Effect of Saffron (Crocus sativus) Supplementation on Oxidative Stress, Inflammatory Indices, and Renal and Liver Function Parameters in Patients With Type 2 Diabetes Mellitus: A GRADE-Assessed Systematic Review and Meta-analysis of Randomized Clinical Trials.

Context: Clinical investigation has shown that the addition of saffron or crocin to standard antidiabetic medications improves a patient's metabolic profile, oxidative stress (OS), and inflammatory response. Despite a large number of studies examining the impact of saffron supplementation on OS, inflammation, and renal and liver function parameters, no systematic review or meta-analysis has been conducted to compile the outcomes in patients with type 2 diabetes mellitus (T2DM).

Objective: The current systematic review and meta-analysis was performed to investigate the effect of saffron or crocin intake on OS, inflammation, and renal and liver function parameters in patients with T2DM.

Data sources: Online databases including PubMed, Scopus, ISI Web of Science, and Cochrane Library were searched up to December 2023.

Data extraction: The mean differences and their respective SDs were extracted. Using a random-effects model, the pooled data were calculated as standardized mean difference (SMD) with 95% CI.

Data analysis: 17 eligible randomized controlled trials were included in this meta-analysis. The pooled findings showed that saffron supplementation remarkably decreased the levels of tumor necrosis factor-α (SMD: -0.37; 95% CI: -0.69 to -0.05; I2 = 40.77%, P = .15), interleukin-6 (IL-6) (SMD: -0.38; 95% CI: -0.65 to -0.10; I2 = 0%, P = .68), and malondialdehyde (MDA) (SMD: -0.36; 95% CI: -0.65 to -0.07; I2= 20.51%, P = .02) compared with the control. In addition, based on subgroup analyses, taking ≥100 mg of saffron daily in individuals with T2DM reduced the serum levels of IL-6 (SMD: -0.50; 95% CI: -0.90 to -0.10; I2 = 0%, P = .50) and MDA (SMD: -0.36; 95% CI: -0.68 to -0.03; I2 = 0, P = .97). Furthermore, the level of alanine transaminase was decreased (SMD: -0.43; 95% CI: -0.73 to -0.12; I2 = 0, P = .66) with a treatment period of <60 days of saffron or crocin supplementation.

Conclusion: Larger studies with more follow-up and higher doses of both saffron and crocin are needed in order to understand the efficacy and safety of these herbs for long-term use as routine therapies.

Systematic review registration: PROSPERO registration no. CRD42023458119.