Wild Honey Intoxication in the Remote Himalaya

To the Editor:

Wild honey (also known as mad honey) is believed in some communities to promote general well-being, including the treatment of gastric and coronary artery diseases, cold, and viral infection, as an analgesic, and as a sexual stimulant. During our voluntary work in the remote Himalaya in the Himalayan Rescue Association Manang Clinic (3500 m) in Nepal, we had an interesting case of a patient with wild honey intoxication. A 25-year-old man, Nepali, without any history of disease and drug use was seen late afternoon at the aid post with symptoms of presyncope. The patient complained of significant weakness, alternating hot and cold sensations, tightness in the throat, and a “strange feeling” in the body. History taking revealed a normally fit and well person, with no relevant medical history and no recent ingestion of alcohol, medication, or recreational drugs. There was, however, a recent history of ingestion of freshly harvested wild honey. On his physical examination, the patient had marked bradycardia (heart rate 40 beats per minute, with occasional pulse oximetry heart rate recordings of as low as 35) and hypotension (blood pressure was 100/70 mm Hg, with intermittent readings of as low as 90/60 mm Hg). The patient was appreciably unwell, with symptoms of slow mentation, marked fatigue, and poor coordination. Pupils were equal and reactive, and neurologic examination was otherwise normal. The patient was treated with steroids and antihistamine and observed until he stabilized some hours later. He was discharged to his home under the care of his family. Unfortunately, owing to the remote nature of the aid post in which the patient was seen, sophisticated investigations such as serum analysis and electrocardiography were not available. In this case, without the benefit of real-time constant monitoring and laboratory investigation, such as has been described in previous reports of mad honey toxicity, we were limited to a diagnostic and management process the relied solely upon basic history taking, examination, and resuscitation techniques, which fortunately were, in this case, adequate and sufficient.

The main symptoms of the patient intoxicated by mad honey are dizziness, weakness, excessive perspiration, hypersalivation, paresthesias, cloudy vision, nausea, vomiting, syncope, salivation, hypotension, cardiac rhythm disturbance, and respiratory rate depression. Intoxication may lead to cardiac complications such as sinus bradycardia, sinus arrest, nodal rhythm, and varying degrees of atrioventricular block. ¹ No fatal case has been reported so far. ^{1 –}3 Mad honey intoxication’s symptoms are most likely dose-related. The exact dose that causes the poisoning is not known, but it is reported that the average amount of ingested honey needed for intoxication ranges from 5 g to 30 g. ³ Generally, how severe symptoms are depends on the amount ingested. The concentration of grayanotoxin ingested may differ greatly from case to case. Symptoms start 0.5 to 3 hours after ingesting the honey.^1,3 There is no correlation between the amount of consumed honey and duration of the symptoms. ³ Toxic effects last no longer than 24 hours. ²

Low blood pressure responds to the administration of fluids; thus, vasopressor therapy is rarely needed. The sinus bradycardia and conduction defects usually respond to atropine therapy. A temporary pacemaker may be needed for patients who have third-degree heart block. ²

The agent responsible for the intoxication of the mad honey is grayanotoxin, which occurs in the nectar of some rhododendrons species.^2,3 These species grow on the mountains of the eastern Black Sea region of Turkey and also in Japan, in some parts of North America, in Brazil, and in Nepal. ³ Most cases of this unusual type of the food poisoning have been seen on the Black Sea coast of Turkey. ^{1 –}3

Maejima et al ⁴ stated that grayanotoxins act in 3 steps on the voltage-dependent sodium channel. First, the grayanotoxin binds to the voltage-dependent sodium channel in its open state. Second, the bound toxin modifies the sodium channel and makes inactivation impossible. Third, the activation potential of the modified sodium channel is shifted in the direction of hyperpolarization. By increasing sodium influx through the cell membrane, grayanotoxins may affect action potential at the sinoatrial node. In addition to this effect, grayanotoxins may also mediate their effects by other mechanisms. It is proposed that in addition to alterations in cell membrane sodium permeability, an increase in vagal tone results from grayanotoxin ingestion and may contribute to the toxic effect. ⁵ Grayanotoxin acts like a cholinergic agent and causes dose-dependent hypotension, bradycardia, and respiratory rate depression. Onat et al ⁵ concluded that the cardiotoxic effect of grayanotoxins develops in the M2 muscarinic receptors. It was reported that selective M2 muscarinic receptor antagonists restore heart rate, whereas a nonselective muscarinic antagonist, atropine sulfate, improves both bradycardia and respiratory rate depression. ⁵ Although the spectrum of symptoms reveals a similarity to that observed with cholinergic poisoning, the study conducted by Gunduz et al ¹ did not confirm the hypothesis that mad honey poisoning should be regarded as cholinergic poisoning. In that study, the level of serum pseudocholinesterase in patients with mad honey poisoning was not decreased. ¹

Being in such a remote health post like Manang, where people strongly believe in alternative medicine, it is important to keep in mind that wild honey can be the cause of symptoms. When a previously healthy patient reports symptoms of unexplained symptomatic hypotension and bradycardia, wild honey intoxication should be considered. Close observation and symptomatic treatment were sufficient in our case, but the potential for deterioration or the complications of preexisting illness must be considered by the attending clinician.