Route Of Exposure

Honey is produced by domesticated and many wild bees from flower nectar and other plant secretions. Honey was used by early humans as a food and a medicine, and honey found in Pharaohs' tombs in Egypt in modern times has still been edible. More than 300 types of honey are recognised, the most common being buckwheat and clover. The main division of these types is between flower and forest honey, the former coming predominantly from meadow-like areas and flower nectar.

The taste of honey is due mostly to the essential oils in the nectar. As nectar and other secretions vary considerably in these oils (and in sugar, protein, mineral and water content) from one kind of plant to another, so honey will vary; and weather and soil are additional factors. The colour of honey also varies, from nearly colourless to deep red-amber – mainly according to the type of nectar from which it is made. In general, the darker the colour of the honey, the stronger the flavour.

The bee stores the nectar in a tiny compartment known as the honey sac. The bee then mixes enzymes and glandular excretion into the nectar to convert the sucrose (disaccharide) to more simple sugars (mono-saccharides). The nectar then becomes honey, which consists mainly of two simple sugars, dextrose and levulose. But over 180 different compounds and 22 sugars have been found in honey. Honey contains many volatile components, of which at least 35 have been identified. Honey also contains choline and acetyl choline.

Enzymes in honey are extremely important, playing a major role in converting the nectar: these enzymes include invertase, diastase, oxisase, catalase, glycerophosphatase, amylases and phosphates. At least one product of the conversion, hydrogensuperoxide, can destroy bacteria.

The honey in the honey bee's sac is called ‘unripe Honey’ and is passed by the honey bee to a worker bee at the hive. The ‘unripe Honey’ is dried by these worker bees, who expose it as a thin film to the warm dry currents in the hive. When no more than 18-20% of the original water remains, the now-‘ripened’ honey is sealed in a cell with a wax cap; where it is left to mature and finish the ripening process. Then it can be harvested by the beekeeper, or eaten by the bee colony.

The pollens present in honey vary from region to region. As honey is made from many plant sources, any of the ‘parent’ plants' pollen may be found in the honey. Possible sources of plant nectar include acacia, blue gum, citrus, clover, cosmos, eucalyptus, heather, Cape fynbos, grape, lucerne, sunflower, and other wild flowers. Exotic varieties include avocado, litchi and mango.

Honey is sold in the comb, as the extracted liquid, and in solid and granular forms. It is a common ingredient in pastry, sweets and sauces, especially in ethnic cuisines that predate the availability of processed sugars.

Other hive products include bee pollen, propolis, royal jelly, and beeswax, all of which play roles in health care and beauty care.

Royal jelly is produced within the bodies of worker bees and has complex etherogeneous mixtures of sugar, fatty acids, nectar, proteins, minerals and glandular secretions of bees; but its exact chemical composition has not been defined.

Bee glue, commonly known as propolis, is obtained mainly from the bark of poplar trees. In the hives, the glue is used to stabilise the cells and honeycombs and to protect the bees against invaders and cold weather. Propolis has been employed medicinally, chiefly in ointment and plasters for surgery and other treatment of wounds. Beeswax is a common additive in food and non-food consumer products.

Honey may be used as a natural means of giving colour, scent and emollient properties to cosmetics. The aroma and colour depend on the plants from which the nectar was taken. Honey has been used to impart both aroma and taste to cigarettes.

Clinical Relevance

Allergen Description

No allergens have been characterised, but early studies indicated the presence of 10 to 19 proteins between 14 kDa and 500 kDa with allergenic potential. Subsequently, honey, bee venom, honey bee body components, and pollens were shown to be the main sources of allergens detected in honey. The allergens detected in pollens will depend on the source of the honey. Compositae pollen is a frequent source of allergens. Mould spores and algae may also be present. Calculations are that 10 grams of honey contains 20 to 10 000 grains of pollen, which retain their allergenic properties during the honey-making process.

In a study of honey derived from sunflower, IgE binding to proteins of 54 kDa, 60 kDa, and 72 kDa, or to a 30 kDa/33 kDa double band, or to both, were identified. The higher-molecular-mass proteins were also detected in locust tree, European chestnut and forest honey. The proteins detected represented bee products, as IgE binding to these proteins was inhibited by extracts of honey bee heads and isolated bee venom sacs. The 30 kDa/33 kDa bands were shown to be sunflower honey-specific. In 7 out of 10 honey-allergic individuals, serum IgE bound to bee-specific components. The authors concluded that proteins derived from secretions of pharyngeal and salivary glands of honey bee heads and pollen proteins contained in the honey were responsible for allergic reactions to honey.

In a study of 3 Honey-allergic patients, proteins of 54, 46, 17 and 16 kDa were detected. However, attempts to identify the proteins with most common honey allergens failed. The authors concluded that if bee-derived components are not proven to be involved in honey sensitisation, other protein sources such as nectar should not be disregarded.

Potential Cross Reactivity

Cross-reactivity would depend on the component to which the honey-allergic individual is allergic, e.g. sunflower pollen or Compositae pollen.

Clinical Experience

IgE-mediated reactions

Honey appears to be a common self-reported allergy. However, it may be that honey only uncommonly induces symptoms of food allergy in sensitised individuals. In a study of 4 331 students, none was allergic to honey. The hypothesis that honey allergy should be more prevalent because of the presence of pollen allergens in honey was negated in a study in which 46 patients with pollen allergy were challenged with either honey or a placebo through a double-blind method, and either no reactions or negligible reactions were reported.

Nonetheless, in sensitised individuals ingested honey can result in reactions varying from cough to anaphylaxis. Components in honey responsible for the reactions are usually thought to be pollens (in particular those from the Compositae family) or glandular secretions and body material. Pollen present will depend on the source of the honey and will vary from region to region. Some authors suggest that allergy to honey should be considered in any patient with unresolved food allergy.

Although allergy to honey is thought to be uncommon, some authors have accumulated a number of reports of honey-allergic individuals. A study described 23 patients allergic to honey who all displayed allergic symptoms after ingestion of honey or honey-containing products – symptoms ranging from itching in the oral mucosa to anaphylactic shock. A study described 22 patients with a history of systemic allergic symptoms following honey ingestion who underwent skin- and serum-specific IgE tests with 3 different kinds of Swiss honey (dandelion, forest and rape), pollen of Compositae species, celery tuber, extract of bee pharyngeal glands, honey bee venom and bee whole body extract. The results indicated that 75% of these honey-allergic patients were sensitised to dandelion honey and 13 of the 22 to Compositae pollen as well. Nine of the honey-allergic patients were sensitised to honey bee venom, and 3 also to bee pharyngeal glands and to bee whole body extract.

Several case reports illustrate the various adverse allergic reactions ascribed to honey. A 68-year-old housewife who complained of abdominal pain after eating honey since her childhood also reported the recent onset of accompanying urticaria. She was initially able to eat forest honey but not flower honey but then was unable to tolerate either. Serum-specific IgE tests were negative. A 46-year-old woman described acute urticaria and nasal discharge after eating coconut, vanilla and honey. Skin- and serum-specific IgE to honey were negative. A 63-year-old man developed recurrent generalised urticaria and angioedema while on chemotherapeutic agents; these reactions were associated with the ingestion of honey and royal jelly. Skin and serum IgE to honey were negative, and the reactions stopped with cessation of honey and royal jelly ingestion. A 50-year-old man experienced acute angioedema after tasting honey each of 3 times. A 60-year-old male experiencing diarrhoea for 25 years, with no aetiology being found, had experienced 4-5 episodes of acute urticaria from honey.

Allergy to honey has been reported in children. A 12-year-old was reported to have experienced 2 episodes of angioedema with dysphagia, dysphonia, and dyspnoea a few minutes after the ingestion of honey. IgE antibody tests to honey and bee venom were negative, but prick-by-prick IgE tests with artisan honey were positive.

In a study of food allergy in 674 Spanish patients, the prevalence of food allergy was 9.1%. Honey was positive in one of 31 patients challenged. A cross-sectional, descriptive, questionnaire-based survey was conducted in Toulouse schools in France to determine the prevalence of food allergies among schoolchildren. Of 2 716 questionnaires, 192 questionnaires reported a food allergy, of which only one self-reported allergy to honey.

Allergic reactions may be severe, resulting in anaphylaxis. Two case reports of anaphylaxis and generalised urticaria or angioedema due to honey and royal jelly ingestion in patients sensitised to mugwort were described: A 55-year-old woman with allergic rhinitis developed angioedema of the lips and tongue, cough, rhinorrhoea and profound hypotension ten minutes after eating honey, and a 22-year-old male with allergic rhinitis developed generalised urticaria and angioedema of the lips immediately after eating a small amount of royal jelly. Skin-specific IgE using the prick-by-prick test to fresh honey and/or royal jelly was positive. Serum-specific IgE was positive in both. Anaphylaxis due to honey containing mesquite pollen and Sunflower pollen has been reported.

Anaphylaxis caused by honey ingestion has also been described in a 14-month-old infant. He had been given approximately one teaspoon of honey several times until he was six months old. At 14 months of age his mother gave him approximately five teaspoons of honey. After five minutes his lips swelled, and within 10 minutes urticaria, angioedema, cough and wheezing occurred. A subsequent prick-to-prick skin test performed with the implicated honey (and with honey frequently consumed in Turkey that is made from another two species) was positive for the honey that had been eaten, negative for flower honey, and weakly positive for honey composed of mixed flower and pine honey. Skin-prick tests with common pollens and pinus pollen were also negative.

Mugwort belongs to the Compositeae family, as does Sunflower. A 24-year-old man developed rhinitis and conjunctivitis over 5 years of exposure to Sunflower pollen. All respiratory and occular symptoms disappeared after he was removed from exposure, but he had a food-allergic reaction while he was eating Honey containing 30% Sunflower pollen. The Honey responsible was shown to significantly inhibit Sunflower pollen-specific IgE.

Similarly, anaphylaxis to honey was described having occurred in a 19 year old female with rhinoconjunctivitis and sensitized to Compositae pollen. Ten minutes after eating bread and honey she developed angioedema of the lips and tongue, runny nose, cough, dyspnoea, and collapsed, requiring hospitalization. Skin prick tests were positive to mugwort, ragweed, dandelion, and goldenrod. The prick to prick test was positive to 'Millefiori' (obtained from bees foraging on Compositae) and also to sunflower, lime tree, and gum tree honey, and negative for other kinds of honey, including the frequently used chestnut honey and acacia honey. The authors suggested that the allergen responsible was probably derived from Compositae pollen, but also in pollen from plants of different families.

Further evidence for pollen from plants of the Compositeae family affecting the allergenicity of Honey is found in a study of 9 patients with hay fever, with or without asthma, who experienced systemic allergic reactions after ingestion of natural Honeys from 2 local areas (Andujar and Granada). Pollen analysis showed a high level in Sunflower pollen (23.6% of pollen grains) in the Honey from Andujar but not in that from Granada. Conjunctival challenge with Camomile extract for specific IgE was positive, suggesting to the authors that pollen of Compositae may be responsible for IgE-mediated allergic reactions to certain natural foods. A 42-year-old beekeeper with an inhalant allergy to Compositae pollen experienced an allergic reaction to honey which contained Compositae pollen. She was asymptomatic to honey that contained no Compositae pollen.

Nonetheless, although sunflower or other Compositae may be a significant factor, other constituents in honey may be responsible for these adverse reactions. In 23 patients allergic to honey (including sunflower honey), with symptoms ranging from itching in the oral mucosa to anaphylactic shock, proteins derived from secretions of pharyngeal and salivary glands of honey bee heads found in the honey were responsible for causing allergic reactions to honey. Nonetheless, the constituents responsible for allergy may not be found, as in the case of 3 patients, all with a similar clinical history of sensitisation to honey and the presence of skin- and serum-specific IgE to crude honey extract, but not to pollen proteins or proteins from Hymenoptera insects or other common allergens present in honey.

A widely-held belief that honey relieves the symptoms of allergic rhinoconjunctivitis could not be substantiated. Indeed, patients with allergic rhinitis may be at increased risk of allergy to honey, as indicated in a study of 448 patients with rhinoconjunctivitis in which 3 individuals were found to be honey-allergic.

Allergic contact cheilitis induced by repeated contact with propolis-enriched honey has been described.

Occupational asthma caused by honey has been reported in a 42-year-old woman working for 8 years in quality control in a company producing breakfast cereal. She developed an intermittent wheeze, cough, dyspnoea, and generalised rash starting within 1 hour of the spraying of a vanilla and honey mixture onto the cereal. During this process, clouds of the mixture could be seen in the air and would settle on the workers’ clothes and exposed skin. Skin-specific IgE testing for 24 common allergens was negative, but positive for honey. An inhalational challenge with honey extract resulted in an immediate and a delayed asthmatic reaction. Serum-specific IgE to honey was significantly high.

Similarly, seasonal occupational allergy to honey bee body dust was described in an individual working in a honey processing plant. Severe asthma coincident with the seasonal honey-packing process occurred; symptoms correlated with duration of exposure inside the plant, and improved in other environments. Skin- and serum-specific IgE and bronchial provocation tests with honey bee whole body extract were positive. Exposure to bee body parts was attributed to loading of honeycomb frames.

It is important to consider that honey may be a ‘hidden’ allergen, as illustrated by the report of a patient, diagnosed with anaphylaxis due to honey, who suffered two episodes of urticaria after the ingestion of white coffee, probably due to contamination by incomplete cleaning of the containers previously used for serving infusions containing honey.

Other reactions

Honey contains fructose in excess of glucose, which may lead to incomplete fructose absorption associated with abdominal symptoms and/or diarrhoea. In a study of 20 healthy volunteers, each drank the following solutions: 20g lactulose, 100g honey, 50g honey, and 35g of a glucose and fructose mixture. Within 10 hours after the ingestion of the 100g honey and 50g honey solutions and the glucose-fructose mixture, 6, 3 and 0 of the volunteers, respectively, reported loose stools, suggesting that carbohydrate malabsorption after ordinary doses of honey is frequent in healthy adults and may be associated with abdominal complaints.

Honey poisoning (or ‘honey Intoxication’) was described over 4 decades ago, and occurs because of the presence of grayanotoxins (formerly known as andromedotoxins, acetylandromedol, and rhodotoxin). Grayanotoxins are present in honey produced from the nectar of rhododendrons in particular. The presence of specific grayanotoxins varies with different plant species. Other names associated with this condition are rhododendron poisoning, mad honey intoxication and grayanotoxin poisoning. Symptoms of poisoning are dose-dependent and may occur after a few minutes to two or more hours, and include salivation, vomiting, and paresthesia, circumorally and/or of the extremities. Hypotension and sinus bradycardia may develop.

Grayanotoxin poisoning most commonly results from the ingestion of grayanotoxin-contaminated honey, although it may result from the ingestion of the leaves, flowers, and nectar of rhododendrons. Not all rhododendrons produce grayanotoxins, but Rhododendron ponticum (which grows extensively on the mountains of the eastern Black Sea area of Turkey, and also in Japan, Nepal, Brazil, and some parts of Europe) is a common cause, as are a number of species native to the United States, including western azalea (Rhododendron occidentale), the California rosebay (Rhododendron macrophyllum), and Rhododendron albiflorum.

Grayanotoxin-contaminated honey may be derived from other members of the Ericaceae family, to which rhododendrons belong. Mountain laurel (Kalmia latifolia) and sheep laurel (Kalmia angustifolia) are the most important alternate sources of the toxin. Although the majority of honey-induced poisonings has been reported in Turkey, a Swiss study documented 8 cases of honey-induced poisoning at a single hospital. The most prominent symptoms were loss of consciousness, weakness, severe salivation, sweating, vomiting and diarrhoea.

Numerous studies have shown that the ingestion of honey is linked to infant botulism. Honey samples across the United States have tested positive for Clostridium botulinum spores and toxins. Such substantial evidence led the Centers for Disease Control to recommend that honey not be given to infants younger than 12 months old. The high osmotic pressure of honey prevents most infectious agents from growing in it. Honey does not contain Clostridia bacteria but can contain its spores, which may germinate and produce toxins in the intestinal tracts of infants, although they have not been shown to do so in adults. Infant botulism from honey has been reported worldwide. Symptoms may include constipation, poor feeding, generalised weakness, poor head control, difficulties in sucking and swallowing, and cranial nerve dysfunction.

Pyrrolizidine alkaloid-containing plants are a significant source of honey worldwide and may be a potential threat to health, especially for infants and foetuses, as honey from these plants may contain pyrrolizidine alkaloid compounds such as jacoline, jacozine, jacobine, seneciphylline and senecionine. Honey from ragwort (Senecio jacobaea) is a particular risk. Pyrrolizidine alkaloids may also occur in honey from Echium plantagineum (Paterson's curse).

Fifteen persons developed atropine poisoning following consumption of wasp honey produced from Datura plants near the wasp nests. Two deaths occurred from heatstroke because of the poisoning, high environmental temperatures and intensive physical activity. Similarly, repeated atropine poisoning was described resulting from intermittent ingestion of atropine-containing honey.

Honey may be contaminated by various antibiotics or herbicides, including asulam (and its antibacterially active metabolite, sulphanilamide) and chloramphenicol. In a German study, 100 honey samples from various countries in Eurasia, Oceania, and the Americas were analysed for tetracyclines, streptomycin, and sulfathiazole, and 42% of the samples were positive.

A 34-year-old Spanish woman with a lifelong history of seasonal rhinoconjunctivitis and honey intolerance (pyrosis and abdominal pain) developed anorexia, abdominal pain, diarrhoea, peripheral blood hypereosinophilia and elevated total serum IgE levels 3 weeks after starting ingestion of bee pollen. A duodenal biopsy showed eosinophilic infiltration of the mucosal layer.