Shark cartilage is a popular anti-cancer remedy, which is obtained from the cartilage of mainly two shark species.
Even though some basic research suggests that shark cartilage has anti-angiogenic and cytotoxic effects, there is no evidence from five controlled and eight uncontrolled studies to show that it is helpful in the treatment of cancer.Records of adverse effects exist for the oral supplementation of shark cartilage as well as the injection or enema procedure but no serious events are on record.
Citation
Edzard Ernst, CAM Cancer Collaboration. Shark cartilage [online document], Sep 15, 2020.
Document history
Latest update: September 2020
Next update due: September 2023
Scientific name / brand name / common name
The commonly used name for the preparation is shark cartilage. Commercial products are sold as Cartilate, Cartilade, BeneFin, AE-941, U-995, Neovastat, Better Shark MC and numerous other brand names.
Ingredients
Cartilage is part of the skeletal system composed of elastic, translucent tissue. Sharks’ skeletal structure is not made of bones but of cartilage. Shark cartilage is obtained from the spiny dogfish shark Squalus acanthias and the hammered shark Sphyrna lewini and is available in either capsule or powder form. Shark cartilage products contain glycoproteins, such as phyrastitin 1 and 2.
Application and dosage
Administration is usually either orally in capsule form or rectally by enemas of shark cartilage mixed with sterile water or by subcutaneous injection but is not normally applied intravenously. From clinical studies we know that for refractory metastatic renal cell carcinoma, a specific water-soluble shark cartilage extract, AE-941 (Neovastat), 60 to 240 mL per day has been used1,2. For the treatment of solid tumors, 30 to 240 mL daily has been used3. For cutaneous Kaposi’s Sarcoma, shark cartilage 3,750 to 4,500 mg per day has been used4. Commercial products typically suggest doses ranging from 500 mg to 4.5g, given in two to six divided doses daily5.
History / providers
In 1963 it was discovered that tumour growth was partly dependant upon angiogenesis6. William Lane published a book in 1992 entitled Sharks Don’t Get Cancer7. The claim is incorrect – sharks can get cancer of their cartilage8,9. Numerous manufacturers offer commercial preparations available as food supplements, sold without restriction, through various outlets. In 1995, over 40 brands were on the market.
In 2000 Lane was prohibited by the Federal Trade Commission from claiming that “BeneFin or any other shark cartilage product prevents, treats or cures cancer”, until he can provide substantial evidence to support this claim. Since shark cartilage has been promoted as a cancer cure, there has been a measurable decline in shark populations.
Claims of efficacy
It is claimed that a protein in shark cartilage can shrink tumour size, slow or stop the growth of cancerous cells and help reverse bone disease such as osteoporosis7,10. Providers claim that shark cartilage is effective in cancer because of anti-angiogenic properties. Shark cartilage is also claimed to have antitumor, antioxidant, anti-inflammatory and anti-atherogenic actions, although these putative actions are so far poorly supported by credible clinical research.
Mechanisms of action / alleged indication
Angiogenesis enables new blood vessels and, consequently, tumours to grow. All cartilage, including human, contains anti-angiogenic factors. When shark cartilage is taken orally, they are being digested rather than absorbed into the bloodstream. Therefore no effects after oral administration should be expected.
Some basic research studies have suggested direct toxicity against tumour cells. The inhibition of tumour angiogenesis has been relatively well documented in in-vitro studies One study, for instance, found that tamoxifen has significant anti-angiogenic activity that can be potentiated by shark cartilage32. Another laboratory study suggested that the development of papillary and solid tumours in mice can be significantly delayed25.
Shark cartilage contains inhibitors of tumour angiogenesis11-13,34, and immune modulators14 and may have cytotoxic activity in vitro35. The polypeptides identified included acidic and basic fibroblast growth factor, angiogenin and transforming growth factors alpha and beta15. Many of the formulations of commercially available shark cartilage contain little or no anti-angiogenic activity. Furthermore, not all cancers are affected by anti-angiogenic factors. Reliable dose-response data and bioavailability studies are not available.
Prevalence of use
The popularity of shark cartilage seems to have peaked between 1990 and 2000 but more recent data suggest it is still commonly used by cancer patients16. Reliable prevalence data are not available. In a survey including 100 patients with various types of cancer shark cartilage was among the most commonly used therapies17. In an earlier survey including 143 advanced cancer patients, 10.7% of respondents were consuming preparations of shark cartilage18. More recent survey data imply that 7% of lymphoma survivors use shark cartilage preparations36. An article in a non-peer-reviewed magazine reports that shark cartilage is a $5 billion-a-year business, with pills and powders sold in health food shops to more than 25.000 people every year19.
Legal issues
Shark cartilage products are marketed as dietary supplements and therefore are not submitted to medicines regulation. Pre-market evaluation and approval by the US Food and Drug Administration (FDA) are not required for dietary supplements. The FDA has not approved of the use of cartilage as a treatment for cancer or any other medical condition. Providers of dietary supplements are not legally permitted to make any claims on the packages of their products for preventing or curing any disease. In practice, such claims are, however, often made via books, websites etc.
Controlled trials
AE-941/Neovastat was administered in a randomised phase III trial of BeneFin including 331 patients with advanced solid tumours (including lung, prostate, breast, and kidney tumours)3. They were randomly assigned to receive either 30 to 240 mL/day cartilage or a placebo divided into three to four oral doses a day. Survival was the principal endpoint measured in this trial, but quality of life was also assessed. The results of these trials, however, have not been fully reported. A retrospective analysis involving a subgroup of patients with advanced non-small cell lung cancer suggests that AE-941/Neovastat is able to lengthen the survival of patients with this disease.
Two randomized phase III trials of AE-941/Neovastat in patients with advanced cancer have been approved by the United States Food and Drug Administration (FDA). In one trial in patients with stage III non-small cell lung cancer, treatment with oral AE-941/Neovastat plus chemotherapy and radiation therapy was compared to treatment with placebo plus the same chemotherapy and radiation therapy. Overall survival was not improved in patients taking the shark cartilage preparation20. In the second trial, treatment with oral AE-941/Neovastat was compared to treatment with placebo in patients with metastatic renal cell carcinoma21. Results from this second phase III trial have not been reported in the peer-reviewed literature.
Loprinzi published a double-blind, placebo-controlled randomised clinical trial of adjuvant therapy with shark cartilage administered three to four times daily to 83 patients with incurable breast or colorectal cancers22. The primary endpoint, survival, showed no difference between the patients receiving shark cartilage and those receiving placebo in addition to standard care. Similarly, quality of life showed no inter-group differences.
Another randomised trial suggested an anti-angiogenic effects of shark cartilage in healthy volunteers23.
Uncontrolled trials
Several uncontrolled clinical studies have been published, which suggest anti-cancer effects of shark cartilage24-31. The results of these studies tend to imply that shark cartilage is effective in changing the natural history of various types of cancer or positively influencing related variables. Yet, due to their uncontrolled nature, these investigations cannot establish cause and effect.
Contraindications
Pregnancy, lactation.
Precautions/warnings
Liver diseases.
Adverse effects
Orally, shark cartilage can cause taste disturbances, nausea, vomiting, dyspepsia, constipation, hypotension, dizziness, hyperglycemia, hypoglycemia, hypercalcemia, altered consciousness, decreased motor strength, decreased sensation, erythema, peripheral edema, generalized weakness, fatigue, and decreased performance1,24,28,30. It might also cause signs of acute hepatitis, including low-grade fever, jaundice, yellowing of eyes, right upper quadrant tenderness, and elevated liver enzymes33-34.
Interactions
Interactions with the following drugs are conceivable: diuretics, insulin, interferon, thalidomide.
Quality issues
Large variations exist in the purity and concentration of commercially available preparations
Neovastat clinical trial abstracts. Presented at the American Association for Cancer Research 92nd annual meeting. March 27, 2001.
Batist G, Patenaude F, Champagne P, et al. Neovastat (AE-941) in refractory renal cell carcinoma patients: report of a phase II trial with two dose levels. Ann Oncol 2002;13:1259-63. Accessed 15th of September 2020.
Sauder DN, Dekoven J, Champagne P, et al. Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. J Am Acad Dermatol 2002;47:535-41. Accessed 15th of September 2020.
Hillman JD, Peng AT, Gilliam AC, Remick SC. Treatment of Kaposi Sarcoma with oral administration of shark cartilage in a Human Herpes virus 8-seropositive, Human Immunodeficiency Virus-Seronegative homosexual man. Arch Dermatol 2001;137:1149-52. Accessed 15th of September 2020.
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Lane IW. Comac L. Sharks don’t get cancer. How shark cartilage can save your life. New Your: Avery, 1992.
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Lee A, Langer R Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983;221:1185-7. Accessed 15th of September 2020.
Bargahi A, Rabbani-Chadegani A, Bargahi A et al. Angiogenic inhibitor protein fractions derived from shark cartilage. Biosci Rep 2008;28:15-21. Accessed 15th of September 2020.
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Hyodo I, Amano N, Eguchi K et al. Nationwide survey on complementary and alternative medicine in cancer patients in Japan. J Clin Oncol 2005;23:2645-54. Accessed 15th of September 2020.
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Batist G, Champagne P, Hariton C, et al. Dose-survival relationship in a phase II study of Neovastat in refractory renal cell carcinoma patients. [Abstract] Proceedings of the American Society of Clinical Oncology 2002;21:A-1907.
Loprinzi CL, Levitt R, Barton DL, Sloan JA, Atherton PJ, Smith DJ, Dakhil SR, Moore DF Jr, Krook JE, Rowland KM Jr, Mazurczak MA, Berg AR, Kim GP; North Central Cancer Treatment Group. Evaluation of shark cartilage in patients with advanced cancer – a north central cancer treatments group trial . Cancer 2005;104:176-82. Accessed 15th of September 2020.
Berbari P, Thibodeau A, Germanin L, Saint-Cyr M, Gaudreau P, Elkhouri S, Dupont E, Garrel DR, Elkouri S. Antiangiogenic effects of the oral administration of liquid cartilage extracts in humans. J Surg Res 1999;87:108-13. Accessed 15th of September 2020.
Mathews J. Media feeds frenzy over shark cartilage as a cancer treatment. J Natl Cancer Inst 1993;85:1190-1191. Accessed 15th of September 2020.
Barber R, Delahunt B, Grebe SKG, Davis PF, Thornton A, Slim GC. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Research 2001;21:1065-70. Accessed 15th of September 2020.
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Leitner SP, Rothkopf MM, Haverstick L, et al. Two phase II studies of oral dry shark cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to standard treatment. [Abstract] Proceedings of the American Society of Clinical Oncology 1998;17:A-240.
Rosenbluth RJ, Jennis AA, Cantwell S, et al. Oral shark cartilage in the treatment of patients with advanced primary brain tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 1999;18:A-554.
Champagne P, Aeterna Laboratories, Incorporated Phase II Study of AE-941 (Neovastat) in Patients With Early Relapse or Refractory Multiple Myeloma, AETERNA-AE-MM-00-02, Clinical trial, Closed.
Miller DR. 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. Accessed 15th of September 2020.
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;14:362.
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Simard B, Bouamrani A, Jourdes P, Pernod G, Dimitriadou V, Berger F et al. Induction of the fibrinolytic system by cartilage extract mediates its antiangiogenic effect in mouse glioma. Microvascular Research 2011; 82(1):6-17. Accessed 15th of September 2020.
Bargahi A, Hassan ZM, Rabbani A, Langroudi L, Noori SH, Safari E et al. Effect of shark cartilage derived protein on the NK cells activity. Immunopharmacology & Immunotoxicology 2011; 33(3):403-409. Accessed 15th of September 2020.
Habermann TM, Thompson CA, LaPlant BR, Bauer BA, Janney CA, Clark MM et al. Complementary and alternative medicine use among long-term lymphoma survivors: a pilot study. American Journal of Hematology 2009; 84(12):795-798. Accessed 15th of September 2020.
