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Shark Cartilage and Arthritis: A review and pilot Clinical Trials in Animals and Humans
By Robert C Greenberg D.C. and Howard Benedikt, D.C

This study was conducted using Cartilade® and Cartequine® brand shark cartilage products. (Cartilage USA, Elmsford, New York).

Shark cartilage in the form of Cartilade® has been used by thousands of people with bone and joint problems with apparent benefits. This study was aimed at assessing the safety and efficiency of Cartilade® in animals and humans. The administration of oral Cartilade® or Cartequine® (Cartilage USA, Elmsford, New York) to seven humans and seven horses with osteoarthritis or traumatic arthritis in open label, uncontrolled, pilot clinical studies showed a beneficial overall effect. Cartilade® was well tolerated without adverse effect.
Numerical scores of disability and clinical signs of arthritis showed statistically significant improvement with Cartilade® therapy in patients whom conventional medical treatment had generally failed. The findings, together with other observations in the literature, dictate the need for further prospective controlled clinical trials of Cartilade® as promising therapy for arthritis in humans and animals.

Introduction.

Considerable interest has focused on the use of cartilage for the treatment of arthritis in animals and man. The rationale for the use of shark cartilage as therapy for arthritis and osteoporosis relates to both its biological effects and general nutrient composition. Cartilage has a putative effect on angiogenesis in vivo. It is composed of calcium, phosphorus, chondroitin sulfate and other elements that are required to maintain optimal skeletal health. While the in vitro demonstration of an antiangiogenic affect of cartilage is clear, questions remain about a consistent demonstration of an in vivo effect.

The objectives of this article are to review the evidence to date for an effect of cartilage on arthritis and to report on early clinical experiences with the use of 100% pure shark cartilage in the treatment of arthritis in humans and animals, respectively.

Methods.

Human Trial

Seven patients (5 F, 2 M, age range 32 to 82 years) with moderate to severe, symptomatic osteoarthritis received 100% pure shark cartilage for ninety days. Each patient had failed conventional medical therapy and in some circumstances alternative therapy.......

Animal Trial.

To determine the tolerability and efficacy of 100% pure cartilage in the treatment of common joint diseases in the athletic horse, seven thoroughbred racehorses (3 F and 4 M, age range 3-6 years) were entered into an open label trial of for arthritis. The horses were selected from three different training stables in California and all were in active daily training and periodic competition. Although the horses were in good general health and were deemed "racing sound," each suffered from mild to moderate degrees of osteoarthritis or degenerative joint change in two or more joints. Each horse underwent an examination prior to entry into the study and on a weekly basis thereafter for 8 weeks. The animals received 10 g daily of 100% pure shark cartilage for 10 days followed by 5 g daily for a further 50 days. During the study the horses remained on a daily training regimen and each animal was monitored daily for general well-being, appetite and any adverse effects of the study medication. .....

There are several published and unpublished observations that support the use of the cartilage in the treatment of arthritis and other inflammatory disorders that are angiogenesis dependent (1,3,4,5). The present human study in Dr. Greenberg's practice is the only study of cartilage in any disease state that has been subjected to statistical analysis and shows benefit. In William Lane's overviews (2,5) of the subject (1991, 1992), he describes personal communications with Orloff (1985), who is credited with the successful use of oral Cartilade® (9mg/day) in the alleviation of pain from degenerative joint disease in a 49-year-old female patient (2).

The successful use of shark cartilage in the treatment of osteoarthritis or degenerative joint disease in six patients have been reported by William Lane (2). These six patients underwent nine outpatient visits during which 9 gm/day of shark cartilage were administered orally for the first four weeks of therapy and 4.5 gm/day were administered for the second four week period. Assessments were undertaken of the patient symptoms and the tolerability of the shark cartilage. Of the six patients in the study, three completed the entire assessment, whereas one patient attended for several visits and two patients were seen on only one occasion. Lane (2) reports Orloff's observations (Orloff, 1989, personal communication to Lane, 1991) as showing an approximate 50% decrease in pain in the three patients completing the study and varying degrees of amelioration of symptoms in others. In this study, there was a confirmed reduction of pain during physical exercise in two patients (2).

Studies in animals have shown quite promising results with the use of cartilage for the treatment of arthritis of diverse form. Rauis (3) presented important data to the British Small Animal Veterinary Association Congress in 1991 on the beneficial effects of a prototype preparation of shark cartilage for the treatment of secondary arthritis in the dog. This work has been summarized (Lane, 1991; Lane and Comac, 1992), but variably interpreted (Lane and Comac, 1992). Rauis (1991) utilized Cartilade® brand of shark cartilage in ten dogs with lameness due to the following disorders alone or in combination: joint fracture (2), hip dysplasia (4), joint dislocation (2), spondylopathy (2) and rupture of the cruciate ligament (2). The presence of osteoarthritis was confirmed by x-ray in all animals. In this study, each dog received one capsule of Cartilade (740 mg) per 5 kg of body weight per day for three weeks and other treatments were withdrawn for the duration of the study.

Evaluations of the dogs were made at days 0, 8, 15, 21 and 36 of the study and clinical scores of disability were made between 0 and 5 days for each of several clinical parameters in the dogs. These parameters included local swelling, atrophy of regional muscles, joint crepitation and/or pain, lameness before action, lameness after action and difficulty in negotiating an obstacle. Lameness was clearly defined as difficulty to walk or run after several hours of immobility (lameness before action), involving the climbing the climbing of stairs and/or the capacity to get over an obstacle that had not been previously overcome by the animal.Rauis (3) considered the number of animals in the study to be insufficient to reach global conclusions, but several beneficial outcomes were noted in these animal studies. No significant side effects of the administration of the prototype preparation of Cartilade® administration were encountered in the study and the study compound was considered very easy to administer to the animals, since it mixed readily with dog meals and nine out of ten animals were reported to "like"; the dietary supplement very much. Rauis (3) reported that in all cases the owners indicated that their dogs were much more active and even apparently "happy." This status was ascribed to the apparent relief of the pain that had been experienced by the animals. The main beneficial effect in the study seemed to be reduction in the local swelling and inflammation in the joints of the dogs. Rauis (3) described the overall effect on functional parameters in the dogs as "impressive." In this non-label, non-blinded study, Cartilade® appeared effective and safe to administer in the treatment of canine osteoarthritis.

Dr. John F. Prudden (1985) is to be credited with pioneering studies of the use of cartilage in the treatment of arthritis of varying type and degree of severity. Early observations of the clinical effects of bovine cartilage by Prudden and Balassa (1) led to the use of bovine cartilage by both parenteral and oral administration to treat osteoarthritis and inflammatory arthritis in humans. These studies were based on the reasoning that abnormalities of the polysaccharide component of cartilage was a key abnormality in the joints of patients with osteoarthritis. This notion is supported to some degree by the findings that a stimulation of protein-chondroitin sulfate synthesis occurs as a consequence of the administration of articular cartilage. Prudden and Balassa reasoned that by supplying the building blocks of cartilage, they could promote resynthesis of healthy cartilage. This is an example of the widely practiced, but clinically unproven, concept of "protomorphogenesis."

In these studies (1), sterilized bovine cartilage solution (Catrix-S) was administered by subcutaneous injection to 26 patients with long-standing osteoarthritis. These patients had varying degrees of functional disabilities (1), and most of these patients had evidence of marked joint degeneration, which had been confirmed by x-ray. Prudden and Balassa (1) reported an excellent result from bovine cartilage therapy in terms of improvement in pain and disability in 17 cases, good improvement in 6 cases, marginal benefit in two cases and no benefit in one case. Despite the parenteral administration of cartilage in this study, no toxicity was observed. The parenteral administration of cartilage may be considered potentially dangerous because of the introduction of the antigenic load of foreign protein. Although the work of Prudden and Balassa was not in the form of a controlled clinical trial, it would appear that the beneficial effects observed by them may not be explicable by chance alone.

Prudden (cited by Kirchhof and Kirchhof, 1995 performed studies on patients with rheumatoid arthritis and reported favorable responses on subcutaneous administration of bovine cartilage suspension for periods up to 35 days. Thereafter, "booster" doses of cartilage were given at intervals of approximately three to four weeks in a manner determined by the therapeutic response of the patient. In these studies, there were 9 patients with severe rheumatoid disease who had marked joint swelling and/or immobility. Six of these patients were described as having a "good" result from cartilage treatment whereas three were described as having an "excellent" result. One out of the 9 patients in the study was particularly notable, since she was a 57-year-old female who had progressive rheumatoid disease with resultant severe immobility. The response of this patient to cartilage administration was considered dramatic by Prudden (7). After an initial three months period where the patient reported that her joints were becoming more swollen, there was a progressive improvement with restoration to reasonable activity. This improvement was sustained for at least three and one half years following one cartilage treatment course.

One of the most important studies of cartilage preparations in the treatment of osteoarthritis was performed by Rejholec (8) who undertook a five-year, double-blind study of the effect of a bovine cartilage preparation in 147 patients with osteoarthritis who were divided into three study groups. One study group received placebo and the other two received an extract of bovine cartilage. In the cartilage treated groups, pain scores were reduced by more than 85% compared with only 5% reduction of pain scores in the placebo treated group. At the end of five years, joint degeneration was noted to be significantly less in the cartilage treated group compared with the control group. Rejholec (8) produced limited outcome data but indicated that significantly less time was lost from work in the subjects who received cartilage with the control group. One year following the studies of Rejholec, Brown and Weiss published their findings of angiogenic stimulators in the joint fluid of patients with osteoarthritis. These findings added weight to the rationale for the use of cartilage and other "antiangiogenic" compounds in the treatment of osteoarthritis. The present studies performed in seven humans and seven horses have produced a favorable outcome and they provide further supportive evidence for a potential role of shark cartilage in the treatment of arthritis. As with all clinical studies to date on the use of shark cartilage for the treatment of arthritis, the observations have not been made in a double blind controlled manner that permits firm conclusions. However, the study in seven patients showed a statistically significant improvement in several objective measures of arthritis in the small sample. The mechanism of the effect of cartilage on the treatment of arthritis remains unknown, but it seems likely that an effect may be mediated by the antiangiogenic properties of shark cartilage. These current studies, together with previous data, support the need for future large scale prospective, controlled trials of the use of cartilage in the treatment of arthritis in humans and animals. If Cartilade® or Cartequine® can be shown to be effective in further prospective studies then these preparations may be a highly useful alternative therapies of natural origin for the treatment of osteoarthritis.

References:
1. Prudden, J.F., Balassa, L. The biological activity of bovine cartilage preparations. Semin Arthritis Rheum 3:287-321, 1974
2. Lane, I.W. Shark cartilage: Its potential medical applications. Journal of Advanced Medicine 4:263-271, 1991.
3. Rauis J. Use of shark cartilage in the treatment of secondary osteoarthritis in the dog. British Small Animal Veterinary Association (BSAVA) Congress, 1991. Manchester, UK.
4. Brown RA, Weiss J. Neovascularization and its role in the osteoarthritic process. Ann Rheum Dis., 1988, 47:881-885.
5. Lane, I.W., Comac , L. Sharks Don’t Get Cancer. Garden City, NY. Avery Publishing Group, 1992, updated 1993.
6. Holt S., Nutriceuticals and Angiogenesis: New Therapeutic Horizons. Alternative and Complimentary Therapies. 1:243-247, 1995.
7. Kirchhof D., Kirchhof E., The successful use of bovine tracheal cartilage in the treatment of cancer. Belgrade, Montana. Kriegel & Associates Publishers, 1995.
8. Rejholec V., Long-term studies of antiosteoarthritic drugs: An assessment. Seminars in Arthritis and Rheumatism. 17:35-63,

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