The role of your cancer health professional is to create an environment of openness and trust, and to help in making informed decisions about alternative/ complementary therapies. Collaboration will improve the safe integration of all therapies during your experience with cancer. The "Summary" and "Professional Evaluation/ Critique" sections of this Unconventional Therapies manual are cited directly from the medical literature, and are intended to help in the objective evaluation of alternative/ complementary therapies.

Summary

"Shark cartilage proved worthless in the first careful scientific study for such products last year [involving shark cartilage treatment for cancer.]" (Associated Press)

"There is a protein in cartilage that can inhibit angiogenesis in test-tube laboratory research. However, this does not mean that cartilage can fight tumors in the human body. In addition to the difficulties involved in translating lab results into research on live patients; cartilage has other potential problems. The most serious problem is that the active ingredient in shark cartilage is too large to be absorbed into the blood stream from the digestive tract, and actually perform any function. This is what happens to the shark cartilage promoted for human use. There is no firm evidence that cartilage treatment is effective against cancer... Given the available evidence or lack of evidence, it is difficult to recommend shark cartilage even as an adjunct to conventional cancer treatments. Certainly, it is not recommended as first or main cancer therapy." (Cassileth)

Description/ Source/ Components

"Cartilage is the part of the skeletal system composed of elastic, translucent tissue, most of which converts to bone as animals grow to adulthood. However, some cartilage remains in areas such as the ears, nose, and knees. Because sharks have no bones, cartilage is the primary component of their skeletal system." (Cassileth)

"Cartilage is obtained from the spiny dogfish shark, Squalus acanthias, and the hammerhead shark, Sphyrna lewini." (Fetrow)

Shark cartilage is available in capsule or powder forms.

"Shark cartilage is typically cleaned by hand, dried and crushed into a fine powder." (Ward)

The administering procedure requires a blender and a big syringe. Shark cartilage powder is mixed with sterile water and given to the patients rectally, and later by pills. (60 Minutes)

"Shark cartilage requires... typically 60 to 90 grams each day either orally or by enema. Patients often take shark cartilage by enema because of the high doses required and because shark cartilage tastes very bad, often inducing nausea in the amount recommended." (Cassileth)

"For cancer treatment, typical dosages of commercially available shark cartilage dietary supplements range from 500 mg to 4,500 mg [0.5 grams to 4.5 grams] daily, depending on the type of preparation and the amount of 'pure' shark cartilage contained." (Fetrow)

It is sold as a food supplement in health food stores. (60 Minutes)

AE-941 is a cartilage extract. Although derived from shark cartilage, it is different from the raw product. (Wilson)

Neovastat is synonymous with AE-941.

History

"The idea that shark cartilage may have an effect in cancer treatment actually is based on one of the most promising areas of contemporary cancer research: angiogenesis. Angiogenesis refers to a process necessary to the growth of tumors. In order to remain alive, tumors[,] like all cells and body parts, require fresh supplies of blood and oxygen. If a tumor has no blood vessels to 'feed it,' it will not continue to grow but will die. Scientists are now working to discover effective ways of halting the blood supply to tumor cells." (Cassileth)

The theory of preventing angiogenesis (formation of new blood vessels) was first proposed by Dr. Judah Folkman, of Harvard University, in 1971. This theory was validated by Dr's Robert Langer and Anne Lee at MIT. (Williams;Lee)

Dr. I. William Lane, a biochemist and nutritionist, became interested in sharks when he worked in marine resources. Lane, PhD, holds a bachelors and masters degree in Nutrition from Cornell University and a doctorate in Agricultural Biochemistry from Rutgers University. (Smith) (Walker)

"Lane has studied the medical application of shark cartilage as a healing agent since 1982. Currently, Lane heads Cartilage Consultants, Inc., in Short Hills, New Jersey." (Ward)

"The National Cancer Institute (NCI) will sponsor phase III trials to test the efficacy of AE-941/ Neovastat... The studies include a multicentre phase III, double-blind, placebo-controlled trial in which AE-941/ Neovastat... will be administered to several hundred cancer patients in hospitals and institutions across the United States and Canada. Pending regulatory review, the trials are scheduled to begin in early 1999." (Anonymous 1999)

Proponent/ Advocate Claims

"Advocates claim that shark cartilage can reduce tumor size, slow or stop the growth of cancer, and help reverse bone diseases such as osteoporosis." (Cassileth)

Tumours develop networks of blood vessels which provides "the tumours with necessary blood supply and energy to survive and grow." Proponents believe that shark cartilage contains a protein that can prevent the blood vessels from forming and starve the tumours. (Ontario)

According to Lane, in a 16-week clinical trial study conducted in Cuba involving 29 terminally-ill cancer patients, 14 of those people are alive and well two years after the study. (Smith)

"In one ongoing study, 50% (10 out of 20) of cancer patients taking shark cartilage reported an improved quality of life, including less pain and better appetite." (Mathews 1993)

Data from one laboratory study (not on human subjects) "suggest that tamoxifen has significant anti-angiogenic activity that can be potentiated by shark cartilage. Combination therapy may be effective in preventing or treating solid tumors." (McGuire)

"In 1983, Lee and Langer demonstrated that a shark cartilage extract... contains a substance that strongly inhibits tumor angiogenesis and restricts tumor growth. (Lee)... These data led to the development of a variety of commercial derivatives of shark cartilage proposed as antiangiogenic preparations. To date, only one of these extracts, AE-941 has been characterized for its antiangiogenic properties in vitro and in vivo and is engaged in clinical in-patient trial for cancer..." (Castronovo)

"Marc Riviere, Aeterna's vice president of clinical affairs, says that laboratory studies showed the substance (which the firm calls Neovastat) [AE-941] blocked blood-vessel development, suggesting it would block tumor growth, and that in small-scale human studies, those receiving a higher dose of Neovastat experienced less tumor progression and weight loss than did those taking lower doses." (Couzin)

"Although there are still intense discussions on the value of cartilage as antiangiogenic agents, there are now sufficient data that support that the derivatives of AE-941 extract from shark cartilage contain antiangiogenic compound(s) that is (are) active in vitro and in vivo. The bioavailability of these compounds appears to be efficient since biological response was demonstrated in animals receiving the derivatives orally. Appropriate phase III clinical trials should demonstrate the therapeutic value of AE-941 in human cancer. It is also crucial to isolate, purify, and characterize the active molecule(s) that is (are) responsible for the biological properties of AE-941." (Castronovo)

Professional Evaluation/ Critique

"The complete absence of clinical studies indicating any degree of efficacy among the thousands of cancer patients treated with shark cartilage suggests that, despite early in vitro results and extensive commercial publicity, this product offers no significant benefit for cancer patients." (Spencer)

Lane's "support of cartilage as a dried, pulverized dietary supplement was challenged in a 1996 U.S. Cancer Treatment Research Foundation study, which showed using the powder had no benefit. Lane's response was that researchers used 'generic-grade' shark instead of his own 'clinical-grade' brand." (Wilson)

"Many of the commercially available shark cartilage food supplements contain only binding agents or fillers. Therefore, without reliable dose-response data and bioavailability studies, it is difficult to determine if these products have true antiangiogenic activity." (Fetrow)

"A 12-week, phase I/II trial on 60 patients with advanced cancer evaluated the cancer safety and efficacy of [commercially available] shark cartilage. The trial concluded that shark cartilage had no anticancer activity and no effect on the quality of life. (Miller)" (Fetrow)

A study done by Horsman and colleagues "investigated the potential of shark cartilage extracts to inhibit the growth and metastatic spread of a murine solid tumour... Two different commercially available extracts of shark cartilage (Sharkilage and MIA Shark Powder) were dissolved in water and orally administered to the mice at doses that ranged from 5 to 100 mg [milligrams] per mouse... Compared to non-drug treated animals, daily administration of the shark cartilage extracts did not show any adverse toxicity (as measured by changes in body weight and lethality.) More importantly, none of the shark cartilage doses tested had any retarding effect on the growth of the primary tumour, nor did they inhibit the development of metastasis seen in the lungs of the tumour-bearing mice at autopsy." These results offer no support for the proposed use of shark cartilage extracts as an anti-cancer therapy. (Horsman)

"Several studies have examined the effectiveness of shark and bovine cartilage against cancer. However, none adhere to scientifically accepted principles of research design, so their results are not meaningful. The results have not even been published." (Cassileth)

During a trial in Cuba, tumours of some patients became smaller but began to grow again sometime later. (60 Minutes)

"Because most macromolecules [i.e. proteins] are usually not absorbed by the intestinal tract, it is questionable that oral administration of shark cartilage can release some compounds into the blood... Currently there is no evidence that shark cartilage offers any benefit to patients with cancer." (Fetrow)

"These food supplements are taken orally and one might ask whether the two glycoproteins allegedly responsible for the antiangiogenic activity reach the blood stream at all, since macromolecules are not usually absorbed by the intestinal tract. " (Ernst)

The notion that "sharks don't get cancer" is not true. Some sharks were found to have chondrosarcomas, cancers that grow in the cartilage. Other tumors reported include blood cell, brain, skin, kidney, and several other types of cancers. (Cancer Letter)

Shark cartilage "is also unlikely to work on the several kinds of cancers that do not rely on the process of angiogenesis." (McCutcheon)

The shark population is diminishing because they have low reproductive rate. "If sharks continue to be hunted ruthlessly, major ecological problems could result." (Mathews 1992)

Toxicity/ Risks

"Shark cartilage has been deemed non-toxic by the U.S. Food and Drug Administration (FDA)." (Northern) (Smith)

"Some products labeled as 100% pure shark cartilage may contain additives and fillers which may destroy its effectiveness." (Ontario)

Some "copycat" shark cartilage products have no antiangiogenic effect while some contain high bacteria counts. (Williams)

"Children, pregnant women, women planning to become pregnant and who have had a recent major injury or surgery should not use shark cartilage as it stops the growth of new blood vessels." (Ontario)

"One case of presumed hepatitis attributable to shark cartilage has been reported. (Ashar)" (Spencer)

Very high doses are reported to be needed: range of 40-90g per day for 6-9 months. (Nakashima)

"Shark cartilage is stated to be an important source of calcium when, in fact, it is a dangerous source of too much calcium when taken in what is labeled the `therapeutic' dose." (Prudden)

Costs

The cost is approximately $44 for 100 capsules. (Ontario, 1994)

A typical regimen of shark cartilage costs $700 per month [U.S.]. (Cassileth, 1998)

References

Anonymous. NCI to sponsor phase III trials of liquid shark cartilage angiogenesis inhibitor [news]. Oncology (Huntingt.) 1999;13:82.

Ashar B, Vargo E. Shark cartilage induced hepatitis. Ann Intern Med 1996;125:780.

Associated Press. FDA seeks to halt marketing of shark tissue as cancer cure. AP release. Dec. 10, 1999.

Cancer Letter (Anonymous). Sen. Mack seeks NCI support for shark cartilage research. The Cancer Letter 1994 Aug 5;20(31):1.

Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998:197-200.

Castronovo V, et al. Cartilage as a source of natural inhibitors of angiogenesis. Antiangiogenic Agents in Cancer Therapy 1999:175-183.

Couzin J. Beefed-up NIH center probes unconventional therapies [news]. Science 1998;282:2175-6.

Dupont E, et al. Angiostatic and antitumoral activity of Neovastat, a molecular fraction derived from shark cartilage. American Association for Cancer Research, San Diego, CA 1996.

Dupont E, et al. Angiostatic and antitumoral activity of AE-941 (Neovastat-R), a molecular fraction derived from shark cartilage (Meeting Abstract). Proc Annu Meet Am Assoc Cancer Res 1997;38:A1530.

Dupont E, et al. In vitro and in vivo anti-tumor activity of Neovastat (AE-941), an angiostatic agent derived from shark cartilage. American Association for Cancer Research, San Diego, CA 1996.

Ernst E. Shark cartilage for cancer? Lancet 1998;351:298.

Fetrow CW, Avila JR. Professional's handbook of complementary and alternative medicines. Springhouse, Pennsylvania: Springhouse Corporation 1999:595-598.

Horsman MR, et al. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma 1998;37:441-5.

Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983 Sep 16;221:1185-1187.

McCutcheon L. Taking a bite out of shark cartilage. Skeptical Inquirer 1997 Sept/Oct:44-48.

McGuire TR, et al. Tamoxifen and shark cartilage: potential anti-angiogenic combination. (Abstract from American College of Clinical Pharmacy Annual Meeting St. Louis, 1994) Pharmacotherapy 1994;14(3):362.

Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. Journal of the National Cancer Institute 1993 Aug 4;85(15):1190-1191.

Mathews J. Sharks still intrigue cancer researchers. Journal of the National Cancer Institute 1992 July 1;84(13):1000-1002.

Miller DR, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-55.

Nakashima L. BC Cancer Agency verbal communication 1996.

Northern seas shark cartilage. (BCCA Cancer Information Centre search file 2361)

Ontario Breast Cancer Information Exchange Project. Guide to unconventional cancer therapies. 1st ed. Toronto: Ontario Breast Cancer Information Exchange Project, 1994.

Prudden JF. Cartilage as therapy. Adjuvant Nutrition in Cancer Treatment Symposium, Tampa, Florida, Sept 27, 1997:A26.

60 Minutes. July 11, 1993 transcript. (BCCA Cancer Information Centre search file 2361)

Smith J. 'Shark doctor' starts to make waves with cancer theories. The West Ender 1995 July 20:25.

Spencer JW, Jacobs JJ. Complementary/alternative medicine: an evidence based approach. Toronto: Mosley, 1999:154-55.

Walker M. The shark: a floating nutritional factory. (Search file 2361)

Ward N. Shark cartilage: cancer-fighting potential brings hope to many cancer patients. Media Relations, Inc. (BCCA Cancer Information Centre search file 2361)

Williams DG. The continuing story behind shark cartilage. Alternatives 1993 Jan;4(19):145-152.

Wilson B. Can shark cartilage take a bite out of tumours? georgia,times,serif Straight 1999 Apr 25 - May 1.

Revised February 2000