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Background and aimsDietary regimens are crucial in the management of non-alcoholic fatty liver disease (NAFLD). The effects of intermittent fasting (IF) have gained attention in this regard, but further research is warranted. Thus, we aimed to ascertain the overall effects of the 5:2 IF diet (5 days a week of normal food intake and 2 consecutive fasting days) in patients with NAFLD compared to a control group (usual diet).Methods and resultsA 12-week randomized controlled trial was performed to evaluate the effects of the 5:2 IF diet on anthropometric indices, body composition, liver indices, serum lipids, glucose metabolism, and inflammatory markers in patients with NAFLD. The IF group (n = 21) decreased body weight (86.65 ± 12.57–82.94 ± 11.60 kg), body mass index (30.42 ± 2.27–29.13 ± 1.95 kg/m2), waist circumference (103.52 ± 6.42–100.52 ± 5.64 cm), fat mass (26.64 ± 5.43–23.85 ± 5.85 kg), fibrosis (6.97 ± 1.94–5.58 ± 1.07 kPa), steatosis scores/CAP (313.09 ± 25.45–289.95 ± 22.36 dB/m), alanine aminotransferase (41.42 ± 20.98–28.38 ± 15.21 U/L), aspartate aminotransferase (34.19 ± 10.88–25.95 ± 7.26 U/L), triglycerides (171.23 ± 39.88–128.04 ± 34.88 mg/dl), high-sensitivity C-reactive protein (2.95 ± 0.62 −2.40 ± 0.64 mg/L), and cytokeratin-18 (1.32 ± 0.06–1.19 ± 0.05 ng/ml) values compared to the baseline and the end of the control group (n = 23)—p ≤ 0.05 were considered as significant. However, the intervention did not change the levels of high-density lipoprotein cholesterol, total cholesterol, low-density lipoprotein cholesterol, fasting blood sugar, insulin, HOMA-IR, and total antioxidant capacity.ConclusionAdhering to the 5:2 IF diet can reduce weight loss and related parameters (fat mass and anthropometric indicators of obesity), as well as hepatic steatosis, liver enzymes, triglycerides, and inflammatory biomarkers in patients with NAFLD.