Is Isocaloric Intermittent Fasting Superior to Calorie Restriction? A systematic Review and Meta-Analysis of RCTs

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. 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). 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. [Display omitted] •This systematic review and meta-analysis identified 20 studies that compared isocaloric IF with calorie restriction. Our analyses indicate that isocaloric Intermittent fasting is not superior to calorie restriction in improving adults’ and elderlies’ health.•The health benefits induced by intermittent fasting are calorie restriction dependent.•Intermittent fasting does not provide additional health benefits beyond those achieved by calorie restriction.•Combining intermittent fasting with calorie restriction is an effective approach for achieving health.