Ackee Fruit Toxicity

The ackee tree is indigenous to West Africa, where it is called ankye or ishin. Thomas Clarke, Jamaica's first botanist, introduced the plant to the island in 1778, after obtaining the seeds from a West African slave ship. However, the ackee tree, Blighia sapida, was named after the infamous Captain William Bligh, who took the fruit from Jamaica to the Royal Botanic Gardens in England. The tree also grows in other West Indian Islands such as Cuba, Haiti and Barbados, in Central America, and in Southern Florida. ^[4]

An association between ackee poisoning and Jamaican vomiting sickness was first noted in 1875 and documented in 1904. In 1937, Jordan and Burrows found a water-soluble toxic material in the seed and pods of the ackee fruit. In 1954, Hassal et al were the first to isolate two toxic compounds in their crystalline form. These compounds were called hypoglycin A and hypoglycin B because of their hypoglycemic activity.

Two toxic water-soluble substances can be extracted from the fruit. The first toxin, hypoglycin A, is L-α -amino-β -[methylene cyclopropyl]propionic acid. Hypoglycin B is a γ -L-glutamyl derivative of hypoglycin A and is less toxic than hypoglycin A. Hypoglycin A, but not hypoglycin B, can be found in the aril of the fruit. The unripe fruit has a much higher concentration of hypoglycin A (approximately 20 times) than that of the ripe aril. Both components are found in the seeds. Therefore, the seeds and the membrane at the base of the seed mantle are always poisonous.

Hypoglycin A, which is now simply called hypoglycin, is metabolized by means of transamination and oxidative decarboxylation to methylene cyclopropyl acetic acid (MCPA). MCPA forms nonmetabolizable carnitine and coenzyme A (CoA) esters, thereby depressing tissue levels of these cofactors and making them less available for other biochemical reactions. Hypoglycemia results because both CoA and carnitine are necessary cofactors for long-chain fatty acid oxidation and because oxidation is a requisite for active gluconeogenesis. MCPA also inhibits the dehydrogenation of several acyl-CoA dehydrogenases, including butyryl CoA, glutaryl CoA, and isovaleryl CoA. As a result of the inhibition of butyryl CoA dehydrogenase, the oxidation of long-chain fatty acids stops at the level of hexanoyl CoA and butyryl CoA. This effect leads to the decreased production of nicotinamide adenine dinucleotide (NADH) and acetyl CoA.

Because NADH and acetyl CoA are required as a cofactor of 3-phosphoglyceraldehyde phosphate dehydrogenase and as an activator of pyruvate carboxylase, respectively, their diminished concentration contributes to the inhibition of gluconeogenesis. The inhibition of glutaryl CoA dehydrogenase results in the accumulation of glutaryl CoA, which could inhibit transmitochondrial malate transport, a rate-limiting step in the early phase of gluconeogenesis, and consequently suppress gluconeogenesis. Altered levels of circulating insulin do not cause hypoglycemia associated with hypoglycin action.

Potential risk behaviors for ackee poisoning include consumption of unripe fruit or ackee that has been forcibly opened and reuse of the water in which an unripe ackee has been cooked. 

Undernutrition is also thought to be associated with individualized susceptibility to Jamaican vomiting sickness and the severity of the disease.  Even at the lower levels of hypoglycin found in the arils, daily ingestion can produce a cumulative and delayed hypoglycemic effect that can be lethal in starving children. ^[5]

The epidemiology of ackee poisoning has not been well characterized, and the true incidence and mortality rate are believed to be underreported.  The FDA regulates the importation of ackee fruit to the United States, allowing only up to 100 ppm of hypoglycin A content in cans of ackee fruit ^[6] ; to date, 2 cases of ackee poisoning have been reported in the United States. The first was in Ohio in a Jamaican woman who presented with Jamaican vomiting sickness after a meal of ackee fruit. ^[7] The second was in Connecticut in a young Jamaican man who presented with cholestatic jaundice secondary to the chronic ingestion of ackee fruit. ^[8]

Since 1976, over 500 poisonings have been linked to ackee fruit in Jamaica and other countries. ^[9]  In late 2000, the CDC provided technical support to the Ministry of Health in Haiti during an outbreak of ackee poisoning in the northern region of that country. ^{[10, 11]}  More than 100 cases of acute illness and death were reported.

From 1998-2001, reports detailed 16 deaths of children in Surinam along the River Maroni, which separates Surinam and French Guyana. The deaths were subsequently linked to ackee fruit poisoning as result of the misuse of the plant by Maroon witch doctors to "cure" some pathologies especially acute forms of diarrhea in children. ^[9]  In 2015, ackee fruit poisoning was reported in 8 Nigerian siblings resulting in one death. ^[12]

Ackee is consumed mostly in West Africa and Jamaica; therefore, most cases have occurred in blacks. No difference in the sex distribution is noted. In Jamaica, the annual rate of ackee poisoning is 2 cases per 100,000 persons younger than 15 years and 0.4 case per 100,000 persons older than 15 years.

Before treatments were developed, the mortality rate was as high as 80%. With treatment most patients make a full recovery. If untreated, disease progression includes profound hypoglycemia, acidosis, hypovolemia, seizures, coma, and death. The onset of hypoglycemia is delayed for a few hours, but once present rapidly progresses. Deaths have been reported within 12 to 48 hours. ^[3]  

Patients should be educated about the danger of eating unripe or forcibly opened ackee fruit. Instruct patients to discard the water in which the fruit was prepared. Inform patients about the symptoms and signs of ackee fruit poisoning and the importance of immediately seeking medical attention.