Ingredient review —Collagen
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
Dosing & administration
Cellulite
General outcomes from A-level evidence
No data currently available.
Dosing & administration
2.5 g (as porcine derived bioactive collagen peptides, Type I collagen, Verisol®) per day for 6 months
Outcomes
degree of cellulite and skin waviness
dermal density
Effects observed to greater extent in subjects with normal BMI compared with higher BMI (31)
Class of evidence
b
Hypertension
General outcomes from A-level evidence
No data currently available.
Dosing & administration
2.9 g per day (as chicken derived collagen hydrolysate) for 12 weeks
Outcomes
systolic BP, trending decrease in diastolic BP, brachial-ankle pulse wave velocity
serum NO (15)
Class of evidence
b
Injury prevention/tissue repair
General outcomes from A-level evidence
No data currently available.
Dosing & administration
5 g or 15 g gelatin (enriched with 48 mg vit C) three times per day, 1 hour before exercise for 3 days
Outcomes
serum glycine, proline, hydroxyproline and hydroxylysine (1 hour peak)
collagen and mechanics in blood-treated ligaments
15 g doubled collagen I propeptide (32)
Class of evidence
c
Dosing & administration
Vitamin C enriched 15 g gelatin, hydrolyzed collagen or gummy (equal gelatin/collagen content), 1 hour prior to exercise
Outcomes
amino acids in each group, procollagen I N-terminal peptide in gelatin & collagen group
Low number of subjects & large variability caused to significant differences (18)
Class of evidence
c
Joint pain & exercise induced joint pain
General outcomes from A-level evidence
No data currently available.
Dosing & administration
1.2 g (as bovine derived collagen hydrolysate, AminoLock®) per day for 6 months
Outcomes
pain via VAS score (6)
Class of evidence
b
Dosing & administration
40 mg (as chicken derived undenatured type II collagen, UC-II®) per day for 120 days
Outcomes
knee extension compared to placebo & baseline, exercise time before joint pain (21)
Class of evidence
b
Dosing & administration
10 g (as collagen hydrolysate, CH-alpha®) per day for 24 weeks
Outcomes
joint pain while resting, walking, standing, carrying objects, & lifting.
Effect greater in patients with arthralgia who also had less pain while running and changing direction (8)
Class of evidence
b
Dosing & administration
5 g (as bioactive collagen peptides, Fortigel®) per day for 12 weeks
Outcomes
activity-related pain intensity (41)
Class of evidence
b
Dosing & administration
500 mg (derived from egg shell membrane, NEM®) per day for 2 weeks
Outcomes
the biomarker C-terminal cross-linked telopeptide of type-II collagen (CTX-II), immediate stiffness, recovery pain & recovery stiffness (28)
Class of evidence
b
Osteoarthritis
General outcomes from A-level evidence
No data currently available.
Dosing & administration
40 mg (as chicken-derived cartilage, undenatured Type II collagen, UC-II®) per day for 180 days
Outcomes
overall WOMAC score, & subscales for pain, stiffness & physical function in the knee (20)
Class of evidence
b
Dosing & administration
10 g (as collagen hydrolysate) per day for 6 months
Outcomes
knee joint discomfort via VAS & WOMAC scales (4)
Class of evidence
b
Dosing & administration
500 mg (derived from eggshell membrane, NEM®) per day for 8 weeks
Outcomes
knee pain and stiffness (29)
Class of evidence
b
Dosing & administration
2 g (as chicken derived hydrolyzed collagen Type II, BioCell®) per day for 70 days
Outcomes
VAS pain & WOMAC scores, & difficulty of physical activity (30)
Class of evidence
b
Osteoporosis prevention
General outcomes from A-level evidence
No data currently available.
Dosing & administration
5 g (as bioactive collagen peptides, Fortibone®) per day for 12 months
Outcomes
spine and neck bone mineral density, N-terminal propeptide of type I collagen (P1NP) (14)
Class of evidence
b
Pressure ulcers
General outcomes from A-level evidence
No data currently available.
Dosing & administration
15 g (as collagen protein hydrolysate) three times per day for 8 weeks
Outcomes
ulcer healing as measured by PUSH tool scores (16)
Class of evidence
b
Rheumatoid arthritis
General outcomes from A-level evidence
No data currently available.
Dosing & administration
0.1 mg per day for 1 month, then 0.5 mg for 2 months (as chicken derived Type II hydrolyzed collagen)
Outcomes
swollen and tender joint frequency (38)
Class of evidence
b
Dosing & administration
0.02 mg, 0.1 mg, 0.5 mg, or 2.5 mg (as chicken derived Type II collagen) for 24 weeks. Patients allowed to maintain NSAID/steroid usage
Outcomes
Paulus criteria with 0.02 mg, with trend of decreasing scores with higher doses for Paulus & ACR criteria, & swollen/tender joints (3)
Class of evidence
b
Dosing & administration
0.1 mg (as chicken derived Type II collagen) per day for 24 weeks
Outcomes
pain, morning stiffness duration, tender & swollen joint count, HAQ & efficacy scores. 68.57% & 40.95% patients met ACR20 & ACR50 criteria. MTX more effective in all measures, but had more adverse events (42)
Class of evidence
b
Dosing & administration
0.1 mg (as chicken derived Type II collagen) per day for 24 weeks)
Outcomes
All results same as above but 41.55% & 16.89% patients met ACR20 & ACR50 criteria (39)
Class of evidence
b
Skin aging
General outcomes from A-level evidence
No data currently available.
Dosing & administration
5 g per day (as fish cartilage Type I hydrolyzed collagen, Pure Gold Collagen®) for 8 weeks
Outcomes
dry skin, wrinkles, nasolabial fold depth
collagen density, skin firmness (5)
Class of evidence
b
Dosing & administration
10 g per day (fish-derived collagen peptides, Peptan®) for 8 weeks
Outcomes
collagen density, collagen fragment size
collagen fragmentation (2)
Class of evidence
b
Dosing & administration
2.5 g per day (as porcine-derived bioactive collagen peptides, Verisol® Type I collagen) for 8 weeks
Outcomes
eye wrinkle volume by 20%, and by 11.5% 4 weeks after end of treatmen
procollagen type I & elastin content by 65% & 18%, respectively (26)
Class of evidence
b
Dosing & administration
2.5 g, 5 g & 10 g (as scaled collagen hydrolysate), or 10 g (as pig skin collagen hydrolysate) per day for 4 weeks
Outcomes
skin moisture in a dose dependent manner.
Significant difference between 5.0 g and 10.0 g at ages >30 (23)
Class of evidence
b
Dosing & administration
2.5 g or 5 g (as porcine Type I collagen hydrolysate, Verisol®) per day for 8 weeks
Outcomes
skin elasticity, no difference between doses. Greatest effect on ages > 50 (27)
Class of evidence
b
Dosing & administration
5 g (as fish derived collagen hydrolysate either as high or low dipeptide to product ratio) per day for 8 weeks
Outcomes
skin moisture & elasticity
wrinkles & roughness in supplement with higher Pro-Hyp and Hyp-Gly compared to lower and placebo (11)
Class of evidence
b
Dosing & administration
1 g (fish derived Type I collagen hydrolysate) per day for 12 weeks
Outcomes
skin moisture, elasticity
wrinkles (13)
Class of evidence
b
Dosing & administration
10 g per day (fish derived, or porcine derived collagen peptides, Peptan®) for 8 weeks
Outcomes
skin moisture (12% fish, 28% porcine) (2)
Class of evidence
c
Type II diabetes
General outcomes from A-level evidence
No data currently available.
Dosing & administration
6.5 g (as marine collagen peptides) twice per day for 3 months
Outcomes
FBG, GHbA1C, fasting blood insulin, total TGs, total cholesterol, LDL & free fatty acids, hs-CRP, NO
insulin sensitivity, HDL, bradykinin, PGI2 & adiponectin (44)
Class of evidence
b
Dosing & administration
6.5 g (as marine collagen peptides) twice per day for 3 months
Outcomes
free fatty acids, hs-CRP, resistin & prostacyclin
tendency in CYP450, leptin & NO
adiponectin & bradykinin (43)
Class of evidence
b
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)
References
- Armiento, A. R., Alini, M., & Stoddart, M. J. (2018). Articular fibrocartilage - Why does hyaline cartilage fail to repair? Advanced Drug Delivery Reviews, 1-17. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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). ()
- 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. ()
- Moskowitz, R. W. (2000). Role of collagen hydrolysate in bone and joint disease. Seminars in Arthritis and Rheumatism,30(2), 87-99. ()
- 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. ()
- 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. ()
- 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 ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()
- 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. ()