Histamine Toxicity from Fish

Updated: Oct 05, 2021
  • Author: Alexei Birkun, III, MD, PhD; Chief Editor: Timothy E Corden, MD  more...
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Practice Essentials

Histamine fish poisoning results from the consumption of inadequately preserved and improperly refrigerated fish. [1] It resembles an allergic reaction but is actually caused by bacterially-generated toxins in the fish's tissues. [2]

Previous terms for histamine fish poisoning were scombroid fish poisoning, pseudoallergic fish poisoning, histamine overdose, or mahi-mahi flush. The term scombroid was used because the first fish species implicated in this poisoning were from the suborder Scombridae, which includes mackerel, tuna, marlin, swordfish, albacore, bonito, skipjack, and almost 100 other species. The term histamine fish poisoning is now considered more appropriate because many cases are from nonscombroid fish. Examples include mahi-mahi (dolphin fish), amberjack, herring, sardine, anchovy, and bluefish. [3]

Symptoms of histamine fish poisoning resemble an acute allergic reaction and usually appear 10–60 minutes after eating contaminated fish. Typical manifestations of histamine fish poisoning include skin flushing on the upper half of the body, rash (see the image below), gastrointestinal (GI) complaints, and throbbing headache. [4]  (See Presentation.) Generally, the diagnosis is made on clinical grounds; no laboratory tests are necessary. If confirmation is required, histamine levels in uneaten portions of the suspect fish can be measured. In addition, elevated histamine levels can be measured in patients’ urine. [4, 5] (See Workup.)

An example of a typical histamine toxicity rash, i An example of a typical histamine toxicity rash, in this case from tuna. Image courtesy of Amanda Oakley, MBChB, FRACP.

See 5 Cases of Food Poisoning: Can You Identify the Pathogen?, a Critical Images slideshow, to help identify various pathogens and symptoms related to foodborne disease.

Without treatment, histamine fish poisoning resolves within 12 to 48 hours with no long-term sequelae. Even severe cases improve rapidly within one to three hours from initiation of antihistamines. [1, 6]  In severe cases, patients may require treatment for bronchospasm or hypotension. (See Treatment and Medication.)



Histamine poisoning directly relates to improper preservation and inadequate refrigeration. Histidine decarboxylase (HDC), found in Escherichia coli, Morganella morganii, and in Proteus and Klebsiella species, converts histidine, present in fish tissue, to histamine. Without adequate cooling, these bacteria multiply, increasing the histidine-to-histamine conversion rate and raising histamine levels. In fish left at room temperature, the histamine concentration rapidly increases, reaching toxic concentrations within 12 hours.

In healthy fish, histamine is normally present at levels less than 0.1 mg per 100 g. In contrast, samples of fish that produce poisoning contain histamine levels of at least 20-50 mg per 100 g of fish. [7, 8]

A second agent in fish tissues has been theorized to play a role in histamine toxicity because attempts to recreate the symptoms by orally feeding people histamine have failed. This may be because pure histamine is poorly absorbed in the GI tract, and the liver and intestinal mucosa can deactivate histamines.

This putative second causative agent, possibly saurine (histamine hydrochloride), may enhance the activity of histamine, facilitate its absorption, or prevent its inactivation by histamine N- methyltransferase or diamine oxidase. Other postulated second agents are cadaverine or putrescine. [9, 10]



The fish species most commonly implicated in histamine toxicity are scombroid dark-meat fish (eg, tuna, mackerel, skipjack, bonito, marlin) and nonscombroid species, such as mahi-mahi (dolphinfish), amberjack, sardine, yellowtail, herring, and bluefish. [3, 4] Although rare, cases involving whitefish also have been reported. [11]

Toxin production occurs when inadequate refrigeration after the catch allows the multiplication of bacteria that contain histidine decarboxylase, which converts amino acid histidine in the fish tissues to histamine. Histidine decarboxylase can continue to produce histamine in the fish even if the bacteria are inactivated; in addition, the enzyme remains stable while frozen and may be reactivated very rapidly after thawing. [12] Subsequent cooking, smoking, or canning of the fish does not eliminate the histamine, so both raw and cooked fish may cause symptoms.

Affected fish do not have a distinctive appearance or odor. After preparation, the fish may look honeycombed. Taste is a relatively insensitive measure of toxicity, since the lowest levels of histamine sufficient to cause symptoms cannot be tasted. Occasionally, fish with higher histamine concentrations may have a pungent, peppery taste.

Bacterial proliferation (and thus, histamine production) occurs unevenly in the fish, depending partly on temperature discrepancies. For example, tissue closer to the surface of a previously frozen mass of fish will thaw sooner and may contain more histamine.

The degree of symptoms in individuals consuming the same meal may be quite variable. Magnitude of symptoms may be related to the following:

  • Individual differences in sensitivity to or metabolism of histamine (eg, symptoms may be markedly worse in persons taking isoniazid because of blockade of GI tract histaminase)
  • Size of the portion consumed
  • The amount of histamine in the consumed portion
  • Whether the portion was from the same fish
  • The amount and type of other foods consumed along with the fish


The fish species most commonly implicated in histamine toxicity live in temperate or tropical waters, making populations on adjacent land areas more likely to experience outbreaks. Nevertheless, histamine fish toxicity is worldwide in scope, affecting people of all races, both sexes, and all ages.

According to the 2019 Annual Report of the American Association of Poison Control Center National Poison Data System (AAPC-NPDS), 122 single exposures to histamine toxicity were reported. [13]

Histamine toxicity from fish makes up 3% of food-borne disease outbreaks reported to the CDC, but is likely highly underreported. During 2009-2015, 85 outbreaks of confirmed histamine fish poisoning involving 250 illnesses were reported to the CDC, with one hospitalizaiton and no deaths. [14]

In 2019, 51 cases of histamine toxicity in 11 states were traced by the US Food and Drug Administration (FDA) to yellowfin/Ahi tuna imported from two suppliers in Viet Nam. [15]



Patients with histamine fish toxicity have a good prognosis. Improvement is usually rapid and sequelae are rare. The clinical course may be prolonged and of greater severity in patients with a history of atopy. In 2019, the AAPCC-NPDS reported 40 minor outcomes, 24 moderate outcomes, 2 major outcomes, and no deaths. [13]

Reported complications include severe bronchospasm, angioedema, hypotension, pulmonary edema, and cardiogenic shock. Patients with comorbid illnesses such as coronary artery disease are at risk for acute coronary syndromes caused by the tachycardia and hypotension associated with severe cases. Rarely, fatalities have been reported. [16]


Patient Education

Patients should be informed that their illness was caused by toxins in the fish they consumed, and be reassured that the episode did not result from allergy to fish. The clinician should explain that histamine toxicity results from bacterial proliferation in inadequately refrigerated fish and advise patients on proper handling to prevent toxicity in fish prepared at home.

Patients should be advised that in most cases, histamine does not impart a distinctive appearance or odor to affected fish. However, patients should not continue eating a fish if they note an unusual peppery, bitter taste.