Effects of intermittent fasting and caloric restriction on inflammatory biomarkers in individuals with obesity/overweight: A systematic review and meta-analysis of randomized controlled trials

Introduction: Obesity is characterized by chronic low-grade inflammation. This study presents an updated systematic review and meta-analysis on the effect of caloric restriction (CR) and intermittent fasting (IF) on plasma inflammatory biomarkers (C-reactive protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6) in individuals with obesity/overweight compared with unrestricted or ad libitum feeding. Methods: PubMed, Web of Science, and SCOPUS databases were searched for randomized controlled trials (RCTs) reporting inflammatory biomarkers after at least 8 weeks of intervention. Standardized mean differences (SMDs) were calculated using a fixed effect model. Heterogeneity was determined using I-2 statistics. Sensitivity analysis was conducted using the "leave-one-out" approach. Results: Relatively few RCTs have investigated the effect of IF on inflammatory biomarkers than with CR (6 vs. 15). Analysis of pooled data showed that CR was associated with a significant reduction in CRP with low heterogeneity (SMD -0.15 mg/L [95% CI -0.30 to -0.00], p = 0.04; I-2 = 0%, p = 0.69) and IL-6 with high heterogeneity (SMD -0.31 pg/mL [95% CI -0.51 to -0.10], p = 0.004; I-2 = 73%, p = 0.001). IF was associated with a significant decrease in TNF-alpha with moderate heterogeneity (SMD -0.32 pg/mL [95% CI -0.63 to -0.02], p = 0.04; I-2 = 44%, p = 0.13). No associations were detected between IF and CRP or IL-6 and CR and TNF-alpha. Conclusion: CR may be more effective in reducing chronic low-grade inflammation than IF. However, there were some concerns regarding the included studies' randomization and allocation sequence concealment process.