By Dónal P. O’Mathúna, PhD, lecturer in Health Care Ethics, the School of Nursing, Dublin City University, Ireland.
Shark cartilage is a popular cancer remedy fraught with controversy. William Lane, PhD, did much to bring the remedy to public attention through his books Sharks Don’t Get Cancer (1992) and Sharks Still Don’t Get Cancer (1996). Subsequent publicity led to significant media attention, including an appearance on “60 Minutes” (1993). While that television show reported remarkable improvements in cancer patients treated with shark cartilage, the medical literature has been consistently critical of the findings.1 Although one study found it was the most popular cancer remedy recommended in health food stores,2 the FDA sought an injunction against manufacturers for promoting the product as a cancer treatment.3 Among Dutch cancer patients, 60% have used the Houtsmuller Diet, named after a Dutch physician who claimed a diet rich in shark cartilage and other vitamins cured his malignant melanoma; but the doctor has since admitted he never had cancer.4 Given the popularity of shark cartilage products, professionals should be aware of the evidence available for its use in treating cancer.
Background
Although shark cartilage is recommended for psoriasis, inflammatory joint diseases, and macular degeneration, most interest and research has focused on its use in treating cancer. Interest in cartilage to treat cancer began in the 1950s, primarily focused on bovine cartilage. Attention was directed toward shark cartilage in the 1970s, and basic research through the 1980s produced interesting in vitro findings. Then Lane’s books brought public attention. His book Sharks Don’t Get Cancer claimed that some substance in sharks’ cartilage protected them from cancer. However, several dozen documented cases of benign and malignant cancers in sharks date back to 1913.5 Lane’s 1996 book acknowledged this, but noted that the incidence of cancer in sharks is very low. However, a recent review of marine research concluded that shark cancer rates are unknown because they have never been systematically examined.5 Even if the incidence of cancer in sharks is low, this provides no support for using cartilage to treat cancer. Nonetheless, research is demonstrating that extracts made from shark cartilage hold promise as cancer treatments.6
Pharmacology
Commercial shark cartilage products consist of powered shark skeletons, which make up 6% of a shark’s whole body weight.7 This powder contains 40% protein, up to 20% chondroitin sulfate and glucosamine, up to 25% calcium, and glycoproteins.4 Several extracts of shark cartilage are also under investigation for anticancer activity. U-995 had in vitro activity, but not when given orally to animals. Another, AE-941 (Neovastat, Aeterna Laboratories, Canada), is a water-soluble extract from which 95% of inert cartilage material has been removed. It has in vitro activity, is orally active, and is the first shark cartilage extract to reach phase III clinical trials as an anti-cancer agent.6 This extract also has been shown to stimulate tissue plasminogen activator (t-PA) and thus to have potential in treating vascular disorders.8 A clear distinction must be made between such purified extracts and the crude material typically marketed as shark cartilage.
Mechanism of Action
Although several mechanisms of action have been proposed, the one with some supportive evidence is that of antiangiogenesis. In 1971, Judah Folkman published a seminal paper proposing that agents that block the development of blood vessels could be used to treat cancer.9 Angiogenesis is the production of new blood vessels that occurs in humans primarily during fetal development, inflammation, wound healing, and malignancy. Tumor growth requires new vascularization to permit exchange of nutrients and waste. Inhibiting this process would prevent tumors from growing beyond a couple of millimeters in diameter.10 Antiangiogenic factors have been found in bovine, human, and shark cartilage.7 Some from other sources are in various stages of clinical trials as anticancer agents.11
Clinical Studies
Early animal experiments demonstrated that shark cartilage and its extracts had antiangiogenic and antitumor activity in mice, rabbits, and chick embryos.10 However, shark cartilage was not administered orally in these experiments. Oral administration was examined in mice with the SCCVII tumor model, which is known to be responsive to conventional anticancer therapies, including antiangiogenic agents.12 Mortality, tumor size, and metastatic spread were not reduced compared to controls.
Human studies with shark cartilage began with two conducted by Lane.1 In the first, 29 patients with a variety of cancers were given 0.5 g/kg/d rectally. Lane reported improvements in 55% of the patients, but the details remain unpublished in peer-reviewed literature. In another open trial, eight patients with end-stage cancers of various types were given 30 g/d shark cartilage by enema and, for women, also vaginally. After 11 weeks, seven patients reported improvements and five were reported as tumor-free. Improvement was not measured objectively. The National Cancer Institute concluded that these studies provide little evidence to support the use of shark cartilage.
Abstracts from five trials were identified by the authors of an extensive review of shark cartilage research.4 Three abstracts reported no benefit from shark cartilage in patients with breast, prostate, or refractory brain cancers; one found a positive trend among cancer patients; and another found improved quality of life in 10 of 20 subjects enrolled. Analysis of all these studies is limited by the lack of published details.
One clinical trial has been published in the peer-reviewed literature.11 Miller et al enrolled 60 patients with several types of advanced, previously treated cancers. All subjects received 1 g/kg shark cartilage orally, divided into three doses taken before meals. Predetermined criteria for a complete response and a partial response were not met by any patient. Overall, no improvement in quality-of-life scores was found. The median time to tumor progression was similar to that reported elsewhere for patients receiving supportive care only or placebo in controlled trials. The authors concluded that for the dose and types of cancer involved in this trial, shark cartilage showed no anticancer activity.
As mentioned above, AE-941 is an extract of shark cartilage that has demonstrated anticancer activity in Phase I and II trials. These studies have been in non-small cell lung cancer and renal cell carcinoma. For example, 80 patients with advanced, refractory lung cancer were enrolled in a multicenter, open-label, dose-escalation study.13 Of the 48 patients with unresectable, advanced non-small cell lung cancer, those receiving more than 2.6 mL/kg/d survived significantly longer than those receiving lower doses (median, 6.1 v. 4.6 months; P = 0.026). In addition, 26% of the high-dose patients had stable disease compared to 14% in the low-dose group. This purified shark cartilage extract is now in Phase III trials.
Adverse Effects
In the Miller et al trial, the most common adverse effects were gastrointestinal disturbances, with 10% of the subjects discontinuing shark cartilage because of their severity.11 In general, crude shark cartilage, and its extracts, are tolerated well in recommended doses. Theoretically, the high calcium content of crude preparations could be problematic in patients with renal disease or at risk for arrhythmias.4 Antiangiogenic effects could interfere with wound healing after surgery or trauma. Participants in clinical trials of other antiangiogenic agents should avoid shark cartilage to prevent interference or potentially adverse synergistic effects. Shark cartilage should be avoided during pregnancy and breast feeding due to the risk of interference with normal fetal and infant angiogenesis.
Formulation
Manufacturers of powdered shark cartilage products typically recommend between 500 mg and 4.5 g daily, taken in 2-6 divided doses.
Conclusion
The oral use of powdered shark cartilage to treat cancer is not supported by clinical studies. As a recent review concluded, “It is notable that despite more than a decade of evaluation of shark cartilage, not a single controlled study has established any efficacy of crude cartilage extracts against cancer.”5 However, shark cartilage is a source of antiangiogenic products, some of which are progressing through clinical trials and may lead to effective treatments. Such products also hold the potential to be synthetically derived, thus sparing the natural shark population which has been measurably depleted over the past 15 years (sharks are also fished for their meat and oil, and for sport, as well as for their cartilage).5
Recommendation
Patients with cancer should be encouraged not to place hope in powdered shark cartilage products. Although the products are generally well tolerated, they do carry some risk of gastrointestinal discomfort and may interfere with other conditions. In addition, a month’s supply can cost $700-1000.4 Such costs may be acceptable with an effective product, but not with one that has failed to produce results that have stood up to professional review. Patients should instead be encouraged to pursue the treatments that have been shown to be effective for their particular form of cancer.
References
1. Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. J Natl Cancer Inst 1993;85: 1190-1191.
2. Gotay CC, Dumitriu D. Health food store recommendations for breast cancer patients. Arch Fam Med 2000;9:692-699.
3. Food and Drug Administration. FDA takes action against firm marketing unapproved drugs (Dec. 10, 1999). Available at: www.fda.gov/bbs/topics/ANSWERS/ANS00988.html. Accessed April 22, 2005.
4. Hammerness P, et al. Shark cartilage monograph: A clinical decision support tool. J Herb Pharmacother 2002;2:71-93.
5. Ostrander GK, et al. Shark cartilage, cancer and the growing threat of pseudoscience. Cancer Res 2004; 64:8485-8491.
6. Gonzalez RP, et al. Shark cartilage as source of anti-angiogenic compounds: From basic to clinical research. Biol Pharm Bull 2001;24:1097-1101.
7. Gingras D, et al. Shark cartilage extracts as antiangiogenic agents: Smart drinks or bitter pills? Cancer Metastasis Rev 2000;19:83-86.
8. Ratel D, Glazier et al. Direct-acting fibrinolytic enzymes in shark cartilage extract: Potential therapeutic role in vascular disorders. Thromb Res 2005; 115:143-152.
9. Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-1186.
10. Barber R, et al. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Res 2001;21:1065-1069.
11. Miller DR, et al D. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-3655.
12. Horsman MR, et al. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol 1998;37:441-445.
13. Latreille J, et al. Phase I/II trial of the safety and efficacy of AE-941 (Neovastat) in the treatment of non-small-cell lung cancer. Clin Lung Cancer 2003;4: 231-236.
O'Mathuna DP. Shark cartilage to treat cancer. Altern Med Alert 2005;8(6):61-64.
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