What is type II collagen, and where does it come from?

Type II collagen is the main collagen of cartilage. Its molecule is made of three identical chains, called alpha 1(II) chains, while type I collagen, the type found in skin, bone and tendon, is made of two alpha 1(I) chains and one alpha 2(I) chain. Most research extracts it from chicken sternal cartilage, and it is described in two forms: undenatured, with its triple helix intact, or hydrolysed into small peptides.

In short:

• What it is: one of the 28 members of the collagen family, the main collagen of cartilage
• Structure: three identical alpha 1(II) chains wound into a triple helix (type I has two kinds of chain)
• Raw material in research: mostly chicken sternal cartilage, a co-product of land animals; also shark, skate and sturgeon cartilage
• Forms: undenatured (about 300 kDa, helix intact) or hydrolysed (peptides of about 3–6 kDa)
• Daily amount: no Thai RDI, because it is not an essential nutrient

This article covers what type II collagen is, what it is made from and how its forms differ. For collagen in general, what happens to collagen you eat and its other forms, see What happens to collagen you eat? and What kinds of collagen are there?

What is type II collagen?

Collagen is not a single protein but a family. Shoulders and Raines (2009), in the Annual Review of Biochemistry, describe collagen as the most abundant protein in animals: a fibrous, structural protein made of three helical chains wound around each other.

How many types of collagen are there?

A 2011 review by Ricard-Blum says the collagen family has 28 members, all of which contain at least one triple-helical part, and that some collagens are found only in certain tissues. They are numbered with Roman numerals, so "type II" is the second member of the family.

Where is type II collagen found?

The protein database UniProt describes type II collagen as the collagen of cartilaginous tissues. A 2019 review by León-López and colleagues in Molecules sums up the difference in one line: type I is the most common in skin, bone, teeth, tendon, ligaments and organs, while type II is present in cartilage.

How is type II collagen different from type I?

Both are fibre-forming collagens built from three chains, but the chains are not the same.

Chains and amino acids

Every collagen chain is built from a repeating pattern of three amino acids, written Gly-X-Y. Glycine comes every third position, and the other two positions are often proline and hydroxyproline. Proline and hydroxyproline together are called imino acids, and how many there are affects how stable the helix is.

Sources: chain composition, location and chain length from UniProt entries P02458 and P02452; location and raw materials for type I from León-López and colleagues (2019); raw materials for type II from the studies below. UniProt gives the length of the chain as it is first made in the cell; part of it is trimmed off before the finished molecule forms.

How big is one chain?

León-López and colleagues say each collagen alpha chain has about 1,014 amino acids and a molecular weight of about 100 kDa, and that the whole collagen molecule is about 300 kDa. In chicken type II collagen, Cao and colleagues (2013) measured a chain of 110 kDa; Jeevithan and colleagues (2014) measured about 120 kDa in shark type II collagen.

What is type II collagen made from?

It is extracted from cartilage, because type II is the main collagen of cartilage.

Chicken sternal cartilage

The cartilage at the lower tip of the chicken breastbone, the sternum, is the source most often used in research. Akram and Zhang (2020), at the Chinese Academy of Agricultural Sciences, describe chicken sternal cartilage as a co-product of land animals. In Thailand, the same piece of cartilage is familiar as a deep-fried snack, sold as เอ็นไก่ทอด or กระดูกอ่อนไก่ทอด.

Fish cartilage

Researchers have also extracted type II collagen from the cartilage of fish. Jeevithan and colleagues (2014), at Shanghai Ocean University, used silvertip shark cartilage, and a 2020 study by Zhu and colleagues at the Ocean University of China used the cartilage of skate and sturgeon, finding type II collagen made of three chains of about 135 kDa. These studies treat fish cartilage as another possible source; most type II collagen in research comes from chicken.

How is type II collagen extracted from chicken cartilage?

The basic method in research is to dissolve the collagen out of the cartilage with an enzyme, then purify it.

Enzyme and purification

Cao and colleagues (2013), at the University of Shanghai for Science and Technology, purified type II collagen from chick sternal cartilage in three steps: digestion with pepsin (an enzyme from the stomach), precipitation with salt (NaCl) and ion-exchange chromatography. The purified collagen retained more intermolecular crosslinks through the preparation, and it dissolved well between pH 1 and 3.5.

Ultrasound

Akram and Zhang (2020) added ultrasound to the extraction. With 36 minutes of ultrasound, the yield of collagen reached 84.14% based on protein weight. The triple helix stayed the same, but longer ultrasound (36 minutes or more) changed some of the secondary structure. The study is from a single laboratory, so it shows what is possible, not how commercial raw material is made.

How does temperature affect extraction?

A 2016 study by Thuanthong and colleagues at Prince of Songkla University in Thailand notes that collagen from fish skin is usually extracted at low temperature, and that high temperature might break down the triple helix. The researchers extracted type I collagen from Nile tilapia skin at 5, 15 and 25°C. With 0.5 M acetic acid, extraction at 25°C for 5 hours gave the highest efficiency (73.73%), about 1.7 times that at 5°C, and did not affect the triple helix. This is type I collagen from fish skin, not type II.

Does type II collagen from different animals differ?

Yes, in its imino acid content and in the temperature at which the helix comes apart. The table puts together laboratory results from three studies, including fish skin collagen from Thailand for comparison.

The chicken type II collagen had the most imino acids and the highest transition temperature. Benjakul and colleagues at Prince of Songkla University chose bigeye snapper because it is widely used for surimi in Thailand, so its skin is a by-product. In the shark study, the hydroxyproline content was 92.7–113 mg/g in the collagen extracts.

The limits: each study used one source and one laboratory method, and the temperatures were measured by different methods on purified collagen in solution. The figures show that collagen from different animals differs, not how a particular raw material behaves.

What do undenatured, hydrolysed and gelatin mean?

These words describe what has happened to the triple helix, and they apply to type II collagen in the same way as to other collagens.

Sources: León-López and colleagues (2019); gelatin from Harvard's The Nutrition Source.

What does "undenatured" mean?

Denaturing a protein means changing its folded shape without breaking the chain. For collagen, León-López and colleagues explain that denaturing native collagen turns its three chains into loose, random coils. "Undenatured" type II collagen is therefore type II collagen whose triple helix is still in place.

What does "hydrolysed" mean?

Hydrolysis breaks the chains themselves into short pieces. León-López and colleagues give the size of hydrolysed collagen as about 3–6 kDa, compared with about 300 kDa for the whole molecule, so a hydrolysed piece is roughly 50 to 100 times smaller. Hydrolysed type II collagen is type II collagen that has been through this process; it is no longer in a helix.

Which foods contain type II collagen?

In animal cartilage. Harvard's The Nutrition Source says collagen in food comes from animal flesh with connective tissue and from the bones and skin of fish, and plants contain none.

Cooked cartilage

The same source says gelatin is made by boiling animal bones, cartilage and skin for several hours.

What happens to it when eaten?

Collagen eaten in food is a protein. The Nutrition Source explains that in digestion it is broken down into amino acids, which are used wherever the body needs protein. More on this is in What happens to collagen you eat?

Is there a recommended daily amount of type II collagen?

No. Type II collagen is not an essential nutrient, so it has no value in the Thai Reference Daily Intakes (Thai RDIs). The Thai RDIs give a value for total protein, which is 50 g a day, but not for any single protein such as collagen.

Who should be careful with type II collagen?

People who must avoid chicken or fish

In research, type II collagen is extracted mostly from chicken cartilage, and also from the cartilage of sharks and other fish. Anyone who must avoid chicken or fish, for health or religious reasons, should check the source of the raw material.

People who are pregnant, breastfeeding or taking medicines

People who are pregnant, breastfeeding or taking regular medication should speak to a doctor or pharmacist first, and tell their healthcare providers about any dietary supplements they use.

If you are pregnant, breastfeeding, take regular medication or are under a doctor's care, speak to a doctor or pharmacist before taking dietary supplements.

Dietary supplements are not intended to prevent, treat or cure any disease.