Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth?

Hamza El Hadi, Roberto Vettor, Marco Rossato, Hamza El Hadi, Roberto Vettor, Marco Rossato

Abstract

Obesity is one of the major epidemics of this millennium, and its incidence is growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver disease (NAFLD) has become a disease of increasing prevalence and a leading cause of morbidity and mortality closely related to cardiovascular disease, malignancies, and cirrhosis. It is believed that oxidative stress is a main player in the development and progression of NAFLD. Currently, a pharmacological approach has become necessary in NAFLD because of a failure to modify lifestyle and dietary habits in most patients. Vitamin E is a potent antioxidant that has been shown to reduce oxidative stress in NAFLD. This review summarizes the biological activities of vitamin E, with a primary focus on its therapeutic efficacy in NAFLD.

Keywords: nonalcoholic fatty liver disease; obesity; oxidative stress; vitamin E.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of tocopherols and tocotrienols (with permission from reference [8]).
Figure 2
Figure 2
Multiple parallel-hit hypothesis of nonalcoholic fatty liver disease (NAFLD). Obesity together with dietary habits and environmental factors can lead to raised serum levels of free fatty acids (FFAs) and cholesterol, development of insulin resistance, adipocyte proliferation, and dysfunction in the intestinal microbiome. Insulin resistance acts on adipose tissue, worsening adipocyte dysfunction, induces hepatic de novo lipogenesis (DNL) and release of proinflammatory adipokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, which also exacerbates the insulin resistance state. The increased hepatic FFAs flux which derives from the above processes and from an altered activity of the gut microbiome leads to accumulation of triglycerides (TGs) and “toxic”levels of FFAs, free cholesterol, and other lipid metabolites which cause mitochondrial dysfunction, oxidative stress with the production of reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress with the activation of the unfolded protein response (UPR), all leading to hepatic inflammation and fibrogenesis (nonalcoholic steatohepatitis, NASH). Increased intestinal permeability of gut-derived microbial products such as lipopolysaccharides (LPS) contributes to the activation of the inflammasome, ER stress, and activation of inflammatory cascades. Epigenetic factors are also involved in progression to NASH or persistence in a stable stage of disease (with permission from [34]). VLDL: very low density lipoprotein.

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