Ellagic acid supplementation on oxidative stress, antioxidative capacity and inflammation biomarkers: A systematic review and dose–response meta-analysis of randomized controlled trials

Context: Ellagic acid demonstrates potential in the prevention and management of oxidative stress and inflammation markers; however, the effects of supplementation, optimal dosage, and timing are still uncertain. Objective: This study aimed to assess the effects of ellagic acid supplementation on oxidative stress and inflammation markers such as malondialdehyde (MDA), total antioxidant capacity (TAC), and C-reactive protein (CRP). Data Sources: A systematic search of databases (PubMed, ISI Web of Science, and Scopus) identified relevant studies until March 2024. Study Eligibility Criteria: Eligible studies had to meet criteria including specific study designs (Randomized controlled clinical trials (RCT) or quasi-experimental), comparison of ellagic acid effects between control and intervention groups, and availability of data on ellagic acid’s impact on oxidative stress and inflammation markers. Outcome measures focused on markers of oxidative stress and inflammation such as MDA,TAC and CRP. Data Extraction: Two independent reviewers collected information, such as specifics of ellagic acid intervention, study features, study methodology, participant attributes, intervention specifics, evaluated outcomes, and findings linked to the outcomes explored in the present study. Data Analysis: Data from 5 eligible studies were analyzed, encompassing a total of 240 individuals for MDA levels, 171 participants for TAC levels, and 142 individuals for CRP levels. The results from six comparisons across five studies using a random-effects model showed that ellagic acid supplementation significantly reduced MDA levels (Weighted mean difference (WMD): −0.631 µM/L, 95 % confidence interval (CI): −1.009, −0.254; p: 0.001). Additionally, pooled data from 4 studies with 5 treatment arms indicated a significant increase in TAC levels with ellagic acid supplementation (WMD: 0.743 mg/dL, 95 % CI: 0.141, 1.345; p: 0.016). Analysis of 3 trials involving 142 individuals revealed a significant decrease in CRP levels by 3.00 ng/ml (95 % CI: −4.046, −1.954; p < 0.001) with ellagic acid supplementation. TAC levels significantly increased in individuals taking ellagic acid supplements at doses of 180 and 200 mg/day, with a meaningful enhancement in TAC in studies with an 8-week intervention but not in those lasting 12 weeks (P > 0.05). There was no significant correlation between changes in TAC levels and dosage (P, 0.06), but a significant association was found between the duration of ellagic acid supplementation. One of the basic limitations of this study is the scarcity of prior research, making the findings more of a summary and hypothesis generator for future studies. Conclusions: Supplementation with ellagic acid demonstrates positive impacts on oxidative stress and inflammation when administered at higher doses (180 or 200 mg/day) over a shorter intervention period. Given the limited number of studies conducted in this area, the available evidence to support the findings is insufficient and additional trials are needed to further investigate and clarify this association.