Effect of saffron on depression, anxiety and mood disorder: a GRADE assessed systematic review and meta-analysis of 34 randomized controlled trials

Background This study presents a systematic review and meta-analysis evaluating the effects of Crocus sativus L. (saffron) supplementation on anxiety, depression, and mood disorders in adults. Given the inconsistent findings of prior clinical trials, the authors synthesized evidence from randomized, placebo-controlled trials to clarify saffron's overall efficacy on mental health outcomes.Methods The review was conducted in accordance with PRISMA guidelines, with comprehensive searches of SCOPUS, PubMed, and Web of Science up to July 2025. Eligible studies included adult participants and interventions lasting at least four weeks, with saffron as the sole difference between intervention and control groups. Risk of bias was assessed using Cochrane tools, and the certainty of evidence was evaluated using the GRADE framework. Pooled effects were calculated as WMDs with 95%CI, and heterogeneity was explored through subgroup and meta-regression analyses.Results A total of 34 RCTs comprising 1769 participants were included. Saffron supplementation significantly reduced scores on BDI (14 trials; 817 participants; WMD = −4.39, 95% CI: −6.64 to −2.15, p < 0.001, I2 = 92.3%) and the BAI (6 trials; 339 participants; WMD = −5.06, 95% CI: −8.44 to -1.68, p = 0.003, I2 = 94.8%). No significant effects were observed for the HDRS, HARS, or POMS. The certainty of evidence was rated as moderate according to the GRADE Working Group criteria.In conclusion, the findings suggest that saffron supplementation may be an effective complementary intervention for reducing self-reported depressive and anxiety symptoms in adults. Lack of clinician-rated effects underscores need for high-quality trials.