Historic Accounts of Rhododendron and Azalea Poisoning
In William Watson's 1911 book, Rhododendrons and Azaleas, he has this account of Rhododendron and Azalea toxicity:
Note: Watson's book is considered the first treatise on Rhododendrons and Azaleas for gardeners. It was soon followed by Monograph of Azaleas, by Ernest Henry Wilson and Alfred Rehder (1921), Rhododendrons for Amateurs by E. H. M. Cox (1924), and Rhododendrons for Everyone by Frank Kingdon Ward (1926). In the 1921 book, Alfred Rehder writes:
In 1967, David Leach (author of Rhododendrons of the World) did extensive research on anecdotes in history about rhododendron poisoning and published it in the Brooklyn Botanic Garden Record, Vol. 21, No. 4:
From Alberta Government (http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/webdoc1376)
From University of Pennsylvania Veterinary School (http://cal.vet.upenn.edu/projects/poison/plants/ppazale.htm)
From Purdue University Veterinary School (http://www.vet.purdue.edu/toxic/plant10.htm)
From U S Food & Drug Administration Center for Food Safety & Applied Nutrition Food borne Pathogenic Microorganisms and Natural Toxins 1992 (Bad Bug Book)
Honey Intoxication (Food And Drug Information)
1. Name of Toxin: Grayanotoxin (formerly known as andromedotoxin, acetylandromedol, and rhodotoxin)
2. Name of Acute Disease: Honey Intoxication
Honey intoxication is caused by the consumption of honey produced from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The specific grayanotoxins vary with the plant species. These compounds are diterpenes, polyhydroxylated cyclic hydrocarbons that do not contain nitrogen. Other names associated with the disease are rhododendron poisoning, mad honey intoxication or grayanotoxin poisoning.
3. Nature of Disease: The intoxication is rarely fatal and generally lasts for no more than 24 hours. Generally the disease induces dizziness, weakness, excessive perspiration, nausea, and vomiting shortly after the toxic honey is ingested. Other symptoms that can occur are low blood pressure or shock, bradyarrhythima (slowness of the heart beat associated with an irregularity in the heart rhythm), sinus bradycardia (a slow sinus rhythm, with a heart rate less than 60), nodal rhythm (pertaining to a node, particularly the atrioventricular node), Wolff-Parkinson-White syndrome (anomalous atrioventricular excitation) and complete atrioventricular block.
4. Normal Course of the Disease: The grayanotoxins bind to sodium channels in cell membranes. The binding unit is the group II receptor site, localized on a region of the sodium channel that is involved in the voltage-dependent activation and inactivation. These compounds prevent inactivation; thus, excitable cells (nerve and muscle) are maintained in a state of depolarization, during which entry of calcium into the cells may be facilitated. This action is similar to that exerted by the alkaloids of veratrum and aconite. All of the observed responses of skeletal and heart muscles, nerves, and the central nervous system are related to the membrane effects.
Because the intoxication is rarely fatal and recovery generally occurs within 24 hours, intervention may not be required. Severe low blood pressure usually responds to the administration of fluids and correction of bradycardia; therapy with vasopressors (agents that stimulate contraction of the muscular tissue of the capillaries and arteries) is only rarely required. Sinus bradycardia and conduction defects usually respond to atropine therapy; however, in at least one instance the use of a temporary pacemaker was required.
5. Diagnosis of Human Illness: In humans, symptoms of poisoning occur after a dose-dependent latent period of a few minutes to two or more hours and include salivation, vomiting, and both circumoral (around or near the mouth) and extremity paresthesia (abnormal sensations). Pronounced low blood pressure and sinus bradycardia develop. In severe intoxication, loss of coordination and progressive muscular weakness result. Extrasystoles (a premature contraction of the heart that is independent of the normal rhythm and arises in response to an impulse in some part of the heart other than the sinoatrial node; called also premature beat) and ventricular tachycardia (an abnormally rapid ventricular rhythm with aberrant ventricular excitation, usually in excess of 150 per minute) with both atrioventricular and intraventricular conduction disturbances also may occur. Convulsions are reported occasionally.
6. Associated Foods: Grayanotoxin poisoning most commonly results from the ingestion of grayanotoxin-contaminated honey, although it may result from the ingestion of the leaves, flowers, and nectar of rhododendrons. Not all rhododendrons produce grayanotoxins. Rhododendron ponticum grows extensively on the mountains of the eastern Black Sea area of Turkey. This species has been associated with honey poisoning since 401 BC. A number of toxic species are native to the United States. Of particular importance are the western azalea (Rhododendron occidentale) found from Oregon to southern California, the California rosebay (Rhododendron macrophyllum) found from British Columbia to central California, and Rhododendron albiflorum found from British Columbia to Oregon and in Colorado. In the eastern half of the United States grayanotoxin-contaminated honey may be derived from other members of the botanical family Ericaceae, to which rhododendrons belong. Mountain laurel (Kalmia latifolia) and sheep laurel (Kalmia angustifolia) are probably the most important sources of the toxin.
7. Relative Frequency of Disease: Grayanotoxin poisoning in humans is rare. However, cases of honey intoxication should be anticipated everywhere. Some may be ascribed to an increase consumption of imported honey. Others may result from the ingestion of unprocessed honey with the increased desire of natural foods in the American diet.
8. Target Population: All people are believed to be susceptible to honey intoxication. The increased desire of the American public for natural (unprocessed) foods, may result in more cases of grayanotoxin poisoning. Individuals who obtain honey from farmers who may have only a few hives are at increased risk. The pooling of massive quantities of honey during commercial processing generally dilutes any toxic substance.
9. Analysis in Foods: The grayanotoxins can be isolated from the suspect commodity by typical extraction procedures for naturally occurring terpenes. The toxins are identified by thin layer chromatography.
10. Selected Outbreaks: Several cases of grayanotoxin poisonings in humans have been documented in the 1980s. These reports come from Turkey and Austria. The Austrian case resulted from the consumption of honey that was brought back from a visit to Turkey. From 1984 to 1986, 16 patients were treated for honey intoxication in Turkey. The symptoms started approximately 1 h after 50 g of honey was consumed. In an average of 24 h, all of the patients recovered. The case in Austria resulted in cardiac arrhythmia, that required a temporal pacemaker to prevent further decrease in heart rate. After a few hours, pacemaker simulation was no longer needed. The Austrian case shows that with increased travel throughout the world, the risk of grayanotoxin poisoning is possible outside the areas of Ericaceae-dominated vegetation, namely, Turkey, Japan, Brazil, United States, Nepal, and British Columbia. In 1983 several British veterinarians reported an incident of grayanotoxin poisoning in goats. One of the four animals died. Post-mortem examination showed grayanotoxin in the rumen contents.
Department of Cardiology, Division of Pacing and Electrophysiology, Institute of Cardiology, Istanbul University, Haseki-Fatih, Istanbul, Turkey and Department of Cardiology, Cerrahpasa School of Medicine, Istanbul University, Fatih, Istanbul, Turkey
In this study, two hospitals in Turkey evaluated the history of non-commercial honey intake in all patients referred to our institution for investigation of slow heart rate or atrioventricular (AV) conduction abnormalities. Between April 2008 and December 2008, 173 patients were referred to our institution for assessment of sinus bradycardia and various degrees of AV block and/or permanent pacemaker implantation. All patients were questioned about history of honey intake. Detailed evaluation revealed a history of daily honey intake for a long period of time in five of the patients (2.8%). This non-commercial honey was made by different amateur beekeepers in eastern Back Sea region of Turkey. Discontinuation of honey intake resulted in prompt normalization of conduction and significant symptomatic improvement. None of the patients were admitted to hospital and all were asymptomatic during 3 months follow-up. Holter monitoring for 24-h revealed no abnormality at first and third month.
Dr. Ugur Turk, from Central Hospital, Izmir, Turkey, reports on the cases of a 68 year old father and 27 year old son who were both admitted to the Izmir emergency department at the same time with symptoms of vomiting and dizziness. Surface ECGs revealed both patients to have complete atrioventricular block and atrial flutter with slow ventricular responses.
When a history was taken both father and son reported that their breakfasts over the past three mornings had included high amounts of honey from the Black sea region of Turkey. This information immediately triggered Turk and colleagues to consider that their patients could be suffering from ‘mad honey poisoning’.
Mad honey poisoning occurs after people consume honey contaminated with grayanotoxin, a chemical contained in nectar from the Rhododendron species ponticum and luteum. Grayanotoxin is a neurotoxin that binds to the sodium channels in the cell membrane, maintaining them in an open state and prolonging depolarisation.
Mad honey poisoning generally lasts no more than 24 hours, with symptoms of the mild form including dizziness, weakness, nausea, vomiting, excessive perspiration, hypersalivation and paraesthesia. Symptoms of the more severe form include syncope, seizures, complete atrioventricular block and even fatal tachyarrhythmias (due to oscillatory after potentials).
While no specific antidote exists for grayanotoxin poisoning mild cases can be treated with atropine and selective M2 muscarinic receptor antagonists; while for the more severe form treatment options include temporary pacemaker implantation, and vasopressor agents.
The possibility of honey poisoning, says Dr. Turk, should always be considered in previously healthy patients admitted with unexplained hypotension, bradycardia and other rhythm disturbances. The condition occurs most frequently in people who have consumed honey from the Black sea region of Turkey, a major bee keeping area that is also the native habitat of Rhododendron ponticum and luteum.
The symptoms of both father and son resolved without the need for any medications and they were discharged from hospital on the fourth day. When their honey was sent away for melissopalynology, (analysis of the pollen contained in honey) the result revealed it did indeed contain pollen from Rhododendron ponticum and luteum..
[U. Turk, E. Tuncer, E. Alioglu. Mad honey: so sweet pass out. FP 1297. Arrhythmias Poster Session. 25 June 2013. 14:00 local time.]
Hungry Children in Daehongdan Die from Eating Azalea Flowers
Children in North Korea died after eating azalea flowers in Daehongdan County. In Sambong Middle School, 9 students were dead from azalea poisoning. Adults know what to eat and what not, but young children can’t tell and just put anything in their mouths because they are hungry. After eating three or four potatoes, they are still hungry and they run up to the mountains and pluck anything to eat. This spring, they ate fistful of azalea petals several times and they died of poisoning. Chang Mi-oak says, ‘They pick basketful of azalea petals and eat them, but if they eat too much at one time, it causes gastrospasms. If they eat them when their stomach is empty, they will die foaming in their mouth. I suffered gastrospasms when I ate azalea. Adults like me cannot control hunger; it is needless to say in case of children.’
Lee Sung-ja says, ‘I warn my older child everyday. The older one would not do, but my younger one may eat flowers while I am not around. So whenever they go out together I admonish the older one, ‘don’t let your brother eat flowers’ several times. My older one tells me that many of his classmates die and asks me, ‘Mother, what can I do?’ It pains me greatly. Children who have no parents die so easily.’Return to Top
Rhododendron ponticum, the plant Sherlock mentions as being in Addlestone, can cause temporary paralysis—or at least it does in Guy Ritchie's Sherlock Holmes movie. In the 2009 film, Sherlock Holmes proposed that the villian Lord Blackwood used hydrated Rhododendorn ponticum as a way to arrange his own fake execution. Some of the symptoms of being dosed with the toxin can make you seem like you’re dead when you’re not and they used the toxin in the 2009 Sherlock Holmes movie for that exact purpose. “Here is a toxin refined from the nectar of Rhododendron ponticum. It’s quite infamous in the region of Turkey, bordering the Black Sea, for its ability to induce an apparently mortal paralysis. Enough to mislead a medical mind.” Sherlock also uses this poison on Gladstone (his dog) to illustrate his point.
It was also mentioned in the third episode of Season 2 of BBC's Sherlock (TV series), and has been speculated to have been a part of Sherlock's fake death scheme. During the search for the missing children, Sherlock identifies the vegetation sample from a footprint as belonging to the same plant that can induce a death-like sleep, reducing a hearbeat to almost nothing. It can also result in watery eyes which is observed in this episode and is very out of character for Holmes.
It’s not terribly poisonous, about 100 grams need to be ingested by a 25 kg child to seriously poison them, but it is a problem for livestock – particularly sheep, goats and cows – who munch on the flowers and get seriously sick. If you boil it down and concentrate the liquid… well that’s a different story. The toxin is water soluble, so it can be extracted from the leaves and flowers.
The toxin is called grayanotoxin. It binds to specific sodium ion channels in the victim's cell membranes and prevents inactivation, causing persistent activation of muscle and nerve cells. This causes a range of symptoms based on where the activated cells are located, such as muscle weakness, vomiting, sweating, salivation, seizures, and either dangerously slow or dangerously fast heartbeat, depending on the dose. In the end, it can cause death.
Honey from Rhododendron ponticum and Rhododendron luteum took out an army in 401 BC lead by Xenophon of Athens against Persia – hundreds of soldiers vomiting and unable to walk for a day. No-one died, unlike in 67 BC, where the army of Mithradates VI killed Pompey the Great’s soldiers while they were incapacitated. Pompey's soldiers consumed honey made from Rhododendron deliberately left behind by Pontic forces. It was biological warfare, defeat had never tasted sweeter.
Rhododendron poison, made a comeback after 2400 years on the big screen!
"That Why The Lady is a Tramp" by David G. Leach in the Journal of the American Rhododendron Society, October 1982, pp 151-2
David Leach reported on an incidence of rhododendron poisoning at Inverewe Gardens in Scotland:
Mr. Robert Hebb, Director of Horticulture of the Cary Arboretum, Millbrook, New York, was leading a group of American gardeners through the rhododendron collection at Inverewe Gardens in Scotland. When he stopped to photograph the salmon-pink flowers of 'Lady Chamberlain.', he jostled a branch and two drops of nectar fell on his finger. Preoccupied with his photography, he unthinkingly removed the sticky nectar by putting his finger in his mouth. Hebb knew almost immediately that he had created a serious problem. Within one or two minutes, the pleasantly sweet nectar produced a "pins and needles" tingling sensation in his fingers and toes, accompanied by numbness and lack of control in his limbs, such as when they "fall asleep."
Within five minutes, his coordination was so impaired that he had great difficulty walking to a nearby bench. He felt weighed down by an overwhelming depression. He had a suffocating foreboding of death. He was unable to speak intelligibly, but felt the need to hide his condition from his companions. The acute symptoms lasted 20 to 25 minutes. He then returned to the group, walking with difficulty. Speaking slowly, he was able to explain his pale and shaken appearance.
In another twenty minutes he became extremely thirsty and hungry. His mind cleared. In an hour and forty minutes after the incident, he became drowsy and a headache intensified. After sleeping for an hour, he awakened without symptoms of any kind.
Many of these are the classic symptoms of Grayanotoxin poisoning. It produces a narcotic action on the brain, difficult breathing, paralysis, convulsions, and ultimately respiratory failure. As little as 28 milligrams kills a rabbit in a few hours. Mr Hebb was lucky to recover without medical intervention. Not everyone is as fortunate.
From Purdue University (http://vet.purdue.edu/)
From Cornell Veterinary Medicine
Recipe #1 for Rhododendron Poisoning in Goats
Recipe #2 for Rhododendron Poisoning in Goats
Directory of Contents for Henning's Rhododendron & Azalea Pages
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