Vol. 11, Issue 4 (2025)

Osteoarthritis is a debilitating joint disease characterized by progressive cartilage breakdown and limited treatment options. Undenatured type II collagen has gained significant attention as a nutraceutical that harnesses the body’s immune system through oral tolerance. By interacting with gut-associated lymphoid tissue, undenatured type II collagen stimulates regulatory T cells that effectively suppress joint inflammation and promote cartilage repair. Extensive preclinical studies across multiple species including bovine, porcine, squid, chicken, and Nile tilapia demonstrate Undenatured type II collagen’s consistent ability to reduce key inflammatory mediators (IL-1β, TNF-α), inhibit cartilage-degrading enzymes (MMP-13), reducing cartilage degradation markers (CTX-II, COMP), and preserve joint structure. Clinical investigations reveal promising improvements in pain, joint function, and cartilage thickness in osteoarthritis patients treated with undenatured type II collagen. Despite these encouraging results, clinical evidence is still preliminary, highlighting the urgent need for large, randomized, placebo-controlled trials to establish undenatured type II collagen role in promoting cartilage health. This review underscores undenatured type II collagen’s potential to reduce cartilage degradation and to promote cartilage repair in OA.