Effects of gluten-free diet on metabolic syndrome components and anthropometric indices in patients with nonalcoholic fatty liver disease: An open-label randomized clinical trial

NAFLD is a great clinical concern because fat accumulation in the liver is more than 5–10 % of the liver weight. NAFLD is the most common liver disease worldwide, in the first stage, it presents with fatty liver (steatosis) and then transitions to an advanced state, such as advanced fibrosis, cirrhosis and liver cancer [1]. The overall prevalence and incidence of NAFLD were reported to be 32.4 % and 46.9 cases per 1000 person-years, respectively. It has been reported that its incidence in men is greater than that in women [2]. Its prevalence was estimated to be approximately 33.9 % in Iran [[3], [4]]. Owing to the high prevalence of this disease, it can affect the quality of life of patients and impose a heavy economic burden worldwide [5]. The prevalence of NAFLD is associated with several factors, including age, sex, ethnicity and the presence of sleep apnea [6]. Additionally, strong associations have been reported between NAFLD and obesity, insulin resistance, type 2 diabetes and metabolic syndrome (MS) [7].

Although various pharmacological treatments have been investigated for NAFLD, no specific medication has been established, and lifestyle modification with weight loss remains the corner of management [[8], [9], [10]]. Regular physical activity, for example, can reduce the intrahepatic TG content and ameliorate hepatocellular damage [11]. It has been reported that physical activity can improve hepatocellular damage in patients with NAFLD via a reduction in the intrahepatic TG content [[12], [13], [14]]. In addition to lifestyle modification and physical activity, several nutritional strategies have also been investigated for their potential to improve metabolic health in individuals at risk of NAFLD. For example, a systematic review and meta-analysis of randomized controlled trials reported that green coffee extract supplementation can beneficially influence various cardiometabolic risk factors, supporting the role of dietary approaches in managing metabolic dysfunction [15]. Intermittent fasting has also been shown to beneficially restructure the gut microbiome, as reported in studies on Ramadan and non-Ramadan fasting, highlighting the role of dietary patterns in modulating liver–metabolic health [16]. Similarly, adherence to healthy dietary patterns such as the dietary approach to stop hypertension (DASH) and Mediterranean diets has been associated with lower BP even in nonhypertensive populations, underscoring the potential of dietary strategies to improve metabolic risk factors [17].

Emerging evidence also suggests a potential link between gut health and liver disease through the gut–liver axis. In this context, celiac disease (CD), an autoimmune condition triggered by gluten, has been associated with several hepatic abnormalities, including elevated liver enzymes, autoimmune cholestatic liver disease, and even NAFLD [18]. Gluten exposure in genetically susceptible individuals induces mucosal inflammation, villous atrophy, and malabsorption of nutrients (fats, proteins, carbohydrates, vitamins, and minerals), whereas a GFD can reverse these effects and restore gut barrier function. Interestingly, some studies have reported that a GFD may improve liver function and reduce progression to severe liver disease in patients with CD [19]. However, little is known about the potential metabolic or hepatic benefits of a GFD in nonceliac patients with NAFLD. Considering the increasing global burden of NAFLD and its close links with obesity and MS, exploring the effects of a GFD in this population may provide novel insights into the role of dietary gluten in liver–metabolic interactions [4,[20], [21]].

CD, an inherited autoimmune multisystemic disorder caused by the interaction of gluten protein with genetic and environmental factors, triggers a T-cell mediated immune response. This interaction leads to villous atrophy, inflammation and damage to the intestinal mucosa and results in the malabsorption of nutrients such as fats, proteins, carbohydrates, vitamins and minerals [[22], [23]]. Therefore, affected individuals present a spectrum of clinical symptoms consisting of iron deficiency anemia, osteoporosis, herpes-like skin lesions, elevated liver enzymes, and neurological disorders [24]. Both intestinal and extraintestinal symptoms are also present in patients with nonceliac gluten sensitivity, another class of gluten-associated disorders [25].

Some studies have demonstrated an increased risk of type 1 diabetes [26], thyroid disease [27], autoimmune endocrinological disorders [28], psychiatric disorders [29], inflammatory bowel diseases [30], reproductive disorders [31], and malignancies [32] in patients with CD. Various types of liver dysfunction, including unexplained elevations in liver enzyme levels, autoimmune cholestatic liver disease, NAFLD, nonspecific autoimmune hepatitis and cholangitis, have been reported among patients with CD [[33], [34], [35], [36], [37]]. Data also show that cases of cirrhosis rarely occur in patients with CD, who, in some cases, even need liver transplantation. CD affects 2.5 % of cirrhotic patients [38]. A GFD may reduce the progression of severe liver disease progression to hepatic failure [39]. In this study, we aimed to investigate the relationships between a GFD and anthropometric indices, lipid profiles, BP, FBS and the grade of improvement in HS in patients with NAFLD within a 3-month intervention period.

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