by Dr. Molan, University of Waikato, New Zealand An Ancient Medicine Rediscovered Honey is one of the oldest medicines. Its use is recorded in Sumerian clay tablets estimated to be 4,000 years old, and in Egyptian papyri dated from 1900 to 1250 B.C. It is also mentioned in the Veda, the sacred scriptures of Hinduism, thought to be about 5,000 years old, and in the Holy Qu'ran and the Talmud. Hippocrates (460-357 B.C.) used many of the Egyptian prescriptions. He found that honey "cleans sores and ulcers of the lips, heals carbuncles and running sores." Celsus (circa 25 A.D.) used honey for many different purposes: as a laxative, as a cure for diarrhea and upset stomach, for coughs and throat maladies, to agglutinate wounds and for eye diseases. Honey has continued to be used in medicine ever since, but little was known about how it worked. It was not until the late 19th century that bacteria were found to be the cause of infections. Although there are several reports in medical journals in the 1930's of honey being effec tive in clearing wounds of bacterial infection, it was not recognized in these reports that it had been established in laboratory work in 1919 that honey has antibacterial activity. It was not until the mid-1940's that more intensive laboratory studies were carried out, but by this time antibiotics were becoming available for the treatment of infections, and honey was displaced from use in medicine. Despite the advent of antibiotics, honey has continued to be used in folk medicine, and it is from this pool of knowledge that the re-introduction of honey into modern medicine has come. There have been numerous reports in medical journals of this folk remedy being used as a last resort on infected wounds, burns and ulcers that were not responding to antibiotic treatment. The remedy was in all cases found to be remarkably effective. This effectiveness is being recognized in an increasing number of reports. In 1989, an editorial in the Journal of the Royal Society of Medicine expressed the opinion that "the time has now come for conventional medicine to lift the blinds off this 'traditional remedy' and to give it its due recognition." Recent Research Many researchers have reported that honey varies in the potency of its activity. Despite this, none of the reports in the medical journals mentions any selection of the honey used. At the University of Waikato we have investigated how much variation there is in the antibacterial activity of honey likely to be used medically. Commercial apiarists supplied 345 samples of honey from 26 different floral sources for the study. The samples of honey were tested against staphylococcus aureus, the most common wound-infecting species of bacteria. The activity of each sample was compared with that of a reference antiseptic, phenol (carbolic). It was found that the activity varied from a level that was the equivalent of 58% phenol to a level that was below the limit of detection (2% phenol). One third of the samples tested were of this low level of activity. The results of this research (recently published internationally in the Journal of Pharmacy and Pharmacology) show the importance of selecting the honey used for medical purposes. 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 (primarily hydrogen peroxide generated by the glucose oxidase enzyme in the honey) then become important. Considering that carbolic disinfectant is usually used with a phenol concentration of 4-5%, it is evident that selected honeys can remain antibacterial when extensively diluted by body fluids. Another finding in this research was that hydrogen peroxide was not the only antibacterial substance involved in some types of honey. When testing samples of the honeys with the enzyme catalase added to remove the hydrogen peroxide, it was found that only two of the 26 floral types of honey contained significant levels of this additional antibacterial activity. In one of these, vipers bugloss honey, the level of activity was quite low. In the other, Manuka honey, the additional antibacterial activity was in some samples quite high, although it is important to note that half of the 60 samples tested had very low levels or none of this additional antibacterial activity. This additional antibacterial activity was considered to be important enough to warrant further investigation. As a project for her recently completed M.Sc. thesis, Dawn Willix compared the antibacterial activity of an average-level Manuka honey with that of an average-level honey with activity due to hydrogen peroxide, testing them on seven different species of bacteria chosen as the ones most commonly involved in wound infection. The percentage (by volume) of each type of honey needed to completely prevent the growth of each species of bacteria was found to be: Manuka Other Honey Honey Escherichia coli 3.7 7.1 Proteus mirabilis 7.3 3.3 Pseudomonas aeruginosa 10.8 6.8 Salmonella typhimurium 6.0 4.1 Serratia marcescens 6.3 4.7 Staphylococcus aureus 1.8 4.9 Streptococcus pyogenes 3.6 2.6 Although some species of bacteria are more sensitive to the action of one type of honey than they are to the other, on average there is little difference. The most notable point is that these "average" honeys can be diluted nearly ten-fold yet still completely halt the growth of all the major wound-infecting species of bacteria. Also notable is the finding that an "average" Manuka honey will still halt staphylococcus aureus when diluted with 54 times its volume of fluid: this is not only the most common wound-infecting species, but is notorious for developing resistance to antibiotics. The work has recently been carried further by microbiologists at Waikato Hospital looking at the effect of these two honeys on their collection of strains of MRSA--strains of staphylococcus aureus that cause ward closures in hospitals because they are resistant to most or all of the commonly used antibiotics. All of the strains have been found to have their growth halted completely by the honeys diluted to 5-10%. Similar sensitivity has been found in some other recent work, carried out at the University of Waikato, in which we tested the bacterial species that cause mastitis in dairy cattle. If honey is as effective in the udder as it is in the laboratory in stopping the growth of these bacteria, then it would be a very useful alternative to antibiotics as it would not need the milk to be held back because of unacceptable residues from the treatment. Injection of honey up the teat of a cow should cause no problems when it is considered that it can safely be put in the eye for the treatment of eye infections. Stomach Ulcers In the traditional medicine of some parts of the world honey has also been used to treat dyspepsia and stomach ulcers. There are numerous reports of this treatment being used successfully in clinics in Russia in modern times, and a recent report of a clinical trial in Egypt which established that this traditional remedy is in fact effective. However, there has been no explanation of how honey works in this treatment, which has prevented the treatment from being considered seriously by many in the medical profession. In the last few years it has been recognized that dyspepsia and stomach ulcers are frequently caused by infection of the stomach by a species of bacteria, helicobacter pylori. The possibility that the healing effect of honey on the stomach may be through its acting on this bacterium was suggested by Niaz Al Somai at the University of Waikato. In collaboration with microbiologists at the Waikato Hospital he tested strains of helicobacter pylori isolated from biopsy samples of stomach ulcers, using the same two honeys that had been tested on the wound-infecting species of bacteria. It was found that the honey with hydrogen peroxide activity did not prevent the growth of cultures of helicobacter pylori when added at concentrations up to 50%, but the Manuka honey completely halted growth of the bacterium at a concentration of 5%. A clinical trial was organized to find out if Manuka honey has the same effect on the bacterium in the stomach as it does when they are on agar plates. There is much interest in this possibility because conventional therapy for stomach ulcers is far from satisfactory. Drugs which prevent secretion of acid in the stomach may allow an ulcer to heal but it frequently re-appears. Only if helicobacter pylori is eliminated is a lasting cure achieved, but it is a very difficult infection to clear. A combination of antibiotics and bismuth is required, and unpleasant side-effects often result. There is also the consideration that a very large amount of money is spent on the pharmaceuticals currently used to treat stomach ulcers. If honey is shown by clinical trial to be a reasonable alternative it would be a much cheaper option. The trial was abandoned without completion because the gastroenter- ologists were not entering sufficient patients, so no conclusive results were obtained regarding the ability of the treatment with Manuka honey to clear the bacterial infection. However, there was a clear indication that the patients taking the honey with antibacterial activity had significant relief from the discomfort and pain associated with their illness, whereas the patients taking honey without antibacterial activity did not. (Neither group of patients knew whether they were taking active or inactive Manuka honey, nor did their gastroenterologists know. The dosage used was 3/4 oz of honey four times a day, 1 hour before meals or at bedtime.) Update On Current Research This presentation is to provide an update on the current research into the antibacterial activity of honey being carried out at Waikato University under the direction of Dr. Peter Molan. A priority at the present time is to provide scientific evidence of the effectiveness an d safety of using honey as an alternative to conventional forms of treatment for skin and gastro-intestinal infections in the medical field and mastitis, wounds and scours in the veterinary fields. We have numerous reports, both scientific papers and personal communications, of honey being used successfully to treat ulcers, bedsores, wounds, burns, and dermatitis which were not responding to usual methods of treatment, but it has proven difficult to convince those in the medical and veterinary professions that honey is a safe effective remedy to use. Sterilization of honey One of the main objections to using honey has been that it may introduce a new infection from bacteria or spores present in the honey. Although it is generally thought that honey is a sterile product, bacteria and spores are able to survive in the honey but it is unlikely that they will actually grow in it unless the water content is too high. One report has shown that disease causing bacteria introduced into honey samples were capable of surviving 1.5 months to 2.4 years at 214F. Heat treatment or filtration through microporous membranes which are capable of preventing the passage of bacteria and spores are the usual ways medical products are sterilized. Sterilization of honey by heat treatment is not suitable because any hydrogen peroxide activity would be lost, and although it is more heat stable, there is also a reduction in the non-peroxide activity of Manuka honey at the temperatures required to ensure complete sterilization of honey. Filtration is also not suitable because of the high viscosity of honey, and particles present in the honey which block up the pores in the membranes. Gamma-irradiation, which is used to sterilize items such as surgical gloves and dressings which cannot be heat sterilized, was suggested as a possible alternative for sterilizing honey for use in hospitals. It may also be worth considering as an alternative to heat treatment of honey which is required when exporting to the Australian market. To determine whether this would have any effect on the antibacterial activity of the honey, samples were tested for activity before and after gamma-irradiation. The results showed that there was no significant reduction in the antibacterial activity of honeys containing hydrogen peroxide activity and Manuka honeys with non-peroxide activity. Clinical Trial on Wound Healing In conjunction with staff at Waikato Hospital a clinical trial is in its preliminary stages using honey as a wound dressing. The aim is to compare the effectiveness of honeys with the two different types of activity (hydrogen peroxide, and the non-peroxide activity of Manuka honey) and also compare these with a standard treatment. So far only Manuka honey has been used, and good results are being obtained. Honey for the Treatment of Gastroenteritis Currently, with funding by the Honey Industry Trust, a study is being carried out to determine whether organisms which cause gastroenteritis (diarrhea and vomiting), are sensitive to the peroxide and non-peroxide antibacterial activity of honeys. Again many reports have indicated that honey is an effective remedy for stomach upsets. One report in the British Medical Journal suggested that it shortened the duration of bacterial diarrhea and was as effective as glucose at promoting the re-absorption of sodium and water from the intestines. As the major problem with gastroenteritis is that the patient becomes dehydrated, dosing with honey would help to replace lost electrolytes and provide an energy source as well. A pasture blend honey with a high hydrogen peroxide activity and a Manuka honey with a medium non-peroxide activity are being compared with an artificial honey ( a mixture of sugars at an acid pH similar to that found in honey). The artificial honey is used as a control to determine whether the antibacterial activity is due solely to the high sugar and low pH of honey or to some other factors present only in the honeys. The results show that the organisms tested so far are inhibited by concentrations of 5-8% pasture blend ( high peroxide ) and 7-11% Manuka honey but it requires 20-30% artificial honey to have the same effect, clearly showing that factors other than sugar and pH are providing the antibacterial activity. Although the bacteria tested so far have been isolated from human infections the indications are that honey could be equally effective and valuable as a remedy for scours in young animals such as calves. It could also be used as an organic alternative to the antibiotic food supplement currently used for other animals including piglets and poultry. This avoids the problem of antibiotic residues. Bacteria isolated from animal sources will be tested in the next stage of the study. Effect of Honey on Fungi Another project recently funded by the Honey Industry Trust was to determine whether honey had any activity against a range of dermatophytes, i.e. fungi causing skin infections such as ringworm and athletes foot. All the fungi species tested were inhibited by low concentrations of the hydrogen peroxide activity but considerably higher concentrations of Manuka type non-peroxide activity were necessary for inhibition. 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