Efficacy and safety of green-lipped mussel powder supplementation in adults with knee osteoarthritis: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Knee osteoarthritis (OA) is a prevalent degenerative joint disease associated with pain, functional limitation, and reduced quality of life. Although nonsteroidal anti-inflammatory drugs are widely prescribed, long-term use is limited by safety concerns. Green-lipped mussel powder (GLMP) has demonstrated anti-inflammatory and chondroprotective effects in preclinical studies. This trial evaluated the efficacy and safety of GLMP supplementation in adults with knee OA. METHODS: Adults aged 40-75 years with symptomatic radiographic knee OA were randomly assigned (1:1) to receive GLMP (1,000 mg/day) or placebo for 12 weeks. Assessments occurred at baseline, week 6, and week 12. The primary endpoint was change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary endpoints were WOMAC subscales (pain, stiffness, physical function), visual analog scale (VAS) pain, and inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). The per-protocol (PP) set included 93 participants (GLMP, 47; placebo, 46); the intention-to-treat (ITT) set included 100. RESULTS: A total of 100 participants were randomized and included in the ITT population, and 93 completed the study and were included in the PP population. In the PP analysis, GLMP resulted in greater improvement in WOMAC total score at week 12 than placebo (between-group difference - 3.66; 95% CI - 6.87 to - 0.45; p = 0.032). Significant between-group differences were also observed for WOMAC pain (p = 0.026), WOMAC physical function (p = 0.027), and VAS pain (between-group difference - 19.93 mm; 95% CI - 25.31 to - 14.55; p < 0.001). In the ITT analysis, the overall pattern of results was consistent with that observed in the PP analysis. WOMAC physical function (p = 0.042) and VAS pain (p < 0.001) remained significantly improved with GLMP, whereas WOMAC total score showed a non-significant trend favoring GLMP (p = 0.061). No significant between-group differences were observed in CRP or ESR levels. No clinically meaningful safety concerns were identified. CONCLUSIONS: Twelve-week supplementation with GLMP was associated with improvements in pain and physical function in adults with mild-to-moderate knee OA. Improvements in pain-related outcomes were observed consistently across PP and ITT analyses, although the primary WOMAC total outcome reached statistical significance only in the PP population. GLMP was well tolerated and may have potential as a complementary nutritional intervention for symptom management in individuals with knee OA. TRIAL REGISTRATION: The study was registered with the Clinical Research Information Service (CRIS; registration number KCT0008821) on September 22, 2023, and the full study protocol is available on the CRIS website (https://cris.nih.go.kr).