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What is it?

Description

Collagen is used to form connective tissues, including skin, bone, cartilage, tendons, ligaments, hair, and nails, and is built from peptide chains consisting of glycine and a combination of other amino acids, most often proline and hydroxyproline. (35) The five most common types of collagen include Type I (dermis, tendon, ligaments, bone), Type II (cartilage, vitreous body, nucleus pulposus), Type III (skin, vessel wall, reticular fibers), Type IV (basal lamina, epithelial layer of basement membranes), Type V (lung, cornea, hair, fetal membranes, bones). (34) Type X collagen may have a role in bone health, (33) particularly through the mineralization of cartilage in the subchondral bone. (1) Supplements may contain collagen derived from bovine, porcine, marine, fish, and other sources, (35) such as eggshell membranes. (28)

Not be confused with: Colostrum

Main uses

Joint pain and inflammatory disorders
Skin, bone, and tissue repair
Other cardiovascular and endocrine applications

Formulations

Form
Bioavailability
Collagen hydrolysate
Lower molecular weight increases plasma hydroxyproline concentrations more than gelatin sourced from fish skin (37)
Gelatin hydrolysate
Fish derived collagen sources seem to increase plasma amino acids to a greater extent than porcine or chicken sources. (10)(24)
This may be due to the lower relative molecular weight of derived peptides compared with other animal sources. (17)
Undenatured collagen
Lesser GI transport efficiency and digestion than hydrolyzed collagen due to lower molecular weight as shown in vitro. (9)
Used in milligram doses compared with gram doses of gelatin or collagen hydrolysate. (8)(20)(32)

Dosing & administration

Adverse effects

Collagen supplements are generally considered as safe without the common occurrence of adverse effects. (7)(19) Feelings of fullness or disagreeable taste have been reported in rare cases. (22) To avoid the possibility of allergic reactions, consideration of the source of collagen may be required. (29)

Pharmacokinetics

Absorption

  • Collagen hydrolysates are degraded in the digestive tract and are mostly absorbed as amino acids, dipeptides, and tripeptides. (40) 
  • Absorbed via the brush-border membrane using the H+-coupled peptide transporter, PEPT1. (5)
  • Ingestion in tripeptide form may improve absorption efficiency in humans. (40)

Distribution

  • The collagen hydrolysate peptide, PRO-HYP, is distributed to the skin, cartilage, and bone marrow in its intact form, with its highest concentration in gastric and intestinal walls. (12)

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. (25)

Excretion

  • If not reabsorbed by PEPT1 and PEPT2, (12) collagen hydrolysate peptides can be excreted in the urine after ingestion. (40)
References
  1. Armiento, A. R., Alini, M., & Stoddart, M. J. (2018). Articular fibrocartilage - Why does hyaline cartilage fail to repair? Advanced Drug Delivery Reviews, 1-17. ()
  2. 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. ()
  3. 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. ()
  4. 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. ()
  5. Borumand, M. & Sibilla, S. (2014). Daily consumption of the collagen supplement Pure Gold Collagen® reduces visible signs of aging. Clinical Interventions in Aging,9, 1747-1758. ()
  6. 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. ()
  7. 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. ()
  8. 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. ()
  9. 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. ()
  10. 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. ()
  11. 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. ()
  12. 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. ()
  13. 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. ()
  14. 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. ()
  15. 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. ()
  16. 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. ()
  17. León-López, A., Morales-Peñaloza, A., Martínez-Juárez, V. M., Vargas-Torres, A., Zeugolis, D. I., & Aguirre-Álvarez, G. (2019). Hydrolyzed Collagen—Sources and Applications. Molecules, 24(22), 4031. ()
  18. Lis, D. M., & Baar, K. (2019). Effects of different vitamin C–enriched collagen derivatives on collagen synthesis. International journal of sport nutrition and exercise metabolism, 29(5), 526-531. ()
  19. 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. ()
  20. 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). ()
  21. 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. ()
  22. Moskowitz, R. W. (2000). Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis and Rheumatism,30(2), 87-99. ()
  23. 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. ()
  24. 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. ()
  25. 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 ()
  26. 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. ()
  27. Proksch, E., Segger, D., Degwert, J., Schunck, M., Zague, V., & Oesser, S. (2013). 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. ()
  28. 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. ()
  29. 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. ()
  30. 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. ()
  31. 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. ()
  32. 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. ()
  33. 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. ()
  34. 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. ()
  35. 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. ()
  36. 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. ()
  37. 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. ()
  38. 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. ()
  39. 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. ()
  40. 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. ()
  41. 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. ()
  42. 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. ()
  43. 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. ()
  44. 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. ()

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