The effect of pomegranate juice supplementation on C-reactive protein levels: GRADE-assessed systematic review and dose-response updated meta-analysis of data from randomized controlled trials

Pomegranate juice (PJ) has a possible anti-inflammatory effect because of its polyphenol content and antioxidants. However, the anti-inflammatory effect of PJ in randomized controlled trials (RCTs) has not been consistent. A previous meta-analysis conducted in 2016 reported a nonsignificant lowering effect of PJ on C-reactive protein (CRP) levels. This systematic review and meta-analysis aim to update the pooled effect size of PJ supplementation on CRP levels in RCT studies. PubMed, Scopus, and Web of Science databases were comprehensively searched until July 2023. Eligible studies were found by screening, their relevant data was extracted, and a risk of bias assessment was performed. The pooled effect size was calculated using a random effect model as the weighted mean difference (WMD) with a 95% confidence interval. This systematic review included 11 studies with 13 effect sizes and 696 participants. Meta-analysis showed that PJ supplementation led to a significant decrease in CRP levels compared to control groups (WMD: -2.55mg/L; 95%CI: -3.44 to -1.66; p<0.001). Subgroup analysis demonstrated the significant reduction effect of PJ on CRP levels in studies conducted on the both sexes or only females as well as Iranian population, individuals with 40years<less than or equal to>, type 2 diabetes, polycystic ovary syndrome, or trials that intervened with PJ dosage of <250ml/day. Meta-regression and dose-response analysis reported a nonsignificant linear and nonlinear relationship between intervention characteristics (duration and dose of PJ) and CRP changes. The current meta-analysis revealed that PJ supplemantation has a beneficial effect in improving CRP levels. It is recommended to understand this effect better, and find the optimal dose and duration of PJ supplementation to reduce CRP levels in the blood, and repeat meta-analysis after related RCTs are available. For the final proof of these effects, more detailed human studies are needed.