The effects of intermittent fasting diet in comparison with low-calorie diet on lipid profile, glycemic status, and liver fibrosis in patients with non-alcoholic fatty liver (NAFLD): a study protocol for a randomized controlled clinical trial

(2023) 9:145 Karimi et al. BMC Nutrition https://doi.org/10.1186/s40795-023-00794-x BMC Nutrition STUDY PROTOCOL Open Access The effects of intermittent fasting diet in comparison with low‑calorie diet on lipid profile, glycemic status, and liver fibrosis in patients with non‑alcoholic fatty liver (NAFLD): a study protocol for a randomized controlled clinical trial Mehdi Karimi1, Maryam Mofidi Nejad2, Camellia Akhgarjand1, Amir Ali Sohrabpour3, Hossein Poustchi4, Hossein Imani1* and Hamed Mohammadi1 Abstract Introduction Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by an increase in fat in liver cells. The outbreak of NAFLD is estimated to be 32.4% worldwide, with higher rates in Asia and Iran. Nutritional factors such as excessive calorie intake, high fructose intake, copper deficiency, and increased iron intake play an important role in NAFLD. Since there is no specific treatment for NAFLD, intermittent fasting (IF) diet has been suggested as an alternative treatment for obesity and related complications. Previous studies showed the potential positive effects of IF on metabolic health and the reduction of oxidative stress in NAFLD. This randomized controlled trial (RCT) will be aimed to examine the effect of the IF diet in comparison with a low-calorie diet (LCD) on lipid profile, glycemic status, and liver fibrosis in patients with NAFLD. Methods and analysis This is a parallel randomized clinical trial conducted on 52 overweight and obese patients with NAFLD. Participants will be randomly assigned to receive either 16:8 IF (fasting from 8 P.M. to 12 P.M. the next day) or a low-calorie (55% carbohydrate- 30% fat, 15% protein) diet for 12 weeks. Anthropometric measurements, liver assessments, and metabolic evaluations will be assessed before and after the intervention. Primary outcomes include liver steatosis and fibrosis, while secondary outcomes include liver function enzymes, insulin resistance, lipid profile, and anthropometric measurements. Discussion Since obesity and insulin resistance are the most important risk factors of NAFLD, and there is no treatment for it, it seems that lifestyle changes such as low caloric diet like IF and exercise can improve lipid metabolism and liver enzymes. Trial registration Iranian registry of clinical trials (IRCT20170202032367N5). Keywords Intermittent fasting diet, Low-calorie diet, Non-alcoholic fatty liver, Randomized controlled clinical trial *Correspondence: Hossein Imani Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Karimi et al. BMC Nutrition (2023) 9:145 Introduction Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases [1, 2] with a variety of conditions including simple steatosis, nonalcoholic steatohepatitis (NASH), and fibrosis [3, 4]. NAFLD is characterized by an increase in the amount of fat within liver cells without excessive alcohol consumption [5]. The prevalence of NAFLD was estimated to be 32.4% worldwide [6] and in Asia, the outbreak of NAFLD is reported to be 29.6% [7]. In addition, in the Iranian population, the prevalence is estimated to be around 33.9% [8]. Diet appears to play an important role in improving NAFLD [9]. Dietary factors involved in this disease include excess calorie intake, amount of carbohydrates consumed, types of fats consumed, high fructose intake, copper deficiency, and increased iron intake [10]. Currently, there is no specific treatment for NAFLD, however, a combination of increased physical activity and nutritional modifications are the best alternative treatments for this disease [11, 12]. Adherence to a variety of diets, including lowfat and low-carbohydrate diets, has been less successful in reducing and maintaining weight loss and improving metabolic risk factors in obese individuals, so preventing or controlling associated risk factors can be considered as an alternative treatment [13–15]. Recently, intermittent fasting (IF) diet has been used to limit daily energy intake to treat obesity and its complications, and as an antiaging method to extend lifespan compared to traditional low-calorie diets (LCDs( [16, 17]. Several studies suggest that compared to LCD, IF may improve metabolic health including significant reductions in insulin resistance, blood pressure, and blood lipids [18]. Some studies have shown that weight gain is associated with increased inflammation and oxidative stress, which may be one of the triggers of NAFLD [19]. On the other hand, one of the positive effects of the IF diet on reducing oxidative stress was the change in body weight and slight upregulation of the sirtuin-3 gene (SIRT3), which is one of the effective therapeutic strategies in fatty liver [20, 21]. Considering the high complications of this disease and the direct and indirect cost of its complications, it seems that low-cost and effective methods such as IF diets can be effective in controlling and preventing the progression of this disease. Therefore, we decided to investigate the effects of an IF diet on lipid profile, blood glucose, and liver fibrosis markers in patients with NAFLD as a novel disease progression prevention and management method that has been studied to a limited extent [22, 23]. Methods and analysis The present study is a parallel randomized controlled clinical trial that will be performed at Masoud Clinic in Tehran, Iran on patients with NAFLD. All patients must complete Page 2 of 8 and sign an informed written consent before completing their registration. The research has been approved by the Bioethics Committee of TUMS, Tehran, Iran (No. IR.TUMS.MEDICINE.REC.1400.682). This RCT was registered on the IRCT web page (IRCT20170202032367N5). Participants Participants with NAFLD will be recruited based on the inclusion criteria. NAFLD will be diagnosed according to the Fibro Scan (Metavir-score ≤ F2 and co (...truncated)