Collagen & Skin Health
If you are here to find out if collagen is effective at improving skin with scientific references, you are in the right place. If you would also like to understand the physiological mechanisms by which this does or is prevented from occurring, you are still in the right place. So, with that introduction, let us educate ourselves on collagen and its role in skin.
What is Collagen?
Collagen is a helical protein made of three amino acid repeats – typically the amino acids glycine, proline, and hydroxyproline . These repeats of amino acids are used to create protein chains within the cell, in the endoplasmic reticulum, then exocytosed into the extracellular space to form fibrils (three protein chains woven together into a helix); then, sometimes, fibrils can be further stitched together through covalent bonding and create thicker collagen fibers .
What is the function of collagen?
In skin, the function of collagen is to create a structure within the dermis (lower level) of the skin, allowing cells to latch onto this lattice and react to the environment when stimulated, as well as offer a platform to link other skin proteins (elastin, for example) together and create a dense network of proteins holding the epidermis (top layer of skin) up, uniformly . Not only that, blood circulating collagen can bind receptors on fibroblasts and stimulate the production of more collagen and other structural molecules .
 Cell Biology @ Yale [Document]. Yale. http://medcell.med.yale.edu/lectures/connective_tissue.php#:~:text=Fibrous%20collagens%20have%20three%20levels,mechanical%20strength%20of%20collagen%20fibrils
 Lodish, H. (2000). Collagen: The Fibrous Proteins of the Matrix. In Molecular Cell Biology (4th ed.). W.H. Freeman. https://www.ncbi.nlm.nih.gov/books/NBK21582/
 Wu, M. (2020). Biochemistry, Collagen Synthesis. In Biochemistry, Collagen Synthesis. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK507709/
 Vollmer, D., West, V., & Lephart, E. (2018). Enhancing skin health: By oral administration of natural compounds and minerals with implications to the dermal microbiome. International Journal of Molecular Sciences, 19(10), 3059. https://doi.org/10.3390/ijms19103059
 Bolke, L., Schlippe, G., Gerß, J., & Voss, W. (2019). A collagen supplement improves skin hydration, elasticity, roughness, and density: Results of a randomized, placebo-controlled, blind study. Nutrients, 11(10), 2494. https://doi.org/10.3390/nu11102494
 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. https://doi.org/10.3390/nu10070826
 Pyun, H., Kim, M., Park, J., Sakai, Y., Numata, N., Shin, J., Shin, H., Kim, D., & Hwang, J. (2012). Effects of collagen Tripeptide supplement on Photoaging and epidermal skin barrier in UVB-exposed hairless mice. Preventive Nutrition and Food Science, 17(4), 245-253. https://doi.org/10.3746/pnf.2012.17.4.245
 Zague, V., De Freitas, V., Rosa, M. D., De Castro, G. Á., Jaeger, R. G., & Machado-Santelli, G. M. (2011). Collagen hydrolysate intake increases skin collagen expression and suppresses matrix Metalloproteinase 2 activity. Journal of Medicinal Food, 14(6), 618-624. https://doi.org/10.1089/jmf.2010.0085
 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. The American Journal of Pathology, 168(6), 1861-1868. https://doi.org/10.2353/ajpath.2006.051302
 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, 39(3), 428-434. https://doi.org/10.1248/bpb.b15-00624
Acknowledgement: Images created in BioRender
How is collagen synthesized?
In the skin (and most areas of the body), collagen is produced by fibroblasts that take up the necessary amino acids from the extracellular environment and blood stream to stitch them together into chains of 3 amino acid repeats (glycine, proline, and hydroxyproline are common) in the endoplasmic reticulum of the cell to then be exocytosed out of the fibroblast, along with enzymes that further process the fibril (a triple protein helix of these amino acids) . These enzymes (peptidases) cleave the immature collagen to make it a mature collagen fibril capable of coming together into thicker collagen fibers through enzyme mediated covalent bonding, outside of the cell .
Does collagen supplementation improve skin?
The answer is likely yes. According to the research, industry funded and otherwise (public funding, for example), various collagens (tri-collagen, low molecular weight collagen, hydrolyzed collagen, etc.) show benefit for the skin . These benefits extend a variety of outcomes, like greater skin hydration, reduced skin roughness and wrinkling, and increased skin elasticity . Usually, the effects are apparent after 2-3 months of supplementation .
The actual amount to take is rather variable, with some collagens (low molecular weight collagen – LMWC) being effective at 1 gram a day, while collagen peptides shown to be effective at 2.5 grams a day, and hydrolyzed collagen studied at upwards of 20 grams (although research has shown benefit at levels as low as 10 grams a day) . These numbers have not been vetted by a regulating agency, however; they are merely based on studies, so if more or less consumed would be more or equally effective (respectively) is unknown.
Understanding the Physiology & Pathophysiology
As briefly explained before, collagen acts as a structural unit to hold up the skin and the more of it present and linear, the smoother (wrinkle free) the skin. However, as we age, our fibroblasts produce less collagen, while also releasing more metalloproteinases and collagenases (enzymes that destroy proteins/collagen), decreasing collagen in the extracellular matrix . As collagen is necessary for fibroblasts to maintain their elongated shape in the skin, the cells themselves “ball up”, losing their intended shape, which further reduces their ability to produce collagen . This is a cyclical issue that compounds itself over time. This diminished collagen, as well as less and less linear collagen fibers leads to troughs, valleys and peaks in the skin (known as wrinkling).
However, there is another major factor that impacts collagen in skin – the sun. Ultraviolet radiation emanating from the sun that strikes the skin will penetrate into cells – keratinocytes in the epidermis, but in this case, more importantly the fibroblasts of the dermis . This radiation cuts into the cell and damages the genes housed in the nucleus, as well as the generation of free radicals that damage the proteins and other molecules that serve functions within the cell. This radiation also directly damages collagen in the extracellular matrix, leading to wrinkling and drying of the skin due to reduced integrity of the collagen fibers (making them less linear and interact less readily).
Now, collagen supplementation seems to help through a few mechanisms. Collagen, as a tri-amino acid (although sometimes consumed as a di-amino acid), can be absorbed by the intestines using a peptide transporter that allows more than a single amino acid into the blood stream . Once it is in the blood stream and finds itself to the dermis, it performs two primary functions: First, it is taken up by fibroblasts and offers more substrate to be used to generate mature collagen fibers as described previously, and second, it binds receptors on fibroblasts that reduce the expression of proteinases, as well as stimulates the production of more collagen .
This is all true in a general sense, but also against both factors that lead to poor skin quality (aging and UV radiation) . Collagen consumption decreases skin damage by ultraviolet radiation, as well as reverses some of the effects of aging . The mechanisms are likely the same as those written above.