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

Abstract 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.