Tier 2 — strong

Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

David E. Trentham, Roselynn A. Dynesius-Trentham, E. John Orav, Daniel Combitchi, Carlos Lorenzo, Kathryn Lea Sewell, David A. Hafler, Howard L. Weiner
Science 1993 261(5129):1727-1730

Bibliography

PubMed
PMID 8378772
DOI
10.1126/science.8378772
Funding
Supported by NIH grants MO1 RR01032 and AG00294, and by a grant from AutoImmune Inc. Biohack Blueprint assessment: two senior authors and their institution held a disclosed financial interest in AutoImmune Inc., the company commercialising the oral-tolerance collagen therapy under investigation. This is stated in the original article's acknowledgements rather than as a modern-style structured conflict-of-interest section.
Competing interests
Not presented as a separate formal declaration in the article body (the article predates modern COI disclosure norms); a financial interest in AutoImmune Inc. held by two authors and Harvard Medical School is disclosed in the acknowledgements.

Study snapshot

DesignRandomised, double-blind, placebo-controlled phase II clinical trial
ModelAdults with severe, active rheumatoid arthritis
Samplen=60 randomised; n=59 evaluable (28 collagen, 31 placebo)
InterventionSolubilised native (undenatured) chicken type II collagen, 0.1 mg/day orally for 1 month then 0.5 mg/day for 2 months, vs an indistinguishable placebo. This is an oral immune-tolerance mechanism using microgram doses of undenatured collagen — mechanistically and quantitatively distinct from gram-scale hydrolysed collagen peptide supplementation.
Duration3 months (90 days)
EndpointsNumber of swollen joints; Number of tender/painful joints; Joint-swelling and joint-tenderness indices; 15-metre walk time; Complete disease remission

What the study showed, in plain terms

This is a landmark, widely cited 1993 trial — and it is important to be clear about what it actually tested, because it is easy to conflate with the hydrolysed collagen peptide products this site otherwise reviews. It used microgram doses of native, undenatured chicken type II collagen, taken orally to try to induce immune "tolerance" in rheumatoid arthritis, a completely different ingredient, dose scale, and mechanism from gram-scale hydrolysed collagen peptide supplementation for skin, joints, bone or muscle.

In this small, 3-month, placebo-controlled trial, patients on collagen had fewer swollen and tender joints than those on placebo, and four of 28 collagen-treated patients went into complete remission versus none on placebo. No side effects were reported.

It is included in this Data Center as a differentiation and background reference: readers researching "collagen for joints" may encounter undenatured type II collagen (UC-II-type) products marketed on the strength of trials like this one, and should understand that it is not the same ingredient, dose, or evidence base as the hydrolysed collagen peptides covered elsewhere on this site.

Key findings

  • Significant reductions in swollen joint count, tender joint count, joint-swelling index and joint-tenderness index in the collagen group compared with placebo at 1, 2 and 3 months (all p<0.05 for the primary joint measures).
  • Four of 28 patients (14%) in the collagen group achieved complete disease remission during the trial, versus none of 31 in the placebo group.
  • No evidence of sensitisation to collagen (measured by antibodies to type II collagen) and no significant laboratory abnormalities attributed to treatment.
  • No side effects were evident in either group.

What this study can and cannot tell us

  • Small trial (n=60) by modern standards, and conducted in 1993 — well before current treat-to-target rheumatoid arthritis management and modern biologic/DMARD comparators existed.
  • Disclosed financial interest in the sponsor company (AutoImmune Inc.) held by two senior authors and their institution.
  • Tests a fundamentally different product and mechanism — native undenatured type II collagen at microgram oral-tolerance doses — from the hydrolysed collagen peptides reviewed elsewhere in this Data Center; results here cannot be extrapolated to hydrolysed collagen peptide products.
  • Subsequent trials of undenatured type II collagen (UC-II-type) products in osteoarthritis and joint-comfort settings have shown mixed results, so even within its own product category this single 1993 RA trial should not be read as the final word.

Related papers in the corpus

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Tier 3
Collagen hydrolysate for the treatment of osteoarthritis and other joint disorders: a review of the literature
Alfonso E. Bello et al. · Current Medical Research and Opinion · 2006
Tier 4
Therapeutic Efficacy and Safety of Undenatured Type II Collagen Singly or in Combination with Glucosamine and Chondroitin in Arthritic Dogs
M. D'Altilio et al. · Toxicology Mechanisms and Methods · 2007

Editorial review

Reviewed by the Biohack Blueprint research team

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology