Abstract
OBJECTIVE: To assess the effect of intermittent fasting diets, with continuous energy restriction or unrestricted (ad-libitum) diets on intermediate cardiometabolic outcomes from randomised clinical trials. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, and central databases from inception to 14 November 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical trials comparing the association of intermittent fasting diets (alternate day fasting, time restricted eating, and whole day fasting), continuous energy restriction, and ad-libitum diets were included. MAIN OUTCOMES: Outcomes included body weight (primary) and measures of anthropometry, glucose metabolism, lipid profiles, blood pressure, C-reactive protein, and markers of liver disease. DATA SYNTHESIS: A network meta-analysis based on a frequentist framework was performed with data expressed as mean difference with 95% confidence intervals (CIs). The certainty of the evidence was assessed using grading of recommendations assessment, development, and evaluation (GRADE). RESULTS: 99 randomised clinical trials involving 6582 adults of varying health conditions (720 healthy, 5862 existing health conditions) were identified. All intermittent fasting and continuous energy restriction diet strategies reduced body weight when compared with ad-libitum diet. Compared with continuous energy restriction, alternate day fasting was the only form of intermittent fasting diet strategy to show benefit in body weight reduction (mean difference -1.29 kg (95% CI -1.99 to -0.59), moderate certainty of evidence). Additionally, alternate day fasting showed a trivial reduction in body weight compared with both time restricted eating and whole day fasting (mean difference -1.69 kg (-2.49 to -0.88) and -1.05 kg (-1.90 to -0.19), respectively, both with moderate certainty of evidence). Estimates were similar among trials with less than 24 weeks follow-up (n=76); however, moderate-to-long-term trials (≥24 weeks, n=17) only showed benefits in weight reduction in diet strategies compared with ad-libitum. Furthermore, in comparisons between intermittent fasting strategies, alternate day fasting lowered total cholesterol, triglycerides, and non-high density lipoprotein compared with time restricted eating. Compared with whole day fasting, however, time restricted eating resulted in a small increase in total cholesterol, low density lipoprotein cholesterol, and non-high density lipoprotein cholesterol. No differences were noted between intermittent fasting, continuous energy restriction, and ad-libitum diets for HbA(1c) and high density lipoprotein. CONCLUSIONS: Minor differences were noted between some intermittent fasting diets and continuous energy restriction, with some benefit of weight loss with alternate day fasting in shorter duration trials. The current evidence provides some indication that intermittent fasting diets have similar benefits to continuous energy restriction for weight loss and cardiometabolic risk factors. Longer duration trials are needed to further substantiate these findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05309057.