About Herbs

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.

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).

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

Obtained from the spiny dogfish shark and hammerhead shark ⁽¹³⁾, shark cartilage is promoted as a dietary supplement to treat cancer ^{(18) (19) (20) (22)}, arthritis, osteoporosis, Kaposi's sarcoma ⁽²³⁾, macular degeneration, psoriasis ⁽²¹⁾, and inflammatory disorders.
Shark cartilage extracts show antiangiogenic and antitumor activities 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)}. Shark cartilage has been studied for Kaposi's sarcoma ⁽²³⁾, metastatic renal cell carcinoma ⁽²²⁾, and multiple myeloma ⁽²⁰⁾ 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 ⁽²⁵⁾. 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⁾.
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.

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⁾.

The manufacturers of Neovastat (AE-941), a shark cartilage 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. Oral administration of Neovastat has produced anti-tumor effects in mouse models ⁽⁴⁾. 

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⁾.

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

Frequent: Altered taste.
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⁾.

None known

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

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 to 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 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.