Effects of grape seed extract on immune-related gene expression, inflammatory biomarkers, disease activity, and quality of life in patients with ulcerative colitis: a randomized, triple-blind, placebo-controlled trial

Abstract Grape seed extract (GSE), a polyphenol-rich nutraceutical with antioxidant and anti-inflammatory properties, has shown promising effects in preclinical colitis models; however, clinical evidence in patients with ulcerative colitis (UC) remains limited. This study provides novel clinical evidence in patients with UC. In order to, this randomized, triple-blind, placebo-controlled trial investigated the effects of GSE supplementation on immune-related gene expression, inflammatory biomarkers, disease activity, and quality of life in patients with mild-to-moderate UC. A total of sixty-six patients were randomly assigned to receive either GSE (600 mg/day) or placebo (600 mg/day) for 12 weeks. Disease activity was assessed using the Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ), and quality of life using the Inflammatory Bowel Disease Questionnaire‐9 (IBDQ-9). Twenty-nine participants per group completed the study. Serum High-Sensitivity C-reactive Protein (hs-CRP) decreased significantly in both groups, with a greater reduction in the GSE group compared with placebo at study end (between-group P = 0.002; change P = 0.018). SCCAIQ scores decreased significantly within the GSE group ( P = 0.023), with no significant between-group difference. No significant between-group differences were observed for Interleukin-17 (IL-17) or Erythrocyte Sedimentation rate (ESR). Expression of T-box Transcription Factor T-bet (T-bet) and Retinoic Acid-Related Orphan Receptor-γt (RORγt) decreased, while Forkhead Box P3 (FOXP3) and GATA Binding Protein 3 (GATA3) increased in both groups, with no significant differences between the groups. IBDQ-9 scores demonstrated no significant difference. In summary, GSE consumption led to a significant reduction in hs-CRP levels and a modest within-group improvement in disease activity. However, no superiority of GSE over placebo was observed for other study outcomes. Further clinical trials with larger sample sizes and inclusion of patients across a broader spectrum of disease activity are warranted to fully elucidate the therapeutic potential of GSE in UC. Clinical trial registration: This trial was registered at the Iranian Registry of Clinical Trials (IRCT20120415009472N28; September 5, 2023).