A fishy therapy: a thriving but controversial dietary supplement.

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.

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.

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 AEterna 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 antiangiogenic 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.