Halt the Auto-Immune Attack of Arthritis
By Michael Downey
UC-II® Modulates Osteoarthritis
Turning their attention to osteoarthritis, scientists tested UC-II®, a proprietary form of undenatured type II chicken collagen, on horses and larger dogs. These animals are, like humans, very susceptible to osteoarthritis.
Only a specific undenatured form of collagen, which maintains its unique molecular structure, can retrain the immune system not to overreact to exposed collagen fibers. To understand this crucial difference, see the box on the next page.
Dogs with osteoarthritis given UC-II® were found to exhibit significant reductions in overall pain, in pain after limb manipulation, and in lameness after physical exertion—within 90 days.6 There were no adverse side effects. When UC-II® was then withdrawn for the next 30 days, the pain and exercise-associated lameness returned.6
These findings were confirmed when a subsequent study on arthritic dogs found that UC-II® produced the same significant decrease in arthritic pain—again, within 90 days.7
A longer study found that while arthritic dogs given UC-II® were measured to experience significant improvements in pain and mobility after 30 and 60 days, they showed the greatest benefit after 120 days of supplementation. By that point, the UC-II® group was measured to have a 62% reduction in overall pain, a 78% reduction in exercise-associated lameness—and a surprising 91% reduction in pain upon limb manipulation!13
A later placebo-controlled study confirmed these observations. After 120 days, dogs treated with UC-II® were assessed to have a 77% reduction in overall pain, an 84% reduction in exercise-associated pain, and an 83% reduction in pain upon limb manipulation. No adverse effects were found—even after a thorough check of liver, kidney, and heart function.26
A longer, more precision-based study was undertaken in 2011, using a high-tech ground force plate employing a special piezoelectric sensor. This apparatus allowed researchers to measure with a high degree of accuracy, the exact force and weight that dogs placed on each arthritic limb. Dogs given the undenatured UC-II® formulation were able to place more weight on sore limbs and use them more naturally, relative to those given either placebo or the combination of chondroitin-plus-glucosamine. Monthly tests of kidney and liver function, pulse rate, temperature, and weight found no adverse effects.The data from the groundforce plate study showed that dogs in the UC-II® only group showed continued improvement after 150 days, at which time supplementation was discontinued.154
In a large, placebo-controlled study, researchers administered oral doses of UC-II® to horses. They measured reductions of 88% in overall pain, and 78% in pain during limb manipulation among horses given UC-II®. These benefits were seen after 150 days of supplementation.8
Studies demonstrated that UC-II® alone produced much greater results in relieving arthritis in dogs and horses than the combination of chondroitin and glucosamine sulfate alone.8,13 However, the same researchers found that combining UC-II®, with chondroitin and glucosamine sulfate produced the greatest benefits, substantially alleviating pain and improving function.15 This suggests the possibility that humans may be found to benefit from the dual action of these two treatments together. While impressive evidence indicates that undenatured type II collagen inhibits processes responsible for the progression of arthritis, the glucosamine-and-chondroitin combination has previously been shown to repair damaged joints.10,14 Scientists then shifted their focus to the effect of UC-II® on osteoarthritis in humans.
Targeting Osteoarthritis in Humans
Evidence had already established the effectiveness of undenatured type II collagen in inhibiting the symptoms of rheumatoid arthritis in humans. However, it would be necessary to separately establish this unique ability of UC-II® in human cases of osteoarthritis. To achieve this, researchers employed a stringent study protocol: a randomized, double-blind, clinical study on humans.
In a study of this type, 52 adults suffering from osteoarthritis with an average age of 59 were randomly assigned to receive daily either two 20 mg capsules of UC-II®, or a combination of four 375 mg capsules of glucosamine plus four 300 mg chondroitin sulfate. All patients were assessed at 30-day intervals.4
The researchers found that in just 90 days, UC-II® provided “significant enhancement in daily activities, suggesting an improvement in their quality of life.”4
In the same trial, the researchers employed the standardized WOMAC (Western Ontario McMaster Osteoarthritis Index) scale to accurately assess symptoms. They concluded that 40 mg a day of UC-II® reduced osteoarthritis symptoms assessed by the WOMAC scale by 33%—in only 90 days. By comparison, the combination of 1,500 mg a day of glucosamine and 1,200 mg a day of chondroitin sulfate reduced WOMAC scores in the same period by only 14%.4
The team of scientists then used the Visual Analog Scale (VAS)—which is used to assess pain—to corroborate these results. Using this measure, they found pain scores decreased by 40% for the UC-II® group, while pain scores for the glucosamine/chondroitin group decreased just 15%.4
Finally, using the Lequesne’s Functional Index—a measure specifically of pain during daily activities, such as walking—the study team found that UC-II® reduced the score for this type of pain by 20%, while the combination of glucosamine plus chondroitin lowered the score by only 6%.4
All results were observed in just 90 days.
This compelling human research crowns a series of studies indicating that undenatured type II cartilage induces oral tolerance to exposed collagen, inhibiting the immune response that inflames joints and further degrades joint cartilage.
Recent research has revealed that cartilage erosion caused by wear-and-tear is not the immediate cause of osteoarthritis—it is only the initial trigger.
Scientists now know that osteoarthritis, like rheumatoid arthritis, is an abnormal immune-system overreaction to exposed collagen fibers in joint cartilage.
Until this discovery, the standard treatment has been risky NSAIDs and immune suppressants, which have no effect on the underlying cause of this immune reaction.
Oral introduction of type II chicken collagen desensitizes the immune system to collagen fibers, “teaching” inflammatory killer T-cells to ignore exposed collagen in the joints.
This unique intervention works by activating induced oral tolerance, the natural pathway that effectively “short-circuits” the immune response behind arthritis—halting disease activity.
Controlled clinical studies indicate that undenatured type II collagen uniquely inhibits inflammatory joint pain, joint swelling, and impaired function in both rheumatoid and osteoarthritis.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
1. Shamir L, Ling SM, Scott WW Jr, et al. Knee x-ray image analysis method for automated detection of osteoarthritis. IEEE Trans Biomed Eng. 2009 Feb;56(2):407-15. 2. Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly, The Framingham Study. Am J Epidemiol. 2002;156:1021-7. 3. Scott DL, Berry H, Capell H, et al. The long-term effects of non-steroidal anti-inflammatory drugs in osteoarthritis of the knee: a randomized placebo-controlled trial. Rheumatology (Oxford). 2000 Oct;39(10):1095-101.
4. Crowley DC, Lau FC, Sharma P, 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(6):312-21.
5. Goldring SR, Scanzello CR. Plasma proteins take their toll on the joint in osteoarthritis. Arthritis Res Ther. 2012 Mar 5;14(2):111.
6. Deparle LA, Gupta RC, Canerdy TD, et al. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II®) in therapy of arthritic dogs. J Vet Pharmacol Ther. 2005 Aug;28(4):385-90.
7. Peal A, D’Altilio M, Simms C, et al. Therapeutic efficacy and safety of undenatured type-II collagen (UC-II®) alone or in combination with (-)-hydroxycitric acid and chromemate in arthritic dogs. J Vet Pharmacol Ther. 2007 Jun;30(3):275-8.
8. Gupta RC, Canerdy TD, Skaggs P, et al. Therapeutic efficacy of undenatured type-II collagen (UC-II®) in comparison to glucosamine and chondroitin in arthritic horses. J Vet Pharmacol Ther. 2009 Dec;32(6):577-84.
9. Trentham DE, Dynesius-Trentham RA, Orav EJ, et al. Effects of oral administration of type II collagen on rheumatoid arthritis. Science. 1993 Sep 24;261(5129):1727-30.
10. Barnett ML, Kremer JM, St Clair EW, et al. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 1998 Feb;41(2):290-7.
11. Barnett ML, Combitchi D, Trentham DE. A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis Rheum. 1996 Apr;39(4):623-8.
12. Wei W, Zhang L-L, Xu J-H. A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Research & Therapy. 2009;11:R180.
13. D’Altilio M, Peal A, Alvey M, et al. Therapeutic efficacy and safety of undenatured type II collagen singly or in combination with glucosamine and chondroitin in arthritic dogs. Toxicol Mech Methods. 2007;17(4):189-96.
14. Gupta RC, Canerdy TD, Lindley J, et al. Comparative therapeutic efficacy and safety of type-II collagen (UC-II®), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate. J Anim Physiol Anim Nutr. Epub 2011 May 30.
15. Bagchi D, Misner B, Bagchi M, et al. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration. Int J Clin Pharmacol Res. 2002;22(3-4):101-10.
16. Heinegard D, Saxne T. The role of the cartilage matrix in osteoarthritis. Nat Rev Rheumatol. 2011 Jan;7(1):50-6.
17. Cohen ES, Bodmer HC. Cytotoxic T lymphocytes recognize and lyse chondrocytes under inflammatory, but not non-inflammatory conditions. Immunology. 2003 May;109(1):8-14.
18. Wang Q, Rozelle AL, Lepus CM, et al. Identification of a central role for complement in osteoarthritis. Nature Medicine. Nov 6 2011.
19. Adatia A, Rainsford KD, Kean WF. Osteoarthritis of the knee and hip. Part I: aetiology and pathogenesis as a basis for pharmacotherapy. J Pharm Pharmacol. 2012 May;64(5):617-25. 20. Tarkowski A, Klareskog L, Carlsten H, Herberts P, Koopman WJ. Secretion of antibodies to types I and II collagen by synovial tissue cells in patients with rheumatoid arthritis. Arthritis Rheum. 1989 Sep;32(9):1087-92.
21. Singh G, Wu O, Langhorne P, Madhok R. Risk of acute myocardial infarction with nonselective non-steroidal anti-inflammatory drugs: a meta-analysis. Arthritis Res Ther. 2006;8(5):R153.
22. Thomas MC. Diuretics, ACE inhibitors and NSAIDs—the triple whammy. Med J Australia. Feb 2000;172(4):184-5.
23. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional nonsteroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ (Clinical research ed.) June 2006;332(7553):1302-8.
24. Trelle S, Reichenbach S, Wandel S, et al. Cardiovascular safety of non-steroidal anti inflammatory drugs: network meta-analysis. BMJ (Clinical research ed.) 2011 Jan 11;342:c7086.
25. Rennard BO, Ertl RF, Gossman GL, Robbins RA, Rennard SI. Chicken soup inhibits neutrophil chemotaxis in vitro. Chest. 2000 Oct;118(4):1150-7.
26. Gupta RC, Barnes M, Minniear J. et al. Pain reduction measured by ground force plate in arthritic dogs treated with type-II collagen. Presented at Society of Toxicology 48th Annual Meeting, March 2009. 108(1);Abstract 769:159.
27. Cremer MA, Rosloniec EF, Kang AH. The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease. J Mol Med (Berl). 1998 Mar;76(3-4):275-88.
28. Corthay A, Backlund J, Broddefalk J, et al. Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis. Eur J Immunol. 1998 Aug;28(8):2580-90.
29. Meyer O. Oral immunomodulation therapy in rheumatoid arthritis. Joint Bone Spine. 2000;67(5):384-92.
30. Park KS, Park MJ, Cho ML, et al. Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis. Mod Rheumatol. 2009;19(6):581-9.
31. Min SY, Park KS, Cho ML, et al. Antigen-induced, tolerogenic CD11c+,CD11b+ dendritic cells are abundant in Peyer’s patches during the induction of oral tolerance to type II collagen and suppress experimental collagen-induced arthritis. Arthritis Rheum. 2006 Mar;54(3):887-98.
32. Weiner HL. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today. 1997 Jul;18(7):335-43.
33. Zhu P, Li XY, Wang HK, et al. Oral administration of type-II collagen peptide 250-270 suppresses specific cellular and humoral immune response in collagen-induced arthritis. Clin Immunol. 2007 Jan;122(1):75-84.
34. Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7443-6.
35. Faria AM, Weiner HL. Oral tolerance. Immunol Rev. 2005;206:232-59.
36. Available at: http://www.cdc.gov/nchs/fastats/arthrits.htm. Accessed April 3, 2012.
37. Lanas A, Garcia-Tell G, Armada B, Oteo-Alvaro A. Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis. BMC Med. 2011 Apr;14(9):38.