S4861 Saffron as an Adjuvant Therapy for Improvement of Ulcerative Colitis, a Multicenter Clinical Trial Assessing Inflammatory and Clinical Outcomes

Introduction: here are known challenges for treatment of inflammatory bowel disease in spite of diverse available drugs. We aimed to study saffron as an additional intervention to improve clinical and laboratory markers of ulcerative colitis (UC) patients. Case Description/Methods: A multicenter double-blind placebo-controlled clinical trial was conducted across Yazd, Egypt, and the United States of America (Washington, D.C.), involving 68 UC patients. The efficacy of 50 mg saffron was evaluated through clinical and laboratory assessments, including 16S rDNA analysis of the gut microbiome in stool samples and serum PBMCs profiling of Howard University patients. The study protocol was approved by Howard University’s Institutional Review Board (Approval Number: IRB-20-MED-26). Discussion: Results: In the Yazd cohort (n = 37), the high-dose saffron group showed significant reductions in C-reactive protein (4.1 to 2.8, P = 0.001), fecal calprotectin (318 to 187, P = 0.007), and Partial Mayo Score (PMS, 2.0 to 1.1, P = 0.05). SCCAI also improved (2.6 to 1.56, P = 0.03), however, HDRS changes were not significant but showed a declining trend (15 to 9.5, P = 0.1). In the Egypt cohort (n = 20), similar trends were observed, with C-reactive protein (13.7 to 9.7) and fecal calprotectin (211 to 124), along with improvements in SCCAI (8.1 to 6.8) and quality of life (1.4 to 1.1), though P-values were >0.05. In the USA (Howard University) cohort, patients (n = 4) showed consistent improvements in clinical and laboratory markers. This was reversed during an 8-week washout period but was restored after a second saffron cycle administration. Pro-inflammatory cytokines (tumor necrosis factor-α, IFN-ɣ, IL-6, IL-17, IL-2, and IL-4) decreased, while anti-inflammatory cytokines (IL-10, and TGF-β) increased. Gut microbiome analysis revealed a reduction in gamma Proteobacteria and an enrichment in Ruminococcaceae. Saffron significantly improved clinical and laboratory markers in UC patients, suggesting its potential as an adjuvant therapy to reduce reliance on immunosuppressants. Clinical Trial Registration: NCT04749576.