Encyclopedia entry

Oral tolerance and undenatured collagen

Undenatured Type II collagen (UC-II) is taken at 40 mg per day for joint comfort. Hydrolysed Type I collagen for skin is taken at 5 to 15 g per day. The dose unit difference (milligrams vs grams) is not a typographical error. The two products work by entirely different mechanisms. UC-II works through oral tolerance, an immune-system pathway; hydrolysed Type I works through nutritional absorption.

What oral tolerance is

The gut-associated lymphoid tissue (GALT) constantly samples the contents of the gut and decides what is friend and what is foe. Most food antigens trigger a tolerance response: the immune system learns to treat them as safe and downregulates the inflammatory response in tissue where the same antigens are encountered. Oral tolerance is the basis of conventional immunotherapy for some allergies.

How this applies to UC-II

The hypothesis behind UC-II for joint comfort is that small daily doses of undenatured (intact triple-helix) Type II collagen, presented through the gut, train the immune system to dampen the autoimmune-style response that occurs in some inflammatory joint conditions. The Type II collagen in cartilage is the same molecule; oral tolerance to it appears to reduce joint inflammation in published trials.

Why the dose is so small

Oral tolerance works at antigen exposure levels; pumping in grams of intact Type II would overwhelm the tolerogenic pathway and risk shifting to an inflammatory response. 40 mg is the dose that has shown joint outcomes in published trials (most notably Crowley 2009 and Lugo 2016). Increasing the dose does not improve outcomes and risks the opposite effect.

Why hydrolysed Type II does not have the same effect

Hydrolysis breaks the triple-helix structure. The oral tolerance pathway depends on the intact molecule being presented to gut immune tissue. Hydrolysed Type II would behave like hydrolysed Type I or Type III, contributing amino acids to the body\'s collagen synthesis pool but not engaging the tolerance pathway.

Related: Type I vs Type II · hydrolysed vs native.