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.
General: Orally, collagen type II seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, nausea, and vomiting.
-
Orally, one incident of mild hypertension was reported as being possibly related to collagen type II in a clinical trial of children (
101719).
-
Orally, collagen type II might cause itching. In two cases, the itching was associated with skin eruption (
44451,
101717,
101719).
-
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).
-
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).
-
Orally, liver function abnormalities, including elevated transaminase levels, have been reported in some clinical research, but this is uncommon (
3111,
44451,
101717).
-
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).
-
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).
-
Orally, edema occurred in two patients taking collagen type II in clinical research (
101717).
POSSIBLY EFFECTIVEOsteoarthritis. Oral collagen type II seems to improve stiffness, pain, and function by a small amount in patients with knee osteoarthritis, but any benefit on joint space narrowing is unclear.
Details:
Clinical research in patients with knee osteoarthritis shows that taking a specific collagen type II (UC-II, InterHealth Nutraceuticals, Inc.) 40 mg daily for up to 6 months reduces symptoms, such as stiffness, pain, and physical functioning, by about 20% when compared with baseline (97238,97239). Taking this product might also improve some symptoms, such as pain and stiffness, when compared with glucosamine 1500 mg plus chondroitin 1200 mg (97239). A small clinical study in patients with knee osteoarthritis and type 2 diabetes shows that taking a specific collagen type II (UC II, SEMNL Biotechnology) 40 mg daily for 3 months improves pain by 36%, compared with 5% in those receiving placebo (107466).
It is unclear if taking collagen type II is more beneficial than exercise. A small clinical study in females with knee osteoarthritis shows that taking a specific collagen type II (Motilex Caps, Aspen Pharmaceutics) at an unknown dose daily for 6 weeks may improve physical functioning and pain but does not improve range of motion when compared with usual care. However, physical functioning, rigidity, and pain were not improved when compared with twice-weekly standardized exercise (110734).
Collagen type II is also studied in combination with other ingredients. A small clinical study shows that taking a specific combination product (AR7 Joint Complex, Robinson Pharma) containing collagen type II, methylsulfonylmethane (MSM), cetyl myristoleate, lipase, vitamin C, turmeric, and bromelain orally for 12 weeks reduces symptoms, with 43% and 46% of patients reporting joint pain and stiffness, respectively, compared with 71% and 71% in those receiving placebo. However, the combination product does not appear to improve joint space narrowing (19314).
POSSIBLY INEFFECTIVERheumatoid arthritis (RA). Despite some conflicting results, oral collagen type II does not seem to improve symptoms of RA when compared with standard treatments.
Details:
Three moderately large clinical studies in patients with RA, some of whom were using disease modifying antirheumatic drugs (DMARDs), show that taking chicken collagen type II 100-2500 mcg daily or bovine collagen type II 100-500 mcg daily for 6 months does not improve clinical response rates based on American College of Rheumatology (ACR) criteria when compared with placebo (3111,44446,101718). Other clinical research in patients stabilized on oral methotrexate shows that switching to chicken collagen type II 500 mcg orally daily actually increases disease activity when compared with continued treatment with methotrexate (44456). While some clinical research in patients not taking DMARDs shows that taking chicken collagen type II 100 mcg daily may reduce symptoms, the response rates based on ACR20 and ACR50 criteria are greater for patients treated with methotrexate 10 mg weekly when compared with chicken collagen type II (44451,101717). One clinical study shows that taking low dose chicken collagen type II 20 mcg daily for 24 weeks improves clinical response according to the Paulus criteria, but not according to the ACR criteria, when compared with placebo. Other preliminary research in patients who discontinued treatment with immunosuppressants and DMARDs shows that taking chicken collagen type II 100 mcg orally daily for 1 month, followed by 500 mcg daily for 2 months, improves symptoms in some patients when compared with placebo (44454).
INSUFFICIENT RELIABLE EVIDENCE to RATEBack pain. Although there has been interest in using oral collagen type II for back pain, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Gout. Although there has been interest in using oral collagen type II for gout, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Joint pain. Oral collagen type II may modestly reduce joint pain.
Details:
A small clinical study in patients with joint pain due to exercise shows that taking a specific collagen type II product (UC-II, InterHealth Nutraceuticals, Inc.) 40 mg daily for 4 months may increase the duration of pain-free exercise by about 1.5 minutes when compared with baseline (101744). Another small clinical study in patients with non-arthritic knee pain shows that taking a specific chicken-derived collagen type II product (NEXT-II, Ryusendo Co.) 3.2 mg daily for 12 weeks modestly improves knee pain, stiffness, and function when compared with placebo (110733). However, it is unclear whether these results apply to patients with overweight or obesity since they were excluded from this study.
Juvenile idiopathic arthritis (JIA). It is unclear if oral collagen type II is beneficial for JIA.
Details:
Some small clinical studies show that taking chicken collagen type II may improve symptoms such as swollen and tender joint scores when compared with baseline in some patients. However, the lack of a control group in these studies limits the reliability of these results (3112,101719).
Neck pain. Although there has been interest in using oral collagen type II for neck pain, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Pain (acute). Although there has been interest in using oral collagen type II for acute pain after trauma, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Postoperative pain. Although there has been interest in using oral collagen type II for joint pain after surgery, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Range of motion. It is unclear if oral collagen type II improves range of motion; study results are in conflict.
Details:
Small clinical studies in healthy people with joint pain due to exercise who took a specific collagen type II product (UC-II, InterHealth Nutraceuticals, Inc.) have conflicting results (101744,110732). In one study, taking 40 mg daily for 4 months increases knee extension by about 6 degrees when compared with placebo, but does not improve knee flexion (101744). However, the other study shows that taking 40 mg daily for 6 months does not improve knee extension but increases knee flexion by about 3 degrees when compared with placebo (110732). Results are similar in a small clinical study in patients with non-arthritic knee pain. In this study, taking a specific chicken-derived collagen type II product (NEXT-II, Ryusendo Co.) 3.2 mg daily for 12 weeks does not improve knee extension but increases knee flexion by about 5 degrees when compared with placebo (110733).
Urticaria. Although there has been interest in using oral collagen type II for urticaria associated with stress, there is insufficient reliable information about the clinical effects of collagen type II for this condition.
Uveitis. It is unclear if oral collagen type II is beneficial for uveitis.
Details:
Preliminary clinical research in children with uveitis associated with juvenile idiopathic arthritis shows that taking collagen type II (Colloral, AutoImmune Inc.) 60 or 540 mcg daily for 6 months does not improve ophthalmic outcomes when compared with baseline (101719).
More evidence is needed to rate collagen type II for these uses.
Individuals who are allergic to other collagen-containing products should not use supplements containing collagen type II. Collagen products, including dietary collagen in the form of gelatin and bovine collagen products used in corneal shields, have been associated with allergic reactions in some patients (
3127).
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).
Monographs are reviewed on a regular schedule. See our
for details. The literature evaluated in this monograph is current through 3/30/2023. This monograph was last modified on 5/26/2023. If you have comments or suggestions, please