eMedicine Specialties > Emergency Medicine > Toxicology

Plant Poisoning, Hypoglycemics

Author: Jennifer Coles Schecter, MD, Staff Physician, Department of Emergency Medicine, Lahey Clinic, Burlington, MA
Coauthor(s): Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate, Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Nov 10, 2009

Introduction

Background

More than 270 plant species have been identified as having hypoglycemic potential. Many of these plants are used in developing countries in the treatment of diabetes. The most well known of these plants are listed below:

• Herb fenugreek (Trigonella foenum-graecum)
• Bitter melon gourd (Momordica charantia)
• Climbing ivy gourd (Coccinia indica)
• Mamijava (Enicostemma littorale)
• Asian ginseng (Panax ginseng)
• American ginseng (Panax quinquefolius)
• Siberian ginseng (Eleutherococcus senticosus)
• Ackee tree (Blighia sapida)
• Prickly pear (Opuntia robusta)
• Yellow bells (Tecoma stans [family Bignoniaceae])

Most of the plants studied have shown minimal-to-moderate effects on glucose regulation, with the exception of ackee fruit and bitter melon. Bitter melon produces hypoglycemia via steroidal saponins (charantin, insulinlike peptides, and alkaloids), but it has never been reported to result in fatality. This article focuses on the potentially fatal effects produced by ackee fruit ingestions. Ackee fruit causes profound hypoglycemia due to hypoglycin A, a toxic compound contained in the fruit. In addition, several references regarding other plants with hypoglycemic effects have been included.

Ackee fruit is produced biannually by the tropical evergreen tree, Blighia sapida. Although indigenous to West Africa, it is commonly found in the Caribbean islands, Central America, South America, and southern Florida. In South America, the fruit has been used to treat colds, fever, and diseases as varied as edema and epilepsy, though no clinical trials support these uses. In Jamaica, ackee fruit is a food staple, commonly prepared like scrambled eggs or boiled with fish. The fruit itself is 10 cm wide and weighs 100 g. It houses 3 glossy, black seeds contained within a straw- to red-colored husk and covered by a thick, oily appearing yellow aril. The outer aril is closed in unripe ackee fruit. Upon ripening, the aril spontaneously opens. Unripe fruit and the water used to cook it are toxic and cause Jamaican vomiting sickness when ingested.

Fatal epidemics of this illness have been well studied in Haiti, West Africa, and Jamaica. These epidemics tend to coincide with food shortages. The disease is characterized by profound hypoglycemia and intractable vomiting. Before widespread recognition of the hypoglycemia produced by this illness, the mortality rate approached 80%.

Pathophysiology

Two water-soluble toxins are present in unripe ackee fruit, hypoglycin A and hypoglycin B. Hypoglycin A is L-alpha-amino-beta-[methylene cyclopropyl]propionic acid. Hypoglycin A is found in both the aril and the seeds of the unripe fruit. Hypoglycin B is a gamma-L-glutamyl derivative of hypoglycin A and is found only in the seeds of the fruit.

Hypoglycin A is metabolized by transamination and oxidative decarboxylation to form methylenecyclopropylacetic acid (MCPA). MCPA then forms nonmetabolizable carnitine and coenzyme A (CoA) esters, rendering them unavailable for other metabolic reactions. Hypoglycemia results because CoA and carnitine are required for long-chain fatty acid oxidation, and oxidation is required for gluconeogenesis. Thus, hypoglycemia results from an inability to perform gluconeogenesis. This inhibition of fatty acid metabolism also results in the accumulation of unusual dicarboxylic acids that are subsequently excreted in the urine such as 2-ethyl malonate, 2-methyl succinate, glutarate, and adipate.

Additionally, MCPA inhibits acyl-CoA dehydrogenases. Inhibition of butyryl CoA dehydrogenase stops the oxidation of long-chain fatty acids at the level of hexanoyl CoA and butyryl CoA, causing decreased production of nicotinamide adenine dinucleotide (NADH) and acetyl CoA. Their lowered concentration further inhibits gluconeogenesis. Hypoglycin A does not affect insulin release or serum insulin levels in animal models.

It is postulated that increased concentrations of glutaric acid may have an inhibitory effect on glutamic acid decarboxylase, causing a decrease in GABA production and an increase in concentration of glutamate. This mechanism can explain the proconvulsive effect of hypoglycin A.

Frequency

United States

The true incidence of ackee poisoning is unknown. Ackee fruit sales are illegal in the United States, likely leading to underreporting. Cases have been reported after consumption of fruit illegally shipped or transported by travelers. Several isolated, nonfatal cases have been reported in Ohio, Connecticut, and New York.

Though shipment of ackee fruit into the United States is still banned, the Food and Drug Administration (FDA) is considering modifying this ban. Research by Whitaker et al has led to evaluation of sampling plans to detect hypoglycin A in ackee fruit. This research will help the FDA to develop a cost-effective monitoring program to reduce lots of misclassified product and to increase consumer safety.^1,2

International

• Jamaica: Although endemic to Jamaica, the epidemiology of ackee poisoning is not well characterized. The true incidence is likely underreported. Incidence has been estimated at 2 cases per 100,000 annually for persons younger than 15 years and 0.4 case per 100,000 persons annually for those older than 15 years.³
• West Africa: Based on recent epidemics, the incidence in children aged 2-6 years is estimated to be about 40 cases per 100,000 population.
• Other: Most cases occur in developing nations in Africa and the Caribbean. Incidence rates in other areas have not been well studied.

Mortality/Morbidity

Ackee poisoning has killed an estimated 5,000 people since 1886. Children are more likely than adults to experience fatal complications of ackee poisoning. The most well-studied epidemics have been in Haiti, Jamaica, and West Africa.

• Jamaica: Large-scale poisonings reach epidemic proportions typically during the winter months. Between January 1989 and July 1991, 28 patients reported symptoms of ackee poisoning. Six of 28 patients died. The most common symptoms were vomiting, coma, and seizures. Seven of the patients had confirmed hypoglycemia. Most of the cases occurred between January and March.³
• West Africa: In 1998, in Burkina Faso, an epidemic of fatal encephalopathy was linked to ackee poisoning. Between January and May of 1998, 29 children aged 2-6 years died. The clinical presentation was similar to that of Jamaican vomiting sickness and toxic hypoglycemic syndrome; the most common symptoms included hypotonia, convulsions, and coma.⁴
• Haiti: From November 2000 to March 2001, 60 cases with symptoms consistent of ackee poisoning (ie, continuous vomiting, abdominal pain, loss of consciousness, convulsions within 24 h) were recorded in 2 districts of Haiti's Northern Province. Retrospective analysis confirmed 31 of the 80 cases were related to consumption of ackee fruit. The mean age of the victims ranged from 6 months to 88 years, with a median of 7 and an average of 16. The case-fatality rate was 52%.⁵

Race

Reported cases in Africa, Jamaica, and Haiti occurred in blacks.

Sex

In reported cases, no difference in sex distribution was noted.

Age

Poisoning is more common in persons younger than 15 years, and severe poisoning is more common in the pediatric population.

Clinical

History

• Typically, ackee fruit poisoning causes epidemics, with multiple children becoming ill.
• The patient may provide a history of ingesting unripe ackee fruit or water in which unripe ackee had been cooked. More than one family member may be ill.
• Sudden onset of vomiting begins 2-6 hours after ingestion with generalized epigastric discomfort. However, symptoms may appear within minutes.
• After a period of prostration lasting up to 18 hours, a second bout of vomiting may occur. 
• Unless treatment is given, this episode can progress to seizures, coma, and death.
• In severe poisoning, death usually occurs within 12 hours after ingestion.

Physical

• Nausea and vomiting occur in 75% of patients; severe vomiting may be followed by a quiescent phase, followed by recurrent vomiting.
• Diaphoresis and pallor may be observed.
• Tachypnea, tachycardia, and hypotension due to dehydration may be noted.
• Weakness and paresthesias may be present.
• Seizures, generalized tonic clonic, occur in 24% of patients.
• Drowsiness and coma occurs in 25% of patients.
• Death in severe, untreated cases can reach 80%.

Causes

• Causes include ingestion of unripe ackee fruit, canned ackee fruit, ackee fruit that has been forcibly opened or water in which unripe ackee fruit has been cooked.

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