Description
Shark cartilage is obtained from the cartilage of mainly two shark species. It has been promoted as an over-the-counter supplement for a variety of diseases including cancer. Its use as an anti-cancer remedy was based on the misconception that sharks cannot get cancer. Some in vitro and animal research suggested that shark cartilage has anti-angiogenic and cytotoxic effects.
Efficacy
Survival: Although some uncontrolled studies showed encouraging results, the evidence from two RCTs (n=379, n=83) did not show shark cartilage to prolong survival. The larger RCT also did not show any significant differences between groups for time to disease progression, progression-free survival, or tumour response rates.
Safety
Shark cartilage is generally well tolerated. Only minor and transient adverse events mainly effecting the gastrointestinal tract have been reported.
Description and background
Shark cartilage is a type of connective tissue that provides structural support to the fins of sharks. Its use as a medicinal supplement gained popularity in the 1970s, largely due to the misconception that sharks are immune to cancer. This led to the hypothesis that human consumption of shark cartilage could potentially confer cancer resistance. William Lane published a book in 1992 entitled Sharks Don’t Get Cancer (Lane 1992). 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.
The commonly used name for the preparation is shark cartilage. Manufacturers offer commercial preparations as food supplements. Brand names include Carticin, Cartilade™, BeneFin™ and Neovastat (AE-941).
Ingredients and quality issues
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.
Large variations exist in the purity and concentration of commercially available preparations. Neovastat (AE-941) is a highly purified extract of shark cartilage. It is not available over the counter and has been primarily used in clinical trials and research settings.
Alleged indications
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 osteoporosis (Lane 1992). 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. (NatMed Pro 2022)
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. In clinical studies, a specific water-soluble shark cartilage extract, AE-941 (Neovastat), 60 to 240 mL per day has been used for refractory metastatic renal cell carcinoma. (Batist 2002) For the treatment of solid tumours, 30 to 240 mL daily has been used (Batist 2002). For cutaneous Kaposi’s Sarcoma, shark cartilage 3,750 to 4,500 mg per day has been used (Hillman 2001). Commercial products typically suggest doses ranging from 500 mg to 4.5g, given in two to six divided doses daily (Fetrow 1999).
Mechanisms of action
Shark cartilage contains inhibitors of tumour angiogenesis (Lee 1983, Simard 2011) and immune modulators (Bargahi 2014) and may have cytotoxic activity (Bargahi 2011). The polypeptides identified included acidic and basic fibroblast growth factor, angiogenin and transforming growth factors alpha and beta (Folkman 1987).
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 cartilage (McGuire 1994). Another laboratory study suggested that the development of papillary and solid tumours in mice can be significantly delayed (Barber 2001). The results of an RCT in 29 healthy male volunteers, receiving two different doses of shark cartilage or placebo, suggest that the liquid cartilage extract contained an antiangiogenic component bioavailable in humans by oral administration. (Berbari 1999)
Many of the formulations of commercially available shark cartilage contain little or no anti-angiogenic activity. 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. Furthermore, not all cancers are affected by anti-angiogenic factors. Reliable dose-response data and bioavailability studies are not available.
Legal issues
Shark cartilage products are marketed as dietary supplements and therefore are not submitted to medicines regulation. Providers of dietary supplements are not legally permitted to make any claims on the packages of their products for preventing or curing any disease. Neovastat (AE-941) has been primarily used in clinical trials and is not freely available as an over-the-counter product.
Two published RCTs in cancer patients (Lu 2010; Loprinzi 2005) are available. While several uncontrolled clinical studies have suggested anti-cancer effects of shark cartilage (e.g. Latreille 2003; Leitner, 1998; Miller 1998; Rosenbluth 1999; Saad 2001), these results have not been confirmed by the RCTs.
Description of included studies
Survival
A double-blind, placebo-controlled RCT investigated the efficacy of AE-941 in 379 inoperable stage III non-small cell lung cancer (NSCLC) patients undergoing chemo- and radiotherapy. (Lu 2010) For the primary endpoint overall survival no statistically significant difference was reported between the AE-941 group (n=188; median survival = 14.4 months, 95% CI 12.6 to 17.0) and the placebo group (n=191; median survival = 15.6 months, 95% CI 13.8 to 18.1; P=0.73). Furthermore, there were no statistically significant differences between groups in terms of time to disease progression, progression-free survival, or tumour response rates.
Another double-blind, placebo-controlled RCT evaluated adjuvant therapy with Benefin® shark cartilage administered three to four times daily to 83 patients with incurable breast or colorectal cancers. (Loprinzi 2005) 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.
Adverse effects
Shark cartilage is generally well tolerated and associated with mild and transient adverse effects only. Orally, shark cartilage can cause taste disturbances, nausea, vomiting, dyspepsia, constipation, dizziness, erythema, hypotension. (MSKCC 2023; NatMed 2022)
Serious adverse events are rare and can include altered consciousness, decreased motor strength, decreased sensation, generalized weakness, hepatitis, hyperglycaemia, hypoglycaemia, and peripheral oedema. (NatMed 2022)
Interactions
Theoretically, shark cartilage might interfere with immunosuppressive therapy. Although in vitro suggests that shark cartilage might stimulate immune responses, this has not been reported in humans. (NatMed 2022)
Contraindications
Theoretically, shark cartilage might exacerbate autoimmune disease. (NatMed 2022).
Precautions/warnings
Insufficient reliable information is available for the use of shark cartilage during pregnancy and lactation.
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.
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.
Bargahi A, Rabbani-Chadegani A, Bargahi A et al. Angiogenic inhibitor protein fractions derived from shark cartilage. Biosci Rep 2008;28:15-21.
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.
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.
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.
Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
Folkman J, Klagsburn M. Angiogenic factors. Science 1987;235:442-7.
Folkman J, Long DM, Becker FF. Growth and metastasis of tumour organ culture. Cancer 1963;16:453-67.
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.
Lane IW. Comac L. Sharks don’t get cancer. How shark cartilage can save your life. New Your: Avery, 1992.
Latreille J, Batist G, Laberge F, Champagne P, Croteau D, Falardeau P, Levinton C, Hariton C, Evans WK, Dupont E. 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 Jan;4(4):231-6.
Lee A, Langer R Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983;221:1185-7.
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.
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.
Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK et al. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. Journal of the National Cancer Institute 2010; 102(12):859-865.
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.
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.
MSKCC, Memorial Sloan Kettering Cancer Center. Shark Cartilage., 2023. Accessed August 2024.
NatMed Pro, Natural Medicines Datababase. Shark cartilage [online database, requires subscription], April 2022. Accessed June 2024.
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.
Saad F, Klotz L, Babaian R, Lacombe L, Champagne P, and Dupont E. Phase I/II trial on AE-941 (Neovastat) in patients with metastatic refractory prostate cancer (abstract presentation). Canadian Urological Association Annual Meeting (June 24-27, 2001).
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.
Citation
CAM Cancer Consortium. Shark cartilage, November 22, 2024.
Document history
Assessed as up to date in August 2024, August 2020, January 2019 and April 2016 by Barbara Wider; updated and revised by Edzard Ernst in April 2013, November 2011, April 2010. Summary first published in September 2005, authored by Edzard Ernst.
