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.

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.

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.

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.