Dose‐Dependent Effect of Crocin on Depressive and Anxiety Symptom Scores: A GRADE‐Assessed Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Background

Although several clinical trials have examined the effects of crocin on the symptoms of depression and anxiety, their findings have not yet been synthesized comprehensively. Therefore, this systematic review and meta‐analysis aimed to determine the dose‐dependent effect of crocin supplementation on depressive and anxiety symptom scores.

Methods

A comprehensive search was performed in the PubMed, Scopus, and ISI Web of Science until April 2026. The change in depressive and anxiety symptom scores for each 30 mg/d increase in crocin supplementation was estimated and then the standardized mean difference (SMD) with 95% CI was calculated. We also assessed the publication bias, sensitivity analysis and heterogeneity by standard methods. Certainty of evidences was evaluated through the GRADE Tool.

Results

Fourteen randomized controlled trials (RCTs) were included. Each 30 mg/day increasing in crocin supplementation can decreased scores of depressive symptoms by −3.37 (95% CI: −4.80, −1.94; I ²  = 97.1%, GRADE = moderate). A slight linear reduction in the depressive symptom scores was observed ( p _nonlinearity  = 0.47, p _{dose–response}  = 0.001). Each 30 mg/day crocin can led to −2.73 reduction in anxiety symptom scores (95% CI: −4.17, −1.06; I ²  = 97%, GRADE = high). Anxiety symptom scores reduced with a slight linear slope ( p _nonlinearity  = 0.9, p _{dose–response}  = 0.02).

Conclusion

In conclusion, crocin supplementation may improve symptom scores of both depression and anxiety in a dose–response manner. However, these results are based on clinical trials with relatively small sample sizes, almost conducted in one country. Well‐designed RCTs across diverse regions with adequate sample sizes are required to confirm these findings.

Trial Registration: Prospero Code: CRD42024591281