Collagen, Dissected Chemically. Things You Should Know in Choosing the Right Collagen.


Collagen is the most abundant protein in your body. It occurs naturally as your body produces and stores it. It is a structural protein seen in connective tissue throughout your body, including skin, bones, tendons, and ligaments. Its key role is to help tissues resist stretching, preventing wrinkles and sagging skin. The word collagen is derived from the Greek word “kolla” meaning glue. So basically, collagen is the “glue” that sticks the whole body together.

Unfortunately, as you grow old, your body synthesizes less collagen and may no longer absorb collagen as well, causing the storage of collagen to gradually deplete. The production begins to diminish at about mid to late twenties, and continues. It decreases even more in women after menopause. Collagen also decreases with other factors such as smoking, sugar consumption and harmful ultraviolet rays exposure. Therefore, it is not unusual that a handful of people attempt to restore collagen through collagen supplementation. Most are hydrolyzed, which means the collagen has been broken down, making it easier for digestion. If you’re one those being doubtful about how efficient is collagen supplementation in reinstating collagen levels in your body, here in this article we share about the background chemistry of collagen that you may or may not know for your consideration.


Collagen = Gly-Pro-Hyp

Basically, collagen protein molecules consist of three chains of smaller peptides. The most common tripeptide unit of collagen is made up of Gly-Pro-Hyp, namely glycine, proline and hydroxyproline. Appearance of dipeptide chains, particularly Prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly), in the blood after ingestion and subsequent unwinding of triple alpha-helix peptide chain of collagen, significantly enhances growth of fibroblasts, which has been associated with beneficial effects such as improvement of skin disorders and joint pains.1 Population of fibroblasts in turn stimulates cell proliferation and cell migration, eventually accelerates cell turnover.


Collagen Types I and III = 95%

Nearly 28 types of collagen have been discovered, but collagen type I is the most common in skin, bone, teeth, tendon, ligaments, vascular ligature, and organs.2 Collagen types I and III contribute around 95% of the skin composition and are in charge of the resilience, strength, durability, and elasticity in the skin property.3  


Smaller or Bigger Collagen?

The composition and degree of hydrolysis of collagen are factors that elevate functional properties such as antioxidant capacity, antimicrobial activity, and improved bioavailability.2 Hydrolyzed collagen is small peptides that are highly soluble in water2 with the lower molecular weights (0.3-8 kDa). Consequently, hydrolyzed collagen is easier to be absorbed by the intestine and distributed in the human body, as compared to native collagen which has high molecular weights (285–300 kDa).2  In terms of functional advantages, hydrolyzed collagen presents more superior therapeutic loading, better digestibility, and lower allergenicity, compared to native collagen.2 To demonstrate the point of digestibility, more than 63.4% of the collagen was absorbed in the form of peptide through the intestine of our body digestive system.4 Studies in humans have found that the peptides in collagen peak in the blood after 2 hours of ingestion, and continue to be significantly elevated even after 4 hours.5 These small peptide units from oral collagen supplementation then supply the raw materials for human collagen production.


Is there a need for Vitamin C?

Many collagen supplements in the market incorporate vitamin C into the product. This is because vitamin C plays a crucial role in connective tissue healing, being a cofactor for prolyl hydroxylase and lysyl hydroxylase.6 These enzymes catalyze the reaction involved in supporting the proper folding of the stable collagen triple-helix structure. In other words, vitamin C promotes collagen cross-linking and synthesis.



We now understand the three main criteria on how to choose collagen supplement chemically, namely the collagen type, native or hydrolyzed collagen, and molecular weight lower than 8 kDA.

In summary, the higher the degree of hydrolysis of collagen, the smaller the molecular weight, resulting in greater bioavailability, and more of the collagen peptide types I and III can be absorbed by your body, coupled with vitamin C, establishing more health benefits of antioxidant activity on the skin and joint conditions.


  1. Asai TT, Oikawa F, Yoshikawa K, Inoue N, Sato K. Food-Derived Collagen Peptides, Prolyl-Hydroxyproline (Pro-Hyp), and Hydroxyprolyl-Glycine (Hyp-Gly) Enhance Growth of Primary Cultured Mouse Skin Fibroblast Using Fetal Bovine Serum Free from Hydroxyprolyl Peptide. Int J Mol Sci. 2020 Jan; 21(1): 229.
  2. Leon-Lopez A, Morales-Penaloza A, Martinez-Juarez VM, Vargas-Torres A, Zeugolis DI, Aguirre-Alvarez G. Hydrolyzed Collagen—Sources and Applications. Molecules. 2019 Nov; 24(22): 4031.
  3. Lin P, Hua N, Hsu YC, Kan KW, Chen JH, Lin YH, Lin YH, Kuan CM. Oral Collagen Drink for Antiaging: Antioxidation, Facilitation of the Increase of Collagen Synthesis, and Improvement of Protein Folding and DNA Repair in Human Skin Fibroblasts. Oxidative Medicine and Cellular Longevity. Volume 2020 |Article ID 8031795.
  4. Wang L, Wang Q, Qian J, Liang Q, Wang Z, Xu J, He S, Ma H. Bioavailability and Bioavailable Forms of Collagen after Oral Administration to Rats. J. Agric. Food Chem. 2015, 63, 14, 3752–3756.
  5. Sato K, Iwai K, Aito-Inoue M. Identification of food-derived bioactive peptides in blood and other biological samples. J AOAC Int. Jul-Aug 2008;91(4):995-1001.
  6. DePhillipo NN, Aman ZS, Kennedy MI, Begley JP, Moatshe G, LaPrade RF. Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthop J Sports Med. 2018 Oct; 6(10): 2325967118804544.