About Herbs, Botanicals & Other Products

Brand Name

Carticin, Cartilade™, BeneFin™, Neovastat (Æ-941)

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Clinical Summary

Obtained from the spiny dogfish shark and hammerhead shark (1), shark cartilage is promoted as a dietary supplement to treat cancer (2) (3) (4) (5), arthritis, osteoporosis, Kaposi sarcoma (6), macular degeneration, psoriasis (7), and inflammatory disorders. Shark cartilage extracts show antiangiogenic and antitumor activities in vitro (8) (9) and in animal models (10) (11) (12) (13), but clinical use remains controversial due to lack of bioavailability data and unsatisfactory patient outcomes in clinical trials (1) (14). Shark cartilage has been studied for Kaposi sarcoma (6), metastatic renal cell carcinoma (5), and multiple myeloma (4) in early phase clinical trials. A recent study showed that Neovastat (AE-941), purified shark cartilage extract, did not improve survival in patients with non-small cell lung cancer (15). Neovastat has shown efficacy against psoriasis (7). Most trials report low toxicity, but regular consumption of a shark cartilage supplement was associated with reversible hepatic dysfunction in a 57-year-old man (16). The Federal Trade Commission has barred three manufacturers from making unsubstantiated claims of efficacy for their shark cartilage products. Shark cartilage should not be confused with bovine cartilage.

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Purported Uses
  • Arthritis
  • Cancer prevention
  • Cancer treatment
  • Colitis
  • Diabetic retinopathy
  • Glaucoma
  • Hemorrhoids
  • Immunostimulation
  • Inflammation
  • Kaposi sarcoma
  • Macular degeneration
  • Osteoarthritis
  • Osteoporosis
  • Psoriasis
  • Wound healing
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Constituents
  • Glycoproteins: Sphyrnastatin 1 and 2
  • Glycosaminoglycans: Chondroitin sulphate, keratan sulphate
  • Calcium salts
  • Proteins: Collagen
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Mechanism of Action

The glycoproteins sphyrnastatin 1 and 2 and other unidentified factors (1) are thought responsible for the activity of shark cartilage (SC), which shows strong antiangiogenic activity and inhibition of tumor neovascularization in numerous in vitro and animal studies (17). Theories for its mechanism include interference with endothelial cell migration and adhesion via modification of adhesion protein organization and inhibition of collagenase (18). A more recent study in murine glioma models suggest that induction of t-PA plays an essential role (19). Intraperitoneal administration suppresses sarcoma-180 growth and B16-F10 melanoma metastasis in mice (9) (11), but oral bioavailability is questionable based on the results of mouse models (20). The manufacturers of Neovastat (AE-941), a shark cartilage extract, report that in vitro this formulation inhibits embryonic vascularization (21), endothelial cell proliferation (22), tubulogenesis, VEGF binding to endothelial cells, VEGF-dependent tyrosine phosphorylation of the VEGF receptor, and the VEGF-dependent increase in vascular permeability. They also claim that it inhibits serine elastase and matrix metalloproteinase activity(23). Oral administration of Neovastat has produced anti-tumor effects in mouse models (10).

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Pharmacokinetics

Large macromolecules such as those associated with the antiangiogenic properties of shark cartilage are not usually absorbed by the intestinal tract and may be digested by proteolytic enzymes in the gut, but studies show that certain large proteins can be absorbed. No bioavailability studies with shark cartilage preparations are published, as it is unclear which active component to look for in the blood (1). One study in humans found a significant decrease in endothelial cell density within an inert subcutaneous implant following oral administration of a liquid shark cartilage extract, giving some support to the oral bioavailability of its antiangiogenic factors (13).

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Warnings
  • Commercially available supplements contain varying amounts of shark cartilage. Some are composed primarily of fillers and may not have any biological activity.
  • Neovastat (AE-941) is a highly purified extract of shark cartilage. It is an investigational new drug and is not available to the general public. Other shark cartilage products may not have similar properties.
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Contraindications

Patients with liver disease should use shark cartilage supplements with caution.

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Adverse Reactions

Frequent: Altered taste.
Infrequent: Nausea, vomiting, dyspepsia, constipation, diarrhea, anorexia, hypoglycemia in a known type II diabetic patient (5).
Case Report: A 57-year-old man experienced nausea, vomiting, diarrhea, anorexia, jaundice, low-grade fever, scleral icterus, and elevated liver function tests after consuming a shark cartilage supplement for 10 weeks. Normal liver function resumed after discontinuation of the supplement (16).

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Herb-Drug Interactions

None known

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Herb Lab Interactions

Periodic liver function tests should be performed with long-term use.

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Literature Summary and Critique

Lu C, Lee JJ, Komaki R, et al. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: A randomized phase III trial. J Natl Cancer Inst 2010;102:1-7.
In this phase III clinical trial, 379 patients with unresectable stage III non-small cell lung cancer (NSCLC) were randomized to receive 120 ml of AE-941 or placebo orally for six years along with chemotherapy (combination of carboplatin and paclitaxel, or cisplatin and vinorelbine). The primary and secondary endpoints were overall survival and time to progression, progression-free survival, tumor response rate, and toxic effects. Addition of AE-941 to standard chemotherapeutic regimens did not affect overall survival nor the secondary endpoints compared with placebo. This study shows that shark cartilage products are not useful for the treatment of NSCLC.

Miller DR, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol 1998;16:3649-55.
An open-label, nonrandomized phase I/II study of Cartilade™ shark cartilage (SC) supplementation in 60 patients with stage III and IV recurrent, refractory, and/or metastatic solid tumors. Patients received 1 g/kg SC powder daily in three divided doses. Ten patients were either lost to follow up or refused further therapy before 6 weeks. Five patients withdrew because of gastrointestinal toxicity. No complete or partial responses were observed. Overall, no improvement in FACT-G quality of life scores was observed. Survival was not compared with a historical control and patient number was too small to make meaningful statistical comparisons. This trial does not support the use of commercially available shark cartilage supplements in the treatment of end-stage cancers.

Batist G, 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.
This was a phase II trial to determine the safety and efficacy of Neovastat (AE-941). Either 60 ml/day or 240 ml/day of Neovastat was given orally to 144 patients with solid tumors refractory to standard treatments. Neovastat seems to be well tolerated by patients at these dose levels. Taste alteration was the most common side effect. However, no dose-limiting toxicity was reported. On the 22 patients with renal cell carcinoma, the high-dose group had significantly longer survival than the low-dose group (16.3 months vs 7.1 months; p=0.01). However, this trial was not randomized. Some patients who started on the lower dose (60 ml/day) were subsequently reassigned to take the higher dose (240 ml/day). The author pointed out that due to the design of the study, no firm conclusions can be drawn on the efficacy of Neovastat.

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References
  1. Ernst E, Cassileth BR. How useful are unconventional cancer treatments? Eur J Cancer. Oct 1999;35(11):1608-1613.
  2. Leitner SP ea. Two phase II studies of oral dry shark cartilage powder (SCP) with either metastatic breast or prostate cancer refractory to standard treatment. Proc Am Soc Clin Oncol. 1998;17:A240.
  3. Rosenbluth RJ ea. Oral shark cartilage in the treatment of patients with advanced primary brain tumors. A phase II pilot study. Proc Am Soc Clin Oncol. 1999;18:A554.
  4. Miller DR, Anderson GT, Stark JJ, et al. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. J Clin Oncol. Nov 1998;16(11):3649-3655.
  5. 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. Aug 2002;13(8):1259-1263.
  6. Hillman JD, Peng AT, Gilliam AC, et al. Treatment of Kaposi sarcoma with oral administration of shark cartilage in a human herpesvirus 8-seropositive, human immunodeficiency virus-seronegative homosexual man. Arch Dermatol. Sep 2001;137(9):1149-1152.
  7. 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. Oct 2002;47(4):535-541.
  8. Sheu JR, Fu CC, Tsai ML, et al. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res. Nov-Dec 1998;18(6A):4435-4441.
  9. Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science. Sep 16 1983;221(4616):1185-1187.
  10. Barber R, Delahunt B, Grebe SK, et al. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Res. Mar-Apr 2001;21(2A):1065-1069.
  11. Weber MH, Lee J, Orr FW. The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. Feb 2002;20(2):299-303.
  12. Davis PF, He Y, Furneaux RH, et al. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res. Sep 1997;54(2):178-182.
  13. Berbari P, Thibodeau A, Germain L, et al. Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res. Nov 1999;87(1):108-113.
  14. Loprinzi CL, Levitt R, Barton DL, et al. Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer. Jul 1 2005;104(1):176-182.
  15. Lu C, Lee JJ, Komaki R, et al. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst. Jun 16 2010;102(12):859-865.
  16. Ashar B, Vargo E. Shark cartilage-induced hepatitis. Ann Intern Med. Nov 1 1996;125(9):780-781.
  17. Oikawa T, Ashino-Fuse H, Shimamura M, et al. A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis. Cancer Lett. Jun 15 1990;51(3):181-186.
  18. Chen JS, Chang CM, Wu JC, et al. Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells. J Cell Biochem. Jun 6 2000;78(3):417-428.
  19. Simard B, Bouamrani A, Jourdes P, et al. Induction of the fibrinolytic system by cartilage extract mediates its antiangiogenic effect in mouse glioma. Microvasc Res. Jul 2011;82(1):6-17.
  20. Horsman MR, Alsner J, Overgaard J. The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. Acta Oncol. 1998;37(5):441-445.
  21. Gingras D, Renaud A, Mousseau N, et al. Shark cartilage extracts as antiangiogenic agents: smart drinks or bitter pills? Cancer Metastasis Rev. 2000;19(1-2):83-86.
  22. Falardeau P, Champagne P, Poyet P, et al. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. Dec 2001;28(6):620-625.
  23. Gingras D, Renaud A, Mousseau N, et al. Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound. Anticancer Res. Jan-Feb 2001;21(1A):145-155.
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How It Works

Bottom Line: Shark cartilage is not effective in treating cancer.

Since cartilage is a body tissue in which no blood vessels are present, researchers guessed that certain molecules isolated from shark cartilage could inhibit the growth of blood vessels. This action, called anti-angiogenesis, was seen when shark cartilage was directly applied to tumors in a test tube. However, when these extracts were given by mouth (how all over-the-counter shark cartilage supplements are taken), no anti-tumor effect occurred in mice or in humans.
A purified shark cartilage product called Neovastat (AE-941) can reduce tumor size in animals. However, it did not improve survival in lung cancer patients.

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Purported Uses
  • To treat and prevent cancer
    Studies in animals and humans do not support this use. Even though shark cartilage showed promise in laboratory studies, it is probably not absorbed through the gut into the bloodstream.
  • To stimulate the immune system
    No scientific evidence supports this use.
  • To reduce inflammation in conditions such as arthritis, osteoarthritis, hemorrhoids, colitis, and psoriasis
    No scientific evidence supports this use.
  • For faster wound healing
    No scientific evidence supports this use.
  • To reduce bone loss in osteoporosis
    No scientific evidence supports this use.
  • To treat degenerative eye conditions such as glaucoma, macular degeneration, and diabetic retinopathy
    No scientific evidence supports this use
  • To treat Kaposi sarcoma
    There is one case report of regression of Kaposi sarcoma in a man who took low-dose shark cartilage for a prolonged period. However, this may have been a chance occurrence, so it does NOT support the use of shark cartilage for this disease.
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Patient Warnings
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If

You have a history of liver disease (In one patient, prolonged use of shark cartilage was associated with liver dysfunction, which reversed upon discontinuation of the supplement).

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Side Effects
  • Gastrointestinal effects have been reported but are rare: Nausea, vomiting, upset stomach, constipation, diarrhea, and loss of appetite.
  • Hypoglycemia (low blood sugar) was reported in one patient with type II diabetes.
  • Tell your doctor immediately if you develop the following symptoms: fever, jaundice (yellowing of the skin), nausea, vomiting, diarrhea, and/or yellowing of the whites of the eyes. These may indicate serious liver problems.
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Special Point
  • Over-the-counter shark cartilage supplements contain varying amounts of shark cartilage. Some are composed mainly of fillers and may not have any biological activity. Furthermore, it is debated whether the large proteins responsible for shark cartilage's activity are absorbed through the gastrointestinal tract, or whether they are simply digested and rendered useless.
  • The Federal Trade Commission has barred three manufacturers from making unsupported health claims for their shark cartilage products.
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Dosage (Inside MSKCC Only)
This field is only visible to only Inside MSKCC users.
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Aliases
AE-941
Cartilade
Neovastat
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: December 6, 2011