Mad Honey (Grayanotoxins)

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Mad honey is a special type of honey that contains grayanotoxins. It’s been used for thousands of years as a biological weapon, a medicine, and as a recreational drug.

The substance can provide somewhat recreational effects at certain doses, yet it comes with a clear possibility of poisoning. The concentration of grayanotoxins varies between batch, making it difficult to use mad honey in an acceptably safe way.

Symptoms

The core symptoms of mad honey poisoning include nausea, vomiting, salivation, headache, blurred vision, sweating, weakness, circumoral paresthesia, tongue numbing, fainting, drowsiness, drunkenness, tingling, and seizures.

Most of the concerning effects involve the cardiovascular system. It very often results in significantly low heart rate (bradycardia) and low blood pressure (hypotension.) With the conduction disorders arising from the toxins, it can lead to 1st to 3rd-degree heart block, asystole, and myocardial infarction.

Dose

For traditional medical reasons, around 1 teaspoon is a fairly common dose. More than 1 tablespoon is associated with more overt symptoms, including recreational ones. Yet even 1 tablespoon has the potential to be dangerous.

Case reports

(Onat, 1991)

  • Case 1
    • 48-year-old male
    • 2 tablespoons of honey that had been brought from Trabzon, Turkey
    • Had weakness, dizziness, and faintness an hour after administration
    • Previously used smaller amounts without issue
    • Exam
      • BP of 60/20
      • HR of 34
    • No nausea, vomiting, sweating, or syncope
    • ECG showed sinus bradycardia at 25 and occasional AV nodal escape beats
  • Case 2
    • 74-year-old male
    • Weakness, dizziness, fainting, and sweating 30 minutes after using some honey from Trabzon, Turkey
    • Didn’t have nausea, vomiting, or syncope.
    • Exam
      • BP of 60/30
      • HR of 35
    • Had a barrel chest with sibilant ronchi and coarse rales
    • ECG showed sinus bradycardia at 37, second degree AV block, and incomplete right bundle branch block.
  • Both responded dramatically to atropine (1-2 mg)
    • HR and blood pressure normalized within several minutes
  • Case 1 required consistent doses of atropine, while Case 2 didn’t.
  • Both normal within 24 hours.
  • Analysis
    • Honey from Case 1 was provided and microscopic examination showed Rhododendron ponticum pollens.
  • Honey extract then tested in rats
    • More impact at 5 mg/kg than 1 mg/kg
      • 12.9% of control respiration
      • 53.5% of control heart rate
      • 47.8% of control BP
    • Animals showed AV junctional escape rhythms, AV block of 2 and 3 degrees, and occasional ventricular premature beats.
    • Atropine restored both HR and respiration, while AF-DX 116 (selective M2 muscarinic antagonist) only worked on heart rate, not respiration.
      • Since humans mainly show cardiac effects, AF-DX 116 or another selective M2 muscarinic antagonist could be better than atropine.
        • And therefore the M2 muscarinic receptors are connected to cardiac effects.

(2012)

  • 69-year-old male
  • History of syncope and sinus arrest with a junctional escape rhythm of 32 bpm, leading to pacemaker implant.
  • Patient said the syncope and heart rhythm disturbances came after honey eating.
    • He had bought honey from Turkey’s Black Sea region
  • Every time he used the honey at 3 teaspoons he developed bradycardia and an episode of fainting.
    • When abstaining, the symptoms went away.
    • When returning, the symptoms reappeared.

(Poon, 2008)

  • 57-day-old infant
  • Given a plant known as “red flower” because friends said it would help with coughing.
  • Within 20 minutes, the baby vomited once and developed twitching in all four limbs.
    • Became cyanotic and unresponsive.
  • Brought to ED
    • Unresponsive, respiratory distress, and poor peripheral circulation.
    • ECG showed sinus bradycardia and BP of 62/33
    • Symptoms suggestive of seizure
    • Excessive salivation
  • Intubated and placed on mechanical ventilation
  • IV benzodiazepines provided; seizures stopped within 2 hours post-admission
  • Atropine 0.1 mg IV given based on possibility of cholinergic poisoning
    • More wasn’t provided because the baby had normal cholinesterase levels and HR had returned to normal.
  • HR normalized about 3 hours after admission; took a day for pupil constriction to go away.
  • Urine, blood, and plant samples tested.
    • Identified Rhododendron species, likely Rhododendron simsii.
    • Grayanotoxin 1 identified as the primary toxin in the plant and child’s urine.

(Uzun, 2013)

  • 15-year-old male
  • Ate 150 mL of honey two hours before presenting to hospital
  • Complained of dizziness and malaise
  • BP of 75/50 and HR of 45
  • Given isotonic fluid and atropine
    • BP became 120/80 and HR became 73
  • Patient complaints, hemodynamic status, and pathological ECG findings all improved within 1 hour.

(Sumerkan, 2011)

  • 48-year-old male
  • Presented to ED with dizziness and nausea
    • Symptoms began 2 hours after ingesting 1 tablespoon (15 grams) of “mad honey”
  • HR: 54
  • BP: 80/60
  • Cardiac enzymes (CK, CK-MB, and troponin) were also elevated.
  • Diagnosis: Acute anterior wall myocardial infarction
  • Pollen analysis confirmed the honey was heavily contaminated with Rhododendron species pollen.

(Bilir, 2014)

  • 67-year-old male
  • Took a “spoonful” of honey; leading to fainting, nausea, vomiting, and loss of consciousness.
  • Presented to ED complaining of weakness on his right extremities.
  • BP: 60/40 and HR: 40 and respiration: 10
  • GCS of 9, non-cooperative, and non-oriented
  • Given oxygen and 1 mg IV atropine and saline
  • Following therapy, symptoms improved and GCS went to 13.
    • New BP of 110/60 and HR of 84

(Yaylac, 2013)

  • 58-year-old male
  • Presented to ED with nausea, vomiting, dizziness, blurred vision
    • Those symptoms began 30 min after eating honey brought from the Black Sea region of Turkey.
  • HR: 41 and respiration: 16 and BP: 50/30
  • Sinus bradycardia and negative T waves
  • Normal saline provided; 2 mg atropine IV
  • BP and HR returned to normal
    • And normal sinus rhythm ECG with no T wave abnormalities was seen

(Eller, 2008)

  • 56-year-old male
  • Ate several rolls filled with honey and honeycombs brought into Austria by a friend from Turkey.
  • Within 1 hours, felt ill
  • Within 2 hours, had anginal pain, nausea, and cold sweat.
  • Presented
    • Severe bradycardia at 37
    • Hypotension at 65/35
    • Drowsy and vomited large amounts of yellow gastric juice
  • ECG showed complete AV block with idioventricular escape rhythm
    • This was successfully dealt with using 0.5 mg atropine
  • Another dose of atropine needed after 45 min to keep HR and BP in a good range.

(Sayin, 2011)

  • 87-year-old female
  • Taking a tablespoon of mad honey every morning for 3 months
  • Presented to ED after an episode of syncope
  • Presented
    • Depressed mental status, hypotension of 60/30, bradycardia of 48
  • ECG showed sinus bradycardia with left bundle branch block and extremely long QTc interval (810 ms)
  • Given IV fluid and dopamine
  • Then given 1 mg atropine IV, which led to dramatic improvement in HR and BP.
  • QTc down to 510 ms by next ECG
  • And QTc was at 470 ms in the post-hospital Grayanotoxin-free period

(Dur, 2014)

  • 65-year-old male
  • Took 2 spoons (60 mL) of honey
  • Presented at ED with dizziness, cold sweating, and tickling in the throat.
    • Symptoms developed 3 hours post-administration of honey.
  • Presented
    • Tachypnea – 25
    • BP: 70/40
    • HR: 52
  • Given fluid and atropine
  • More fluid required in the next 5 hours due to lack of improvement in BP.

(Choo, 2008)

  • 67-year-old male
  • History of CVA, hypertension, and angina.
  • Symptoms began 2 hours after taking 20 mL of mad honey
  • Presented with general weakness and dizziness
    • In cardiogenic shock
  • Temp: 35.5°C
  • BP: 70/50
  • HR: 45
  • Consciousness was clear; but he complained of chest discomfort and dizziness
  • ECG showed junctional rhythm
  • Fluid provided along with atropine
    • HR was 71 with a normal sinus rhythm within 15 min of atropine; BP up to 90/55

(Baltaci, 2011)

  • 52-year-old female
  • Had some honey produced in the Surmene plateaus in Turkey
  • Dizziness and fatigue
  • Presented with BP of 70/40 and HR of 45
  • Atrial fibrillation and complete AV block seen on ECG
  • Given atropine 1 mg IV
    • HR went to 60 and BP went to 90/70
  • Patient discharged after seeing normal sinus rhythm on ECG on 2nd day

(Dogan, 2015)

  • 89-year-old female
  • Ate 2 to 3 spoons of honey two hours before admission
  • Nausea, weakness, and faintness
  • Admission
    • Conscious and cooperative
    • Temp: 36°C
    • BP: 90/60
    • HR: 50
  • ECG showed sinus bradycardia at 48
  • Lab
    • Elevated liver enzymes, including AST of 1025, ALT of 817, ALP of 177, GGT of 298, and LDH of 799.
  • Diagnoses with bradycardia-hypotension and acute hepatitis associated with mad honey poisoning

(Weiss, 2010)

  • 70-year-old male
  • Symptoms began 30 min before presentation
  • Syncope, nausea, vomiting, and brief loss of vision
  • Presentation
    • Temp of 36.8°C, respiration of 16, BP of 110/60, and HR of 34
  • Second degree heart block with intermittent 2:1 conduction and preterminal negative T waves
  • AV block successfully terminated with atropine
  • Patient’s son brought in a jar of homemade honey from the Black Sea region of Turkey to show what he had likely eaten.

(Karabag, 2015)

  • 55-year-old female
  • Ingestion of 3 tablespoons of mad honey purchased from an unlicensed local vendor
  • 1 hour after taking the honey: nausea and chest tightness that radiated to her left arm
    • Weakness, dizziness, and cold shivers.
  • Had symptoms for 5 hours (chest tightness and pain) before showing up to ED
  • Chest pain and signs of acute inferior myocardial infarction on ECG
  • Presented
    • BP of 70/45, HR of 46, and oxygen of 95%
    • Short 1/6 systolic murmur at all auscultation points
  • On some leads, ECG showed ST elevation and ST segment depression.
  • Mild elevation of creatine kinase-MB and troponin 1
  • Diagnosed with inferior myocardial infarction
  • Treatment
    • 1 mg atropine IV, 600 mg clopidogrel, 300 mg ASA, and fluids
  • After treatment, which eventually also included atorvastatin, her BP and HR normalized and the ST elevation also returned to baseline.

(Gunduz, 2007)

  • 60-year-old male
  • Few spoonfuls of honey
  • Dizziness and syncope
  • Examination
    • BP: 160/60
    • HR: 75
  • Bradycardia suddenly developed and asystole increased while an ECG was being administered.
    • Patient lost consciousness.
  • 0.5 mg atropine IV was able to resolve the asystole and unconsciousness
  • Given a temporary pacemaker for a couple days

(Bayram, 2012)

  • 36-year-old male
  • 2 – 3 teaspoons of honey purchased from the eastern Black Sea region
  • Presented with dizziness, lightheadedness, fatigue, and syncope
    • Symptoms began 4-5 hours after taking the honey
  • Four consecutive syncopal episodes
  • BP of 110/55 and HR of 56
  • Atrial fibrillation with a low ventricular response seen on ECG
  • Atrial fibrillation continued to be seen on future ECG readings; though HR was 76
  • Medical cardioversion was decided upon
  • Amiodarone loading and maintenance began
  • HR returned to sinus rhythm after 25 hours.

(Yaylacis, 2012)

  • 54-year-old male
  • Two hours after honey ingestion had nausea, vomiting, dizziness, and chest pain
    • Took 2 tablespoons of Black Sea region honey
  • Presented
    • HR of 40 and BP of 70/40
  • ECG showed atrial fibrillation and slow ventricular response
  • Fluids and atropine 1 mg IV provided

(Sayin, 2012)

  • 76-year-old male
  • Took 3 teaspoons of mad honey obtained  from an amateur beekeeper
  • 2 hours later for the onset of symptoms
  • Impaired general condition, chest pain, dizziness, nausea, and vomiting.
  • Presented
    • BP of 60/40 and HR of 30
  • Given fluids and 1 mg atropine IV
  • ECG revealed first-degree AV block and ST segment elevation; also LBBB
  • Received acetylsalicylic acid and enoxaparin as well
    • Chest pain was eventually relieved and ST and LBBB normalized
  • Cardiac markers showed mild elevations of troponin and CK-MB
  • ST elevation and LBBB attributed to coronary ischemia due to deep hypotension and bradycardia.

(Koda, 2015)

  • 61-year-old male
  • Consumed approximately 50 grams of Rhododendron flowers from his garden
    • Symptoms began 1 hour later
  • Dizziness, severe nausea, and abdominal discomfort
  • Presented
    • Conscious but felt severely ill with nausea and abdominal discomfort
    • Temp of 35.5°C, BP of 80/50, and HR of 45, and respiration of 24.
    • Mild kidney injury with elevated creatinine shown in blood test
  • ECG showed sinus bradycardia at 47
  • Given fluids and atropine to good effect
    • Prompt response from BP and HR
  • Atropine was eventually readministered 4 hours later to get HR back over 50

(Bilir, 2016)

  • 5-month-old male infant
  • Given 2 teaspoons of honey to treat coughing for a couple days
  • 4 hours after last ingestion, he began to vomit and became drowsy.
  • Presented
    • GCS of 10
  • All symptoms resolved after 5 hours post-arrival

(Ocak, 2013)

  • 39-year-old female
  • Ingested 2 teaspoons of mad honey
    • Then onset of symptoms 45 min later
  • Presented with nausea and near-syncope
    • BP of 75/50, HR of 49, temp of 36.5°C
  • ECG revealed sinus bradycardia
  • Atropine .5 mg IV given when HR fell to 40
    • HR and BP returned to normal
  • Though quickly developed polymorphic VT
    • Given lidocaine; VT was aborted
  • Then developed chest pain after rhythm returned to sinus
    • ECG showed ST elevation over inferior and lateral leads; ST depression over V1-V2
  • Chewable acetylsalicylic acid 300 mg and heparin IV given
    • Quick resolution of ST
  • Cardiac enzymes were mildly elevated

(Altun, 2014)

  • 70-year-old male
  • Took 100 mL of honey brought from Akcakoca, a city in the western Black Sea region of Turkey, for breakfast
  • Symptoms began 30 to 45 min after ingestion of 1 teaspoon of honey
    • Presyncope and hypotension; general weakness and dizziness
  • Exam
    • Hypotension of 80/60
    • ECG showed complete AV block with nodal rhythm
  • Vital signs significantly improved after fluids; no atropine required

(Lee, 2007) – Involving plants instead of mad honey

  • 76-year-old male
  • Used about 10 azalea blossoms
  • 1 hour later he began to have symptoms and was admitted
  • Dizziness and general inertia
  • Exam
    • BP of 70/50, HR of 45, temp of 36°C
    • Drowsiness
    • ECG showed sinus bradycardia
  • Atropine 1 mg IV resolved all the symptoms and restored normal sinus rhythm

(Yarlioglues, 2011) – Two people with myocardial infarction (inferior)

  • 50-year-old male and 42-year-old female
    • Had mad honey 3 hours before presentation
    • Taken for sexual performance
    • Previously had headaches and dizziness from it, but they continued use.
    • Had increased dose from 1 teaspoon each to 1 tablespoon each on the morning of presentation.
  • Presented with confusion and chest pain
  • Male
    • BP of 70/40
    • HR of 35
    • ECG showed complete AV block, ventricular rate of 42, and ST segment elevation in the inferior leads.
  • Female
    • BP of 85/55
    • HR of 45
    • ECG showed AV nodal rhythm, ventricular rate of 42, and ST segment elevation in the inferior leads.
  • Treatment
    • Both quickly improved with 1 mg atropine
      • Quick rise in BP and HR; resolution of chest pain and ST elevations within 5 minutes
  • Diagnosis
    • Myocardial infarctions likely brought on by excessive bradycardia and hypotension.
    • Acute inferior MIs occurred within 3 hours of ingestion
  • Cardiac troponin 1
    • 18.7 ng/mL in male and 13.4 ng/mL in female around 6 hours after onset of chest pain
  • Analysis of the honey confirmed grayanotoxin-containing rhododendron pollen.

(Alsancak, 2016) – Unusual case of it triggering Kounis syndrome

  • 58-year-old male
    • Took honey from the eastern Black Sea region of Turkey in order to help digestive disorder.
  • Nausea and chest pain for 1 hour
  • BP of 90/70
  • HR of 45
  • Unexplained abnormal skin findings during exam.
  • ECG showed ST elevation and sinus bradycardia of 47
  • Diagnosis
    • Acute posterolateral myocardial infarction
  • Given 300 mg ASA and 600 mg clopidogrel + heparin
  • ECGs showed no improvement in ST elevation, but also lack of symptoms of Takotsubo Cardiomyopathy
  • Troponin was 0.464 ng/mL and CK-MB was 7.82 —- Both elevated, indicative of heart damage.
  • Due to severe hypotension and bradycardia, also given atropine and fluids. Not effective.
  • Diagnosed with Kounis syndrome, an allergic reaction that causes acute coronary syndrome.
    • IV antihistamines led to alleviation of chest pain and ST elevation
  • First case of Kounis Syndrome allergic myocardial infarction from mad honey, showing need for antihistamine in some cases.

(Akinci, 2008) – Myocardial infarction

  • 66-year-old male
    • Taking special honey from the Black Sea area for 5 days
  • Dizziness and sense of compression in his chest
  • BP of 70/40 and HR of 35
  • ECG showed ST elevation at inferior leads and sinus bradycardia
  • Saline and IV atropine 2 mg led to BP and HR increases
  • Chest pain was ongoing and ST elevation persisted; was taken to catheterisation lab for primary percutaneous coronary intervention.
    • Angiogram was normal.
  • Troponin level of 12.71 ng/mL
    • Yet it had been negative at admission
  • Diagnosis: Acute inferior myocardial infarction with normal coronary arteries due to mad honey ingestion.
    • Likely from excessive bradycardia and hypotension resulting in coronary hypoperfusion.
  • Analysis of honey confirmed grayanotoxin presence.

(Saritas, 2011)

  • 70-year-old male
    • No history of cardiovascular disease
  • Took a few teaspoons of mad honey
  • Presented with weakness, palpitation, nausea, and vomiting.
  • BP of 60/20
  • HR of 105
  • ECG: Paroxysmal atrial fibrillation and intermittent left bundle branch block.
  • Hypotension improved rapidly with saline.
  • Rhythm returned to normal sinus rhythm 6 hours post-admission
  • Discharged on the 2nd day

(Dilber, 2002)

  • 8-year-old male
  • Suddenly developed nausea, vomiting, weakness, dizziness, and impaired consciousness.
    • Symptoms began 1 hour after drinking three spoons of honey for abdominal pain.
  • Temp of 36.4°C, HR of 45, and BP of 85/45
  • ECG showed sinus bradycardia
  • Treated with atropine and dopamine
    • For symptomatic treatment of hypotension and bradycardia.
  • 30 min post-admission
    • Tonic-clonic seizure lasting 2 minutes
  • 7 hours post-admission
    • Began to regain consciousness

(Kavakli, 2011)

  • 45-year-old male
  • Few dessert spoons of mad honey
  • Complaints of dizziness and diplopia began 4 hours after consumption
  • BP of 70/50 and HR of 45
  • ECG: sinus bradycardia and followed by negative T waves on the anterior derivations.
  • Fluids provided and 1 mg atropine
    • HR went to 60 and BP went to 99/55
  • Symptoms and ECG abnormalities resolved by 12 hours post-admission

(Oguzturk, 2012)

  • 45-year-old female
  • 2-3 tablespoons of honey from the East Black Sea region
  • Within 2 hours, complained of lightheadedness, cold sweating, dizziness, nausea, asthenia, and discomfort in the epigastric region.
  • BP of 70/50 and HR of 44
  • ECG showed complete AV block
  • 1 mg atropine IV provided
    • HR was 65 and BP was 110/70 within ten minutes

(Akinci, 2015) – Suicide attempt

  • 19-year-old male
  • Took five spoonfuls of mad honey with suicidal intention
    • Said “I only wanted to end my troubles.”
    • And he felt taking a large amount of mad honey was the easiest way to end his life.
    • Said he also occasionally used one teaspoon for stomach ache and palpitation, but he knew large amounts could lead to poisoning or death.
  • Presented to ED with fluctuation in consciousness, vertigo, nausea, vomiting, and a shortness of breath.
  • BP of 60/40 and peak HR of 36
  • ECG showed sinus bradycardia

(2008)

  • 41-year-old male with coronary artery disease
  • Symptoms began after using mad honey
    • Severe substernal chest pain for an hour; radiating to shoulders and left arm
  • Presented with severe chest pain
  • Had ST depression, low BP
    • BP of 60/30
  • Elevated troponin 1 and CK-MB levels
  • Coronary angiography showed normal epicardial arteries.
  • Diagnosed with myocardial infarction
  • Treated: aspirin, IV fluid, heparin.
  • Angina symptoms and ST depression resolved with improvement in BP.

(Cagli, 2009)

  • 48-year-old male with no heart disease history
  • Breakfast included nearly 100 mL of honey from Zonguldak in the western Black Sea region
    • Had it 8 hours before presentation
  • Presented to ED after episode of syncope 20 minutes earlier
  • Paramedics noticed severe bradycardia
    • Atropine resolved the syncope
  • HR of 33 and BP of 80/60
  • ECG: complete AV block with ventricular rate of 31
  • Honey analysis
    • Confirmed presence of pollen from rhododendron species.

(Dubey, 2009)

  • 56-year-old male with history hypertension and dyslipidemia
    • Also had coronary angiogram 3 years prior showing double-vessel disease
    • So he was on aspirin, atenolol, atorvastatin, and nitrates.
  • Presented with profuse sweating
    • HR of 43 and BP of 60/40
  • Conscious, but complained of chest tightness, dizziness, and nausea
  • Echo: Mild mitral regurgitation and a left ventricular ejection fraction of 65%
  • Treated with atropine and saline
    • The second dose of atropine
  • With 10 min of second dose, HR was 70

(Aliyev, 2009)

  • 70-year-old male
  • Symptoms began 15 min after taking one teaspoon of honey made by amateur beekeeper.
  • Presented with syncope and signs of severe bradycardia and hypotension
    • Also confused
  • BP of 60/30 and HR of 35
  • ECG: Nodal escape rhythm
    • Frequently interrupted by runs of sinus bradycardia and ventricular asystole
  • Treatment
    • Atropine, dopamine, fluid replacement, insertion of temporary transvenous pacemaker
  • Led to stabilization

Case series

(Gunduz, 2006)

  • 8 people used honey in 2005
  • Presented with similar symptoms like nausea, vomiting, hypotension, and bradycardia.
  • Each used 20 – 150 grams of honey, unaware that it was mad honey.
  • Bradycardia: 40.9 (32 – 48)
  • Hypotension: 81.3/42.5 (70-90 and 40-60)
  • 4/8 had severe bradycardia and 1 of those 4 had complete atrioventricular block
    • The other 3 had nodal rhythm and were monitored in ED for 12 hours.
  • Treatment
    • All received 0.5 mg atropine IV
    • 3/8 with symptomatic bradycardia and the 1/8 with complete AVB were given a second dose of 0.5 mg atropine IV due to lack of HR/BP improvement after five minutes.
  • Most were discharged within 48 hours. 1/8 received a temporary pacemaker.

(Jauhari, 2009)

  • Seven medical students went to the same restaurant and ignored the warnings from the owner regarding how much honey to eat.
    • Restaurant owner got the wild honey from an area near Rhododendrons growing in abundance.
  • They used between 2-3 tablespoons and 10 tablespoons.
  • They all had GI distress within 15-20 minutes
  • They also had a burning sensation in their throat, excessive salivation, nausea, and vomiting.
  • Following by diplopia, blurred vision, dilated pupils, sluggish reaction to light, palpitations, and hypotension.
  • Some had other CNS symptoms like unconsciousness, deep gasping respiration, respiratory depression, and apnea.
  • HR: Ranged from 48 to 82
  • BP: Ranged from 80 to 110 / 40 to 80
  • When one of the paper authors took 1 Tbsp (15 mL) of the same honey,  they didn’t have any notable symptoms.

(Ozturk, 2011)

  • Case 1
    • 79-year-old male
    • Used four spoons of “bitter honey”
    • Presented with vomiting, nausea, and severe dizziness.
    • BP of 80/60
    • HR of 17
    • 1 mg IV atropine given, leading to HR of 48
    • ECG showed complete AV block; he received a temporary pacemaker implant
    • On subsequent days his ECG records were normal; pacemaker was removed
  • Case 2
    • 55-year-old male
    • Used 6 spoons of “bitter honey”
    • Presented with dizziness, fatigue, nausea, vomiting, and syncope.
    • BP of 120/80
    • HR of 52
    • Subsequent ECG showed resolution of abnormal sinus rhythm.

(Yilmaz, 2006)

  • Two small towns in Kastamonu province of Turkey
  • 66 patients who had ingested honey were admitted to the hospital
  • Means
    • Age: 51.95
    • Dose: 13.45 grams (5 – 30)
    • Dizziness: 100%
    • Weakness: 100%
    • Cloudy vision: 88%
    • Nausea: 45.4%
    • Vomiting: 31.8%
    • Syncope: 17.6%
    • Salivation: 4.7%
    • SBP: 70.08
    • DBP: 45.25
    • HR: 47.96
  • Treatment
    • IV fluids and atropine (0.5 to 2 mg)
  • No deaths

(Eroglu, 2013)

  • April 2011 to April 2012 at Marmara University
  • 38 patients diagnosed with mad honey poisoning during that time
  • Age: 51
  • Dizziness and unconsciousness affected 26/38 patients
  • Nausea/vomiting in 12; chest pain in 2
  • No deaths; only 18 were followed-up in the ICU for persistent bradycardia and to rule out acute coronary syndrome.

(Yavuz, 1991)

  • Retrospectively looked at 23 cases from two parts of the Black Sea region of Turkey from 1983 to 1986
    • Trabzon and Inebolu
  • Dose: 2 teaspoons to 5 tablespoons
  • Symptoms began within 30 min when large amounts were used; but onset could be up to 2 hours with smaller doses.
  • Symptoms
    • 100% hypotension, 95% bradycardia, 91% nausea/vomiting, 74% sweating, 74% dizziness, 67% impaired consciousness, 35% exhaustion, 30% fainting, 22% blurred vision or diplopia, 33% cyanosis, 33% chills.
  • ECG
    • 63% had bradycardia, 31% had junctional rhythm, 6% had complete AV block, and 6% had Wolff-Parkinson-White syndrome with sinus bradycardia.
  • Treatment
    • IV fluids, atropine, vasopressive agents.
    • Isoproterenol given to a patient with complete AV block

(Demircan, 2009)

  • 6 year period in Turkey
  • 21 patients found
  • Basically all presented with bradycardia and dizziness
  • Also nausea, vomiting, sensations of motion, blurry vision, weakness, sweating, perioral paresthesia, chest pain, near syncope, and syncope.
  • Highly variable dosing: From 50 to 300 grams
  • 2/21 had AV junctional nodal rhythm, 1 had new left bundle branch block, and 1 had atrial fibrillation with low ventricular rate.
    • Those with left bundle branch block and atrial fibrillation may have had underlying conduction issue (hypothetical).
  • All given fluids; some received atropine
    • Atropine generally led to increase HR and BP
  • One failure to respond to atropine
    • 59-year-old female needed dopamine treatment for HR and BP normalization after failure to respond.

(Aygun, 2016)

  • Case series showing hypothermia
  • Case 1
    • 66-year-old male
    • Symptoms began 2 hours after consumption of mad honey (1 – 2 teaspoons)
    • Previously had honey without as severe symptoms.
    • Vertigo, nausea, vomiting, and faintness.
    • BP of 70/40m HR of 30, respiration of 20, and temp of 34°C
    • Sinus bradycardia shown on ECG
    • Fluids and atropine
      • Within 30 min, BP was 110/70 and HR was 65, and temp was 35°C
  • Case 2
    • 57-year-old male
    • Sudden-onset sweating and faintness 3 hours after taking 2 “dessert” spoonfuls of honey
      • User believed this honey was going to keep him healthy and was more medicinal since it had a “sharper” taste.
      • Never experienced adverse effects from the honey.
    • Loss of consciousness, chills, headache
    • Presented
      • BP of 60/40, HR of 46, respiration of 20, temp of 35°C
    • ECG showed sinus bradycardia
    • Atropine 1 mg IV given
      • Leading to HR of 95 and BP of 110/75
  • Case 3
    • 79-year-old female
      • Had hypertension and was on hypertension drugs for 5 years.
    • Symptoms began 2 hours after 1 “dessert” spoonful of mad honey
    • Nausea, vomiting, and vertigo
    • Presented
      • BP of 70/40, HR of 40, respiration of 18, and temp of 35°C
    • Sinus bradycardia shown on ECG
    • Atropine 1 mg IV given
      • HR increased to 70 after 30 minutes

(Lim, 2016) – Cases involving Nepalese honey

  • Two Nepalese men presented simultaneously in ED
  • Case 1
    • 43-year-old male
    • 1 – 2 tablespoons of “wild” honey brought from Nepal 2 hours before onset of symptoms
    • Syncope, bradycardia, and hypotension
    • Regained consciousness by presentation
    • BP of 83/45 and HR of 45
    • ECG
      • Second-degree type 1 heart block with ventricular rate of 36
    • Developed recurrent episodes of bradycardia and hypotension, requiring further atropine and then dopaminergic support.
  • Case 2
    • 44-year-old male
    • 1 – 2 tablespoons of “wild” honey brought from Nepal 2 hours before onset of symptoms
    • Syncope, bradycardia, and hypotension
    • Regained consciousness by presentation
    • BP of 68/36 and HR of 39
    • ECG
      • Junctional bradycardia with ventricular rate of 38
  • Treatment
    • Atropine and fluids in both cases, allowing for resolution of conduction abnormalities.
  • Toxicology
    • Revealed grayanotoxins inside the honey.

(Okuyan, 2010)

  • 44 patients between Jan 2005 and July 2007
    • Patients excluded: cardiac enzyme elevations, chest pain, or known coronary artery disease.
  • Dose: 20 to 200 grams of mad honey
  • Onset: 10 minutes to 4 hours
  • 40/42 had nausea, vomiting, dizziness, fainting, and sweating.
  • 5/42 had syncope
  • 1/42 had a generalized seizure
  • Vitals
    • BP: 73.1/52.1
    • HR: 38
  • ECG
    • 18 had sinus bradycardia, 15 had complete AV block, 9 had nodal rhythm.
  • Treatment
    • 33 responded well to 0.5 – 1 mg of IV atropine
    • 7 needed dopamine at vasopressor doses and parenteral saline
    • None required temporary cardiac pacing
  • All discharged in 12-36 hours
  • Prior medications
    • 8 were on beta blockers
      • Mean HR and BP were significantly lower in connection with beta blocker use
    • 10 were on antihypertensive medications
  • Reasons for use
    • 8/33 male patients said they believed it could be a sexual stimulant.
    • Most used it as a natural medication for their illnesses.

(Sutlupinar, 1993)

  • 11 cases of poisoning from 1983 to 1988
    • Investigation of cases coupled with microscopic and chromatographic examination of honey samples
  • Dose: 1 teaspoon to 2 tablespoon
  • Some people reported regularly using at least 1 teaspoon for GI complaints
  • Presented with nausea, vomiting, hypotension, bradycardia, and faintness.
    • Two severe cases involved bradycardia that was very severe at 26-40
  • Majority of patients showed signs of shock, were in a state of fatigue and restlessness, and were unable to answer questions.
    • Dryness of the skin was also noted.
  • TLC investigation confirmed the present of Grayanotoxins in toxic honey and in extract from Rhododendron ponticum leaves.

(Ozhan, 2004)

  • 19 patients in 2002
  • Presenting with nausea, vomiting, hypotension, bradycardia, and fainting.
  • Dose: 30 to 180 grams of honey several hours before admission
  • Presented
    • All had bradycardia
    • 15/19 had hypotension
  • 4/19 suddenly had symptoms upon standing and they sustained head trauma due to falling, probably from sudden hypotension and collapse.
    • 3/4 had small hematomas on their heads.
  • 2/19 had severe bradycardia and 4/19 had complete AVB
  • 16/19 received 0.5 mg atropine
    • 3 required another dose of atropine (all had AVB) due to a lack of HR and BP response with the first dose.

(Demir, 2011)

  • April to June 2010
  • 21 patients
  • Dizziness (21), weakness (21), excessive perspiration (18), nausea/vomiting (18), and low blood pressure (14).
    • 5 had syncope
  • Mean HR: 56
  • Mean SBP: 102
  • ECG
    • 10 normal sinus rhythm, 7 sinus bradycardia, 3 nodal rhythm, 1 atrial fibrillation.
  • Atropine given to 18

(Silici, 2015) – Systematic review of 1199 cases

  • 1199 cases from 84 published articles
    • First case was in 1981
  • Dizziness in 51%, bradycardia in 50%, nausea in 38%, vomiting in 36%, presyncope in 27%, blurred vision in 20%, impaired consciousness in 11.67%, chest pain in 9.16%, syncope in 16%, hypotension in 20%, confusion in 2.83%, cyanosis in 1.92%, collapse in 2%.
  • 72% had sinus bradycardia and 45% had complete AV block
  • Most common treatments: atropine and fluids
    • Although 20.74% received other agents like aspirine, ASA, and heparine.
  • 14.90% were admitted to ICU
  • 75.12% reported a dose between 1 and 5 tablespoons.
  • ECG
    • 23% had ST elevation
    • 8.69% had atrial fibrillation
    • 0.26% had myocardial infarction
    • 0.09% had wolf parkinson white syndrome
    • 0.09% had asystole

(Akca, 2012)

  • 37 patients
  • Nausea, vomiting, hypotension, bradycardia, and syncope.
  • HR of 51.78 (range of 30 to 112)
  • BP: 97.4/56.48
  • 16 received 1 mg atropine
    • Second dose needed in one case due to lack of response
  • Patients largely responded to atropine and saline
    • Though 2 required extra dopamine infusion
  • 5 with AVB admitted to coronary ICU
  • Temporary pacemaker required in one
  • Atrial fibrillation in 5

(Aliyev, 2009)

  • April 2008 – December 2008
  • 173 patients presenting for bradycardia and/or pacemaker implantation
  • 5/173 had a history of ongoing non-commercial honey use for at least 3 months
  • All had various degrees of AV conduction abnormality combined with narrow QRS complexes
  • Cessation of honey use led to rapid symptomatic release and ECG improvement
  • The cases showed with dizziness and presyncope
    • Along with AV block (type 1 or type 2)
    • Dosage per day was 3-5 teaspoons up to a max of 10 teaspoons

(Sohn, 2014)

  • 15 patients used mad honey bought from the Himalayan region of Nepal
  • Mean dose: 47 cc (47 mL)
  • Mean onset: 36 minutes
  • Mean BP: 68.3/47.6
  • HR: 40.9
  • Respiration: 20.3
  • ECG
    • Sinus bradycardia in 8, junctional bradycardia in 4, complete AV block in 2, atrial fibrillation with slow ventricular response in 1.
  • Treatment
    • 4 only received saline
    • 11 received saline and atropine
  • HR and BP normalized in all within 24 hours.

(Bostan, 2010)

  • March 2008 to December 2008
  • 33 patients in Turkey
  • HR: 55.35
  • BP: 77.86/46.42
  • Symptoms
    • 27 had nausea-vomiting
    • 26 had dizziness
    • 18 had mental confusion
    • 16 had sweating
    • 4 had blurred vision
    • 4 had syncope or fainting
  • Dose: 43.88 grams
  • Onset: 1.64 hours

References

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(2016) Mad Honey-Related Intoxication in an Infant: A Case Report

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(2015) A case of human poisoning by grayanotoxins following honey ingestion: elucidation of the toxin profile by mass spectrometry.

(2015) Mad honey intoxication: A systematic review on the 1199 cases.

(2015) Type 2 myocardial infarction after ingestion of mad honey in a patient with normal coronary arteries

(2015) Suicide Attempt with Mad Honey: Case Report

(2015) A case of acute hepatitis following mad honey ingestion

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(2014) Mad honey intoxication mimicking acute coronary syndrome.

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(2014) Analgesic effects of mad honey (grayanotoxin) in mice models of acute pain and painful diabetic neuropathy.

(2014) Mad honey poisoning presenting as transient ischemic attack

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(2013) Electrocardiographic ST segment changes due to the mad honey intoxication

(2013) A child with bradycardia and hypotension related to mad honey intoxication

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(2013) Mad honey intoxication: what is wrong with the blood glucose? a study on 46 patients.

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(2011) Mad-honey intoxication confirmed by pollen analysis.

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(2011) Mad-Honey Sexual Activity and Acute Inferior Myocardial Infarctions in a Married Couple

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(2010) Honey intoxication and the Bezold-Jarisch reflex.

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(2009) Bradycardia and severe hypotension caused by wild honey poisoning.

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(2009) Chronic mad honey intoxication syndrome: a new form of an old disease?

(2009) Does mad honey poisoning require hospital admission?

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