Undenatured type II collagen for knee osteoarthritis
What it found
In people with knee osteoarthritis, undenatured type II collagen reduced pain and improved function and range of motion in the short and mid term.
Animal studies also showed less inflammation and joint damage.
What they found
Studies in people
Pain and function in people
In several randomized controlled trials, people with knee osteoarthritis who took undenatured type II collagen (usually 40 mg daily) reported less pain and better physical function than those taking a placebo. Some studies also found improvements in stiffness and quality of life.
Range of motion
People taking undenatured type II collagen showed improved knee flexibility and range of motion in some studies, including healthy people with activity-related joint discomfort.
Comparison with other supplements
In some trials, undenatured type II collagen worked as well as or better than a combination of glucosamine and chondroitin for pain and function.
Safety
No adverse events related to undenatured type II collagen were reported in the human studies included in this review.
Animal and lab studies
Animal studies
In rats and mice with induced osteoarthritis, undenatured type II collagen reduced inflammatory markers and joint damage, and improved gait and motor function. Higher doses tended to work better.
Other findings
How it might work
The authors describe a mechanism called oral tolerance, where undenatured type II collagen interacts with immune tissues in the gut and may reduce inflammation and support cartilage repair.
What the authors conclude
“In addition, administration of UC-2 is safe and efficacious in the short- and mid-term, reducing inflammation and pain, and improving function, ROM and overall QoL.”
Also in their conclusions
- They conclude that undenatured type II collagen is safe and effective in the short and mid term for reducing pain and improving function, range of motion, and quality of life in knee osteoarthritis.
- They call for more adequately powered, prospective, multi-center, non-randomized and randomized controlled trials with longer follow-up to establish long-term efficacy and justify routine clinical use.
How it was done
Knee osteoarthritis causes pain and reduced function, and current treatments have limitations and do not address the underlying cause. The authors wanted to review whether undenatured type II collagen could help manage it.
They searched medical databases for studies on undenatured type II collagen and knee osteoarthritis, and found 12 studies: 3 in animals, 8 in people, and 1 with both. They also checked clinical trial registries for ongoing studies.
What it can’t tell you
- Most studies were small and followed people for only a few months, so the long-term effects are not known.
- The studies did not compare undenatured type II collagen with common treatments like corticosteroids or viscosupplementation.
- Animal results may not reflect what happens in people.
Who paid
- Conflicts
- The authors report no conflict of interest.
- Authors work at
- University of Salerno, Italy; Sapienza University of Rome, Italy; Queen Mary University of London, UK
The paper
- Title
- Undenatured type II collagen for knee osteoarthritis
- Type
- ReviewThe authors read earlier studies and describe what they found. It isn’t a new study.
- Evidence
- Studies in people · animals · lab
- Summarised from
- Full text
- Cite
- Gupta A, Maffulli N (2025). Undenatured type II collagen for knee osteoarthritis. Annals of medicine. doi:10.1080/07853890.2025.2493306Free full textPubMed 40253594DOI
Summary written 26 Sep 2026. Check it against the paper before it changes what you eat. How we summarise papers · Report an error