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
Processing time: 129 Days and 1.4 Hours
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide, affecting approximately 25% of the general population. To date, there are no licensed disease-modifying treatments to attenuate global burden of NAFLD. A growing body of evidence suggests that NAFLD is characterised at a cellular level by impaired mitochondrial fat oxidation. L-carnitine, a naturally occurring nutrient, is a key mediator of mitochondrial fuel selection and promotes lipid oxidation. In this article, we synthesise available evidence of a role for L-carnitine supplementation in the treatment of NAFLD.
L-carnitine has gained traction in recent years as a potential tool for the treatment of metabolic disorders including type 2 diabetes and heart disease. At the nexus of glucose and lipid metabolism, L-carnitine promotes mitochondrial lipid oxidation and enhances tissue metabolic flexibility. It may confer protective effects in NAFLD through these mechanisms. There is a critical unmet need for broadly applicable, population based treatment in NAFLD, which inspired this narrative and quantitative synthesis.
In this study, we aimed to systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry, liver fat and insulin sensitivity in NAFLD.
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. A protocol for the systematic review was published a priori in the PROSPERO database (Reference: CRD42018107063).
Results from the synthesised evidence suggest that L-carnitine is associated with a significant reduction in serum alanine aminotransferase (ALT), the most commonly used biomarker of hepatocellular injury. In two robust, high-quality randomised trials, L-carnitine supplementation reduced liver fat significantly. Further, in subgroup analysis of studies assessing insulin resistance, L-carnitine supplementation was associated with a significant reduction in the HOMA-IR.
We present an argument for further robust, randomised trial data evaluating mechanisms of action of L-carnitine on liver and muscle tissue in NAFLD populations. Currently availabile evidence suggests that as a naturally occurring, broadly applicable and cost-effective agent, L-carnitine could be an effective tool for patients in clinical practice as an adjunctive treatment for NAFLD. However, we emphasise that further research using robust and validated endpoints is required to consolidate existing evidence of benefit.
Micronutrient supplementation presents a novel and exciting avenue for the treatment of population-level diseases, including NAFLD. A broader impact of L-carnitine on metabolic health (including improved insulin sensitivity) could have implications beyond NAFLD alone and its effect in other metabolically challenged populations deserves attention. Ultimately, further well-conducted prospective, randomised data will be required to translate a speculative benefit of L-carnitine in NAFLD into the clinical sphere.