The Honey Made Me Go Mad! POISONOUS HONEY, ITS HISTORICAL AND SOCIAL CONTEXTS, AND ITS TOXIC ORIGINS...

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The Honey Made Me Go Mad! POISONOUS HONEY, ITS HISTORICAL AND SOCIAL CONTEXTS, AND ITS TOXIC ORIGINS 1

Transcript of The Honey Made Me Go Mad! POISONOUS HONEY, ITS HISTORICAL AND SOCIAL CONTEXTS, AND ITS TOXIC ORIGINS...

The Honey Made Me Go Mad!

POISONOUS HONEY, ITS HISTORICAL AND SOCIAL CONTEXTS, AND ITS

TOXIC ORIGINS1

People the world over have eaten honey for millenia.

Some claim that honey has healing and medicinal powers, such as killing bacteria, alleviating arthritis, reducing allergies, lowering cholesterol, increasing virility and enhancing pleasure.

But some honey is toxic...

While some claims about medicinal qualities are shown to be true in scientific literature, others are pure folklore.

The folklore persists, with people seeking out toxic honey, believing that it will open their minds or improve their romantic relationships.

The Earliest Information…

When Xenophon’s Army Got Sick:The Account That Went Down in History3

Xenophon, a well known general of the Greek army of 5th century BCE, was one of the first people to record information about toxic honey.

In Anabasis, an account of his expeditions against the Persian Empire, he writes about his soldiers poisoned from honey during his retreat from Babylon in 401 BC.

They stopped to rest near an enchanting forest full of beehives. The soldiers took honey from the hives, ate it, and got terribly ill. Xenophon describes dizziness, vomiting, seizing, “drunkenness” and “madness.”

Folklore and CultureIn spite of Xenophon’s earliest account, people continue to talk about the supposed benefits of mad honey...

Around the Mediterranean, the Middle East, New Zealand and parts of Southeast Asia, the Black Sea region of Turkey, and in China and Tibet, among other places, “mad honey” is sometimes intentionally eaten because people mistakenly think that it: - Is a mind opening drug- Enhances sexual pleasure- Increases virility

The huge majority of cases of honey poisoning that reach scientific journals come from Turkey. But, remember – the way that honey becomes toxic is not endemic to Turkey. What seems to flourish in Turkey more than other places are specious rumors about “deli bal,” mad honey.

So, how does honey become toxic? Is it the bees?

Toxins travel. The toxin responsible for turning honey travels far before it is ingested.

Honey bees make honey from the pollen and nectar of flowering plants. The bees carry pollen and nectar all over their bodies back to the hive, where it gets into the honey.

It was discovered long ago that certain pollens contain a toxin, later named Grayanotoxin, that bees unwittingly transfer into the honey.

It’s not the bees. It’s a family of plants.

Hmm, those leaves look familiar… What kind of tree is this swarm hanging from???

Ericacea: A Large Family… Grayanotoxin is found on the leaves, and in the nectar and pollen of a very large family of plants called the Ericaceas. Ericacea are native not only to the Mediterranean and Black Sea regions of Europe and the Middle East, but to many regions of the world.

The most notable of the Ericacea are the many Rhododendron species, which include Azaleas. However, grayanotoxin has been found in other species belonging to the Ericacea family.

Because it has been found on leaves as well as flowers, there is some question as to whether only flowering plants carry grayanotoxin.

Here is one common taxonomical classification for this family of plants (I’ve come across more than one):

Plantae Embryophyta Magnoliopsida Ericales Ericaceae

So, where there are flowering Ericaceas, there may be toxic honey.

Grayanotoxin: Another Large Family• Scientific articles from the early and mid 20th century are characterized by a debate about how

many toxins from Rhododendron exist, and about their similarities and differences.

• Early terms referring to different grayanotoxins, which are still used today are: andromedotoxin; rhodotoxin; acetylandromedol and grayanol.

At present, these terms loosely refer to the same toxins…

• …Because, scientists now use a system of Roman numerals and subtypes to identify types of grayanotoxin. Examples:

Grayanotoxin III Subtype IIGrayanotoxin I Subtype V

• Over thirty types of grayanotoxin have been identified.

• Grayanotoxin is a neurotoxin and muscle cell toxin.

Grayanotoxin: A nerve and muscle cell toxin.

Grayanotoxin is a plant toxin that acts as a neurotoxin and muscle cell toxin. Its most noted mechanism of action is the depolarization of sodium (Na+) channels in the cell membrane.

Chemists call grayanotoxins3 diterpenes or diterpenoids. They are a group of organic molecules containing a long chain of about 20 Carbon atoms with branching methyl and hydroxyl groups.

Isoprene Terpene Diterpene/Diterpenoid

• Diterpenes are compounds made of Terpenes, molecules with the molecular structure C10H6.

• Terpenes are made of Isoprenes, a small molecule with structure C5H8.

Here are more pictures of grayanotoxin molecules, along with molecular structure of some similar lipid-soluble neurotoxins…4

grayanotoxin iii

grayanotoxin ix

As you can see, most grayanotoxin is fairly simple in structure.

Grayanotoxin keeps the Sodium ion channel in a permanent state of depolarization and activation, until the toxin clears from the body.

Most grayanotoxins bind to the Type 2 binding site of the ion channel.

When permanently activated, the channel can’t do its job of balancing ion concentration, and therefore electrical charge, across the cell. This has numerous effects throughout the body.

These are images of the voltage-gated Na+ channel…

The Absorption and Distribution of Grayanotoxin

All cases of honey poisoning or grayanotoxin poisoning in humans and animals are due to eating contaminated honey (in the case of humans,) or eating the leaves and flowers of Ericacea (in the case of goats, sheep, or wild boars, for example).

Grayanotoxin is absorbed in the gastrointestinal system of a host organism, and transferred to the blood, which carries it to target cell sites.

It is feasible that a very large amount of the toxin spread over the skin could lead to signs and symptoms of toxicity. But, reports of this are hard to come by.

Action and EffectsBy putting Na+ channels in the central nervous system in a permanent state of activation (depolarization), grayanotoxin has far reaching effects on the respiratory and cardiovascular systems.• Although it competes for ligands in muscle cells as well, the

toxin’s effects on respiratory and cardiac activity (the heart and lungs), originate in the nervous system.

• The biggest danger is a heart attack due to bradycardia. • Sinus bradycardia may also occur. • Unpleasant, but non-life-threatening effects include stinging

in the mouth and throat, salivation, blurry vision, nausea and vomiting.

• Other symptoms of toxic honey poisoning include dizziness, confusion and in rare cases, hallucinations.

How Is Grayanotoxin Metabolized?

• Grayanotoxin in processed by the 2 phases of biotransformation.

• As toxins go, grayanotoxin clears very rapidly from the body, from a couple hours to one day.

• Length of metabolism and severity and danger of toxicity depend on the size of the dose.

• Humans with honey poisoning have usually eaten from 5 to 30 grams of grayanotoxin.

Elimination: How can you flush it out more quickly?

• Fluids.

• Activated Charcoal. A very dry, porous form of carbon is sometimes administered for the first 24 hours. It is highly absorbent, and is meant to soak up fluids in the body containing the grayanotoxin.

• In extreme cases, pumping the stomach. Used when a patient isn’t vomiting on their own, or if they have ingested a very large quantity of toxin.

• Waiting. A lot of cases that present in the emergency room are not as serious as they feel. Doctors have sometimes chosen to treat very uncomfortable and upset patients with fluids and supervision alone!

Are There Ericacea in New Mexico?

Yes. This is a “Texas Madrone”.(just one kind of Ericacea)

Other species include: Texas Madrone Arbutus xalapensisArizona Madrone Arbutus arizonicaThe “strawberry tree” Arbutus marina

And NM gardeners sometimes grow Non-Native species in their gardens.

So, watch your honey, beekeepers!

Are you a beek? “What can I do as a beekeeper?”

1. Get to know fellow beekeepers in your state or region.

2. Familiarize yourself with the flowering, pollen- and nectar-generating plants in your environment – where do your bees fly?

3. If there are Ericaceas in your area, share honey! Sharing honey with other beekeepers dilutes the concentrations of toxin that may exist in a single batch.

Endnotes (Images)1. Azalea bush. http://www.flickr.com/photos/8002022@N05/37989406642. The Persian Army: The Return of the 10,000 Under Xenophon http://karenswhimsy.com/persian-

army.shtm3. http://texasento.net/bee-swarm.html4. The Persian Empire, 490 B.C. http://en.wikipedia.org/wiki/Xenophon5. http://www.sciencedirect.com/science/article/pii/S08986568020008526. Terpenes. http://www.nky-kk.co.jp/terpene.jpg7. Voltage-gated sodium channel. https://wikispaces.psu.edu/display/230/Membrane+Potential,

+Ion+Transport+and+Nerve+Impulse8. Texas Madrone. http://en.wikipedia.org/wiki/Arbutus_xalapensis9. Spoonful of Honey.http

://xeniagreekmuslimah.wordpress.com/2010/10/12/foods-mentioned-in-the-qur%E2%80%99an-the-amazing-honey/

10. Can’t Sleep? http://fiercegreymouse.blogspot.com/2012/01/insomnia-cant-sleep.html

References:1. Demircan A, Keles A, Bildik F, Aygencel G, Dogan N, Gomez H. Mad honey sex: therapeutic misadventures from an ancient biological

weapon. Toxicology. 2009; 54, 6: 824-29.2. Erturk, O, Karakas P, Pehlivan D, Nas N. The antibacterial and antifungal effects of rhododendron derived mad honey and extracts of four

rhododendron species. Turkish Journal of Biology. 2009; 33: 151-158.3. Gunduz, A, Merice E, Baydin A, Topbas M, Uzun H, Turedi S, Kalkan A. Does mad honey poisoning require hospital admission? American

Journal of Emergency Med. 2009; 27: 424-427.4. Gunduz A, Turedi S, Oksuz H. The honey, the poison, the weapon. Wilderness and environmental medicine. 2011; 22: 182-4.5. Gunduz A, Turedi S, Russell R, Ayaz F. Clinical review of grayanotoxin/mad honey poisoning past and present. Clinical Toxicology. 2008; 46:

437-442.6. Harborne J, Baxter H. Dictionary of Plant Toxins. West Sussex, England: John Wiley & Sons. 1996; p.183.7. Hogdson E, Mailman R, Chambers J. Dictionary of Toxicology. London, UK: Macmillan Reference Ltd. 2000: p. 231.8. Koca, I, Koca A. Poisoning by mad honey: a brief review. Food and Chemical Toxicology. 2007; 45: 1315-18.9. Michie D, Litterick A, Crews C. The influence of outdoor windrow composting on the concentration of grayantoxins in rhododendron leaves.

Compost Science and Utilization. 2011; 19, 1: 44-51.10. Moran N, Peter D, Perkins M, Richardson A. The pharmacological actions of andromedotoxin, an active principle from rhododendron

maximum. The Journal of Pharmacology and Experimental Therapeutics. 1954; 110: 415-432.11. Ott J. The delphic bee: bees and toxic honeys as pointers to psychoactive and other medicinal plants. Economic Botany. 1998; 52, 3: 260-

266.12. Popescu, R, Krupitza G, Kopp B. Novel insights into the mechanism of action of grayanotoxin III. Planta Medica. 2009; 75.13. Sayin M, Dogan S, Aydin M, Karabag T. Extreme QT interval prolongation caused by mad honey consumption. Canadian Journal of

Cardiology. 2011; 27: 870e17-e19.14. Scott, P, Coldwell B, Wiberg G. Grayanotoxins. Occurrence and analysis in honey and a cmparison of toxicities in mice. Toxicology. 1971; 9:

179-184.15. Sumerkan, M, Agirbasli M, Altundag E, Bulur S. Mad-honey intoxication confirmed by pollen analysis. Clinical Toxicology. 2011; 49: 872-873.16. Tadamasa T, Araho D, Osakabe K, Katai M, Narama I, Matsura T, Katawaka J, Tetsumi T, Sato M. Isolation of iso-grayanotoxin II from leaves of

leucothoe grayana max. it’s x-ray crystallographic analysis and acute toxicity in mice. Chemical Pharmacology Bullitin. 2000; 48, 1: 142-144.17. Wexler, P. Encyclopedia of Toxicology. San Diego, CA: Academic Press. 1998; p. 421.

Thank You! to the reference librarians at Zimmerman and Centennial libraries for helping me use all the tools available to me.

Yes, it’s true. Honey does have medicinal qualities. Its antibacterial and antifungal properties can soothe a sore throat or help heal a wound. Drink tea with honey.