Undenatured Type II Collagen Protects Against Arthritis

By | November 29, 2016

The two most common types of arthritis are rheumatoid arthritis and osteoarthritis.

Rheumatoid arthritis is an inflammatory autoimmune disease, whereby the immune system attacks the lining of joints. The inflamed joint lining leads to bone and cartilage destruction, and loss of function. This highly disabling disease causes pain, swelling and stiffness in joints, thus limiting mobility and reducing quality of life.

Osteoarthritis (OA) is a degenerative joint disease that involves cartilage breakdown and bone remodelling. Although it is often thought to result from wear and tear on joints, increasing evidence shows that inflammation plays a critical role in the pathogenesis of OA.

(Photo by: Esther Max)

Drawbacks Of Current Treatment For RA & OA

The present treatment for arthritis involves analgesiscs, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and conventional disease-modifying antirheumatic drugs (DMARDs) and biologics.

Analgesics (pain killers) are used for managing arthritis pain but have no effects on inflammation and disease progression. Acetaminophen is the common over the counter analgesic for easing moderate pain. At high doses, it increases the risk of liver toxicity (hepatoxicity) and high blood pressure. Prescription opiods are effective in treating chronic pain but can cause side effects such as nausea, constipation and drowsiness.

Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve pain and inflammation. They are associated with kidney and gastrointestinal side effects (especially in elderly people) and increased cardiovascular risk.

Corticosteroids (commonly known as steroids) are highly anti-inflammatory agents. While they provide fast and significant relief from pain and inflammation, there are concerns of toxicity and serious side effects from long term use. Complications arising from the use of corticosteroids include osteoporosis and increased risk of fractures, immunosuppression and increased risk of infections,  weight gain, diabetes, hypertension, glaucoma, cataracts and Cushing’s syndrome.

Disease-modifying antirheumatic drugs (DMARDs) slow the disease progression, suppress joint damage and reduce symptoms, thereby improving physical function and quality of life in patients with moderate to severe RA. Although DMARDs address the underlying pathology of RA, they suppress the entire immune system and increase the risk of serious infection over time. Toxic side effects of DMARDs include increased risk of malignancies, retinal damage, diabetes, kidney failure, hepatoxicity, congestive heart failure, demyelinating disease and cytopenia.

Not all RA patients respond favourably to DMARDs. Some patients experience inadequate or no response to initial DMARD treatment while others lose response to treatment over time.

DMARDs are divided into 2 classes: conventional DMARDs and biologics.

Conventional DMARDs (eg: methotrexate, hydroxychloroquine and sulfasalazine) are slow-acting, so may take weeks or months for them to work.

Biologics are a newer class of DMARDs, targeting specific inflammatory cells, cellular interactions and cytokines that mediate tissue damage in RA. They work faster and are far more expensive, than conventional DMARDs. They are prescribed for patients who fail to respond to treatment with conventional DMARDs.

All the current drug treatments for arthritis are associated with adverse effects and high toxicities, hence limiting their long term use. Despite the introduction of biologics which has improved prognosis for many RA sufferers, there is still no clinically effective treatment.

Consequently, arthritis sufferers have turned to natural nutraceuticals to relieve pain and other symptoms associated with the disease. Nutraceuticals have received much attention due to their potential nutritional, safety and therapeutic effects. Undenatured type 2 collagen (UC-II) is a novel nutraceutical ingredient that interferes with the destructive inflammatory process and prevents cartilage breakdown in arthritis.

Type 2 Collagen: Potential Antigen For RA & OA

The antigen (causative agent) of RA is unclear. However, type 2 collagen is a potential antigen as it is the most abundant protein of human cartilage. In addition, animals injected with type 2 collagen developed inflammatory arthritis similar to RA. This suggests that immune responses to type 2 collagen could play a role in the pathogenesis of RA. For unexplained reasons, the immune system identifies type 2 collagen as an antigen, i.e. a foreign or harmful substance, and attacks it. This results in progressive degeneration of the joint structure and function, accompanied by joint swelling, pain and inflammation.

Degradation products of type 2 collagen in urine are also associated with the progression of articular damage in OA.

Undenatured Type 2 Collagen (UC-II) Protects Against Arthritis

Human and animal studies have shown that oral administration of native or undenatured type 2 collagen (UC-II) prevents and improves RA and OA.

How Does UC-II Work

UC-II works via oral tolerance, a method that suppresses antigen specific immune response after oral application of antigen.

When taken orally, low doses of UC-II antigen interact with  gut-associated lymphoid tissue (the largest organ immune system in the body) in the small intestines to turn off T-cell attack to type 2 collagen in the cartilage. This desensitisation process (a.k.a. oral tolerance) prevents the immune system from recognising endogenous type 2 collagen in the cartilage as antigen.

Human Clinical Trials of UC-II On Osteoarthritis (OA)

1. A clinical trial1 was conducted to evaluate the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+I) in treatment of moderate to severe knee osteoarthritis. 52 subjects were randomised to receive 30 mg of UC-II or 1500 mg of glucosamine hydrochloride plus 1200 mg chondroitin sulfate (G+C) daily for 90 days.

Results: UC-II was found to be more effective than G+I in reducing pain, stiffness and physical function in the knee.

Conclusion: Patients treated with UC-II showed significant enhancement in daily activities, and thus improvement in quality of life.

2. In a following study2, the efficacy and tolerability of UC-II for moderate to severe knee osteoarthritis were compared to placebo and glucosamine hydrochloride plus chondroitin (GC). 191 subjects with OA were randomised into 3 groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G + 1200 mg C) or placebo for 180 days.

Results: At the end of the study (day 180), the UC-II group reported significant reduction in pain, stiffness and physical function, compared to placebo and GC groups. These results confirm the findings in the previous study (#1 above).

Conclusion: UC-II significantly improved knee function in OA subjects, compared to placebo and to GC, and was well tolerated.

3. Another study3 assessed the effect of UC-II on knee function in healthy subjects without prior history of arthritis but who experienced knee pain with strenuous physical activity. 55 subjects who reported knee pain after taking part in a standardised stepmill performance test were randomised to receive placebo or 40 mg of UC-II daily for 120 days.

Results: The UC-II group showed significant improvement in average knee extension compared to the placebo group and to baseline. Knee extension is necessary for function and sports activities. Loss of knee extension can cause altered gait pattern affecting the ankle and hip, and difficulty in running and jumping. A permanent loss of 3-5º of extension can lead to development of early arthritis.

The UC-II group also exercised longer before experiencing any initial joint discomfort at day 120, compared to baseline.  There were no significant changes in average knee extension and time to onset of initial joint pain in  the placebo group.

Conclusion: This study shows the benefits of UC-II usage in healthy individuals. Daily supplementation with 40 mg of UC-II supports joint function and flexibility in healthy subjects. It has the potential to alleviate joint pain that occasionally arises from strenuous physical activity and extend time of pain free exertion.

Human Clinical Trials Of UC-II On Rheumatoid Arthritis (RA)

1. In a pilot study(4), 10 patients with RA were taken off their immuno-suppressive and disease-modifying drugs. They were given 0.1 mg of native type II collagen daily for 1 month and followed by 0.5 mg for the next 2 months.

Results: 6 out of 10 patients experienced significant improvement in morning stiffness, 1-minute walk time and grip strength after taking native type II collagen for 3 months. 1 patient reported remission with discontinuation of  nonsteroidal anti-inflammatory drug (NSAID). There were no side effects.

2. Based on the positive results of the pilot study in #1 above, a phase 2 trial(4) was conducted to determine the clinical efficacy of oral native type II collagen  on RA. 60 patients with severe, active RA were randomised to receive either native type II collagen at the same dosages used in the pilot study (#1 above) or a placebo for 90 days.

Results: The collagen group reported significant improvement in joint swelling and tenderness, the number of tender/painful and swollen joints, and 15-minute walk time. 4 patients in the collagen group experienced complete remission while none in the placebo group did. There were no side effects.

Conclusion: This study shows that oral administration of small quantity of native type II collagen is safe and can improve signs and symptoms of active RA.

3. In a pilot trial(5) of oral type II collagen in the treatment of juvenile rheumatoid arthritis (JRA), 10 patients with JRA between the ages of 8 and 14 years old were treated orally with type II collagen for 3 months.

Results: 8 out of 10 patients had reductions in both swollen and tender joint counts at the end of 3 months. 1 patient achieved complete remission of RA by the end of treatment.

Conclusion: Oral type II collagen may be a safe and effective treatment for JRA.

uc ii collagen arthritis, best joint supplement, natural arthritis relief

Undenatured Type 2 Collagen (Click on image for more info)

Why The Undenatured (Native) Form Of Type 2 Collagen Is Important

Studies show that type 2 collagen in the undenatured form induces oral tolerance while the denatured form does not.

Denatured (hydrolyzed) type 2 collagen has been processed with harsh chemical or high temperature, which makes it inacitve and ineffective in modulating immune responses. No studies have shown that denatured type 2 collagen is beneficial for arthritis. In fact, the administration of denatured type 2 collagen has no effect on the incidence or severity of arthritis. Unfortunately, most type II collagen supplements contain the denatured form.

The UC-II used in studies is derived from chicken sternum cartilage.


Human clinical trials and animal studies have demonstrated the safety and therapeutic efficacy of UC-II for OA and RA. It may also support joint function and flexibility in healthy people who experience joint pain following strenuous physical activity or exercise.

Oral administration of small doses of UC-II suppresses the autoimmune response responsible for arthritis and interferes with the inflammatory process. This prevents or slows the development and progression of arthritis, thus, effectively reduces joint pain, swelling and stiffness.

1. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764342/
2. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731911/
3. Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4015808/
4. Effects of Oral Administration of Type-II Collagen on Rheumatoid Arthritis https://www.ncbi.nlm.nih.gov/pubmed/8378772
5. A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis https://www.ncbi.nlm.nih.gov/pubmed/8630112


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