Cartilage (Bovine and Shark)

What is cartilage?

Cartilage is a type of tough, flexible connective tissue that forms parts of the skeleton in many animals. Cartilage contains cells called chondrocytes, which are surrounded by a network of several types of collagen (a fibrous protein) and proteoglycans, which are combinations of protein and glycosaminoglycans (a type of carbohydrate).

What is the history of the discovery and use of cartilage as a complementary or alternative treatment for cancer?

Cartilage from cows (bovine cartilage) and sharks has been studied as a treatment for cancer and other medical conditions for more than 30 years. The mistaken belief that sharks, whose skeletons are made mostly from cartilage, do not develop cancer caused some of the initial interest in cartilage as a possible treatment for cancer. Although malignant tumours are rare in sharks, a variety of cancers have been detected in these animals.

Early studies used extracts of bovine cartilage. The ability of bovine cartilage to reduce inflammation (redness, swelling, pain, and feeling of heat) was first described in the early 1960s. The first report that bovine cartilage contains at least one angiogenesis inhibitor (a substance that blocks the formation of new blood vessels that cancer needs to grow) was published in the mid 1970s. The use of bovine cartilage extracts to treat cancer patients in clinical trials (research studies with people), and the ability of these extracts to kill cancer cells directly and to stimulate animal immune systems, were first described in the mid-to-late 1980s.

The first report that shark cartilage contains at least one angiogenesis inhibitor was published in the early 1980s. There are 2 published reports (1998 and 2005) of clinical trials of shark cartilage as a treatment for cancer (see Question 6). The interest in studying shark cartilage results in part from the abundance of cartilage in sharks and from the apparently higher level of antiangiogenic activity in shark cartilage as compared with bovine cartilage.

What is the theory behind the claim that cartilage is useful in treating cancer?

Three theories have been proposed to explain how cartilage acts against cancer:

As cartilage is broken down by the body, it releases products that kill cancer cells.

Cartilage stimulates the body’s immune system to kill cancer cells.

Cartilage produces substances that block angiogenesis.

Based on laboratory and animal studies, there is more support for the third theory than for the first and second theories. Cartilage, a tissue that does not contain blood vessels, is relatively resistant to cancer cells. If the theory that cartilage can prevent angiogenesis is correct, the substances in cartilage that stop the formation of new blood vessels might also help prevent metastasis (the spread of cancer).

How is cartilage administered?

In animal studies, cartilage products have been administered in a variety of ways: by mouth, in either a liquid or a powdered form; injected into a vein or into the abdomen; applied to the skin; or placed in slow-release plastic pellets that were surgically implanted.

In studies with people, cartilage products have been given by mouth in liquid, powdered, or pill form; applied to the skin; injected under the skin; or given by enema (injected as a liquid into the rectum). The dose and duration of cartilage treatment have varied in studies with people, in part because different types of products have been tested.

Have any preclinical (laboratory or animal) studies been conducted using cartilage?

The potential of cartilage as a treatment for cancer has been investigated in many laboratory and animal studies. These studies have focused on the ability of bovine and shark cartilage products to kill cancer cells in the laboratory, the potential of cartilage to stimulate the immune system, and the antiangiogenic properties of cartilage.

In one laboratory study, cells from several types of human cancers were treated with Catrix, which is a powdered preparation of bovine cartilage. Although high levels of Catrix inhibited the growth of cancer cells by at least 50%, it is not clear whether this effect was specific to cancer cells because the effect of Catrix on normal cell growth was not tested.

AE–941/Neovastat (a liquid extract of shark cartilage) has been reported to stop the growth of a variety of cancer cell types in the laboratory. The results, however, have not been published in a peer-reviewed scientific journal.

In contrast, a published study of a commercially available powdered shark cartilage reported that the cartilage had no effect on the growth of human astrocytoma cells in the laboratory. (Astrocytoma is a type of cancer that begins in the brain or spinal cord.)

Although the potential of cartilage to stimulate the immune system has been investigated in both laboratory and animal studies, only one of these studies has been published in the peer-reviewed scientific literature. This study reported that Catrix (a bovine cartilage product) stimulated parts of the immune systems of mice when it was injected into the abdomen or into a vein, but not when it was given by mouth. To date, no studies of the ability of shark cartilage to stimulate the immune system have been published.

A large number of laboratory and animal studies on the antiangiogenic abilities of cartilage have been published. Overall, these studies have detected the presence of at least 3 angiogenesis inhibitors in bovine cartilage and at least 2 angiogenesis inhibitors in shark cartilage.

Studies of the effects of powdered shark cartilage given by mouth to mice and rats have been published in the peer-reviewed scientific literature. One study found that powdered shark cartilage prevented the development of blood vessels, while another study showed that it reduced the growth of gliosarcomas, a type of brain cancer. A third study indicated that two powdered shark cartilage products (Sharkilage and MIA Shark Powder) did not stop the growth or the spread of a type of skin cancer.

Have any clinical trials (research studies with people) been conducted using cartilage?

Since the 1970s, more than a dozen clinical studies of cartilage as a treatment for cancer have been conducted. Results from 5 of these studies have been published in peer-reviewed scientific journals. Although more clinical studies are under way, the evidence to date has not proven the effectiveness of cartilage as a cancer treatment.

One of the 5 published studies compared the use of shark cartilage to a placebo (an inactive substance that looks the same as, and is given the same way as, the substance being tested) in cancer patients. Two of the other published clinical studies evaluated the use of Catrix as a treatment for various cancers. A fourth study looked at Cartilade, a commercially available powdered preparation of shark cartilage, in patients with several types of advanced cancer.

A randomized clinical trial (a study in which the participants are assigned by chance to separate groups that compare different treatments) studied the use of shark cartilage in patients who had either terminal breast cancer or terminal colorectal cancer. Patients were randomly assigned to receive either shark cartilage or a placebo. There was no difference in the quality of life or survival rate between the two groups.

A case series (a group or series of case reports that contains detailed information about individual patients) examined 31 patients who were treated with Catrix given by injection under the skin and/or by mouth. Three of these patients (who had skin cancer) also received Catrix applied to the skin. The amount of Catrix used per dose, the total number of doses, and the length of treatment in this series varied from patient to patient. Some patients were treated for 7 months, while others received the treatment for more than 10 years. Nineteen patients had all signs of their cancer disappear (remission); 10 patients saw their tumours shrink; 1 patient had neither growth nor shrinkage of the tumour (stable disease); and 1 patient did not respond to therapy. About half of the patients whose cancer went into remission, however, eventually had a recurrence (reappearance of the signs and symptoms of cancer). It is difficult to draw conclusions from this study because there was no comparison group, and all but 8 patients whose cancer went into remission received standard cancer therapy before and/or at the same time they received Catrix.

A phase II clinical trial evaluated Catrix given by injection under the skin to 9 patients whose cancers did not respond to radiation therapy and/or chemotherapy. The patients were given the same amount in each dose, but the length of treatment and the total number of doses varied. It was reported that 1 patient went into remission for more than 39 weeks. The other 8 patients did not respond to treatment with Catrix. The researchers also looked at whether Catrix had an effect on the immune system in these patients, but no consistent trend or changes were seen.

A phase I/II clinical trial tested the safety and effectiveness of Cartilade given by mouth to 60 patients with advanced cancer. All but 1 patient had been treated with standard therapy before the trial; none of the patients received standard therapy during the study. Among the 50 patients able to be evaluated (patients for whom enough information was collected to study them), 10 patients experienced stable disease for 12 weeks or more; however, the tumours eventually began to grow again. None of the 50 patients experienced a remission or shrinkage of their cancer.

Other studies have been conducted with Catrix, powdered shark cartilage, and AE–941/Neovastat, but the results have not been published in peer-reviewed scientific journals.

Laboratory, animal, and human data provided by the manufacturers have led to several clinical trials of shark cartilage in patients with cancer. People who are interested in taking part in clinical trials should talk with their health care provider.

Have any side effects or risks been reported from cartilage?

The side effects associated with cartilage treatment are usually described in the scientific literature as mild or moderate. Treatment with the bovine cartilage product Catrix is associated with inflammation at the injection sites, a bad taste in the mouth, fatigue, nausea, upset stomach, fever, dizziness, and swelling of the scrotum (the sac that contains the testicles).

Treatment with powdered shark cartilage has been associated with nausea, vomiting, abdominal cramping and/or bloating, constipation, abnormally low blood pressure, abnormally high blood sugar, general weakness, and abnormally high levels of calcium in the blood. The high level of calcium in shark cartilage may contribute to the development of high levels of calcium in the blood of people who have used it. Also, one case of hepatitis has been associated with the use of powdered shark cartilage. Nausea and vomiting are the most common side effects reported following treatment with AE–941/Neovastat.

The FDA has received several reports of adverse events (illness or injury) in people who took cartilage products. The reported side effects of shark cartilage have included loss of vision in the right eye, tachycardia (rapid heartbeat), enlargement of the prostate, headache, and body pain. One person who used shark cartilage reported the development of lymphoma (cancer that starts in the lymphatic system). Jaundice, weight loss, fever, chills, poor appetite, and abdominal pain were reported by another person who took shark cartilage. These two people, however, were taking other nutritional products in addition to cartilage. It is not clear whether the symptoms were caused by 1 of the nutritional products, an interaction of the products, or unrelated factors.

Is cartilage approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

Numerous cartilage products are sold commercially in the United States as dietary supplements. In the United States, dietary supplements are regulated as foods, not drugs. This means that, unless the manufacturer makes specific disease prevention or treatment claims, evaluation and approval by the FDA are not required before the manufacturer can market the product.

Consumers should be aware that dietary supplements may vary a great deal from one batch to another. Dietary supplements are not formally reviewed for manufacturing consistency, and binding agents (substances that make loose mixtures stick together) and fillers may be added during production. Therefore, the result of a particular clinical study may be pertinent only to a particular product from a particular batch made by a specific manufacturer.

Source: Medic8