Shark Cartilage Extract

Generic name: Sphyrna Lewini (Hammerhead Shark), Squalus Acanthias (spiny Dogfish Shark)
Brand names: Hammerhead Shark, Matrix Metalloproteinase Inhibitors, Shark Cartilage, Spiny Dogfish Shark

Usage of Shark Cartilage Extract

Anti-inflammatory effects

Shark cartilage may be useful in inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, and, in some cases, osteoarthritis. Specifically, it may be beneficial due to its anti-angiogenic effects as well as the presence of high levels of anti-inflammatory mucopolysaccharides such as glucosamine sulfate and chondroitin sulfate. Improvements in inflammation may be noticed as soon as 1 to 2 weeks after initiating treatment with shark cartilage; however, if no improvement occurs, patients should be advised to continue treatment for 6 to 8 weeks before a decision is made to discontinue.(Milner 1999)

Animal and in vitro data

Shark cartilage polysaccharide given to rats at 9 mg/day for 24 days exerted beneficial effects in a model of rheumatoid arthritis (RA). Supplementation reduced paw swelling, inhibited IL-6 and IL-12 secretion, and improved radiologic change of the bone. While shark cartilage was not better than methotrexate on these parameters, the inflammatory process in RA rats without treatment led to increases in levels of the proinflammatory cytokines IL-6 and IL-12.(Chuan-Ying 2012) Similarly, another murine model found that shark cartilage attenuated inflammation when dosed at 3 mg/kg/day orally for 2 weeks.(Chen 2012) However, in an in vitro study, shark cartilage stimulated production of proinflammatory cytokines and chemokines, as well as activated signaling pathways; in vivo, this could lead to exacerbations of inflammatory diseases such as irritable bowel syndrome.(Merly 2015)

Clinical data

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.(Cohen 2003)

A study examining the role of shark cartilage extract in psoriasis noted anti-inflammatory properties.(Dupont 1998)

Antimicrobial effects

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.(Moore 1993) 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.

Antioxidant effects

In an in vitro study, shark cartilage served as a scavenger against reactive oxygen species and protected cells against inactivation and mutagenesis, suggesting potential antioxidant effects.(Felzenszwalb 1998)

Cancer

There have been many claims regarding the role of shark cartilage as a cure for cancer. The fact that sharks rarely get cancer has led to the theory that because sharks are cartilaginous fish, and cartilage is avascular and contains agents that inhibit vascularization (angiogenesis, promotion of new blood vessels needed for tumor growth and metastasis), the cartilage from sharks can, therefore, cure cancer. The inhibited vascularization theoretically prevents formation of tumors; hence, in humans, use may inhibit tumor angiogenesis and thus possibly cure cancer.(Masslo 1993) Inhibition of angiogenesis through vascular endothelial growth factor and matrix metalloproteinase (MMP), particularly MMP-2, -9, -12, and -13 by shark cartilage extract has been demonstrated.(Jabłońska-Trypuć 2016, Patra 2012, Sauder 2002) It has also induced apoptosis in endothelial cells.(Patra 2012)

Animal and in vitro data

Some of the earliest published data on use of shark cartilage for anticancer effects come from an experimental cornea model in rabbits. Pellets of shark cartilage derived from basking sharks (Cetorhinus maximus) were placed into rabbit corneas, along with V2 carcinoma cells. At 19 days, corneas treated with shark cartilage did not contain any 3-dimensional tumors, unlike the control corneas.(Lee 1983) The study authors suggested that further exploration in experimental models is needed to determine the angiogenesis inhibitory effects of shark cartilage.

An acidic ethanol-precipitate fraction of shark cartilage was associated with reduced incidence and number of adenocarcinomas in the pancreatic ducts of hamsters. Additionally, this fraction inhibited MMP-9.(Kitahashi 2012)

Clinical data

Limited quality clinical studies have been conducted; however, results for some have not been published, (NML_2022) and findings from others are inconclusive.

In a survey of long-term lymphoma survivors (6 to 20 years), 7% (95% confidence interval, 2% to 17%) of patients reported shark cartilage use.(Habermann 2009) In late 1992, incomplete and nonreplicated clinical studies (unpublished) conducted in Havana, Cuba, purported to show some benefit in terminally ill cancer patients. The National Cancer Institute reviewed these studies and decided against researching shark cartilage.(Masslo 1993)

A case report described clinical and histological regression of early-stage cutaneous Kaposi sarcoma in a 45-year-old man positive for human herpesvirus-8 and negative for HIV. Initially, the patient received a 3-month course of ganciclovir with no clinical resolution. Shark cartilage supplementation was then initiated at 3,750 mg divided twice daily for the first 3 months. After 3 months, the Kaposi sarcoma lesion had decreased in size. The dose was increased to 4,500 mg divided 3 times daily for the remainder of the approximately 3-year treatment period.(Hillman 2001) In a phase 2, open-label study of 144 patients with refractory renal cell carcinoma, the effects of shark cartilage extract on survival were assessed. Patients were given either 60 mL/day or 240 mL/day of the extract orally, divided twice daily. Patients treated with the 240 mL/day dose had a longer median survival time (16.3 months) compared with those receiving 60 mL/day (7.1 months; P=0.01).(Batist 2002)

In a 2005 two-armed, randomized, double-blind, placebo-controlled clinical trial in patients with incurable breast or colorectal cancer (N=88), shark cartilage powder was initiated at 24 g and titrated upward as tolerated every 3 days, towards a goal of 96 g given in 3 or 4 divided doses. Results demonstrated no improvement in survival or quality of life (QOL) in patients who received shark cartilage compared with placebo; in fact, QOL variables were confirmed to be significantly worse with shark cartilage supplementation at weeks 2 and 3 (P=0.005 and P=0.05, respectively). For the 24 patients who remained in the study at month 3, QOL, measured using the Symptom Distress Scale, was significantly better in the shark cartilage group (P=0.04), with Linear Analogue Self-Assessment test scores indicating higher emotional and spiritual well-being (P=0.05 and P=0.01, respectively). However, given the very low number of patients in each arm at month 3, results should be interpreted with caution. The most frequent severe toxicities experienced in the shark cartilage group and not observed in the placebo group included diarrhea, dyspnea, leukopenia, neutropenia, and bone pain; most adverse effects were mild to moderate.(Loprinzi 2005)

In a randomized, double-blind, placebo-controlled, phase 3 trial of patients with stage III non–small cell lung cancer treated with chemoradiotherapy, the addition of shark cartilage did not improve overall patient survival compared with placebo. In addition, time to progression, progression-free survival, and tumor response rates were not different between shark cartilage and placebo groups. It should be noted that the study was closed before reaching the targeted sample size due to insufficient accrual of patients.(Lu 2010)

In a study of patients with advanced cancer (breast, colorectal, lung, prostate, non-Hodgkin lymphoma, brain, and unknown tumor), shark cartilage was inactive and had no beneficial effects on QOL.(Miller 1998)

Colonic anastomoses

Following colonic anastomosis in rabbits, administration of shark cartilage increased connective tissue and vascularization without impacting microbial growth or translocation. Bursting pressure (139.29 mm Hg vs 85 mm Hg) and hydroxyproline levels (4.59±0.26 g/mg tissue vs 2.55±0.21 g/mg tissue) were higher in the shark cartilage group compared with controls (P<0.05 for both comparisons). Shark cartilage positively impacted collage synthesis and promoted better vascularization in the anastomosis regions, thereby increasing the strength of the anastomosis.(Sulu 2013)

Fibrinolytic effects

An in vitro study demonstrated that shark cartilage possesses plasmin-independent fibrinolytic activity. Shark cartilage decreased clot firmness; however, there was no impact on clotting time and kinetic parameters.(Ratel 2005)

Immunostimulatory effects

In an in vitro study, a fraction of shark cartilage–derived protein exerted immunostimulatory effects on the cytotoxic activity of natural killer cells.(Bargahi 2011)

Macular degeneration

Due to shark cartilage's antiangiogenic effects, improved or stabilized visual acuity has been reported in a small cohort of patients with macular degeneration.(Hammerness 2002) Additional studies are needed before recommendations can be made regarding the use of shark cartilage in macular degeneration.

Psoriasis

Shark cartilage extract may be beneficial in the management of psoriasis by inhibiting the neovascularization of psoriatic plaques.

Animal and in vitro data

In chick embryos, shark cartilage extract inhibited neovascularization and types 1 and 4 collagenase activity in a concentration-dependent manner.(Dupont 1998)

Clinical data

In a phase 1/2, open-label clinical trial, the effects of shark cartilage extract were assessed in 49 patients with plaque psoriasis. Patients were randomized to receive a regimen of 30, 60, 120, or 240 mL/day extract orally twice daily for 12 weeks, with an additional 12-week follow up period. Only 12 of the 49 patients completed the entire 24-week study. Psoriasis Area and Severity Index (PASI) score improved by 20% or greater in 30.8%, 41.7%, and 50% of patients receiving 60, 120, and 240 mL/day, respectively. Those receiving 30 mL/day did not show an improvement in PASI score.(Sauder 2002) The high withdrawal/dropout rate in this study limits interpretation of the data.

In another study examining the potential role of shark cartilage extract in psoriasis, investigators applied shark cartilage to the ventral forearms, followed by Balsam of Peru, a skin irritant. All doses tested prevented skin irritation, suggesting anti-inflammatory properties.(Dupont 1998)

Uric acid–lowering effects

In a murine model, the basic peptide fraction of shark cartilage was found to exert uric acid–lowering activity.(Murota 2010) At least one of the peptides, Tyr- Leu-Asp-Asn-Tyr, maintains antihyperuricemic activity when administered orally.(Murota 2014)

Shark Cartilage Extract side effects

The most commonly reported adverse effects are mild to moderate and include GI distress and nausea.Hammerness 2002 Taste alterations have also been noted.Batist 2002 Because shark cartilage supplements often contain high levels of calcium (eg, elemental calcium 600 to 780 mg daily), hypercalcemia may occur, particularly in patients with cancer. In 2 case reports of patients with cancer, it was suggested that episodes of symptomatic hypercalcemia were associated with shark cartilage supplementation, especially when used in combination with multivitamins that provide additional calcium and vitamin D.Lagman 2003

A case of immunoglobulin E–mediated allergic occupational asthma has been documented in a 29-year-old man who worked in a dietetic product production facility. Symptoms included chest tightness, cough, and dyspnea that required management with bronchodilators and several hospital admissions. Peak expiratory flow rate decreased by more than 20% during work periods and, along with other symptoms, improved on the weekends and holidays.San-Juan 2004 Another case report described a 38-year-old white man working in a facility that ground shark cartilage. After about 10 months of exposure, he reported dyspnea, coughing, and wheezing, symptoms associated with shark cartilage exposure, and was diagnosed with asthma. Six months later, he reported shortness of breath at work and died; the autopsy report indicated the presence of mucus casts and numerous emphysematous blebs, and confirmed asthma as the cause of death.Ortega 2002 This case is confounded by the patient's smoking history but may be linked to occupational exposure to shark cartilage.

A case report described a 57-year-old man with hepatitis presumed to be induced by shark cartilage. He reported a 3-week history of nausea, vomiting, diarrhea, and anorexia and was found to have elevated liver enzyme, bilirubin, and alkaline phosphatase levels. He had begun taking shark cartilage 10 weeks prior to hospitalization but had reportedly discontinued taking the supplements a few days before his symptoms began due to an odor from the supplements. Six weeks following discharge, he had normal liver function.Ashar 1996

Before taking Shark Cartilage Extract

Avoid use. 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.(CAM Cancer 2020, Hammerness 2002)

How to use Shark Cartilage Extract

Commercial doses range from 0.5 to 4.5 g/day, given in 2 to 6 divided doses.(CAM Cancer 2020)

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.(Hammerness 2002)

Cancer: Studies have evaluated 80 to 100 g/day or 1 to 1.3 g/kg/day of ground extract in 2 to 4 divided doses.(Hammerness 2002) Doses of the shark cartilage derivative AE-941, used in clinical trials, have ranged from 30 to 240 mL/day or 20 mg/kg twice daily.(Hammerness 2002) In patients with incurable breast and colorectal cancer, a powder formulation was initially dosed at 24 g/day and titrated upward every 3 days to a target dose of 96 g/day, administered in divided doses 3 to 4 times a day.(Falardeau 2001)

Joint diseases: 0.2 to 2 g/kg/day in 2 to 3 divided doses have been suggested.(Hammerness 2002)

Psoriasis: 0.4 to 0.5 g/kg/day for 4 weeks, with dosage reduced to 0.2 to 0.3 g/kg/day for 4 additional weeks if skin lesions improve. Topical preparations containing shark cartilage 5% to 30% are also available.(Hammerness 2002)

Warnings

In an analysis of calcium supplements in Korea, shark cartilage–containing calcium supplements were among the highest in mercury and cadmium content, with levels that could be toxic in pediatric and elderly populations.Kim 2004 In another study testing 16 shark cartilage products, 15 of the 16 contained BMAA (a neurotoxin found in the fins of several species of shark and potentially linked to degenerative brain disease) at concentrations ranging from 86 to 265 mcg/g; mercury content was low in these shark fin products.Mondo 2014 Caution should be used.

What other drugs will affect Shark Cartilage Extract

Coadministration of shark cartilage with other drugs (eg, calcium supplements, thiazide diuretics) may increase calcium levels.(Hammerness 2002)

Alpha-lipoic acid: Calcium Salts may decrease the absorption of alpha-lipoic acid. Alpha-lipoic acid may decrease the absorption of calcium salts. Consider therapy modification.(Thioctic September 2014)

Baloxavir marboxil: Polyvalent cation-containing products may decrease the serum concentration of Baloxavir marboxil. Avoid combination. This interaction only applies to orally administered polyvalent cation-containing products.(Xofluza October 2018)

Bictegravir: Calcium salts may decrease the serum concentration of bictegravir. Consider therapy modification. This interaction is limited to orally administered calcium salts.(Biktarvy February 2018)

Bisphosphonate derivatives: Polyvalent cation-containing products may decrease the serum concentration of bisphosphonate derivatives. Consider therapy modification. Only oral preparations of bisphosphonate derivatives and oral polyvalent cation containing products are expected to participate in this interaction.(Actonel April 2015, Bonefos September 2011, Boniva April 2015, Didronel April 2015, Fosamax February 2015, Skelid March 2010)

Cabotegravir: Polyvalent cation-containing products may decrease the serum concentration of cabotegravir. Consider therapy modification. This interaction only applies to orally administered cabotegravir and orally administered polyvalent cation containing products.(Vocabria January 2021)

Calcium acetate: Calcium salts may enhance the adverse/toxic effect of calcium acetate. Avoid combination.(PhosLo March 2011)

Calcium channel blockers: Calcium salts may diminish the therapeutic effect of calcium channel blockers. Monitor therapy.(Bar-Or 1981, Haft 1986, O’Quinn 1990, Salerno 1987, Schoen 1991, Wohns 1991)

Cardiac glycosides: Calcium salts may enhance the arrhythmogenic effect of cardiac glycosides. Monitor therapy.(Ejvinsson 1978, Leahey 1978, Nola 1970, Smith 1972, Vella 1999)

Deferiprone: Polyvalent cation-containing products may decrease the serum concentration of Deferiprone. Consider therapy modification. This interaction only applies to orally administered polyvalent cation containing products.(Ferriprox July 2019, Ferriprox April 2018)

Dobutamine: Calcium salts may diminish the therapeutic effect of dobutamine. Monitor therapy. This interaction is likely most clinically significant with IV calcium administration.(Butterworth 1992)

Dolutegravir: Calcium salts may decrease the serum concentration of dolutegravir. Consider therapy modification. This interaction is only anticipated with oral administration of calcium salts.(Federspiel 2021, Juluca November 2017, Tivicay May 2014)

Eltrombopag: Polyvalent cation-containing products may decrease the serum concentration of eltrombopag. Consider therapy modification. This interaction only applies to orally administered polyvalent cation containing products.(Promacta August 2015, Williams 2009)

Elvitegravir: Polyvalent cation-containing products may decrease the serum concentration of elvitegravir. Consider therapy modification. This interaction only applies to orally administered polyvalent cation containing products.(HHS 2020, Genvoya February 2019, Kang-Birken 2019, Ramanathan 2013, Stribild January 2019)

Estramustane: Calcium salts may decrease the absorption of estramustine. Consider therapy modification.(Emcyt 2003, Gunnarsson 1990)

Fluoride: Calcium salts may decrease the serum concentration of fluoride. No action needed. This interaction only applies to ingested fluoride products, but does not apply to topical fluoride products (eg, gels, creams, mouthwashes, pastes).(Flura-Drops September 2019, Spencer 1980)

Lycopene: Calcium salts may decrease the serum concentration of lycopene. No action needed. This interaction only applies to orally administered calcium salts.(Borel 2016)

Moxifloxacin (systemic): Calcium salts may decrease the absorption of moxifloxacin (systemic). No action needed. This interaction only applies to orally administered moxifloxacin and orally administered calcium salts.(Moxifloxacin January 2022, Stass 2001)

Multivitamins/Fluoride (with ADE): Multivitamins/Fluoride (with ADE) may increase the serum concentration of calcium salts. Calcium Salts may decrease the serum concentration of Multivitamins/Fluoride (with ADE). More specifically, calcium salts may impair the absorption of fluoride. Consider therapy modification.(Bjelakovic 2011, EtheDent 2002, Hathcock 2007, Peacock 2010)

Multivitamins/Minerals (with ADEK, folate, iron): Multivitamins/Minerals (with ADEK, folate, iron) may increase the serum concentration of calcium salts. Monitor therapy.(Bjelakovic 2011, Hathcock 2007, Peacock 2010)

PenicillAMINE: Polyvalent cation-containing products may decrease the serum concentration of PenicillAMINE. Consider therapy modification. This interaction only applies to orally administered polyvalent cation containing products.(Brewer 1993, Cuprimine November 2015, Harkness 1982, Lyle 1976, Osman 1983)

Phosphate supplements: Calcium salts may decrease the absorption of phosphate supplements. Consider therapy modification. Only oral preparations of phosphate supplements and calcium salts are expected to participate in this interaction.(Heaney 2002, Lau 1998)

Quinolones: Calcium salts may decrease the absorption of quinolones. Of concern only with oral administration of both agents. Consider therapy modification. Only oral preparations of quinolone antibiotics and calcium salts are expected to participate in this interaction.(Frost 1989, Hoffken 1985, Kays 2003, Lehto 1994, Nix 1990, Sahai 1993, Schentag 1988, Shiba 1992, Shimada 1992, Staff 2001)

Ratelgravir: Polyvalent cation-containing products may decrease the serum concentration of raltegravir. Consider therapy modification. This interaction likely applies only to orally-administered polyvalent cation-containing products.(Bacchi 2011, HHS HIV 2019, HHS Antiretroviral 2019, Isentress May 2017, Moss 2012)

Strontium ranelate: Calcium salts may decrease the serum concentration of strontium ranelate. Consider therapy modification. This interaction applies only to orally administered calcium salts.(Protelos July 2012)

Tetracyclines: Calcium salts may decrease the serum concentration of Tetracyclines. Consider therapy modification. This interaction only applies to concurrent use of oral tetracyclines and oral calcium salts.(Jung 1997, Minocin August 2010, PhosLo March 2011, Tetracycline June 2009, Vibramycin April 2007)

Thiazide and thiazide-like diuretics: Thiazide and thiazide-like diuretics may decrease the excretion of calcium salts. Continued concomitant use can also result in metabolic alkalosis. Monitor therapy.(Drinka 1984, Gora 1989, Hakim 1979, Parfitt 1969)

Thyroid products: Calcium salts may diminish the therapeutic effect of thyroid products. Consider therapy modification.(Butner 2000, Csako 2001, Diskin 2007, Irving 2014, Mazokopakis 2008, Schneyer 1998, Singh 2000, Singh 2001, Zamfirescu 2011)

Trientine: Polyvalent cation-containing products may decrease the serum concentration of trientine. Consider therapy modification. This interaction only applies to orally administered polyvalent cation containing products.(Brewer 1993, Cuvrior April 2022, Syprine December 2016, Walshe 1982)

Vitamin D analogs: Calcium salts may enhance the adverse/toxic effect of vitamin D analogs. Monitor therapy.(Dovonex March 2015, ErgoCalciferol October 2018, Fosamax Plus D August 2019, Hectorol November 2018, One-Alpha September 2020, Rayaldee December 2019, Rocalctrol November 1998, Vectical July 2020, Zemplar March 2011)

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