Type 2 Collagen For Arthritis & Joint Pain (UC-II): An Overlooked Intervention

Beginning in late February 2017, I noticed some numbness in my right index finger along with uncontrolled twitching.  At the time, I figured it was likely from excessive computer use, in particular, frequently clicking the mouse.  Though the numbness and twitching abated, I went on to develop pain in the back of the same hand with the formerly numb and twitching fingertip.  Initially, the pain was fairly mild yet still uncomfortable enough to deter me from using the computer.

Based on a bit of self-reflection and research, I figured it was likely an RSI (repetitive stress injury) or CTD (cumulative trauma disorder) resulting from a combination of: overuse of the computer (typing and clicking) and cell phone (texting), muscle tension (from stress), poor ergonomics (putting pressure on nerves), and lifting heavy weights.  That said, even after taking significant time off of work (over a month), the pain continued to worsen.  Eventually the pain became so bad that I was unable to turn a doorknob, wash dishes, or operate a simple TV remote without experiencing a sharp, stabbing sensation.

Each time I used my hands it felt as though they were recovering from being beaten with a hammer.  The backsides of my hands were most affected by the pain – specifically between my knuckles and wrists; neither hand was worse than the other – both were insanely painful.  After 1-2 months of resting my hands and hoping that the pain would spontaneously resolve, the pain remained awful and I forced myself to see a doctor.

The doctor examined my symptoms and pointed out that I also had eye inflammation (conjunctivitis).  He went on to diagnose me with arthritis and prescribed a combination of voltaren gel (4x per day) and meloxicam tablets (as needed) – neither provided much benefit.  Because none of the prescriptions were helping, I began researching alternative treatments for arthritis and stumbled upon undenatured type 2 collagen.

What is collagen? (3 Types)

Before reading any further, you should probably understand what collagen is.  Collagen is the most abundant protein within the human body and is comprised of amino acids:  glycine, proline, hydroxyproline, and arginine.  The combination of amino acids within collagen support our body’s bones, ligaments, tendons, hair, skin, and nails.  Consuming a balanced diet helps the body synthesize collagen.

Types of collagen: There are several types of collagen within the body.

  • Type 1 collagen: Comprises 90% of skin, hair, nails, organs, bones, and ligaments.
  • Type 2 collagen: Applies to cartilage within the body.
  • Type 3 collagen: Applies to fibrous protein in bone, cartilage, dentin, tendon, and various connective tissues.

What is undenatured type 2 collagen (UC-II)?

Undenatured type 2 collagen sold as “UC-II” is a patented form of undenatured type 2 collagen (undenatured means not processed/denatured by high heat or chemicals) derived specifically from chicken sternum cartilage along with other inactive ingredients.  Undenatured type 2 collagen (UC-II) is different from hydrolyzed/denatured collagen in that it contains active ingredients that modulate the immune system.  The immunomodulators contained within undenatured type 2 collagen decrease the secretion of enzymes that metabolize endogenous type 2 collagen, which attenuates part of the inflammatory response commonly observed in arthritis and joint disorders.

What happens to the joints in arthritis?

Osteoarthritis: In osteoarthritis, the immune system generates an attack on the joints to induce inflammation, swelling, and pain.  This inflammatory attack is mediated and/or exacerbated by exposed microscopic collagen fibers.  The immune system mistakes these collagen fibers as being akin to pathogenic cellular invaders, ultimately signaling for killer T-cells to attack the joints with these collagen fibers.

When the killer T-cells reach the joints, proinflammatory cytokines are released in attempt to eviscerate collagen – mistaken as a pathogenic cellular invader.  After the proinflammatory cytokines are released, even more killer T-cells are sent to the joints – and a vicious circle of joint degradation is set in motion and maintained.  Ultimately, a cell-destroying protein cluster known as the “membrane attack complex” (MAC) is released and binds to cartilage-generating cells.

Binding of membrane attack complexes (MAC) to cartilage-generating cells facilitates the secretion of complement-component proteins, inflammatory biomarkers, and enzymes.  The combination of these proteins, inflammatory biomarkers, and enzymes continue degrading cartilage matrixes in the joints.  Thereafter, as cartilage matrixes are attacked and destroyed by the immune system, they secrete byproducts in the process such as: fibromodulin.

The byproducts such as fibromodulin secreted in the process of cartilage matrix death reinforces continued joint-tissue damage.  So to summarize: exposed small surface collagen fibers are responsible for the primary immune attack on joints, but secondary effects and signaling cascades eventually degrade joint cartilage.  This causes persons to experience a combination of joint pain, swelling, redness, and grinding – known as osteoarthritis.

Rheumatoid arthritis: In rheumatoid arthritis, the immune system mistakenly attacks components of joints such as the synovial fluid, synovial membranes, and exposed cartilage.  As a result of this attack, a pronounced inflammatory response occurs whereby levels of proinflammatory cytokines skyrocket.  (This is why many people with rheumatoid arthritis exhibit abnormally high levels of C-reactive protein in bloodwork).

This autoimmune-mediated attack on joints inevitably leads to the exposure of collagen fibers (somewhat similar to as occurs among individuals with osteoarthritis).  Predictably, collagen fibers are then mistaken by the immune system as invader cells whereby an additional immune reaction occurs: killer T-cells are released, inflammation increases, and more killer T-cells are sent to the joints – followed by: membrane attack complexes, component-component proteins, and various enzymes to further degrade the joints.  As you would expect, this yields a vicious circle of incessant joint pain, swelling, and redness.

Note: The above explanations regarding osteoarthritis and rheumatoid arthritis are gross oversimplifications.  I tried to reference the disease processes that are most relevant in regards to treatment with undenatured type 2 collagen.

How does undenatured type 2 collagen (UC-II) treat arthritis and joint pain?

Misinformation: There’s much misinformation being spread on the internet about “collagen” for the treatment of arthritis and joint disorders.

Many articles have been written about general collagen for the management of joint pain – without knowledge that only the specific type known as undenatured type 2 collagen (UC-II) is supported by some evidence as a potentially-efficacious therapeutic intervention.

Moreover, many people, including some professionals (e.g. ScienceBasedMedicine) have gone as far as to deem “collagen an implausible supplement for joint pain.”

Clearly many haven’t bothered researching the correct format of collagen to administer for joint pain or the likely mechanism by which it would attenuate joint pain.

A common misunderstanding is that undenatured type 2 collagen (UC-II) supplements function by delivering extra type 2 collagen (from the supplement) to the body.

Some believe that the collagen supplements are lubricating or somehow accumulating in their joints to decrease inflammation and pain – but this is not the case. (R)

Mechanism of actionOral tolerance.  The actual mechanism by which undenatured type 2 collagen treats arthritis and joint pain is via induction of “oral tolerance.”  Oral tolerance refers to a diminished immune response as a result of previously administered antigens.  Repeated oral administration of undenatured type 2 collagen has been shown to induce oral tolerance – essentially retraining the immune system to stop attacking arthritic joints.

Undenatured type 2 collagen has a unique molecular structure that interferes with the joint-attacking autoimmune response.  Specifically, undenatured type 2 chicken collagen prevents the immune system from overreacting to exposed collagen proteins.  In turn, this effect: minimizes/eliminates unwanted immune-mediated joint attacks, allows joints to heal, and ultimately minimizes symptoms of arthritis and joint pain. (R1, R2)

More detailed explanation of collagen’s mechanism of action…

Regular oral administration of undenatured type 2 collagen modulates T-cell reactivity such that T-cells stop perceiving endogenous collagen as a foreign cellular invader.

Within the lower portion of your small intestine, there are concentrations of immune tissue known as “Peyer’s patches.”  The Peyer’s patches essentially train the immune system to react in specific ways to molecules introduced to the body.  In Peyer’s patches, the immune system learns to identify molecular shapes that are safe based on the foods that we eat.

Whenever regularly ingesting a substance such as by eating, T-cells in Peyer’s patches become desensitized to the molecular structure of that particular substance.  This desensitization means that the T-cells no longer assume the substance to be invasive or a cellular threat.  Once a particular substance is deemed safe by the T-cells, it’s unlikely to trigger an immune response and inflammation (such as might occur in the case of an allergic reaction).

When undenatured type 2 collagen is consumed orally and travels through the digestive tract (as opposed to within the bloodstream), T-cells in the Peyer’s patches become desensitized to its molecular structure.  As a result of T-cell desensitization to undenatured type 2 collagen, T-cells begin ignoring (and stop attacking) exposed endogenous collagen fibers within joints of persons with arthritis.  In other words, T-cells no longer initiate an immune attack on exposed endogenous collagen because the endogenous collagen has the same molecular structure as that of the undenatured type 2 collagen.

The aforementioned T-cell desensitization is referred to by researchers as “induced specific oral tolerance.”  Once oral tolerance to collagen has been established, inflammation significantly decreases, as does pain, swelling, and redness associated with arthritis and other joint disorders.

Why undenatured type 2 collagen from chicken sternum?

There are many types of collagen being sold as supplements including: denatured, type 1/type 3, as well as collagen derived from other animals (cows).  The problem is that these other formats of collagen do NOT induce specific oral tolerance – and thus, are completely ineffective to administer for joint disorders like arthritis.

  1. Undenatured: Most commercial collagen supplements are denatured, meaning they’ve been modified via heating or processing. Only undenatured collagen is useful for joint pain because, if denatured, the collagen loses its 3D molecular structure.  Denaturing causes the helical shape to uncoil and alter whereby it becomes utterly useless for induction of specific oral tolerance.  By using undenatured collagen, it’s able to retain its 3D molecular structure – the same as the collagen in your body.
  2. Type 2 collagen from chicken sternum: Type 2 collagen is what’s necessary to stop the immune onslaught on your joints (not type 1 and/or type 3). Furthermore, the type 2 collagen must be derived from chickens – studies using collagen from other animals (e.g. cows) failed to find induction of oral tolerance.  The sternum of chickens is among the richest sources of natural collagen and has the most scientific support as a potentially-therapeutic supplement for arthritis and joint pain.
  3. Patented UC-II: The patented formula of UC-II (registered trademark) has been specifically investigated and proven to survive its passage through the digestive tract such that it retains its molecular structure when it reaches the Peyer’s patches. (Other forms of collagen – even type 2 – may break down and/or lose structure before reaching Peyer’s patches).

Brief historical recap: How undenatured type 2 collagen was discovered to be therapeutic for arthritis

Researchers have long known that, among persons with arthritis and joint disorders, the immune system reacts to and attacks exposed collagen.  For this reason, scientists began conducting experiments to determine how they could inhibit or interfere with immune reactivity to collagen.  It would eventually be discovered that a component within chicken soup facilitated anti-inflammatory effects such that, after consumption, sites of inflammation were shielded from immune attacks.

After further investigation, researchers determined that type 2 chicken collagen favorably modulated immune function and induced tolerance to exposed collagen.  Chicken collagen was first investigated as an intervention for rheumatoid arthritis, however, when normally processed (denatured), type 2 collagen failed to induce oral tolerance.  Later, it was realized that in order to induce oral tolerance, the type 2 collagen must remain undenatured (unprocessed) to retain bioactivity within the human body (for induction of oral tolerance).

Type 2 Collagen for Arthritis (Studies)

Included below are all studies that I was able to find in PubMed in which undenatured type 2 collagen was evaluated as an intervention for arthritis (osteoarthritis and/or rheumatoid).  I’ve listed the studies by date of publication (starting with the most recent), summarized important aspects of each study, and discussed the outcomes of each study.  Understand that the quality of evidence derived from each study is subject to variation based on variables such as sample size, design, and duration.

2016: Efficacy and tolerability of an undenatured type II collagen supplement in modulating knee osteoarthritis symptoms: a multicenter randomized, double-blind, placebo-controlled study.

Researchers Lugo, Saiyed, and Lane (2016) conducted a study in which the efficacy and tolerability of undenatured type 2 collagen (UC-II) were investigated for the treatment of knee osteoarthritis.  The efficacy and tolerability of UC-II were compared to a placebo and a combination supplement of glucosamine hydrochloride plus chondroitin sulfate (GC).

  • Participants: 191 volunteers with knee osteoarthritis
  • Design: Randomized controlled
  • 3 groups: UC-II (40 mg), GC (1500 mg G & 1200 mg C), placebo
  • Trial duration: 180 days
  • Primary measure: Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) score – change from baseline through day 180
  • Secondary measures: Lequesne Functional Index (LFI), Visual Analog Scale (VAS) for pain, and WOMAC subscales
  • Results: UC-II recipients exhibited significant reductions in total WOMAC scores compared to the placebo (p = 0.002) and GC (p = 0.04). UC-II recipients also exhibited significant reductions in all WOMAC subscales (pain, stiffness, and physical function) – compared to GC (pain, stiffness) and placebo (pain, stiffness, physical function).  All interventions were well-tolerated with no safety issues.

It was concluded that UC-II supplementation is well-tolerated and can significantly attenuate knee joint symptoms among patients with knee osteoarthritis.  Because this was a relatively large randomized controlled trial, and UC-II was found to be both safe and effective, it substantiates the usage of UC-II for the treatment of knee osteoarthritis. (R)

2016: Effects of Native Type II Collagen Treatment on Knee Osteoarthritis: A Randomized Controlled Trial.

A group of researchers including: Bakilan, Armagan, Ozgen, Tascioglu, Bolluk, Alatas (2016) conducted a randomized controlled trial to determine the effectiveness of oral native (undenatured) type 2 collagen when co-administered with acetaminophen for the treatment of cartilage degradation among patients with knee osteoarthritis.

  • Participants: 39 patients with knee osteoarthritis
  • Design: Randomized controlled
  • 2 groups: acetaminophen (1500 mg) vs. UC-II (10 mg) + acetaminophen (1500 mg)
  • Trial duration: 3 months
  • Measures: Visual Analog Scale (VAS) at rest and while walking; Western Ontario McMaster (WOMAC) pain; WOMAC function; Short Form-36 (SF-36) scores – change from baseline through 3 months
  • Biomarkers: Coll2-1, Coll2-1NO2, Fibulin-3 (analyzed via urine) – change from baseline through 3 months
  • Results: UC-II + acetaminophen recipients exhibited significant improvements in VAS walking, WOMAC function, and quality of life (SF-36). Acetaminophen-only recipients exhibited significant improvements in some subscales of the SF-36 and VAS walking.  Direct comparison of the 2 groups demonstrated significantly greater improvement on VAS walking scores among recipients of UC-II + acetaminophen – compared to recipients of acetaminophen-only.

Researchers concluded that native type 2 collagen plus acetaminophen yields significantly greater therapeutic benefit than standalone acetaminophen for the treatment of knee osteoarthritis.  Despite the favorable result in support of native type 2 collagen for the treatment of knee osteoarthritis, this was a fairly small-scale trial (with just 19 participants per group).  For this reason, most would consider the study to be underpowered – generating low quality or questionable evidence.

Underpowered studies are notorious for generating false positives, and in this case, it’s fair to be skeptical of the outcome – especially considering that urinary biomarkers of osteoarthritis remained unchanged from baseline to endpoint.  Obviously, a larger-scale trial would strengthen the quality of the aforementioned findings.  Nonetheless, the outcome supported the efficacy of native type 2 collagen when combined with acetaminophen for the treatment of knee osteoarthritis. (R)

2013: Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

A study by Lugo, Saiyed, Lau, Molina, Pakdaman, Shamie, Udani (2013) tested the efficacy of UC-II for the treatment of joint pain following strenuous exercise among healthy adults.  For the study, researchers recruited healthy individuals who experienced joint pain after engaging in a stepmill performance test.  Among those who reported pain from the step-mill test, the efficacy and tolerability of UC-II were evaluated for the enhancement of joint function and reduction of joint pain.

  • Participants: 55 healthy persons with knee pain after a step-mill performance test
  • Design: Randomized controlled (double-blind)
  • 2 groups: UC-II (40 mg/day) vs. placebo
  • Trial duration: 120 days
  • Primary measures: Joint function (degree of knee flexion and extension) and pain recovery (amount of time needed to recover from joint pain after the step-mill exercise) after 120 days – compared to baseline and placebo.
  • Results: UC-II recipients exhibited significant improvements in average knee extension compared to placebo (p = 0.011) and baseline (p = 0.002) after 120 days. It was also mentioned that improvements in average knee extension among UC-II recipients were significant compared to baseline by Day 90 (p = 0.045).  Among placebo recipients, no significant improvement in knee extension was observed throughout the entire study.  Moreover, UC-II recipients were capable of exercising for a longer duration before experiencing initial joint discomfort at Day 120 – compared to baseline and placebo recipients.

It was concluded that daily supplementation with UC-II (40 mg) effectively improves knee joint extension, lengthens the duration of pain-free strenuous exercise, and attenuates joint pain resulting from strenuous physical activity – among healthy adults.  Because no adverse effects occurred, UC-II (40 mg) was considered safe and well-tolerated.  Though this study didn’t recruit patients with arthritis, it demonstrates that undenatured type 2 collagen effectively enhances joint function, minimizes joint pain, and delays joint pain onset from physical activity – providing further evidence that it may be a useful intervention for general joint pain, and potentially, more serious joint conditions (e.g. arthritis). (R)

2009: Safety and efficacy of undenatured type II collagen in the treatment of osteoarthritis of the knee: a clinical trial.

A host of researchers Crowley, Lau, Sharma, Evans, Guthrie, Bagchi, Bagchi, Dey, Raychaudhuri (2009) conducted a clinical trial in which the safety and efficacy of UC-II were evaluated for the treatment of knee osteoarthritis – compared to the combination of glucosamine hydrochloride plus chondroitin sulfate (GC).

  • Participants: 52 patients with knee osteoarthritis
  • Design: Randomized controlled
  • 2 groups: UC-II (40 mg/day) vs. G+C (1500 mg/1200 mg/day)
  • Trial duration: 90 days
  • Measures: WOMAC scores; Lequesne’s functional index; 100-mm VAS pain scale.
  • Results: UC-II recipients exhibited significant reductions in all measures (WOMAC, Lequesne index, VAS scores) at Day 90 compared to baseline. WOMAC scores after 90 days indicated reductions of 33% (UC-II group) and 14% (G+C group).  VAS scores after 90 days indicated reductions of 40% (UC-II group) and 15.4% (G+C group).  Lequesne’s functional index after 90 days indicated 20% reductions (UC-II group) and 6% (G+C group).

Researchers concluded that undenatured type 2 collagen appears safe, effective, and superior to a combination of glucosamine hydrochloride plus chondroitin sulfate for the treatment of knee osteoarthritis.  Recipients of type 2 collagen exhibited fewer adverse reactions than recipients of glucosamine/chondroitin and fewer administrations of “rescue medication” throughout the 90 days.  Though there are limitations associated with this study (e.g. small sample size), it further supports the administration of UC-II for the treatment of knee osteoarthritis. (R)

2009: Therapeutic efficacy of undenatured type-II collagen (UC-II) in comparison to glucosamine and chondroitin in arthritic horses.

This study is a bit different than most already discussed – mostly because it involved investigating the efficacy of UC-II among horses with arthritis (as opposed to humans).  It is worth noting that, many supplements which are safe and/or effective in animals, are not safe and/or effective in humans.  Nonetheless, I felt as though the research by Gupta, Canerdy, Skaggs, et al. (2009) was worth summarizing.

  • Participants: Horses with arthritis
  • Design: Randomized controlled
  • 3 groups: UC-II (320, 480, 640 mg/day); G+C (5.4/1.8 g/day); placebo
  • Trial duration: 150 days
  • Measures: Overall pain (observation of walk/trot), limb flexion-induced pain (after the walk/trot), physical function, liver/kidney function
  • Results: Horses receiving UC-II (320, 480, 640 mg/day) exhibited major reductions in arthritis pain (p = 0.05). Horses receiving G+C exhibited significant reductions in pain compared to baseline (p = 0.05), the efficacy was notably less than UC-II at doses of 480 and 640 mg/day.  As was likely expected, horses receiving the placebo exhibited no change in arthritis pain from baseline.

It was concluded that supplementation with UC-II effectively treats arthritis pain and improves joint function in horses.  Additionally, because various biomarkers (e.g. liver, kidney, temperature, respiration rate) remained unchanged, UC-II was considered well-tolerated.  Though this study doesn’t apply to humans, it demonstrates that UC-II safely and effectively attenuates arthritis in animals. (R)

2005: Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

Deparle, Gupta, Canerdy, et al. (2005) evaluated the safety and efficacy of glycosylated undenatured type 2 collagen (UC-II) for the treatment of arthritis in dogs.  It was noted that, in large breed dogs, arthritis is fairly common due to various factors like: obesity, injury, aging, immune dysfunction, and genetic predispositions.  Though this isn’t a human trial, some may think it’s worthy of a mention, so I’ve outlined the findings below.

  • Participants: 15 dogs in three groups
  • Design: Randomized trial
  • Groups: UC-II (1 mg/day); UC-II (10 mg/day); no UC-II
  • Duration: 90 days (3 months)
  • Measures: Lameness and pain were evaluated weekly for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were collected to examine renal biomarkers (creatinine and blood urea nitrogen) and hepatic biomarkers (alanine aminotransferase and aspartate aminotransferase).
  • Results: Dogs that received UC-II (1 mg/day or 10 mg/day) for 90 days exhibited significant reductions in overall pain, pain during limb manipulation, and lameness after physical exertion. Recipients of the 10 mg/day reaped most substantial therapeutic benefit.

Based on the results of this study, it appears as though UC-II is effective for the treatment of arthritis in dogs.  Additionally, because no significant changes were observed in serum renal and hepatic biomarkers during treatment, UC-II was considered safe and well-tolerated.  Obviously because this was a relatively small-scale trial, and the sample consisted of dogs – results shouldn’t be extrapolated to human populations.  That said, this provides more evidence in support of UC-II as a treatment for arthritis. (R)

2002: The safety and efficacy of chicken type II collagen on uveitis associated with juvenile rheumatoid arthritis.

Thompson, Barron, Whitcup, Robinson (2002) conducted a study in which they evaluated the safety and efficacy of chicken type 2 collagen in treating uveitis associated with juvenile rheumatoid arthritis (JRA).  For reference, uveitis is a form of eye inflammation within the middle layer of the eye wall (uvea) characterized by redness, blurred vision, and/or pain.  Uveitis is common among individuals with juvenile rheumatoid arthritis.  (Although this study isn’t entirely relevant, I wanted to summarize below).

  • Participants: 13 patients with JRA plus uveitis without prior exposure to collagens
  • Design: Pilot study (non-randomized, non-controlled)
  • Groups: Low-dose (60 mcg) and high-dose (540 mcg)
  • Measures: Ophthalmologic analysis (anterior chamber cells, flare, vitreous haze, visual acuity, etc.). Arthritis outcomes from the American College of Rheumatology core set were also assessed.
  • Results: 4 participants (2 low-dose, 2 high-dose) exhibited improved ophthalmologic measures, 2 participants (1 low-dose, 1-high dose) exhibited worsening of ophthalmologic measures. That said, 6 of the 13 participants exhibited improvements in symptoms of juvenile rheumatoid arthritis (JRA) as evidenced by changes on American College of Rheumatology core set scores.

Researchers concluded that type 2 collagen from chickens (UC-II) appeared safe, however, its efficacy for the treatment of uveitis and juvenile rheumatoid arthritis was inconclusive.  Based on the results of this pilot study, researchers hypothesized UC-II to be ineffective for the management of uveitis.  Still, even in this very small-scale trial, UC-II seemed somewhat useful in the management of juvenile rheumatoid arthritis symptoms. (R)

1999: Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid arthritis.

McKown, Carbone, Kaplan, et al. (1999) sought to determine if bovine type 2 collagen might prove efficacious for the treatment of rheumatoid arthritis – when utilized as an adjunct to conventional pharmacotherapy (e.g. immunomodulators).

  • Participants: 190 patients with rheumatoid arthritis
  • Design: Randomized, double-blind, placebo-controlled
  • Duration: 6 months
  • Groups: Placebo vs. Bovine C-II (0.1 mg/day for 1 month – then 0.5 mg/day for 5 months)
  • Measures: ACR-20 (American College of Rheumatology test) – change from baseline through 6 months
  • Results: No statistically significant differences were observed among patients who received the bovine C-II compared to the placebo. Moreover, no significant changes were observed in either group on the ACR-20 after 6 months compared to baseline.  It was noted that the placebo group actually fared slightly better on several measures than the collagen group.

It’s clear that this study does not support the usefulness of bovine collagen (type 2) for the adjunct treatment of arthritis.  That said, the type 2 bovine collagen utilized for this study is markedly different than undenatured type 2 chicken collagen.  Unlike type 2 bovine collagen, undenatured type 2 chicken collagen appears more effective than a placebo. (R)

1998: Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial.

Barnett, Kremer, St Clair, et al. (1998) conducted one of the first and largest trials in which the safety and efficacy of oral type 2 collagen were assessed among a large cohort of patients with rheumatoid arthritis.

  • Participants: 274 patients with rheumatoid arthritis (83% completed the study)
  • Design: Randomized controlled, multicenter
  • Groups: UC-II (20, 100, 500, or 2500 mcg/day) vs. placebo
  • Duration: 24 weeks (6 months)
  • Measures: Response rates were assessed with 3 composite measures, including: Paulus criteria, American College of Rheumatology criteria for RA improvement, and the requirement of equivalent to/greater than 30% reduction in swollen/tender joint counts.
  • Results: Trends indicated that recipients of 20 mcg oral type 2 collagen improved in all 3 composite measures. That said, statistically significant improvements were only observed among recipients of 20 mcg oral type 2 collagen on the Paulus criteria – compared to recipients of the placebo.

It was reported that patients with serum antibodies to C-II baseline were more likely to respond to UC-II treatment.  Researchers further mentioned that the efficacy observed at the lowest dosage (20 mcg/day) is similar to what was observed in animal studies.  It is thought that the lowest dosages preferentially induce disease-suppressing regulatory cells (oral tolerance), whereas higher dosages might not.  In summary, type 2 collagen was found to be safe, tolerable, and therapeutic among patients with rheumatoid arthritis. (R)

1996: A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis.

Barnett, Combitchi, Trentham (1996) were among the first to test the potential usefulness of oral chicken type 2 collagen for the treatment of arthritis.  For their study, researchers recruited 10 participants who had been diagnosed with juvenile rheumatoid arthritis (JRA).  Below is a brief synopsis of the study and its findings.

  • Participants: 10 patients with juvenile rheumatoid arthritis (JRA)
  • Design: Pilot (non-randomized, non-controlled)
  • Duration: 12 weeks
  • Measures: Swollen/tender joint count and score; grip strength; 50-foot walking time; duration of morning stiffness; patient/physician global scores of disease severity – assessed each month
  • Results: 8/10 participants exhibited significant reductions in swollen/tender joint counts after 3 months of UC-II. Average changes from baseline in swollen and tender joint counts among responders were -61% and -54% – respectively.

It was concluded that oral chicken type 2 collagen may be safe and efficacious for the treatment of juvenile rheumatoid arthritis (JRA).  No adverse effects were reported and a majority of patients responded favorably.  That said, this was merely a proof-of-concept study devoid of randomization, proper controls, and a large sample.  Nevertheless, this small study provides a modicum of evidence to support the idea that undenatured type 2 collagen may prove useful for arthritis. (R)

1993: Effects of oral administration of type II collagen on rheumatoid arthritis.

Trentham, Dynesius-Trentham, Orav, et al. (1993) recruited patients with severe rheumatoid arthritis to test the effectiveness of chicken type 2 collagen against a placebo.  They organized a randomized, controlled, and double-blinded study with 60 patients.  This was the earliest study that I could find in which chicken type 2 collagen was investigated for the treatment of arthritis.

  • Participants: 60 patients with rheumatoid arthritis
  • Design: Randomized controlled (double-blind)
  • 2 groups: Chicken type 2 collagen vs. Placebo
  • Duration: 3 months
  • Measures: Number of swollen joints and tender joints
  • Results: Significant decreases in the total number of swollen and tender joints occurred in patients who received chicken type 2 collagen for 3 months – whereas this did not occur among recipients of the placebo. What’s more, a total of 4 patients who received the collagen exhibited complete remission of the disease.

It was concluded that oral tolerance via ongoing supplementation with chicken type 2 collagen is clinically effective for the treatment of rheumatoid arthritis.  No side effects were observed, suggesting that chicken type 2 collagen is safe and well-tolerated.  Though a larger sample size would’ve been better, this provides strong support for the idea that chicken type 2 collagen may treat rheumatoid arthritis. (R)

Note: If newer studies are published analyzing the efficacy of undenatured type 2 collagen for the treatment of arthritis (any subtype), be sure to inform me in the comments section – preferably with a link to the study.  I’d love to highlight and discuss any future results.  Finally, understand that there are limitations associated with the studies above – it’s your job to determine what they are by reading the studies (I’m trying to keep this brief).

What are some key findings from the research of collagen for arthritis & joint pain?

Because I know most people probably won’t bother reading the studies I’ve referenced, and many won’t even skim over the condensed summaries of each study posted above, I’ve compiled and listed some key findings from the research (of type 2 collagen for the treatment of arthritis).

  • Collagen type matters: The specific type of collagen that is administered for arthritis and/or joint pain makes a difference. Only undenatured type 2 collagen derived from chickens appears efficacious for the treatment of arthritis and joint pain.  Forms of collagen that are not “undenatured,” “type 2,” or derived from “chickens” – do not facilitate therapeutic effects.
  • Effective: As of current, the data are unanimous in suggesting that undenatured type 2 chicken collagen is effective for the treatment of arthritis and joint pain. Though much of the data are not necessarily of the highest possible quality as to garner clinical support, several robustly-designed studies reported therapeutically-significant effects of type 2 collagen for arthritis and joint function.  The fact that no studies have reported undenatured type 2 chicken collagen as being ineffective is a good sign for the supplement.  What’s more, in addition to humans, undenatured type 2 chicken collagen exhibits therapeutic potential in animals such as dogs and horses with arthritis.
  • Low dose sometimes better (?): While it’s always best to use the minimal effective dose, the optimal dose of collagen for the treatment of arthritis may vary based on the subtype. For osteoarthritis and general joint pain, it seems as though 40 mg per day is ideal.  However, for rheumatoid arthritis and juvenile rheumatoid arthritis, it’s thought that an extremely low dose (e.g. 6 mcg) is actually better for induction of specific oral tolerance than high doses.
  • Many types of arthritis: Preliminary evidence indicates that undenatured type 2 collagen appears to provide symptomatic relief in many types of arthritis, including: osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis.  It has strongest scientific support for usage in the treatment of osteoarthritis, but appears helpful among patients with rheumatoid and juvenile rheumatoid subtypes.
  • Safe: All studies to date are consistent in suggesting that undenatured type 2 collagen is safe for humans and animals. Zero adverse reactions or safety concerns associated with undenatured type 2 chicken collagen were reported in the literature.  Moreover, this favorable safety profile has been demonstrated regardless of whether administered as a standalone or adjunct.
  • Serum antibodies: Evidence suggests that presence of serum antibodies to C-II prior to treatment is associated with a significantly increased likelihood of deriving therapeutic benefit from UC-II supplementation. In other words, it’s likely that certain individuals will derive greater benefit from UC-II supplementation than others for the treatment of arthritis, largely based upon presence of pre-treatment C-II serum antibodies.
  • Well-tolerated: Not only is undenatured type 2 collagen safe, but it’s well-tolerated. Most patients report few side effects from daily supplementation with UC-II – even at high doses.  While side effects can occur, they are far more common with other medications and supplements than type 2 collagen.

What dosage of type 2 collagen should you take for arthritis?

Because I’m not a medical professional and don’t pretend to be one, I’m not going to give dosing instructions.  If you’d like to know what dose of undenatured type 2 collagen is likely safe and/or most effective for the treatment of your arthritis or joint condition – consult a licensed medical doctor (preferably a rheumatologist).  A medical professional will be able to determine whether type 2 collagen is likely safe in accordance with: your current medical status and daily regimen of medications and/or supplements.

Though I will not give dosing instructions, I will underscore the dosages of undenatured type 2 collagen that were considered safe and efficacious in the literature.  Keep in mind that the dose of type 2 collagen that’s optimal for the treatment of osteoarthritis may not necessarily be the same dose that’s optimal for rheumatoid arthritis – or age-related joint pain.  Moreover, effective doses may be subject to individual variation based things like: whether it’s utilized as an adjunct or monotherapy; genetics; and presence of serum antibodies.

  • Osteoarthritis (OA): 40 mg per day (UC-II). Research is unanimous in suggesting that 40 mg per day of UC-II is effective for the treatment of knee osteoarthritis. If administered as an adjunct to acetaminophen (1500 mg), it seems as though a dose of 10 mg per day (UC-II) elicits symptomatic reduction.
  • Rheumatoid arthritis: 20 mcg per day (?). As of current, it remains unclear as to what the optimal dosage of type 2 collagen would be for patients with rheumatoid arthritis. Some research indicates that lower doses are superior to large doses for the induction of oral tolerance.  Larger doses such as 100 mcg, 500 mcg, and 2500 mcg were not deemed effective.  For this reason, it may be a good idea to start with a very tiny dose, and if no effect is observed, gradually titrate upwards.
  • Juvenile rheumatoid arthritis (JRA): 60 mcg per day (?). The most effective dosage of type 2 collagen for the treatment of juvenile rheumatoid arthritis is unknown. One study reported that a tiny dose of just 60 mcg per day improved symptoms.  Some research suggests that lower doses are superior to large doses.
  • Joint pain: 40 mg per day. One quality study was conducted in which type 2 collagen was assessed for the treatment of strenuous exercise-induced joint pain in healthy adults. The dose of UC-II that facilitated significant improvements in joint function and reductions of joint pain was 40 mg.

Note: There are other types of arthritis for which type 2 collagen has not been assessed as a treatment.  If you aren’t sure what dose will work best for your specific subtype of arthritis and/or joint pain – get some advice from a doctor.

What about “hydrolyzed collagen” for arthritis – is it safe and/or effective?

Hydrolyzed collagen is a form of collagen distinct from undenatured type 2 collagen that has been investigated for the treatment of arthritis and joint pain.

In 2016, a systematic review was published by Porfírio and Fanaro in which the efficacy of hydrolyzed collagen was assessed as a complementary intervention for the treatment of osteoarthritis and osteoporosis.

In the review, it was noted that collagen hydrolysate is not only safe, but that it contains a combination of amino acids that stimulate the synthesis of collagen within extracellular cartilage matrixes.

The reviewers were able to find 9 experimental studies (human, animal, and in-vitro) published between 1994 and 2014 in which hydrolyzed collagen was investigated for joint conditions.

Results of the review indicated that collagen hydrolysate is associated with maintenance of bone composition and strength, as well as the proliferation of cartilage.

Reviewers concluded that hydrolyzed collagen facilitates a favorable therapeutic effect in both osteoarthritis and osteoporosis such that it may increase bone mineral density, protect cartilage, and reduce joint pain.

Because most studies included in the review were of extremely low quality, it’s far too premature to suggest that hydrolyzed collagen is an efficacious agent for the treatment of arthritis and/or joint pain.

Nonetheless, most evidence indicates that, when ingested at recommended dosages, hydrolyzed collagen appears safe as a nutraceutical – with few side effects and adverse reactions.

For this reason, some individuals may wish to supplement hydrolyzed collagen along with undenatured type 2 collagen for a potential add-on benefit. (R)

FAQs: Type 2 Collagen for Arthritis

Below I’ve compiled and answered some frequently asked questions associated with using type 2 collagen for the treatment of arthritis and joint pain.  Most people want to know things like: how long they need to take collagen to notice benefit, whether their joint pain will return if they discontinue supplementation, whether collagen is safe for them to take, as well as the specific collagen I’d recommend.

Is it safe to take type 2 collagen for arthritis?

If you’re unsure about whether undenatured type 2 collagen is safe for arthritis or another medical condition – talk to a doctor.  Though the internet is a great resource for learning about supplements, medications, and medical conditions – it should not be used to replace professional medical advice.  To ensure that collagen is safe for you as an individual – consult a primary care physician or rheumatologist.  That said, most trials of type 2 collagen in humans reported the supplement as extremely safe and well-tolerated with few side effects.

How long do you need to take type 2 collagen to get results?

It is unclear as to how long you’ll need to consistently supplement with collagen to derive noticeable therapeutic benefit.  Some people will report pain reductions immediately (e.g. within a week), whereas others will require longer treatment duration.  Though I cannot be sure, I’d assume that individuals who report substantial benefit within just 1-2 weeks of supplementation are probably exhibiting placebo effects.  (That said, any favorable effect – even if a placebo effect – is probably good in the case of joint pain).

If you’re serious about getting results with collagen for the treatment of arthritis, I’d recommend daily administration (at properly-calibrated doses for your specific arthritis or joint pain) for at least 90 to 120 days (3 to 4 months).  Though the collagen may elicit therapeutic effects quickly, it may take an extended period for joint degradation to markedly decrease and/or joint function to markedly improve.  If you don’t notice any therapeutic benefit within 120 days, it’s probably safe to say that collagen isn’t effective for your particular condition.

If you stop taking it will joint pain return?

Among individuals who respond well to collagen, many want to know whether ceasing supplementation and/or cycling off of it for a period of time will result in a relapse of symptoms.  For a majority of the population with arthritis and/or joint pain, discontinuation of collagen supplementation will result in symptomatic resurgence.  Assuming you derived therapeutic benefit from collagen, if you discontinue its supplementation, unwanted symptoms of joint pain will likely return within several weeks.

In rare cases, it is reasonable to suspect that, timely supplementation with type 2 collagen may disrupt the onset of osteoarthritis, and if continued for a sufficient duration, the supplementation might reverse the condition until it is effectively “cured.”  In these rare cases, cessation of supplementation (assuming the osteoarthritis fully reversed) won’t lead to a return of joint pain because the joints will have regenerated and immune attacks will cease.  That said, all patients with rheumatoid arthritis should expect a relapse after discontinuation.

What collagen do I recommend if you have arthritis?

Below are links to specific types of collagen I’d recommend for persons with arthritis.  These are products that I would personally utilize if I had any type of arthritis.  (Affiliate disclosure: I earn commission when you buy these products.  The price is the same to you regardless of whether you buy through me, but by purchasing through my site – you help compensate me for my research).

Undenatured type 2 collagen (UC-II)

This is the type of collagen that is most supported by evidence for the treatment of arthritis and joint pain.  Always ensure that the collagen is “undenatured,” “type 2 collagen,” and derived from “chicken” (e.g. chicken sternum).  As I’ve already mentioned, type 2 collagen derived from bovine was less effective than a placebo – chickens are the answer.  You can find many quality brands of UC-II on Amazon – I’ve linked to a product that I personally use.

Hydrolyzed collagen

As I’ve mentioned, there’s little evidence to substantiate the effectiveness of hydrolyzed collagen for the treatment of arthritis and/or joint conditions.  Still, because evidence indicates that hydrolyzed collagen (at recommended dosages) is generally safe for human consumption, some may wish to utilize it as a supplement for its speculative therapeutic potential.  There are many quality brands of hydrolyzed collagen that you can purchase on Amazon and/or use with your other collagen.

However, understand that co-administration of undenatured type 2 collagen plus hydrolyzed collagen hasn’t been well-researched – it’s fair to hypothesize that the combination of collagens might be less effective for the treatment of joint conditions than undenatured type 2 collagen as a standalone.  I’ve personally utilized hydrolyzed collagen and have noted modest subjective improvements in joint recovery after exercise – but this could be a placebo effect or nothing more than inaccurate self-analysis on my part.

Final thoughts on Type 2 collagen for arthritis

Though I don’t think Type 2 collagen is a miracle supplement for arthritis sufferers, I do think it has potential to attenuate symptoms of arthritis, joint conditions, and other autoimmune diseases – especially when administered early in disease progression and/or as an adjunct.  Still, I think its efficacy will be subject to significant variation based on an individual’s: specific signature of immune activation, gene expression, and the underlying cause of their arthritis.  Some people will likely find that type 2 collagen effectively controls their symptoms, some will derive mild-to-moderate benefit, and others will claim that it’s completely useless (in that symptoms remained unchanged or severe even after supplementation).

Do I currently have arthritis?  Do I take collagen?

My doctor’s initial diagnosis of arthritis and my poor response to over-the-counter anti-inflammatory agents, voltaren gel, and prescription anti-inflammatories (e.g. meloxicam) is what led me down the rabbit hole of searching for alternative interventions to treat arthritis.

This search led me to discover undenatured type 2 collagen – which I’ve been taking now on a daily basis for months.

Later I would find out that what my primary care doctor suspected was arthritis – was actually a misdiagnosis.

I would later receive a diagnosis of bilateral median and radial nerve pain (based on abnormal EMG results) from a neurologist and rheumatologist – each of whom I am still seeing quarterly (as they are still unsure of the cause(s) of my presentation).

I haven’t experienced any side effects from collagen supplementation – but also haven’t experienced any major improvement – likely because my joints weren’t the underlying problem… it was median nerve-related in my case.

Below are the exact brand names of collagen that I take:

Affiliate disclosure: The above are affiliate links to products that I use.  The first product is the “undenatured Type 2 collagen” that I use and the second product is hydrolyzed collagen that may provide additional benefit.  If you’re going to order one type for your joints, get the UC-II.

Have you tried undenatured type 2 collagen (UC-II) for arthritis?

If you’ve either tried taking and/or are currently taking type 2 collagen for arthritis or joint pain, leave a comment below.  To help myself and others better understand your experience with collagen supplementation, you may want to answer some of the following questions within your comment.

  • Have you been formally diagnosed with arthritis by a medical doctor?
  • What type of arthritis do you have? (e.g. OA, RA, JRA, etc.)
  • What specific type of collagen do you take? (e.g. hydrolyzed vs. undenatured; type 2 vs. 1/3; chicken-derived vs. bovine-derived)
  • What is the exact brand of collagen that you take?
  • Are you taking collagen as a standalone agent or with other medications/supplements? – If so, how can you be sure whether any benefit is from collagen or the other substances you’re using it with?
  • How long have you been consistently taking collagen?
  • Subjectively, has collagen supplementation reduced any of your symptoms? (If so, what symptoms were reduced?
  • What would you rate the efficacy of collagen? (On a scale from 1 to 10 – higher numbers = higher efficacy).

If you have any additional thoughts on collagen supplementation for the treatment of arthritis and/or joint pain, mention them within your comment.

1 thought on “Type 2 Collagen For Arthritis & Joint Pain (UC-II): An Overlooked Intervention”

  1. Drew – great article, very informative and digestible. I’ve been looking into undenatured Type-II as well for minor knee joint pain and have read a few of the studies you listed above. (will read the other new-to-me as well).

    After researching how the UC-II works, it seems that developing oral tolerance at the Peyer’s patches to transform naive T-cells into activated Regulatory T-cells that proceed to mediate the joint inflammation is the pathway.

    I guess my question is whether the UC-II molecules, in stimulating the t-cell activation, act a reagent (i.e. are consumed by the reaction) or more like a catalyst whereby a single UC-II molecule can activate multiple t-cells and not breakdown right away. This is about the limit of my molecular biology knowledge, just wanted to see if you came across anything in your research that would explain this part of the mechanism.

    Also, here’s a report that looked at the Lonza brand UC-II compared to another supplier from Spain. Not all undenatured Type-II supplements are the same it appears.

    Keep up the great writing and thanks for doing a lot of the heavy lifting on this topic.


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