Immunonutrition in Ulcerative Colitis: A Preclinical Study of Arginine, Glutamine, and HMB

In a single DSS-induced rat study, oral supplementation with arginine, glutamine, and HMB produced greater histopathological improvement and broader reductions in inflammatory and oxidative-stress measures than single agents in a DSS-induced colitis model.

Previous preclinical work showed that single immunonutrients can lower selected inflammatory markers and oxidative damage. In contrast, the combined arginine–glutamine–HMB formulation yielded a wider, more balanced modulation across cytokine and metabolic networks, suggesting that integrated immunometabolic interventions may better restore mucosal homeostasis in colitis models.

At the transcript level, glutamine alone reduced IL6 and COX2 expression. The arginine–glutamine–HMB mixture, however, produced broader pathway-level effects across multiple inflammatory and oxidative-stress readouts; notable exceptions included some proinflammatory transcripts that did not fall—NOS2 was reported as elevated in the mixture group.

Certain oxidative-stress markers, notably MDA and MPO, reached statistical significance with the mixture, while several gene-expression changes and other biomarker comparisons did not achieve significance in the reported study.

These biomarker shifts paralleled superior histopathological restoration in the mixture-treated animals, supporting biological plausibility for a symptomatic and tissue-level benefit in this model.

These results are strictly preclinical. Species differences, dosing, formulation, timing, and formal safety profiling remain key translational gaps. Independent replication, dose-finding studies, protein-level validation, and early-phase human biomarker feasibility work are necessary next steps before any clinical application can be considered.

Key Takeaways:

• An arginine–glutamine–HMB combination produced broader reductions in histologic injury, inflammatory biomarkers, and oxidative stress than single supplements in DSS-colitis models.
• Translational researchers and people with ulcerative colitis, who may be prioritized for early feasibility and biomarker-driven studies.
• Priority actions include independent replication, protein-level validation, dose–response assessment, and early human biomarker feasibility work before clinical application is considered.