Mad Honey Research Articles

Mad honey disease: A challenging encounter in the emergency department.

Be aware of potential severe interactions between aged honey containing grayanotoxins and alcohol. Such combinations can exacerbate symptoms like syncope and hypotension, especially in elderly patients with pre-existing conditions, necessitating careful evaluation and management.

Mad Honey Poisoning: Another Substance causing Muscarinic Overactivity

Mad honey syndrome is the poisoning by Grayanotoxin, produced by plants of genus Rhododendron of Ericacea family. Grayanotoxin poisoning is relatively uncommon and is encountered mostly in Nepal and Turkey, where the plants are found in abundance. The similarity between the symptoms of Grayanotoxin toxicity and organophosphate compounds (OPC) poisoning poses the challenge of differentiating between the two, and a possibility of atropine poisoning while treating as OPC poisoning. Here we report the first ever case of “Mad Honey Syndrome” in Bangladesh, where meticulous history taking helped us in proper diagnosis and appropriate management. J Bangladesh Coll Phys Surg 2024; 42: 383-386

Mad honey (wild honey) poisoning: clinical case series from Nepal.

Mad honey is commonly used for hypertension, and coronary artery disease, and as a sexual stimulant. Patients with mad honey poisoning present with dizziness, nausea, syncope, blurred vision, bradycardia, and hypotension with ECG findings of sinus bradycardia, complete AV block, and ST elevation. Here, the authors report five cases admitted to our tertiary care center following the consumption of mad honey. The amount of ingestion of honey varies from 1 to 2 teaspoons (~10-20ml). Most of the cases presented with chief complaints of nausea, dizziness, and vomiting, and all the cases had hypotension and bradycardia. Two cases were admitted to the ward and three of them were admitted to the ICU for further management. They were managed with intravenous fluid, injection atropine along with adjunctive vasopressor and oxygen whenever necessary. Mad honey contains grayanotoxin extracted from the nectar of Rhododendron species. This honey contains grayanotoxin, which binds to sodium channels in its open state causing hyperpolarization of the sodium channel predominantly causing gastrointestinal, neurological, and respiratory symptoms. Intravenous fluids and injection atropine are the mainstays of management in an ICU setup. Some also may require vasopressors. Mad honey poisoning is rare, and limited cases have been reported in Nepal. Physicians should consider mad honey poisoning in cases with ingestion history and clinical symptoms, as it may be a clinical diagnosis due to limited lab tests for grayanotoxin intoxication. Supportive management still forms the cornerstone for its management after diagnosis.

Evaluation of tumor-suppressive properties and apoptotic functions of Mad Honey and Vincristine applications in a rat model of breast cancer

In this study, the suppressive effects of vincristine and Turkish mad honey alone and in co-applications were biochemically, hematologically, and histopathologically investigated in a mammary tumor model induced with 7,12-dimethylbenz[a]anthracene (DMBA) in rats. A total of 72 rats, 43-49 days old, were divided into 6 groups of 12 rats each. The control group (CG) consisted of healthy rats. The vehicle group (VG) received only vehicle substance and the cancer control group (CCG) was given only DMBA. DMBA and the honey group (HG) given group. DMBA and the vincristine (VinG) given group, and DMBA, the vincristine-honey group (VHG) received both Turkish mad honey and vincristine. Turkish mad honey and/or vincristine was given in the last 4 weeks of the 13-week trial period. White blood cell and lymphocyte counts differed significantly in the CCG and VG groups. Alanine transaminase and total protein levels were higher in the CCG and VinG groups. Aspartate transaminase was higher in the CCG, HG and VG groups. Caspase-3 and Bax protein levels were in the HG and VHG groups significantly higher than CCG. In caspase-8 protein level VHG significantly higher than other groups. Caspase -9 protein level was in CG and VG groups significantly lower than other groups. Bcl-xL increased more in the CCG group. Anaplasia was reduced in the HG and VinG groups, although apoptosis and other cellular damages increased. It was concluded that mad honey and vincristine could be considered together as effective therapeutic agents in this model of DMBA-induced breast cancer.

The relationship between oxidative stress and apoptosis of histopathological changes in the ovary made by mad honey containing grayanotoxin

The purpose of this study is to determine the effects of grayanotoxin in mad honey on ovarian tissue folliculogenesis in terms of cell death and nitric oxide expression. Three groups of 18 female Sprague-Dawley rats were formed. The first group received mad honey (80 mg/kg), the second group received normal honey (80 mg/kg), and the third group was the control. The first and second groups received normal and mad honey by oral gavage for 30 days before being sacrificed under anesthesia. Caspase 3 immunostaining showed a moderate to strong response, particularly in the mad honey group. In the mad honey group, immunostaining for caspase 8 and caspase 9 revealed a moderate immunoreaction in the granulosa cells of the Graaf follicles. The majority of Graaf follicles exhibited TUNEL positive in the mad honey group. The iNOS immunoreaction revealed a high level of expression in the mad honey group. In all three groups, eNOS immunostaining showed weak reactivity. According to the findings of apoptotic and nitric oxide marker expression, it was determined that mad honey may result in an increase in follicular atresia in ovarian follicles when compared to normal honey and control groups.

Anaphylactic shock following the mad honey consumption: a case report

Introduction: Mad honey consumption is a common practice in Nepal for medicinal and consumption purposes, but it can lead to severe adverse effects. Grayanotoxin I and Grayanotoxin III isoforms found in rhododendron interfere with voltage-gated sodium channels resulting in gastrointestinal symptoms, and cardiovascular effects such as low blood pressure, abnormal heart rhythms, cardiac arrest, and abnormal electrical conduction in the heart, as well as rare central nervous system disorders. Here the authors report a case of Mad honey consumption leading to anaphylactic shock along with its investigations and management. Case presentation: The authors present a case of a 51-year-old female who developed anaphylactic shock after consuming mad honey. The patient experienced symptoms including nausea, vomiting, abdominal pain, sweating, dizziness, facial and lip swelling, but no chest pain, loss of consciousness, abnormal body movement, or dyspnoea. The patient had no prior medical conditions, regular medications, or history of allergic reactions to honey or pollen. Discussion: Mad honey intoxication is caused by grayanotoxins, with distinct cardiac effects for different types of grayanotoxins. Symptoms include bradycardia, hypotension, abdominal pain, dizziness, and nausea, which subsided within 24 h following the initial management. The presence of grayanotoxin can be detected using specialized instrumentation, but it may not be available in all medical facilities. Co-intoxication with alcohol or propolis may also occur. Conclusion: This case highlights the importance of recognizing and managing complications associated with mad honey consumption, particularly in regions where it is prevalent. Prompt medical attention is advised if unusual symptoms occur after honey consumption.

Evaluation of the combined effects of Turkish mad honey and 5-Fluorouracil in colon cancer model in rats

It was aimed to evaluate the regressive effect of grayanotoxin-rich Turkish mad honey and 5-fluorouracil (5-FU), separately and together by using the N-methyl-N-nitrosourea (MNU)-induced colon cancer modelling in rats. Study groups were designed as control group (CG), cancer control group (CCG), 5-Flourouracil group (FUG), Turkish mad honey group (HG), Turkish mad honey and 5-FU combined group (FU-HG). White blood cell (WBC), lymphocyte, eosinophil, basophil, serum lactate dehydrogenase (LDH), total oxidant status (TOS), and total protein values of the rats in the CCG were significantly lower than the values of the rats in the CG, whereas serum Bcl-2 and survivin levels were significantly higher in the rates belonged to the CCG in comparison to those in the CG. The presence of anaplastic epithelial cells, vascularization, precancerous changes, and inflammatory infiltration detected in the colon and small intestine of the rats in FU-HG, FUG, HG were less intense (P<0.05) compared to the findings in the rats in CCG. In conclusion, mad honey and 5-FU reduced anaplastic cell growth and oxidative stress via suppressed anti-apoptotic activity. Considering the histopathological findings in the liver and kidney, no toxicity occurred related to mad honey and 5-FU metabolization. Therefore, the combined use of these two substances may be an alternative method in the treatment of colon cancer.

An investigation of the anti-hypertensive effect of mad honey and Rhododendron luteum sweet extract induced by N- ω -Nitro L-Arginine Methyl Ester (L-NAME) in rats

An investigation of the anti-hypertensive effect of mad honey and Rhododendron luteum sweet extract induced by N- ω -Nitro L-Arginine Methyl Ester (L-NAME) in rats

Mad honey poisoning presenting with syncopal attack: a case report.

The authors report a case of 62 years old male with mad honey poisoning who was presented to the emergency department with loss of consciousness and had bradycardia and hypotension on arrival. The patient received intravenous fluids, atropine, and vasopressor support and was closely monitored in the coronary care unit for 48h. Grayanotoxin I and II are believed to be primarily responsible for mad honey intoxication and act by persistent activation of voltage-gated sodium channels. Hypotension, dizziness, nausea, vomiting, and impaired consciousness are the common presentation of mad honey intoxication. Toxic effects are usually mild and close monitoring for 24-48h is sufficient but life-threatening complications like cardiac asystole, convulsions, and myocardial infarction have also been reported. Most cases of mad honey intoxication only need symptomatic treatment and close observation but the potential for deterioration and life-threatening complications must also be considered.

Management of mad honey intoxication with suspected anaphylaxis in Nepal: a case report.

The authors reported the case of a middle-aged male patient who presented with blurring of vision, passage of loose stools, vomiting, and profuse sweating after ingestion of honey. He also had a history of loss of consciousness. On presentation, he was hypotensive and tachypneic with cold, clammy extremities. His ECG showed sinus bradycardia. The authors made a diagnosis of mad honey intoxication with suspected anaphylaxis. The authors treated him with intravenous normal saline, epinephrine, and atropine. He again developed hypotension and bradycardia in a few hours, for which hydrocortisone was administered, following which his heart rate was normalized in 2h. Overall, the recovery time in our patient was 8h. The patient was counseled to avoid consuming mad honey and did well on his monthly follow-up. Our patient had signs and symptoms suggesting intoxication following ingestion of mad honey with suspicion of anaphylaxis. Similar to other reported cases, the patient had sinus bradycardia and hypotension. Epinephrine and atropine were administered to treat hypotension and bradycardia, respectively. Also, refractory hypotension was managed by intravenous hydrocortisone. Usually, atropine and saline infusion are sufficient to manage these cases, and simultaneous use of epinephrine and atropine should be avoided unless indicated. Our case highlighted the approach to diagnosing and treating mad honey intoxication with suspected anaphylaxis.

Mad Honey and the Poisoner King: A Case of Mass Grayanotoxin Poisoning in the Roman Military.

We describe an episode of mass poisoning during the ancient Third Mithridatic War. In a brutal and well-planned ambush, forces from the Kingdom of Pontus destroyed a Roman column through the clever use of "mad honey." Incapacitated by the acute poisoning, the Romans were unable to hold off the Pontic forces. We conclude that the debilitating symptoms that the Roman soldiers experienced were due to the presence of grayanotoxins in the honey. Although they were likely self-limiting, developing these symptoms in an enemy ambush made a lethal combination. The "mad honey" environmental threat continues to persist in the Black Sea region to this day and is an etiology that modern physicians should be aware of.

Worldwide distribution and clinical characteristics of mad honey poisoning cases.

Mad honey poisoning is a common public health problem that can be seen in many parts of the world. In this study, the symptoms and clinical findings of mad honey poisoning cases and their distribution worldwide were investigated based on current data. PubMed, Scopus, Web of Science and Google Scholar databases were searched. The demographic characteristics of the cases, clinical findings, amount of consumed honey, duration of hospitalization, and data of the region where mad honey was produced were recorded. 900 cases were identified. The majority of poisoning cases (91.44%) were reported from mad honey produced in Turkey, Nepal (4.67%) came second and Korea (1.56) third. The majority of cases in Turkey were due to honey produced in the Black Sea Region. It was also determined that the mad honey was produced in the west Black Sea Region in most of the cases (35.22%), followed by the east Black Sea Region with a rate of 33.22%. In poisonous cases, it was determined that the mad honey was mostly produced in Rize, followed by Trabzon and Kastamonu, respectively. The most common signs of mad honey poisoning were bradycardia (88.48%) and hypotension (76.04%). The majority of cases have been reported from Turkey. When examining where the mad honey was produced in Turkey, it was seen that the western Black Sea Region came first, and the eastern Black Sea Region came second. Rize came first among the provinces, followed by Trabzon and Kastamonu. There is a parallelism between the distribution of mad honey poisoning cases and the distribution areas of Rhododendron species. However, although Rhododendron species show a widespread distribution throughout the world, why the majority of the cases were reported from Turkey draws attention as an issue that needs to be investigated.

826: THE LAND OF MILK, HONEY, AND . . . GRAYANOTOXIN???!!

Introduction: Grayanotoxins, also known as andromedotoxin, acetylandromedol or rhodotoxin, are derived from the plants belonging to genera of the Ericaceae (heath) family. The toxin binds to the group II receptor site in voltage-gated sodium channels and produces a continued action of vagal stimulation resulting in decreased blood pressure and decreased heart rate. Due to this action, some cultures consume this toxin intentionally for medical benefits. Rarely does this intoxication lead to death in humans. Description: Our patient was a 49-year-old female with no past medical history who presented to the emergency department a sudden onset of nausea, vomiting, and intermittent hypotension. The patient had recently traveled to her home country of Nepal. Upon her return, she had nasal congestion decided to make tea. To sweeten the tea, she added honey that she had bought while abroad. Shortly after ingesting the honey, her symptoms began. Her husband, who also had the honey at the same time, experienced similar symptoms. Initially, she was bradycardic to the fifties for EMS but in the sixties on arrival to the ER. She was significantly hypotensive in emergency department, which responded to 2 liters of intravenous fluids. Her nausea and vomiting had ceased with antiemetics, and the rest of her physical examination was normal. Due to the co-ingestion of the honey and emergence of symptoms, poison control was called and attributed these symptoms to “Mad Honey Syndrome,” a grayanotoxin toxicity that can occur from wild honeys is select regions, including Nepal. Discussion: This care highlights the continued need to take complete histories on our patients including all medications taken, both prescribed and not prescribed. For critical care providers, our differential diagnosis of shock grows by the day and makes this diagnosis even more difficult to make at times. Ultimately the patients’ symptoms abated, and both husband and wife were discharged home.

Wide diversity of pollens in honey samples from Indian Himalayan neighbourhoods: a melissopalynological study

Melissopalynological analysis of 34 honey samples (17 summer and 17 autumn samples) collected from feral colonies of Indian hive bee (Apis cerana), European bee (Apis mellifera) and rock bee (Apis dorsata) during 2011 – 2015 from the Shimla Hills of Himachal Pradesh (India) was performed. Pollen from plant taxa belonging to 43 families was found in the honey samples. Of 34 honey samples from the Shimla Hills, 18 were unifloral with 12 pollen types as predominant and the remaining 16 samples were multifloral. The predominant pollen plant taxa of summer were Pyrus sp., Malus domestica, Prunus amygdalus, Prunus sp., Eucalyptus camaldulensis, Citrus sp. and Rhododendron arboreum. In autumn, the predominant pollen plant taxa were Leucaena leucocephala, Salvia officinalis, Eriobotrya japonica, Impatiens balsamina and Prinsepia utilis. Melissopalynological analysis of summer honey collected from Summer Hill and Sarahan tagged these as “mad honey”, since Rhododendron pollen was predominant. The pollen spectrum indicated a diverse bee plant flora, which is promising indicator to augment the beekeeping industry in this region.

Bioactive Properties and Phytochemical Screening of Mad Honey Bee Pollen

Introduction: Mad honey is widely used in folk medicine in the Black Sea region of Turkey for its medicinal properties, but its pollen is not collected by mad honey producers and its benefits are unknown. Methods: In this study, water and ethanol extracts of mad honey bee pollen from four different plateaus in the Black Sea region of Turkey were researched for their antioxidant and antimicrobial properties. Phytochemical analyses were carried out and the data were supported with UV-Vis spectrophotometry. Antimicrobial activity was researched against four Gram-positive and four Gram-negative bacteria, one fungus, and one yeast. The results were compared with standard antioxidants and antibiotics. Results: The ethanol extracts of the samples from Sinop (P5), Giresun (P7), and Trabzon (P8) were the most active samples as antioxidants, and almost all the extracts of R. ponticum bee pollen were effective on the tested microorganisms. However, P5–8 showed better values for B. cereus, E. feacalis, E. coli, and P. aeruginosa. Conclusion: It has been proven that mad honey bee pollen is a natural product with previously unknown medicinal properties and rich phytochemical content. Future research and clinical trials are important to scientifically support its benefits in complementary medicine.

COMPARISON OF POLLEN MORPHOLOGIES EXAMINATION OF SOME Rhododendron SPECIES - PLANT SOURCE OF MAD HONEY

Honey is one of the important natural products used for apitherapeutic purposes as well as food consumption. The authenticity of the products to be used for apitherapy is very important. Botanical origin is one of the most critical factors affecting the characterization of bee products, especially honey. Therefore, melissopalynological analysis is essential in honey samples. In this study, the pollen morphologies of four different Rhododendron taxa, the origin of the monofloral "Mad honey" used for apitherapeutic purposes in Turkey, were examined. Five different measurement parameters have been used to investigate the pollen morphology of the plants. As a result, it can be said that pollen morphology has an important place in confirming the botanical origin of “Mad honey”.

Evaluation of the antioxidant potential of the mad honey collected from the black sea region in Turkey

Objective: Mad honey (Rhododendron honey) is produced by honeybees from Rhododendron flowers and contains grayanotoxins, antioxidants, flavonoid and phenolic properties. The mad honey samples are collected from Turkey's Black Sea region by local residents and are sold as mad honey in free market conditions. This study was planned to evaluate the total phenolic content, total flavonoid content and total antioxidant capacity and protein profiles with SDS-Page electrophoresis determined the mad honey samples collected from seven different locations from Black Sea region by local residents.
 Material and Method: Total phenolic content was determined by the modified Folin-Ciocalteu method. Total flavonoid content was determined by colorimetric method using aluminum chloride (AlCl3). Total antioxidant activity was calculated according to the free radical scavenging effect of 1,1-diphenyl-2-picryl hydrazyl (DPPH). Protein profiles evaluated with SDS-Page electrophoresis.
 Results and Conclusions: In Turkey, in the Black Sea Region, antioxidant potential of the honey samples known as mad honey, collected from seven different locations by local people, were evaluated. The mean total phenolic contents of the mad honey samples were found as 285,44±118,43 (125.85 to 471.18) mg GAE/kg honey, the mean total antioxidant activities were found as 29,68±7,2 (21.71 to 35.03) mg AAE/kg honey and the mean total flavonoid contents were found as 27,26±4,79 (19.93 to 39.18) mg QE/kg honey.
 The results revealed that the mad honey samples examined in this study were a good source of antioxidant, flavonoid and phenolic content at varying levels depending on the characteristics of the region where they were collected.

Watershed infarction after honey intoxication

Watershed infarction indicates ischemic lesions at the junction of two central artery regions. These lesions are the cause of 10% of all brain infarctions. In watershed infarctions, disrupted hemodynamics constitute the pathophysiology. A specific type of honey in the Black Sea region of Turkey, “mad honey,” contains grayanotoxin and may cause intoxication. We herein report a case with watershed infarction after honey intoxication. The patient presented with dizziness and paresthesia in the left arm after eating “mad honey.” Imaging revealed carotid stenosis and watershed infarction.

Pollen and Physicochemical Analysis of Honey Samples from Akçakoca and Yığılca District (Western Black Sea)

Turkey, with its rich flora and high endemism proportion in a temperate zone, is highly favorable for beekeeping. In the studied area, two honeybees are present: Apis mellifera anatoliaca and the Yığılca local honeybee, which has been determined as local ecotype of anatoliaca in the Black Sea region. The main objective of this study was to determine the botanical sources of honey samples, which are produced by these two honeybees, from Akçakoca and Yığılca district. Chestnut and mad honey samples were obtained from local beekeepers. Pollen types in the honey samples were identified and determined the frequency classes. Castanea sativa was identified as the predominant pollen among the honey samples of Anatolian honeybee; these samples were classified as monofloral honey. Besides, Rhododendron ponticum and Lysimachia verticillaris pollens were found to be the important minor pollens in the mad honey samples of Anatolian honeybee. Mad honey samples from the Yığılca local honeybee were a multifloral honey and included Rhododendron ponticum and five other pollens as important minor pollen. In addition, physicochemical analyses were also performed. The honey samples gathered from the Yığılca district were deemed acceptable. On the other hand, the honey samples from the Akçakoca district were found acceptable except for moisture content. Also, 104 plant specimens were collected around beehives and 54 taxa were reported as melliferous plants. The Sorensen similarity coefficient, calculating among the melliferous plants of two localities (Akçakoca and Yığılca), was 51.85%. Diversity of melliferous plants was also higher in Yığılca than in Akçakoca.

A New Risk Factor for Hepatic Encephalopathy: Ingestion of Mad Honey

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in the severe liver dysfunction and is characterized by a wide range of central nervous system symptoms. HE precipitated with mostly infections, gastrointestinal bleeding, diuretic overdose, electrolyte imbalance, constipation and drugs. Traditional local foods for example honey can contain toxins for the liver and could cause acute decompensation in patients with chronic liver disease (CLD). This toxins can cause dose related severe symptoms. Spectrum of the symptoms are from nausea vomiting to life threatening bradycardia and/or hypotension. In this paper; we reported first time in English literature a cirrhotic case with HE due to consumption of mad honey.