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.