Is isocaloric intermittent fasting superior to calorie restriction? A systematic review and meta-analysis of RCTs

Background and aim: Intermittent fasting (IF) has been demonstrated to enhance human health through several mechanisms. However, it is still unclear whether those health benefits are independent of caloric restriction (CR)-induced weight loss. This systematic review and meta-analysis aimed to compare isocaloric IF and CR regarding anthropometric measurements, adherence, metabolic profile, inflammatory biomarkers, and adipokines in adults and elderlies. Methods and results: Comprehensive research was conducted usin four major databases including Embase, PubMed, Scopus, and Google Scholar without date restriction. Mean differences of the change from baseline ± change SD were calculated as the differences between IF and CR groups. Subgroup analysis was performed according to intervention duration (short-, medium-, and long-term). To determine the reliability of our findings, GRADE assessment was performed. As a result, 20 RCTs were included in this systematic review and meta-analysis. IF groups had significant reductions in fat mass (kg) (P = 0.006) and Interleukin-6 (P < 0.00001) in the short term and fat mass (%) (P = 0.0002), waist circumference (P = 0.005), fasting blood insulin (P < 0.00001) and HOMA-IR (P = 0.04) in the long term. CR groups had significantly lower hunger (P = 0.003), fatigue (P = 0.04), and TG (P = 0.03). Conclusions: IF may be an effective alternative to CR but is not superior to CR in enhancing human health. Due to the low number of long-term studies, future studies should focus on conducting longitudinal randomized trials comparing IF and CR in different populations, age groups, and IF patterns.