Collagen

Pronunciation

Collagen (kaw-lah-jen)

Summary

Collagen is found throughout the body in connective tissues and fibrous tissues including skin, bone, cartilage, tendons, ligaments, intervertebral discs, hair, cornea, blood vessels, and the reticular fibers of most organs (67). Collagen is built from peptide chains consisting of glycine and a combination of other amino acids, most commonly proline and hydroxyproline (69). Approximately 28 different kinds of collagens exist, but five of the most common types include type I (dermis, tendons, ligaments, bone), type II (cartilage, vitreous body, nucleus pulposus), type III (skin, vessel wall, reticular fibres), type IV (basal lamina, epithelial layer of basement membranes), and type V (lung, cornea, hair, fetal membranes, bones) (67). Type X collagen may have a role in bone health (65), particularly through the mineralization of cartilage in the subchondral bone (2). Supplements may contain collagen derived from bovine, porcine, marine and other sources (69), such as eggshell membranes (58).

Main Medical Uses

Evidence supports the use of collagen in treating conditions involving joint pain (11) including osteoarthritis (6, 9, 10, 11, 17, 19, 27, 41, 44, 53, 60), activity-related joint pain (15, 43, 58, 77), and rheumatoid arthritis (5, 6, 7, 8, 22, 73, 75, 78). It may be used in treating or preventing exercise-induced injury (64), osteoporosis (38, 53), type II diabetes (79, 80), and hypertension (39, 59). Evidence also supports its use to treat brittle nail syndrome (31) and a number of dermatological applications (14), including pressure ulcers (28, 40), edematous fibrosclerotic panniculopathy (cellulite) (61), and skin aging (3, 13, 32, 37 45, 50, 52, 55, 56, 66).

Collagen-guide-Fullscript

Dosing and Administration

For an explanation of the classes of evidence, please see the Rating Scales for Evidence-Based Decision Support.

Adverse Effects

Collagen supplements are generally considered as safe without the common occurrence of adverse effects (14, 41). Feelings of fullness or disagreeable taste have been reported in rare cases (48). To avoid the possibility of allergic reactions, consideration of the source of collagen may be required (57).

Forms

Collagen is extracted from the skins, bones, cartilage, and tendons of animal sources using hot water (e.g. above 40 degrees Celcius (26)), creating gelatin. Enzymes can hydrolyze gelatin into collagen hydrolysate which is the main form of collagen used in dietary supplements (70). Gelatin is derived from denatured and partially hydrolyzed collagen and has a molecular weight of 100kDa (68). It can be further refined by proteinases into collagen peptides with molecular weights between 0.3-8kDa. The lower molecular weight of hydrolyzed collagen ultimately provides advantages in absorption and distribution compared to native collagen (67).

Collagen is made up of several amino acids, which may affect its absorption and bioactivity (26). Hydrolysates consist primarily of glycine (GLY), proline (PRO), hydroxyproline (HYP), glutamic acid (GLU), arginine (ARG), alanine (ALA), as well as other essential and non-essential amino acids (66), such as aspartic acid (ASP), threonine (THR), serine (SER), cysteine (CYS), valine (VAL), methionine (MET), isoleucine (ILE), leucine (LEU), tyrosine (TYR), phenylalanine (PHE), lysine (LYS), and histidine (HIS) (72).

Associated Interactions & Depletions

Despite evidence for the effectiveness of collagen supplementation in rheumatoid arthritis, some trials report no effect of bovine Type II supplementation in rheumatoid arthritis when added to existing medication (i.e.. methotrexate, hydroxychloroquine, gold sodium thio-glucose or gold sodium thiomalate, sulfasalazine, azathioprine, auranofin, D-penicillamine, or prednisone) (46). Additionally, chicken-derived Type II collagen supplementation may not maintain methotrexate’s anti-inflammatory effects (29), though it may induce fewer adverse events (78).

Pharmacokinetics

Absorption

Similarly to other proteins, collagen hydrolysates are degraded in the digestive tract and are mostly absorbed as amino acids, dipeptides, and tripeptides (76) via the brush-border membrane using the H+-coupled peptide transporter, PEPT1. Subsequently, they enter the bloodstream by crossing the basolateral membrane (66). Ingestion in tripeptide form may improve absorption efficiency in humans (76).

Distribution

The collagen hydrolysate peptide, PRO-HYP, has been shown to be distributed to the skin, cartilage, and bone marrow in its intact form, with its highest concentration in gastric and intestinal walls (36).

Synthesis

Metabolism

The liver metabolizes collagen peptides, though many HYP-containing peptides (some of which can be larger than tripeptides) can pass through the liver to enter systemic circulation (51).

Excretion

If not reabsorbed by PEPT1 and PEPT2 (36), collagen hydrolysate peptides can be excreted in the urine after ingestion (76).

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  1. Albaugh, V. L., Mukherjee, K., & Barbul, A. (2017). Proline precursors and collagen synthesis: Biochemical challenges of nutrient supplementation and wound healing. The Journal of Nutrition,147(11), 2011-2017.
  2. Armiento, A. R., Alini, M., & Stoddart, M. J. (2018). Articular fibrocartilage – Why does hyaline cartilage fail to repair? Advanced Drug Delivery Reviews,1-17.
  3. Asserin, J., Lati, E., Shioya, T., & Prawitt, J. (2015). The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: Evidence from an ex vivo model and randomized, placebo-controlled clinical trials. Journal of Cosmetic Dermatology,14(4), 291-301.
  4. Atayde, S. R., Velosa, A. P., Catanozi, S., Bianco, V. D., Andrade, P. C., José Eduardo De Castro M. Rodrigues, . . . Teodoro, W. R. (2018). Collagen V oral administration decreases inflammation and remodeling of synovial membrane in experimental arthritis. Plos One,13(7).
  5. Ausar, S. F., Beltramo, D. M., Castagna, L. F., Quintana, S., Silvera, E., Kalayan, G., … Bianco, I. D. (2001). Treatment of rheumatoid arthritis by oral administration of bovine tracheal type II collagen. Rheumatology International,20(4), 138-144.
  6. Bagchi, D., Misner, B., Bagchi, M., Kothari, S. C., Downs, B. W., Fafard, R. D., & Preuss, H. G. (2002). Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: A mechanistic exploration. International Journal of Clinical Pharmacology Research,22(3-4), 101-110.
  7. Barnett, M. L., Combitchi, D., & Trentham, D. E. (1996). A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis. Arthritis & Rheumatism,39(4), 623-628.
  8. Barnett, M. L., Kremer, J. M., Clair, E. W., Clegg, D. O., Furst, D., Weisman, M., . . . Trentham, D. E. (1998). Treatment of rheumatoid arthritis with oral type II collagen: Results of a multicenter, double-blind, placebo-controlled trial. Arthritis & Rheumatism,41(2), 290-297.
  9. Bello, A. E., & Oesser, S. (2006). Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders:a review of the literature. Current Medical Research and Opinion,22(11), 2221-2232.
  10. Benito-Ruiz, P., Camacho-Zambrano, M., Carrillo-Arcentales, J., Mestanza-Peralta, M., Vallejo-Flores, C., Vargas-López, S., . . . Zurita-Gavilanes, L. (2009). A randomized controlled trial on the efficacy and safety of a food ingredient, collagen hydrolysate, for improving joint comfort. International Journal of Food Sciences and Nutrition,60(2), 99-113.
  11. Brunello, E., & Masini, A. (2016). NEM brand eggshell membrane effective in the treatment of pain and stiffness associated with osteoarthritis of the knee in an Italian study population. International Journal of Clinical Medicine,07(02), 169-175.
  12. Bruyère, O., Zegels, B., Leonori, L., Rabenda, V., Janssen, A., Bourges, C., & Reginster, J. (2012). Effect of collagen hydrolysate in articular pain: A 6-month randomized, double-blind, placebo controlled study. Complementary Therapies in Medicine,20(3), 124-130.
  13. Choi, S. Y., Ko, E. J., Lee, Y. H., Kim, B. G., Shin, H. J., Seo, D. B., . . . Kim, M. N. (2013). Effects of collagen tripeptide supplement on skin properties: A prospective, randomized, controlled study. Journal of Cosmetic and Laser Therapy,16(3), 132-137.
  14. Choi, F. D., Sung, C. T., Juhasz, M. L., & Mesinkovsk, N. A. (2019). Oral collagen supplementation: A systematic review of dermatological applications. Journal of Drugs in Dermatology,18(1), 9-16.
  15. Clark, K. L., Sebastianelli, W., Flechsenhar, K. R., Aukermann, D. F., Meza, F., Millard, R. L., . . . Albert, A. (2008). 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Current Medical Research and Opinion,24(5), 1485-1496.
  16. Coleman, S., Nixon, J., Keen, J., Wilson, L., McGinnis, E., Dealey, C., … Nelson, A. (2014). A new pressure ulcer conceptual framework. Journal of Advanced Nursing,70(10), 2222-2234.
  17. Crowley, D. C., Lau, F. C., Sharma, P., Evans, M., Guthrie, N., Bagchi, M., . . . Raychaudhuri, S. P. (2009). Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: A clinical trial. International Journal of Medical Sciences,6(6), 312-321.
  18. Curtis, E. M., Moon, R. J., Dennison, E. M., Harvey, N. C., & Cooper, C. (2016). Recent advances in the pathogenesis and treatment of osteoporosis. Clinical Medicine,16(4), 360-364.
  19. Danesch, U., Seybold, M., Rittinghausen, R., Treibel, W., & Bitterlich, N. (2014). NEM brand eggshell membrane effective in the treatment of pain associated with knee and hip osteoarthritis: Results from a six center, open label german clinical study. Journal of Arthritis,3(3), 1-5.
  20. Dar, Q., Schott, E. M., Catheline, S. E., Maynard, R. D., Liu, Z., Kamal, F., . . . Zuscik, M. J. (2017). Daily oral consumption of hydrolyzed type 1 collagen is chondroprotective and anti-inflammatory in murine posttraumatic osteoarthritis. Plos One,12(4).
  21. Demarco, V. G., Aroor, A. R., & Sowers, J. R. (2014). The pathophysiology of hypertension in patients with obesity. Nature Reviews Endocrinology,10(6), 364-376.
  22. Farboud, A., & Choy, E. (2010). Serological investigation of IgG levels and subclasses in rheumatoid arthritis patients following ingestion of bovine type II collagen: Results of a double blind, randomised controlled trial. Clinical Rheumatology,30(2), 193-199.
  23. Feng, M., & Betti, M. (2017). Transepithelial transport efficiency of bovine collagen hydrolysates in a human Caco-2 cell line model. Food Chemistry,224, 242-250.
  24. Firestein, G. S., & Mcinnes, I. B. (2017). Immunopathogenesis of rheumatoid arthritis. Immunity,46(2), 183-196.
  25. Friedmann, D., Vick, G., & Mishra, V. (2017). Cellulite: A review with a focus on subcision. Clinical, Cosmetic and Investigational Dermatology,10, 17-23.
  26. Fu, Y., Therkildsen, M., Aluko, R. E., & Lametsch, R. (2018). Exploration of collagen recovered from animal by-products as a precursor of bioactive peptides: Successes and challenges. Critical Reviews in Food Science and Nutrition,1-17.
  27. García-Coronado, J. M., Martínez-Olvera, L., Elizondo-Omaña, R. E., Acosta-Olivo, C. A., Vilchez-Cavazos, F., Simental-Mendía, L. E., & Simental-Mendía, M. (2018). Effect of collagen supplementation on osteoarthritis symptoms: A meta-analysis of randomized placebo-controlled trials. International Orthopaedics,43(3), 531-538.
  28. Graumlich, J. F., Blough, L. S., Mclaughlin, R. G., Milbrandt, J. C., Calderon, C. L., Agha, S. A., & Scheibel, L. W. (2003). Healing pressure ulcers with collagen or hydrocolloid: A randomized, controlled trial. Journal of the American Geriatrics Society,51(2), 147-154.
  29. Hauselmann, H., Caravatti, M., Siefert, B., Wang, K., Bruckner, P., Stucki, G., & Michel, B. A. (1998). Can collagen type II sustain a methotrexate-induced therapeutic effect in patients with long-standing rheumatoid arthritis? A double-blind, randomized trial. British Journal of Rheumatology,37(11), 1110-1117.
  30. Henrotin, Y., Labasse, A., Franck, T., Bosseloir, A., Bury, T., & Deberg, M. (2013). Collagen catabolism through Coll2-1 and Coll2-1NO2 and myeloperoxidase activity in marathon runners. SpringerPlus,2(1), 92.
  31. Hexsel, D., Zague, V., Schunck, M., Siega, C., Camozzato, F. O., & Oesser, S. (2017). Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails. Journal of Cosmetic Dermatology,16(4), 520-526.
  32. Inoue, N., Sugihara, F., & Wang, X. (2016). Ingestion of bioactive collagen hydrolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double-blind placebo-controlled clinical study. Journal of the Science of Food and Agriculture,96(12), 4077-4081.
  33. Iwai, K., Zhang, Y., Kouguchi, T., Saiga-Egusa, A., Shimizu, M., Ohmori, T., . . . Morimatsu, F. (2009). Blood concentration of food-derived peptides following oral intake of chicken collagen hydrolysate and its angiotensin-converting enzyme inhibitory activity in healthy volunteers. Nippon Shokuhin Kagaku Kogaku Kaishi,56(6), 326-330.
  34. Kahn, S. E., Cooper, M. E., & Prato, S. D. (2014). Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future. The Lancet,383(9922), 1068-1083.
  35. Kallis, P. J., & Friedman, A. J. (2018). Collagen powder in wound healing. Journal of Drugs in Dermatology,17(4), 403-408.
  36. Kawaguchi, T., Nanbu, P. N., & Kurokawa, M. (2012). Distribution of prolylhydroxyproline and its metabolites after oral administration in rats. Biological and Pharmaceutical Bulletin,35(3), 422-427.
  37. Kim, D., Chung, H., Choi, J., Sakai, Y., & Lee, B. (2018). Oral intake of low-molecular-weight collagen peptide improves hydration, elasticity, and wrinkling in human skin: A randomized, double-blind, placebo-controlled study. Nutrients,10(7), 826.
  38. König, D., Oesser, S., Scharla, S., Zdzieblik, D., & Gollhofer, A. (2018). Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women—A randomized controlled study. Nutrients,10(1), 97.
  39. Kouguchi, T., Ohmori, T., Shimizu, M., Takahata, Y., Maeyama, Y., Suzuki, T., . . . Tanabe, S. (2013). Effects of a chicken collagen hydrolysate on the circulation system in subjects with mild hypertension or high-normal blood pressure. Bioscience, Biotechnology, and Biochemistry,77(4), 691-696.
  40. Lee, S. K., Posthauer, M. E., Dorner, B., Redovian, V., & Maloney, M. J. (2006). Pressure ulcer healing with a concentrated, fortified, collagen protein hydrolysate supplement. Advances in Skin & Wound Care,19(2), 92-96.
  41. Liu, X., Machado, G., Eyles, J., Ravi, V., & Hunter, D. (2018). Dietary supplements for treating osteoarthritis: A systematic review and meta-analysis. British Journal of Sports Medicine,52, 1-10.
  42. Liu, J., Zhang, B., Song, S., Ma, M., Si, S., Wang, Y., . . . Guo, Y. (2014). Bovine Collagen Peptides Compounds Promote the Proliferation and Differentiation of MC3T3-E1 Pre-Osteoblasts. PLoS ONE,9(6).
  43. Lugo, J. P., Saiyed, Z. M., Lau, F. C., Molina, J. P., Pakdaman, M. N., Shamie, A., & Udani, J. K. (2013). Undenatured type II collagen (UC-II®) for joint support: A randomized, double-blind, placebo-controlled study in healthy volunteers. Journal of the International Society of Sports Nutrition,10(1), 48.
  44. Lugo, J. P., Saiyed, Z. M., & Lane, N. E. (2015). Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: A multicenter randomized, double-blind, placebo-controlled study. Nutrition Journal,15(1).
  45. Matsumoto, H., Ohara, H., Ito, K., Nakamura, Y., & Takahashi, S. (2006). Clinical effects of fish type I collagen hydrolysate on skin properties. ITE Letters on Batteries, New Technologies & Medicine,7(4).
  46. Mckown, K. M., Carbone, L. D., Kaplan, S. B., Aelion, J. A., Lohr, K. M., Cremer, M. A., . . . Postlethwaite, A. E. (2001). Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid arthritis. Arthritis & Rheumatism,42(6), 1204-1208.
  47. Mobasheri, A., & Batt, M. (2016). An update on the pathophysiology of osteoarthritis. Annals of Physical and Rehabilitation Medicine,59(5-6), 333-339.
  48. Moskowitz, R. W. (2000). Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis and Rheumatism,30(2), 87-99.
  49. Ohara, H., Matsumoto, H., Ito, K., Iwai, K., & Sato, K. (2007). Comparison of quantity and structures of hydroxyproline-containing peptides in human blood after oral ingestion of gelatin hydrolysates from different sources. Journal of Agricultural and Food Chemistry,55(4), 1532-1535.
  50. Ohara, H., Ito, K., Iida, H., & Matsumoto, H. (2009). Improvement in the moisture content of the stratum corneum following 4 weeks of collagen hydrolysate ingestion. Nippon Shokuhin Kagaku Kogaku Kaishi,56(3), 137-145.
  51. Osawa, Y., Mizushige, T., Jinno, S., Sugihara, F., Inoue, N., Tanaka, H., & Kabuyama, Y. (2018). Absorption and metabolism of orally administered collagen hydrolysates evaluated by the vascularly perfused rat intestine and liver in situ. Biomedical Research,39(1), 1-11.
  52. Park, J., & Schwartz, S. R. (2012). Ingestion of BioCell Collagen, a novel hydrolyzed chicken sternal cartilage extract; enhanced blood microcirculation and reduced facial aging signs. Clinical Interventions in Aging,7, 267-273.
  53. Porfírio, E., & Fanaro, G. B. (2016). Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: A systematic review. Revista Brasileira De Geriatria E Gerontologia,19(1), 153-164.
  54. Praet, S. F., Purdam, C. R., Welvaert, M., Vlahovich, N., Lovell, G., Burke, L. M., . . . Waddington, G. (2019). Oral supplementation of specific collagen peptides combined with calf-strengthening exercises enhances function and reduces pain in Achilles tendinopathy patients. Nutrients,11(1), 76.
  55. Proksch, E., Schunck, M., Zague, V., Segger, D., Degwert, J., & Oesser, S. (2014). Oral intake of specific bioactive collagen peptides reduces skin wrinkles and increases dermal matrix synthesis. Skin Pharmacology and Physiology,27(3), 113-119.
  56. Proksch, E., Segger, D., Degwert, J., Schunck, M., Zague, V., & Oesser, S. (2014). Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: A double-blind, placebo-controlled study. Skin Pharmacology and Physiology,27(1), 47-55.
  57. Ruff, K. J., Winkler, A., Jackson, R. W., Devore, D. P., & Ritz, B. W. (2009). Eggshell membrane in the treatment of pain and stiffness from osteoarthritis of the knee: A randomized, multicenter, double-blind, placebo-controlled clinical study. Clinical Rheumatology,28(8), 907-914.
  58. Ruff, K. J., Morrison, D., Duncan, S. A., Back, M., Aydogan, C., & Theodosakis, J. (2018). Beneficial effects of natural eggshell membrane versus placebo in exercise-induced joint pain, stiffness, and cartilage turnover in healthy, postmenopausal women. Clinical Interventions in Aging,13, 285-295.
  59. Saiga-Egusa, A., Iwai, K., Hayakawa, T., Takahata, Y., & Morimatsu, F. (2009). Antihypertensive effects and endothelial progenitor cell activation by intake of chicken collagen hydrolysate in pre- and mild-hypertension. Bioscience, Biotechnology, and Biochemistry,73(2), 422-424.
  60. Schauss, A. G., Stenehjem, J., Park, J., Endres, J. R., & Clewell, A. (2012). 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. Journal of Agricultural and Food Chemistry,60(16), 4096-4101.
  61. Schunck, M., Zague, V., Oesser, S., & Proksch, E. (2015). Dietary supplementation with specific collagen peptides has a body mass index-dependent beneficial effect on cellulite morphology. Journal of Medicinal Food,18(12), 1340-1348.
  62. Scott, A., Backman, L. J., & Speed, C. (2015). Tendinopathy: Update on pathophysiology. Journal of Orthopaedic & Sports Physical Therapy,45(11), 833-841.
  63. Shakibaei, M., Buhrmann, C., & Mobasheri, A. (2011). Anti-inflammatory and anti-catabolic effects of TENDOACTIVE® on human tenocytes in vitro. Histology and Histopathology,26(9), 1173-1185.
  64. Shaw, G., Lee-Barthel, A., Ross, M. L., Wang, B., & Baar, K. (2016). Vitamin C–enriched gelatin supplementation before intermittent activity augments collagen synthesis. The American Journal of Clinical Nutrition,105(1), 136-143.
  65. Shen, G. (2005). The role of type X collagen in facilitating and regulating endochondral ossification of articular cartilage. Orthodontics and Craniofacial Research,8(1), 11-17.
  66. Sibilla, S., & Borumand, M. (2014). Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging. Clinical Interventions in Aging,9, 1747-1758.
  67. Sibilla, S., Godfrey, M., Brewer, S., Budh-Raja, A., & Genovese, L. (2015). An overview of the beneficial effects of hydrolysed collagen as a nutraceutical on skin properties: Scientific background and clinical studies. The Open Nutraceuticals Journal,8(1), 29-42.
  68. Silva, S. A., Michniak-Kohn, B., & Leonardi, G. R. (2017). An overview about oxidation in clinical practice of skin aging. Anais Brasileiros De Dermatologia,92(3), 367-374.
  69. Silvipriya, K., Kumar, K., Bhat, A., Kumar, B., John, A., & Lakshmanan, P. (2015). Collagen: Animal sources and biomedical application. Journal of Applied Pharmaceutical Science,5(3), 123-127.
  70. Song, H., & Li, B. (2017). Beneficial effects of collagen hydrolysate: A review on recent developments. Biomedical Journal of Scientific & Technical Research,1(2), 1-4.
  71. Song, H., Meng, M., Cheng, X., Li, B., & Wang, C. (2017). The effect of collagen hydrolysates from silver carp (Hypophthalmichthys molitrix) skin on UV-induced photoaging in mice: Molecular weight affects skin repair. Food & Function,8(4), 1538-1546.
  72. Sun, L., Chang, W., Ma, Q., & Zhuang, Y. (2016). Purification of antioxidant peptides by high resolution mass spectrometry from simulated gastrointestinal digestion hydrolysates of alaska pollock (Theragra chalcogramma) skin collagen. Marine Drugs,14(10), 186.
  73. Trentham, D., Dynesius-Trentham, R., Orav, E., Combitchi, D., Lorenzo, C., Sewell, K., . . . Weiner, H. (1993). Effects of oral administration of type II collagen on rheumatoid arthritis. Science,261(5129), 1727-1730.
  74. Wang, L., Wang, Q., Liang, Q., He, Y., Wang, Z., He, S., . . . Ma, H. (2014). Determination of bioavailability and identification of collagen peptide in blood after oral ingestion of gelatin. Journal of the Science of Food and Agriculture,95(13), 2712-2717.
  75. Wei, W., Zhang, L., Xu, J., Xiao, F., Bao, C., Ni, L., . . . Wang, R. (2009). A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Research & Therapy,11(6), R180.
  76. Yamamoto, S., Deguchi, K., Onuma, M., Numata, N., & Sakai, Y. (2016). Absorption and urinary excretion of peptides after collagen tripeptide ingestion in humans. Biological & Pharmaceutical Bulletin Biological and Pharmaceutical Bulletin,39(3), 428-434.
  77. Zdzieblik, D., Oesser, S., Gollhofer, A., & König, D. (2017). Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides. Applied Physiology, Nutrition, and Metabolism,42(6), 588-595.
  78. Zhang, L., Wei, W., Xiao, F., Xu, J., Bao, C., Ni, L., & Li, X. (2008). A randomized, double‐blind, multicenter, controlled clinical trial of chicken type II collagen in patients with rheumatoid arthritis. Arthritis & Rheumatism,59(7), 905-910.
  79. Zhu, C., Li, G., Peng, H., Zhang, F., Chen, Y., & Li, Y. (2010). Effect of marine collagen peptides on markers of metabolic nuclear receptors in type 2 diabetic patients with/without hypertension. Biomedical and Environmental Sciences,23(2), 113-120.
  80. Zhu, C., Li, G., Peng, H., Zhang, F., Chen, Y., & Li, Y. (2010). Treatment with marine collagen peptides modulates glucose and lipid metabolism in Chinese patients with type 2 diabetes mellitus. Applied Physiology, Nutrition, and Metabolism,35(6), 797-804.