Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation

Abstract

Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

A Diterpenoid, 14-Deoxy-11, 12-Didehydroandrographolide, in Andrographis paniculata Reduces Steatohepatitis and Liver Injury in Mice Fed a High-Fat and High-Cholesterol Diet

“…In this study, deAND treatment lowered hepatic lipid peroxide and increased antioxidant enzyme activities could be explained by Nrf2 induction and, thereafter, lowered oxidative stress in the liver ( Figure 6). It is known that a constant increase in lipotoxicity, followed by increases in oxidative stress and inflammation may promote the progress from NAFLD to NASH and impair liver function [2]. The present study is the first to demonstrate that deAND ameliorates steatohepatitis, liver fibrosis, and liver damage partially by enhancing hepatic Nrf2-mediated downstream antioxidant enzyme activities and suppressing NLRP3 inflammasome activation in HFHC diet-induced fatty liver disease.…”

“…Mice treated with 0.1% deAND showed mildly lowered oxidative stress, as indicated by increasing GSH content and GSH reductase activity, and a significantly reduced inflammation by lowering TNF-α level in liver. Because increased oxidative stress, lipotoxicity, and inflammation play key roles in the progression of many fatty liver diseases [2], it is suggested that 0.1% deAND treatment may reduce HFHC diet-induced steatohepatitis and liver damage.…”

“…Its estimated global prevalence is about 25% [1]. Oxidative stress and inflammation in the liver are believed to play an important role in the development and progression of this disease [2]. Recent studies have demonstrated that accumulations of high cholesterol and cholesterol crystals in the livers increased cholesterol-induced 14-deoxy-11,12-didehydroandrographolide (deAND), neoandrographolide, 14-acetylandrographolide, and 14-deoxyandropholide [14].…”

The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management

“…However, the effects of ω3 supplementation on improving severe liver injury markers, such as inflammation and fibrosis are not well‐established. It is important to consider that the controversial results on ω3 could be because of differences in methodology, the duration of the nutritional intervention, levels of intake, their sources, the EPA/DHA relationship, the chemical composition of ω3 and the patient’s genetic background …”

“…It is important to consider that the controversial results on ω3 could be because of differences in methodology, the duration of the nutritional intervention, levels of intake, their sources, the EPA/DHA relationship, the chemical composition of ω3 and the patient's genetic background. 10 The contribution of dietetic cholesterol in NAFLD is not clear.…”