Collagen type II hydrolysate for patients with arthritis and individuals with high level of physical activity. Elgenoflex. Vitaminized - buy joint supplements online

COLLAGEN TYPE II: THE ADVANTAGE OF ELGENOFLEX

Collagens are structural proteins found in various connective tissues. Of the 28 known types of collagens [1], type II is the major collagen found in cartilage. A molecule of type II collagen consists of three identical polypeptide chains produced by the COL2A1 gene. Another, less abundant cartilage collagen is type XI, each molecule of which combines a type II chain and two chains of another type. Thus, type II chains are necessary to form both type II and type XI collagens.

 

The importance of collagen type II in cartilage is confirmed by a number of skeletal disorders caused by mutations in the COL2A1 gene, such as Kniest dysplasia and Stickler syndrome [2]. The former is characterized by short, deformed bones, enlarged joints, and pain in joints that restricts patients’ movement [3,4]. The latter results in defects in facial bone development and a variety of other symptoms such as arthritis (which develops early in life) and abnormalities in the vertebrae and at the ends of long bones [5,6].

 

A substantial number of studies have documented the beneficial effect of supplementation with various forms of collagen. Collagen type II hydrolysates are used most often, both in healthy people and in patients with musculoskeletal disorders [7]. Like other ingested proteins, collagens are hydrolyzed in the digestive tract and cannot be directly incorporated into human tissues. Nevertheless, their ingestion may be beneficial because it may stimulate production of endogenous collagens. At least two likely mechanisms of this stimulation have been suggested. One is that collagens have specific amino acid composition and their synthesis requires much higher amounts of two particular amino acids, glycine and proline, than the synthesis of other proteins. The intake of collagens, especially collagen hydrolysates, may help increase the availability of these amino acids in the body and thus facilitate the synthesis of endogenous collagen [8].

 

Another possible mechanism may rely on the regulatory role of collagen fragments. The appearance of collagen-derived di- and tri-peptides in the blood has been reported after the ingestion of collagen hydrolysates derived from bovine and chicken collagens [9,10]. Although di- and tri-peptides cannot be directly used as building blocks for the synthesis of new collagen, some lines of evidence suggest that they can act as regulatory molecules to increase the production of collagen type II [11] and hyaluronic acid [12]. Therefore, it seems plausible that similar mechanisms may in part be responsible for the beneficial effects of collagen hydrolysates in vivo, although this remains to be demonstrated. Below we consider several examples of studies that have documented the beneficial effect of collagen type II hydrolysates (including studies conducted in the USA using the same collagen type II hydrolysate as in Elgenoflex) and their components hyaluronic acid and chondroitin sulfate.

 

The main component of Elgenoflex (approximately 2/3 by weight) is BioCell Collagen, produced by BioCell Technology LLC (Newport Beach, CA, USA). It is a collagen type II hydrolysate derived from chicken sternal articular cartilage, which also contains low-molecular-weight glycosaminoglycans (hyaluronic acid and chondroitin sulfate) [13,14]. These two additional components may also have beneficial effects (see below).

 

Сollagen type II hydrolysate for patients with arthritis and individuals with high level of physical activity

A randomized, double-blind, placebo-controlled pilot study enrolled eight healthy, physically active volunteers who experienced muscle and connective tissue strain and damage because of intense exercise [13]. The participants received BioCell Collagen (3 g daily) or a placebo for six weeks and were subjected to a muscle-damaging resistance exercise challenge twice during the week following the supplementation period. The authors found a lower increase in serum markers for muscle tissue damage and enhanced stress resilience (as indicated by better performance at the repeated challenge) in the BioCell Collagen group in comparison with the placebo group [13], although the small size of the groups did not allow evaluation of the statistical significance of the findings.

 

A randomized, double-blind, placebo-controlled trial involved 80 patients with osteoarthritis in the knee and/or hip joints [15]. The authors found that ingestion of BioCell Collagen (2 g daily) for 10 weeks resulted in a significant reduction in pain in comparison with the placebo group. Both the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and physical activity were significantly improved in comparison with the placebo group after five weeks of BioCell Collagen supplementation, and this effect persisted until the end of the trial (10 weeks). No difference in tolerability was noted between BioCell Collagen and the placebo [15]. These data suggest that formulations containing BioCell Collagen, such as Elgenoflex, can be expected to be beneficial for patients with osteoarthritis. Studies that used BioCell Collagen did not report any serious side effects.

 

A randomized, double-blind, controlled study that enrolled 250 patients with knee osteoarthritis used a similar collagen type II hydrolysate preparation (10 g daily for three months) [16]. The authors found significant improvement in knee joint comfort, especially in patients with the greatest joint deterioration and those who consumed less meat.

 

An important study was a randomized, placebo-controlled, double-blind, pilot trial conducted by McAlindon and colleagues [17], who used sophisticated imaging technology based on magnetic resonance imaging (MRI) to accurately measure short-term changes in knee hyaline cartilage in osteoarthritis patients taking collagen hydrolysate. The authors found an increase in proteoglycan content in knee cartilage in the collagen group and hydrolysate group, but a decrease in the placebo group, with a statistically significant difference after 24 weeks [17].

 

Collagen type II hydrolysates are also effective in patients with rheumatoid arthritis. For example, a phase III clinical trial (503 participants in total) compared the effects of a chicken type II collagen hydrolysate (0.1 g daily for 24 weeks) with those of methotrexate, an approved rheumatoid arthritis drug [18]. The authors found that the collagen hydrolysate alleviated rheumatoid arthritis symptoms. Although its efficacy was slightly lower than that of methotrexate, it had fewer side effects.

 

Thus, collagen type II hydrolysates have beneficial effects in healthy people with strenuous physical activity as well as patients with osteoarthritis and rheumatoid arthritis.

 

Beneficial effects of hyaluronic acid in patients with osteoarthritis. Hyaluronic acid is necessary for the production of synovial fluid in the joints and is a component of articular cartilage; intra-articular injections are widely used in patients with osteoarthritis [19,20]. Several clinical trials have shown that oral administration of hyaluronic acid may also be effective. The obvious advantages of oral administration are that patients can avoid the discomfort of regular injections and can take the supplements at home, without having to visit a clinic.

 

A pilot randomized, double-blind, placebo-controlled trial conducted in the USA enrolled 40 patients with osteoarthritis, who received an extract of chicken combs with high content (~60%) of hyaluronic acid (80 mg daily, corresponding to ~50 mg of hyaluronic acid daily) for eight weeks [21]. The authors found statistically significant improvements in the WOMAC scores in both the hyaluronic acid group and the placebo group, but the improvement in the hyaluronic acid group was significantly higher than that in the placebo group. Similar changes were found in several markers of life quality: whereas both groups showed statistically significant improvements compared to baseline, the improvements in pain and social functioning were greater in the hyaluronic acid group than in the placebo group [21].

 

Similar results were obtained in a randomized, double-blind, placebo-controlled study that was conducted in Japan and enrolled 43 patients with knee osteoarthritis, who received a chicken comb extract (equivalent to 60 mg of hyaluronic acid daily) for 16 weeks [22]. In the hyaluronic acid group, the authors found moderate but significant improvements in parameters related to pain and walking function or going up and down stairs, although not in joint flexion or swelling. Although improvements were also observed in the placebo group, they were not statistically significant [22]. The authors also examined the markers of collagen degradation and synthesis and found that the synthesis to degradation ratio was increased in the hyaluronic group [22]. This finding indicates that the presence of hyaluronic acid in collagen type II hydrolysates would have a synergistic positive effect in osteoarthritis patients.

 

Chondroitin sulfate for joint health

Chondroitin sulfate is a component of a number of proteoglycans in the extracellular matrix, where it plays a variety of regulatory roles. Similar to hyaluronic acid, chondroitin sulfate is an important component of the synovial fluid and cartilage, and is widely used as a separate supplement in patients with osteoarthritis (see review by Iovu and colleagues [23] and references therein). Despite a large number of clinical trials that used chondroitin sulfate, there has been a continuous controversy over the last decade regarding its efficiency [24]. Possible causes of confusion might include the “placebo effect” (improvements seen in groups taking a placebo) and the difficulty in quantitatively assessing pain. To address the latter issue, Monfort and colleagues have recently used functional magnetic resonance imaging (fMRI) to assess pain in osteoarthritis patients taking chondroitin sulfate or a placebo for four months [25]. In this phase IV, randomized, double-blind trial, the patients taking chondroitin sulfate but not those in the placebo group tended to report reduced subjective pain, but this effect did not reach statistical significance. However, imaging of the pain-processing region of the brain, which is activated when a person perceives pain, demonstrated a statistically significant reduction in pain in the chondroitin sulfate group, which was significantly greater than that in the placebo group [25]. These findings not only confirm the efficacy of chondroitin sulfate but also set a precedent for the use of a technique that may help resolve uncertainties in the efficacy of other supplements that are assumed to alleviate pain. The US Federal Drug Administration (FDA) considers chondroitin sulfate as a food supplement; in European countries, it is recognized as an osteoarthritis drug [26].

 

Finally, it should be noted that collagen hydrolysates are generally recognized as safe, which has been confirmed by the World Health Organization (WHO) and the European Commission for Health and Consumer Protection; gelatin (denatured collagen from which the hydrolysates are produced) is also recognized as safe by the US Food and Drug Administration (FDA) [8].

References

1. Kadler, K.E., Baldock, C., Bella, J. & Boot-Handford, R.P. Collagens at a glance. J Cell Sci 120, 1955-1958 (2007).
2. Winterpacht, A. et al. Kniest and Stickler dysplasia phenotypes caused by collagen type II gene (COL2A1) defect. Nat Genet 3, 323-326 (1993).
3. Gilbert-Barnes, E., Langer, L.O., Jr., Opitz, J.M., Laxova, R. & Sotelo-Arila, C. Kniest dysplasia: radiologic, histopathological, and scanning electron microscopic findings. Am J Med Genet 63, 34-45 (1996).
4. Spranger, J., Winterpacht, A. & Zabel, B. Kniest dysplasia: Dr. W. Kniest, his patient, the molecular defect. Am J Med Genet 69, 79-84 (1997).
5. Nowak, C.B. Genetics and hearing loss: a review of Stickler syndrome. J Commun Disord 31, 437-453; 453-434 (1998).
6. Liberfarb, R.M. et al. The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genet Med 5, 21-27 (2003).
7. Van Vijven, J.P. et al. Symptomatic and chondroprotective treatment with collagen derivatives in osteoarthritis: a systematic review. Osteoarthritis Cartilage 20, 809-821 (2012).
8. Sibila, S., Godfrey, M., Brewer, S., Budh-Raja, A. & Genovese, L. An overview of the beneficial effects of hydrolysed collagen as a nutraceutical on skin properties: scientific background and clinical studies. Open Nutraceuticals J 8, 29-42 (2015).
9. Iwai, K. et al. Identification of food-derived collagen peptides in human blood after oral ingestion of gelatin hydrolysates. J Agric Food Chem 53, 6531-6536 (2005).
10. Sugihara, F., Inoue, N., Kuwamori, M. & Taniguchi, M. Quantification of hydroxyprolyl-glycine (Hyp-Gly) in human blood after ingestion of collagen hydrolysate. J Biosci Bioeng 113, 202-203 (2012).
11. Oesser, S. & Seifert, J. Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen. Cell Tissue Res 311, 393-399 (2003).
12. Ohara, H., Iida, H., Ito, K., Takeuchi, Y. & Nomura, Y. Effects of Pro-Hyp, a collagen hydrolysate-derived peptide, on hyaluronic acid synthesis using in vitro cultured synovium cells and oral ingestion of collagen hydrolysates in a guinea pig model of osteoarthritis. Biosci Biotechnol Biochem 74, 2096-2099 (2010).
13. Lopez, H.L., Habowski, S.M., Sandrock, J., A., K. & Ziegenfuss, J.Y. Effects of BioCell Collagen on connective tissue protection and functional recovery from exercise in healthy adults: a pilot study. Int J Radiat Oncol Biol Phys 11(Suppl 1), P48 (2014).
14. Schwartz, S.R. & Park, J. Ingestion of BioCell Collagen, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs. Clin Interv Aging 7, 267-273 (2012).
15. Schauss, A.G., Stenehjem, J., Park, J., Endres, J.R. & Clewell, A. Effect of the novel low molecular weight hydrolyzed chicken sternal cartilage extract, BioCell Collagen, on improving osteoarthritis-related symptoms: a randomized, double-blind, placebo-controlled trial. J Agric Food Chem 60, 4096-4101 (2012).
16. Benito-Ruiz, P. et al. A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. Int J Food Sci Nutr 60 Suppl 2, 99-113 (2009).
17. McAlindon, T.E. et al. Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. Osteoarthritis Cartilage 19, 399-405 (2011).
18. Wei, W. et al. A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther 11, R180 (2009).
19. Anderson, I. The properties of hyaluronan and its role in wound healing. Prof Nurse 17, 232-235 (2001).
20. Bannuru, R.R., Vaysbrot, E.E., Sullivan, M.C. & McAlindon, T.E. Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: a systematic review and meta-analysis. Semin Arthritis Rheum 43, 593-599 (2014).
21. Kalman, D.S., Heimer, M., Valdeon, A., Schwartz, H. & Sheldon, E. Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial. Nutr J 7, 3 (2008).
22. Nagaoka, I. et al. Evaluation of the effects of a supplementary diet containing chicken comb extract on symptoms and cartilage metabolism in patients with knee osteoarthritis. Exp Ther Med 1, 817-827 (2010).
23. Iovu, M., Dumais, G. & du Souich, P. Anti-inflammatory activity of chondroitin sulfate. Osteoarthritis Cartilage 16 Suppl 3, S14-18 (2008).
24. Zheng, C., Wei, J. & Lei, G. Is chondroitin sulfate plus glucosamine superior to placebo in the treatment of knee osteoarthritis? Ann Rheum Dis 74, e37 (2015).
25. Monfort, J. et al. Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled clinical trial. Arthr Rheum 65, 2146 (2015).
26. Jordan, K.M. et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis62, 1145-1155 (2003).