Undenatured Collagen Type II


Collagen is a natural protein formed in your body. In fact, it’s the most common type of protein in the human body, and in most animals, as well. You’ll find it playing a central role in muscle tissues, bone, tendons, and even on blood vessels. Collagen is also what gives your skin the strength and elasticity it needs.

Tissue Collagen Make Up:

  • Cartilage-20% of mass
  • Bone-90% organic mass
  • Tendon-90% by dry weight

The amino acids which make up collagen are:

  • Glycine-Makes up about 33% of collagen
  • Proline-Makes up about 10% of collagen
  • Hydroxyproline-Makes up about 10% of collagen
  • Glutamine
  • Arginine

In reality, collagen is the natural ‘glue’ that clasps everything together. It reinforces various structures in the body as well the robustness of our skin. There are several different forms of collagen in our body, but 80 to 90% of them are Type I, II or III. But, majority of them are type I, and the type I collagen fibrils possess massive tensile strength, meaning they can be stretched without being severed.

Undenatured collagen type II, also called UC-II, is derived naturally – it generally comes from chicken cartilage. Undenatured means that the collagen is completely intact in its natural form. This compared to collagen peptides that have been broken down into smaller components.

How Does Undenatured Collagen Type II Work?

A key part of joint degeneration is chronic inflammation. In patients with both OA and RA, small doses of UC-II have been shown to decrease the levels of inflammatory cytokines – proteins that cause inflammation and discomfort in those with these types of arthritis. This reduction allows patients to experience less pain and discomfort, and reduces the severity of the arthritic condition in general.

The mechanism behind UC-II influence on osteoarthritis is not well defined. However, researchers believe UC-II interacts with special immune cells in the digestive tract, called T regulatory cells, that than migrate to areas of concentrated inflammation and release chemical signals that modify the local cellular environment. The T cells positively influence the inflammatory process resulting in synthesis of new cartilage components and reduction of pain.


Canadian researchers evaluated the effect UC-II on a group of patients with osteoarthritis of the knee. The investigators found that UC-II significantly improved physical function, reduced stiffness, and reduced pain. (Crowley et al. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int. J. Med. Sci. 2009, 6)

Researchers at the University of California at Davis, examined the effect of UC-II on a rat model of osteoarthritis. The authors concluded the UC-II improved the mechanical function of the rat knee joint and prevented excessive deterioration of cartilage. (Bagi et al. Oral administration of undenatured native chicken type II collagen Osteoarthritis Cartilage. 2017 Dec;25(12):2080-2090.)


How Does Undenatured Collagen Type II Compare with Other Supplement Options?

Both glucosamine and chondroitin have long been used by patients suffering from OA and RA, as well as a range of other joint-related issues that cause pain and discomfort. How does the collagen-derived supplement compare to those two, more established options?

A study published in the International Journal of Medical Sciences attempted to answer that exact question. Patients involved in the study were given either a placebo, a dose of glucosamine and chondroitin, or a dose of UC-II. The study lasted for several months, with results being studied for over 90 days.

Both groups of patients being given actual supplements noted an immediate reduction in pain and discomfort, as well as with inflammation after starting their supplementation. However, those taking the UC-II supplement noted significantly better results initially. They also noted another significant improvement by the 90-day mark. Those taking glucosamine and chondroitin experienced the same level of improvement throughout the study, never reaching the level of pain and inflammation reduction achieved by those taking UC-II.

Safety First

UC-II is generally well tolerared. Potential side effects include constipation and headaches. As with any consideration of any form of supplementation consult your healthcare provide prior to use if you are pregnant, nursing, taking any medications or have any medical conditions. Discontinue use and consult your doctor is any adverse reactions occur.


D'Altilio M, Peal A, Alvey M, Simms C, Curtsinger A, Gupta RC, Canerdy TD, Goad J, Bagchi M, Bagchi D. Therapeutic efficacy and safety of undenatured type II collagen singly or in combination with glucosamine and chondroitin in arthriticdogs. Tox Mech Methods 2007; 17:189-196.

Gupta RC, Bagchi D, Skaggs P, Burke R, Wegford K, Goad JT, Canerdy TD, Barnett D and Bagchi M. Therapeutic efficacy ofundenatured type-II collagen (UC-II) in comparison to glucosamine  and chondroitin in arthritic horses. J Vet Pharmacol Ther 2008;

Barnett ML, Combitchi D, Trentham DE. A pilot trial of oraltype II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum 1996; 39(4):623-8.

Bruyere O, Reginster JY. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs Aging 2007; 24:573-580.

Asnagli H, Martire D, Belmonte N, Quentin J, Bastian H, Boucard-Jourdin M,et al. Type 1 regulatory T cells specific for collagen type II as an efficientcell-based therapy in arthritis. Arthritis Res Ther. 2014;16(3):R115.

Di Cesare ML, Micheli L, Zanardelli M, Ghelardini C. Low dose native type II collagen prevents pain in a rat osteoarthritis model. BMC Musculoskelet Disord. 2013;14:228. doi:10.1186/1471-2474-14-228.

Asnagli H, Martire D, Belmonte N, Quentin J, Bastian H, Boucard-Jourdin M, et al. Type 1 regulatory T cells specific for collagen type II as an efficient cell-based therapy in arthritis. Arthritis Res Ther. 2014;16(3):R115.