Selection of honey for use as a wound dressing | Bibliography of medical usage of honey
Honey as an Antimicrobial agent | Publications from the Honey Research Unit
The Potential for using honey to treat wounds infected with MRSA and VRE ( PDF File)
Activity of honey against wound-infecting bacteria ( including "Superbugs") ( PDF File)
Introduction:
That honey has antibacterial properties has been known for more than a century 1. Although it has been used as a medicine since ancient times in many cultures 2,3, in its ancient usage there was no recognition of its antibacterial properties it was just known to be an effective remedy. This is not surprising considering that it is only since the latter part of the last century that it has become known that many ailments are the result of infection by microorganisms. Now it can be seen that the effectiveness of honey in many of its medical uses is probably due to its antibacterial activity. It is well established that honey inhibits a broad spectrum of bacterial species. There are many reports of bactericidal as well as bacteriostatic activity. There have also been reports of honey having antifungal activity. These numerous reports of the antimicrobial activity of honey have been comprehensively reviewed 4: the collation of data shows that honey is active against a wide range of bacterial and fungal species, many of which cause infections. However, there are ailments which may be treated with honey which have not had the infectious agents tested for their sensitivity to the antimicrobial activity of honey. Also, there has not been much distinction made in the different types of antimicrobial activity in honey to which the various microbial species are sensitive. For serious consideration to be given to the use of honey as a therapeutic agent it is necessary that these aspects be further investigated.
The Antimicrobial properties of honey.
The numerous reports of investigations which have established the nature of the antimicrobial factors in honey are cited in a comprehensive review of this subject 4,5. A brief summary of what has been established is given here.
2.1. Explanation of Antibacterial Activity
2.1.1. Osmotic effect Honey is a saturated or super-saturated solution of sugars, 84% being a mixture of fructose and glucose. The water content is usually only 15-21% by weight. The strong interaction of these sugar molecules with water molecules leaves very few of the water molecules available for microorganisms. This "free" water is what is measured as the water activity (aw): mean values for honey have been reported from 0.562 to 0.62. Although some yeasts can live in honeys that have a high water content, causing spoilage of the honey, the aw of ripened honey is too low to support the growth of any species, no fermentation occurring if the water content is below 17.1%. Many species of bacteria have their growth completely inhibited if the aw is in the range 0.94-0.99. These values correspond to solutions of a typical honey (aw of 0.6 undiluted) of concentrations from 12% down to 2% (v/v). On the other hand, some species have their maximum rate of growth when the aw is 0.99, so inhibition by the osmotic (water-withdrawing) effect of dilute solutions of honey obviously depends on the species of bacteria.
2.1.2. Acidity Honey is characteristically quite acidic, its pH being between 3.2 and 4.5, which is low enough to be inhibitory to many animal pathogens. The optimum pH for growth of these species normally falls between 7.2 and 7.4. The minimum pH values for growth of some common wound-infecting species is: Escherichia coli, 4.3; Salmonella sp., 4.0; Pseudomonas aeruginosa, 4.4; Streptococcus pyogenes, 4.5. Thus in undiluted honey the acidity is a significant antibacterial factor. But if honey is diluted, especially by body fluids which are well buffered, the pH will not be so low and the acidity of honey may not be an effective inhibitor of many species of bacteria.
2.1.3. Hydrogen Peroxide The major antibacterial activity in honey has been found to be due to hydrogen peroxide produced enzymically in the honey. The glucose oxidase enzyme is secreted from the hypopharyngeal gland of the bee into the nectar to assist in the formation of honey from the nectar. The hydrogen peroxide and acidity produced by the reaction: glucose + H2O+ O2 --> gluconic acid + H2O2 serve to preserve the honey. The hydrogen peroxide produced would be of effect as a sterilising agent only during the ripening of honey. Full-strength honey has a negligible level of hydrogen peroxide because this substance is short-lived in the presence of the transition metal ions and ascorbic acid in honey which catalyse its decomposition to oxygen and water. The enzyme has been found to be practically inactive in full-strength honey, it giving rise to hydrogen peroxide only when the honey is diluted. This is because the acidity produced in the action of the enzyme drops the pH to a point which is too low for the enzyme to work any more. On dilution of honey the activity increases by a factor of 2,500 - 50,000, thus giving a "slow-release" antiseptic at a level which is antibacterial but not tissue-damaging.
2.1.4. Phytochemical Factors The evidence for the existence of other antibacterial factors is mainly that the peroxide-generating system does not account for all of the observed antibacterial activity, but there have also been some reports of isolation of antibacterial substances from honey that are not hydrogen peroxide. Furthermore, it has ben found that heating honey, which inactivates the glucose oxidase, causes loss of activity against some species whilst it is retained against others. Although the stability of the enzyme varies in different honeys, there have been reports of honeys with stability well in excess of this variation, showing that there must be an additional antibacterial factor involved. The most direct evidence for the existence of non-peroxide antibacterial factors in honey is seen in the reports of activity persisting in honeys treated with catalase to remove the hydrogen peroxide activity. Several chemicals with antibacterial activity have been identified in honey by various researchers: pinocembrin, terpenes, benzyl alcohol, 3,5-dimethoxy-4-hydroxybenzoic acid (syringic acid), methyl 3,5-dimethoxy-4-hydroxybenzoate (methyl syringate), 3,4,5-trimethoxybenzoic acid, 2-hydroxy-3-phenylpropionic acid, 2-hydroxybenzoic acid and 1,4-dihydroxybenzene. However, the quantities of these present were far too low to account for any significant amount of activity.
2.2. Variation in Antibacterial Activity In almost all reports on the medical use of honey as an antibacterial agent no consideration is given to the selection of type of honey for therapeutic use. Aristotle, c.350 B.C. 6, and Dioscorides, c.50 A.D. 7, recommended that honey collected in specific regions and seasons (and therefore presumably from different floral sources) be used for the treatment of particular ailments, but in modern medicine clinical practitioners have not heeded these views nor the laboratory findings of large differences in the antibacterial potency of different honeys. It was recognised more than 40 years ago that there are differences in the antibacterial activity of different honeys, and a method was devised to determine the "inhibine number" of honeys as a measure of their antibacterial activity. The "inhibine number" is the degree of dilution to which a honey will retain its antibacterial activity, representing sequential dilutions of honey in steps of 5% from 25% to 5%. Studies measuring the "inhibine number" of honeys report activity to range over the five-fold difference in concentration in the dilution series, and studies using a wider range of dilutions report the minimum inhibitory concentrations of the honeys tested to range from 25 to 0.25%, >50 to 1.5%, 20-0.6%, and 50-1.5%. The data showed activities to be fairly well spread over these ranges. A study of 345 samples of New Zealand honeys 8 found a large number with low activity (36% of the samples had activity near or below the level of detection), the rest having almost a Gaussian distribution over a twenty-fold range of activity. The major variations seen in overall antibacterial activity are due to variation in the level of hydrogen peroxide that arises in honey, and in some cases to the level of non-peroxide factors. Hydrogen peroxide can be destroyed by components of honey: it can be degraded by reaction with ascorbic acid and metal ions, and by the action of the enzyme catalase which comes from the pollen and nectar of certain plants, more from the nectar. Also, very large differences have been found between honeys from different floral sources in the thermal stability of their glucose oxidase content, and in the sensitivity of this hydrogen peroxide-producing enzyme to denaturation by light because of a photosensitizing component that comes from some floral sources.
Although it appears that the honey from certain plants has better antibacterial activity than that from others, there is not enough evidence for such definite conclusions to be justified because the data are from small numbers of samples. However, honeys from some sources have been been studied in large enough numbers or have been included in enough different studies for some trends to be noted. Honeydew honey from the conifer forests of the mountainous regions of central Europe has been found to have particularly high antibacterial activity. Also honey from manuka (Leptospermum scoparium) in New Zealand has been found to have a high activity, about half of this type of honey having an exceptionally high level of non-peroxide activity 9.
Thus it is important that when honey is to be used as an antimicrobial agent it is selected from honeys that have been assayed in the laboratory for antimicrobial activity. It is also important that honey for use as an antimicrobial agent be stored at low temperature and not exposed to light, so that none of the glucose oxidase activity is lost. Although all honey will stop the growth of bacteria because of its high sugar content, when the sugars are diluted by body fluids this antibacterial action is lost. The additional antibacterial components then become important.