View Full Version : Grayanotoxin Poisoning - Honey

06-04-2014, 12:25 PM
Some may find this thread recently posted on ProMed to be of interest.

Published Date: 2014-06-02 13:21:07
Subject: PRO> Grayanotoxin poisoning, honey - China (02): (HK) New Zealand, clarification
Archive Number: 20140602.2513242

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Date: Wed 28 May 2014
From: Alan Julian <alan@nzvp.co.nz> [edited]

[re: ProMED-mail Grayanotoxin poisoning, honey - China: (Hong Kong) susp 20140527.2499989]
This item on grayanotoxin states, "travelers to areas such as the Black Sea region of Turkey, North America, Korea, Japan, Nepal, and New Zealand should pay special attention as there have been reported cases of grayanotoxin poisoning which were attributed to honey from these areas."

The toxin most commonly associated with honey in New Zealand is derived from plants of the _Coriaria_ spp (commonly called tutu). "Both tutin and hyenachin, a hydroxytutin have been isolated from poisonous honey; the latter is not present in tutu but in the honeydew on the tutu leaves. The honeydew is excreted on to the tutu leaves by the naturalized passion vine hopper, _Scolypopa australis_. Bees feed on the latter when normal nectar sources are scarce." Veterinary Clinical Toxicology 3rd ed. 2006. p344. Parton K, Bruere AN, Chambers JP.

There are restrictions on harvesting honey from areas with large numbers of tutu plants during the at risk periods.

Alan Julian BVSc. DACVP
Veterinary Pathologist
New Zealand Veterinary Pathology
New Zealand

[We appreciate Dr Julian's update regarding the warning that included New Zealand. - Mod.TG]

See Also
Grayanotoxin poisoning, honey - China: (Hong Kong) susp 20140527.2499989
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Published Date: 2014-05-27 18:46:28
Subject: PRO/AH/EDR> Grayanotoxin poisoning, honey - China: (Hong Kong) susp
Archive Number: 20140527.2499989

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A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Sun 25 May 2014
Source: Hong Kong Information Services [edited]

The Centre for Health Protection (CHP) of the Department of Health is today [25 May 2014] investigating a case of suspected mad honey poisoning, and hence urged members of the public to buy honey from a reliable source or apiary.

The patient is a 49-year-old woman who developed dizziness, abdominal pain, nausea and transient loss of consciousness yesterday [24 May 2014] about one hour after consuming honey at home. She was subsequently admitted to the Intensive Care Unit of Hong Kong Adventist Hospital for further management. She is currently in stable condition.

Her clinical diagnosis is suspected grayanotoxin poisoning.

Initial enquiries by the CHP revealed that the honey was brought from Nepal by the patient. Two food collaterals have remained asymptomatic so far. The CHP's investigations are proceeding.

"Mad honey poisoning is caused by ingestion of honey containing grayanotoxins derived from plants belonging to the _Ericaceae_ family, including rhododendrons. Grayanotoxins are neurotoxins which can affect nerves and muscles. Symptoms of poisoning include nausea, vomiting, diarrhoea, dizziness, weakness, excessive perspiration, hypersalivation and paresthesia shortly after ingestion. In severe cases, hypotension, bradycardia, or shock may occur," a CHP spokesman explained.

Members of the public are reminded to take heed of the following preventive advice:
- buy honey from a reliable source or apiary;
- discard honey with bitter or astringent taste as grayanotoxin-containing honey may cause a burning sensation in the throat;
- seek more information on the types of flowers used to produce the honey whenever possible; and
- travelers to areas such as the Black Sea region of Turkey, North America, Korea, Japan, Nepal, and New Zealand should pay special attention as there have been reported cases of grayanotoxin poisoning which were attributed to honey from these areas.

Communicated by:
ProMED-mail Rapporteur Mary Marshall

[Grayanotoxin in honey, now referred to as "mad honey" has been known for centuries.

Grayanotoxin containing honey, called "mad honey", can cause dramatic effects when ingested as has already been recorded by the Greek warrior-writer Xenophon in 401 BC in his Anabasis "... but the swarms of bees in the neighborhood were numerous, and the soldiers who ate of the honey all went off their heads, and suffered from vomiting and diarrhea, and not one of them could stand up, but those who had eaten a little were like people exceedingly drunk, while those who had eaten a great deal seemed like crazy, or even, in some cases, dying men. So they lay there in great numbers as though the army had suffered a defeat, and great despondency prevailed. On the next day, however, no one had died, and at approximately the same hour as they had eaten the honey they began to come to their senses; and on the 3rd or 4th day they got up, as if from a drugging."

Grayanotoxins, also known as andromedotoxin, acetylandromedol, or rhodotoxin, can be derived from the leaves, twigs, or flowers of plants belonging to genera of the _Ericaceae_ (heath) family [3-7], comprising among others the _Rhododendron_, _Pieris_, _Agarista_, and _Kalmia_ genera. The toxin is also present in a number of products originating from the family members, such as honey, labrador tea, cigarettes, and a variety of decoctions used in alternative medicine [5, 8]. Its chemical structure has been fully elucidated as a diterpene, a polyhydroxylated cyclic hydrocarbon with a 5/7/6/5 ring structure that does not contain nitrogen [9]. More than 25 grayanotoxin isoforms have been isolated from _Rhododendron_ [10]. 3 members of the large grayanotoxin family have been demonstrated to be of particular relevance in the reported clinical cases [11]. Grayanotoxin 1 and 2 have been found in the honey, leaves, and flowers of _R. ponticum_ and _R. flavum_ as reported in multiple case reports in the eastern Black Sea area [3, 5, 12]. Grayanotoxin 1, present in _R. simsii_, has been reported from a case in Hong Kong [8], while in the honey from Grouse Mountain, British Columbia, Canada, which causes a similar type of poisoning, only grayanotoxins 2 and 3 were found [12]. Currently, grayanotoxin 1 and 3 are thought to be the principal toxic isomers [4, 11-13].

A number of clinical signs have been associated with mad honey disease [3, 4]. Most often hypotension, cardiac rhythm disorders (1st, 2nd, and 3rd degree AV block, asystole, and sinus bradycardia), nausea and/or vomiting, sweating, dizziness, and impaired consciousness have been observed. More rarely, syncope, blurred vision or diplopia, and salivation have been described. In some rare cases, convulsion [24], atrial fibrillation [25], asystole, and myocardial infarction were observed [19, 26, 27]. Symptoms occur most often within 20 min to 3 h after ingestion and remain for 1-2 days. In severe cases presented at the emergency room, treatment most often consists of atropine (0.5 mg once, or twice in case of non-response with respect to blood pressure and heart rate; 2 mg once) and saline (100 mL/h) [19, 27]. The main symptoms are believed to be caused by continued sodium channel activation, cell depolarisation and hence stimulation of the vagal nervous system. Whether grayanotoxin also acts directly on cardiomyocytes via sodium channel interference still has to be determined. While a number of cases of mad honey ingestion are believed to be accidental, deliberate intoxication may originate from the general belief that mad honey can act as an aphrodisiac, or as a treatment for gastritis and peptic ulcers, weakness, arthritis, diabetes or hypertension [28, 29]. It is speculated that such therapeutic intake may form the basis of chronic mad honey intoxication syndrome that is characterized by sinus bradycardia, 1st and 2nd degree AV block, dizziness, and presyncope [21].

Portions of this comment were extracted from
Jansen SA, Kleerekooper I, Hofman ZL, et al: Grayanotoxin poisoning: 'mad honey disease' and beyond. Cardiovasc Toxicol. 2012 Sep; 12(3): 208-15. doi: 10.1007/s12012-012-9162-2. The full article and references are available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404272/.
- Mod.TG

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06-04-2014, 12:30 PM
aw jeez. WOnderful.