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Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II Versus Cartilage Building with Hydrolysed Collagen II

Authors:
  • Dr Varsha's Health Solutions

Abstract and Figures

Rheumatoid Arthritis is known to have a T cell mediated autoimmune aetiology causing joint cartilage destruction. Osteoarthritis, though regarded as a degenerative disease, also shows a T cell immune response and inflammatory cartilage damage. Both types of Arthritis at a cellular level show T helper cell activation, involvement of pro-inflammatory cytokines and increased destruction of cartilage by Matrix Metalloproteinase enzymes. There is also evidence of relative suppression of anti-inflammatory cytokines and T regulatory cells which can perpetuate the cartilage loss. Supplementing hydrolysed Collagen type II to aid the body rebuild joint cartilage in the scenario of continuous cartilage destruction may not give the desired results. Therefore, reduction of inflammatory cartilage damage through the mechanism of specific immunomodulation by preventing immune response against collagen type II in joint cartilage, appears to be a scientifically rational option in both Rheumatoid Arthritis and Osteoarthritis.
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Archives of Orthopedics and Rheumatology V2 . I2 . 2019
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       
       
Archives of Orthopedics and Rheumatology
ISSN: 2639-3654
Volume 2, Issue 2, 2019, PP: 04-11
Understanding Collagen Supplements in Arthritis –
Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
Varsha Narayanan1*, Rajesh Gandhi2
1
2
drvarsha@rediffmail.com
*Corresponding Author: Varsha Narayanan, Health and Pharmaceutical Consultant, Dr Varsha’s Health Solutions,
Andheri west, Mumbai, India.
Abstract
Rheumatoid Arthritis is known to have a T cell mediated autoimmune aetiology causing joint cartilage
destruction. Osteoarthritis, though regarded as a degenerative disease, also shows a T cell immune response
     

 
which can perpetuate the cartilage loss. Supplementing hydrolysed Collagen type II to aid the body rebuild
joint cartilage in the scenario of continuous cartilage destruction may not give the desired results. Therefore,
           
 
option in both Rheumatoid Arthritis and Osteoarthritis.
Keywords: Rheumatoid Arthritis, Osteoarthritis, Cartilage, Undenatured Collagen Type II, T cell, autoimmune,

5Archives of Orthopedics and Rheumatology V2 . I2 . 2019
       
      

   

   


       

       
      
       
  
      
       
      
6 
     

      
 
      

     
 
      
       

 

7


      


       
       
        

8 
        

          
        
found in RA patients.9
       
       
      
    
    
      
         
      


     

     
    
      
      
   
     

        
    



    
     
    

      
       
       

  


   



     
      
      
      

       
      
   27   
  
        
 
Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
6
Archives of Orthopedics and Rheumatology V2 . I2 . 2019
       

17
      

      
       

19
      
       
     

      
         
         
   
       
        17
     
        
      


  
       
    
      
   
     
 
     
  

     
destruction issuppressed.

      
     
      
      
      

Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
Fig 1. Mechanism of Action of Undenatured (Native) Collagen Type II.
7Archives of Orthopedics and Rheumatology V2 . I2 . 2019
     

      
      
Arthritis.



22

        
      



        

Later two separate studies   
     

        

  
      
     



     
  
  23       
        
       

      

       

    
P 


     

      
   
      
studies.

     
      

        
      
      
    
      
 


      


       
Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
 Difference between Undenatured and Hydrolysed Collagen Type II
 
1

      
peptides
2        


        

3 
       
       

     


       
     


     
    

8
Archives of Orthopedics and Rheumatology V2 . I2 . 2019
         
 
       



   
     


      
        
           
         
         
   
      
             
  
  


    
   
          
       





        
26      
    


       
      
     
27     

     
     
     
       
       
    

  
     



      

21
     
      
        
across 18 Orthopaedic doctors in India.28 

       



headache) was seen.

      
     
       
    
      




       
      
     
      
29  

       
      
      
       


       

and function in OA and other arthritic conditions.
    
       
       
     
progression of osteoarthritis in patients diagnosed
Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
9Archives of Orthopedics and Rheumatology V2 . I2 . 2019
    30  

        
         

   
remained unchanged. (P < 0.01)

        
 
    
     


       

purchasing it on their own. It is important to therefore
     
       
     
   
     

       

      
       
        
     
   

   

  
     
    
     



[1]

     

[2]

     [3]
Am Fam
Physician.
   
   
    
 s   

        


t
        [6]

      

[7]
       
       
    
    
      
76
           [8]
    

       [9]
       
 
  
    
    
   
  

[10] 
and pain   

[11] w      
      
    
    
     
    
     .
8
Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
10
Archives of Orthopedics and Rheumatology V2 . I2 . 2019
      [12]

     

 

      [13]
n

     
  

      
        
   
    

      

[16]


     
   
  

[17]
       
    
    
      

[18]




[19]

         [20]
        



[21]

     

r
[22]
       


           [23]
     

 
      

           
     

     Arthritis
Research & Therapy 



 International Journal
of Medical Sciences 
       [26]
      
    
    


       [27]
      
     
     

         [28]

      
 
      

 [29]      
the treatment of osteoarthritis and other joint
       
Res Opin.
Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
11 Archives of Orthopedics and Rheumatology V2 . I2 . 2019
       [30]
   
  
      
on osteoarthritis.   .  

Understanding Collagen Supplements in Arthritis – Immunomodulation with Undenatured Collagen II
Versus Cartilage Building with Hydrolysed Collagen II
Citation:
Varsha Narayanan, Rajesh Gandhi
.
Understanding Collagen Supplements in Arthritis
           .
Archives of Orthopedics and Rheumatology. 2019; 2(2): 04-11.
Copyright: © 2019
Varsha Narayanan, Rajesh Gandhi
.
This is an open access article distributed under the
Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
... However, the pathological processes in KOA need to be constrained in order for HC to be optimized. Therefore, treatments should begin with CU-II that can exert an immune-modulatory effect first [26]. Possibly for a period of up to 6 months. ...
... Type 1 collagen in supplemental from is hydrolyzed and dissolved into smaller peptides. It is altered into a denatured form of collagen for better absorption.This has been proven to have several beneficial effects in the joint[25] [26]. It affects fibroblasts in the ECM to rebuild collagen. ...
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p class="abstract"> Background: Osteoarthritis (OA) is the most common musculoskeletal conditions affecting the quality of life. Undenatured collagen type II has emerged as one of the promising treatment options in treatment of OA. Despite being available in India, clinical safety and efficacy have not been evaluated. We performed a non-interventional, real-life study to determine its safety and efficacy in Indian population. Methods: A non-interventional, real-life study was performed in patients with OA of knee by 18 orthopaedicians in India. Patients enrolled were followed-up at day 30 (visit 2), day 60 (visit 3) and day 90 (visit 4). Efficacy was assessed by Western Ontario McMaster Osteoarthritis Index (WOMAC) and Visual Analogue scale (VAS) on each visit. Safety was assessed by incidence of suspected adverse events (AEs), and abnormal laboratory parameters. Results: Among 291 enrolled patients 226 patients completed the study. Mean age of the population was 56.2±8.7 years and 53.3% of them were females. In 291 patients included in safety analysis, at least one treatment emergent adverse event (TEAE) was seen in 4.47% patients. None of the AEs were serious or resulted in termination of patient from the study. Nausea (1.37%) and headache (1.03%) were the common AEs. Treatment with undenatured collagen type II was associated with significant reduction in WOMC score (p<0.0001) and VAS scores (p<0.0001) from baseline to day 90. Conclusions: Undenatured collagen type II is safe and efficacious in Indian patients with OA. This can be considered early in the initial management of OA.</p
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Objective Antifibrillar collagen type II (anti-CII) antibody-positive patients with rheumatoid arthritis (RA) have early but not late signs of increased inflammation and joint erosions. We wanted to replicate this in a large RA cohort, and to relate to human leukocyte antigen (HLA)-DRB1* alleles. Methods Anti-CII and anti-cyclic citrullinated peptide (CCP)2 were measured at baseline in 773 patients with RA from the Swedish Epidemiological Investigation in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality Register (SRQ) registry, and 1476 with HLA-DRB1* information. Comparisons were done concerning C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), Disease Activity Score encompassing 28 joints based on ESR (DAS28), DAS28CRP, pain-Visual Analogue Scale (VAS), global-VAS and Health Assessment Questionnaire Score (HAQ) at eight occasions during 5 years, and association with HLA-DRB1* alleles. Results Anti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to 6 months, whereas anti-CCP2 associated with SJC and DAS28 from 6 months to 5 years, but not earlier. The anti-CII-associated phenotype was strong, and predominated in anti-CII/anti-CCP2 double-positive patients. Anti-CII was associated with improvements in CRP, ESR, SJC, TJC and DAS28, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time. Anti-CII-positive patients achieved European League Against Rheumatism good or moderate response more often than negative patients. Anti-CII was positively associated with HLA-DRB1*01 and HLA-DRB1*03, with significant interaction, and double-positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking was associated with elevated anti-CCP2 levels, smokers had lower anti-CII levels. Conclusions Anti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse to the clinical, genetic and smoking associations described for anticitrullinated protein peptide autoantibodies. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA.
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Background Undenatured type II collagen (UC-II) is a nutritional supplement derived from chicken sternum cartilage. The purpose of this study was to evaluate the efficacy and tolerability of UC-II for knee osteoarthritis (OA) pain and associated symptoms compared to placebo and to glucosamine hydrochloride plus chondroitin sulfate (GC). Methods One hundred ninety one volunteers were randomized into three groups receiving a daily dose of UC-II (40 mg), GC (1500 mg G & 1200 mg C), or placebo for a 180-day period. The primary endpoint was the change in total Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) from baseline through day 180 for the UC-II group versus placebo and GC. Secondary endpoints included the Lequesne Functional Index (LFI), the Visual Analog Scale (VAS) for pain and the WOMAC subscales. Modified intent-to-treat analysis were performed for all endpoints using analysis of covariance and mixed model repeated measures, while incremental area under the curve was calculated by the intent-to-treat method. ResultsAt day 180, the UC-II group demonstrated a significant reduction in overall WOMAC score compared to placebo (p = 0.002) and GC (p = 0.04). Supplementation with UC-II also resulted in significant changes for all three WOMAC subscales: pain (p = 0.0003 vs. placebo; p = 0.016 vs. GC); stiffness (p = 0.004 vs. placebo; p = 0.044 vs. GC); physical function (p = 0.007 vs. placebo). Safety outcomes did not differ among the groups. ConclusionUC-II improved knee joint symptoms in knee OA subjects and was well-tolerated. Additional studies that elucidate the mechanism for this supplement’s actions are warranted. Trial registrationCTRI/2013/05/003663; CTRI/2013/02/003348.
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BACKGROUND: Recent studies show that enzymatically hydrolyzed collagen, the collagen peptide is absorbed and distributed to joint tissues and has analgesic and anti-inflammatory properties. A double blind placebo controlled randomized trial with collagen peptides isolated from pork (PCP) and bovine bone (BCP) sources was carried out to study the effectiveness of orally supplemented collagen peptide to control the progression of osteoarthritis in patients diagnosed with knee osteoarthritis. Improvement in treatment was assessed with reduction in Western Ontario McMaster Universities (WOMAC), visual analogue scale (VAS) and Quality of Life (QOL) scores from baseline to 13 weeks (Visit 7). Safety and tolerability were also evaluated. RESULTS: There was significant reduction from base line to Visit 7 in the primary end points of WOMAC and VAS scores and in the secondary end point of QOL score in subjects with PCP and BCP groups, while in subjects with placebo group the end point indices remained unaltered. Furthermore, all the score levels of WOMAC, VAS and QOL decreased significantly (p < 0.01) in study group compared to placebo group in Visit 7. CONCLUSION: The study demonstrated that the collagen peptides are potential therapeutic agents as nutritional supplements for the management of osteoarthritis and maintain joint health.
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UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects, who reported knee pain after participating in a standardized stepmill performance test, were randomized to the placebo (n = 28) or the UC-II (40 mg daily, n = 27) cohort for 120 days. Joint function was assessed by measuring knee flexion and knee extension as well as time to experiencing and recovering from joint pain following strenuous stepmill exertion. After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 +/- 1.3o vs 74.0 +/- 2.2o; p = 0.011) and to baseline (81.0 +/- 1.3o vs 73.2 +/- 1.9o; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 +/- 1.9o vs 73.2 +/- 1.9o; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 +/- 0.5 min, p = 0.019), compared to baseline (1.4 +/- 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities.
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Previous studies have shown that undenatured type II collagen (UC-II) is effective in the treatment of rheumatoid arthritis, and preliminary human and animal trials have shown it to be effective in treating osteoarthritis (OA). The present clinical trial evaluated the safety and efficacy of UC-II as compared to a combination of glucosamine and chondroitin (G+C) in the treatment of OA of the knee. The results indicate that UC-II treatment was more efficacious resulting in a significant reduction in all assessments from the baseline at 90 days; whereas, this effect was not observed in G+C treatment group. Specifically, although both treatments reduced the Western Ontario McMaster Osteoarthritis Index (WOMAC) score, treatment with UC-II reduced the WOMAC score by 33% as compared to 14% in G+C treated group after 90 days. Similar results were obtained for visual analog scale (VAS) scores. Although both the treatments reduced the VAS score, UC-II treatment decreased VAS score by 40% after 90 days as compared to 15.4% in G+C treated group. The Lequesne's functional index was used to determine the effect of different treatments on pain during daily activities. Treatment with UC-II reduced Lequesne's functional index score by 20% as compared to 6% in G+C treated group at the end of 90-day treatment. Thus, UC-II treated subjects showed significant enhancement in daily activities suggesting an improvement in their quality of life.
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