Benefits
Knee joint pain and stiffness, studied in adults with knee osteoarthritis
In a 180-day placebo-controlled trial in 191 adults with knee osteoarthritis, 40 mg a day of UC-II lowered total WOMAC score, pain and stiffness more than placebo and improved total WOMAC more than glucosamine plus chondroitin. The maker sponsored the trial and employed two of its three authors. A review with a limited meta-analysis of 8 trials found better pain and WOMAC scores than control but called for larger studies.
Compared with glucosamine plus chondroitin
In a 90-day randomized trial in 52 adults with knee osteoarthritis and no placebo group, UC-II 40 mg a day reduced WOMAC scores by 33% versus 14% with glucosamine 1,500 mg plus chondroitin 1,200 mg, and pain scores by 40% versus 15.4%. The trial was small and supported by the maker. In the larger 180-day trial, UC-II beat glucosamine plus chondroitin on total WOMAC but not on every measure.
Knee comfort and range of motion during exercise in healthy adults
In a 120-day placebo-controlled trial in 55 healthy adults with knee discomfort during exercise, UC-II 40 mg a day improved knee extension compared with placebo. A 24-week trial in 96 similar adults found slightly better knee flexion than placebo (3.2 vs 0.2 degrees). Both trials were funded by the maker, and time to first knee discomfort improved only versus baseline, not versus placebo.
Mechanism of action
Oral tolerance (proposed)
UC-II is thought to work through oral tolerance: small amounts of intact type II collagen meet immune cells in the gut, which may calm immune reactions against joint cartilage. Reviews describe this as the main proposed mechanism, but it has not been measured directly in the human trials cited here, and the trial authors called for studies of how it works.
Clinical trials
Randomized, double-blind trial without a placebo group: UC-II 40 mg a day versus glucosamine 1,500 mg plus chondroitin 1,200 mg for 90 days (Crowley et al. 2009, Int J Med Sci)
52 adults with knee osteoarthritis, 26 per group.
UC-II reduced WOMAC scores by 33% versus 14% and pain scores by 40% versus 15.4%; only the UC-II group improved significantly from baseline on all measures. The study was small and was supported by InterHealth, the maker at the time.
Multicenter randomized, double-blind, placebo-controlled trial of UC-II 40 mg a day, glucosamine 1,500 mg plus chondroitin 1,200 mg, or placebo for 180 days (Lugo et al. 2016, Nutr J)
191 adults with knee osteoarthritis at 13 centers in southern India.
UC-II lowered total WOMAC score more than placebo (p = 0.002) and more than glucosamine plus chondroitin (p = 0.04), and improved WOMAC pain, stiffness and function versus placebo. Safety outcomes did not differ between groups. The maker sponsored the study and employed two of the three authors.
Randomized, double-blind, placebo-controlled trial of UC-II 40 mg a day for 120 days (Lugo et al. 2013, J Int Soc Sports Nutr)
55 healthy adults with knee discomfort after a standard stepmill test (27 UC-II, 28 placebo).
After 120 days, knee extension was better with UC-II than placebo (81.0 vs 74.0 degrees). The UC-II group exercised longer before first discomfort than at baseline (2.8 vs 1.4 minutes), a within-group change that did not differ significantly from placebo. No product-related adverse events occurred. The maker funded the study and employed three of the authors.
Multicenter randomized, double-blind, placebo-controlled trial of UC-II 40 mg a day for 24 weeks (Schön et al. 2022, J Integr Complement Med)
96 healthy adults aged 20 to 55 with knee discomfort during a step-down test.
Knee flexion increased more with UC-II than placebo (3.23 vs 0.21 degrees). Extension rose within the UC-II group but did not differ significantly from placebo. Three authors were employees of Lonza, the maker.