Long-term Effects of Intermittent Fasting on Weight Loss and Metabolic Risk Factors: A Systematic Review of Randomized Controlled Trials

Obesity is rising globally, posing public health challenges and highlighting the need for effective, evidence-based dietary interventions. Intermittent fasting (IF), involving alternating periods of eating and fasting, is a promising alternative to continuous energy restriction (CER) for metabolic health. This systematic review evaluated the long-term effects (≥12 months) of IF compared with control diets on body weight and markers of metabolic health in adults with overweight or obesity. MEDLINE/PubMed and Scopus were systematically searched through July 2025 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, and study quality was assessed using the Cochrane Risk of Bias 2 (ROB2) tool. Fifteen randomized controlled trials were included. Alternate-day modified fasting (ADMF) was the only approach demonstrating superior weight loss, outperforming both CER and ad libitum diets. Time-restricted eating (TRE) with caloric restriction (CR) resulted in greater reductions in body fat mass compared with CER, with a comparable effect observed when TRE was implemented without CR versus an ad libitum diet. ADMF may provide an advantage in improving insulin sensitivity, as evidenced by greater reductions in fasting insulin and Homeostatic Model Assessment of Insulin Resistance; however, it appeared to be associated with higher total and low-density lipoprotein cholesterol levels relative to CER. Overall, IF is as effective as other dietary approaches for long-term weight management and cardiometabolic risk improvement. ADMF may provide a modest advantage in weight loss and insulin sensitivity compared with CER, whereas TRE with CR may lead to greater reductions in fat mass than CER. Future research should focus on personalized nutrition aligned with circadian and metabolic factors.