Shark Cartilage

Health Care Professional Information

Brand Name

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

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 also been studied for Kaposi sarcoma (6), metastatic renal cell carcinoma (5), and multiple myeloma (4) in early phase clinical trials. Neovastat (AE-941), a purified shark cartilage extract, did not improve survival in patients with non-small cell lung cancer (15), but is effective 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.

Purported Uses
  • Arthritis
  • Cancer prevention
  • Cancer treatment
  • Colitis
  • Diabetic retinopathy
  • Glaucoma
  • Hemorrhoids
  • Immunostimulation
  • Inflammation
  • Kaposi sarcoma
  • Macular degeneration
  • Osteoarthritis
  • Osteoporosis
  • Psoriasis
  • Wound healing
Constituents
  • Glycoproteins: Sphyrnastatin 1 and 2
  • Glycosaminoglycans: Chondroitin sulphate, keratan sulphate
  • Calcium salts
  • Proteins: Collagen
    (1)
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 murine glioma model suggests 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 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 in vitro. 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).
A diet containing the acidic ethanol-precipitate-fraction of a water extract of shark cartilage significantly increased serum inhibitory activity against matrix metalloproteinase (MMP)-9 and reduced the number of adenocarcinomas in the pancreatic duct in a hamster model (24).

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). A 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).

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.
Contraindications

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

Adverse Reactions

Infrequent: Nausea, vomiting, dyspepsia, constipation, diarrhea, anorexia, hypoglycemia in a 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).

Herb Lab Interactions

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

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.

Dosage (Inside MSKCC Only)
This field is only visible to only OneMSK users.
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.
  24. Kitahashi T, Ikawa S, Sakamoto A, et al. .Ingestion of proteoglycan fraction from shark cartilage increases serum inhibitory activity against matrix metalloproteinase-9 and suppresses development of N-nitrosobis(2-oxopropyl)amine-induced pancreatic duct carcinogenesis in hamster. J Agric Food Chem. 2012 Feb 1;60(4):940-5.

Consumer Information

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.

Purported Uses
  • To treat and prevent cancer
    Studies in animals and humans do not support this use.
  • To treat Kaposi sarcoma
    There is one case report of regression of Kaposi sarcoma in a patient who took low-dose shark cartilage for a prolonged period.

    There is no scientific evidence to support the following claims:
  • To stimulate the immune system
  • To reduce inflammation in conditions such as arthritis, osteoarthritis, hemorrhoids, colitis, and psoriasis
  • For faster wound healing
  • To reduce bone loss in osteoporosis
  • To treat degenerative eye conditions such as glaucoma, macular degeneration, and diabetic retinopathy
     
Research Evidence

Cancer Treatment
In a study, 379 patients with unresectable stage III non-small cell lung cancer (NSCLC) received 120 ml of AE-941 (shark cartilage product) or placebo, orally for six years along with chemotherapy. Addition of AE-941 to standard chemotherapy did not affect overall survival. This study shows that shark cartilage products are not useful for the treatment of NSCLC.

.

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 when supplement use was discontinued).

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.
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.
E-mail your questions and comments to aboutherbs@mskcc.org.