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Honey in otorhinolaryngology: When, why and how?
European Annals of Otorhinolaryngology, Head and Neck diseases (2011) 128, 133—137
REVIEW OF THE LITERATURE
Honey in otorhinolaryngology: When, why and how? A. Werner , O. Laccourreye ∗ Université Paris-Descartes, Service d’oto-rhinolaryngologie et de chirurgie cervicofaciale, hôpital européen Georges-Pompidou, Assistance publique—hôpitaux de Paris, 20—40, rue Leblanc, 75015 Paris, France Available online 9 February 2011
KEYWORDS Honey; Otorhinolaryngology
Summary In this review of the literature devoted to the use of honey, the authors analyse the composition, indications, benefits and adverse effects of this product in otorhinolaryngology and head and neck surgery. Published data indicate that honey applied topically to skin and mucosal wounds and/or burns and administered orally as antitussive medication (after the first year of life) is highly effective with no adverse effects. The physiological action of honey is the result of various mechanisms (osmotic, detersion, bactericidal action). Various medicinal honeys are available worldwide, but only one has Food and Drug Administration approval for the treatment of wounds. After the first year of life, the use of food honey appears to be as effective as medicinal honey, while decreasing the overall cost of treatment. © 2011 Elsevier Masson SAS. All rights reserved.
Introduction Religious texts describe honey as a great gift to mankind (Table 1) and honey has been used for medicinal purposes for more than 4000 years [1]. Sumerian tablets dating from 2100 B.C. describe the use of honey in various recipes and dressings [1]. About 500 remedies are also described in the Smith, Ebers and Kahum papyruses written in Egypt between 2000 and 1000 B.C. [1]. In India, at the same period, Ayurvedic physicians considered that honey acted on the essential elements (air, fire, bile and circulation) that determine man’s equilibrium and Susrhuta, a surgeon of the time, advised coating honey mixed with butter to an infected ear lobe after piercing [1]. Hippocrates prescribed honey for burns, boils and abscesses, while Dioscorides, a physician of the Roman army
∗
Corresponding author. Tel.: +01 56 093 463; fax: +01 56 093 468. E-mail address: [email protected] (O. Laccourreye).
in 50 B.C., used honey to treat wounds and inflammation of the throat and tonsils [1]. In the Hippocratic Corpus, honey is mentioned 542 times (particularly in the treatise on gynaecology and internal diseases, but also for pleurisy, diseases of the ileum, as a suppository for haemorrhoids, or by application to the eye and on wounds) and notes that: . . .‘‘wine and honey are wonderfully adapted to man; both in health and in disease, they are administered wisely and justly according to the individual constitution’’ [2]. Finally, Galen, in De Naturalibus Facultatibus, wrote that honey is ‘‘. . . excellent for the elderly, but harmful to the hot tempered. . .’’ [2]. However, the first modern scientific article devoted to the healing properties of honey was only published in 1936 [3] and although the literature devoted to honey has continued to grow, with more than 920,000 hits on the Google search engine in 2010 for the combination of ‘‘honey’’ and ‘‘treatment’’, to our knowledge, no article has been published on this subject in the French otorhinolaryngology literature. In view of this lack of data, the authors decided to review the medical literature (PubMed
1879-7296/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.anorl.2010.12.002
134 Table 1
A. Werner, O. Laccourreye Honey in religious texts.
Origin
Quotation
Homeric hymn to hermes
‘‘. . . yellow honey. . . the gods’ sweet food. . .’’
The Bible Psalm 119: verse 103 Exodus 33: 8
Koran Sourate 16: verses 68—69
‘‘How sweet are Your words to my taste, sweeter than honey to my mouth’’ ‘‘And I am come down to deliver them out of the hand of the Egyptians, and to bring them up out of that land unto a good land and a large, unto a land flowing with milk and honey...’’ ‘‘And your Lord inspired the bees, saying: ‘Take you habitations in the mountains and in the trees and in what they erect. Then, eat of all fruits, and follow the ways of your Lord made easy (for you).’ There comes forth from their bellies, a drink of varying colour wherein is healing for men. Verily, in this is indeed a sign for people who think.’’
search), and study the composition, mechanism of action, indications and adverse effects of honey in otorhinolaryngology as well as the future prospects of this gift of the gods.
Composition of honey Honey is an acidic product (pH 4) with a variable chemical composition according to the flowers from which it is derived. On average, it is composed of about 80% sugars (glucose, fructose, sucrose, levulose, maltose, sucrose), 17 to 20% water, and 4% of various other substances (pollen grains, proteins, enzymes, hydrogen peroxide, amino acids, organic acids, polyphenols, vitamins (except for vitamin A), minerals, and more than 100 volatile substances (alcohols, esters, aromatic substances) [1]. The low water concentration of honey helps to prevent the growth of micro-organisms (yeasts, fungi, bacteria), but as this product is hygroscopic, when left in contact with air for several months, its relative humidity increases to more than 50%, resulting in fermentation [1]. The composition of honey varies according to its source, the harvest season, the plants from which nectar is gathered, the modalities of honey collection and storage. As honey is produced by bees, which collect dust deposited on plants during pollen gathering, honey is subject to various potential sources of contamination. The best-known form of contamination is that due to the pesticides, antibiotics and acaricides used by beekeepers and farmers. However, the quantities of these contaminants are very small and below the limits accepted by the international literature [4]. Contamination by Caesium (134 and 137) mainly affects heather honey and is due to atmospheric nuclear tests and the Chernobyl accident. Finally, honey is not sterile and can contain bacteria (B. subtilis and C. botulinum). In 2005, Nevas et al. [5], in an analysis of 235 types of honey taken from hives in Nordic countries (Denmark, Norway, Sweden), demonstrated the presence of Clostridium botulinum (serotype A, B, E or F) with an incidence ranging from 2 to 26% depending on the country. However, honey can be sterilized by gamma radiation (2.5 cGy) without loosing its biological properties [6].
Biological effects The two main biological effects of honey are its antiseptic and healing properties. These properties are classically attributed to two factors: hydrogen peroxide (H2 O2 ) and hyperosmolarity [7,8]. The H2 O2 present in honey acts as a detergent in relation to bacteria present in the wound. The hyperosmolarity of honey, induced by its very high sugar content, generates a physical effect: by absorbing water, the sugars present in honey modify the surface osmotic pressure in the wound, which mechanically prevents any bacteria present from adhering and proliferating and also reduces local inflammation by promoting exudation. These biological effects provide ideal conditions for the development of granulation tissue and healing. In addition to these two factors, recent studies have demonstrated direct antibacterial effects for two components of honey: methylglycoxal (MGO) and a protein, bee-defensin 1 [8—10]. The various published in vitro studies analysing the local antibacterial activity of honey emphasize that: • this activity concerns a large number of bacteria (Escherichia coli whether or not beta-lactamase producing, Enterococcus whether or not vancomycinresistant, Staphylococcus aureus whether or not methicillin-resistant, Pseudomonas aeruginosa whether or not ciprofloxacin-resistant, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter, and Streptococcus); • the antibacterial activity of honey is 5- to 11-fold higher than that obtained by application of sugar solutions, thereby demonstrating that the antibacterial activity is not simply due to the osmotic effect of its sugars [8—15]. The many in vitro studies that have compared various types of honey emphasize variations in their respective hydrogen peroxide, MGO and bee-defensin 1 protein concentrations, with preferences very clearly influenced by the author’s nationality. The current standard in terms of honey is situated in the south hemisphere and Australian and New Zealand articles all conclude on the superior efficacy of their honey, Manuka honey derived from an indigenous tree
Honey in otorhinolaryngology: When, why and how? Table 2
135
The main types of medicinal honey marketed in the world.
Honey name
Company name
Country
Price
Medihoney®
MediHoney TM Comvita Medical Derma Sciences Triticum Company Advancis Mediprof
Australia New Zealand USA Netherlands England Netherlands, Belgium, England, Greece
10 D
L-Mesitran® Activon® Honeysoft®
(Leptospermum scoparium). However, Irish authors conclude on the superiority of Chilean honey derived from the Ulmo bush (Eucryphia cormen) compared to Manuka honey [12]. In an Indian study from Madras, the authors concluded on the superiority of the local honey (Khadikraft) compared to Australian Manuka or British honey [13], while all Malaysian authors highlight the advantages of Tualang honey and Dutch authors report that Manuka honey does not contain bee-defensin 1 protein [8,14]. All of these comparisons, with unanimous conclusions concerning the healing and therapeutic efficacy of these various types of honey, are not devoid of economic influences, as several medicinal honeys are now available on the market (Table 2). The current market of products intended for the treatment of wounds is considerable. In the USA, in 2010, financial reviews estimated this market at 14 trillion dollars [16] and the North American company Derma Sciences Inc. (Princeton, New Jersey), specialized in skin care products, recently acquired a Manuka honey-based paste approved by the Food and Drug Administration for the treatment of wounds that it markets under the brand name of Medihoney® . It should also be emphasized that the presence of proteins and polyphenols (caffeic acid, chrysin, galangin, quercetin, apigenin, pinobanksin, pinocembrin, acacetin) in honey also confers an antioxidant and potentially antimitotic action. Several studies have demonstrated that application of honey to the tumour site inhibited tumour growth in vivo in mice and the growth of various cancer cell lines in vitro [11,17,18], but no clinical study has yet been conducted in man to confirm this potential antitumour action.
Therapeutic properties of honey Honey is a food and topical application or ingestion of honey for medicinal purposes treatments must be performed daily. By topical application (Table 3), the wound is cleaned with physiological saline and honey is then applied with a compress. Deep wounds can be filled to three quarters, then covered with a dressing. Three meta-analyses devoted to evaluation of the healing properties of honey have been conducted over the last 10 years. The first two meta-analyses, published in 2001 and 2008, devoted to the beneficial effects of honey in burns and superficial wounds and acute and chronic wounds (venous, arterial, diabetic ulcers), concluded that analysis of the studies published before 2000 and the 19 randomized studies published since 2000 did not formally
13.59 D 8.45 D On request
and scientifically (due to the many, major methodological biases) demonstrate the superiority of honey, compared to other treatments [7,19]. However, the authors also reported that the results obtained with honey dressings in terms of healing, infection control and sterilization are often superior to those obtained with conventional dressings with or without concomitant antibiotic therapy [7,19]. The most extensive experience of the use of honey in the field of wound healing was reported by a French surgeon from Limoges, Prof. Descottes. Based on a cohort of more than 3000 wounds, 94% of which corresponded to postoperative wound dehiscences, this author emphasized the benefits of honey (healing after failure of conventional treatment, two-fold faster healing rate with than tulle gras dressings, very good cosmetic quality of healing, 98% success rate), and the low cost of the thyme honey used [20]. Visavidia et al. [21], in Great Britain, emphasized the value of first-line honey dressings on rapidly infected postoperative maxillofacial wounds in their everyday clinical practice. These published results are in line with our experience of the regular use of honey in our department since 1970, under the influence of Prof. Henri Laccourreye, by twice daily topical application and regular oral ingestion several times a day, to treat salivary fistula after head and neck cancer surgery or for any healing problems after head and neck surgery. According to Ganacias-Acuna [22], honey can also be combined with the use of negative pressure to promote wound healing. In the last meta-analysis published in 2008, devoted to the role of honey in oncology, Bardy et al. [23] while concluding on the poor quality of the 40 or so studies analysed due to various methodological problems, also emphasized that honey is as effective as usual treatments for radiation mucositis, radiation dermatitis, chemotherapy-induced hand-foot syndrome and/or postradiotherapy wounds of the skin or oral cavity. The efficacy of honey in radiation mucositis was recently confirmed by Rashad et al. [24], who highlighted the efficacy of honey in prevention of serious mucositis by topical application onto the oral mucosa followed by ingestion of 20 ml of honey 15 minutes before, 15 minutes after, and 6 hours after each radiochemotherapy session (60—66 Gray; 2 cGy/week; cisplatin 20 mg/m2 once a week). Recurrent labial herpes lesions also appear to be very sensitive to topical application of honey. In a randomized study comparing honey application several times a day (four times daily for 15 minutes) versus acyclovir (six times daily), based on analysis of the healing time, pain relief, resolution of local signs and prevention of acute attacks, Al-Waili [25]
136 Table 3
A. Werner, O. Laccourreye How to apply honey on a wound.
Clean the wound with physiological saline Apply honey Shallow wound: compress soaked in honey (30 ml of honey for a 10 × 10 cm compress) Deep wound: directly fill 3/4 of the wound with honey Cover with an absorbent or occlusive dressing Change the dressing once or twice a day (rinsing with physiological saline) until the appearance of granulation tissue, then every 48 hours
concluded on the significant superiority of honey (P < 0.05) and attributed the therapeutic effect obtained to the presence of copper, ascorbic acid and hydrogen peroxide in honey, which inactivate the Herpes simplex virus, and to local inactivation of prostaglandins. A last potential indication for honey appears to be cough and respiratory difficulties in children following upper respiratory tract infections. In a double-blind study conducted in the United States in 2009 on 105 children comparing buckwheat honey versus a classical dextromethorphan-based antitussive (Drill® , Humex® ) and no treatment, the authors concluded on the superiority of honey in the treatment of nocturnal cough in children over the age of 1 year: less cough and better sleep for the child and the parents [26].
Limitations and adverse effects of honey Due to its acidic pH, honey can cause unpleasant or even painful feelings during application or ingestion that may limit its use. In a study in rats comparing honey dressings and conventional dressings for the treatment of auricular burns, Hashemi et al. [27] reported that the chondritis rate was higher in the group treated with honey. The proximity of cartilage may, therefore, constitute a limiting factor to the healing efficacy of honey. Similarly, according to Descottes [20], a history of local radiotherapy limits the healing properties of honey on skin wounds. Allergy to honey or its ingredients and pollutants is extremely rare, but possible [1]. The main issue concerning the adverse effects of honey concerns the risk of botulism. Due to the presence of Clostridium botulinum spores (but not botulinum toxin) in honey derived from many hives [5] and inactivation of these spores by low-dose gamma radiation (2 cGy) [6], it is frequently recommended in the medical literature that only irradiated honey should be ingested and/or applied to wounds. However, there are no published cases of botulism in adults following the ingestion or topical application of honey, despite the fact that the very great majority of studies on honey were conducted in developing or lowincome countries, in which gamma sterilization of honey is not performed. Similarly, in France, no cases of botulism were reported in the cohort published by Descottes [20] (in which honey does not appear to have been sterilized) or in our own experience (in which a commercially available food honey has been used since 1970 to treat salivary fistula and/or wounds after neck surgery). Finally, the cases of botulism reported in adults in France are not related to ingestion of honey despite the fact that this product is extensively used by the population [28]. However, several cases
of botulism related to honey have been reported in infants under the age of 1 year in the United States and France, where the incidence of this disease has been increasing since 2000 [26,28,29]. In these cases, honey is ingested as treatment or as a food supplement. Clostridium botulinum then proliferates in an immature gastro-intestinal system and produces botulinum toxin which subsequently induces botulism. Honey, that has not been sterilized by gamma radiation, should therefore not be used as a sweetener, food substrate and/or in the context of medicinal ingestion in infants under the age of 1 year [26,28,29]. In the light of the published scientific data and the experience acquired over the last 30 years in Limoges, in Prof. Descottes’ Department of Surgery [20], and in Paris, in the Department of Otorhinolaryngology and Head and Neck Surgery at Laënnec hospital and then, at the Georges Pompidou European hospital (no cases of botulism reported after application of honey to neck wounds, pharyngostome and/or radiation mucositis), the food honey available in France can, therefore, be used in patients over the age of 1 year in otorhinolaryngology and head and neck surgery with no medicolegal risks at the present time.
Conclusion In this age of budget restrictions and optimization of medical resources, the research and development of effective and inexpensive treatments constitute a major concern for all clinicians. In this context, application of honey to inflamed mucosa and head and neck skin or mucosal wounds provides a real therapeutic benefit. The local action of honey on multiresistant bacteria also participates in more effective antibiotic practices. The antitussive action of honey also appears to be useful in infants over the age of 1 year. The other properties (antioxidant and antimitotic) of systemic administration of honey need to be formally demonstrated by in vivo studies, although many articles based on animal experimentation and cell culture are in favour of these effects. None of the thousands of varieties of honey available throughout the world appears to be truly superior. Various countries, such as Australia and the United States have already developed the medicoeconomic use of this product. When will a French medicinal honey be available?
Conflicts of interest statement None.
Honey in otorhinolaryngology: When, why and how?
Acknowledgements The authors would like to thank Progrès 2000 for technical and financial support for this study.
References [1] Magalon G, Vandwijck R. Guide des plaies. Du pansement à la chirurgie. Montrouge: John Libbey Eurotext ed; 2003, 103. [2] Byl S. La thérapeutique par le miel dans le corpus hippocraticum. Aspetti della terapia nel corpus Hippocraticum. Atti del IX◦ colloque international hippocratique. Florence: Olschki LS ed.; 1999. p. 119—24. [3] von Gonzenbach W, Hoffman S. Zucker Honig Wundbalsamein ihrer Wirkung auf infizierte Wunden, Ein experimentelle Studie. Schweitz Med Wchschr 1936;1:425—9. [4] Garcia MA, Fernandez MI, Melgar MJ. Contamination of honey with organophosphorus pesticides. Bull Environ Contam Toxicol 1996;54:528—32. [5] Nevas M, Lindström M, Hautamäki K, et al. Prevalence and diversity of Clostridium botulinum types A, B, E and F in honey produced in the Nordic countries. Int J Food Microbiol 2005;25:145—51. [6] Postmes T, van den Bogaard AE, Hazen M. The sterilization of honey with cobalt 60 gamma radiation; a study of honey spiked with spores of Clostridium botulinum and Bacillus subtilis. Experientia 1995;29:986—9. [7] Moore OA, Smith LA, Campbell F, et al. Systematic review of the use of honey as a wound dressing. BMC Complement Altern Med 2001;1:2. [8] Kwakman PHS, te Velde AA, de Boer L, et al. How honey kills bacteria. FASEB J 2010;24:2576—82. [9] Mavric E, Wittmann S, Barth G, et al. Identification and quantification of methylglycoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand. Mol Nutr Food Res 2008;52:483—9. [10] Adams CJ, Boult CH, Deadman BJ, et al. Isolation by HPLC and characterisation of the bioactive fraction of New Zealand manuka (Leptospermum scoparium) honey. Carbohydr Res 2008;343:651—9. [11] Swellam T, Miyanaga N, Onozawa M, et al. Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies. Int J Urol 2003;10:213—9. [12] Sherlock O, Dolan A, Athman R, et al. Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. BMC Complement Altern Med 2010;10:1—5.
137 [13] Mullai V, Menon T. Bactericidal activity of different types of honey against clinical and environmental isolates of Pseudomonas aeruginosa. J Altern Complement Med 2007;13:439—41. [14] Hern Tze Tan, et al. The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey. BMC Complement Altern Med 2009;9:34. [15] French VM, Cooper RA, Molan PC. The antibacterial activity of honey against coagulase-negative staphylococci. J AntiMicrobial Chemother 2005;56:228—31. [16] www.Euroinvestor.fr:news:Story.aspx?id 11108399 Derma Sciences Receives CE Mark for Algicell® ; 2010. [17] Hamzaoglu I, Saribeyoglu K, Durak H, et al. Protective covering of surgical wound with honey impedes tumor implantation. Arch Surg 2000;135:14—7. [18] Fukuda M, Kobayashi K, Hirono Y, et al. Jungle honey enhances immune function and antitumor activity. eCAM 2009;10:1—8. [19] Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev 2008;8(4):CD005083. [20] Descottes B. Cicatrisation par le miel, l’expérience de 25 années. Phytothérapie 2009;7:112—6. [21] Visavidia BG, Honeysett J, Danford MH. Manuka honey dressing: an effective treatment for chronic wound infections. Br J Oral Maxillofac Surg 2008;46:696—7. [22] Ganacias-Acuna EF. Active leptospermum honey and negative pressure wound therapy for non healing post-surgical wounds. Ostomy Wound Manage 2010;56:10—2. [23] Bardy J, Slevin NJ, Mais KL, et al. A systematic review of honey uses and its potential value within oncology care. J Clin Nursing 2008;17:2604—23. [24] Rashad UM, Al-Gezawy SM, El-Gezawy E, et al. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol 2009;123: 223—8. [25] Al-Waili NS. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions. Med Sci Monit 2004;10:94—8. [26] Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med 2007;161:1140—6. [27] Hashemi B, Bayat A, Kazemei T, et al. Comparison between topical honey and mafenide acetate in treatment of auricular burn. Am J Otolaryngol 2011;32:28—31. [28] Boyer A, Salah A. Clinical and epidemiological characteristics of botulism in France. Ann Med Int 2002;153:300—10. [29] King LA, Popoff MR, Mazuet C, et al. Infant botulism in France, 1991—2009. Arch Pediatr 2010;17:1288—92.
REVIEW OF THE LITERATURE
Honey in otorhinolaryngology: When, why and how? A. Werner , O. Laccourreye ∗ Université Paris-Descartes, Service d’oto-rhinolaryngologie et de chirurgie cervicofaciale, hôpital européen Georges-Pompidou, Assistance publique—hôpitaux de Paris, 20—40, rue Leblanc, 75015 Paris, France Available online 9 February 2011
KEYWORDS Honey; Otorhinolaryngology
Summary In this review of the literature devoted to the use of honey, the authors analyse the composition, indications, benefits and adverse effects of this product in otorhinolaryngology and head and neck surgery. Published data indicate that honey applied topically to skin and mucosal wounds and/or burns and administered orally as antitussive medication (after the first year of life) is highly effective with no adverse effects. The physiological action of honey is the result of various mechanisms (osmotic, detersion, bactericidal action). Various medicinal honeys are available worldwide, but only one has Food and Drug Administration approval for the treatment of wounds. After the first year of life, the use of food honey appears to be as effective as medicinal honey, while decreasing the overall cost of treatment. © 2011 Elsevier Masson SAS. All rights reserved.
Introduction Religious texts describe honey as a great gift to mankind (Table 1) and honey has been used for medicinal purposes for more than 4000 years [1]. Sumerian tablets dating from 2100 B.C. describe the use of honey in various recipes and dressings [1]. About 500 remedies are also described in the Smith, Ebers and Kahum papyruses written in Egypt between 2000 and 1000 B.C. [1]. In India, at the same period, Ayurvedic physicians considered that honey acted on the essential elements (air, fire, bile and circulation) that determine man’s equilibrium and Susrhuta, a surgeon of the time, advised coating honey mixed with butter to an infected ear lobe after piercing [1]. Hippocrates prescribed honey for burns, boils and abscesses, while Dioscorides, a physician of the Roman army
∗
Corresponding author. Tel.: +01 56 093 463; fax: +01 56 093 468. E-mail address: [email protected] (O. Laccourreye).
in 50 B.C., used honey to treat wounds and inflammation of the throat and tonsils [1]. In the Hippocratic Corpus, honey is mentioned 542 times (particularly in the treatise on gynaecology and internal diseases, but also for pleurisy, diseases of the ileum, as a suppository for haemorrhoids, or by application to the eye and on wounds) and notes that: . . .‘‘wine and honey are wonderfully adapted to man; both in health and in disease, they are administered wisely and justly according to the individual constitution’’ [2]. Finally, Galen, in De Naturalibus Facultatibus, wrote that honey is ‘‘. . . excellent for the elderly, but harmful to the hot tempered. . .’’ [2]. However, the first modern scientific article devoted to the healing properties of honey was only published in 1936 [3] and although the literature devoted to honey has continued to grow, with more than 920,000 hits on the Google search engine in 2010 for the combination of ‘‘honey’’ and ‘‘treatment’’, to our knowledge, no article has been published on this subject in the French otorhinolaryngology literature. In view of this lack of data, the authors decided to review the medical literature (PubMed
1879-7296/$ – see front matter © 2011 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.anorl.2010.12.002
134 Table 1
A. Werner, O. Laccourreye Honey in religious texts.
Origin
Quotation
Homeric hymn to hermes
‘‘. . . yellow honey. . . the gods’ sweet food. . .’’
The Bible Psalm 119: verse 103 Exodus 33: 8
Koran Sourate 16: verses 68—69
‘‘How sweet are Your words to my taste, sweeter than honey to my mouth’’ ‘‘And I am come down to deliver them out of the hand of the Egyptians, and to bring them up out of that land unto a good land and a large, unto a land flowing with milk and honey...’’ ‘‘And your Lord inspired the bees, saying: ‘Take you habitations in the mountains and in the trees and in what they erect. Then, eat of all fruits, and follow the ways of your Lord made easy (for you).’ There comes forth from their bellies, a drink of varying colour wherein is healing for men. Verily, in this is indeed a sign for people who think.’’
search), and study the composition, mechanism of action, indications and adverse effects of honey in otorhinolaryngology as well as the future prospects of this gift of the gods.
Composition of honey Honey is an acidic product (pH 4) with a variable chemical composition according to the flowers from which it is derived. On average, it is composed of about 80% sugars (glucose, fructose, sucrose, levulose, maltose, sucrose), 17 to 20% water, and 4% of various other substances (pollen grains, proteins, enzymes, hydrogen peroxide, amino acids, organic acids, polyphenols, vitamins (except for vitamin A), minerals, and more than 100 volatile substances (alcohols, esters, aromatic substances) [1]. The low water concentration of honey helps to prevent the growth of micro-organisms (yeasts, fungi, bacteria), but as this product is hygroscopic, when left in contact with air for several months, its relative humidity increases to more than 50%, resulting in fermentation [1]. The composition of honey varies according to its source, the harvest season, the plants from which nectar is gathered, the modalities of honey collection and storage. As honey is produced by bees, which collect dust deposited on plants during pollen gathering, honey is subject to various potential sources of contamination. The best-known form of contamination is that due to the pesticides, antibiotics and acaricides used by beekeepers and farmers. However, the quantities of these contaminants are very small and below the limits accepted by the international literature [4]. Contamination by Caesium (134 and 137) mainly affects heather honey and is due to atmospheric nuclear tests and the Chernobyl accident. Finally, honey is not sterile and can contain bacteria (B. subtilis and C. botulinum). In 2005, Nevas et al. [5], in an analysis of 235 types of honey taken from hives in Nordic countries (Denmark, Norway, Sweden), demonstrated the presence of Clostridium botulinum (serotype A, B, E or F) with an incidence ranging from 2 to 26% depending on the country. However, honey can be sterilized by gamma radiation (2.5 cGy) without loosing its biological properties [6].
Biological effects The two main biological effects of honey are its antiseptic and healing properties. These properties are classically attributed to two factors: hydrogen peroxide (H2 O2 ) and hyperosmolarity [7,8]. The H2 O2 present in honey acts as a detergent in relation to bacteria present in the wound. The hyperosmolarity of honey, induced by its very high sugar content, generates a physical effect: by absorbing water, the sugars present in honey modify the surface osmotic pressure in the wound, which mechanically prevents any bacteria present from adhering and proliferating and also reduces local inflammation by promoting exudation. These biological effects provide ideal conditions for the development of granulation tissue and healing. In addition to these two factors, recent studies have demonstrated direct antibacterial effects for two components of honey: methylglycoxal (MGO) and a protein, bee-defensin 1 [8—10]. The various published in vitro studies analysing the local antibacterial activity of honey emphasize that: • this activity concerns a large number of bacteria (Escherichia coli whether or not beta-lactamase producing, Enterococcus whether or not vancomycinresistant, Staphylococcus aureus whether or not methicillin-resistant, Pseudomonas aeruginosa whether or not ciprofloxacin-resistant, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter, and Streptococcus); • the antibacterial activity of honey is 5- to 11-fold higher than that obtained by application of sugar solutions, thereby demonstrating that the antibacterial activity is not simply due to the osmotic effect of its sugars [8—15]. The many in vitro studies that have compared various types of honey emphasize variations in their respective hydrogen peroxide, MGO and bee-defensin 1 protein concentrations, with preferences very clearly influenced by the author’s nationality. The current standard in terms of honey is situated in the south hemisphere and Australian and New Zealand articles all conclude on the superior efficacy of their honey, Manuka honey derived from an indigenous tree
Honey in otorhinolaryngology: When, why and how? Table 2
135
The main types of medicinal honey marketed in the world.
Honey name
Company name
Country
Price
Medihoney®
MediHoney TM Comvita Medical Derma Sciences Triticum Company Advancis Mediprof
Australia New Zealand USA Netherlands England Netherlands, Belgium, England, Greece
10 D
L-Mesitran® Activon® Honeysoft®
(Leptospermum scoparium). However, Irish authors conclude on the superiority of Chilean honey derived from the Ulmo bush (Eucryphia cormen) compared to Manuka honey [12]. In an Indian study from Madras, the authors concluded on the superiority of the local honey (Khadikraft) compared to Australian Manuka or British honey [13], while all Malaysian authors highlight the advantages of Tualang honey and Dutch authors report that Manuka honey does not contain bee-defensin 1 protein [8,14]. All of these comparisons, with unanimous conclusions concerning the healing and therapeutic efficacy of these various types of honey, are not devoid of economic influences, as several medicinal honeys are now available on the market (Table 2). The current market of products intended for the treatment of wounds is considerable. In the USA, in 2010, financial reviews estimated this market at 14 trillion dollars [16] and the North American company Derma Sciences Inc. (Princeton, New Jersey), specialized in skin care products, recently acquired a Manuka honey-based paste approved by the Food and Drug Administration for the treatment of wounds that it markets under the brand name of Medihoney® . It should also be emphasized that the presence of proteins and polyphenols (caffeic acid, chrysin, galangin, quercetin, apigenin, pinobanksin, pinocembrin, acacetin) in honey also confers an antioxidant and potentially antimitotic action. Several studies have demonstrated that application of honey to the tumour site inhibited tumour growth in vivo in mice and the growth of various cancer cell lines in vitro [11,17,18], but no clinical study has yet been conducted in man to confirm this potential antitumour action.
Therapeutic properties of honey Honey is a food and topical application or ingestion of honey for medicinal purposes treatments must be performed daily. By topical application (Table 3), the wound is cleaned with physiological saline and honey is then applied with a compress. Deep wounds can be filled to three quarters, then covered with a dressing. Three meta-analyses devoted to evaluation of the healing properties of honey have been conducted over the last 10 years. The first two meta-analyses, published in 2001 and 2008, devoted to the beneficial effects of honey in burns and superficial wounds and acute and chronic wounds (venous, arterial, diabetic ulcers), concluded that analysis of the studies published before 2000 and the 19 randomized studies published since 2000 did not formally
13.59 D 8.45 D On request
and scientifically (due to the many, major methodological biases) demonstrate the superiority of honey, compared to other treatments [7,19]. However, the authors also reported that the results obtained with honey dressings in terms of healing, infection control and sterilization are often superior to those obtained with conventional dressings with or without concomitant antibiotic therapy [7,19]. The most extensive experience of the use of honey in the field of wound healing was reported by a French surgeon from Limoges, Prof. Descottes. Based on a cohort of more than 3000 wounds, 94% of which corresponded to postoperative wound dehiscences, this author emphasized the benefits of honey (healing after failure of conventional treatment, two-fold faster healing rate with than tulle gras dressings, very good cosmetic quality of healing, 98% success rate), and the low cost of the thyme honey used [20]. Visavidia et al. [21], in Great Britain, emphasized the value of first-line honey dressings on rapidly infected postoperative maxillofacial wounds in their everyday clinical practice. These published results are in line with our experience of the regular use of honey in our department since 1970, under the influence of Prof. Henri Laccourreye, by twice daily topical application and regular oral ingestion several times a day, to treat salivary fistula after head and neck cancer surgery or for any healing problems after head and neck surgery. According to Ganacias-Acuna [22], honey can also be combined with the use of negative pressure to promote wound healing. In the last meta-analysis published in 2008, devoted to the role of honey in oncology, Bardy et al. [23] while concluding on the poor quality of the 40 or so studies analysed due to various methodological problems, also emphasized that honey is as effective as usual treatments for radiation mucositis, radiation dermatitis, chemotherapy-induced hand-foot syndrome and/or postradiotherapy wounds of the skin or oral cavity. The efficacy of honey in radiation mucositis was recently confirmed by Rashad et al. [24], who highlighted the efficacy of honey in prevention of serious mucositis by topical application onto the oral mucosa followed by ingestion of 20 ml of honey 15 minutes before, 15 minutes after, and 6 hours after each radiochemotherapy session (60—66 Gray; 2 cGy/week; cisplatin 20 mg/m2 once a week). Recurrent labial herpes lesions also appear to be very sensitive to topical application of honey. In a randomized study comparing honey application several times a day (four times daily for 15 minutes) versus acyclovir (six times daily), based on analysis of the healing time, pain relief, resolution of local signs and prevention of acute attacks, Al-Waili [25]
136 Table 3
A. Werner, O. Laccourreye How to apply honey on a wound.
Clean the wound with physiological saline Apply honey Shallow wound: compress soaked in honey (30 ml of honey for a 10 × 10 cm compress) Deep wound: directly fill 3/4 of the wound with honey Cover with an absorbent or occlusive dressing Change the dressing once or twice a day (rinsing with physiological saline) until the appearance of granulation tissue, then every 48 hours
concluded on the significant superiority of honey (P < 0.05) and attributed the therapeutic effect obtained to the presence of copper, ascorbic acid and hydrogen peroxide in honey, which inactivate the Herpes simplex virus, and to local inactivation of prostaglandins. A last potential indication for honey appears to be cough and respiratory difficulties in children following upper respiratory tract infections. In a double-blind study conducted in the United States in 2009 on 105 children comparing buckwheat honey versus a classical dextromethorphan-based antitussive (Drill® , Humex® ) and no treatment, the authors concluded on the superiority of honey in the treatment of nocturnal cough in children over the age of 1 year: less cough and better sleep for the child and the parents [26].
Limitations and adverse effects of honey Due to its acidic pH, honey can cause unpleasant or even painful feelings during application or ingestion that may limit its use. In a study in rats comparing honey dressings and conventional dressings for the treatment of auricular burns, Hashemi et al. [27] reported that the chondritis rate was higher in the group treated with honey. The proximity of cartilage may, therefore, constitute a limiting factor to the healing efficacy of honey. Similarly, according to Descottes [20], a history of local radiotherapy limits the healing properties of honey on skin wounds. Allergy to honey or its ingredients and pollutants is extremely rare, but possible [1]. The main issue concerning the adverse effects of honey concerns the risk of botulism. Due to the presence of Clostridium botulinum spores (but not botulinum toxin) in honey derived from many hives [5] and inactivation of these spores by low-dose gamma radiation (2 cGy) [6], it is frequently recommended in the medical literature that only irradiated honey should be ingested and/or applied to wounds. However, there are no published cases of botulism in adults following the ingestion or topical application of honey, despite the fact that the very great majority of studies on honey were conducted in developing or lowincome countries, in which gamma sterilization of honey is not performed. Similarly, in France, no cases of botulism were reported in the cohort published by Descottes [20] (in which honey does not appear to have been sterilized) or in our own experience (in which a commercially available food honey has been used since 1970 to treat salivary fistula and/or wounds after neck surgery). Finally, the cases of botulism reported in adults in France are not related to ingestion of honey despite the fact that this product is extensively used by the population [28]. However, several cases
of botulism related to honey have been reported in infants under the age of 1 year in the United States and France, where the incidence of this disease has been increasing since 2000 [26,28,29]. In these cases, honey is ingested as treatment or as a food supplement. Clostridium botulinum then proliferates in an immature gastro-intestinal system and produces botulinum toxin which subsequently induces botulism. Honey, that has not been sterilized by gamma radiation, should therefore not be used as a sweetener, food substrate and/or in the context of medicinal ingestion in infants under the age of 1 year [26,28,29]. In the light of the published scientific data and the experience acquired over the last 30 years in Limoges, in Prof. Descottes’ Department of Surgery [20], and in Paris, in the Department of Otorhinolaryngology and Head and Neck Surgery at Laënnec hospital and then, at the Georges Pompidou European hospital (no cases of botulism reported after application of honey to neck wounds, pharyngostome and/or radiation mucositis), the food honey available in France can, therefore, be used in patients over the age of 1 year in otorhinolaryngology and head and neck surgery with no medicolegal risks at the present time.
Conclusion In this age of budget restrictions and optimization of medical resources, the research and development of effective and inexpensive treatments constitute a major concern for all clinicians. In this context, application of honey to inflamed mucosa and head and neck skin or mucosal wounds provides a real therapeutic benefit. The local action of honey on multiresistant bacteria also participates in more effective antibiotic practices. The antitussive action of honey also appears to be useful in infants over the age of 1 year. The other properties (antioxidant and antimitotic) of systemic administration of honey need to be formally demonstrated by in vivo studies, although many articles based on animal experimentation and cell culture are in favour of these effects. None of the thousands of varieties of honey available throughout the world appears to be truly superior. Various countries, such as Australia and the United States have already developed the medicoeconomic use of this product. When will a French medicinal honey be available?
Conflicts of interest statement None.
Honey in otorhinolaryngology: When, why and how?
Acknowledgements The authors would like to thank Progrès 2000 for technical and financial support for this study.
References [1] Magalon G, Vandwijck R. Guide des plaies. Du pansement à la chirurgie. Montrouge: John Libbey Eurotext ed; 2003, 103. [2] Byl S. La thérapeutique par le miel dans le corpus hippocraticum. Aspetti della terapia nel corpus Hippocraticum. Atti del IX◦ colloque international hippocratique. Florence: Olschki LS ed.; 1999. p. 119—24. [3] von Gonzenbach W, Hoffman S. Zucker Honig Wundbalsamein ihrer Wirkung auf infizierte Wunden, Ein experimentelle Studie. Schweitz Med Wchschr 1936;1:425—9. [4] Garcia MA, Fernandez MI, Melgar MJ. Contamination of honey with organophosphorus pesticides. Bull Environ Contam Toxicol 1996;54:528—32. [5] Nevas M, Lindström M, Hautamäki K, et al. Prevalence and diversity of Clostridium botulinum types A, B, E and F in honey produced in the Nordic countries. Int J Food Microbiol 2005;25:145—51. [6] Postmes T, van den Bogaard AE, Hazen M. The sterilization of honey with cobalt 60 gamma radiation; a study of honey spiked with spores of Clostridium botulinum and Bacillus subtilis. Experientia 1995;29:986—9. [7] Moore OA, Smith LA, Campbell F, et al. Systematic review of the use of honey as a wound dressing. BMC Complement Altern Med 2001;1:2. [8] Kwakman PHS, te Velde AA, de Boer L, et al. How honey kills bacteria. FASEB J 2010;24:2576—82. [9] Mavric E, Wittmann S, Barth G, et al. Identification and quantification of methylglycoxal as the dominant antibacterial constituent of Manuka (Leptospermum scoparium) honeys from New Zealand. Mol Nutr Food Res 2008;52:483—9. [10] Adams CJ, Boult CH, Deadman BJ, et al. Isolation by HPLC and characterisation of the bioactive fraction of New Zealand manuka (Leptospermum scoparium) honey. Carbohydr Res 2008;343:651—9. [11] Swellam T, Miyanaga N, Onozawa M, et al. Antineoplastic activity of honey in an experimental bladder cancer implantation model: in vivo and in vitro studies. Int J Urol 2003;10:213—9. [12] Sherlock O, Dolan A, Athman R, et al. Comparison of the antimicrobial activity of Ulmo honey from Chile and Manuka honey against methicillin-resistant Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. BMC Complement Altern Med 2010;10:1—5.
137 [13] Mullai V, Menon T. Bactericidal activity of different types of honey against clinical and environmental isolates of Pseudomonas aeruginosa. J Altern Complement Med 2007;13:439—41. [14] Hern Tze Tan, et al. The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey. BMC Complement Altern Med 2009;9:34. [15] French VM, Cooper RA, Molan PC. The antibacterial activity of honey against coagulase-negative staphylococci. J AntiMicrobial Chemother 2005;56:228—31. [16] www.Euroinvestor.fr:news:Story.aspx?id 11108399 Derma Sciences Receives CE Mark for Algicell® ; 2010. [17] Hamzaoglu I, Saribeyoglu K, Durak H, et al. Protective covering of surgical wound with honey impedes tumor implantation. Arch Surg 2000;135:14—7. [18] Fukuda M, Kobayashi K, Hirono Y, et al. Jungle honey enhances immune function and antitumor activity. eCAM 2009;10:1—8. [19] Jull AB, Rodgers A, Walker N. Honey as a topical treatment for wounds. Cochrane Database Syst Rev 2008;8(4):CD005083. [20] Descottes B. Cicatrisation par le miel, l’expérience de 25 années. Phytothérapie 2009;7:112—6. [21] Visavidia BG, Honeysett J, Danford MH. Manuka honey dressing: an effective treatment for chronic wound infections. Br J Oral Maxillofac Surg 2008;46:696—7. [22] Ganacias-Acuna EF. Active leptospermum honey and negative pressure wound therapy for non healing post-surgical wounds. Ostomy Wound Manage 2010;56:10—2. [23] Bardy J, Slevin NJ, Mais KL, et al. A systematic review of honey uses and its potential value within oncology care. J Clin Nursing 2008;17:2604—23. [24] Rashad UM, Al-Gezawy SM, El-Gezawy E, et al. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol 2009;123: 223—8. [25] Al-Waili NS. Topical honey application vs. acyclovir for the treatment of recurrent herpes simplex lesions. Med Sci Monit 2004;10:94—8. [26] Paul IM, Beiler J, McMonagle A, et al. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med 2007;161:1140—6. [27] Hashemi B, Bayat A, Kazemei T, et al. Comparison between topical honey and mafenide acetate in treatment of auricular burn. Am J Otolaryngol 2011;32:28—31. [28] Boyer A, Salah A. Clinical and epidemiological characteristics of botulism in France. Ann Med Int 2002;153:300—10. [29] King LA, Popoff MR, Mazuet C, et al. Infant botulism in France, 1991—2009. Arch Pediatr 2010;17:1288—92.