Collagen type II (native) is the main structural protein in cartilage. It is also found in other types of connective tissue. Most supplemental collagen type II comes from chicken sources, although some comes from bovine sources (44454,44456,101717,101718). This monograph discusses only native (undenatured) collagen type II.

POSSIBLY SAFE ...when used orally in doses up to 40 mg daily for up to 24 weeks (3111,44446,97238,97239,101717,101718,101744,110732).

PREGNANCY AND LACTATION: Insufficient reliable information available; avoid using.

•  Cardiovascular

  Orally, one incident of mild hypertension was reported as being possibly related to collagen type II in a clinical trial of children (101719).

•  Dermatologic

  Orally, collagen type II might cause itching. In two cases, the itching was associated with skin eruption (44451,101717,101719).

•  Gastrointestinal

  Orally, the most common adverse effects of collagen type II reported in clinical studies are gastrointestinal and include constipation, nausea, vomiting, and abdominal pain. These occurred in up to 7% of patients taking collagen type II (44451,97238,97239,101717,101719). Anorexia was also reported, but this was much less common (44451).

•  Hematologic

  Orally, one incident each of blood in urine and a decrease in white blood cell count were reported for patients taking collagen type II in clinical research (101717).

•  Hepatic

  Orally, liver function abnormalities, including elevated transaminase levels, have been reported in some clinical research, but this is uncommon (3111,44451,101717).

•  Neurologic/CNS

  Orally, headache, dizziness, and insomnia have been reported for patients taking collagen type II in clinical studies, but these events are uncommon (44451,97238,97239,101717).

•  Renal

  Orally, one case of mild proteinuria was reported as being possibly related to use of collagen type II in a clinical trial of children (101719).

•  Other

  Orally, edema occurred in two patients taking collagen type II in clinical research (101717).

• Adult

  Oral:

  Collagen type II has most often been used in doses of 40 mg daily for 4-6 months. See Effectiveness section for condition-specific information.

• Standardization & Formulation

  In most clinical trials, collagen type II has been isolated from chicken sternum and solubilized in 0.1 M acetic acid (3111,44446,44454,101717,101718). One type of collagen type II (UC-II, InterHealth Nutraceuticals, Inc.) 40 mg provides 10.4 mg of collagen type II (101744).
  
  An evaluation of two commercially available collagen powders derived from chicken sternum (b-2Cool, Bioiberica; UC-II, Lonza Consumer Health) has demonstrated issues with product standardization. While total collagen content was in line with the certificate of analysis provided by both manufacturers, the average collagen type II content of b-2Cool was only 0.13%, well below the specification of at least 4%. Additionally, differences in the size of the collagen fibers and the antigenic epitopes suggest that these two products are not interchangeable (107468).

 ALLERGIES

There is insufficient reliable information available about the presentation or treatment of overdose with collagen type II.

There is insufficient reliable information available regarding the pharmacokinetics of collagen type II.

General: Collagen type II is a structural protein found in cartilage (44454,44456).

Anti-inflammatory effects: The rationale of using collagen type II for pain syndromes is based on the theory of oral tolerance. This theory hypothesizes that oral administration of small quantities of antigens causes biological processes that suppress inflammation at the cellular level, suppress response to delayed-hypersensitivity antigens, and eliminate the cells that respond to antigens. Although evidence suggests this theory might be true in animals, it is unproven in humans (3126). Based on the theory of oral tolerance, when individuals with rheumatoid arthritis take oral collagen, the collagen should cause certain areas of the gut to generate T-cells that are absorbed by the body. Then, in the body, these T-cells are activated by joint collagen and they secrete cytokines that suppress inflammation. Cytokines thought to be involved include interleukin (IL)-4, IL-10, and transforming growth factor beta (3111,3112,3125). Oral administration of collagen is also believed to decrease the expression of pro-inflammatory cytokines including IL-1, IL-2, IL-6, and IL-8; tumor necrosis factor (TNF)-alpha; and interferon gamma (3111). So far, the studies determining the efficacy of chicken collagen type II demonstrate conflicting results (3125,3112), but these studies have used microgram doses.

In rodent models of osteoarthritis and aging, administration of collagen type II attenuates inflammatory response and oxidative stress and improves motor function and symptoms (107466,107467,107469).

Bone effects: In a mouse model of aging, administration of collagen type II increases bone mineralization and formation and decreases bone resorption (107467).