Non-alcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease globally, with a 20–30% reported prevalence. It includes a wide range of liver diseases, from simple steatosis to non-alcoholic steatohepatitis (Gowda et al. 2009), leading to cirrhosis, liver cancer, and death (Rayyan et al., 2018). The pathogenesis of NAFLD has remained undisclosed, but it is mainly influenced by lifestyle, such as diet and physical activity (Angulo, 2002). NAFLD management has become a significant challenge to healthcare providers due to the rising rates of obesity worldwide (Del Ben et al., 2014). NAFLD along with insulin resistance (IR) has been proposed as the hepatic manifestations of metabolic syndrome (MS) (Kermani et al., 2017, Kermani et al., 2017) as the common pathophysiological mechanism (Aller et al., 2015). Generally, fatty liver patients have risk factors associated with cardiovascular diseases (such as hypertension, impaired blood lipids, obesity, decreased physical activity, insulin resistance, endothelial disorders, and inflammation), which put them at risk of cardiovascular disease (Lu et al., 2013). Also, NAFLD increases the risk of cardiovascular disease as an independent factor (Wójcik-Cichy et al., 2018). There is no effective treatment for non-alcoholic steatohepatitis, which has led to various therapeutic approaches. Some published articles proposed that NAFLD is a liver manifestation of MS, so improving the metabolic status associated with MS is likely to effectively treat fatty liver (Seo et al., 2012, Aller et al., 2015). Regarding the significant role of oxidative stress in the pathogenesis of NASH and the low levels of serum antioxidants in these patients, researchers pay more attention to the use of antioxidants for the treatment of NAFLD (García-Lafuente et al., 2009, Liu et al., 2015).

Saffron (Crocus sativus L) is a food additive widely used due to its colour and taste. A wide range of remedial activities for Saffron are associated with its main components, including crocin, crocetin, and safranal. According to several studies, Saffron and its active ingredients have been used as antioxidants, anti-inflammatory, analgesic, antidepressant, hypotensive, anticancer, scavenger of free radicals, and pro-inflammatory cytokines (Mashmoul et al., 2013, Razavi and Hosseinzadeh, 2015). Sheng et al. (2006) have stated that crocin prevents the absorption of fat and cholesterol, and this prevention is nearly related to the hydrolysis of fat. Moreover, crocin has increased the faecal excretion of fat and cholesterol in the rats but did not eliminate bile acids. Crocin could not directly prevent cholesterol absorption from rat jejunum, yet it was observed to selectively block the acting of pancreatic lipase as a competitive inhibitor. Also, another important mechanism of crocin is supposed to be preserving the hepatocyte membrane integrity through its antioxidant properties (Algandaby, 2016).

Based on the literature review that the present study’s researchers conducted, this trial is the first study to assess the effects of saffron supplementation on cardiovascular risk factors, liver steatosis, and fibrosis in NAFLD patients. Therefore, the researchers designed this randomised, double-blind, placebo-controlled clinical trial to investigate the effects of Saffron supplementation and lifestyle modification on liver enzymes, cardiovascular risk factors, hepatic elasticity, and echogenicity in patients with NAFLD.