Adjunctive nutraceutical strategies in ulcerative colitis: From molecular pathways to clinical outcomes.
Ulcerative colitis is a chronic inflammatory disease of the large intestine, involving flare-ups and remissions. Its exact causes are unclear, but genetic susceptibility, immune dysregulation and environmental influences promote development. Conventional treatments have improved management, but some patients only respond partially or experience adverse effects. Nutraceuticals, used alongside conventional treatments, have been investigated to address these issues. This review examines recent findings regarding the role of nutraceuticals in disease management, with a particular focus on their mechanisms of action, efficacy and tolerability. Rather than treating mechanistic, preclinical and clinical data as equivalent, the work critically evaluates the directness and certainty of the underlying evidence. Curcumin, flavonoids, resveratrol and saffron-derived phytochemicals have anti-inflammatory, antioxidant and immunomodulatory activities, which are achieved by modulating signalling pathways associated with NF-κB, Nrf2 and JAK/STAT. The potential role of probiotics, prebiotics and synbiotics, in modulating gut inflammation, is also discussed. The combined use of curcumin and 5-aminosalicylic acid in mild-to-moderate ulcerative colitis, is currently supported by the most consistent randomised clinical evidence. In contrast, the evidence for most other compounds, advanced-therapy combinations and microbiota-targeted interventions remains preliminary, heterogeneous or of low-to-very-low certainty. The long-term safety of these products, the formulation equivalence and the potential interactions with other drugs and nutraceuticals remain largely unaddressed evidence gaps. In conclusion, current evidence suggests a plausible but not yet fully established role for nutraceutical strategies, in supporting remission in ulcerative colitis. Additional trials are required to define formulations, dosing and patient selection criteria before clinical application can be recommended.