How It Works
Bottom Line: Shark cartilage is NOT effective in treating cancer. Even though laboratory studies initially showed promising results, shark cartilage cannot be absorbed through the gut into the bloodstream. Neovastat is an experimental shark cartilage extract that has not been fully tested in humans. It is not sold over-the-counter like most shark cartilage products, which contain mostly fillers and inactive ingredients.
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 has occurred in mice or in humans.
A purified shark cartilage product called Neovastat (AE-941) shows more promising results in laboratory tests. Given orally, AE-941 reduced tumor size in mice with breast cancer, bone tumors, or glioblastoma. The injectable form of this product is now being used in clinical trials for multiple myeloma and cancer of the kidney.
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.
Research Evidence
Cancer treatment:
Sixty patients with late stage recurrent, refractory, and/or metastatic cancer volunteered to take part in a trial examining the effect of oral shark cartilage on quality of life and disease progression. Patients had cancer of the lung, breast, colon, prostate, brain, or non-Hodgkin's lymphoma. They took one gram of shark cartilage daily for every kilogram of body weight (i.e., a 60 kg woman would receive 60 g/day). Five patients withdrew because of gastrointestinal complaints. None of the patients experienced complete or partial responses (tumor shrinkage), and overall they did not report improved quality of life. This trial does not support the use of over-the-counter shark cartilage supplements in the treatment of end-stage cancers.
The National Center for Complementary and Alternative Medicine (NCCAM) is currently sponsoring clinical trials of Neovastat, a purified shark cartilage extract that is not sold over-the-counter, and a product called BeneFin®. The clinical trials are studying several types of cancers, and no results have yet been published.
A high oral dose of Neovastat has been associated with longer survival time in patients with kidney cancer in a phase II study.
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.
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).
Side Effects
Gastrointestinal effects are reported but rare: Nausea, vomiting, upset stomach, constipation, diarrhea, 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. For this reason, injected extracts such as Neovastat may prove to be more effective.
The Federal Trade Commission has barred three manufacturers from making unsupported health claims for their shark cartilage products.
Brand Name
Carticin, Cartilade™, BeneFin™, Neovastat (Æ-941)
Clinical Summary
Obtained from the spiny dogfish shark and hammerhead shark
(13). This supplement is used to treat cancer
(18) (19) (20) (22), arthritis, osteoporosis, Kaposi's sarcoma
(23), macular degeneration, psoriasis
(21), and inflammatory disorders. It should not be confused with
bovine cartilage. Many OTC products contain mostly binding agents or fillers with little or no activity. The Federal Trade Commission has barred three manufacturers from making unsubstantiated claims of efficacy for their shark cartilage products. Shark cartilage extracts show strong antiangiogenic and antitumor activity in vitro
(3) (9) and in animal models
(4) (6) (10), but clinical use remains controversial due to lack of bioavailability data and unsatisfactory patient outcomes in clinical trials
(13) (24). The NCCAM is currently sponsoring trials of Neovastat (AE-941), a purified shark cartilage extract, in combination with conventional therapies for NSCLC, as well as BeneFin for advanced colorectal and breast cancers. A pilot study of shark cartilage in Kaposi's sarcoma
(23), a phase III trial of Neovastat in metastatic renal cell carcinoma
(22), and a registration phase II trial for refractory multiple myeloma are underway
(20). Neovastat has shown efficacy against psoriasis
(21). 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
(15).
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
Mechanism of Action
The glycoproteins sphyrnastatin 1 and 2 and other unidentified factors
(13) 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
(12). Theories for its mechanism include interference with endothelial cell migration and adhesion via modification of adhesion protein organization and inhibition of collagenase
(11). Intraperitoneal administration suppresses sarcoma-180 growth and B16-F10 melanoma metastasis in mice
(6) (9), but oral bioavailability is questionable based on the results of mouse models
(5).
AEterna Laboratories, Inc., the manufacturers of Neovastat (AE-941), a SC extract, report that in vitro this formulation inhibits embryonic vascularization
(1), endothelial cell proliferation
(2), tubulogenesis, VEGF binding to endothelial cells, VEGF-dependent tyrosine phosphorylation of the VEGF receptor, and the VEGF-dependent increase in vascular permeability. They also claims that it inhibits serine elastase and matrix metalloproteinase activity. Unlike OTC preparations, oral administration of Neovastat has produced anti-tumor effects in mouse models
(4). Higher oral dose of Neovastat have been associated with longer survival time in patients with renal cell carcinoma
(22). Neovastat can be used against psoriasis due to its antiangiogenic effect
(21).
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
(13). 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
(14). The manufacturers of Neovastat (AE-941) claim that phase I-II trial results show that it is orally bioavailable and safe, but data from this study have not been published
(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
Frequent:Taste alteration.
Infrequent: Nausea, vomiting, dyspepsia, constipation, diarrhea, anorexia, hypoglycemia in a known type II diabetic patient
(22).
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
(15).
Herb-Drug Interactions
None known
Lab Interactions
Periodic liver function tests should be performed with long-term use.
Literature Summary and Critique
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 to 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.
References
- Gingras D. Shark cartilage extracts as antiangiogenic agents: smart drinks or bitter pills? Cancer Metastatis Rev 2000;19:83-6.
- Falardeau P, et al. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol 2001;28:620-5.
- Sheu JR, et al. Effect of U-995, a potent shark cartilage-derived angiogenesis inhibitor, on anti-angiogenesis and anti-tumor activities. Anticancer Res 1998;18:4435-42.
- Barber R, et al. Oral shark cartilage does not abolish carcinogenesis but delays tumor progression in a murine model. Anticancer Res 2001;21:1065-70.
- 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;37:441-5.
- Weber MH, Lee J, Orr FW. The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol 2002;20:299-303.
- Gingras D, et al. Matrix proteinase inhibition by AE-941, a multifunctional antiangiogenic compound. Anticancer Res 2001;21:145-56.
- Dupont E, et al. Antiangiogenic and antimetastatic properties of Neovastat (AE-941), an orally active extract derived from cartilage tissue. Clin Exp Metastasis 2002;19:145-53.
- Lee A, Langer R. Shark cartilage contains inhibitors of tumor angiogenesis. Science 1983;221:1185-7.
- Davis PF, et al. Inhibition of angiogenesis by oral ingestion of powdered shark cartilage in a rat model. Microvasc Res 1997;54:178-82.
- Chen JS, et al. Shark cartilage extract interferes with cell adhesion and induces reorganization of focal adhesions in cultured endothelial cells. J Cell Biochem 2000;78:417-28.
- Oikawa T, 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 1990;51:181-6.
- Ernst E, Cassileth BR. How useful are unconventional cancer treatments? Eur J Cancer 1999;35:1608-13.
- Berbari P, et al. Antiangiogenic effects of the oral administration of liquid cartilage extract in humans. J Surg Res 1999;87:108-13.
- Ashar B, Vargo E. Shark cartilage-induced hepatitis. Ann Intern Med 1996;125:780-1.
- Fetrow CW, et al. Professional's Handbook of Complementary and Alternative Medicines. Philadelphia: Springhouse; 1999.
- Mathews J. Media feeds frenzy over shark cartilage as cancer treatment. J Natl Cancer Inst 1993;85:1190-1.
- Leitner SP, et al. 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.
- Rosenbluth RJ, et al. 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.
- 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.
- Sauder DN, 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.
- 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 Aug;13(8):1259-63.
- Hillman JD, 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. 2001 Sep;137(9):1149-52.
- Loprinzi CL, et al. Evaluation of shark cartilage in patients with advanced cancer: a North Central Cancer Treatment Group trial. Cancer 2005; 105(1): 176-82.
