Genacol® Studies: Oral Collagen for Rheumatoid Arthritis  
  Oral Collagen for Rheumatoid Arthritis

Reprinted from Medical Sciences Bulletin Published by Pharmaceutical Information Associates, LTD

Rheumatoid arthritis (RA) is a common and often debilitating disease characterized by the inflammation of synovial membranes, leading to deterioration of joint cartilage and bone. Since RA is associated with human lymphocyte antigen DR4 (HLA-DR4), the disease is thought to be autoimmune in origin. Type II collagen is probably the autoantigen involved in RA, since it is the most abundant structural protein in cartilage and since immunizing animals with this protein induces an arthritis resembling RA. Therapy includes steroids, nonsteroidal anti-inflammatory agents, and immunosuppressants, which are associated with significant toxicity and only partially control symptoms. Recently a Harvard Medical School team reported that oral tolerization (desensitization) is an effective and nontoxic technique for suppressing the symptoms of RA

Oral tolerization involves feeding the patient the antigen thought to be involved in the autoimmune attack. It takes advantage of the fact that a foreign protein entering the body via the digestive tract apparently suppresses the immune response to that protein, rather than triggering it. A number of groups have studied oral tolerization in animals to suppress autoimmune diseases resembling certain human diseases, including human sclerosis (MS) uveitis, and diabetes, as well as RA. In one clinical trial involving 30 MS patients, the oral administration of bovine myelin antigens decreased the number of T cells that reacted with myelin basic protein, the autoantigen in MS.

In the first Harvard trial, Trentham et al. administered very small doses of solubilized Type II collagen to 10 patients with refractory RA. After discontinuing immunosuppressive and disease-modifying drugs (methotrexate, mercaptopurine, azathioprine, or auranofin), patients were given 0.1 mg of collagen daily for 1 month, and then 0.5 mg for the next 2 months. The dosage was chosen on the basis of animal studies. Clinical response was defined as a 50% or greater improvement in the number of swollen and tender joints, accompanied by a 50% or greater increase in two additional measures (morning stiffness, 15-meter walking time, grip strength, Westergren erythrocyte sedimentation rate, or physician or patient global assessment), lasting for at least 2 months after the treatment period. Six of the 10 patients showed substantial clinical response, and one showed a complete response (disease remission) lasting 26 months. There were no adverse effects.

On the basis of results of this phase I trial, a 90-day, double-blind, phase II trial was conducted involving 60 patients with severe, active RA. Patients received either placebo or solubilized Type II collagen (1.0 mg for 1 month, then 0.5 mg for 2 months). At the study's end, 59 of the 60 patients were evaluable: 28 had received collagen, and 31 placebo. Compared with the placebo group, the collagen group showed significant improvements in joint swelling, tenderness or pain (as well as in indices of swelling or tenderness) and in 15-meter walking time at months 1, 2, and 3. During the period when patients were off immunosupressants, those receiving collagen showed stability or improvement, while those in the placebo group tended to deteriorate (with the exception of four patients who showed a substantial placebo effect). Four patients in the collagen group showed complete resolution of disease, while none of the placebo patients showed remission. No side effects or laboratory effects were seen (including rheumatoid factor and antibodies to Type II collagen).

Feeding Type II collagen to RA patients may alter T cell function, either by causing T cell anergy or by triggering the production of suppressor T cell that migrate to joints and block T cell-mediated inflammation. A longer multi-center trial is needed, which would include a washout period and 6 months of treatment. "If longer term efficacy is established" said the investigators, "oral collagen would be a preferable treatment because it is not toxic." The Harvard trials were sponsored AutoImmune, a Lexington, MA biotechnology company founded in 1988 to commercialize oral tolerization. (Trentham DE et al. Science. 1993; 261 1727-1730. Barinaga M. Science. 1993; 261 : 1669-1670.)

Clinical Report on the Effects of Collagen Type II For Subjective Pain Relief

Pain syndromes are a part of many people's daily lives. It can render them disabled in some manner or it can be a degenerative chronic residual from trauma or disease processes. Our objective was to analyze the effectiveness of Collagen Type II versus placebo treatment on these people, and report the results and measure the response by the subject.

AUTHORS - Drs. K. Buckman, J. Gutierrez; et al
OBJECTIVE - To compare the effects of placebo versus Collagen Type II on the course of pain syndromes.
Placebo - Made of capsules containing standard ingredients of no nutritional or synthetic value.
Collagen Type II - Each treatment of 4 capsules containing 400 mg. of Collagen Type II. Collagen Type II naturally contains 15% of Glucosamine Sulfate and 15% of Chondroitin Sulfate.

Research design and methods
We entered 89 random subjects with various types of pain syndromes. All subjects were interviewed and asked to describe their subjective pain and where their pain was located. They were also asked if they had been given a new prescription or any changes on their current medical regiment. If there were changes in the subjects regiment, that subject was not included in the study. Each subject was told the program would last three months.

The subjects were asked to follow the directions on the bottle:

  1. Take 4 capsules of the Collagen Type II in the morning with orange juice
  2. Take twenty to thirty minutes before they ate breakfast
  3. Record what day they responded to treatment

The following descriptions of pain were given by the subjects:

  • Rheumatoid Arthritic Pain
  • Osteoarthritis Joint Pain
  • Post Surgical Joint Pain
  • Post Traumatic Pain
  • Fibrositis
  • Gouty Arthritis
  • Lumbosacral Pain with/without radicular pain
  • Cervical Spine Pain with/without radicular pain

89.9% of the subjects received pain relief at some level within 45 days of taking the Collagen Type II capsules.

All subjects were compliant with taking four capsules a day. After end trial interviews we found that 9% of the subjects took more than four, but less than seven capsules a day.

Table 1. Results of response to pain relief by (X) days:

Days to response 0-7 days 8-21 days 21-45 days Totals
Rheumatory Arthritis 9 6 3 18
Osteoarthritis 7 12 5 24
Fibrosis 4 7 2 13
Lumbosacral w/ history of herniated disc 3 6 3 12
Chronic Post Traumatic Pain 2 4 3 9
Gouty Arthritis 2     2
Cervical Spine w/ history of herniated disc   1 1 2
Placebo     (1) (1)
Non responsive     9 9
Totals 27 36 26 89

The total without a response of less pain in 45 days was nine or approximately 10.1% and only (one) placebo subject recorded a response in 45 days.

Side Effects
Only one subject had nausea. It was noted that he was on other medications as well.

Collagen Type II treatment had a significant effect on subjective pain syndromes. Most subjects responded to Collagen Type II in the first 21 days of the trial. Many of these pained subjects had previously been on long term, pharmaceutical treatment programs.

Many subjects responded by initiating life style changes due to lack of pain. Many were excited by the increase in their daily activity. The results have prompted the authors to develop specific disease/pain syndrome trials in the near future.

"The results were overwhelmingly positive for pain relief and the side benefits were remarkable! This product has changed my life significantly."
Dr. C. Searling, Fresno, CA

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