Published online Feb 28, 2020. doi: 10.13105/wjma.v8.i1.4
Peer-review started: October 22, 2019
First decision: December 5, 2019
Revised: December 17, 2019
Accepted: February 15, 2020
Article in press: February 15, 2020
Published online: February 28, 2020
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.
To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry, liver fat and insulin sensitivity in NAFLD.
Search strategies, eligibility criteria and analytic methods were specified a priori (PROSPERO reference: CRD42018107063). Ovid MEDLINE, Ovid EMBASE, PubMed, 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.
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).
Pooled results indicate that L-carnitine supplementation attenuates ALT, liver fat and insulin resistance in NAFLD cohorts, confirming a beneficial effect of L-carnitine for a highly prevalent condition with a growing economic burden.
Core Tip: Non-alcoholic fatty liver disease (NAFLD) presents a major public health challenge. As a leading cause of abnormal liver chemistry, rising in prevalence together with obesity and insulin resistance, there is critical unmet need to identify cost-effective, population-based treatment. We synthesised evidence from randomised trials published to date evaluating the effect of dietary L-carnitine supplementation on transaminases, liver fat and insulin resistance in NAFLD. We demonstrate a significant reduction in serum alanine aminotransferase, homeostasis model of insulin resistance and liver fat with dietary L-carnitine supplementation. L-carnitine could therefore present a novel therapeutic tool for NAFLD and its metabolic associations.