Abstract
Avian eggshell membrane (ESM) is a protein-rich fibrous biomaterial from egg-processing waste. It contains collagens, glycosaminoglycans, hyaluronic acid, chondroitin sulfate, and bioactive peptides, supporting joint homeostasis. This narrative review evaluates ESM as a multi-functional platform for joint health. ESM reduces IL-1β, TNF-α, and IL-6, modulates NF-κB and Keap1/Nrf2/HO-1 antioxidant pathways, and inhibits cartilage-degrading enzymes MMP-3, MMP-13, and ADAMTS-5. Clinical trials indicate 300–500 mg/day improves pain, stiffness, and physical function in knee osteoarthritis, with benefits within 7–10 days. At 500 mg/day, pain decreased by 72.5% at day 30 in an open-label study, while a randomized trial reduced WOMAC pain by 15.9% and stiffness by 12.8% versus placebo at day 10. A crossover trial reported improvements of 14.9% in WOMAC, 12.3% in pain, 18.2% in stiffness, and 15.2% in function at day 30. A dose-response trial showed reduced knee pain and improved quadriceps strength with 300 and 500 mg/day. Meta-analyses confirmed improvements over placebo. Processing method influences bioactivity and bioavailability, yet no head-to-head trial has established clinical equivalence. Structural joint outcomes in humans remain undemonstrated. ESM is well tolerated, but long-term and disease-modifying evidence is still needed. Preclinical evidence suggests potential canine joint-health applications, while animal studies indicate bone effects.