Effect of 12-week intermittent calorie restriction on liver fat content in comparison with standard-of-care in patients with nonalcoholic fatty liver disease: a study protocol for a randomized controlled trial (FLICR)

Abstract Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and can result in various complications. Owing to the lack of effective pharmacological therapies, life style modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR), which consists of alternating phases of extreme energy restriction and regular energy intake, is a novel dietary approach for NAFLD treatment. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice, such as the lack of appropriate assessment tools, different cut-offs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial to evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (nonalcoholic fatty liver disease-intermittent calorie restriction [FLICR]). Methods: We will include adult (19–75 years) NAFLD patients diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥25 kg/m2 [n=36] and non-obese group: BMI <25 kg/m2 [n=36]), and followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks. Discussion: This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy. Trial registration: This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health, ClinicalTrials.gov as NCT05309642 (date of registration: April 4, 2022), https://clinicaltrials.gov/ct2/show/NCT05309642.