UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study

J Integr Complement Med. 2022 Jun;28(6):540-548. doi: 10.1089/jicm.2021.0365. Epub 2022 Apr 4.


Objective: Joint-related stress models have been used in the past to induce a standardized load on physical structures, allowing researchers to observe changes in perceived stress on joints as accurately as possible in healthy individuals. Previous studies support the efficacy of UC-II® undenatured type II collagen ("undenatured collagen") supplementation in maintaining joint health. The purpose of this study was to assess the effect of undenatured collagen on knee flexibility in healthy subjects who experience activity-related joint discomfort (ArJD). Methods: This randomized, double-blind, placebo (PLA)-controlled study was conducted in healthy subjects with ArJD who had no history of osteoarthritis, or joint diseases. Ninety-six (n = 96, 20-55 years old) subjects who reported joint discomfort while performing a standardized single-leg-step-down test were randomized to receive either PLA (n = 48) or 40 mg of undenatured collagen (n = 48) supplementation daily for 24 weeks. Range of motion (ROM) flexion and extension were measured using a digital goniometer. Results: At the end of the study, a statistically significant increase in knee ROM flexion was observed in the undenatured collagen group versus the PLA group (3.23° vs. 0.21°; p = 0.025). In addition, an increase in knee ROM extension by 2.21° was observed over time in the undenatured collagen group (p = 0.0061), while the PLA group showed a nonsignificant increase by 1.27° (p > 0.05). Subgroup analysis by age showed a significant increase in knee ROM flexion in subjects >35 years old in the undenatured collagen supplemented group compared with PLA (6.79° vs. 0.30°; p = 0.0092). Conclusion: Overall, these results suggest that daily supplementation of 40 mg of undenatured collagen improved knee joint ROM flexibility and extensibility in healthy subjects with ArJD.

Keywords: joint flexibility; knee joint function; range of motion; undenatured collagen.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Collagen Type II* / therapeutic use
  • Humans
  • Knee Joint* / drug effects
  • Knee Joint* / physiology
  • Middle Aged
  • Range of Motion, Articular / drug effects
  • Young Adult


  • Collagen Type II