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Type-II Collagen

Type II collagen (CII) is a peptide and component of joint cartilage. Its oral ingestion appears to reduce autoimmunity to the body's own CII, resulting in less inflammation in instances of osteoarthritis and rheumatism and benefits to joint health.

Our evidence-based analysis on type-ii collagen features 70 unique references to scientific papers.

Research analysis led by and reviewed by the Examine team.
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Summary of Type-II Collagen

Primary information, health benefits, side effects, usage, and other important details

What is type II collagen?

Type II collagen (CII) is a peptide and a major component of joint cartilage. When taken as a supplement, CII is usually in one of two forms: undenatured or hydrolyzed. Undenatured collagen has been minimally processed at a low temperature to keep its peptides mostly intact. Hydrolyzed CII has been processed with a higher degree of heat, acid, and enzymes, resulting in the breakdown of peptides from larger forms into smaller ones.

What are type II collagen’s main benefits?

The primary benefit of undenatured CII appears to be improvement in joint pain, mainly in the context of osteoarthritis and rheumatoid arthritis. Hydrolyzed CII (also known as CII hydrolysate) may improve skin health/appearance and reduce joint pain.

What are type II collagen’s main drawbacks?

By and large, CII seems fairly safe. One potential concern is that collagen (in dosages of around 10 grams per day) has been shown to increase oxalate levels in urine, likely because collagen consists of approximately 10% hydroxyproline, and a major metabolite of hydroxyproline is oxalate. As a result, higher doses of CII could increase the risk of oxalate-based kidney stones in susceptible individuals.

How does type II collagen work?

Undenatured CII has been proposed to improve joint pain through an effect on the immune system. More specifically, CII peptides are thought to induce the formation of regulatory T cells (Tregs) in areas of the gut known as Preyer’s patches. These Tregs can enter circulation, where they produce anti-inflammatory compounds (e.g., IL-10), which in theory can inhibit inflammation and tissue damage in joints.

The hydrolysis of type II collagen seems to result in the breakdown of the most immunologically active peptides, meaning that the effect of hydrolyzed collagen on joints may not act via this mechanism. However, in higher doses, hydrolyzed CII might improve joint pain by supplying the amino acids used to repair the damaged tissue.

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How to Take

Recommended dosage, active amounts, other details

The dose of CII taken depends on whether it is denatured (hydrolyzed) or undenatured. For skin and joint health, the daily dose of hydrolyzed collagen is around 10 grams per day. For treatment of osteoarthritis and rheumatoid arthritis, undenatured collagen is taken at a much lower daily dose (often around 40 milligrams), and while it doesn't need to be taken at any particular time of the day, it may be ideal to take it on an empty stomach before breakfast.

CII should not be taken as a protein supplement because it has a lackluster amino acid profile.

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Human Effect Matrix

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The Human Effect Matrix summarizes human studies to tell you what effects Type-II Collagen has on your body, how much evidence there is, and how strong these effects are.

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Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
grade-b Minor High See all 5 studies
Limited research suggests a small benefit for osteoarthritis patients and a modest benefit for those with rheumatoid arthritis. It's unclear what the optimal dose is, and it may depend on the form. 1 mg of solubilized collagen, 10 g of hydrolyzed collagen, and 40 mg of undenatured collagen are all supported by research, while 20 mcg of native collagen actually coincided with a greater reduction in rheumatoid arthritis pain than higher doses in one study.
grade-c Minor - See study
One study in healthy people with joint discomfort during exercise found that those taking 40 mg of undenatured collagen could exercise somewhat longer without getting sore than the placebo group. Notable effects were only seen after taking collagen for 2-3 months but persisted for up to 6 months.
grade-c Minor - See 2 studies
Limited research suggests a reduction in pain, but the studies available don't provide evidence for an improvement in the other symptoms.
grade-c Minor Very High See all 3 studies
Limited research suggested an improvement in pain, swelling, stiffness, and tenderness.
grade-c - - See study
One study in rheumatoid arthritis patients reported that collagen didn't seem to influence c-reactive protein, but they didn't provide the data.
grade-c - - See study
No apparent effect in one study on rheumatoid arthritis.
grade-c - - See study
No apparent effect in one study on rheumatoid arthritis.

Studies Excluded from Consideration

Note: The above HEM contains information on both hydrolyzed collagen supplements and undenatured collagen supplements despite significant dose differences between the two

  • Used alongside calcitonin injections[1]

  • Confounded with chondroitin and hyaluronic acid[2]

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Things to Note

Primary Function:

Other Functions:

Also Known As

hydrolyzed collagen, solubilized collagen, CII, shark gelatin, gelatin, collagen

Do Not Confuse With

Colostrum (different protein with a similar name)

  • CII supplements are derived from animals and thus not vegan-friendly

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Click here to see all 70 references.