P. C. Molan
Honey Research Unit, Department of Biological Sciences, University of Waikato, Hamilton, New Zealand

Introduction

The usage of honey as a medicine is referred to in the most ancient written records. Honey was prescribed by the physicians of many ancient races of people for a wide variety of ailments. The ancient usage of honey as a wound dressing has been described by Beck & Smedley, Majno and by Forrest. The ancient Egyptians, Assyrians, Chinese, Greeks and Romans all used honey, in combination with other herbs and on its own, to treat wounds and diseases of the gut. The Muslim prophet Mohammed recommended the use of honey for the treatment of diarrhoea. Aristotle (350 BC) wrote of honey being a salve for wounds and sore eye. In ancient times honey from Attica had a special reputation as a curative substance for eye disorder. Dioscorides (c.50 AD) wrote of honey being " good for sunburn and spots on the face" and "for all rotten and hollow ulcers". He also wrote that "honey heals inflammation of the throat and tonsils, and cures coughs" and "mollifies the prepuce so that it can be pulled back over the bared glans penis".

The usage of honey as a medicine has continued into present-day folk-medicine. In India lotus honey is said to be a panacea for eye disease. The ancient usage of honey for coughs and sore throats has also continued into the traditional medicine of modern times Other examples of current day usage of honey in folk medicine are: as a traditional therapy for infected leg ulcers in Ghana; as a traditional therapy for earache in Nigeria; as a traditional therapy in Mali for the topical treatment of measles, and in the eyes in measles to prevent corneal scarring. Honey also has a traditional folklore usage for the treatment of gastric ulcers.

There has been a renaissance in the usage of honey as a medicine in more recent times. In outlining the resurgence of its usage in modern professional medicine, Zumla and Lulat in 1989 referred to honey as "a remedy rediscovered", and expressed the opinion, "The therapeutic potential of uncontaminated, pure honey is grossly underutilized. It is widely available in most communities and although the mechanism of action of several of its properties remains obscure and needs further investigation, the time has now come for conventional medicine to lift the blinds off this 'traditional remedy' and give it its due recognition." Possibly the increasing interest in the use of alternative therapies is the result of the development of antibiotic resistance in bacteria becoming a major problem; or because people are experiencing the sometimes severe side-effects of many pharmaceuticals, which in the currently prevailing ambience of "chemophobia" may be sufficient to give rise to an aversion to all synthetic drugs.

However, there is a tendency for some practitioners to dismiss out of hand any suggestion that treatment with honey is worthy of consideration as a remedy in modern medicine. An editorial in Archives of Internal Medicine assigned honey to the category of "worthless but harmless substances". Other medical professionals have clearly shown that they are unaware of the research that has demonstrated the rational explanations for the therapeutic effects of honey. Many are not even aware that honey has an antibacterial activity beyond the osmotic effect of its sugar content, yet there have been numerous microbiological studies that have shown that in many honeys there are other components present with a much more potent antibacterial effect.

The ancient physicians who prescribed honey for various ailments would have had no knowledge of the principles involved in its medicinal action, just an empirical knowledge gained from its effective usage. But modern physicians generally require there to be a rational explanation for its medicinal action before a traditional , or "complementary", medicine is given any consideration. Much has been written on the subject outside the professional medical and scientific literature, but many people, especially medical professionals, treat such reports with scepticism, especially since much of the popular literature claims honey to be almost a panacea. The more convincing professional reports are scattered through a very wide range of journals, and some of the explanations for the medicinal effects of honey are to be found in articles unrelated to honey. Hence this review was undertaken to bring together the evidence that supports the use of honey as a medicine.

The first part of this review will cover the therapeutic effects that have been observed when honey is used as a medicine, and the data from observations, experiments and clinical trials that constitutes the evidence honey is an effective medicine. The second part will cover the explanation of the various therapeutic effects of honey.

Treatment of wounds

The medical literature on treating wounds with honey has been recently reviewed in specialist wound care journals, with focus on the medical evidence and with focus on the clinical aspects. Here the focus is on the therapeutic effects observed when honey is used as a wound dressing, which will have their mechanism explained later. In the numerous reports in the medical literature on the use of honey as a wound dressing the types of wounds on which honey has been successfully used are very varied: abrasions, amputations, abscesses, bed sores (pressure sores, decubitus ulcers), burns, burst abdominal wounds following caesarean delivery, cancrum, cervical ulcers, chilblains, cracked nipples, cuts, diabetic foot ulcers and other diabetic ulcers, a fistula, foot ulcers in lepers, infected wounds arising from trauma, large septic wounds, leg ulcers, malignant ulcers, sickle cell ulcers, skin ulcers, surgical wounds, tropical ulcers, wounds to the abdominal wall and perineum, varicose ulcers. Of particular note are the successful use of honey to treat Fournier’s gangrene, a rapidly spreading infection that is usually managed by aggressive surgical removal of infected tissue, and wounds from surgery for cancer of the vulva, which are difficult to treat because they are in a position where it is difficult to prevent infection occurring. But the therapeutic effects of the honey that have been observed are common to all of these different types of wounds.

Rapid healing

In several reports the rapidity of healing seen with honey dressings is noted. One report refers to wounds becoming closed in a spectacular fashion in 90% of cases, sometimes in a few days. Another refers to healing being surprisingly rapid, especially for first and second degree burns. Hejase has also noted the rapid healing changes when honey is applied to Fournier’s gangrene. Blomfield is of the opinion that honey promotes healing of ulcers and burns better than any other local application used before. Clinical observations made are that open wounds heal fasterand are ready faster for closure by stitching when dressed with honey (than when dressed conventionally). It has been noted that dressing wounds with honey makes the wound bed suitable early for skin-grafting, and gives prompt "taking" of the skin grafts.

These clinical observations are in line with the findings from comparative clinical trials and studies on wounds on experimental animals. In one case a patient with multiple ulcers on both legs had one leg dressed with honey and the other treated conventionally (with fibrinolysis and calcium alginate dressing): the ulcers on the leg treated with honey healed much more rapidly. In another case a patient with a long abdominal wound that had become infected following surgery had one end of the wound dressed with honey and the other end dressed with Debrisan (a modern hydrocolloid wound dressing material): it took 16 days with the Debrisan to reach the stage of re-growth of skin over the healing wound achieved after 8 days with the honey. For treatment of burst abdominal wounds following caesarean delivery, the period of hospitalisation required was 2 - 7 days (mean 4.5) for a group of 15 patients whose wounds were dressed with honey and closed with adhesive tape, compared with 9 - 18 days (mean 11.5) for the comparative group (19 patients) whose wounds were cleaned with antiseptic and re-stitched.

Stronger evidence is provided from the statistically significant results from randomised controlled clinical trials. A trial comparing honey-impregnated gauze with a commonly used polyurethane film dressing (OpSite®) as a cover for partial thickness burns in two groups of 46 patients found faster healing with the honey (means 10.8 versus 15.3 days). Similarly, another trial comparing honey-impregnated gauze with amniotic membrane (a well-established material used as a temporary "skin") as a cover for partial thickness burns in groups of 40 and 24 patients respectively found the burns treated with honey healed faster (means 9.4 versus 17.5 days). A trial comparing honey with boiled potato peel dressings (another established material used as a temporary "skin") as a cover for partial thickness burns in two groups of 50 patients found faster healing with the honey (means 10.4 versus 16.2 days). A trial comparing honey with silver sulfadiazine, the most commonly used burn dressing, as a cover for partial thickness burns in two groups of 52 patients also found faster healing with the honey: 87% of those treated with honey healed within 15 days compared with 10% of those treated with silver sulfadiazine. A similar trial with two groups of 25 patients found that satisfactory re-growth of skin over the burn had occurred in 84% of those treated with honey by 1 week, 100% by 3 weeks, whereas with silver sulfadiazine it had occurred in only 72% of those treated with honey by 1 week and 84% by 3 weeks. A trial comparing honey with saline dressings in the treatment of pressure ulcers (bed sores) in two groups of 20 patients found faster healing with the honey (means 8.2 versus 9.9 days).

Controlled trials have also been carried out on the treatment of wounds on animals, with microscopic examination of the wound tissues confirming the directly observed faster rates of healing with honey. In a trial comparing honey with silver sulfadiazine on deep burns on the skin of pigs, complete re-growth of skin over the burns was achieved within 21 days with honey whereas it took 28 - 35 days with silver sulfadiazine. A sugar solution was also compared in this trial: this gave the same rate of healing as the honey, but microscopic examination of the tissues showed a better quality of healing with the honey, and cellular evidence of a more advanced state of healing. In a study comparing honey with sugar solution on superficial burns on the skin of rats, healing was seen by microscopic examination of the tissues to be more active and advanced with honey than with the sugar solution. The time taken for complete repair of the wound was significantly less with honey than with no treatment. A study on full-thickness skin wounds on buffalo calves found that honey gave a faster rate of healing than did the antibacterial nitrofurazone and the petroleum jelly control. A study on full-thickness skin wounds on rabbits found that honey gave a faster rate of healing than the untreated control wounds.

Other studies on animals have compared honey with saline, a standard moist dressing for wounds. In a study on infected full-thickness skin wounds on buffalo calves, honey gave the fastest rate of healing compared with ampicillin ointment and saline. A study on deep skin wounds on mice found that the re-growth of tissue was significantly greater, and the area of the wound significantly smaller, in those treated with honey compared with those treated with saline. Another study, on rats, found a statistically significant increase in the rate of healing with floral honey compared with saline, but not with honey from sugar-fed bees

Stimulation of the healing process

Some wounds, termed chronic wounds, may go for long periods, sometimes for years, without the healing process taking place. Leg ulcers and diabetic ulcers are a common examples of this type of wound. Honey has been found to be effective in starting the healing process in non-healing ulcers, some of which had been present for a median time of 1 year, or had been treated for up to 2 years, or had shown no healing over more than 5 years despite usual measures including skin grafts. Honey has also been used successfully on chronic foot ulcers in lepers and diabetic foot ulcers.

Honey has a very low failure rate: in reports of at least 143 chronic wounds treated with honey there was only one failure in one report (a Buruli ulcer: treatment with honey was discontinued after 2 weeks because the ulcer was rapidly increasing in size) and six in another (where the quantity of honey applied was very small). Over all of the other reports covered in a review of the literature, with more than 470 cases treated with honey, there were only five cases where successful healing was not achieved: in one report two were attributed to the poor general quality of the patients who were suffering from immunodepression, one was withdrawn from treatment with honey because of a painful reaction to the honey, and one burn remained stationary after a good initial response; in another it was an ulcer complicated by the presence of varicose veins.

Clearance of infection

Many of the authors reporting the use of honey as a dressing on infected wounds attribute its effectiveness at least partly to its antibacterial properties. Honey is reported to be very effective in cleaning up infected wounds. It action is effective even in treating Fournier’s gangrene, a rapidly spreading erupting infection that is usually treated by aggressive surgical removal of tissue that has died as a result of the infection, which otherwise would support the growth of bacteria. Honey stops the advance of the infection without the need to remove dead tissue.

Honey is effective in clearing infection in wounds where other treatments have failed. One report gave the results of treating with honey dressings 47 patients with wounds and ulcers which had been treated for 1 month to 2 years with conventional therapy (including antibiotics) with no signs of healing, or the wounds were increasing in size. The wounds were of a wide variety of causes. Microbiological examination of swabs from the wounds showed that the wounds with bacteria present became sterile within 1 week and the others remained sterile. The outcomes were reported as "showed remarkable improvement following topical application of honey". A similar report gave the results of treatment with honey dressings of 40 patients, half of which had been treated with "the usual topical measures" (another antiseptic) which had failed. The wounds were large and of a wide variety of causes. The number of species of bacteria isolated from the wounds dropped from 48 to 14 after two weeks of treatment. Of the 33 patients treated only with honey dressings, 29 were healed successfully, with good quality healing, in an average time of 5 - 6 weeks. Another report described honey being used on nine infants with large, open, infected surgical wounds that failed to heal with conventional treatment of at least 14 days of intravenous antibiotic and cleaning the wound with antiseptic. before treatment with honey the wounds were still open, oozing pus, and bacteria were present. A marked improvement was seen in the appearance of the wounds in all of the infants after five days of treatment with honey. The wounds were closed, clean and sterile in all infants after 21 days of application of honey.

The speed with which wounds dressed with honey become clear of infection is remarkable. Wounds have been reported to become sterile in 3 - 6 days, 7 days or 7 - 10 days. But, possibly because of differences between honeys in their antibacterial activity, there have been findings of slower clearance of infection: there have been reports of bacteria still present in wounds after 2 weeks, 3 weeks, and 5 weeks.

Dressing infected wounds with honey gives a clean clear base that allows early grafting, and gives prompt graft taking. By cleaning up the wounds it also allows the wound boundaries to be more clearly defined to facilitate surgical procedures.This is of particular advantage in the case of diabetic and malignant ulcers where surgery is often required.

Perhaps the most important role for honey in wound care will prove to be in the treatment of wounds infected with antibiotic-resistant bacteria. Honey has been shown to be effective in laboratory testing against MRSA, and has been found to be effective in clearing up wounds infected with multi-resistant bacteria.

Cleansing action on wounds

Several authors have reported the cleansing effect of honey on wounds. The standard procedure for the treatment of wounds is to surgically remove any dead tissue (i.e. debride the wound) which would serve to support the growth of infecting bacteria. Otherwise these would produce toxins which would kill more surrounding tissue. Debridement is a painful procedure that usually requires anaesthesia of some sort. Honey has a debriding effect on wounds so that surgical debridement is unnecessaryor a minimum of surgical debridement is required. Dead tissue separates easily from the wound bed after honey has been applied to a wound. The dry crust formed on the surface of a wound is also removed by the application of honey, and no dry scab forms on burns dressed with honey. It has also been noted that dirt is removed with the bandage when honey is used as a dressing, leaving a clean wound.

Infected wounds can be malodorous, especially those infected with anaerobic bacteria. This can be distressing for those who have to treat the wounds, and even more so for the patient, who cannot move away from the smell who may find it embarrassing. Honey has been reported to give rapid deodorisation of offensively smelling wounds.

Stimulation of tissue regeneration

When a wound heals the dead or damaged tissue is replaced by the growth of new connective tissue and a new outer layer of skin (epithelium) spreads over the surface of the wound. The new connective tissue grows in a granular fashion (around newly formed blood vessels), hence is termed granulation. Many have reported that honey promotes the formation of clean healthy granulation tissue and growth of epithelium over the wound. Thus it helps skin regenerate, making plastic surgery unnecessary. It has also been reported that dressing wounds with honey gives little or no scarring.

These clinical observations of stimulation of tissue growth have been corroborated by microscopic examination of wound tissues in studies of the effect of honey on wound healing in animals, where there has been clear evidence seen of stimulation of tissue growth. These studies have also shown a stimulation of the synthesis of collagen, the protein responsible for giving the strength to skin and to scar tissue. The formation of other connective tissue components is also stimulated, and there is improvement of the strength of collagen and of the healed wounds. The stimulation of the development of new blood vessels in the bed of wounds has also been observed.

Reduction of inflammation

The inflammation of surrounding tissues that results from infection of a wound, or directly from the damage to tissues caused by burns, is the major cause of the pain and discomfort associated with wounds. The process of inflammation involves blood capillaries opening up and allowing plasma from the blood to flow out into the surrounding tissues. This causes swelling of the tissues (oedema), the pressure giving rise to damage and discomfort in the healing area. It also causes plasma to exude from open wounds, sometimes in large quantities. Honey has been reported to reduce inflammation, oedemaand exudation. This would account for the soothing effect observed when honey is applied to woundsand the reduction of pain from burns. In some cases there is a rapid diminution of local pain.

The anti-inflammatory effect of honey has also been observed by microscopic examination of wound tissues in studies of the effect of honey on wound healing in animals, where reduction in the number of white blood cells involved in inflammation could be seen. The reduction in inflammation seen when honey is applied to wounds must be a direct anti-inflammatory effect, not just a result of removing inflammation-causing bacteria: the anti-inflammatory effects of honey were seen in animal studies where there was no infection involved.

Comfort of honey dressings

Honey generally causes no pain on dressingor causes only momentary stinging, is non-irritating, and does not cause allergic reaction. In several of the reports of honey being used on wounds the authors have observed that honey has no harmful effects on tissues. Over all the reports of honey being used on wounds, with a total of more than six hundred cases, there have been no reports of any harmful effects of honey on tissues. Nor have any adverse effects been noted in any of the studies in which honey has been applied to wounds on animals. These studies have included microscopic examination of the wound tissues. However, there have been two cases where the pain persisted for 15 minutes and in two cases where the pain was such that the application of honey could not be tolerated.

The pain or discomfort usually associated with changing dressings is minimised when honey dressings are used, which are easy to apply and remove. There is no difficulty removing dressings because there is no adhesion to cause damage to the exposed re-growing tissues on the surface of wounds. Also there is no bleeding when removing dressings. Any honey left on the surface of the wound is easily removed by simple bathing, unlike with many other dressing materials which have to be wiped off or forcefully washed off.

Gastroenteritis

The Holy Hadith records the Muslim prophet Mohammed instructing a man afflicted with diarrhoea to take honey. The Roman physician Celsus, c. 25 AD, used honey as a cure for diarrhoea. Dosage with water and honey is also used by many veterinarians for treatment of diarrhoea in small animals, and dosage with an 8% (v/v) solution of honey has been reported to be effective for the treatment of chronic diarrhoea in a horse. Honey has been used at a concentration of 5% (v/v) in place of glucose in a rehydration fluid (solution of electrolytes) in a clinical trial conducted on 169 infants and children admitted into hospital with gastroenteritis. The patients were randomly assigned into two groups, the control group being treated with the standard rehydration therapy (2% w/v glucose in a solution of electrolytes). Testing showed that in each group there were 18 patients with bacterial diarrhoea. The treatment with honey gave a statistically significant reduction in the duration of the diarrhoea (58 hours c/f 93 hours), and gave no increase in the duration of non-bacterial diarrhoea.

Peptic ulcers and gastritis

Honey has a traditional folklore usage for the treatment of peptic ulcers. Also there are numerous reports of oral dosage of honey being successfully used in modern times to treat upper gastrointestinal dyspepsia, including gastritis, duodenitis and ulceration, particularly in Russia and Arabic countries.

A clinical trial has been reported in which 45 patients with dyspepsia were given no medication other than 30 ml of honey before meals 3 times daily. After treatment with honey the number of patients passing blood (from peptic ulcers) in their faeces had decreased from 37 to 4; the number of patients with dyspepsia had decreased from 41 to 8; the number of patients with gastritis or duodenitis seen on endoscopy had decreased from 24 to 15; the number of patients with a duodenal ulcer seen on endoscopy had decreased from 7 to 2. The healing effect of honey on gastric ulcers has also been shown in a trial carried out on rats with ulcers caused by aspirin. After 3 days of treatment the control group of 10 rats (given saline) had 15 ulcers whereas the group of 10 rats given honey from sugar-fed bees had 8 ulcers and the group of 10 rats given floral honey had 3 ulcers: the differences between these numbers were statistically significant. In a similar study the gastric ulcers in the rats were caused by indomethacin, another non-steroidal anti-inflammatory drug, which is like aspirin in its action. The healing rate achieved with the honey in this study was 70%, measured as the number of ulcers in the honey-treated group compared with an untreated control group.

Other studies with rats have shown that honey also has a preventative action, protecting the stomach from ulceration by substances which commonly cause peptic ulcers in people: a non-steroidal anti-inflammatory drug (indomethacin), and alcohol.


Ophthalmology

In ancient times honey from Attica had a special reputation as a curative substance for eye disorders. Aristotle wrote in 350 BC in section 627a 3 of Historia Animalium that "White honey.... is good as a salve for sore eyes". In India lotus honey in more recent times (1945) lotus honey was said to be a panacea for eye diseases. Honey is also a traditional therapy in Mali for measles, it being put in the eyes to prevent the scarring of the cornea which occurs in this infection.

Meier has referred to honey being used to treat eyes discharging pus. Sarma, an ophthalmic surgeon at Rangaraya Medical College, India, has been treating bacterial corneal ulcers with honey. The use of honey to treat blepharitis (inflammation of the eye-lids), catarrhal conjunctivitis, and keratitis (inflammation of the cornea) has also been reported: good results in general were obtained, with remission in more than 60% of the cases. Another report has described the use of honey in place of petroleum jelly in a 3% sulfidine eye ointment for the treatment of three cases of keratitis: significant improvement in one case and complete restoration of vision in the other two cases resulted from the treatment with honey, yet there had been no effect when treated with the 3% sulfidine in petroleum jelly. This same paper reported the successful treatment with the honey ointment of 28 patients with various ailments of the cornea, successful in all cases; also the effective treatment with honey of syphilitic keratitis, corneal ulcers, injuries to the cornea, and lime burns of the cornea. It also described a case where a lime burn of the cornea was treated with pure honey, with half-vision being restored in 12 days; and reported that several cases of scrofulous keratitis had responded to treatment with pure honey. Mozherenkov and Prokof'eva have reviewed the use of honey in ophthalmology in Russia. Anti-inflammatory, antibacterial and antifungal actions are seen, the honey being applied to the eye under the lower eyelid. It has been used for chemical and thermal burns to the eye, conjunctivitis, and infections of the cornea, being applied undiluted or as a 20 – 50% solution in water.

The results have been reported of treating 102 patients with a variety of ophthalmological disorders not responding to conventional treatment, such as keratitis, conjunctivitis and blepharitis. The honey was applied under the lower eyelid as eye ointment would be applied. Improvement was seen in 85% of the cases, with no deterioration seen in any of the other 15%. There was reported a transient stinging sensation and redness of the eye soon after putting honey in the eye, but never enough to stop the treatment in the 102 cases in the trial. A similar reaction was reported by one of the other authors describing the use of honey in ophthalmology.

Acknowledgments
The assistance of Niaz Al Somai, Anna Blättler, David Foreman, Paola Galimberti and Jacek Krzyzosiak in translating papers is gratefully acknowledged.