Vitamins & Supplements · Collagen supplement
UC-II (Undenatured Type II Collagen)
Undenatured type II collagen (UC-II is a brand name) · also called UC-II, native type II collagen, non-hydrolyzed collagen, colageno tipo II no desnaturalizado
UC-II is a brand of undenatured type II collagen, made from chicken breastbone cartilage and kept in its natural form. Hydrolyzed collagen is the opposite: collagen broken into small pieces. UC-II is studied almost only for knee osteoarthritis. Early trials were positive, but a 2026 trial of 216 people found no benefit over placebo. Most positive trials link to the makers.
General information, not medical advice. Last substantive update · Not medically reviewed. A named clinician has not signed off on this page. How this page is made
About UC-II (Undenatured Type II Collagen)
UC-II is type II collagen from chicken cartilage, kept whole instead of broken down. Trials for knee osteoarthritis are mixed: small positive trials, mostly linked to makers, and two recent trials with no benefit over placebo. Autoimmune disease and chicken allergy are the main cautions.
What UC-II is and how it differs from hydrolyzed collagen
Type II collagen is the main collagen of cartilage. UC-II is a brand of undenatured type II collagen taken from chicken breastbone (sternum) cartilage. Undenatured means it is kept in its natural form. Trial amounts for UC-II are in the milligram range; see the studies table.
Hydrolyzed collagen (collagen peptides) is the opposite. It is collagen from cow, fish or pig tissue deliberately broken into small pieces. Trial amounts for it are in grams. A 2023 review notes that the activity of undenatured collagen depends on how much it has been denatured.
How it is thought to work
The idea is called oral tolerance. A tiny amount of collagen reaches the gut immune system, which is meant to learn to react less to the body's own cartilage collagen. How hydrolyzed collagen might work is itself not established in people.
Oral tolerance has been shown in mouse arthritis models, and a 2024 lab study in people with rheumatoid arthritis found that gene variants affect it. It has not been shown directly in people with knee osteoarthritis.
Food versus pills
Type II collagen is found in chicken cartilage and in bone broth made with cartilage. No USDA or NIH amounts for type II collagen in foods were read, so none are stated.
The trials on this page tested supplements made from chicken cartilage. No trial compared food with pills.
What the research shows
Early trials were positive for knee osteoarthritis. A 6-month trial of 191 people reported lower knee scores than placebo and than glucosamine plus chondroitin. A review of 8 trials pooled similar results.
A 2026 trial of 216 people found no clear difference from placebo, and a 2025 trial of a mixed tablet found none either. No head-to-head trial of UC-II against hydrolyzed collagen was found. A 2024 pooled review of 35 trials found small benefits for collagen products in osteoarthritis but mixed UC-II, hydrolyzed collagen and gelatin together.
At a glance
Traditional uses history, not proof
- Chicken cartilage and bone broth are food sources of type II collagen
- Sold as a joint supplement
Studied for research
- Knee osteoarthritis pain and function, mixed evidence
- Compared with glucosamine plus chondroitin, low certainty
- Exercise-related knee discomfort in healthy adults, low certainty
- Rheumatoid arthritis, mixed and old evidence
- Compared with exercise, very low certainty
- Cartilage protection, skin, bone and muscle, insufficient evidence
Main compounds
- Type II collagen, kept in its natural form
Common forms
- Capsules
- Branded complexes with other ingredients
- Tablets mixing UC-II with hydrolysed collagen
Research links: 2016 trial: UC-II vs placebo and glucosamine plus chondroitin (191 people) · 2026 trial: UC-II vs placebo, glucosamine and diacerein (216 people) · 2023 review: undenatured collagen in knee osteoarthritis (8 trials) · 2024 pooled review of collagen derivatives for osteoarthritis (35 trials) · 2000 trial: oral chicken type II collagen in rheumatoid arthritis · Research Library · Genes & Biomarkers Library
What it is and its history
- Accepted scientific name
- Undenatured type II collagen (UC-II is a brand name)
- Common names
- Undenatured type II collagen (English); Native type II collagen (English); Non-hydrolyzed collagen (English); UC-II (English); Colageno tipo II no desnaturalizado (Spanish); Colageno nativo tipo II (Spanish)
- Family or group
- Protein ingredient. Type II collagen is the main collagen of cartilage. Supplements use it from chicken cartilage in its natural, unbroken form.
- Harvest and processing
- A 2013 trial describes the brand as a patented form of undenatured type II collagen from chicken sternum (breastbone) cartilage. A 2023 review says soluble undenatured type II collagen is mainly made by limited enzyme treatment, and that its activity depends on source, degree of denaturation, way of giving and amount. Hydrolyzed collagen, in contrast, is broken into small pieces on purpose. Details of the process were not read beyond these statements.
- Look-alikes and adulterants
- Name: Hydrolyzed collagen (collagen peptides); Note: Collagen from animal tissue broken into small pieces. It has its own page.; Name: Chicken collagen and eggshell membrane; Note: Other chicken-derived collagen products. Has its own page.; Name: Gelatin; Note: Cooked, partly broken collagen. Has its own page.; Name: Bone broth; Note: A food made by simmering bones. Has its own page.
- Sustainability and conservation
- Not assessed.
What is inside, and how it may work
What it contains and how those compounds act in cells and animals. Laboratory and animal mechanisms are not proven effects in people.
Main compounds
| Compound | Family | Where it is concentrated | Activity studied | Level of evidence |
|---|---|---|---|---|
| Type II collagen, kept in its natural form | protein | Not read from a source. | The ingredient tested in the knee studies and the rheumatoid arthritis studies. 9 8 16 | Human data |
| Hydrolyzed collagen (for contrast) | protein fragments | Not read from a source. | A 2024 pooled review of 35 trials mixed hydrolyzed collagen, gelatin and undenatured type II collagen, so it cannot show how they compare. 7 | Human data |
Mechanisms, receptors and pathways
| Target or pathway | Gene or receptor | What was found | Level |
|---|---|---|---|
| Oral tolerance (proposed) | Immune cells in the gut | The idea is that small amounts of swallowed collagen teach the gut immune system to react less against cartilage collagen. A 2025 review states this as the mechanism; it is not shown directly in people with osteoarthritis. 5 17 | Review of preclinical and clinical studies |
| Gut-joint link in a mouse arthritis model | IL-17 and IL-22 signals | In mice with collagen-induced arthritis, oral undenatured type II collagen given before disease cut the share of mice with arthritis to 50% and lowered IL-17 and IL-22 signals in joints and gut. This is a model of autoimmune arthritis. 12 | Animal research |
| Dose and gene control of oral tolerance in rheumatoid arthritis | A gene variant, SNP A-15,737 | In people with rheumatoid arthritis whose blood cells reacted to collagen, the gene variant was linked to whether oral cow type II collagen reduced the lab immune response. Joint symptoms were not reported. 13 | Human samples (lab response) |
Absorption, metabolism and elimination
- Absorption
- Not found in the sources read. A review says digestive stability in the stomach and gut has been studied in the lab.
- Distribution
- Not found.
- Metabolism
- Not found.
- Elimination
- Not found.
- Bioavailability
- Not compared with hydrolyzed collagen in the sources read.
Isolated compounds versus whole extracts
UC-II is a processed, isolated ingredient from chicken cartilage. Whole foods that contain type II collagen, such as chicken cartilage and bone broth, bring other nutrients and different amounts. No trial compared food with the pills.
Nutritional composition
No USDA or NIH amounts of type II collagen in foods were read, so none are stated. The studied supplement amounts are milligrams a day for UC-II, versus grams for hydrolyzed collagen (see the studies table of each page). They are trial amounts, not advice.
2 mixed findings2 low certainty1 very low certainty2 not enough evidence
What was looked at
The 7 benefits and uses checked for UC-II (Undenatured Type II Collagen), each with how strong the evidence is. Tap one to open it.
- Knee osteoarthritis pain, stiffness and functionMixed findings
- Compared with glucosamine plus chondroitinLow certainty
- Knee discomfort after exercise in healthy adultsLow certainty
- Rheumatoid arthritis (autoimmune joint disease)Mixed findings
- Compared with exercise, and walking testsVery low certainty
- Protecting cartilage or slowing joint damageNot enough evidence
- Skin, bone, tendons, muscle and gutNot enough evidence
Lab markers tracked in the studies
WOMAC score (knee pain, stiffness and function)Knee range of motionCTX-II (blood marker of cartilage breakdown)
What is UC-II (Undenatured Type II Collagen) good for?
The main studied uses and how strong the human evidence is for each. Most trials are short, small and use one or two branded products, and many involve the makers.
Benefits, one by one
Each card is a research question, not a promise. Tap a goal to filter. Open a card to see the studies, doses and limits.
Knee osteoarthritis pain, stiffness and function
Mixed findingsSeveral trials of UC-II in adults with knee osteoarthritis reported lower pain and stiffness scores than placebo, and two 6-month trials were positive. A 2026 trial of 216 people, whose funding was not read, found no benefit over placebo at 24 weeks. A 2025 trial of a tablet that mixed UC-II with hydrolysed collagen also found no difference from placebo. So the picture is mixed, and most positive trials link to the makers.
7 studiesThe trials tested one or two branded products made from chicken carti…
Studies, doses and limits
What the trials found
A 6-month trial of 191 people (authors from the maker) found a bigger fall in the total knee symptom score (WOMAC) with UC-II than with placebo or with glucosamine plus chondroitin. A 90-day trial reported larger score drops with UC-II than with glucosamine plus chondroitin. A 212-person Russian trial of a branded complex with UC-II reported benefit over placebo, without numbers in the abstract. A review of 8 trials (243 people on UC-II) reported better pain and function scores. Against this, a 2026 trial of 216 Thai adults found UC-II differed from placebo by -4.7 WOMAC points (95% CI -18.6 to 9.1) at 24 weeks, not a clear difference, and the 2025 trial of 68 people with a UC-II plus hydrolysed collagen tablet found none either.
Results
Mixed. Small positive trials, mostly linked to makers, sit beside two recent trials that found no benefit over placebo.
Effect sizes as reported
2016: total WOMAC lower than placebo (p = 0.002). 2026: -4.7 points vs placebo (95% CI -18.6 to 9.1). Plain-unit sizes are not in most abstracts.
Why this rating
Mixed because small, positive, maker-linked trials conflict with a larger 2026 trial that found no benefit. Not rated higher because trials are short (3 to 6 months), pain is self-rated, and independent repeats are few.
Form and dose studied
The trials tested one or two branded products made from chicken cartilage. Studied amounts are in the studies table. Results for these products do not carry over to other products.
Who was studied
Adults, mostly women, with mild-to-moderate knee osteoarthritis; ages about 40 to 75.
Limits
Most positive trials were run or paid for by the product makers. Several are short. Self-rated pain scores. One positive trial had no placebo group. No trial showed cartilage repair.
Why researchers looked
Type II collagen is the main collagen of joint cartilage. Researchers asked whether swallowing a small amount, unbroken down, helps painful knee osteoarthritis.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Preliminary mechanism
Proposed, not shown in people. The idea is oral tolerance: small amounts of collagen reach the gut immune system and may calm immune activity aimed at the body's own cartilage collagen. The evidence comes from mouse work and reviews.
A proposed mechanism does not show that the effect happens in people.
No serious problems were reported in these trials. See the Safety tab, especially for people with autoimmune disease or chicken allergy.
Compared with glucosamine plus chondroitin
Low certaintyTwo older trials compared UC-II with glucosamine plus chondroitin, another popular joint product, and both favoured UC-II. A network review that ranked 21 supplements put UC-II third for pain, but rated the evidence quality as low.
4 studiesUC-II and a glucosamine hydrochloride plus chondroitin sulfate produc…
Studies, doses and limits
What the trials found
In the 191-person trial, total WOMAC fell more with UC-II than with glucosamine plus chondroitin at day 180 (p = 0.04). The 2009 trial reported WOMAC down 33% with UC-II against 14% with glucosamine plus chondroitin after 90 days. A 2025 network analysis of 23 trials placed UC-II third for pain with a ranking score of 87%, and rated the overall evidence low quality. In the 2026 trial, glucosamine sulfate also failed to beat placebo.
Results
UC-II looked better than glucosamine plus chondroitin in two small trials. These trials had no strong independent repeat.
Effect sizes as reported
2016: p = 0.04 vs glucosamine plus chondroitin. 2009: WOMAC -33% vs -14%. Network ranking score 87% for pain.
Why this rating
Low: two small trials, one with maker-linked authors and one without numbers of people in the abstract; the network review rates its own evidence as low quality. The 2026 trial found none of the products beat placebo.
Form and dose studied
UC-II and a glucosamine hydrochloride plus chondroitin sulfate product were compared; amounts are in the studies table.
Who was studied
Adults with knee osteoarthritis.
Limits
Comparisons were not against a prescription drug. Rankings in a network review are not effect sizes.
Why researchers looked
Glucosamine plus chondroitin is widely used, so trials used it as a comparison for UC-II.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Not established
Not established. The two products are thought to work differently, but neither mechanism is proven in people.
A proposed mechanism does not show that the effect happens in people.
Safety outcomes did not differ between groups in the 2016 trial.
Knee discomfort after exercise in healthy adults
Low certaintyThree placebo-controlled trials in healthy adults who get knee discomfort during activity reported better knee movement or less discomfort with undenatured type II collagen. All three had authors from the makers, and the effects were modest.
3 studiesTwo trials tested the UC-II brand; one tested a native type II collag…
Studies, doses and limits
What the trials found
In 55 healthy adults, knee extension was better than placebo after 120 days (81.0 vs 74.0 degrees) and people could exercise longer before first discomfort. In 96 healthy adults over 24 weeks, knee bending improved by 3.23 vs 0.21 degrees with placebo. In 74 adults, both groups improved on the KOOS joint score, but collagen helped earlier, and a blood marker of cartilage breakdown (CTX-II) fell with collagen only in people with more discomfort.
Results
Small gains in knee movement and recovery; none of these trials measured long-term joint health.
Effect sizes as reported
Knee extension 81.0 vs 74.0 degrees (p = 0.011); flexion +3.23 vs +0.21 degrees (p = 0.025).
Why this rating
Low: three small trials, each with authors from the product maker, short, with small angle changes and subgroup results.
Form and dose studied
Two trials tested the UC-II brand; one tested a native type II collagen from another maker. Amounts are in the studies table.
Who was studied
Healthy adults aged about 20 to 55 with activity-related knee discomfort and no arthritis.
Limits
All three trials involve the makers. Results are movement angles and short-term recovery, not long-term joint health.
Why researchers looked
Some active people get knee discomfort without arthritis, and researchers asked whether UC-II eases it.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Not established
Not established. The oral tolerance idea has not been tested in healthy adults.
A proposed mechanism does not show that the effect happens in people.
No product-related side effects were reported in the 55-person trial.
Rheumatoid arthritis (autoimmune joint disease)
Mixed findingsOral type II collagen was first tested decades ago in rheumatoid arthritis. A Chinese trial of 503 people compared it with the drug methotrexate and found the drug worked better. An Italian placebo trial of 60 people found no significant benefit and raised the chance of flares in some people. This is not a basis for use in rheumatoid arthritis.
3 studiesChicken or cow type II collagen in micro- to milligram amounts; not t…
Studies, doses and limits
What the trials found
In 503 people, 41.55% on chicken type II collagen met ACR20 improvement at 24 weeks, versus 57.86% on methotrexate; there was no placebo group. In 60 people on chicken type II collagen or placebo for 6 months, improvement was not significantly different, and the authors raised the possibility of flares in some people. A 2024 study found a gene variant linked to whether the immune response to oral collagen settled.
Results
Mixed and old. One trial compared with a drug, one placebo trial was negative.
Effect sizes as reported
ACR20 41.55% (collagen) vs 57.86% (methotrexate). Placebo trial: no significant difference.
Why this rating
Mixed: one large trial without a placebo, one small negative placebo trial, and different products and amounts. Both are old.
Form and dose studied
Chicken or cow type II collagen in micro- to milligram amounts; not the same as modern UC-II products.
Who was studied
Adults with active rheumatoid arthritis.
Limits
No modern UC-II product has been tested in rheumatoid arthritis in the studies read. Different amounts and products.
Why researchers looked
Rheumatoid arthritis is an immune attack on the joints, and the oral tolerance idea began here.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Preliminary mechanism
Proposed: oral tolerance, where swallowed collagen retrains the immune response. Lab studies in people with rheumatoid arthritis found that whether it works may depend on dose and on gene variants.
A proposed mechanism does not show that the effect happens in people.
One trial's authors raised the possibility of flares in some people. People with rheumatoid arthritis should ask their rheumatologist. See the Safety tab.
Compared with exercise, and walking tests
Very low certaintyIn women with knee osteoarthritis, a Brazilian trial with no placebo group found UC-II and an exercise programme both improved walking tests compared with doing nothing, but only exercise improved overall quality-of-life scores.
3 studiesOne UC-II capsule a day in the trial.
Studies, doses and limits
What the trials found
Both the exercise group and the UC-II group did better than the no-treatment group on the 6-minute walk and timed up-and-go tests. WOMAC quality-of-life scores improved significantly only with exercise. A review of 8 trials also reported better walking tests. The 2026 trial found no difference from placebo in functional performance.
Results
UC-II looked like a smaller step than exercise, in one trial with no placebo.
Effect sizes as reported
Walking tests p about 0.01 vs control (UC-II); no effect sizes in the abstract.
Why this rating
Very low: one trial without a placebo group, no sample size in the abstract, and a 2026 placebo trial that found no functional difference.
Form and dose studied
One UC-II capsule a day in the trial.
Who was studied
Women with knee osteoarthritis.
Limits
No placebo group, sample size not in the abstract; a later erratum was published.
Why researchers looked
Exercise is a standard way to help knee osteoarthritis, so researchers compared UC-II with it.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Not established
Not established.
A proposed mechanism does not show that the effect happens in people.
No safety data were given in the abstract.
Protecting cartilage or slowing joint damage
Not enough evidenceReviews say UC-II may help cartilage, but no trial read showed it. The 2026 trial found no difference from placebo in joint space width on imaging. One small trial reported a blood marker of cartilage breakdown fell, in a subgroup.
2 studiesUC-II and a native type II collagen from another maker.
Studies, doses and limits
What the trials found
The 216-person trial measured joint space width and found no difference between UC-II and placebo at 24 weeks. In the 74-person healthy-volunteer trial, CTX-II (a blood marker of cartilage breakdown) fell with collagen in people with higher basal discomfort. Marker changes are not the same as healthier cartilage.
Results
No structural benefit shown.
Effect sizes as reported
No numbers given in the abstracts.
Why this rating
Insufficient: one imaging result with no difference and one blood-marker result in a subgroup.
Form and dose studied
UC-II and a native type II collagen from another maker.
Who was studied
Adults with knee osteoarthritis; healthy adults with discomfort.
Limits
Short trials; no scans of cartilage thickness; blood markers are indirect.
Why researchers looked
Researchers hope any benefit might come from protecting cartilage, not just easing symptoms.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Preliminary mechanism
Proposed through oral tolerance; not shown to change cartilage in people.
A proposed mechanism does not show that the effect happens in people.
See the Safety tab.
Skin, bone, tendons, muscle and gut
Not enough evidenceNo human trial of UC-II for skin, bone, tendons, muscle or gut was found in this research. The trials read were all about knees. Other collagen products have their own pages.
0 studiesNot applicable.
Studies, doses and limits
Results
No evidence either way.
Why this rating
Insufficient: no human trials were found.
Limits
This is an absence of research, not a finding of no effect.
Why researchers looked
Collagen is sold for many purposes, so readers often ask.
Traditional use
UC-II is a branded form of type II collagen, the main collagen in cartilage, taken from chicken breastbone cartilage. It is sold as a supplement for joints, and swallowing it is not the same as showing it rebuilds cartilage.
Proposed mechanism Not established
Not applicable.
A proposed mechanism does not show that the effect happens in people.
Not applicable.
Connections to the rest of health
How UC-II (Undenatured Type II Collagen) connects to the rest of our health knowledge graph. Every link says what kind of connection it is. A safety link (for example to the liver) is a warning, not a benefit. A study that merely mentions a topic never creates a benefit link.
Explore every connection: goals, body systems, organs, symptoms, genes
A. Wellness goals
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Joint Support | Mixed findings | Knee osteoarthritis pain, stiffness and function: Several trials of UC-II in adults with knee osteoarthritis reported lower pain and stiffness scores than placebo, and two 6-month trials were positive. A 2026 trial of 216 people, whose funding was not read, found no benefit over placebo at 24 weeks. A 2025 trial of a tablet that mixed UC-II with hydrolysed collagen also found no difference from placebo. So the picture is mixed, and most positive trials link to the makers. Compared with glucosamine plus chondroitin: Two older trials compared UC-II with glucosamine plus chondroitin, another popular joint product, and both favoured UC-II. A network review that ranked 21 supplements put UC-II third for pain, but rated the evidence quality as low. | 9 4 1 6 5 11 18 3 8 15 10 16 2 13 | |
| Mobility Support | Mixed findings | Knee osteoarthritis pain, stiffness and function: Several trials of UC-II in adults with knee osteoarthritis reported lower pain and stiffness scores than placebo, and two 6-month trials were positive. A 2026 trial of 216 people, whose funding was not read, found no benefit over placebo at 24 weeks. A 2025 trial of a tablet that mixed UC-II with hydrolysed collagen also found no difference from placebo. So the picture is mixed, and most positive trials link to the makers. Knee discomfort after exercise in healthy adults: Three placebo-controlled trials in healthy adults who get knee discomfort during activity reported better knee movement or less discomfort with undenatured type II collagen. All three had authors from the makers, and the effects were modest. | 9 4 1 6 5 11 18 8 15 10 14 |
B. Body systems
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Bones Joints Muscles | Biological association | Mixed findings | Studied for: Knee osteoarthritis pain, stiffness and function Studied for: Compared with glucosamine plus chondroitin | 9 4 1 6 5 11 18 3 8 15 10 16 2 13 14 |
| Immune System | Biological association | Mixed findings | Studied for: Rheumatoid arthritis (autoimmune joint disease) | 16 2 13 |
E. Health conditions
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Rheumatoid arthritis | Not enough evidence | One placebo trial's authors raised the possibility of flares in some people; a drug-comparison trial found the drug worked better. Oral chicken type II collagen did worse than methotrexate in one trial; a placebo trial raised the possibility of flares. Preparation or compound: Oral chicken type II collagen |
2 16 | |
| Knee osteoarthritis | Preliminary | Mixed trials: small positive trials, mostly linked to the makers, and a 2026 trial with no benefit over placebo. Preparation or compound: Undenatured type II collagen |
9 11 |
I. Biomarkers
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| WOMAC score (knee pain, stiffness and function) | Biological association | Mixed findings | Measured in trials: lower. A lab change is not the same as a health benefit. | 9 11 |
| Knee range of motion | Biological association | Low certainty | Measured in trials: higher. A lab change is not the same as a health benefit. | 8 15 |
| CTX-II (blood marker of cartilage breakdown) | Biological association | Not enough evidence | Measured in trials: lower. A lab change is not the same as a health benefit. | 10 |
J. Genes, receptors and enzymes
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| SNP A-15,737 region (ROT1) | Preliminary mechanism | Human samples | Linked to oral tolerance response to cow type II collagen in people with rheumatoid arthritis, in lab tests. | 13 |
L. Active compounds
| Connected to | Kind of connection | Evidence status | Context | Studies |
|---|---|---|---|---|
| Type II collagen, kept in its natural form | Biological association | Human | The ingredient tested in the knee studies and the rheumatoid arthritis studies. | 9 8 16 |
| Hydrolyzed collagen (for contrast) | Biological association | Human | A 2024 pooled review of 35 trials mixed hydrolyzed collagen, gelatin and undenatured type II collagen, so it cannot show how they compare. | 7 |
Each connection is stored with the ingredient, the connected record, the kind of connection, the evidence status, the supporting studies, the preparation or compound involved, and a review date (last reviewed October 26, 2026).
Evidence at a glance: what the research found for 7 outcomes
Each outcome below is one thing researchers measured. Certainty is how far the evidence can be trusted, not how well it works. The full studies are on the next tab.
The evidence
The research centre for UC-II (Undenatured Type II Collagen). Every record here was checked against PubMed or the publisher's page; we never list a study we have not verified.
Evidence by outcome
Bars show how many studies we found for each outcome, not how well it works. People are added up across trials only (reviews are not added, to avoid double counting).
How we rate evidence
High certainty
Several well-run trials or reviews agree; further research is unlikely to change the picture much.
Moderate certainty
Good trials point the same way, but some doubt remains.
Low certainty
Small, short or inconsistent trials. The finding could change with better research.
Very low certainty
Very little or very weak human data. Treat as a possibility only.
Mixed findings
Trials or reviews disagree with each other.
Not enough evidence
Not enough human research to say either way.
Evidence against
Good research found no benefit, or found harm.
We take the reviewers' own risk-of-bias and GRADE statements where they exist, and otherwise judge from study size, design, consistency, directness and whether a product matches what is sold. Many publications do not make evidence high. Method note: We started from our earlier UC-II summary, then re-read PubMed abstracts for every trial and review cited, and added newer trials that change the picture. Only abstracts were read. The NIH Office of Dietary Supplements page could not be read and is marked unverified.
Study library: every study we checked 18
| Study | Design | People | Product, dose, length | Result |
|---|---|---|---|---|
| Alekseeva 2024 [Efficacy and safety of undenatured type II collagen in patients with knee osteoarthritis: a multicenter, prospective, double-blind, placebo-controlled, randomized trial]. Ter Arkh · PMID 38829812 · DOI |
Randomised controlled trial |
212 212 outpatients from 12 centres in Russia with knee osteoarthritis (Kellgren-Lawrence stage II-III) |
A branded complex containing undenatured chicken type II collagen Oral capsule 1 capsule a day (studied in the trial) 180 days · vs Placebo |
The authors report less pain and stiffness, better joint function and quality of life, and a good safety profile compared with placebo. The English abstract gives no numbers. Numbers not given in the abstract (Not given in the abstract) Methods, limits and fundingOutcomes: WOMAC, KOOS, pain scale, quality of life, need for anti-inflammatory painkillers Limitations: The product is described as a complex, so other ingredients may contribute; no numbers in the abstract; funding not read; published in Russian. Funding and conflicts: Funding and conflicts not stated in the abstract. Read: abstract |
| Cazzola 2000 Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study. Clin Exp Rheumatol · PMID 11072596 |
Randomised controlled trial |
60 60 people with long-standing active rheumatoid arthritis |
Chicken type II collagen Oral 0.25 mg a day (studied in the trial) 6 months · vs Placebo |
The collagen group had more ACR20 responders than placebo, but the difference was never statistically significant, and no secondary measure improved significantly. Two collagen-treated people went into clinical remission. The authors concluded oral collagen was ineffective with small, inconsistent benefits, and raised the possibility that in some people it may cause disease flares. No significant difference in ACR20 at any time (Not given in the abstract) Methods, limits and fundingOutcomes: ACR20 response and secondary measures Limitations: Small; an older product and amount; the flare warning is a possibility the authors raise, not a measured finding. Funding and conflicts: No funding statement in the record read. Read: abstract |
| Chen 2025 Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med · PMID 40425393 · DOI |
Network meta analysis |
2455 23 randomised trials, 21 dietary supplements, 2,455 people with osteoarthritis |
Many supplements, including undenatured type II collagen and collagen Oral Varied Varied · vs Placebo |
Undenatured type II collagen ranked third for WOMAC pain (ranking score 87%) and collagen fourth (84%). The authors rate the overall evidence quality as low and say larger, well-designed trials are needed. Ranking scores only for UC-II; no UC-II effect size in the abstract (Not given in the abstract for UC-II) Methods, limits and fundingOutcomes: WOMAC pain and function Limitations: Rankings are not effect sizes; evidence quality rated low; few trials per supplement. Funding and conflicts: No conflict statement in the record read. Read: abstract |
| Crowley 2009 Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial. Int J Med Sci · PMID 19847319 · DOI |
Randomised controlled trial |
Adults with knee osteoarthritis (number of people not given in the abstract) | UC-II undenatured type II collagen, compared with glucosamine plus chondroitin Oral Amounts not given in the abstract 90 days · vs Glucosamine plus chondroitin (no placebo group mentioned) |
UC-II lowered the WOMAC score by 33% compared with 14% in the glucosamine plus chondroitin group after 90 days. Pain scale fell by 40% vs 15.4%. Lequesne index fell by 20% vs 6%. The abstract says the benefit was seen in all measures for UC-II but not for glucosamine plus chondroitin. WOMAC -33% vs -14%; pain scale -40% vs -15.4% (Not given in the abstract) Methods, limits and fundingOutcomes: WOMAC, pain scale (VAS), Lequesne functional index Limitations: Number of participants and statistics are not in the abstract; no placebo group is described; short. Funding and conflicts: The record lists no conflict of interest. The abstract does not name a funder or say whether the product maker took part. Read: abstract |
| Gupta 2025 Undenatured type II collagen for knee osteoarthritis. Ann Med · PMID 40253594 · DOI |
Systematic review |
12 studies: 3 lab or animal studies, 8 human studies and 1 with both | Undenatured type II collagen Oral 40 mg a day in the human studies (studied in trials) Short- and mid-term · vs Placebo or other treatments |
The authors say the effect is thought to work through oral tolerance and that the studies they read showed less pain and better function over the short and middle term with no safety concerns. They also say adequately powered, longer trials are needed before routine use is justified. Not a pooled analysis (Not applicable) Methods, limits and fundingOutcomes: Mechanism, pain, function, range of motion, quality of life, safety Limitations: A narrative summary, not a pooled analysis; wording on mechanism is stronger than the evidence in people; the first author is affiliated with a biologics company. Funding and conflicts: The authors report no conflict of interest. First author's affiliation is a biologics company (Future Biologics). Read: abstract |
| Kumar 2023 Efficacy of undenatured collagen in knee osteoarthritis: review of the literature with limited meta-analysis. Am J Transl Res · PMID 37854210 |
Systematic review |
243 8 randomised trials in adults with early knee osteoarthritis; 243 people took UC-II |
Undenatured collagen type II (UC-II) Oral Varied Follow-up 3 to 6 months · vs Placebo or control |
Pain (VAS) and WOMAC scores were better with UC-II than with placebo, and timed up-and-go and 6-minute walk tests improved from baseline. Complications were similar to other supplements. The authors call the literature limited and ask for larger trials. Numbers not given in the abstract (Not given in the abstract) Methods, limits and fundingOutcomes: Pain scale, WOMAC, knee function, range of motion, complications Limitations: Few trials, short follow-up; the review itself says it is limited; it includes trials without a placebo group. Funding and conflicts: The record lists no conflict of interest. Read: abstract |
| Liang 2024 Efficacy and safety of collagen derivatives for osteoarthritis: A trial sequential meta-analysis. Osteoarthritis Cartilage · PMID 38218227 · DOI |
Systematic review meta analysis |
3165 35 randomised trials in people with osteoarthritis (25 trials, 2,856 people, in the main analysis) |
Collagen derivatives (hydrolyzed collagen, gelatin, undenatured type II collagen and others) Oral Varied by trial Varied · vs Placebo or control |
Small-to-moderate improvement in pain and in function versus control. Collagen derivatives did not raise the risk of side effects or dropouts. Different collagen products were pooled, so the result is not specific to UC-II. Pain SMD -0.35; function SMD -0.31 (Pain -0.48 to -0.22 (moderate certainty); function -0.41 to -0.22 (high certainty)) Methods, limits and fundingOutcomes: Pain and function scores; withdrawals and side effects Limitations: Groups different collagen products together, so it cannot say whether UC-II and hydrolyzed collagen work the same. Pain is self-reported. Cartilage repair was not measured. Funding and conflicts: No conflict statement in the record read. Read: abstract |
| Lugo 2013 Undenatured type II collagen (UC-II) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers. J Int Soc Sports Nutr · PMID 24153020 · DOI |
Randomised controlled trial |
55 55 healthy adults with knee pain after strenuous exercise but no arthritis |
UC-II undenatured type II collagen (chicken sternum) Oral 40 mg a day (studied in the trial) 120 days · vs Placebo |
After 120 days knee extension was better in the UC-II group than placebo (81.0 vs 74.0 degrees, p = 0.011). The UC-II group exercised 2.8 minutes longer before first discomfort versus 1.4 minutes at baseline (p = 0.019). Five UC-II people reported no pain after the test versus one on placebo. No product-related adverse events were seen. Knee extension 81.0 vs 74.0 degrees (p = 0.011) (Not given in the abstract) Methods, limits and fundingOutcomes: Knee extension and flexion; time to first joint discomfort and recovery after a stepmill test Limitations: Small; one test protocol; links to the product maker; not shown to prevent joint damage. Funding and conflicts: Run with a contract research company. The first two authors are listed as employees of the product maker (InterHealth) in the 2016 trial by the same group; the maker is not named in this abstract. Read: abstract |
| Lugo 2016 Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study. Nutr J · PMID 26822714 · DOI |
Randomised controlled trial |
191 191 adults with knee osteoarthritis |
UC-II undenatured type II collagen (chicken sternum cartilage), compared with glucosamine plus chondroitin and with placebo Oral 40 mg a day of UC-II; glucosamine hydrochloride 1,500 mg plus chondroitin sulfate 1,200 mg a day (studied in the trial) 180 days · vs Placebo, and glucosamine plus chondroitin |
At day 180 the UC-II group had a bigger fall in total WOMAC score than placebo (p = 0.002) and than glucosamine plus chondroitin (p = 0.04). Pain, stiffness and function subscales also favoured UC-II over placebo. Safety outcomes did not differ between groups. Total WOMAC: p = 0.002 vs placebo; p = 0.04 vs glucosamine plus chondroitin (Not given in the abstract) Methods, limits and fundingOutcomes: Total WOMAC score (main); Lequesne index, pain scale, WOMAC subscales; safety Limitations: Two authors work for the product maker; a short trial; self-rated symptoms; not repeated by an independent team in the studies read. Funding and conflicts: Two of three authors are employed by InterHealth Nutraceuticals, the maker of the product tested. Read: abstract |
| Moller 2026 Efficacy and tolerability of native (undenatured) type II collagen supplementation for joint health in healthy volunteers: a randomized double-blind placebo-controlled study. Nutr J · PMID 41787523 · DOI |
Randomised controlled trial |
74 74 healthy adults with joint discomfort during physical activity |
Native (undenatured) type II collagen from a different maker than the UC-II brand Oral 40 mg a day (studied in the trial) 180 days · vs Placebo |
Both groups improved on the KOOS score at 180 days. Improvements began earlier with collagen for pain, symptoms and quality of life. In people with milder discomfort, differences between groups were seen at 180 days. In people with more discomfort, CTX-II fell with collagen and rose with placebo. Between-group differences in some subgroups; numbers not in the abstract (Not given in the abstract) Methods, limits and fundingOutcomes: KOOS score, time to recover after exercise, CTX-II (a blood marker of cartilage breakdown) Limitations: Many results come from subgroups; both groups improved; numbers not in the abstract. Funding and conflicts: Two authors work for the product maker (Bioiberica); one was a paid consultant to it. Read: abstract |
| Narkbunnam 2026 A Comparison of Clinical Outcomes Among Undenatured Collagen Type II, Glucosamine Sulfate, and Diacerein on Osteoarthritic Knee Treatment: A Randomized Clinical Trial. JB JS Open Access · PMID 42698930 · DOI |
Randomised controlled trial |
216 216 Thai adults with mild-to-moderate knee osteoarthritis; 208 finished |
UC-II undenatured collagen type II, compared with glucosamine sulfate, diacerein and placebo Oral UC-II 40 mg once a day (studied in the trial) 24 weeks, follow-up to 36 weeks · vs Placebo |
No supplement beat placebo at 24 weeks. UC-II differed from placebo by -4.7 WOMAC points (95% CI -18.6 to 9.1), and no confidence range excluded zero. Results at 36 weeks were similar. Pain, joint space width and function tests did not differ. Adverse events were mild and similar across groups; none were serious. The authors say the results do not support routine use as the only treatment. UC-II vs placebo: -4.7 total WOMAC points at week 24 (-18.6 to 9.1) Methods, limits and fundingOutcomes: Total WOMAC score at week 24 (main); pain scores, joint space width, functional tests; adverse events Limitations: One country; mostly women; the abstract does not list funding (disclosure forms are online and were not read). Funding and conflicts: Funding and conflicts are in forms online that were not read. Read: abstract |
| Pan 2024 Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity. Commun Biol · PMID 38961129 · DOI |
Animal study mouse |
Mice with collagen-induced arthritis (a lab model) | Undenatured type II collagen Oral 7.33 mg per kg three times a week, started before disease (studied in mice) Not given in the abstract · vs Untreated mice |
Treatment cut arthritis in mice to 50% of animals, lowered IL-17 and IL-22 signals in the joints, and protected the gut. The authors say this supports a gut-to-joint link for oral tolerance. Disease incidence 50% in treated mice (Not applicable) Methods, limits and fundingOutcomes: Arthritis incidence, joint and gut immune signals, gut bacteria Limitations: Mice, a model of autoimmune arthritis, not osteoarthritis; given before disease; not proof in people. Funding and conflicts: Three authors are employees of Lonza Greenwood, which sells UC-II. Read: abstract |
| Postlethwaite 2024 Optimizing oral immune tolerance to Type II collagen in patients with rheumatoid arthritis: The importance of dose, interfering medication and genetics. Am J Med Sci · PMID 38897565 · DOI |
Randomised controlled trial |
People with rheumatoid arthritis whose blood cells reacted to type II collagen in the lab | Oral bovine (cow) type II collagen, low-dose or high-dose schedules Oral Micrograms a day, rising every 10 weeks (studied in the trial) 30 weeks · vs Low-dose versus high-dose schedule |
A gene variant (SNP A-15,737) was linked to whether oral collagen reduced the immune cell response in lab tests. The authors conclude a gene region helps decide whether oral tolerance to collagen develops. It does not report joint symptoms. Gene association with immune response in lab tests (Not given in the abstract) Methods, limits and fundingOutcomes: Immune cell interferon-gamma response in lab dishes; gene variants Limitations: Measures a lab immune response, not symptoms; cow collagen; small numbers not given in the abstract. Funding and conflicts: Two authors are named on a university patent; grants from NIH and the US Department of Veterans Affairs. Read: abstract |
| Santana 2023 Comparison between exercise therapy and non-hydrolyzed collagen (UC-II) in functionality and quality of life in women with knee osteoarthritis: A randomized controlled clinical trial. Wien Klin Wochenschr · PMID 35612617 · DOI |
Randomised controlled trial |
Women with knee osteoarthritis (number not given in the abstract) | UC-II non-hydrolyzed collagen, compared with an exercise programme and with no treatment Oral capsule 1 capsule a day (studied in the trial) Not given in the abstract (exercise group had 12 sessions) · vs No-treatment control group (no placebo) |
Walking tests improved in both the exercise group and the UC-II group compared with the control group. Quality of life (WOMAC) improved significantly only in the exercise group. The authors say exercise and UC-II had similar effects on function, but exercise was better for quality of life. 6-minute walk and timed up-and-go better than control in both groups (p about 0.01 for UC-II) (Not given in the abstract) Methods, limits and fundingOutcomes: 6-minute walk test, timed up-and-go test, WOMAC Limitations: No placebo, so people knew whether they took a capsule; sample size not in the abstract; the journal later published an erratum. Funding and conflicts: No funding statement in the record read. Read: abstract |
| Schon 2022 UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study. J Integr Complement Med · PMID 35377244 · DOI |
Randomised controlled trial |
96 96 healthy adults aged 20 to 55 with joint discomfort during activity and no joint disease |
UC-II undenatured type II collagen Oral 40 mg a day (studied in the trial) 24 weeks · vs Placebo |
Knee bending (flexion) improved by 3.23 degrees with UC-II versus 0.21 degrees with placebo (p = 0.025). Extension rose 2.21 degrees over time with UC-II (p = 0.0061); placebo rose 1.27 degrees (not significant). The gain in flexion was larger in people over 35. Flexion +3.23 vs +0.21 degrees (p = 0.025) (Not given in the abstract) Methods, limits and fundingOutcomes: Knee range of motion (flexion and extension) measured with a goniometer Limitations: Small angle changes; measures of range of motion, not pain; authors from the product maker. Funding and conflicts: Three authors are employees of Lonza Greenwood, the company that sells the product. Read: abstract |
| Wei 2009 A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther · PMID 19951408 · DOI |
Randomised controlled trial |
503 503 people with rheumatoid arthritis in China |
Chicken type II collagen (from chicken breast cartilage) compared with methotrexate Oral 0.1 mg a day of collagen versus 10 mg a week of methotrexate (studied in the trial) 24 weeks · vs Methotrexate (no placebo group) |
Both groups improved. At 24 weeks 41.55% of the collagen group and 57.86% of the methotrexate group met the ACR20 improvement criteria (the collagen rate was lower, p < 0.05). Collagen had fewer and milder side effects than methotrexate; stomach complaints were common in both. ACR20 41.55% vs 57.86%; ACR50 16.89% vs 30.82% (Not given in the abstract) Methods, limits and fundingOutcomes: Pain, joint counts, ACR response rates, disease activity, safety Limitations: No placebo group; the collagen did less well than the drug; one country; the authors' conclusion that it is effective goes beyond a drug comparison. Funding and conflicts: No funding statement in the record read. Read: abstract |
| Xu 2023 Undenatured type II collagen and its role in improving osteoarthritis. Ageing Res Rev · PMID 37774932 · DOI |
Narrative review mixed |
Review of lab, animal and human work on undenatured type II collagen | Undenatured type II collagen Oral Varied Varied |
The authors say soluble undenatured type II collagen is mainly made by limited enzyme treatment, and that its activity depends on the raw material, how much it is denatured, how it is given and the amount. They say how structure links to activity and mechanism is unclear. Not applicable (Not applicable) Methods, limits and fundingOutcomes: Extraction, structure, stability, effect on osteoarthritis, mechanism Limitations: A narrative review; mostly lab and animal work. Funding and conflicts: The authors declare no competing interests. Read: abstract |
| Yuenyongviwat 2025 Efficacy of combined undenatured type II collagen and hydrolysed collagen supplementation in knee osteoarthritis: a randomised controlled trial. Sci Rep · PMID 40897777 · DOI |
Randomised controlled trial |
68 68 adults with knee osteoarthritis |
Tablet containing both hydrolysed collagen and UC-II (not UC-II alone) Oral tablet Amount not given in the abstract 12 weeks · vs Placebo |
Both groups improved over time, but there was no difference between collagen and placebo in pain, function, rescue medicine or satisfaction. No side effects were reported in either group. No significant difference between groups (p > 0.05) (Not given in the abstract) Methods, limits and fundingOutcomes: Pain score, KOOS function score, rescue medicine use, satisfaction Limitations: A combined tablet, so the result is not for UC-II alone; short; small. Funding and conflicts: The authors declare no competing interests. The abstract says earlier collagen studies were mostly industry-sponsored. Read: abstract |
What we do not know yet
- No trial compared UC-II directly with hydrolyzed collagen.
- No independent repeat of the early positive trials was found, and the 2026 trial funding was not read.
- No long trial showed that UC-II changes cartilage.
- NIH ODS could not be read, and NCCIH has no collagen page.
- No interaction, pregnancy, breastfeeding, children or allergy data were found.
- No testing of UC-II products for quality or label accuracy was found.
How new research is added
New studies are found by a saved PubMed search and placed in a review queue before the page changes.
Lab markers
What changed in blood or saliva tests during trials. A changed number is not the same as feeling or being healthier, and we give no "normal ranges".
Other 3
WOMAC score (knee pain, stiffness and function)
Lower in trials
A questionnaire where people rate knee pain, stiffness and how hard everyday activities are. Lower is better.
Mixed findingsResults and what it means
Why it was measured
To see whether a supplement changes how the knee feels and works day to day.
Statistical vs. clinical meaning
The score is self-rated. The two largest trials disagree.
Safety implication
Safety outcomes were similar between groups in both trials.
| Study | Result | People | Product |
|---|---|---|---|
| 9 | Total WOMAC fell more with UC-II than with placebo (p = 0.002) and glucosamine plus chondroitin (p = 0.04) at day 180 | 191 adults with knee osteoarthritis | UC-II for 180 days |
| 11 | UC-II minus placebo: -4.7 points (95% CI -18.6 to 9.1) at week 24 | 216 Thai adults with knee osteoarthritis | UC-II for 24 weeks |
Knee range of motion
Higher in trials
How far the knee can straighten (extension) and bend (flexion), measured in degrees with an angle tool.
Low certaintyResults and what it means
Why it was measured
To see whether joint discomfort limits movement and whether a supplement helps it.
Statistical vs. clinical meaning
A few degrees; not shown to matter in daily life.
Safety implication
No product-related side effects reported in the 55-person trial.
CTX-II (blood marker of cartilage breakdown)
Lower in trials
A fragment released into the blood when type II collagen in cartilage breaks down. Higher can mean more breakdown.
Not enough evidenceResults and what it means
Why it was measured
As a stand-in for cartilage wear, since cartilage cannot be measured directly in a supplement trial.
Statistical vs. clinical meaning
A subgroup result on a marker, not proof of healthier cartilage.
Safety implication
Not applicable.
| Study | Result | People | Product |
|---|---|---|---|
| 10 | CTX-II fell with collagen and rose with placebo in people with higher basal discomfort | 74 healthy adults with activity-related joint discomfort | Native type II collagen for 180 days |
Safety
What studies and official sources say about side effects, medicines and who should check first. Each point shows what kind of evidence it comes from.
Main points to know 3
- People with autoimmune disease: an open question. UC-II is proposed to act through the immune system. In one placebo trial in rheumatoid arthritis, the authors raised the possibility that oral type II collagen may cause flares in some people. No safety trial of a modern UC-II product in people with rheumatoid arthritis or other autoimmune disease was read. If you have an autoimmune condition or take medicine that changes the immune system, ask your doctor before using it. Randomised trial (authors' warning) and mechanism idea 2 16
- Source is chicken cartilage. The products tested in these trials are made from chicken breastbone or breast cartilage. No allergy study or case report of UC-II was read. Ask an allergist before using it if you have a chicken allergy. Source fact; absence of evidence 9 16
- Short trials only. The trials ran 3 to 6 months. Long-term safety is not established. Joint pain that is new, swollen or hot, or that comes with fever, should be seen by a doctor and not treated with a supplement. Trial duration (reviews) 6 5
Side effects 5
| Effect | How often | Severity and recovery | Evidence |
|---|---|---|---|
| No difference in safety outcomes from placebo or glucosamine plus chondroitin The abstract does not list specific side effects. | Not different between groups in a 191-person, 180-day trial | Not applicable Not applicable | Randomised trial (authors from the maker) 9 |
| Mild side effects, similar to placebo and other supplements Types of side effects were not given in the abstract. | Comparable across groups in 216 people; none serious | Mild Not stated | Randomised trial 11 |
| No side effects reported | None in 68 people over 12 weeks (combined UC-II and hydrolysed collagen tablet); none product-related in 55 people over 120 days | Not applicable Not applicable | Randomised trials 18 8 |
| Stomach complaints Different amount and product than modern UC-II. | Common in both groups of a 503-person rheumatoid arthritis trial, fewer and milder with chicken collagen than with methotrexate | Mild to moderate Not stated | Randomised trial (no placebo) 16 |
| Possible disease flare in rheumatoid arthritis A possibility the authors raise, not an established finding. | Raised as a possibility in some people; not measured | Not stated Not stated | Authors' statement in a 60 person trial 2 |
Liver
No liver injury from UC-II was found in the sources read. A liver-safety reference (LiverTox) was not opened. One trial abstract says blood and urine safety tests were done, without giving results. 1
How often. No frequency was found.
Monitoring. No agency monitoring advice was found.
This is a safety connection. It is not evidence that UC-II (Undenatured Type II Collagen) supports liver health.
Medicines and supplements 4
| With | Why it matters | Importance | Evidence | What to do |
|---|---|---|---|---|
| Immune-modifying medicines (for example methotrexate and similar drugs) prescription | UC-II is proposed to act on immune tolerance. Whether it adds to or blunts these medicines was not studied. | No interaction study was found. In the 503-person trial collagen was compared against methotrexate, not combined with it. | Absence of evidence; mechanism idea Not enough evidence 16 | Absence of a study is not proof of safety. Tell your doctor or pharmacist about all supplements. |
| Glucosamine and chondroitin supplement | Compared head to head in two trials, not combined. NCCIH says glucosamine and chondroitin may interact with the blood thinner warfarin; that statement is about those supplements, not UC-II. | No interaction between UC-II and glucosamine or chondroitin was reported. | Absence of evidence; regulator statement on other products Not enough evidence 9 4 | Check labels: some joint products combine several ingredients. Ask a pharmacist, especially if you take warfarin. |
| Hydrolyzed collagen in the same product supplement | Some products mix UC-II with hydrolysed collagen. | No side effects were reported in the one trial of a mixed tablet. | Randomised trial Low certainty 18 | Read the full label for all ingredients. |
| Pain medicines such as anti-inflammatory drugs prescription | No mechanism found. | One trial counted use of rescue painkillers as an outcome; no interaction was reported. | Absence of evidence Not enough evidence 18 | Ask a doctor or pharmacist about combining joint supplements with pain medicine. |
Who should check first 5
| Situation | Advice | Evidence |
|---|---|---|
| Rheumatoid arthritis or other autoimmune disease, or taking immune-modifying medicine | Ask your specialist before using. Oral type II collagen was studied in rheumatoid arthritis, with mixed results and a flare warning from one trial. | Randomised trials and mechanism idea 2 16 |
| Chicken allergy | Products are made from chicken cartilage. No allergy data on UC-II were read. Ask an allergist. | Source fact; absence of evidence 9 |
| Pregnancy and breastfeeding | No safety study in pregnancy or breastfeeding was found in the sources read. Ask a doctor or midwife before using it. | Absence of evidence |
| Children | Trials were in adults (about 20 to 75). No data in children were read. Do not give it to a child without a doctor's advice. | Absence of evidence 15 1 |
| Before surgery or with a swollen, hot or fevered joint | A hot, swollen joint with fever can be infection and needs a doctor, not a supplement. Tell your surgeon about all supplements. | General caution (not from a UC II study) |
Overdose, product quality and regulators
Summary. No poisoning or overdose reports for UC-II were found in the sources read.
Animal. Mouse studies of oral undenatured type II collagen in arthritis models did not report toxicity in the abstract read.
High dose or long term signals. Long-term safety beyond 6 months was not found.
Overdose response. Not found.
Genotoxicity. Not researched.
No test of UC-II products for metals, contaminants or label accuracy was found. A review says the activity of undenatured type II collagen depends on the raw material and on how much it was denatured, so how a product is made may matter.
Whether a product is truly undenatured. A 2023 review says the activity of undenatured type II collagen is affected by source material, degree of denaturation, how it is given and the amount. No study checked how many products on the market keep their native form. 17
Branded complexes and tablets. One Russian trial tested a branded complex and one Thai trial tested a tablet that also had hydrolysed collagen. Results from those do not apply to UC-II alone. 1 18
| Body | Action | Date |
|---|---|---|
| NCCIH (US National Center for Complementary and Integrative Health) (United States) | The NCCIH osteoarthritis in-depth page does not mention collagen. It says the evidence on dietary supplements other than glucosamine and chondroitin is too limited for conclusions. There is no NCCIH page on collagen (HTTP 404). source |
When to get medical help
- Swelling of the face, lips or tongue, hives, wheezing or trouble breathing after taking a product: call emergency services.
- A joint that is suddenly hot, red and swollen, especially with fever: see a doctor the same day.
- If you have rheumatoid arthritis and your joints flare, swell more or stay stiff longer after starting a product: stop it and call your rheumatologist.
- Persistent vomiting or stomach pain after a product: stop it and see a doctor.
Stop using the product and contact a clinician or emergency service. In the US, Poison Control is 1-800-222-1222.
General information only, not medical advice. Ask a clinician or pharmacist before use, especially with medicines, in pregnancy or with a health condition. See the Natural Remedy Safety guide.
Frequently asked questions
What is UC-II?
How is UC-II different from hydrolyzed collagen?
Does UC-II help knee osteoarthritis?
Is UC-II better than glucosamine and chondroitin?
Is UC-II the same as hydrolyzed collagen for joints?
No. They are different products with different proposed ways of working. A 2024 review of 35 trials pooled them together, so it cannot say which is better.
Can UC-II help joint discomfort from exercise?
Does UC-II protect or rebuild cartilage?
Is UC-II useful for rheumatoid arthritis?
Can UC-II be a problem for people with autoimmune disease?
It is proposed to act on the immune system. One trial's authors raised the chance of flares in some people with rheumatoid arthritis. No modern safety trial exists. Ask your doctor.
Is UC-II safe?
Can people with chicken allergy use UC-II?
UC-II is made from chicken cartilage. No allergy study was found. Ask an allergist.
Explore by health goal
Editorial transparency
- Written by
- AlternativeMed editorial team. Research compiled with AI assistance, then checked against the sources listed.
- Medical review
- None. This page has not been reviewed by a physician or pharmacist.
- First published
- 2026-10-26
- Last substantive update
- 2026-10-26
- How we research
- We started from our earlier UC-II summary, then re-read PubMed abstracts for every trial and review cited, and added newer trials that change the picture. Only abstracts were read. The NIH Office of Dietary Supplements page could not be read and is marked unverified.
- How we rate evidence
- See "How we rate evidence" in the Evidence tab.
- Independence
- No product is promoted on this page. No affiliate links are shown. Several trials were run with the makers; this is flagged where the abstracts show it.
Sources 18
Each source was opened and checked. Where we read only the abstract, it says so. The small numbers in the text point here.
- Alekseeva LI, Kashevarova NG, Taskina EA, Strebkova EA, Korotkova TA, Sharapova EP et al.. [Efficacy and safety of undenatured type II collagen in patients with knee osteoarthritis: a multicenter, prospective, double-blind, placebo-controlled, randomized trial].. Ter Arkh. 2024. PMID 38829812. DOI 10.26442/00403660.2024.05.202788. (abstract)
- Cazzola M, Antivalle M, Sarzi-Puttini P, Dell'Acqua D, Panni B, Caruso I. Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study.. Clin Exp Rheumatol. 2000. PMID 11072596. (abstract)
- Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ et al.. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis.. J Integr Med. 2025. PMID 40425393. DOI 10.1016/j.joim.2025.04.008. (abstract)
- Crowley DC, Lau FC, Sharma P, Evans M, Guthrie N, Bagchi M et al.. Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial.. Int J Med Sci. 2009. PMID 19847319. DOI 10.7150/ijms.6.312. (abstract)
- Gupta A, Maffulli N. Undenatured type II collagen for knee osteoarthritis.. Ann Med. 2025. PMID 40253594. DOI 10.1080/07853890.2025.2493306. (abstract)
- Kumar P, Bansal P, Rajnish RK, Sharma S, Dhillon MS, Patel S et al.. Efficacy of undenatured collagen in knee osteoarthritis: review of the literature with limited meta-analysis.. Am J Transl Res. 2023. PMID 37854210. (abstract)
- Liang CW, Cheng HY, Lee YH, Liao CD, Huang SW. Efficacy and safety of collagen derivatives for osteoarthritis: A trial sequential meta-analysis.. Osteoarthritis Cartilage. 2024. PMID 38218227. DOI 10.1016/j.joca.2023.12.010. (abstract)
- Lugo JP, Saiyed ZM, Lau FC, Molina JP, Pakdaman MN, Shamie AN, Udani JK. Undenatured type II collagen (UC-II) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.. J Int Soc Sports Nutr. 2013. PMID 24153020. DOI 10.1186/1550-2783-10-48. (abstract)
- Lugo JP, Saiyed ZM, Lane NE. Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.. Nutr J. 2016. PMID 26822714. DOI 10.1186/s12937-016-0130-8. (abstract)
- Moller I, Martinez K, Terradillos-Guillen A, Costa-Larrion E, Martinez-Puig D, Velasco-Alvarez J. Efficacy and tolerability of native (undenatured) type II collagen supplementation for joint health in healthy volunteers: a randomized double-blind placebo-controlled study.. Nutr J. 2026. PMID 41787523. DOI 10.1186/s12937-026-01302-0. (abstract)
- Narkbunnam R, Awirotananon K, Chareancholvanich K, Achawakulthep C, Adulkasem N, Chatmaitri S et al.. A Comparison of Clinical Outcomes Among Undenatured Collagen Type II, Glucosamine Sulfate, and Diacerein on Osteoarthritic Knee Treatment: A Randomized Clinical Trial.. JB JS Open Access. 2026. PMID 42698930. DOI 10.2106/JBJS.OA.26.00225. (abstract)
- Pan P, Wang Y, Nyirenda MH, Saiyed Z, Karimian Azari E, Sunderman A et al.. Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity.. Commun Biol. 2024. PMID 38961129. DOI 10.1038/s42003-024-06476-z. (abstract)
- Postlethwaite AE, Jiao Y, Yang C, Dong W, Aelion JA, Wang B et al.. Optimizing oral immune tolerance to Type II collagen in patients with rheumatoid arthritis: The importance of dose, interfering medication and genetics.. Am J Med Sci. 2024. PMID 38897565. DOI 10.1016/j.amjms.2024.06.008. (abstract)
- Santana ETN, da Cunha Machado S, Brandao Lima VN, DeSantana Filho VJ, Dos Santos Maciel LY, de Farias Neto JP et al.. Comparison between exercise therapy and non-hydrolyzed collagen (UC-II) in functionality and quality of life in women with knee osteoarthritis: A randomized controlled clinical trial.. Wien Klin Wochenschr. 2023. PMID 35612617. DOI 10.1007/s00508-022-02037-8. (abstract)
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Where to buy
Check the label first. Whatever you buy, look for these:
- The amount of the active ingredient per serving, not just the front-label claim
- A third-party testing mark (USP, NSF or ConsumerLab)
- Other ingredients and allergens
- Ask a pharmacist about interactions with your medicines
Talk to a pharmacist or doctor before you start any supplement, especially if you take medicines. See the Safety tab for interactions.
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