Efficacy and safety of undenatured collagen type II in modulating knee joint function in healthy and osteoarthritis subjects: a systematic review and meta-analysis

Collagen has emerged as a potential pharmacotherapeutic intervention for knee osteoarthritis (OA). This study evaluates the effectiveness and safety of undenatured collagen type II among patients with knee OA and healthy subjects without joint-related disease but experiencing activity-related joint discomfort. Systematic literature search was conducted through PubMed, Embase, and Cochrane up to June 2024, and a total of 17 articles were included in the final analysis. The primary outcome was efficacy: Western Ontario and McMaster Universities (WOMAC) score, visual analog scale (VAS) score, Lequesne’s functional index (LFI), and knee range of motion (ROM). The secondary outcome was safety: adverse events (AEs) and serious AEs. In patients with knee OA, undenatured collagen type II significantly decreased knee OA symptoms and improved the quality of life (QoL) by significant reductions of WOMAC scores (pain: −9.24 [P = 0.004], stiffness: −6.47 [P = 0.091], physical function: −7.31 [P = 0.043], total: −9.83 [P < 0.001]), VAS (−1.87; P = 0.006), LFI (−2.17; P < 0.001) and knee ROM. Treatment in healthy people reduced VAS scores and significantly increased the step number to the first onset of pain over the baseline (P < 0.05). The treatment was safe with no significant individual AE (headache: RR = 0.34, diarrhoea: RR = 0.48) and total AE (RR = 1.0090) in both populations. This study highlights the benefits and safety of undenatured collagen type II to improve knee health and QoL in patients with knee OA and healthy subjects.