Collagen Research

Collagen and the human body, hydrolyzed collagen and supplementation


Collagen is the most important protein produced by the human body. As the main component of connective tissue, it is the most abundant protein in humans, accounting for approximately one third of the total protein mass. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Depending upon the degree of mineralization, collagen tissues may be rigid (bone), compliant (tendon) or more gradient (cartilage). The role of collagen in the human body is very important because it helps in the development of the organs, the healing of wounds and tissue, and, the repair of cornea, gums, and scalp. Collagen also helps in bone and blood vessel reparation. In the cornea, collagen tissue gets mechanical and optical properties. It is present in biological functions of the cell such as proliferation, cell survival, and differentiation. So, collagen is present in the human body as a whole in bones, tendons, ligament, hair, skin, and muscles. 

Nearly 28 types of collagen have been identified, but collagen type I is the most common in skin, bone, teeth, tendon, ligaments, vascular ligature, and organs. 90% of collagen in the human body is type I collagen. Collagen type II is present in the cartilages. For collagen type III, the skin, muscle, and blood vessels are the most common sources of this protein. Type IV has been reported in the epithelium-secreted layer of the basement membrane and the basal lamina. Collagen type V is one of the principal components of cell surfaces and placenta.

As all proteins, collagen is composed of amino acids. The amino acid composition of collagen is a characteristic feature of this protein, containing 19 amino acids, including hydroxyproline (which does not occur in other proteins). Its atypical amino acid composition is characterized by a high content of hydroxyproline, proline and glycine.1 2 3 

Collagen is the major insoluble fibrous protein found in the extracellular matrix of the skin (together with elastin and hyaluronic acid), giving support to the structure of the skin. Healthy levels of collagen are necessary for a healthy skin and to preserve skin firmness and elasticity. Type I collagen is the main component of human skin (approx. 80%) with collagen type III making up the remainder of skin collagen (approx. 15%). Collagen is mainly produced by fibroblasts in the connective tissues - a type of mesenchymal cells mostly located in the dermis of the skin. With age, the ability to replenish collagen naturally decreases as fibroblasts become less active and production decreases. Aging is a natural process which involves changes in the human body, including the decline of collagen.4 5

Thus as we age, we lose collagen. Collagen loss in the body starts at 18–29 years of age, after 40 years the human body can lose around 1% per year, and at around 80 years collagen production in the body can decrease 75% overall in comparison to that of young adults. Collagen loss has very observable consequences to the skin - the largest organ in the human body, responsible for, protecting the organism from external damages, regulating temperature and performing other bodily functions.

Collagen and elastic fibers and hyaluronic acid are the skin's major structural constituents. Because of aging and the loss of collagen, the skin suffers morphologic, structural, and functional deterioration, which results in a.o. the formation of lines and wrinkles. It can be aggravated by certain lifestyle choices like smoking and external factors like sun exposure. There are also other factors contributing to this such as free radicals in the organism, deficient diet, alcoholism, and disease.6 7 8

To compensate collagen loss due to aging, it is possible to take collagen (based) supplements. Supplementation is most effective in the form collagen peptides (i.e. hydrolyzed collagen). Collagen peptides are short chains of amino acids extracted from collagen via a process called enzymatic hydrolysis (also enzymatic hydrolyzation).

Collagen peptides, whether orally ingested or topically administered, have shown to have positive effects on human health and beauty. Collagen for humans is vital for the elasticity, flexibility and strength of skin, tendons and ligaments, but also of the cornea, cartilage, bones, blood vessels and gut With oral ingestion of hydrolyzed collagen (and other active compounds), it is thought that the peptides will move through the human body and reach the places where fibroblasts are located, resulting in stimulation of fibroblasts to produce more collagen. Clinical studies (see below) have shown that (long-term) supplementation of hydrolyzed collagen leads to reporting of improvement in, for example, skin elasticity and hydration.9 10

Collagen for supplementation is generally extracted from byproducts of mammals (e.g. bovine, porcine or ovine) or marine animals (such as fish and jellyfish). Fish-derived collagen peptides are receiving more and more attention due to their favorable characteristics and fewer consumer reservations compared to mammal-derived ingredients. Collagen obtained from marine sources are mostly of type 1 collagen - the type which is produced and stored in cells in skin and connective tissues and also plays an important role in bone tissue.11 12

Studies on the impact of marine collagen peptides on health and appearance

Marine collagen hydrolysate has an anti-aging effect on human skin. A recent clinical trial demonstrated a significant increase in skin elasticity in a group of women aged 35-55 years.13 The same group of scientists from the University of Kiel, Germany, also demonstrated a significant reduction in skin wrinkles after daily consumption of a collagen hydrolysate.14

A comprehensive study of the effect of oral collagen peptide supplement on skin-aging involving clinical trials with Japanese and Caucasian women showed good effect on skin moisturization. The fish collagen peptides were shown to increase the skin moisture level by 12 % in a period of 8 weeks. A consistent increase in the skin collagen density over 12 weeks was confirmed by increased dermal echogenicity. Ex vivo studies confirmed the results of the clinical trials and showed an increased amount of water-binding glycosaminoglycans and collagen content in human skin explants incubated with fish collagen peptides.15

A 2019 systematic literature review of studies on dermatological applications of oral collagen supplementation found in several studies that the short and long-term use of oral collagen supplements may be promising for wound healing and skin aging. The findings additionally state that oral collagen supplements also increase skin elasticity, hydration, and dermal collagen density. The review paper then concludes that collagen supplementation is generally safe with no reported adverse events.16 Another systematic literature review from 2020 assesses studies regarding the effects of collagen supplements on skin health parameters in healthy and patient subjects, focusing on mechanisms of action. The evidence obtained from this systematic literature review paper indicates that oral administration of intact or hydrolyzed collagen improves clinical manifestation of skin health. The review paper concludes that almost all of the included studies reported the beneficial effects of collagen supplementation, with no inconsistencies seen in this regard between studies.17

The conventional way to apply active compounds to skin and hair is the topical administration. Collagen peptides in the range of 0.6-12 kDa can adsorb onto keratin structures like skin and hair. They form a protective layer that prevent damage and moisture loss. Larger molecules bind stronger to those structures, but the water solubility decreases with increasing size. On hair, the collagen peptides also diffuse into the fibrous hair cells. Used in hair styling and dying applications, they protect against chemical damage.18 High molecular weight, but also smaller collagen peptide fragments in a range from 1-3 kD were shown to bind stronger especially on bleached or waved hair structures.19

Products containing active collagen peptides have long been present in the US and European pharmaceutical and food markets. Many scientific and preclinical studies show various positive effects on tendon flexibility, ligament stability, muscle and bone integrity and bone metabolism. One study showed that collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men. The objective of this study was to assess the influence of post-exercise protein supplementation with collagen peptides v. placebo on muscle mass and muscle function following resistance training in elderly subjects with sarcopenia and the results demonstrated that compared with placebo, collagen peptide supplementation in combination with resistance training further improved body composition by increasing fat-free mass, muscle strength and the loss in fat mass.20 

Another study investigated the effect of specific fish-derived collagen peptides on collagen expression, post-translational modification and mineralization in an osteoblastic cell culture. Fish collagen peptides were shown to upregulate the gene expression of collagen-modifying enzymes and this effect led to an increased collagen synthesis and positive effects on collagen quality and matrix mineralization in the osteoblasts.21

Literature list

1. Shoulders, M. D., & Raines, R. T. (2009). Collagen structure and stability. Annual review of biochemistry, 78, 929-958.

2. Wu, M., & Crane, J. S. (2018). Biochemistry, Collagen Synthesis.

3. Gauza-Włodarczyk, M., Kubisz, L., & Włodarczyk, D. (2017). Amino acid composition in determination of collagen origin and assessment of physical factors effects. International Journal of Biological Macromolecules, 104, 987-991.

4. Varani, J., Dame, M. K., Rittie, L., Fligiel, S. E., Kang, S., Fisher, G. J., & Voorhees, J. J. (2006). Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation. The American journal of pathology, 168(6), 1861-1868.

5. Cheng, W., Yan-hua, R., Fang-gang, N., & Guo-an, Z. (2011). The content and ratio of type I and III collagen in skin differ with age and injury. African Journal of Biotechnology, 10(13), 2524-2529.

6. Ganceviciene, R., Liakou, A. I., Theodoridis, A., Makrantonaki, E., & Zouboulis, C. C. (2012). Skin anti-aging strategies. Dermato-endocrinology, 4(3), 308-319.

7. 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.

8. Baumann, L. (2007), Skin ageing and its treatment. J. Pathol., 211: 241-251.

9. Czajka, A., Kania, E. M., Genovese, L., Corbo, A., Merone, G., Luci, C., & Sibilla, S. (2018). Daily oral supplementation with collagen peptides combined with vitamins and other bioactive compounds improves skin elasticity and has a beneficial effect on joint and general wellbeing. Nutrition Research, 57, 97-108.

10. de Miranda, R. B., Weimer, P., & Rossi, R. C. (2021). Effects of hydrolyzed collagen supplementation on skin aging: a systematic review and meta‐analysis. International Journal of Dermatology.

11. Subhan, F., Ikram, M., Shehzad, A., & Ghafoor, A. (2015). Marine collagen: an emerging player in biomedical applications. Journal of food science and technology, 52(8), 4703-4707.

12. Lim, Y. S., Ok, Y. J., Hwang, S. Y., Kwak, J. Y., & Yoon, S. (2019). Marine collagen as a promising biomaterial for biomedical applications. Marine drugs, 17(8), 467.

13. 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 Pharmacol Physiol 27:47–55.

14. Proksch, E., Schunck, M., Zague, V., 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.

15. 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.

16. 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: JDD, 18(1), 9-16.

17. Barati, M., Jabbari, M., Navekar, R., Farahmand, F., Zeinalian, R., Salehi‐Sahlabadi, A., Abbaszadeh, N., Mokari-Yamchi, A. & Davoodi, S. H. (2020). Collagen supplementation for skin health: A mechanistic systematic review. Journal of Cosmetic Dermatology.

18. Schrieber, R., Gareis, H. (2007) Gelatine Handbook: Theory and Industrial Practice. Wiley-VCH, Weinheim, 347 pp.

19. Mintz, GR., Reinhart, GM., Lent, B. (1991) Relationship between collagen hydrolysate molecular weight and peptide substantivity to hair. Journal of the Society of Cosmetic Chemists 42, 35-44.

20. Zdzieblik, D., Oesser, S., Baumstark, M. W., Gollhofer, A., & König, D. (2015). Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. The British journal of nutrition, 114(8), 1237–1245.

21. Yamada, S., Nagaoka, H., Terajima, M., Tsuda, N., Hayashi, Y., & Yamauchi, M. (2013). Effects of fish collagen peptides on collagen post-translational modifications and mineralization in an osteoblastic cell culture system. Dental materials journal32(1), 88-95.

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