IngredientsShark cartilage is not a defined single product. Native shark cartilage is harvested as the tough elastic cartilage, or endoskeleton, of multiple species of shark and contains proteins, proteoglycans, glycosaminoglycans, minerals, carbohydrate, and lipid. Shark cartilage is obtained primarily from the spiny dogfish shark Squalus acanthias and the hammerhead shark Sphyrna lewini. The blue shark (Prionace glauca) is also a commercially important source. The entire skeleton of P. glauca is composed of cartilage, which comprises approximately 6% of its bodyweight. Because sharks belong to the class Chondrichthyes, cartilage is part of the skeletal system composed of elastic, translucent tissue, and sharks' skeletal structure is made entirely of cartilage rather than bone.
Manufacturers offer commercial preparations as food supplements, with brand names including Carticin, Cartilade™, BeneFin™, and Neovastat (AE-941). Shark cartilage is available in either capsule or powder form. Several very different products are marketed as "shark cartilage," including aqueous extracts of the homogenized cartilage; the processing of powdered shark cartilage preparations may include extensive washing, soaking, and/or bleaching. 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. Dogfish shark cartilage (sold as Cartilade) is available in 200-, 500-, and 740-mg gelatin capsules, requiring dozens to hundreds of capsules daily to reach recommended doses. Administration is usually either orally in capsule form or rectally by enemas of shark cartilage. Large variations exist in the purity and concentration of commercially available preparations.
A simple chemical analysis shows that unadulterated, dry shark cartilage comprises approximately 41% ash, 39% protein, 12% carbohydrate, 7% water, less than 1% fiber, and less than 0.3% fat.
Shark cartilage has been used medicinally for thousands of years, particularly in ancient China where its use is documented. In traditional Chinese medicine, shark fins are believed to help in areas of rejuvenation, appetite enhancement, and blood nourishment, and to be beneficial to vital energy, kidneys, lungs, bones, and many other parts of the body. Shark fin soup was reported in Ming dynasty writings and by the Qing dynasty was considered a "traditional part of formal banquets"; it was considered one of the eight treasured foods from the sea, popular with Chinese emperors because it was rare and highly elaborately prepared. By the time of the Qing dynasty, shark fin soup was in high demand.
Cartilage powder is used as a traditional Chinese medicine for arthritis and cancer treatment. Shark cartilage is a popular food in Japan, where it is regarded as having health benefits. In Japan, shark fins and cartilage are sold by herbalists as a powder, in tablet form, or as whole fins.
Shark fin and cartilage products sold as extracts, dry powders, and in capsules are marketed based on traditional Chinese medicine claims that they nourish the blood, enhance appetite, and energize multiple internal organs.
Indigenous populations in coastal regions have also utilized different parts of the shark for their reputed ability to aid in wound healing and support overall wellness. The major cartilage-consuming countries are Australia, India, Japan, and the USA, although it is used or consumed in many other countries, especially Hong Kong, Taiwan, China, and increasingly Europe.
While shark fin has been used for centuries in Asia, in recent years it has become more popular in the West. A book called Sharks Don't Get Cancer, published in 1992, popularized the idea of shark cartilage as an alternative cancer treatment in the West, and powdered shark cartilage became sold as a dietary supplement. Shark cartilage has become one of the most commonly recognized supplements in the United States. Growing interest in the shark cartilage derivative AE-941 (Neovastat, Aeterna Laboratories Inc., Canada) occurred when preclinical studies demonstrated antiangiogenic, antitumor, and anti-inflammatory properties. Several clinical trials were conducted using AE-941, and the US Food and Drug Administration granted orphan drug status to the agent in 2002.
Shark cartilage is composed of approximately 40% protein, including troponin-I, tetranectin-type protein, collagenase, cartilage-derived inhibitor, and tissue inhibitor of metalloproteinases (TIMPs). The glycoproteins sphyrnastatin-1 and sphyrnastatin-2, as well as galactosamines and glucosamine, are also present. P. glauca cartilage contains collagen type II, which makes it suitable as a bioactive ingredient in cosmeceutical products.
Shark cartilage contains 5% to 20% glycosaminoglycans, including chondroitin sulfate-D, chondroitin-6-sulfate, and keratin sulfate, as well as calcium salts. Cartilage contains cells called chondrocytes, which are surrounded by collagen (a fibrous protein) and proteoglycans, which are made of protein and carbohydrate. Quantitative and compositional analysis of disaccharides after enzymatic depolymerization showed that the amount of chondroitin sulfate in shark cartilage powder samples ranged from 0% to 28.92 ± 0.03%, indicating considerable variability among commercial preparations.
Chondroitin sulfate (CAS No. 9082-07-9) is the most studied glycosaminoglycan in shark cartilage. Chondroitin sulfate reduces inflammation mediators and the apoptotic process and is able to reduce protein production of inflammatory cytokines, inducible nitric oxide synthase (iNOS), and matrix metalloproteinases (MMPs).
Cartilage is a natural source of material with strong antiangiogenic activity. Initially, cartilage was considered as a possible natural source of antiangiogenic compounds due to its known avascular nature. Purified antiangiogenic factors from shark cartilage, such as U-995 and Neovastat (AE-941), have shown antiangiogenic and antitumor activity. Sphyrnastatin-1 and sphyrnastatin-2 also have antiangiogenic activity and have been reported to inhibit neovascularization.
Research has identified the broad-spectrum aminosterol antibiotic squalamine in the dogfish shark. Squalamine has shown bactericidal activity against both gram-negative and gram-positive bacteria. It is also fungicidal and induces activity against protozoa. This discovery implicated a unique steroid acting as a potential host-defense agent in vertebrates and provided for a new family of broad-spectrum antibiotics. However, because of harvest conditions, preparations are often contaminated by other shark tissues (e.g., shark liver containing squalamine), and possibly by heavy metals (e.g., mercury) and bacterial and viral contaminants acquired during storage and/or processing.
The primary mechanism investigated for shark cartilage is anti-angiogenesis. The fact that sharks rarely develop cancer has led to the theory that, because sharks are cartilaginous fish and cartilage is avascular and contains agents that inhibit vascularization (angiogenesis, the promotion of new blood vessels needed for tumor growth and metastasis), cartilage from sharks can inhibit cancer.
Preclinical data on chick embryo, human umbilical vein endothelial cells, and other studies showed evidence of antiangiogenic activity of AE-941, including inhibition of endothelial cell proliferation via induction of apoptosis. In vitro studies showed that molecules in AE-941 specifically interfere with the binding of vascular endothelial growth factor (VEGF) to its receptor and inhibit several matrix metalloproteinases (MMPs), including MMP-2, -9, and -12.
Shark cartilage also inhibits substances called matrix metalloproteinases (MMPs). These enzymes affect the "extracellular matrix," the framework of substances between cells in the body. MMPs are thought to play a role in diseases of the cornea, gums, skin, blood vessels, and joints, as well as cancer and illnesses that involve excessive fibrous tissue.
In vitro studies have shown that shark cartilage extracts induce a Th1-type inflammatory cytokine response in human leukocytes, and collagen type II alpha 1 protein has been identified as an active cytokine-inducing component in shark cartilage. This finding is considered a potential concern rather than a therapeutic mechanism (see Safety section).
Laboratory and animal studies have looked at whether bovine and shark cartilage products can kill cancer cells, make the immune system more active against cancer, and prevent the body from making the new blood vessels that a tumor needs to grow. In a laboratory study, a liquid form of shark cartilage called AE-941/Neovastat was reported to stop the growth of a number of cancer cell types, though the results were not published in a scientific journal. Several studies have shown that AE-941/Neovastat blocks the growth of new blood vessels. AE-941/Neovastat given by mouth to mice slowed the growth of breast cancer cells and the spread of lung cancer; in the lung cancer study, AE-941/Neovastat increased the effect of the anticancer drug cisplatin.
In one study, twenty prostate or breast cancer patients received 1 gram/kg/day of oral shark cartilage powder for twenty weeks. Both survival times and quality of life were unchanged compared with a placebo control group. In another study, shark collagen was orally administered to sixty patients with different advanced cancers for six weeks; the study noted no complete or partial responses, and outcomes were similar to patients who had received only supportive care.
The North Central Cancer Treatment Group (NCCTG) conducted a key trial at Mayo Clinic. The study was a two-arm, randomized, placebo-controlled, double-blind clinical trial in patients with incurable breast or colorectal carcinoma with good performance status; patients could be receiving chemotherapy and were randomly assigned to receive either a shark cartilage product or an identical-appearing and smelling placebo three to four times each day. Data on 83 evaluable patients were analyzed. There was no difference in overall survival between patients receiving standard care plus shark cartilage versus standard care plus placebo. There was likewise no suggestion of improvement in quality of life. This trial was unable to demonstrate any suggestion of efficacy for this shark cartilage product in patients with advanced cancer.
AE-941, also known as Neovastat, is a standardized, water-soluble, shark cartilage extract with evidence of antiangiogenic and antimetastatic activity. It is a standardized aqueous shark cartilage extract with antiangiogenic properties that was previously evaluated in phase I and II clinical trials. The objective of a subsequent phase III trial was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). A randomized, double-blinded, placebo-controlled, phase III clinical trial enrolled 379 eligible patients in community and academic oncology centers across the United States and Canada between June 2000 and February 2006. This trial of oral AE-941/Neovastat in 379 patients with advanced NSCLC reported that there was no difference in how long patients lived between the group receiving the shark cartilage product and chemoradiotherapy compared to the group receiving placebo and chemoradiotherapy; both kinds of treatment were well tolerated.
Shark cartilage has also been studied for Kaposi sarcoma, metastatic renal cell carcinoma, and multiple myeloma in early phase clinical trials. Four completed clinical trials showed no evidence of efficacy for Neovastat® in the treatment of multiple myeloma, plasma cell neoplasms, breast cancer, lung cancer, kidney cancer, or colorectal cancer.
Overall evidence assessment for cancer: When shark cartilage extracts are administered to cancer patients, no conclusive results have been obtained to support the use of shark cartilage as a cancer treatment. When extracts were given by mouth, no anti-tumor effect occurred in mice or in humans. Shark cartilage extracts showed antiangiogenic and antitumor activities in vitro and in animal models, but clinical use remains controversial due to lack of bioavailability data and unsatisfactory patient outcomes in clinical trials. The US Food and Drug Administration (FDA) has not approved cartilage as a treatment for cancer.
An early widely cited Cuban clinical study of shark cartilage in cancer patients was never published in a peer-reviewed medical journal, and the National Cancer Institute (NCI) later concluded that its results were "incomplete and unimpressive."
Cartilage is a resilient connective tissue that serves as a key component in joint function. As a therapeutic supplement, it has been proposed primarily for managing osteoarthritis, with chondroitin, a component of cartilage, being popular in Europe for this purpose. The most common sources of cartilage supplements are bovine and shark cartilage.
A topical combination preparation containing glucosamine sulfate 30 mg/g, chondroitin sulfate 50 mg/g, and shark cartilage 140 mg/g applied for an 8-week period improved visual analog scores for pain compared with placebo at 4 and 8 weeks in patients with osteoarthritis of the knee. This study tested a multi-ingredient topical formulation and cannot be attributed solely to shark cartilage.
Commercial shark cartilage is a popular dietary supplement taken for the prevention and/or control of chronic disease, including arthritis. The efficacy of shark cartilage in maintaining joint health remains questionable; there is a lack of sufficient reliable information on its effect on immunocompetent cells, and the potential health risks involved have not been adequately assessed.
Overall evidence assessment for osteoarthritis: Properly designed studies have so far failed to find benefits for whole shark cartilage in joint disease, though the component chondroitin sulfate has been more extensively studied on its own. Evidence for shark cartilage specifically in arthritis remains weak and not derived from adequately powered, blinded, controlled human trials.
Shark cartilage extract may be beneficial in the management of psoriasis by inhibiting the neovascularization of psoriatic plaques. In chick embryos, shark cartilage extract inhibited neovascularization and types 1 and 4 collagenase activity in a concentration-dependent manner.
Extracts of shark cartilage were prepared by homogenization and ultrafiltration to derive the active agent termed AE-941. This agent was tested for antiangiogenesis activity using the embryonic vascularization test (a modification of the ex vivo chick embryo culture). AE-941 was also tested for collagenase activity and anti-inflammatory properties using a cutaneous irritation model in humans. A dose-dependent inhibition in embryonic neovascularization as well as in collagenase activity by AE-941 was demonstrated. When test compounds were applied to the forearms of test subjects, AE-941 was shown to have anti-inflammatory properties. Anecdotal data suggested that topical AE-941 had a beneficial effect in psoriasis.
In a phase I/II, open-label clinical trial, the effects of shark cartilage extract were assessed in 49 patients with plaque psoriasis. Neovastat (AE-941), a purified shark cartilage extract, is reported to be effective against psoriasis.
Overall evidence assessment for psoriasis: Evidence is preliminary and based mainly on early-phase, open-label clinical trials and in vitro or animal studies. No large-scale, placebo-controlled, randomized trials for shark cartilage in psoriasis have been published.
Due to shark cartilage's antiangiogenic effects, improved or stabilized visual acuity has been reported in a small cohort of patients with macular degeneration. Additional studies are needed before recommendations can be made regarding the use of shark cartilage in macular degeneration. Evidence is very limited, drawn from a small cohort, and exploratory in nature.
There is one case report of regression of Kaposi sarcoma in a patient who took low-dose shark cartilage for a prolonged period. Shark cartilage has also been studied for Kaposi sarcoma in early phase clinical trials. Evidence is limited to case reports and early-phase trials; no controlled evidence is available.
It has been suggested that the anti-angiogenic properties of shark cartilage may make it helpful for psoriasis. Shark cartilage also inhibits matrix metalloproteinases (MMPs), enzymes that affect the "extracellular matrix." MMPs are thought to play a role in diseases of the cornea, gums, skin, blood vessels, and joints, as well as in cancer and illnesses that involve excessive fibrous tissue. On this basis, shark cartilage has been proposed for a wide variety of medical conditions, from cataracts to scleroderma; however, no meaningful studies confirm any of these applications.
In a murine model, the basic peptide fraction of shark cartilage was found to exert uric acid–lowering activity. At least one of the peptides, Tyr-Leu-Asp-Asn-Tyr, maintains antihyperuricemic activity when administered orally. Human evidence is absent for this use.
Commercial doses range from 0.5 to 4.5 g/day, given in 2 to 6 divided doses. Oral shark cartilage preparations should be taken on an empty stomach, and acidic fruit juices should be avoided for 15 to 30 minutes before and after administration.
Specific dosages reported in clinical trials include:
It is very difficult to address dosing for this substance because of the lack of its characterization. There is no generally accepted standard composition of shark cartilage supplements. There are several different products labeled as shark cartilage, and composition differs among them. It is not known if composition changes by batch as well as by product. No active ingredient of shark cartilage preparations has been definitively defined.
Shark cartilage does not appear to be associated with any serious adverse events, even when taken chronically in gram quantities; however, nonserious side effects have been reported. Nonserious side effects, especially nausea and vomiting, may motivate the individual to discontinue consumption. It should be noted that most clinical trials involved critically ill individuals and thus these gastrointestinal disturbances may be associated with other clinical circumstances or treatments. The incidence of these nonserious side effects is in the range of side effects expected in a placebo group.
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. There has been one report of hepatitis occurring in a person who used shark cartilage.
Research has presented evidence of significant immunological reactivity of components of commercial shark cartilage supplement, which could pose a potential health risk for consumers, particularly those with underlying inflammatory disease such as irritable bowel syndrome and arthritis.
Sharks are long-lived apex predators known to accumulate mercury and other heavy metals over their lifespan. Recently, the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA) was detected and quantified in the fins of seven different species of South Florida sharks. BMAA was detected in fifteen out of sixteen commercial shark cartilage products tested, with concentrations ranging from 86 to 265 μg/g (dry weight). All of the shark fin products also contained low concentrations of mercury. The results of this study demonstrate that shark cartilage products may contain the neurotoxin BMAA.
BMAA has been linked to amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC) of Guam and has been detected in the brains of North American Alzheimer's disease and ALS patients, suggesting that BMAA plays a role as an environmental toxin in neurodegenerative disease. Although the neurotoxic potential of dietary exposure to BMAA is currently unknown, the results demonstrate that shark cartilage products may contain two environmental neurotoxins (BMAA and mercury) that have synergistic toxicities.
The neurotoxic compound methylmercury (MeHg) has been known to bioaccumulate in sharks over their lifespans. Mercury levels in shark muscle often exceed advisory guidelines for safe human consumption. Mercury concentrations measured in fins and muscle samples from 10 species of sharks ranged from 0.05 to 13.23 ng/mg.
Occupational exposure to shark cartilage dust has been documented as a cause of asthma. A report published in the Journal of Allergy and Clinical Immunology (2004) identified occupational asthma caused by shark cartilage dust.
Information regarding safety and efficacy in pregnancy and lactation is lacking. Although no clinical studies have been conducted, there is a risk of impaired angiogenesis.
Coadministration of shark cartilage with other drugs (e.g., calcium supplements, thiazide diuretics) may increase calcium levels. Because shark cartilage contains substantial amounts of calcium salts, the following interactions are documented for calcium-containing products:
Companies that make cartilage products may not have a process in place to check that all batches they make are exactly the same. AE-941 (Neovastat) is a novel standardized water-soluble extract derived from shark cartilage that represents less than 5% of the crude cartilage, underscoring how far purified research extracts differ from commercial over-the-counter powders.
The Federal Trade Commission has barred manufacturers from making unsubstantiated claims of efficacy for their shark cartilage products. Dietary supplements containing shark cartilage have gained popularity in western nations. However, the US Food and Drug Administration (FDA) has been unable to confirm any proclaimed benefits, and available reports of health benefits are questionable.
Health conditions that Shark cartilage may help support.
Shark cartilage provides type II collagen, chondroitin sulfate, and glycosaminoglycans as connective tissue matrix components. Clinical studies have examined shark cartilage for OA and joint connective tissue support, showing some benefits for pain and function. It contains high concentrations of sulfated proteoglycans relevant to connective tissue ECM.
Shark cartilage is a source of chondroitin sulfate and other glycosaminoglycans used as a dietary supplement for joint health. Clinical evidence is primarily derived from its chondroitin sulfate content; some RCTs in OA patients have shown reductions in joint pain and improvements in function. Evidence is less robust than for purified chondroitin sulfate alone, with mixed results in large trials.
Shark cartilage is a traditional Chinese medicine ingredient used for bone, joint, and skin health, and contains chondroitin sulfate, mucopolysaccharides, anti-angiogenic proteins, and calcium. While marketed for OA based on chondroitin content, no well-designed RCTs have confirmed clinical benefit for joint cartilage health from whole shark cartilage specifically. The NCI notes that rigorous studies have not validated joint claims, contrasting with strong evidence for isolated chondroitin sulfate.
Body systems that Shark cartilage may help support.
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