Beneficial and Paradoxical Roles of Anti-Oxidative Nutritional Support for Non-Alcoholic Fatty Liver Disease

Abstract

Oxidative stress is being recognized as a key factor in the progression of chronic liver disease (CLD), especially non-alcoholic fatty liver disease (NAFLD). Many NAFLD treatment guidelines recommend the use of antioxidants, especially vitamin E. Many prospective studies have described the beneficial effects of such agents for the clinical course of NAFLD. However, as these studies are usually short-term evaluations, lasting only a few years, whether or not antioxidants continue to exert favorable long-term effects, including in cases of concomitant hepatocellular carcinoma, remains unclear. Antioxidants are generally believed to be beneficial for human health and are often commercially available as health-food products. Patients with lifestyle-related diseases often use such products to try to be healthier without practicing lifestyle intervention. However, under some experimental NAFLD conditions, antioxidants have been shown to encourage the progression of hepatocellular carcinoma, as oxidative stress is toxic for cancer cells, just as for normal cells. In this review, we will highlight the paradoxical effects of antioxidants against NAFLD and related hepatocellular carcinoma.

Keywords: anti-oxidant; hepatocellular carcinoma; non-alcoholic fatty liver disease.

Figure 1

Oxidative stress and anti-oxidant in non-alcoholic steatohepatitis (NASH) and liver cancer. Red lines; unfavorable effects, Blue lines; favorable effects, AICAR, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside; Nrf2, nuclear factor erythroid 2-related factor; AMPK, AMP-activated protein kinase; Keap1, Kelch-like enoyl-CoA hydratase (ECH) associated protein; Nrf2, nuclear factor erythroid 2-related factor; CPT, carnitine palmitoyltransferase; SOD, superoxide dismutase; GPx, glutathione peroxidase; LCFA-carnitine, long-chain acylcarnitine; TCA-cycle, tricarboxylic acid cycle.

Figure 2

A proposal for the antioxidant treatment application in non-alcoholic fatty liver disease (NAFLD). NAFL, non-alcoholic fatty liver; NASH, Non-alcoholic steatohepatitis; HCC, hepatocellular carcinoma; GLP-1 RA, glucagon-like peptide 1-receptor agonist; DPP-4 Is, dipeptidyl-peptidase-4 inhibitors.