Abstract
BACKGROUND: In non-osteoarthritic individuals, the appearance of joint discomfort with physical activity is a potential indicator of initial joint degeneration. The present study aimed to evaluate the efficacy and tolerability of native (undenatured) type-II collagen in the joint function of healthy volunteers who experienced joint discomfort as a result of physical activity. METHODS: This prospective, randomized, double-blind, placebo-controlled-study, included seventy-four healthy subjects with joint discomfort during physical activity. Participants were randomized to receive placebo (PBO) or native (undenatured) type-II collagen (CN2) at 40 mg/d for 180 days. Joint function and time to recover from knee discomfort after a standardized exercise protocol were evaluated. CTX-II was analyzed as biomarker of cartilage degradation. RESULTS: In both groups a significant improvement in joint function measured with the KOOS score was detected at 180 days, but improvements from baseline were detected earlier in the CN2 as compared to PBO group for KOOS pain, Symptoms and Quality of Life. In the subgroups of subjects with milder basal joint discomfort during activity (VAS≤40 mm) differences between groups in improvement from baseline were detected at 180 days for KOOS pain and Quality of Life subscales. Between-group differences were also detected in time to recover after cycling in the air test. In the subgroups of subjects with higher basal joint discomfort during activity (VAS>40 mm) between-group differences were detected on the progression of CTX-II concentration from baseline, which decreased in CN2 and increased in PBO group. CONCLUSIONS: This study found that supplementation with CN2, containing native (undenatured) type II collagen supports certain aspects of joint health in people who experience joint discomfort after exercise, including improvements in joint function, discomfort and their impact on quality of life. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05282992) on March 16, 2022. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12937-026-01302-0.