Vitamin E and nonalcoholic fatty liver disease

Abstract

Purpose of review Oxidative stress plays a central role in the transition from simple steatosis to nonalcoholic steatohepatitis (NASH). An effective therapeutic strategy is to target reduction in oxidative stress in NASH patients. The aim of this review is to discuss the role of oxidative stress in NASH and biological activities of vitamin E and present available evidence on the therapeutic efficacy of vitamin E in NASH. Recent findings In Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, vitamin E therapy demonstrated a significant improvement in steatosis, inflammation, ballooning, and resolution of steatohepatitis in adult patients with aggressive NASH who do not have diabetes or cirrhosis. Although vitamin E showed a significant resolution of NASH in children, a sustained reduction of alanine aminotransferase was not attained in The Treatment of NAFLD in Children(TONIC) trial. Summary The prevalence of nonalcoholic fatty liver disease (NAFLD) is likely to increase over time due to the epidemics of obesity and diabetes. Presently, there is no definitive treatment for NAFLD. Based on available evidence, vitamin E (RRR-α-tocopherol) is only recommended in NASH adults without diabetes or cirrhosis and with aggressive histology. Validation is needed in children before its use can be recommended. Longer follow-up of randomized controlled trials are needed to assess long-term vitamin E safety.

Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis

“…We and others (5,31,32) have shown that toxininduced steatohepatitis models produce metabolic oxidative stress. The toxin-and diet-induced steatohepatitic injury models that produce metabolic oxidative stress are relevant to clinical outcomes because patients with NASH show oxidative stress and have been hypothesized to augment disease progression (27). Our results demonstrate that CYP2E1 increases lipid peroxidation and oxidative and nitrosative stress upon steatohepatitic injury.…”

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

“…Oxidative stress originating from mitochondria and cytochrome P450 2E1 is considered as a key signal in the pathophysiology of NASH (34,35). Interestingly, studies in animal models and patients show that antioxidants, such as vitamin C, vitamin E, and N-acetylcysteine (NAC), are useful for both protecting against NAFLD and treating this disease (36)(37)(38). ROS affect several cell signaling pathways involved in cell proliferation and tumorigenicity (39,40).…”

Recent advances in dietary supplementation, in treating non-alcoholic fatty liver disease

“…The TONIC randomized controlled trial showed that neither vitamin E nor metformin are superior to placebo in sustaining a reduction in ALT levels of pediatric NAFLD patients [31] . A recent review article concluded that vitamin E is only recommended in adults with NASH who do not have diabetes or cirrhosis, or an aggressive histology [32] . In a meta-analysis, adjuvant vitamin E was not shown to have a significant effect on normalizing serum ALT levels.…”