Crocin Supplementation on Inflammation and Oxidative Stress: A Systematic Review and Meta‐Analysis

ABSTRACT Saffron is the dried stigma of Crocus sativus L. flowers. The yellow‐orange color of saffron comes from crocin, a water‐soluble carotenoid that can be ingested. Crocin is known for its anti‐inflammatory and antioxidant potential. It is believed to affect inflammation and oxidative stress, making it a promising therapeutic option. However, research on its impact is inconclusive. This meta‐analysis aimed to assess the benefits of crocin supplementation and its specific effects on inflammation and oxidative stress markers. A comprehensive search of the literature was conducted up to February 2024 in PubMed/Medline, Scopus, and Web of Science to find suitable randomized clinical trials (RCTs). All participants were adults who were supplemented with crocin as part of the study intervention. The selected trials were subjected to heterogeneity tests using the I 2 statistic. Random effects models were examined based on the heterogeneity tests, and the pooled data were calculated as weighted mean differences (WMD) with a 95% confidence interval (CI). Of the 519 papers that remain after duplications were removed, 13 eligible RCTs were included in the present meta‐analysis. Our findings indicated that crocin supplementation significantly reduced c‐reactive protein (CRP) levels (SMD: −0.50; 95%CI: −0.86 to −0.13; p = 0.008), tumor necrosis factor‐α (TNF‐α) (SMD: −1.96; 95%CI: −2.72 to −1.19; p < 0.001), and interleukin‐6 (IL‐6) (SMD: −3.52; 95%CI: −6.84 to −0.20; p = 0.03). Also, crocin supplementation led to a significant increase in total antioxidant capacity (TAC) (SMD: 1.48; 95%CI: 0.52 to 2.43; p = 0.002). Overall effect size showed that crocin intake failed to change the erythrocyte sedimentation rate (ESR) and malondialdehyde (MDA) levels significantly. Crocin reduces inflammatory markers and increases TAC. The effect of crocin on inflammatory markers was greater in a dose ≥ 30 mg/day and an intervention duration ≥ 12 weeks. However, more studies are needed for definitive conclusions.