Background
Ciguatoxins are a family of toxins that cause a type of food poisoning called ciguatera. Ciguatera is the most common type of non-bacterial seafood poisoning. Ciguatera can be caused by eating reef fish contaminated with ciguatoxins (95315,95316). The fish become contaminated with ciguatoxins after consuming the pretoxin directly from marine dinoflagellates such as Gambierdiscus toxicus, or by bio-accumulation via the marine food chain. Contaminated fish appear normal but can cause gastrointestinal, neurological, and cardiovascular symptoms when consumed by humans (42995,43078,43135,43171). Over 400 normally safe fish species, including the red snapper, barracuda, parrotfish, jacks, surgeon, grouper, humphead wrasse, and moray eel, can become contaminated with ciguatoxins. These fish are more likely to be contaminated if they are fished from areas of recently disturbed coral reefs, such as areas with waterfront construction or following cyclones (6,43031,95315,95316,95319).
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Safety Safety definitions
Unsafe ...when ingested. A single bite of fish contaminated with ciguatoxins will cause a type of food poisoning called ciguatera (6). There have been numerous reports of ciguatera poisoning related to ciguatoxins that have resulted in serious neurological, musculoskeletal, and cardiovascular symptoms; up to 20% mortality has been reported (6,42965,42974,42976,42978,42981,42993,42995,42996,42997,43003,43005,43008,43011,43018,43019,43027) (43028,43033,43038,43039,43048,43050,43053,43058,43063,43071,43078,43087,43088,43090,43099,43102) (43112,43123,43127,43129,43147,43148,43152,43159,43164,43165,43166,43171) (95315,95316,95317,95318,95319,95320,95321,95322,95323,96265,96266,96267,96268,96269).
Unsafe ...when ingested. Ciguatoxins cause a type of food poisoning called ciguatera. There has been one report of a fetus being aborted during acute phase of maternal ciguatera poisoning. Lasting adverse effects have not been reported in most case reports of liveborn infants (6,19611,19612). However, there is one report of an infant born with facial palsy and myotonia after maternal ciguatera poisoning (26148).
Unsafe ...when ingested. Ciguatoxins are excreted in breast milk. GI symptoms and itching have been reported in infants breast-fed by symptomatic mothers. The infants' symptoms resolved with discontinuation of breast-feeding (6,43046).
Effectiveness Effectiveness definitions
There is insufficient reliable information available about the effectiveness of ciguatera.
Natural Medicines rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.
Dosing & administration
Standardization & formulationThere is insufficient reliable information available about the standardization of ciguatoxins.
Adverse effects
Neurologic/CNS: Orally, hallmark neurological symptom caused by ciguatoxins include paresthesias, pruritus, dental pain, joint and muscle aches, headache, and cold allodynia. Possible neuropsychiatric conditions include loss of memory, delirium, and ataxia (42996,43088,43102,43112,43129,43164,43165,95315,95316,95317,95318,95319,95320,95322,95323,96265,96266,96267,96268). In case reports, fever, fatigue, lethargy, dizziness, and metallic taste have also occurred (95315,95316,95318,95319,95320,95323,96265). Chronic fatigue syndrome has been reported rarely as a chronic response (42989,43163). Seizures and coma have been reported rarely in severe cases (43152,95315,95319,95321). In the case of a 15-year old boy, ciguatoxins resulted in generalized tonic-clonic seizures. Treatment required physical and occupational therapy to normalize cognitive abilities and re-establish independence. However, 14 months after initiation he still required antiepileptics to prevent tremors and paraesthesias (95321). Neuropathy with demyelination has been reported in a case report (43063).
Neurological symptoms are most common following consumption of contaminated fish from the Indo-Pacific region (43029). These symptoms can last for weeks to months; some symptoms may even be chronic (42974,95315,95320). Pain may be treated with gabapentin and amitriptyline, and chronic fatigue with fluoxetine (43022,95315). Pregabalin has been used at a dose of up to 150 mg twice daily, weaning with resolution of neurological symptoms (95317). Intravenous mannitol has been used to treat neurological symptoms associated with ciguatoxins. However, clinical research does not support the use of mannitol (42997).
Deaths due to ciguatoxin poisoning are relatively rare with estimates of 0.02% to 0.1% of total known poisonings. They are more likely in people of increased age and weight, as well as in those with previous exposure. Known fatal cases have occurred in areas of the Pacific and Indian Oceans, and the Caribbean Sea, and have occurred between 10.3 hours and 25 days after ingestion of the contaminated fish. Deaths are usually associated with eating large amounts of parts of the fish rich in the toxin, such as the head and/or viscera. The fish most likely to cause death is the yellow-edge moray eel, usually caught soon after a large storm causing disturbance of the reef where these fish are commonly found. Deaths are normally due to life-threatening complications in areas without immediate emergency care. Serious neurological adverse effects occurring prior to death include convulsions, coma, brain damage, and evidence of neurological deficits, including ataxia, vertigo, changes in pupil size and rapid eye movements, agitation, delirium, outbursts, panic, pain in joints, paralysis, abnormal breathing patterns and pain response, cerebral edema, and hyperthermia. Respiratory failure and/or depression often occur in association with paralysis of the respiratory muscles (96269).
Musculoskeletal: Neurological effects of ciguatoxins might appear as joint pain or muscle symptoms, such as myalgia, inflammation, spasms, and cramping (42996,43058,43129,95316,95319,95322,95323,96265,96267). Muscle inflammation, as polymyositis, has been reported rarely (43038,43157).
Genitourinary: In case reports, ciguatoxin poisoning has been rarely associated with dysuria (43088,95322,96266). Painful ejaculation for a male with ciguatera poisoning and dyspareunia in an uninfected female partner during sexual intercourse has been reported. It is believed that the symptomology in the female resulted from the transfer of ciguatoxins from the semen of the male during sexual intercourse (43062).
Gastrointestinal: Orally, ciguatoxins can cause gastrointestinal symptoms, which can include some or all of the following: nausea, vomiting, abdominal pain, and diarrhea. These may result in dehydration (42981,43027,43087,43102,43129,43135,43164,43165,95315,95316,95317,95318,95319,95320,95321,95322,95323,96265,96266,96267,96268). The symptoms usually develop in under 12 hours after consumption of contaminated fish and resolve within 24 hours. Gastrointestinal symptoms are most common following the consumption of contaminated fish from the Caribbean (43029). Antiemetics are used during treatment (43165).
Endocrine: Hypokalemia has been reported in case series of ciguatoxin poisoning associated with consumption of contaminated fish (95319).
Dermatologic: Orally, ciguatoxins can cause pruritus and, less commonly, skin rash (43088,43164,95316,95317,95319,95322,96268).
Cardiovascular: Cardiovascular symptoms can occur soon after consumption of ciguatoxin-contaminated fish. These symptoms include hypotension and bradycardia which have been shown in case reports (43019,43027,43129,43156,43164,95315,95318,95319). Chest pain with myocardial ischemia is also possible (95319). Treatment is supportive with atropine or cardiac pacing for bradycardia and intravenous fluids or dopamine for hypotension. Symptoms can last 3-4 days (95315,95318,95319). Deaths due to ciguatoxin are relatively rare with estimates of 0.02% to 0.1% of total known poisonings. They are more likely in people of increased age and weight, as well as in those with previous exposure. Known cases of fatality have occurred in areas of the Pacific and Indian Oceans and the Caribbean Sea, and have occurred between 10.3 hours and 25 days after ingestion of the contaminated fish. Deaths are usually associated with eating large amounts of parts of the fish rich in the ciguatoxin, such as the head and/or viscera. The fish most likely to cause death is the yellow-edge moray eel, which is usually caught soon after a large storm that causes coral reef disturbance. Deaths are normally due to life-threatening complications in areas without immediate emergency care. Although severe neurological adverse effects are more likely to precede fatality with ciguatoxin poisoning, severe prolonged hypotension and bradycardia also increase susceptibility. Death due to myocardial infarction has occurred in two elderly men with ciguatera (96269).
General: Ciguatoxins cause a type of food poisoning called ciguatera. Symptoms of ciguatera usually develop in under 12 hours after consumption of fish contaminated with ciguatoxins. General symptom severity is increased in men aged 30-39 years and in people experiencing a repeat attack (43008). Initial symptoms are gastrointestinal and include nausea, vomiting, abdominal pain, and diarrhea (42981,43027,43087,43102,43129,43135,43164,43165,95315,95316,95317,95318,95319,95320,95321,95322,95323,96265,96266,96267,96268). Later, neurological symptoms occur. These typically include paresthesias, pruritus, joint and muscle aches, headache, ataxia, and cold allodynia. Possible neuropsychiatric conditions include anxiety, depression, loss of memory, and delirium. In case reports, fever, fatigue, lethargy, dizziness, and metallic taste have occurred (95315,95316,95317,95318,95319,95320,95322,95323,96265,96267,96268). Neurological effects of ciguatoxin poisoning might appear as joint pain or muscle symptoms, such as myalgia, inflammation, spasms, and cramping (42996,43058,43129). Seizures and coma have been reported rarely in severe cases (43152,95315,95321). Neurological symptoms can last for weeks to months (95315). Less commonly, cardiovascular symptoms can occur soon after consumption of the contaminated fish. These symptoms include hypotension and bradycardia (43019,43027,43129,43156,43164,95315,95318,95319). Chest pain with myocardial ischemia is also possible (95319). Hypokalemia, acute kidney injury, dysuria, nightmares and hallucination, muscle inflammation, neuropathy with demyelination, dental and eye pain, dry eye and irritation, pupil constriction and dilation, and uncontrolled rapid eye movement have also been reported rarely (42983, 42996,43038,43063,43157,43159,95315,95319,95322,96265,96266).
Ciguatoxins can be detected in the fish to confirm ciguatera. However, the fish is not always available for testing (95315). Treatment is supportive and depends on specific symptoms. The predominate symptoms depend on the geography of the ciguatoxin. In the Caribbean, symptoms are mainly gastrointestinal whereas neurological symptoms are most common in the Indo-Pacific region (43029). Treatment may include atropine or cardiac pacing for bradycardia and intravenous fluids or dopamine for hypotension (95315,95318,95319). Neurological symptoms have been treated with gabapentin, amitriptyline, pregabalin, and/or fluoxetine (43022,43078,95315,95317). Antihistamines have been used for general and itching symptomatic treatment (95316,96268). Ocular lubricants are used for symptoms of dry eye (96266). Antiemetics have been used for gastrointestinal symptoms (43165). Intravenous mannitol has been used to treat neurological symptoms of ciguatoxin poisoning. However, clinical research does not support the use of mannitol (42997).
Deaths due to ciguatoxin are relatively rare with estimates of 0.02% to 0.1% of total known food poisonings. They are more likely in people of increased age and weight, as well as in those with previous exposure. Deaths are usually associated with eating large amounts of parts of the fish rich in the ciguatoxin, such as the head or viscera. Death is normally preceded by serious cardiovascular adverse effects, such as hypotension and bradycardia, as well as serious neurological adverse effects, such as convulsions, coma, brain damage, and evidence of neurological deficits, including ataxia, vertigo, changes in pupil size and rapid eye movements, agitation, delirium, outbursts, panic, pain in joints, paralysis, abnormal breathing patterns and pain response, cerebral edema, and hyperthermia. Respiratory failure and/or depression often occur in association with paralysis of the respiratory muscles (96269).
Renal: In case reports, ciguatoxin poisoning has been rarely associated with acute kidney injury (95315).
Psychiatric: Ciguatera poisoning has presented as a psychiatric disorder (43068). Symptoms caused by ciguatera poisoning include hallucinatory poisoning in 16% of the patients (43159). Nightmares, hallucinations, agitation, and anxiety have been reported in two families (42996). These symptoms lasted between 12 and 30 hours and resolved completely.
Ocular/Otic: Uncontrolled rapid eye movement has been reported in a case report of ciguatoxin poisoning in a 25-year old man (96265). Sore eyes with burning, with continued dry eye with surface irritation after at least one year, has been reported with ciguatoxin poisoning in a 47-year old woman. She was treated with ocular lubricants (96266). Ocular disturbances, such as pupil constriction and dilation and eye pain have also been reported rarely (42983,95322).
Toxicology
Ciguatoxins increase cell permeability to sodium through voltage-gated sodium channels, causing sustained depolarization and spontaneous firing of neurons (95316,95317,96266). Neuropathic pain occurs related to further upregulation of voltage-gated calcium channels and/or modulation of activity at the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor (95317).
Interactions with pharmaceuticals
None known.
Interactions with herbs & supplements
None known.
Interactions with foods
Ciguatoxins can cause ciguatera, a type of food poisoning. Case reports suggest that symptoms of ciguatera can return at a later time following consumption of alcohol. Patients recently diagnosed with ciguatera are advised to avoid alcohol for several months (43166,95315,95316,95321,96266,96267,96268).
Ciguatoxins can cause ciguatera, a type of food poisoning. Case reports suggest that symptoms of ciguatera can return at a later time following consumption of caffeine. Patients recently diagnosed with ciguatera are advised to be cautious about consuming coffee, tea, or chocolate, for several months (95315,96266,96267)
Ciguatoxins can cause ciguatera, a type of food poisoning. Case reports suggest that symptoms of ciguatera can return at a later time following consumption of non-contaminated fish. Patients recently diagnosed with ciguatera are advised to avoid fish for several months (43166,95315,95321,96266,96267).
Ciguatoxins can cause ciguatera, a type of food poisoning. Case reports suggest that symptoms of ciguatera can return at a later time following consumption of meat, such as chicken or pork (95315,95316).
Ciguatoxins can cause ciguatera, a type of food poisoning. Case reports suggest that symptoms of ciguatera can return at a later time following consumption of nuts. Patients recently diagnosed with ciguatera are advised to avoid nuts for several months (95315,95321,96266,96267).
Interactions with lab tests
None known.
Interactions with diseases
None known.
Mechanism of action
General: Ciguatoxins are toxins that accumulate in the flesh, head, and viscera of fish that eat the pretoxin from toxic dinoflagellates, especially those of the genus Gambierdiscus, or flesh and viscera of predatory fish farther up in the food chain (95319,96269). Bottom-feeding, coral-reef fish that live in reefs disturbed by cyclones or hurricanes are the most likely types to accumulate ciguatoxins (6). Fish contaminated with ciguatoxins appear normal, including smell and taste (6). Although commercial testing for ciguatoxin was available, production has been discontinued due to false negative tests (95320). Over 400 normally safe fish species may contain the ciguatoxin. The large predatory reef fish, such as moray eels, snappers, groupers, barracuda, jacks, surgeons, Spanish mackerel, and humphead wrasse are most likely to be contaminated (43004,43018,43053,95315,95319,95320,95323,96266,96269). Fish contaminated with ciguatoxins are most likely to be found in tropical and subtropical regions of the Pacific and Indian Oceans, and the Caribbean (96269). The Cook Island, Rarotonga, has the highest number of cases of ciguatoxin poisoning worldwide (95316).
Ciguatoxic effects: Ciguatoxins are a group of lipid-soluble and heat stable toxins. Because of their lipid-solubility they accumulate in organs of the affected fish (95319,96269). Pacific, Caribbean, and Indian ciguatoxins have been identified based on the body of water in which they are found. The Pacific ciguatoxins seem to be the most potent (42982,95316,95319). Ciguatoxins are made by biotransformation from gambiertoxins formed by dinoflagellates, mainly Gambierdiscus toxicus (96266).
The ciguatoxins increase cell permeability to sodium through voltage-gated sodium channels, causing sustained depolarization and spontaneous firing of neurons (95316,95317,96266). Neuropathic pain occurs related to further upregulation of voltage-gated calcium channels and/or modulation of activity at the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor (95317).
Pharmacokinetics
Absorption: There is insufficient reliable information available about the pharmacokinetics of ciguatoxin in humans. However, laboratory research in animals suggests that ciguatoxins are absorbed rapidly (95264).
Distribution: Ciguatoxins are lipid-soluble. Laboratory research in animals suggests that ciguatoxins are distributed throughout the body, including to organs such as the liver, muscle, and brain (95264).
References
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| 95323 | Klekamp BG, Bodager D, Matthews SD. Use of surveillance systems in detection of a ciguatera fish poisoning outbreak - Orange cCounty, Florida, 2014. MMWR Morb Mortal Wkly Rep. 2015;64(40):1142-4. View abstract. |
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| 96266 | Sheck L, Wilson GA. Dry eye following ciguatera fish poisoning. Clin Exp Ophthalmol. 2010;38(3):315-7. View abstract. |
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| 96269 | Chan TY. Characteristic features and contributory factors in fatal ciguatera fish poisoning--implications for prevention and public education. Am J Trop Med Hyg. 2016;94(4):704-9. View abstract. |
