from their inception until April 2019. Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST), liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for, ALT, AST and HOMA-IR measures separately. Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n = 338). All of the 5 included trials assessed the effect of L-carnitine on serum ALT, identified from Italy, South Korea and Iran. Weighted mean difference(WMD) for ALT between L-carnitine and control groups after intervention was-25.34 IU/L [95%CI:-41.74-(-8.94); P = 0.002]. WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89; P =0.066). In three studies(n = 204), HOMA-IR was evaluated. WMD for HOMA-IR between L-carnitine and control groups was-0.74 units [95%CI:-1.02-(-0.46); P <0.001]. Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P <0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT, liver fat and insulin resistance in NAFLD cohorts, confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.