1 Intermittent Fasting and Its Association with Metabolic, Inflammatory, and Fibrosis-Related Outcomes in Adults with Non-alcoholic Fatty Liver Disease: Findings from a Randomized Clinical Trial https://brieflands.com/journals/amhsr/articles/172370 10.69107/amh-172370 1 Background :Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver dysfunction worldwide and commonly coexists with obesity, insulin resistance, and other metabolic disturbances. Lifestyle-based strategies remain central to disease management, and intermittent fasting has recently emerged as a potentially beneficial nutritional intervention. Objectives :This study aimed to evaluate whether intermittent fasting affects anthropometric measures, inflammatory biomarkers, fibrosis-related indices, and ultrasonographic manifestations of hepatic steatosis in individuals with NAFLD. Methods :This randomized clinical trial included 102 adults with ultrasonography-confirmed NAFLD who were randomly assigned in a 1:1 ratio to either a 16:8 intermittent fasting intervention or a control group for 12 weeks. Clinical and laboratory evaluations were performed at baseline and after the intervention. Outcomes included anthropometric measures, inflammatory markers, liver-related laboratory parameters, noninvasive fibrosis-related indices (FIB-4, APRI, NAFLD Fibrosis Score, and BARD score), and an ultrasonographic assessment of hepatic steatosis. Results :Participants assigned to the intermittent fasting regimen showed significant reductions in body weight, body mass index (BMI), and waist circumference compared with controls (all P < 0.001). Marked reductions were also observed in inflammatory markers, particularly the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). In addition, significant improvements were observed across all evaluated non-invasive fibrosis indices, including FIB-4, APRI, NAFLD Fibrosis Score, and BARD score. Ultrasonographic evaluation demonstrated a greater reduction in hepatic steatosis severity among participants undergoing intermittent fasting than among controls. Conclusions :Intermittent fasting appears to be a feasible and potentially beneficial dietary strategy for patients with NAFLD, with favorable effects on noninvasive, fibrosis-related surrogate markers. Further long-term studies incorporating histological endpoints are needed to clarify its role in preventing or delaying fibrosis progression. 1 7 Morteza Aghajanpour Pasha Department of Gastrointestinal Disease Department, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran morteza_aghajanpoor@yahoo.com Vahid Mousavi Department of Endocrinology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran drsv.mousavi@gmail.com Sandra Saidi Department of Gastroenterology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran saidisandra699@gmail.com Kayvan Baloochi Department of Pathology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran k1baloochi@gmail.com Niloofar Fathipour Department of Internal Medicine, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran Iran lotusfp1373@gmail.com No Keyword 1.pdf [0]Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M.Global epidemiology of NAFLD. Hepatology. 2016;64(1):73-84. [PubMed ID: 26707365]. doi: 10.1002/hep.28431.##[1]Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al.AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. [PubMed ID: 36727674]. [PubMed Central ID: PMC10735173]. doi: 10.1097/HEP.0000000000000323.##[2]European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO).EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402. [PubMed ID: 27062661]. doi: 10.1016/j.jhep.2015.11.004.##[3]Dulai PS, Singh S, Patel J, Soni M, Prokop LJ, Younossi Z, et al.Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology. 2017;65(5):1557-1565. [PubMed ID: 28130788]. [PubMed Central ID: PMC5397356]. doi: 10.1002/hep.29085.##[4]Sanyal AJ, Friedman SL, McCullough AJ, Dimick‐Santos L.Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis. Hepatology. 2015;61(4):1392-1405. [PubMed ID: 25557690]. [PubMed Central ID: PMC4900161]. doi: 10.1002/hep.27678.##[5]Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al.Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-129. [PubMed ID: 19827166]. [PubMed Central ID: PMC2799538]. doi: 10.1002/hep.23276.##[6]Romero-Gómez M, Zelber-Sagi S, Trenell M.Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017;67(4):829-846. [PubMed ID: 28545937]. [PubMed Central ID: PMC11603804]. doi: 10.1016/j.jhep.2017.05.016.##[7]de Cabo R, Mattson MP.Effects of intermittent fasting. N Engl J Med. 2019;381(26):2541-2551. [PubMed ID: 31881139]. [PubMed Central ID: PMC12787741]. doi: 10.1056/NEJMra1905136.##[8]Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG, et al.Flipping the metabolic switch: Understanding and applying the health benefits of fasting. Obesity (Silver Spring). 2018;26(2):254-268. [PubMed ID: 29086496]. [PubMed Central ID: PMC5783752]. doi: 10.1002/oby.22065.##[9]Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM.Early time-restricted feeding improves metabolism. Cell Metab. 2018;27(6):1212-1221. [PubMed ID: 29754952]. [PubMed Central ID: PMC5990470]. doi: 10.1016/j.cmet.2018.04.010.##[10]Holmer M, Lindqvist C, Petersson S, Moshtaghi-Svensson J, Tillander V, Brismar TB, et al.Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial. JHEP Rep. 2021;3(3). 100256. [PubMed ID: 33898960]. [PubMed Central ID: PMC8059083]. doi: 10.1016/j.jhepr.2021.100256.##[11]Cienfuegos S, Gabel K, Kalam F, Ezpeleta M, Wiseman E, Pavlou V, et al.Time-restricted eating reduces weight and metabolic risk. Cell Metab. 2020;32(3):366-378. [PubMed ID: 32673591]. [PubMed Central ID: PMC9407646]. doi: 10.1016/j.cmet.2020.06.018.##[12]Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, et al.Intermittent fasting and human metabolic health. J Acad Nutr Diet. 2015;115(8):1203-1212. [PubMed ID: 25857868]. [PubMed Central ID: PMC4516560]. doi: 10.1016/j.jand.2015.02.018.##[13]Saleh SAK, Santos HO, Găman MA, Cerqueira HS, Zaher EA, Alromaih WR, et al.Effects of intermittent fasting regimens on glycemic, hepatic, anthropometric, and clinical markers in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition ESPEN. 2024;59:70-80. [PubMed ID: 38220409]. doi: 10.1016/j.clnesp.2023.11.009.##