1. Mad Honey Poisoning Anastacia Griego May 4, 2007

2. Overview  We will look at the source of mad honey poisoning as well as the involved toxin’s mechanism of action and the signs and symptoms of this condition

3. Source  Mad Honey Poisoning, also known as “Honey Intoxication” is caused by consuming honey containing the neurotoxic substance called grayanotoxin

4. Source  Grayanotoxin is found in some species of the Rhododendron, most notably Rhododendron ponticum, which is native to Turkey

5. Sources  In the United States, there are several plants related to the rhododendron which also produce grayanotoxins. These plants include 2 :  Rhododendron occidentale (western azalea)  Rhododendron macrophyllum (California rosebay)  Rhododendron albiflorum

6. Origin  Bees gather the grayanotoxin containing pollen and nectar from the rhododendron  Toxin is retained in the honey produced from the poisonous flower products

7. Toxin  There are three main types of grayanotoxin, the least toxic of these is grayanotoxin I with an LD 50 of 4 mg/kg.

8. Toxin  The LD 50 for grayanotoxin II is 1.3 mg/kg in mice  Most toxic honeys only contain 0.1 only contain 0.1 to 0.5 mg/mL to 0.5 mg/mL Note to self: Those injections are not for my benefit…

9. Toxin  There are only a few cases of mad honey poisoning reported each year. Usually from eating tainted honey from Turkey  Mad honey has been used as an alternative therapy for some conditions including gastrointestinal diseases and some poisonings have been linked to this usage 1

10. Toxin  Although the incidence of grayanotoxin poisoning is rare, there is concern that the number of cases per year will rise with the increasing demand for organic products

11. Mechanism  Grayanotoxin targets the nervous system, specifically the gated sodium ion channels which are involved in the initiation and propagation of action potentials across the plasma membrane of the nerve cell.

12. Mechanism  Grayanotoxins bind Na+ channels in nerve cells. Gated Na+ channels bound to grayanotoxin can be stimulated to open at membrane potentials lower than those that trigger opening of normal Na+ channels 2

13. Mechanism  Grayanotoxin is also able to inhibit closing of the Na+ channel once it is open 3  The end result is hyper-stimulation of the nerve cell

14. Signs and Symptoms  Signs and symptoms of grayanotoxin poisoning rarely last more than 24 hours and are usually not fatal 2  Most symptoms are mild and resolve themselves without medical intervention

15. Signs and Symptoms  Some signs of mad honey poisoning include 1 :  Bradycardia  Cardiac arrhythmia  Hypotension  Nausea and Vomiting  Sweating  Chills  Salivation  Dizziness

16. Signs and Symptoms  Signs of mad honey poisoning (cont) 1 :  Weakness  Loss of consciousness  Fainting  Blurred vision  Paresthesia  Cyanosis

17. Grayanotoxin in History  The Anabasis recounts the adventures of the Greek army that was sent to aid the Persian army under Cyrus. In 401 B.C. the Greeks sent to aid the Persians became ill after eating some mad honey, but all recovered within 24 hours of consumption 7

18. Grayanotoxin in History  Hundreds of years later, a troop of soldiers from Pompey was poisoned with mad honey and ambushed while overcome by the symptoms of the poisoning 5

19. References 1.Dilber, Embiya, et al. A Case of Mad Honey Poisoning Presenting with Convulsion: Intoxication Instead of Alternative Therapy. Turk J Med Sci 32 (2002) 361-362 2.Grayanotoxin. accessed April 29, 2007, from http://www.cfsan.fda.gov/~mow/chap44.html http://www.cfsan.fda.gov/~mow/chap44.html 3.Kimura, Takahiro, et al., Novel Site on Sodium Channel α-Subunit Responsible for the Differential Sensitivity of Grayanotoxin in Skeletal and Cardiac Muscle. Molecular Pharmacology. 60 (2001) 865-872

20. References 4.Lee, S.W., et al. Grayanotoxin Poisoning From Flower of Rhododendron mucronulatum in Humans. Bull Environ Contam Toxicol. 2007 5.Sheir, Thomas. Handbook of Toxinology. accessed May 3, 2007 from http://books.google.com/books?id=6oUdkb1hUCYC&pg=PA513&lpg=P A513&dq=ld50+for+grayanotoxin&source=web&ots=eWV9bqNokk&sig =0ujk-ViIP-AB1LDxAlmrMNlVKdM http://books.google.com/books?id=6oUdkb1hUCYC&pg=PA513&lpg=P A513&dq=ld50+for+grayanotoxin&source=web&ots=eWV9bqNokk&sig =0ujk-ViIP-AB1LDxAlmrMNlVKdM http://books.google.com/books?id=6oUdkb1hUCYC&pg=PA513&lpg=P A513&dq=ld50+for+grayanotoxin&source=web&ots=eWV9bqNokk&sig =0ujk-ViIP-AB1LDxAlmrMNlVKdM 6.Sulivan, Ron. “Behold the lovely rhododendron -- and beware its maddening toxins” San Francisco Chronicle February 9, 2005 pg. HO-5 7.Xenophon, Anabasis translation by H. G. Dakyns online, courtesy of Project Gutenberg, accessed May 3, 2007 from www.fordham.edu/halsall/ancient/xenophon- anabasis.html#Project%20Gutenberg www.fordham.edu/halsall/ancient/xenophon- anabasis.html#Project%20Gutenberg www.fordham.edu/halsall/ancient/xenophon- anabasis.html#Project%20Gutenberg