1. Introduction
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that characterized by the lipid droplets accumulation in more than 5% of the hepatocytes. NAFLD encompasses a wide range from simple steatosis to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma.1 The global prevalence of NAFLD is estimated at nearly 25% 2, and in Iran was reported 33.9%.3 The occurrence of NAFLD is closely linked with an increased prevalence of obesity, insulin resistance (IR), oxidative stress (OS), and cardiovascular diseases, metabolic syndrome and Type 2 diabetes diseases.4According the “two-it” model and “multi-parallel hit” hypothesis, IR, increased free radical oxidation products and decreased total antioxidant capacity result in NAFLD progression. Furthermore, dysbiotic has been proposed as a critical risk factor for NAFLD development .1 It has been shown that altering the gut microbiota (GM) profile to phyla Bacteroidetes and Firmicutes, and decreasing Akkermansia muciniphila 5 in NAFLD patients lead to metabolic endotoxemia (ME) that exacerbates obesity, IR, OS and inflammation in these patients.
Due to lack of special pharmacologic treatments to control or improve NAFLD, lifestyle modifications known a first-line approach for NAFLD management.6 It is well established that having a healthy diet and physical activity can reduce the risk of occurrence or progression of this disease. Recently, omega-3 fatty acids (OM3FA) and antioxidants co-administration is considered to treatment and prevention of NAFLD due to low OM3FA dietary intake, the high hepatic n-6: n-3 ratio and the low antioxdant levels in plasma and liver of NAFLD patients.7 Thus, it seems that modification of dietary fats can affect hepatic fat deposition. A meta-analysis found that OM3FA interventions can improve liver functions and steatosis scores in NAFLD patients.8 OM3FA sources might be useful in improvement of the complications of NAFLD by modify the GM and controlling IR, OS, inflammation, lipid metabolism, and hepatic fat deposition.9 However, due to recent concerns regarding fish oil supplements contaminated with heavy metals and consequent side effects, and avoiding vegetarianism and veganism for consuming animal-derived products, modifying OM3FA sources from animal to plant sources has been considered .10
Camelina sativa (L.), known as false flax, is one of the richest dietary sources of OM3FA, with PUFA amounts over 50%, alpha-linolenic acid (ALA) content of 40% to 45%, and linoleic acid (LA) of about 15%, n-3/n-6 PUFA ratio of 1.79–2.17, low SFA content (about 6%), high contents of phytosterols (331–442 mg/100 g), carotenoids (103–198 mg of carotene/kg) and tocopherols (55.8–76.1 mg/100g).11 Inhibited autoxidation of extracted oil by high levels of antioxidants in Camelina sativa oil (CSO) has led to the superiority of this oil than other richest dietary sources of OM3FA, such as flaxseed oil (FSO).11 Furthermore, it has been reported that CSO has less fertilizer contamination compared to other oils .12
According to previous data, plant sources of OM3FA can improve glycemic status 13, ME 14, inflamation15 and OS indices.16However, such effects have mostly been showed in preclinical studies.17,18 Recently, limited clinical trials have reported favorable impacts of CSO on modulation of the lipid profile, OS, and immune system in subjects with impaired glucose metabolism (IGM).19-22 To our knowledge, the effects of CSO intake on glycemic, inflammation, ME, and OS status in NAFLD patients have not been examined. Therefore, we aimed to investigat combined effects of caloric restriction and CSO on glycemic, inflammation, ME, and OS status in NAFLD patients.