Anigiogenesis Inhibiting Proteins and Shark Cartilage

Arthritis Benefits from Shark Cartilage Therapy -- Leon Sculti

Shark Cartilage: Anticancer Agent of Hype? -- School of Pharmacy, Mercer University, Atlanta, GA

Shark cartilage extract promising; Experimental agent starves tumors' lifelines, study suggests -- MSNBC -- March 2001

Shark Cartilage Brings Arthritis Relief to Dogs -- Ben Dow, DVM

Shark Cartilage Research with Dogs: Jacques Rauis DVM University of Liege 1991 (excerpt)

The Arthritis Solution for Dogs by Dr. Shawn Messonier (excerpt)

Shark Cartilage Shows Angiogenesis Inhibiting Properties -- Wellington Medical School, New Zealand

Arthritis Benefits from Shark Cartilage Therapy

By: Leon Sculti

Controversial or Cutting Edge?

Shark cartilage is one of the hottest and most controversial topics debated in medical circles today. Although its mode of action is accepted by established medical principles, the mechanism, or combination of elements responsible for triggering that action, remains a mystery.

Highly touted for its alleged cancer-fighting abilities (and currently under clinical trials by the Food and Drug Administration [FDA] on terminally ill cancer patients in new Jersey), this natural nontoxic substance is now becoming widely accepted as an effective means for treating less fatal degenerative diseases such as osteoarthritis and rheumatoid arthritis.

"Phenomenal" is how Robert C. Greenburgh, B.S., D.C., E.A.S.A., describes the results he has seen from approximately sixty-five arthritis patients who have used, and continue to use, shark cartilage therapy under his care. Greenburgh explains, "When you have arthritis, you have inflammation; you have vascularity and the creation of new blood vessels. Shark cartilage must be the number one choice with inflammation .... it's definitely cutting edge."

Consumers Drive Demand

Right now, approximately 8 million Americans suffer from rheumatoid arthritis and more than 40 million from osteoarthritis. Indeed, up to one-third of all Americans turn to alternative treatments every year. Theoretically, that represents the potential for some 16 million new consumers to enter the shark cartilage market this year alone, seeking relief for arthritis pain. Although these numbers do not explain why traditional medicine and its establishments all but ignore alternative therapies, they do suggest why the demand for such therapies, like shark cartilage, is booming.

"This is a consumer-driven product" explains the health care manager of a major shark cartilage manufacturer. "Sales to [medical] professionals are up 71 percent in the last eight months alone. When a doctor orders our product, he or she is usually doing it for a patient." Sales figures show that medical doctors, with both traditional and holistic philosophies, are the most active group of professionals purchasing shark cartilage, with sales to chiropractors and naturopaths ranking second and third, respectively.

How does Shark
Cartilage Fight Arthritis?

Although researchers have not been able to pinpoint the exact therapeutic agent in shark cartilage, many agree that the primary inflammation-fighting component is a family of complex carbohydrates called mucopolysaccharides. Two members of this family, chondroitin sulfates A and C, have long been used by nutrition medicine practitioners to fight inflammation and enteritis. But for some reason it appears that the naturally occurring forms of these compounds in shark cartilage (which are among the largest produced by any living cells) are more effective than the synthetically refined mucopolysaccharides.

Even more important, when combined with the angiogenesis inhibition properties, which are believed to exist in the proteins, shark cartilage may not only provide inflammation relief, but also inhibit the vascularization of cartilage -- often associated with advanced cases of both osteoarthritis and rheumatoid arthritis --in human joints. Inhibiting the formation of new blood vessels is the number one basis for claims made about shark cartilage's ability to successfully fight cancerous tumors.

Shark cartilage itself appears to have no negative side effects, except for some reported upset stomachs. Its major drawback is the fact that researchers cannot locate and isolate its active elements. many people, like I. William Lane, Ph.D., the most prominent proponent of shark cartilage and author of the book Sharks Don't Get Cancer, feel this is not a drawback, but rather a small tactic to eventually produce a synthetic version of shark cartilage to satisfy those with profit-driven motives. "As soon as it's pinpointed [the therapeutic agent], you can be sure the drug companies will synthesize it," says Lane. To the contrary, others, like Carl Luer, who has done extensive research with shark cartilage, feel that uncertainty is just grounds for skepticism. He says, "If it's effective, that's great." But he adds, "We need to find out what [the active molecule] is, rather than catching sharks, chopping them up, and putting them in pill form." These two contrasting schools of thought give excellent insight to the moral, emotional, and professional dilemma that the advent of shark cartilage has spawned.

Shark Cartilage

Active Elements:
Proteins, Mucopolysaccharides, rest unknown

How supplied:
Capsule, Powder form

First Studies:
Institut Jules Bordet, Brussels, 1988

Early Research with
Bovine Cartilage

It was the research of Robert Langer and Anne Lee, who were studying the antiangiogenetic effect of bovine cartilage in 1983, that eventually brought shark cartilage to the forefront of cancer and arthritis research. Soon after concluding that bovine cartilage did, in fact, possess angiogenesis inhibition properties, Langer and Lee learned why shark cartilage may work even better in producing the same effect.

Because there is so little fat clinging to shark cartilage as compared with bovine cartilage, it requires far less purification, and therefore can be considered "purer" than bovine cartilage. In addition, a shark's skeleton, which represents 6 to 8 percent of its body weight, is comprised entirely of cartilage, making it considerably more abundant than bovine cartilage. Langer and Lee reported that the same therapeutic amount of extract recovered from 500 grams of bovine cartilage could be processed from only 0.5 gram of shark cartilage. Therefore, on a pound-for-pound basis, shark cartilage is 1,000 times more potent as an angiogenetic inhibitor than cartilage obtained from cows or other mammals.

Arthritis Studies

Once shark cartilage came into the limelight, researchers concentrated mostly on conducting cancer studies with it. The first arthritis studies, which are the best-documented, were done using bovine cartilage extracts. Here is a look at some documented arthritis studies.

1. A study conducted by John Prudden was described in Seminars in Arthritis and Rheumatism1. In this study, 28 arthritis patients, all of whom exhibited severe pain and major functional disability, were given a cartilage preparation over a period of three to eight weeks. Of the 28 subjects, 19 showed results that were classified as "excellent"; six were classified as having "good" results; and three were classified as "fair" or showed "no response". It was noted that none showed any ill effects.

2. The results of a long-term study conducted by Dr. Rejholec, Head of Internal Medicine/Rheumatology at Charles University in Prague, Czechoslovakia, were published in Seminars in Arthritis and Rheumatism2. The five-year, double-blind study was done using three groups, with a total of 147 osteoarthritic patients. Two of the three groups were given variations of bovine cartilage extract; the other group (control) received a placebo. The placebo group was encouraged to use various non-steroidal anti-inflammatory drugs (NSAIDs) during active episodes. These results were quite exceptional. The groups treated with the cartilage had average pain scores drop 85 percent, whereas the average pain score of the control group fell only 5 percent over the five years. Also, the actual joint degeneration in the cartilage-treated group was significantly less than that of the control group. At the end of five years, the joint degeneration of the cartilage-treated group was 37 percent of the control group.

3. In 1989, Jose A. Orcasita of the University of Miami School of Medicine administered doses of dry shark cartilage for a period of three weeks to six elderly patients suffering from "significant" to "unbearable" pain from osteoarthritis. In all cases Orcasita reported that pain was markedly reduced and quality of life was vastly improved.3

Clinical Applications Using Shark
Cartilage to Treat Arthritis

Approximately, 15,000 to 18,000 Americans, whether under the supervision of a physician or not, take daily doses of shark cartilage as a treatment for either arthritis or cancer. As of yet, there has been no official protocol concerning the application of shark cartilage to treat arthritis. There is, however, a wealth of information from which to draw.

Based on the research he has been privy to over many years, Lane, who makes it clear that he is not a medical practitioner, reports that "60 to 70 percent of rheumatoid and osteoarthritis cases have experienced successful reduction in pain when given 1 gram of dry powdered shark cartilage per 15 pounds of body weight." If capsules of powdered shark cartilage (assuming they are 740-750 mg each) are administered, that dosage would be equivalent to 1 capsule per 11 pounds of body weight. Lane adds, "The effect with arthritis is rapid. You can usually notice a difference within 2 to 3 weeks, due to the anti-inflammatory agent. If results do not occur within 30 days of treatment, this therapy probably will not work for that particular patient."

Greenburgh, who has adapted shark cartilage therapy in his Missouri practice, uses somewhat different guidelines when treating patients who suffer from arthritis. Like Lane, he uses body weight as a measuring device when determining dosages, but elaborates:"... the stage or state of inflammation is important as well; the bigger the individual and the more advanced the situation, the higher the dosage." He estimates his dosage platform to be "1 gram of dry powdered shark cartilage per every three to five pounds of body weight." Greenburgh employs a 90-day program for his patients and says, "I have never been disappointed ... and have always noticed a significant change for the better when using this 90-day program."

Once treatment has been considered successful, Greenburgh reduces the dosage to a maintenance level of "about 1 to 2 capsules three times a day." When asked what was the best thing about shark cartilage, Greenburgh responded, "The fact that it's been deemed totally nontoxic by the FDA ... I know that I can't hurt anybody." Most doctors familiar with shark cartilage generally agree that: (1) It is most effective when the daily dosage is taken orally, three times a day, in equal amounts, about 15 to 20 minutes before meals; (2) When taking dry powdered shark cartilage, every 1 gram of shark cartilage should be mixed in a blender with 2 oz of nonacidic fruit juice or nectar (capsules can be taken with water); (3) If a patient experiences an upset stomach due to the fishy taste, retention enemas can be applied; (4) Due to the antiangiogenetic effect, children, pregnant women, and people who have experienced a recent heart attack should not be taking shark cartilage. It should also be discontinued three months before and after any major surgical procedure.

Determining the Best Product

Due to the fact that shark cartilage is sold a food supplement in the Untied States, manufacturers of the product must abide by certain FDA regulations. These companies are forbidden to directly claim or indirectly imply through the labeling, advertising, marketing, or promotion of their product that it has any medical or therapeutic value whatsoever. The result of this has been mass confusion in a mass market. Unable to mention primary consumer benefits and selling points, it has become extremely difficult for any one brand to separate itself from the rest, Thus, consumers, doctors, and retailers alike are all left to decipher for themselves which products are truly effective and which are merely cheap imitations.

The Lesser or Two "Evils"?

It is likely that consumer demand will continue for shark cartilage as more and more people experience its benefits. With it being deemed nontoxic by the FDA, shark cartilage does not have many of the side effects such as gastric irritation seen with other prescription arthritis agents o the market such as the NSAIDs. Certainly, this is where shark cartilage has a distinct advantage. One has only to read many of the current advertisements for arthritis pain and medications featured in popular health magazines. A recent ad informed readers that, if taken once a day, the drug "may relieve arthritis pain." However, the ad also warned that this very same drug could cause "serious side effects, including stomach ulcers and intestinal bleeding." In addition, the copy revealed that "the most common side effects associated with the use of [that particular product] can include abdominal pain, constipation, diarrhea, stomach upset, nausea, and skin rash." The drug being advertised was only available with a doctor's prescription.

References
1. Prudden, J. Sem Arthritis and Rheumatism, Summer 1974.
2. Rejholec. Sem Arthritis and Rheumatism, 17(2), Nov. 1987.
3. Let's Live, March 1994, p. 16.

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Shark cartilage extract promising; Experimental agent starves tumors' lifelines, study suggests

Neovastat is derived from the cartilage of the dogfish shark.

By Charlene Laino
MSNBC
March 2001

NEW ORLEANS, March 26 - Patients with advanced kidney cancer given an extract of shark cartilage lived twice as long as would be expected if they hadn't taken the fishy concoction, a small pilot study shows. And three patients - all of whom failed to respond to all standard cancer treatments and probably would have died within eight months - are still alive 31 months after treatment began, researchers said.

THE EXTRACT, a product made from the cartilage of the common dogfish shark that is prepared differently than the shark cartilage pills sold in some natural food stores and over the Internet, is also showing promise in patients with advanced lung and blood cell cancers, said principal investigator Dr. Gerald Batist, a cancer doctor at McGill University in Montreal. Its anti-cancer fighting properties: four chemicals that are what scientists called anti-angiogenesis factors - substances that literally starve the lifelines of tumors, he said. The product, known as Neovastat, is among the most promising entries into the fashionable field of anti-angiogenesis agents, said Dr. William Li, clinical instructor of medicine at Harvard and head of the non-profit Angiogenesis Foundation in Cambridge, Mass. The development of anti-angiogenesis drugs capped a 30-year research process that began when Dr. Judah Folkman of Harvard Medical School had the hypothesis in the 1970s that tumors cannot grow or spread without a steady blood supply to feed them. By developing drugs that block the formation of new vessels, Folkman reasoned, you would eliminate the flow of blood to tumors, much like chopping a plant off at its roots. And without nutrients, tumors, like plants, would be prevented from growing much bigger than a pinhead.

In the past few years, dozen of anti-angiogenesis drugs have entered clinical trials, although none has yet been approved for use as an anti-cancer agent in the United States. But Pierre Falardeau, vice president of scientific affairs at Aeterna, which manufactures the shark cartilage extract, said if all goes as planned, the drug could be available by prescription within a year or two. The drug is "extremely interesting and promising," said Li, a former student of Folkman's. "This the first anti-angiogenesis agent to show a statistically significant - that is, not due to chance - increase in survival in a group of critically ill patients." Extending survival is the Holy Grail of this class of drugs, Li explained. "Of the more than 50 agents in clinical trials, Neovastat is among the elite dozen that have made it to the final stages of human testing and the first to actually show improved survival." Neovastat is also noteworthy for its triple mode of action against the growth of new blood vessels to feed a tumor, he said. The drug blocks a growth factor that signals tumor cells to recruit new blood vessels, inhibits an enzyme needed for cancer cells to invade new tissue, and stimulates cancer cell death, according to Li.

CARTILAGE THE KEY
Shark cartilage was originally studied as it was thought that sharks don't develop cancer and thus must contain anti-cancer agents. Ironically, even though it's since been shown that sharks do develop cancer after all, cartilage was found to be a rich source of anti-angiogenesis factors, Falardeau said.

"The cartilage can be from any species - chickens, fish, whatever," he said. "But sharks are a good source because they are abundant in waters worldwide and widely fished for their meat, with the cartilage normally discarded." The spines of about 100 dogfish sharks are needed to treat one cancer patient for one year, according to Falardeau. The cartilage is crushed up and purified into a liquid that is then frozen. The patient thaws the pint-sized drink - described as "fishy" tasting - before drinking it twice a day. In preparing Neovastat, the researchers use a patented biochemical method to treat the cartilage in such a way that it releases the anti-angiogenesis factors.

STUDY DETAILS
The study, presented here Monday at the annual meeting of the American Association for Cancer Research, enrolled 22 patients with advanced kidney cancer that had spread to other parts of the body and could not be helped by any conventional therapy. Surgery to remove the kidney had failed to stop the cancer from spreading and neither radiation nor chemotherapy successfully killed off remaining cancer cells. Advertisement

Eight patients treated with a low dose of the drug lived an average of 7.1 months, compared to 16.3 months for 14 patients receiving a higher dose. For a patient with this advanced cancer who does not respond to standard treatments, the expected survival time is approximately eight months, Li said. On the basis of the results, all surviving patients have since been given the higher dose: Three are still alive, including one who had developed a tumor on her head that completely disappeared. No significant side effects were observed in the patients. The trial was funded by Aeterna. The National Cancer Institute found the results promising enough that it is funding a larger study in patients with lung cancer, Falardeau said. Trials are also underway in patients with multiple myeloma, a cancer of the blood.

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