Clinical Toxicology (2008) 46, 437–442 Copyright © Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.1080/15563650701666306 LCLT REVIEW Clinical review of grayanotoxin/mad honey poisoning past and present Mad Honey Poisoning Past and Present ABDULKADIR GUNDUZ 1 , SULEYMAN TUREDI 1 , ROBERT M. RUSSELL 1 , and FAIK AHMET AYAZ 2 1 Karadeniz Technical University Faculty of Medicine, Emergency Medicine, Trabzon, Turkey 2 Karadeniz Technical University, Department of Biology, Trabzon, Turkey Grayanotoxin is a naturally occurring sodium channel toxin which enters the human food supply by honey made from the pollen and nectar of the plant family Ericaceae in which rhododendron is a genus. Grayanotoxin/mad honey poisoning is a little known, but well studied, cholinergic toxidrome resulting in incapacitating and, sometimes, life-threatening bradycardia, hypotension, and altered mental status. Complete heart blocks occur in a significant fraction of patients. Asystole has been reported. Treatment with saline infusion and atropine alone is almost always successful. A pooled analysis of the dysrhythmias occurring in 69 patients from 11 different studies and reports is presented. The pathophysiology, signs, symptoms, clinical course, and treatment of grayanotoxin/mad honey poisoning are discussed. In the nineteenth century grayanotoxin/mad honey poisoning was reported in Europe and North America. Currently, documented poisoning from locally produced honey in Europe or North America would be reportable. Possible reasons for this epidemiologic change are discussed. Keywords Grayanotoxin; Rhododendron; Mad honey; Andromedotoxin Introduction Mad honey poisoning is little known outside of Turkey, but it is a well described condition presenting with incapacitating and, sometimes, life threatening bradycardia, hypotension, respiratory depression, and altered mental status. Poisoning occurs when grayanotoxin from the pollen and nectar of certain members of the family Ericaceae, especially Rhodo- dendron L. species, enters the human food supply as “deli bali” (in Turkish) or “mad honey” (1, 2). Mad honey poisoning is frequently reported in the Eastern Black Sea region of Turkey (1, 3–5). It was also well described in North America and Europe 100 years ago (6, 7). It is currently rarely reported outside Turkey and even when occurring in Europe the poisoning has been from honey produced in Turkey (8,9). The reasons for the change in distribution of grayanotoxin/mad honey poisoning are debatable. The pathophysiology, signs, symptoms, clinical course, and treatment of grayanotoxin/mad honey poisoning are well understood. The recognition of this cholinergic toxidrome by a physician practicing in areas where this poisoning is uncommon could be life saving. Ancient history Mad honey poisoning was first described in 401 BC by Xenophon, an Athenian author and military commander (10). In The Anabasis, his report of the campaign against the Persian King Ataxerxes II, he describes an episode of mad honey poisoning which incapacitated his army as they trav- eled through the Black Sea Region of Turkey (10). Mad honey was used as a weapon by King Mithradates IV of north-east Anatolia, Turkey against Pompey the Great in 67 BC. On the advice of his chief adviser, the Greek physi- cian Kateuas, Mithradates IV made a tactical retreat leaving mad honey containing honey combs in the path of the advancing Roman troops who consumed the honey. The Romans, thus incapacitated, were easily overcome (10). Classic works on honey poisoning in the Europe and North America Grayanotoxin/Mad Honey poisoning was well documented in nineteenth century Europe and North America. A 1999 issue of the British Medical Journal reprinted a 1899 British Medical Journal article which described a typical case of mad honey poisoning. Cases from the United States and Germany were discussed in the same article (7). In 1896, Kebler reviewed honey poisoning in the United States (6). This review may have been precipitated by the eight cases of honey intoxication which occurred in Princeton, New Jersey, during the preceding year. He also reported earlier studies in his article. According to Kebler, Barton was Received 7 August 2007; accepted 5 September 2007. Address correspondence to Suleyman Turedi, M.D., Karadeniz Technical University Faculty of Medicine, Emergency Medicine, K.T.U. Tip Fakultesi, Acil Tip AD, Trabzon 61080, Turkey. E-mail: suleymanturedi@hotmail.com Clinical Toxicology Downloaded from informahealthcare.com by Karadeniz Teknik Univ. on 06/22/10 For personal use only.