Clinical Studies in Collagen
Below are some clinical studies in Collagen:
Moskowitz RW
Case Western Reserve University, Division of Rheumatic Diseases,
University Hospitals of Cleveland, OH, USA
OBJECTIVES: To review the current status of collagen hydrolysate in the treatment of osteoarthritis and osteoporosis.
METHODS: Review of past and current literature relative to collagen hydrolysate metabolism, and assessment of clinical investigations of therapeutic trials in osteoarthritis and osteoporosis.
RESULTS: Hydrolyzed gelatin products have long been used in pharmaceuticals and foods; these products are generally recognized as safe food products by regulatory agencies. Pharmaceutical-grade collagen hydrolysate (PCH) is obtained by hydrolysis of pharmaceutical gelatin. Clinical studies suggest that the ingestion of PCH daily reduces pain in patients with osteoarthritis of the knee or hip; blood concentration of hydroxyproline is increased. Clinical use is associated with minimal adverse effects, mainly gastrointestinal, characterized by fullness or unpleasant taste. In a multicenter, randomized, doubleblind, placebo-controlled trial performed in clinics in the United States, United Kingdom, and Germany, results showed no statistically significant differences for the total study group (all sites) for differences of mean pain score for pain. There was, however, a significant treatment advantage of PCH over placebo in German sites.
In addition, increased efficacy for PCH as compared to placebo was observed in the overall study population amongst patients with more severe symptomatology at study onset. Preferential accumulation of 14C-labeled gelatin hydrolysate in cartilage as compared with administration of 14C-labeled proline has been reported. This preferential uptake by cartilage suggests that PCH may have a salutary effect on cartilage metabolism.
Given the important role for collagen in bone structure, the effect of PCH on bone metabolism in osteoporotic persons has been evaluated. Studies of the effects of calcitonin with and without a collagen hydrolysate-rich diet suggested that calcitonin plus PCH had a greater effect in inhibiting bone collagen breakdown than calcitonin alone, as characterized by a fall in levels of urinary pyridinoline cross-links. PCH appeared to have an additive effect relative to use of calcitonin alone.
CONCLUSIONS: Collagen hydrolysate is of interest as a therapeutic agent of potential utility in the treatment of osteoarthritis and osteoporosis. Its high level of safety makes it attractive as an agent for long-term use in these chronic disorders.
The Health Sciences Institute Newsletter
Spring 1997
"Food" for cartilage mends damaged joints
In European medical literature, the appearance of a therapeutic substance derived from collagen - the protein that cartilage is made of - dates back to the early 1920's.
In 1936, this substance, called collagen hydrolysat (Collagen Type II), received the classification known as GRAS: "generally recognized as safe." In recent years, it's been on the market in Germany and Europe as a home remedy and a treatment for diseases of the skeletal system and joints.
In the US, one laboratory picked up on the research, and spent years testing the safety and effectiveness of collagen hydrolysat.
They found that a series of 18 amino acids, which are joined together in chains by peptide bonds. These amino acids are the very same that make up the framework of human cartilage, contributing to its configuration, flexibility and strength.
In other words, this substance supplies your cartilage with the nutrients necessary to rebuild cartilage.
In some studies, animals fed this new substance experienced such significant cartilage growth, researchers could measure it with a ruler! In a controlled study done in 1993, at the Clinical Department of the Veterinary University in Hanover, researchers measured a significant increase in thickness in just a few months.
And the early results in humans are just as exciting!
In one study, 356 people suffering from arthritis in one or more joints - knees, hips, spine - took 1 tablespoon a day for three months. The effectiveness was measured on the basis of subjective statements and on the reduction in the use of anti-inflammatory drugs and reduction in frequency of steroid injections.
Those suffering with knee pain were completely free of complaints.
Test Results: 99.2 percent of the patients showed "good" or "very good" results. Those with knee pain were completely free of complaints after six months of treatment. There were no side effects.
In another study, sixty men and women, ages 8 to 33, with arthritis of the knee, were treated for three months. The patients were examined after one, two and three months. 86 percent reported greater ease climbing stairs, and 58 percent were free of pain while at rest. At the end of the three months, 75 percent of the patients were free of pain. The researchers concluded that cartilage regeneration occurred in 80 percent of the cases.
Clinical Report on the Effects of
Collagen Type II For Subjective Pain Relief
March 1999
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.
RESULTS 89.9% of the subjects received pain relief at some level within 45 days of taking the Collagen Type II capsules. |
COMPLIANCE
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.
CONCLUSION
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
Effects of oral administration of type II collagen on rheumatoid arthritis.
Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL.
Department of Medicine, Beth Israel Hospital, Boston, MA.
Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.
Publication Types:
- Clinical Trial
- Clinical Trial, Phase II
- Randomized Controlled Trial
Nutraceuticals as therapeutic agents in osteoarthritis. The role of glucosamine, chondroitin sulfate, and collagen hydrolysate.
Deal CL, Moskowitz RW.
Division of Rheumatology, Case Western Reserve University School of Medicine, University Hospitals, Cleveland, Ohio, USA.
There are a sufficient number of short-term studies with these agents suggesting efficacy equal to that seen in the symptomatic treatment of OA using NSAIDs. Two recent meta-analyses by McAlindon and colleagues and Towheed et al reviewed clinical trials of glucosamine and chondroitin in the treatment of osteoarthritis. The study by McAlindon and co-workers included all double-blind placebo-controlled trials of greater than 4 weeks' duration, testing oral or parenteral glucosamine or chondroitin for treatment of hip or knee osteoarthritis. Thirteen trials (six with glucosamine, seven with chondroitin) met eligibility criteria. The authors used global pain score or the Lequesne index in the index joint as the primary outcome measure and considered the trial positive if improvement in the treatment group was equal to or greater than 25% compared with the placebo group, and was significant (P < or = .05). All 13 studies reviewed were classified as positive, demonstrating large effects, compared with placebo (39.5% [S.D. 21.9] for glucosamine, 40.2% [S.D. 6.4] for chondroitin). The authors concluded that clinical trials of these two agents showed substantial benefit in the treatment of osteoarthritis but provided insufficient information about study design and conduct to allow definitive evaluation. Towheed and colleagues reviewed nine randomized, controlled trials of glucosamine sulfate in osteoarthritis. In seven of the randomized controlled trials, in which they compared glucosamine with placebo, glucosamine was always superior. In two randomized controlled trials comparing glucosamine to ibuprofen, glucosamine was superior in one and equivalent in one. Methodologic problems, including lack of standardized case definition of osteoarthritis and lack of standardized outcome assessment led the authors to conclude that further studies are needed to determine if route of administration is important and whether the therapeutic effect is site specific. A meta-analysis of chondroitin sulfate trials has also been published. Of the 12 published trials, 4 randomized double-blind placebo or NSAID-controlled trials with 227 patients on chondroitin sulfate were entered into the analysis. All four studies showed chondroitin sulfate to be superior to placebo, with respect to Lequesne index, visual analog scale for pain and medication consumption. Significant changes (P < or = .05) were seen in those treated from day 60 to the study endpoints (150 to 180 days). Pooled data demonstrated at least 50% improvement in the study variables in the chondroitin treated group. Discrepancies in some of the study findings reported in the literature may relate to the composition of the nutritional supplements used. Studies in the United States have revealed that a number of preparations claiming to contain certain doses of glucosamine or chondroitin sulfate have significantly less (or none) of the dosages described. Accordingly, it is essential that studies performed with these agents use preparations that are carefully defined in manufacture. The amounts generally administered are glucosamine, 1500 mg, and chondroitin sulfate, 1200 mg, daily. Although glucosamine has been described as effective when used alone, it is probably reasonable to use the combination pending further studies. The average cost is approximately $30 to $45 per month. In the interim, what should physicians tell their patients when they ask whether these agents are effective, or whether they should or should not take them? The authors emphasize that these agents are not FDA-evaluated or recommended for the treatment of OA. They are available as health food supplements, and the number of studies of toxicity, particularly with respect to long-term evaluations, is limited. The pros and cons of these agents and the published data are described so that patients can make a reasonably informed decision as to whether they wish to proceed with use of these agents in therapy.