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Ciguatera Toxin

Scientific Name(s): Gambierdiscus toxicus (dinoflagellate)
Common Name(s): Ciguatera toxin, Ciguatoxin, CTX, Dinoflagellate toxin

Medically reviewed by Drugs.com. Last updated on Apr 1, 2019.

Clinical Overview

Use

Research reveals no clinical applications for ciguatera toxins.

Dosing

Due to a lack of documentation of any clinical application, dosing recommendations are not available for ciguatera toxin. Safe concentrations of ciguatoxins in fish consumed as meals have not been determined.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Documented adverse reactions.

Interactions

None well documented.

Adverse Reactions

Research reveals no clinical trial data identifying possible adverse effects, aside from known toxicological effects (see Toxicology).

Toxicology

Ciguatoxic fish appear normal in all ways, including smell and taste. The toxin cannot be deactivated by freezing or cooking. Symptoms of ciguatera poisoning are varied and complex; diagnosis is based largely on clinical symptoms and history of fish consumption. Symptoms include GI effects (nausea, vomiting, diarrhea), neurologic effects (numbness, tingling, joint pain, headache, dizziness, temperature inversion [cold perceived as hot]), and cardiovascular effects (dysrhythmia, increased heart rate, hypotension). In severe cases, shock, muscular paralysis, and, rarely, death may occur.

There is no antidote for ciguatera poisoning; therapy includes appropriate rehydration and symptomatic and supportive treatments. Mannitol is the most widely studied therapy.

Source

Ciguatera toxins are produced by the dinoflagellate Gambierdiscus toxicus algae and accumulate throughout the marine food chain in a wide variety of fish.Achaibar 2007 Ciguatoxic fish (including sturgeon, reef sharks, moray eels, parrotfish, jacks, snappers, sea bass, and barracuda) are generally larger predatory fish that accumulate toxins by feeding on smaller tropical reef fish that feed on dinoflagellates, such as G. toxicus. The toxin is concentrated in the flesh and viscera of the larger fish.Achaibar 2007 The environmental factors responsible for G. toxicus blooms are not well understood. Natural disturbances causing damage to reefs may increase the growth of marine algae and ciguatera toxin–producing organisms. Several studies have also linked anthropogenic effects to upsurges of ciguatera; however, the specific factors involved have not been identified, and many human and natural disturbances do not trigger an increase in ciguatera risk.Gingold 2014, Lewis 2006

History

Ciguatera poisoning has reputedly been documented since the T'ang Dynasty (AD 618 to 907), and was also reported by Captain James Cook during his travels to the Pacific Islands in the late 18th century. Case reports and surveillance reports continue to appear in the literature.Achaibar 2007, CDC 2006, CDC 2013, Gingold 2014, Goodman 2013 Many traditional methods for detecting toxicity in fish, such as discoloration of silver and copper metals or repulsion of flies and ants, have been discredited.Dickey 2010

Chemistry

Multiple ciguatoxins have been identified and are often collectively termed "ciguatoxin" or "CTX."Achaibar 2007, Dickey 2010, Yasumoto 2001 Other compounds possibly involved in ciguatera poisoning include maitotoxin, lysophosphatidylcholine, scaritoxin, and ciguatoxin-associated adenosine triphosphatase inhibitor.Hung 2005, Sims 1987 Ciguatoxin is a crystalline, colorless, lipophilic, heat-stable solid that cannot be deactivated by freezing or cooking.Achaibar 2007, Brett 2015, Yasumoto 2001

Uses and Pharmacology

The main pharmacologic action of ciguatoxin is an increase in cell permeability to sodium via voltage-gated sodium channels in cell membranes, causing sustained depolarization and current leakage.Dickey 2010, Friedman 2008 The depolarization of nerve cells leads to neurological symptomology.Friedman 2008 The mechanism of action in humans is reportedly dependent on anticholinesterase activity and cholinomimetic action.Rayner 1968 Ciguatoxin CTX3C has been chemically synthesized, which allows for further study of its action.Hirama 2005

Research reveals no animal or clinical data regarding the use of ciguatera toxin for any clinical application.

Dosing

Due to a lack of documentation of any clinical application, dosing recommendations are not available for ciguatera toxin. Safe concentrations of ciguatoxins in fish consumed as meals have not been determined.Dickey 2010, Friedman 2008

Pregnancy / Lactation

Avoid use. Documented adverse reactions.Briggs 1994

In several published case reports of ciguatera poisoning during pregnancy, fetal symptoms reportedly began simultaneously with the mother's symptoms. Symptoms consisted of tumultuous fetal movements and an intermittent, peculiar fetal shivering. None of the liveborn infants (one fetus was aborted during the acute phase of poisoning) appeared to have lasting effects from ciguatoxin exposure; however, long-term adverse effects could not be completely ruled out in one infant exposed shortly before birth. Ciguatera toxin is excreted in breast milk, with GI and pruritic symptoms reported in infants whose mothers continued to breast-feed during their illness. Breast-feeding should be discontinued to avoid symptoms in breast-feeding infants.Briggs 1994

Interactions

None well documented.

Adverse Reactions

Research reveals no clinical trial data identifying possible adverse effects, aside from known toxicological effects (see Toxicology). Some individuals have experienced recurrence of ciguatera fish poisoning symptoms following the initial exposure; symptom recurrence may be related to immunologically mediated sensitization to ciguatoxin.Friedman 2008

Toxicology

Ciguatoxins are some of the most potent known marine toxins, with a median intraperitoneal lethal dose (LD50) of 0.45 mcg/kg in mice (equivalent to 2 to 5 g of original fish flesh).CDC 1982 Ciguatoxins are associated with a risk of adverse effects at concentrations as low as 0.1 mcg/kg.Friedman 2008

Ciguatoxic fish appear normal in all ways, including smell and taste. The toxin cannot be deactivated by freezing or cooking. There are no reliable biomarkers to determine exposure to the toxin in human samples;Achaibar 2007, CDC 2013, Friedman 2008 however, methods for detecting ciguatoxins in fish have been established.Dickey 2010 The mouse bioassay is the most widely used assay for detection of ciguatoxins in fish.Friedman 2008

The symptoms of ciguatera poisoning are varied and complex; diagnosis is based largely on clinical symptoms and history of fish consumption.Achaibar 2007, Friedman 2008, Goodman 2013 Changes in electroencephalogram activity have been documented in mice.Kumar 2017 Symptoms include GI effects (nausea, vomiting, diarrhea), neurologic effects (numbness, tingling, joint pain, headache, dizziness, temperature inversion [cold things perceived as hot]), and cardiovascular effects (dysrhythmia, increased heart rate, hypotension).Goodman 2013 In severe cases, shock, muscular paralysis, and, rarely, death may occur.CDC 2006

Symptoms usually appear within 1 to 6 hours after ingestion; however, the onset of symptoms is highly variable, with studies reporting a range of less than 1 hour to 48 hours.Achaibar 2007, Friedman 2008, Goodman 2013 Neurological effects may persist for weeks to months, and a small proportion of affected individuals may develop chronic ciguatera, a widespread, multisystem chronic illness.Shoemaker 2010 During the recovery phase, it is recommended that patients avoid fish and alcohol for 3 to 6 months.Achaibar 2007, Friedman 2008, Goodman 2013

There is no antidote for ciguatera poisoning; therapy includes appropriate rehydration and symptomatic and supportive treatments.

Mannitol is the most widely studied therapy for ciguatera poisoning. Mannitol's effect is thought to be mediated via osmotic reduction of neuronal edema; it may also act as a scavenger of free radicals generated by ciguatoxin, thereby reducing the effect of ciguatoxin on sodium and/or potassium channels. As an osmotic diuretic, mannitol should only be used in adequately hydrated patients.Friedman 2008

Other therapeutic agents studied for potential use in managing ciguatoxic effects include atropine, neostigmine, steroids, pralidoxime, vitamins B12 and C, antihistamines, calcium, amitriptyline, morphine, lamotrigine, gabapentin, and pregabalin.Brett 2015, Friedman 2008, Zimmermann 2013 Anticiguatoxin monoclonal antibodies have also been studied.Inoue 2009 One report evaluated the use of hypnosis to address long-lasting effects of ciguatoxin poisoning.Laser 2012

Persons living in or traveling to ciguatera-endemic areas should avoid consuming large predatory reef fish, especially barracuda; eating the head, viscera, or roe of any reef fish; and eating fish caught at sites known to be ciguatoxic. Health care providers who treat patients with GI or neurological symptoms after eating large predatory fish should consider a diagnosis of ciguatera toxicity.CDC 2006

References

Achaibar KC, Moore S, Bain PG. Ciguatera poisoning. Pract Neurol. 2007;7(5):316-322.17885270
Brett J, Murnion B. Pregabalin to treat ciguatera fish poisoning. Clin Toxicol (Phila). 2015;53(6):588.26051385
Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 4th ed. Baltimore, MD: Williams & Wilkins; 1994.
Centers for Disease Control (CDC). Ciguatera fish poisoning - Bahamas, Miami. MMWR Morb Mortal WklyRep. 1982;31(28):391-392.6813670
Centers for Disease Control and Prevention (CDC). Ciguatera fish poisoning - New York City, 2010-2011. MMWR Morb Mortal Wkly Rep. 2013;62(4):61-65.23364271
Centers for Disease Control and Prevention (CDC). Ciguatera fish poisoning—Texas, 1998, and South Carolina, 2004. MMWR Morb Mortal Wkly Rep. 2006;55(34):935-937.16943762
Dickey RW, Plakas SM. Ciguatera: a public health perspective. Toxicon. 2010;56(2):123-136.19782098
Friedman MA, Fleming LE, Fernandez M, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs. 2008;6(3):456-479.19005579
Gingold DB, Strickland MJ, Hess JJ. Ciguatera fish poisoning and climate change: analysis of national poison center data in the United States, 2001-2011. Environ Health Perspect. 2014;122(6):580-586.24618280
Goodman DM, Rogers J, Livingston EH. JAMA patient page. Ciguatera fish poisoning. JAMA. 2013;309(24):2608.23800938
Hirama M. Total synthesis of ciguatoxin CTX3C: a venture into the problems of ciguatera seafood poisoning. Chem Rec. 2005;5(4):240-250.16059875
Hung YM, Hung SY, Chou KJ, et al. Short report: persistent bradycardia caused by ciguatoxin poisoning after barracuda fish eggs ingestion in southern Taiwan. Am J Trop Med Hyg. 2005;73(6):1026-1027.16354806
Inoue M, Lee N, Tsumuraya T, Fujii I, Hirama M. Use of monoclonal antibodies as an effective strategy for treatment of ciguatera poisoning. Toxicon. 2009;53(7-8):802-805.19254735
Kumar G, Au NP, Lei EN, et al. Acute exposure to pacific ciguatoxin reduces electroencephalogram activity and disrupts neurotransmitter metabolic pathways in motor cortex. Mol Neurobiol. 2017;54(7):5590-5603.27613284
Laser ED, Shenefelt PD. Hypnosis to alleviate the symptoms of ciguatera toxicity: a case study. Am J Clin Hypn. 2012;54(3):179-183.22443020
Lewis RJ. Ciguatera: Australian perspectives on a global problem. Toxicon. 2006;48(7):799-809.16930661
Rayner MD, Kosaki TI, Fellmeth EL. Ciguatoxin: more than an anticholinesterase. Science. 1968;160(3823):70-71.5642309
Shoemaker RC, House D, Ryan JC. Defining the neurotoxin derived illness chronic ciguatera using markers of chronic systemic inflammatory disturbances: a case/control study. Neurotoxicol Teratol. 2010;32(6):633-639.20685390
Sims JK. A theoretical discourse on the pharmacology of toxic marine ingestions. Ann Emerg Med. 1987;16(9):1006-1015.3307551
Yasumoto T. The chemistry and biological function of natural marine toxins. Chem Rec. 2001;1(3):228-242.11895121
Zimmermann K, Deuis JR, Inserra MC, et al. Analgesic treatment of ciguatoxin-induced cold allodynia. Pain. 2013;154(10):1999-2006.23778293

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