Grayanotoxin levels in blood, urine and honey and their association with clinical status in patients with mad honey intoxication

Abstract

ObjectivesThe purpose of this study was to investigate whether there is an association between grayanotoxin levels in urine and blood of patients with mad honey intoxication and in the honey consumed, and the resulting clinical picture. The pilot data acquired from this study was analysed in National Forensic Service, Daejeon Institute, South Korea and first results were published as a preliminary study.Patients and methodsThis descriptive study was conducted at a university hospital emergency department in Turkey. 25 cases diagnosed with mad honey intoxication were obtained the study. Samples of mad honey consumed by patients were obtained. Blood and urine specimens were collected at presentation to the emergency department. GTX 1 and GTX 3 levels from patients' blood, urine and honey consumed were investigated simultaneously using the LC-MS/MS system.ResultsMean GTX 1 concentration in blood was 4.82 ng/mL and mean GTX 3 level 6.56 ng/mL. Mean GTX concentration in urine was 0.036 μg/mL and mean GTX 3 level 0.391 μg/mL. Mean GTX I concentration in honeys consumed was 8.73 μg/gr and mean GTX 3 level 27.60 μg/gr.ConclusionThis descriptive study is show grayanotoxin levels in body fluids of patients with mad honey intoxication. No association was determined between grayanotoxin levels in blood and clinical data.

Mad honey: uses, intoxicating/poisoning effects, diagnosis, and treatment

“…Notably, symptoms including vomiting, nausea, nodal rhythms, and second-degree heart block are less severe and less frequent in females as compared to those in males. 45,53,86,[88][89][90] Akca and Kahveci 70 reported that men suffer 5 times more incidences of mad honey poisoning/intoxication as compared to women. However, long term consumption may lead to desensitization of Na + channels in the excitable cells, which precludes intense symptomatic presentation itself.…”

“…Other possible techniques for the detection of grayanotoxin are HPLC, LCMS/MS, nuclear magnetic resonance, and infrared-based technologies. 64,90,[107][108][109][110]130 For corroborative evidence, pollen grains from Rhododendron (its owers are rich in grayanotoxin) can be investigated occasionally in honey samples. Cardiac ischemia and rhythm abnormalities should be checked by ECG.…”

Risks for human health related to the presence of grayanotoxins in certain honey

“…Aygun et al ( 2015 , 2018 ) undertook two separate observational studies to determine the association between GTX levels in blood and urine and the clinical data. In the more recent study (Aygun et al., 2018 ), concentrations of GTX I and III were measured in 25 patients, presented to the Emergency Medicine Department with symptoms of intoxication (see Table 5 and Section 3.1.3 ). Due to few cases reported in the study by Aygun et al ( 2015 ), the data reported for blood are not considered for toxicokinetics.…”

“…Determination of GTXs in honey using a dilute‐and‐shoot approach has been described (Kaplan et al., 2014 ). Extraction of GTXs from biological matrices such as blood and urine require purification and concentration by SPE (Cho et al., 2014 ; Aygun et al., 2018 ). Hwang et al ( 2018 ) extracted dietary supplements and homemade wine with methanol and used SPE for sample clean‐up (Hwang et al., 2018 ).…”

Determination of Grayanotoxins from Rhododendron brachycarpum in Dietary Supplements and Homemade Wine by Liquid Chromatography–Quadrupole Time-of-Flight–Mass Spectrometry and Liquid Chromatography–Tandem Mass Spectrometry

“…However, as indicated above, the consumption of such products can cause intoxication in humans, and the severity of symptoms may vary from mild to life-threatening depending upon the quantity consumed. Indeed, grayanotoxin poisoning remains one of the most frequently encountered causes of food intoxication in Turkey, although cases have also been reported in Austria, Korea, and Nepal. − …”