Figure 1: Rhododendron ponticum – photo by Rasbak at: <Source> viewed September 2017.
By Sam Topalidis, 2017.
In the Black Sea region of Turkey, ‘mad honey’ is produced from the nectar of the Rhododendron ponticum or the Rhododendron luteum which contain grayanotoxin and is consumed as folk medicine. Poisoning due to its consumption has been known for over 2,400 years in Pontos, in north-east Anatolia. Today, people are still admitted to hospital with ‘mad honey’ poisoning, especially from the wider Black Sea region of Turkey. Symptoms include nausea, vomiting, dizziness, confusion, low blood pressure and low heart rate. More research is needed on ‘mad honey’ poisoning and its antioxidant qualities.
What is ‘Mad Honey’?
In the Black Sea region of Turkey, ‘mad honey’ is produced from the nectar of the purple flowering Rhododendron ponticum [named after its occurrence in Pontos] (Figure 1) or the yellow flowering Rhododendron luteum (Figure 2), both of which contain grayanotoxin (a group of toxins). This honey is consumed as folk medicine including as a perceived aphrodisiac. Today, people can still suffer mad honey poisoning, especially in Pontos and the wider Black Sea region. Some of the symptoms exhibited by people with this poisoning include nausea, vomiting, dizziness, confusion, low blood pressure and low heart rate (Demir Akca and Kahveci 2012). Pontic Greeks, who used to live in the Black Sea region of north-east Anatolia up until the early 20th century, knew mad honey as ‘zanton’ or ‘palalon’ (Harissis and Mavrofridis 2013). Today, local Turks call it ‘deli bal’ (Alan et al. 2010).
Mad honey is generally reddish-brown in colour, with its own sharp scent (Gunduz et al. 2011). Grayanotoxins do not pose a problem in commercially produced honey because the mass production of honey dilutes any possible toxic quantities (Gami and Dhakal 2017).
Rhododendrons and Their Toxins
Grayanotoxins are found in Rhododendron plants around the world, e.g. in China, Indonesia, Japan, Myanmar, Nepal, New Guinea, North America, Philippines, Tibet and Turkey. In Turkey, honey produced from these plants in spring is more toxic than that produced in other seasons and has a sharp and biting taste which irritates the throat. Of the cases of mad honey poisoning reported around the world, the original source of honey usually tracks back to the Black Sea region of Turkey or Nepal (Gami and Dhakal 2017).
Rhododendron luteum and Rhododendron ponticum dominate the understories of the forests of the Turkish Black Sea region. They dramatically reduce forest growth and regeneration and local plant diversity (Eşen et al. 2006). Sheep and goats which feed on their young shoots or flowers are poisoned (Alan et al. 2010). The level of grayanotoxin in these plants varies depending on whether it is raining or not when the plants are blooming in late spring. When rainfall is low, the grayanotoxin ratio is high and this increases the likelihood of honey poisoning (Tekinsoy et al. 2017).
In general, [relatively small] beekeepers along the Turkish Black Sea region sell their natural unprocessed honey in local and regional markets. This honey, which may contain grayanotoxin, is unregulated and there is no standard amount of grayanotoxin in one gram of honey (Demir et al. 2011). Sahin et al. (2015) identified that Grayanotoxin III (GTX III) in 10 mad honey samples varied across the Black Sea region but that they were also outstanding in terms of antioxidant activity. The threshold concentration for GTX III toxicity in humans is unknown and may vary from person to person (Note 1).
Figure 2: Rhododendron luteum <Source> viewed September 2017.
Some studies demonstrate that mad honey poisoning is common [in hospital presentations] in summer in the eastern Black Sea region of Turkey (Demir Akca and Kahveci 2012). However, transport of locally produced honey from Turkey or elsewhere, may result in cases in other countries (Jansen et al. 2012). It appears from a review of 84 published articles that the hospital cases of mad honey poisoning generally came from the Trabzon region (Silici and Atayoglu 2015).
Historical References to ‘Mad Honey’ in Pontos
Mad honey poisoning in humans was most probably first recorded to have occurred in 401 BC by some of Xenophon’s 10,000 Greek mercenaries south of modern Maçka, south of Trabzon in north-east Turkey. Xenophon wrote:
… the Greeks took up quarters in numerous villages, which contained provisions in abundance. Now for the most part there was nothing here which they really found strange; but the swarms of bees in the neighbourhood were numerous, and the soldiers who ate of the honey all went off their heads, and suffered from vomiting and diarrhoea, 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 third or fourth day they got up, as if from a drugging. (Xenophon, Book IV, Chapter 8.)
The next historical reference to mad honey poisoning was from Aristotle’s Minor Works. It is not the work of Aristotle but was produced from the Peripatetic School which he founded. The following description is sometimes referred to as from Pseudo-Aristotle.
At Trapezus [Trabzon] in Pontus honey from boxwood has a heavy scent; and they say that healthy men go mad, but that epileptics are cured by it immediately.
Another record of mad honey poisoning in Pontos was by the Pontic Greek historian and geographer Strabo (64–63 BC–ca. 25 AD) who identified the following episode which befell the Roman General Pompey who was fighting Mithradates VI in Pontos in 67 BC:
Now all these peoples who live in the mountains are utterly savage, but the Heptacometae are worse than the rest. Some also live in trees or turrets; and it was on this account that the ancients called them "Mosynoeci," the turrets being called ‘mosyni’. They live on the flesh of wild animals and on nuts; and they also attack wayfarers, leaping down upon them from their scaffolds. The Heptacometae cut down three maniples [around 1,500 soldiers] of Pompey's army when they were passing through the mountainous country; for they mixed bowls of the crazing honey which is yielded by the tree-twigs, and placed them in the roads, and then, when the soldiers drank the mixture and lost their senses, they attacked them and easily disposed of them. (Strabo, Book XII, Chapter 3, 18.) (Note 2.)
Pliny the Elder
The next historical record of mad honey poisoning in Pontos was by the Roman naturalist Pliny the Elder (23–79 AD). He wrote his Naturalis Historia between ca. 70–79 AD where he warned against consuming mad honey from the Black Sea coast of Anatolia.
At Heraclia in Pontus, the honey is extremely pernicious in certain years though it is the same bees that make it at other times. ...
There is a certain plant (Rhododendron Ponticum) which, from the circumstance that it proves fatal to beasts of burden, and to goats in particular, has obtained the name of ‘aegolethron’, (‘goats' death’) and the blossoms … contract most noxious properties. Hence it is that it is not every year that these dangerous results are experienced. ... Persons, when they have eaten of it, throw themselves on the ground to cool the body, which is bathed with a profuse perspiration. (Pliny the Elder, Book XXI, Chapter 44.)
In the country of the Sanni, in the same part of Pontus, there is another kind of honey, which, from the madness it produces, has received the name of ‘mænomenon’ (maddening). This evil effect is generally attributed to the flowers of the rhododendron, with which the woods there abound … (Pliny the Elder, Book XXI, Chapter 45.)
Why Is ‘Mad Honey’ Consumed in Turkey Today?
Mad honey is currently consumed in Turkey as folk medicine for treating bowel disorders, diabetes, gastric pains, high blood pressure and more commonly for its ‘perceived’ aphrodisiac effects (Gami and Dhakal 2017). It is also consumed for its nutritional value.
A small survey of beekeepers who produced mad honey from the northern slopes of the Pontic Mountains from the Trabzon province, reported that they believed the honey’s aphrodisiac properties as the main reason for its consumption in men aged from 41 to 60 years (Demircan et al. 2009). (Note 3.)
Silici and Atayoglu (2015) reviewed 84 published articles with 1,199 cases of mad honey poisoning from 1981 with 82% prepared by Turkish researchers. They determined it was more frequently reported in hospital in males (75%) and between the ages of 41 and 65 years. There were no cases of death reported. This literature review ‘appears’ to support the view that people who suffer from mad honey poisoning, which requires hospital attention, are middle-aged males who consume the honey as a perceived aphrodisiac.
To my surprise, mad honey produced from an area east of Trabzon, can be purchased over the Internet. The website (which will remain nameless) does provide a health warning.
Diagnosis and Treatment of Hospital Patients with ‘Mad Honey’ Intoxication
The most common clinical findings in patients after consuming mad honey is nausea, vomiting, dizziness, confusion and a feeling of fainting. Patients do not usually present to hospital when this occurs and treatment based on local custom is rest and the consumption of salty water or salted yogurt. These people usually recover within a few hours. Patients usually present to hospital with cardiovascular problems such as cardiac arrhythmia [abnormal heart rhythm] with sinus bradycardia [very low heart rates] being particularly common (Tatli 2017). Other symptoms include abnormally low blood pressure. The course and severity of clinical symptoms of mad honey poisoning depend on individual sensitivity to the toxin. Long-term consumption may result in a various degree of desensitization which prevents dramatic symptomatic presentation. Therefore mad honey poisoning symptoms may vary from person to person. The amount of honey needed for intoxication can be as low as 15–30 grams [15 grams is one teaspoon] and symptoms appear within 0.5 to 4 hours. The amount of mad honey needed to produce intoxication depends on the amount consumed and the concentration of grayanotoxins in the honey [which as we have noted varies depending on] the season in which it is produced (Gami and Dhakal 2017).
In hospitals, patients with mad honey poisoning are usually treated symptomatically. Mild hypotension (low blood pressure) and dizziness respond to normal saline infusion. Medicinal atropine is the preferred treatment for patients with very low heart rates and severe hypotension (Gami and Dhakal 2017). Hospital treatment ensures that most patients with mad honey poisoning recover vital signs within the first 24 hours. There is no consensus on how long these patients should be kept under observation in hospital (Tekinsoy et al. 2017).
The prognosis of mad honey poisoning is very good, although the presenting symptoms may seem life threatening. No case fatalities have been found in modern medical literature in Turkey. But there were some fatalities from the 1800s when the medication atropine and normal saline were not available (Gami and Dhakal 2017). However, fatalities have been reported in south-west China (Zhang et al. 2017). (Note 4.)
Mad honey poisoning in humans was most probably first recorded by the Greek General and historian Xenophon in 401 BC, south of Trabzon in Pontos in north-east Anatolia.
The consumption of mad honey, which contains grayanotoxin, continues today and represents a public health problem along the Black Sea coast of Turkey. Rhododendron species, the source of mad honey, are distributed across the Earth. Despite this, why nearly all the hospital reports [predominantly from middle-aged males] of mad honey poisoning originate from Turkey is puzzling (Gunduz et al. 2011).
In Turkey, mad honey intoxication should be considered in the diagnosis in emergency cases of people with very low heart rates and low blood pressure, particularly in middle-aged men (Demir Akca and Kahveci 2012). Mad honey poisoning most often occurs in the Black Sea region of Turkey; however, additional cases have been found worldwide due to consumption of exported Turkish or locally produced mad honey (Jansen et al. 2012). Mad honey intoxication and the honey’s antioxidant qualities need more research.
The principal toxic isomer of grayanotoxin in Rhododendron is Grayanotoxin III (GTX III) although others, GTX I and GTX II, are present in lesser amounts. GTX I is also toxic and GTX II is less toxic (Okuyan et al. 2010).
The translator of my copy of The Geography of Strabo into English (Horace L Jones) states that three maniples amounts to 600 soldiers, unless the Greek word should have been translated to ‘cohort’. I believe that it should have been translated into ‘cohort’ because by 67 BC, the cohort had replaced the maniple in the Roman army. Thus, three ‘cohorts’ would have been around 1,500 soldiers.
For the survey of 10 bee keepers, three age groups were defined: 21 to 40 year olds, 41 to 60 year olds and 61 to 80 year olds. The survey is limited by the selection bias of the beekeepers and the predetermined group of answers and thus may not be reliable (Demircan et al. 2009).
Fatal honey poisoning occurs in south-west China. In the study by Zhang et al. (2017) there were 31 patients diagnosed with honey poisoning (17 women and 14 men) with ages between 3 and 73 years. Eight of these patients died. It was believed that the poisoned honey was derived from the T. hypoglaucum plant (which is known to have poisonous nectar) from the genus Tripterygium wilfordii.
I wish to thank Mr Michael Bennett and Mr Russell McCaskie for their editorial comments.
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