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A Fishy Therapy
A thriving but controversial dietary supplement

Janet Raloff

Shark cartilage is for sale all over the Web. Powders of it, packaged in jars and capsules, are among the products offered at sites specializing in herbal remedies, vitamins, health wares, and bodybuilding aids. These Internet sites claim that the cartilage skeletons of sharks and their close relatives—skates and rays—offer various health benefits. Inhibiting cancer is often at the top of the list. To support that contention, sellers point to studies indicating that something in shark cartilage can inhibit the blood vessel growth that tumors rely on for access to nutrients.

photo

NO BONES. This shark skeleton, on display at the Smithsonian Institution, is all cartilage. As such, it's one of the richest sources of raw material for an industry that sells powdered cartilage as a cancer therapy. To date, however, no major study has shown it to be effective.

J. Miller

The idea that cancer patients who aren't helped by conventional medicine might benefit from ground-up shark skeletons was the central thesis of two books coauthored in the 1990s by nutritionist I. William Lane. Their titles argue that "sharks don't get cancer."

A 60 Minutes television profile of Lane more than a decade ago publicized the controversial cancer treatment. Among business ventures capitalizing on the early interest was Lane Labs of Allendale, N.J. That company was created by Andrew Lane, I. William Lane's son, to sell BeneFin, a shark-cartilage product.

However, shark-cartilage therapy, a large segment of the food-supplements industry, is based on severely flawed premises, according to some scientists.

A new report by one group of them contradicts the view that sharks don't get cancer. Several major recent and ongoing studies have also failed to show any cancer benefit in people from powdered shark cartilage, although a few studies report promise in a mix of chemicals extracted from cartilage as a potential anticancer pharmaceutical.

Even if current cartilage therapy isn't directly harmful, many clinicians worry that its promotion also encourages patients to give up on proven or potentially more-useful therapies.

Much of that promotion also has been deemed illegal by federal agencies, which have recently been moving against some of these products, including BeneFin, as unapproved drugs marketed under the guise of dietary supplements.

How rare?

The claim that sharks in the wild never get cancer first made some people conclude that something in sharks fights the disease. Yet in 1915, scientists reported a spiny dogfish shark from the Straits of Georgia sporting a thyroid tumor. In 1971, researchers described a sandbar shark caught off of Florida that had both a lymphoma and a metastatic adenocarcinoma. Reports of other shark tumors afflicting nervous, digestive, excretory, blood, reproductive, skeletal, endocrine, and skin tissues—and even cartilage—are on file at a national archive devoted to cancer in cold-blooded animals.

How common such shark tumors are, however, remains open to debate.

Gary K. Ostrander is both a marine scientist and a cancer biologist at Johns Hopkins University in Baltimore. In the Dec. 1, 2004 Cancer Research, his team reviews cases of illness in captured sharks and related fish that had been filed with the Registry of Tumors in Lower Animals in Sterling, Va. The team turned up 42 cases affecting 21 species.

Forty-two tumors may not be many, Ostrander acknowledges. However, he points out, sick fish usually don't show up on hooks or in trawlers' nets. They tend to fall prey to healthy fish or just sink to the bottom, where they die of their illnesses. Therefore, he argues, "we wouldn't really expect to see many cancers," especially given that these fish normally cruise in deep waters far from shore.

Carl A. Luer of the Mote Marine Laboratory in Sarasota, Fla., doesn't buy Ostrander's argument. Many sharks and their relatives "are collected either for science or the fishing industry," he observes, "and you don't find the incidence of cancer in them that you see in bony fish."

Also, Luer failed to induce cancer in sharks during 10 years of trying to create an animal model for the human disease. For instance, he showed that the human carcinogen aflatoxin B1, which readily triggers malignancies in fish with bony skeletons, did nothing to sharks.

Indeed, Luer tells Science News, "We were not able to produce anything approaching even a [precancerous] change in sharks."

Adds Robert E. Hueter, director of shark research at the Mote lab, "I've been working with sharks for 30 years, and when you see one in the wild, it tends to be very clean [of disease] when compared to other kinds of marine vertebrates, such as bony fish. Sharks also heal up quickly from any wound—and you hardly ever see a shark that looks old."

But even an absence of cancer in sharks, Hueter readily adds, wouldn't justify using unrefined shark cartilage as a therapy against human cancer.

Too crude

If people enthusiastic about swallowing shark cartilage saw how it's harvested, they might think twice. Vessels that catch the sharks often hold the carcasses for days to weeks without refrigeration.

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HAMMERED. Sharks such as these hammerheads bear few young and reproduce slowly. A growing market for cartilage could further deplete global shark populations, which are already in a nosedive.

©Mote Marine Lab., Herman Gross Collection

Some researchers doubt whether material collected in this way could maintain pharmaceutically useful properties. Because the cartilage undergoes so much decay, Hueter says, "it's just ridiculous to think it might still retain biological activity."

It certainly didn't show anticancer activity in the first major trial of powdered cartilage, conducted by Denis R. Miller, at the Cancer Treatment Research Foundation in Arlington Heights, Ill.

"We had found that a lot of patients, when we asked about their nutritional histories and use of alternative, complementary medicine, said they were taking shark cartilage," Miller notes. So, the foundation funded a study of the supplement's safety and potential efficacy in adults whose cancers of the breast, colon, rectum, prostate, lung, or other organ were not responding to conventional therapies. All participants received the recommended dose of a commercially available product called Cartilade.

Although Miller's group had planned to treat 100 people, recruitment proved difficult. However, by the time that it had 60 participants, a clear trend had emerged, says Miller, now senior director of oncology at Johnson & Johnson Pharmaceutical Research & Development in Raritan, N.J.

"We found no toxicity, but we also didn't find any benefits in tumor response," he recalls. So, his team shut down the study and published its findings in 1998.

More recently, Charles L. Loprinzi's group at the Mayo Clinic in Rochester, Minn., headed a National Cancer Institute–funded, multicenter trial comparing BeneFin and a placebo. This experiment, too, stopped early, after enrolling only about 80 of an initially planned 600 patients with intractable breast or colorectal cancer.

The limited results showed "no suggestion of a [survival] benefit and no evidence of a positive impact on quality of life" from shark cartilage, the researchers reported in New York City at the November 2004 meeting of the Society of Integrative Oncology. Moreover, they noted, by the end of a month, half of the people assigned to the cartilage regimen refused to take the more-than-1-cup daily dose.

Deterring compliance, the researchers noted, was not only the huge dose but also the product's "very fishy smell that you could detect across the room."

Becoming a drug

The strongest evidence that shark cartilage might fight cancer comes from demonstrations that some of its components can stop the growth of new blood vessels. A tumor lures blood vessels to form on its expanding periphery, providing the pipelines to nourish it. Without this extra blood supply, a tumor can't grow.

Several anticancer drugs introduced in the past few years inhibit that process, called angiogenesis (SN: 3/2/02, p. 139). Research by Luer and others has shown that something in fresh cartilage can block angiogenesis. That finding has spurred efforts to isolate the active components with the goal of eventually synthesizing drugs to emulate them. A major trial of the shark-derived components in patients is now under way, supported in part by Æterna Zentaris, a pharmaceutical company headquartered in Quebec.

Its experimental drug, called Neovastat, is "not like the powdered cartilage that you find in health food stores," explains company spokesman Paul Burroughs. Although the chemistry of its anti-angiogenic agents has not been characterized, he says, "we have established a standardized and well-controlled extraction of these materials from the cartilage of spiny dogfish sharks."

Laboratory tests have shown that Neovastat not only prevents blood vessel growth in tumors but also has other potentially anticancer activities, Burroughs says. For instance, the extract triggers suicide in cancer cells (SN: 6/16/01, p. 378) and inhibits enzymes that normally break down tissue around tumors, a process that can permit cancers to spread.

In a trial 2 years ago against metastatic kidney cancer, however, Neovastat failed to prolong survival of patients.

Recently, the National Cancer Institute commissioned Charles Lu, an oncologist at the University of Texas–M.D. Anderson Cancer Center in Houston, to spearhead a new trial of Neovastat against recalcitrant lung cancer. The participants are "people who would typically live for, on average, up to a year and a half," Lu says. All participants will receive either Neovastat or a placebo while continuing to get radiation treatments and chemotherapy.

The 340 patients that the project has enrolled to date represent about half the number that the researchers intend to recruit. A study of that size is large enough "to have the statistical power to tease out any survival benefit" from the cartilage derivative, Lu says.

"We're doing this study because we think that addressing whether there's something special in cartilage—from a shark or any other animal—is important," Lu told Science News.

Federal crackdown

Despite the absence of clear evidence that powdered shark cartilage shuts down angiogenesis, some companies are claiming that their products do just that. Recently, the Web site of Heritage Health Products of Fort Collins, Colo., stated, "Shark cartilage has been proven as an anti-angiogenic agent, as it literally starves a tumor of its blood supply [and] can prove very effective in counteracting … angiogenic-dependent ailments."

Making such health claims has gotten Heritage Health and other cartilage promoters in hot water.

Moves against Lane Labs began in 1997, when the Food and Drug Administration acquired an injunction against the company and its president for the deceptive marketing of three products, including BeneFin. Although Lane Labs claimed that all three were dietary supplements or cosmetics, FDA noted that the company "promoted those products for the treatment of cancer." Such claims rendered the products drugs, the FDA charged.

The agency also cited statements by I. William Lane, a paid consultant to the company, that these products were intended for treating or preventing disease. FDA ordered Lane Labs to pull such claims from all its promotional activities.

When FDA found that the company wasn't complying, the Federal Trade Commission stepped in. In June 2000, it announced that it was fining Lane Labs $1 million for illegal activities.

Still, the case lingers. On July 9, 2004, a U.S. District Court ruled that Lane must end all U.S. distribution of the three products, unless they gain FDA approval as drugs, reimburse all buyers for those products purchased after Sept. 22, 1999, and destroy remaining stocks of the products.

Neither Lane nor any spokesperson for the company could be reached for comment. However, Marc S. Ullman, a New York City attorney whose firm was formerly retained by Lane Labs, told Science News that the court has stayed its call for financial outlays by the company. He added that Lane Labs has indicated that it "intends to comply with all [remaining] orders of the court." Currently, BeneFin appears to be available only via Internet dietary supplements dealers.

Last year, FDA began challenging the marketing of other shark-cartilage products, such as those from Heritage Health.

Other fallout

The claim that shark cartilage has medical value may further threaten already-dwindling shark populations. Manufacturers of cartilage products favor sharks because they're much richer sources of this material than are mammals, which develop cartilage primarily in their joints, observes Merry Camhi of Islip, N.Y., a member of the shark-study group of the International Union for the Conservation of Nature and Natural Resources in Gland, Switzerland.

This focus on sharks is a problem, she and other biologists argue, because these fish are already beleaguered by the demand for their fins (SN: 10/12/02, p. 232) and, to a lesser extent, for their meat (SN: 4/15/00, p. 246). Indeed, a Jan. 29 study in Philosophical Transactions of the Royal Society of London: Biological Sciences reports dramatic declines in large predatory fishes, especially sharks, during the past half century. For instance, shark populations in the North Atlantic and the Gulf of Mexico may now represent just 1 or 2 percent of their abundance 50 to 100 years ago, according to the report, which was written by Ransom A. Myers of Dalhousie University in Halifax, Nova Scotia, and Boris Worm of the Institute for Marine Science in Kiel, Germany.

Several years ago, Camhi analyzed the impact of the cartilage industry on shark populations. She concluded that the market for cartilage "makes [shark fishing] that much more lucrative" and increases pressure on populations of these fish.

This shark trade might be acceptable, Ostrander says, if cartilage therapy actually saved lives. However, he laments, after some 15 years of exploring the concept and conducting several well-controlled trials, scientists have zero evidence that it does.

********

Letters:

I'm sure you published this article in good faith, but I believe that claims for shark cartilage are not made seriously by anyone who studies the role of natural substances in cancer prevention. It was proved ineffective long ago. I think your article does a disservice to honest people who are trying to fight the drug-industry prejudice against natural (profitless) substances to prevent and treat many diseases. Shark cartilage is a red herring.

James Street
Oakland, CA

References:

2004. U.S. District Judge issues permanent injunction against Lane Labs-USA, Inc. and orders firm to refund money to purchasers of illegally marketed unapproved drugs. FDA news release. July 13. Available at FDA.gov.

2003. Æterna Laboratories reports Phase III trial results in renal cell carcinoma with Neovastat. Æterna Laboratories news release. Sept. 24.

2001. Phase III randomized study of shark cartilage (BeneFin™) with advanced colorectal or breast cancer. From the Clinical Trials (PDQ®) online database.

1999. FDA takes action against firm marketing unapproved drugs. FDA talk paper. Dec. 10. Available at The Body.

Batist, G., et al. 2002. Neovastat (Æ-941) in refractory renal cell carcinoma patients: Report of a phase II trial with two dose levels. Annals of Oncology 13(August):1259–1263. Abstract.

Baum, J.K., and R.A. Myers. 2004. Shifting baselines and the decline of pelagic sharks in the Gulf of Mexico. Ecology Letters 7(February):135–145. Abstract.

Béliveau, R., et al. 2002. The antiangiogenic agent Neovastat (Æ-941) inhibits vascular endothelial growth factor-mediated biological effects. Clinical Cancer Research 8(April):1242–1250. Abstract.

Durie, B.G., B. Soehnlen, and J.F. Prudden. 1985. Antitumor activity of bovine cartilage extract (Catrix-S) in the human tumor stem cell assay. Journal of Biological Response Modifiers 4(December):590–595. Abstract.

Federal Trade Commission v. Heritage Health Products Company. April 15, 2004.

Gingras, D., et al. 2003. Neovastat—a novel antiangiogenic drug for cancer therapy. Anti-Cancer Drugs 14(February):91–96. Abstract.

Latreille, J., et al. 2003. Phase I/II trial of the safety and efficacy of Æ-941 (Neovastat®) in the treatment if non-small-cell lung cancer. Clinical Lung Cancer 4(January):231–236. Abstract.

Loprinzi, C.L. 2004. Evaluation of Benefin® shark cartilage in patients with advanced cancer: An NCCTG Trial. Society of Integrative Oncology meeting. November. New York City.

Miller, D.R., et al. 1998. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. Journal of Clinical Oncology 16(November):3649–3655.

Moses, M.A., J. Sudhalter, and R. Langer. 1990. Identification of an inhibitor of neovascularization from cartilage. Science 248(June 15):1408–1410. Abstract.

Myers, R.A., and B. Worm. 2005. Extinction, survival or recovery of large predatory fishes: One contribution of 15 to a theme issue 'Fisheries: A Future?' Philosophical Transactions: Biological Sciences 360(Jan. 29):13–20. Abstract.

Ostrander, G.K., et al. 2004. Shark cartilage, cancer and the growing threat of pseudoscience. Cancer Research 64(Dec. 1):8485–8491. Abstract available at Abstract.

Further Readings:

2004. Company ordered to halt sales of unapproved drugs, reimburse buyers. FDA Consumer 38(Sept./Oct.).

Christensen, D. 2002. Tracking tumors. Science News 161(March 2):139–140. Available at Science News.

Davis, P.F., et al. 1997. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvascular Research 54(September):178–182.

McGuire, T.R., et al. 1996. Antiproliferative activity of shark cartilage with and without tumor necrosis factor-alpha in human umbilical vein endothelium. Pharmacotherapy 16(March–April):237–244. Abstract.

Passwater, R.A., and I.W. Lane. Shark cartilage and cancer, revisited: A follow-up interview . Health World Online. Available at Full Text.

Raloff, J. 2004. Shark finning faces broader sanctions. Science News Online (Dec. 11). Available at Science News.

______. 2002. Rare animals get U.N. protection. Science News 162(Oct. 12):237. Available at Science News.

______. 2002. Clipping the fin trade. Science News 162(Oct. 12):232–234. Available at Science News.

______. 2001. Coming to terms with death. Science News 159(June 16):378–380. Available at Science News.

______. 2000. New protection for much-dogged shark. Science News 157(April 15):246. Available at Science News.

Seppa, N. 2004. Keeping cells under control: Enzyme suppression inhibits cancer spread. Science News 166(Aug. 28):134. Available at Science News.

______. 2004. Gap in the defense: Brain cancer patients short on valuable protein. Science News 165(March 20):180. Available at Science News.

______. 2003. Cancer advance: Treatment combinations stall colorectal cancer. Science News 163(June 7):358. Available at Science News.

Sheu, J.R., et al. 1998. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Research 18(November-December):4435–4441. Abstract.

For further information from the National Cancer Institute on shark-cartilage therapy, go to Cancer.gov.

Sources:

Paul Burroughs
Æterna Zentaris Inc.
1405 boul. du Parc-Technologique
Québec City, Québec G1P 4P5
Canada

Merry Camhi
IUCN Shark Specialist Group
126 Raymond Street
Islip, NY 11751

Robert E. Hueter
Center for Shark Research
Mote Marine Laboratory
1600 Ken Thompson Parkway
Sarasota, FL 34236

LaneLabs-USA
25 Commerce Drive
Allendale, NJ 07401-1600
Web site

Charles L. Loprinzi
Mayo Clinic
200 First Street, S.W.
Rochester, MN 55905

Charles Lu
Unit 432
University of Texas, Houston
M.D. Anderson Cancer Center
P.O. Box 301402
Houston, TX 77230-1402

Carl A. Luer
Marine Biomedical Research Program
Center for Shark Research
Mote Marine Laboratory
1600 Ken Thompson Parkway
Sarasota, FL 34236

Denis R. Miller
J&J PRD
920 Route 202
Raritan, NJ 08869

Gary K. Ostrander
Johns Hopkins University
3400 North Charles Street
231 Garland Hall
Baltimore, MD 21218

Marc S. Ullman
Ullman, Shapiro & Ullman, LLP
299 Broadway, Suite 1700
New York, NY 10007


From Science News, Volume 167, No. 10, March 5, 2005, p. 154.