Evidence for Honey Promoting Wound Healing

on Sunday, 21 April 2013. Posted in Honey Research

The use of honey as a wound dressing material, an ancient remedy that has been rediscovered,...

Summary
The use of honey as a wound dressing material, an ancient remedy that has been rediscovered, is becoming of increasing interest as more reports of its effectiveness are published. The clinical observations recorded are that infection is rapidly cleared, inflammation, swelling and pain are quickly reduced, odor is reduced, sloughing of necrotic tissue is induced, granulation and epithelialisation are hastened, and healing occurs rapidly with minimal scarring. The antimicrobial properties of honey prevent microbial growth in the moist healing environment created. Unlike other topical antiseptics, honey causes no tissue damage: in animal studies it has been demonstrated histological that it actually promotes the healing process. It has a direct nutrient effect as well as drawing lymph out to the cells by osmosis. The stimulation of healing may also be due to the acidity of honey. The osmosis creates a solution of honey in contact with the wound surface which prevents the dressing sticking, so there is no pain or tissue damage when dressings are changed. There is much anecdotal evidence to support its use, and randomized controlled clinical trials that have shown that honey is more effective than silver sulfadiazine and a polyurethane film dressing for the treatment of burns.

Mode of Application of Honey
The procedure that is described in most of the reports is to clean the wound first, even though many describe honey as having a cleansing and deriding action on wounds. Some report abscesses being opened and pockets of pus drained, and necrotic tissue being removed, before dressing wounds with honey. Most report simply washing wounds with saline before dressing with honey, and when dressings are changed.

In many of the reports the honey is spread on the wound then covered with a dry dressing, mostly gauze. The quantity of honey used varies: applied the honey to the dressing then placed it on the wound: either the honey was spread on gauze or the gauze was soaked in honey, or "honey pads" were used. (It has also been reported that covering cracked sore nipples in nursing mothers with gauze soaked in honey can prevent them from becoming infected. Honey-impregnated gauze has also been used to pack cavities of wounds. Others have packed cavities of wound directly with honey and then covered the wound. Cervical ulcerations stubborn to healing have been treated by inserting 85 ml honey in the vagina and holding this in place with a tampon for 3 days. Mostly the dressings are changed daily or every 2 days: or every 2 - 3 days. Another reported dressings being changed once or twice daily until clean granulated wounds were achieved, then once-daily changes. Others have reported changing honey dressings twice daily, 2 - 3 times a day, 3 times daily, and 3 times daily if contaminated with urine or feces, otherwise twice daily.

There is no indication of any of the reported modes of application of honey being decided upon on empirical or theoretical grounds, the large degree of variance in modes appearing to reflect a more notional approach. The spreading of honey on the dressing pad rather than on the wound is much easier to do and is less traumatic for the patient. It also gives a more even coverage of the wound surface. Where deep wounds or abscesses need to be filled with honey the most practicable way of doing this would be to use honey packed in squeeze-out tubes, now available commercially.

Rationally, the amount of honey required per unit area of the wound would depend on the amount of exudation. The various beneficial effects of honey on wound tissues that have been reported would be expected to be reduced or lost if small amounts of honey become diluted by large amounts of exudate. Likewise the frequency of dressing changes required will depend on how rapidly the honey is being diluted by exudate. The effectiveness of honey in reducing inflammation and exudation should lead to less frequent changes being required later. There should be no need to change dressing frequently to prevent bacterial growth under the dressing, as the antibacterial activity of honey will prevent this if there is not excessive dilution by exudate, especially if a honey with a high level of activity is selected.

Clinical Observations
It has been reported from various clinical studies on the usage of honey as a dressing for infected wounds that the wounds become sterile in 3 - 6 days, 7 days or 7 - 10 days. Others have reported that honey is effective in cleaning up infected wounds. It has also been reported that honey dressings halt advancing necrosis.

Honey has also been found to act as a barrier preventing wounds from becoming infected, preventing cross-infection, and allowing burn wound tissue to heal rapidly uninhibited by secondary infection.

It has been reported that sloughs, gangrenous tissue and necrotic tissue are rapidly replaced with granulation tissue and advancing epithelialisation when honey is used as a dressing, thus a minimum of surgical debridement is required. It has been observed that under honey dressings sloughs, necrotic and gangrenous tissue separated so that they could be lifted off painlessly, and others have noted quick and easy separation of sloughs and removal of crust from a wound. Rapid cleansing and chemical or enzymic debridement resulting from the application of honey to wounds have also been reported with no eschar forming on burns. Several other authors have noted the cleansing effect of honey on wounds. It has also been noted that dirt is removed with the bandage when honey is used as a dressing, leaving a clean wound. Honey has also been reported to give deodorization of offensively smelling wounds.

Honey used as a wound dressing has been reported to promote the formation of clean healthy granulation tissue. It has also been reported to promote epithelialisation of the wound. Dumronglert commented that the rapid growth of new tissue is remarkable. Improvement of nutrition of wounds has been observed, also increased blood flow has been noted in wounds and free flow of lymph.

It has been noted that dressing wounds with honey allows early grafting on a clean clear base, with prompt graft taking. It has also been reported that it reduces the incidence of skin graft areas and helps skin regenerate, making plastic reconstruction unnecessary. Others also have noted that skin grafting is found to be unnecessary. It has also been reported that dressing wounds with honey gives little or no scarring.

Another effect of honey on wounds that has been noted is that it reduces inflammation and hastens subsidence of passive hyperaemia. It also reduces oedema and exudation, absorbing fluid from the wound. Honey is reported to be soothing when applied to wounds and to reduced pain from burns, in some cases giving rapid diminution of local pain.

Honey is reported to cause no pain on dressing or to cause only momentary stinging, to be non-irritating, to cause no allergic reaction, and to have no harmful effects on tissues. It has been noted that honey dressings are easy to apply and remove. There is no adhesion to cause damage to the granulating surface of wounds, no difficulty removing dressings, and no bleeding when removing dressings. Any residual honey is easily removed by simple bathing.

These clinical observations provide, in isolation, the lowest level of evidence upon which to base a clinical decision to use honey as a wound dressing. But when compared with the results usually experienced with the more commonly used dressings, they indicate that honey has some actions and attributes that have the potential to make it a very useful wound dressing material. Its physical properties provide a protective barrier and, by osmosis, create a moist healing environment in the form of a solution of honey that does not stick to the underlying wound tissues. The antibacterial properties of honey prevent bacterial colonization of this moist environment, to the extent that unlike other moist wound dressings it is suitable for use on infected wounds. Its antibacterial components show no impairment of the healing process through adverse effects on wound tissues: to the contrary it appears to have a stimulatory effect on tissue regeneration. In addition there are clear indications of an anti-inflammatory action.

Evidence of Effectiveness: Clinical Study
A study has been reported of the treatment with honey dressings of 59 patients with recalcitrant wounds and ulcers, 47 of which had been treated for what clinicians deemed a "sufficiently long time" (1 month to 2 years) with conventional treatment (such as Eusol toilet and dressings of Acriflavine, Sofra-Tulle, or Cicatrin, or systemic and topical antibiotics) with no signs of healing, or the wounds were increasing in size. The wounds were of varied aetiology, such as Fournier's gangrene, burns, cancrum oris and diabetic ulcers, traumatic ulcers, decubitus ulcers, sickle cell ulcers and tropical ulcers. Microbiological examination of swabs from the wounds showed that the 51 wounds with bacteria present became sterile within 1 week and the others remained sterile. In one of the cases, a Buruli ulcer, treatment with honey was discontinued after 2 weeks because the ulcer was rapidly increasing in size. The outcomes of the 58 other cases were reported as "showed remarkable improvement following topical application of honey". Some general observations reported for the outcomes from honey treatment of these recalcitrant wounds were that sloughs, necrotic and gangrenous tissue separated so that they could be lifted off painlessly, within 2 - 4 days in Fournier's gangrene, cancrum oris and decubitus ulcers (but it took much longer in other types). Sloughs and necrotic tissue were rapidly replaced with granulation tissue and advancing epithelialisation. Surrounding oedema subsided, weeping ulcers dehydrated, and foul-smelling wounds were rendered odorless within 1 week. Burn wounds treated early healed quickly, not becoming colonized by bacteria.

A similar study, but with less detail given, was carried out on 40 patients, half of which had been treated with "the usual topical measures" (another antiseptic) which had failed. The wounds were of mixed aetiology: surgical, accidental, infective, trophic, and burns; the average size of the wounds was 57 cm2. One third of the wounds were purulent, the rest were red with a whitish coat. The number of microorganism isolates from the wounds dropped from 48 to 14 after two weeks of treatment. Seven of the patients had necrotic tissue excised after treatment with honey, and three of these had skin grafts. It was noted that the honey delimited the boundaries of the wounds and cleansed the wounds rapidly to allow this. 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. Of the four cases where successful healing was not achieved, 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 study honey was used on (12) 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 aqueous chlorhexidine solution (0.05% w/v) and fusidic acid ointment. These wounds were still open, oozing pus, and swab cultures were positive. Marked clinical improvement was seen in all infants after five days of treatment with topical application of 5 - 10 ml of honey twice daily. The wounds were closed, clean and sterile in all infants after 21 days of application of honey.

These three studies are effectively cross-over trials, in that a baseline of non-responsiveness had been established with other forms of treatment before honey was used. Although this form of evidence is less convincing than when there is a simultaneous treated control group of patients, the consistency of the outcome and the numbers of patients involved make it highly improbable that the change from non-healing to healing was just due to chance rather than to the therapeutic effect of the honey. The reports would have been of more value as evidence if more detail had been given, but even as they are they provide good evidence that honey is effective in promoting the healing of wounds that are not responding to conventional therapeutic procedures. They also provide good evidence of the effectiveness of the antibacterial activity of honey on infected wounds.

Evidence of Effectiveness: Clinical Trials
Twenty consecutive cases of Fournier's gangrene managed conservatively with systemic antibiotics (oral amoxicillin/clavulanic acid and metronidazole) in addition to daily topical application of honey were compared retrospectively with 21 similar cases of Fournier's gangrene managed by the orthodox method (wound debridement, wound excision, secondary suturing, and in some cases scrotal plastic reconstruction in addition to receiving a mixture of systemic antibiotics dictated by sensitivity results from cultures). (The microorganisms cultured in both treatment groups were similar.) Even though the average duration of hospitalization was slightly longer, topical application of honey showed distinct advantages over the orthodox method. Three deaths occurred in the group treated by the orthodox method, whereas no deaths occurred in the group treated with honey. The need for anaesthesia and expensive surgical operation was obviated with the use of honey. Response to treatment and alleviation of morbidity were faster in the group treated with honey. Although some of the bacteria isolated from honey-treated patients were not sensitive to the antibiotics used, the wounds became sterile within 1 week.

The usefulness of honey dressings as an alternative method of managing abdominal wound disruption was assessed in a prospective trial over 2 years compared retrospectively with patients of a similar age over the preceding 2 years. Fifteen patients whose wound disrupted after Caesarean section were treated with honey application and wound approximation by micropore tape instead of the conventional method of wound dressing with subsequent resuturing. (The comparative group, 19 patients, had their dehisced wounds cleaned with hydrogen peroxide and Dakin solution and packed with saline-soaked gauze prior to resuturing under general anesthesia.) It was noted that with honey dressings slough and necrotic were replaced by granulation and advancing epithelialisation within 2 days, and foul-smelling wounds were made odorless within 1 week. Excellent results were achieved in all the cases treated with honey, thus avoiding the need to resuture which would have required general anesthesia. Eleven of the cases were completely healed within 7 days, all 15 within 2 weeks. The period of hospitalization required was 2 - 7 days (mean 4.5), compared with 9 - 18 days (mean 11.5) for the comparative group. Two of the comparative group had their wounds become reinfected, and one developed hepatocellular jaundice from the anaesthetic.

A retrospective study of 156 burn patients treated in a hospital over a period of 5 years (1988-92) found that the 13 cases treated with honey had a similar outcome to those treated with silver sulfadiazine. A prospective randomized controlled trial was carried out to compare honey-impregnated gauze with OpSite® as a cover for fresh partial thickness burns in two groups of 46 patients. Wounds dressed with honey-impregnated gauze showed significantly faster healing compared with those dressed with OpSite® (means 10.8 versus 15.3 days: p < 0.001). Less than half as many of the cases became infected in the wounds dressed with honey-impregnated gauze compared with those dressed with OpSite® (p < 0.001). Another prospective randomised clinical study was carried out to compare honey-impregnated gauze with amniotic membrane dressing for partial thickness burns. Forty patients were treated with honey-impregnated gauze and 24 were treated with amniotic membrane. The burns treated with honey healed earlier compared with those treated with amniotic membrane (mean 9.4 versus 17.5 days: p < 0.001). Residual scars were noted in 8% of patients treated with honey-impregnated gauze and in 16.6% of cases treated with amniotic membrane (p < 0.001).

Honey was compared with silver sulfadiazine-impregnated gauze for efficacy as a dressing for superficial burn injury in a prospective randomized controlled trial that was carried out with a total of 104 patients. In the 52 patients treated with honey, 91% of the wounds were rendered sterile within 7 days. In the 52 patients treated with silver sulfadiazine, 7% showed control of infection within 7 days. Healthy granulation tissue was observed earlier in patients treated with honey (means 7.4 versus 13.4 days). The time taken for healing was significantly shorter with the honey-treated group (p<0.001): of the wounds treated with honey 87% healed within 15 days compared with 10% of those treated with silver sulfadiazine. Better relief of pain, less exudation, less irritation of the wound, and a lower incidence of hypertrophic scar and post-burn contracture were noted with the honey treatment. The honey treatment also gave acceleration of epithelialisation at 6 - 9 days, a chemical debridement effect and removal of offensive smell.

In another prospective randomized controlled trial comparing honey with silver sulfadiazine-impregnated gauze on comparable fresh partial thickness burns, histological examination of biopsy samples from the wound margin as well as clinical observations of wound healing were made to assess relative effects on wound healing in two groups of 25 patients. The time taken for healing was significantly shorter with the honey-treated group (0.001). Of the wounds treated with honey, 84% showed satisfactory epithelialisation by the 7th day, 100% by the 21st day. In wounds treated with silver sulfadiazine, epithelialisation occurred by the 7th day in 72% of the patients and in 84% of patients by 21 days. Histological evidence of reparative activity was seen in 80% of wounds treated with the honey dressing by the 7th day, with minimal inflammation. Of the wounds treated with silver sulfadiazine 52% showed reparative activity, with inflammatory changes, by the 7th day. Reparative activity reached 100% by 21 days with the honey dressing and 84% with silver sulfadiazine. In honey-dressed wounds early subsidence of acute inflammatory changes, better control of infection and quicker wound healing were observed, while in the wounds treated with silver sulfadiazine sustained inflammatory reaction was noted even on epithelialisation. No skin grafting was required for the wounds treated with honey, but four of the wounds treated with silver sulfadiazine converted to deep and required skin grafts.

The trial conducted on infected disrupted abdominal wounds, with a closely matched control group, showed clearly that dressing with honey was more effective than the conventional treatment of the control group in achieving healing of the wounds, as well as obviating the need for suturing. However, the conventional treatment, using antiseptics which can damage tissues and inhibit wound healing, although commonly used, is possibly not the best bench-mark against which to judge the effectiveness of honey. The studies of burn patients treated with honey compared with those treated with silver sulfadiazine, however, showed that honey is as effective as, or more effective than, the topical burn treatment that is the most widely used in modern times. Although the retrospective study did not give details of the cases to allow it to be seen if the cases treated with honey were similar to the ones treated with silver sulfadiazine, the prospective randomized controlled trials were well designed and adequately described, the statistically significant results from large numbers of patients providing convincing evidence that dressing with honey is the best treatment for superficial burns.

Risks and Adverse Effects
No adverse effects have been noted in any of the studies in which honey has been applied topically to experimental wounds. These studies have included histological examination of treated tissues. Honey has been used topically on wounds over thousands of years also without gaining any reputation for adverse effects. The many reports published in more recent times on its clinical usage on open wounds mention no more than a transient stinging sensation in some patients. Generally the topical application of honey on open wounds is reported to be soothing, to relieve pain, be non-irritating, cause no pain on dressing, and give no secondary reactions.

Allergy to honey is rare, but there could be an allergic reaction to either the pollen or the bee proteins in honey. In reports of clinical studies where honey was applied to open wounds of a total of 134 patients it was stated that there were no allergic or adverse reactions. However, an occurrence of a minor hemorrhage soon after application of honey has been mentioned in reference to an unrecorded case. Reference has been made to dehydration of tissues if too much honey is applied to a wound, but it has been stated that the hydration of the tissues is easily restored by saline packs. Because honey contains up to 40% glucose there is a theoretical risk of it adversely elevating the blood glucose level of diabetics when applied topically on a large open wound.

Honey sometimes contains spores of clostridia, which poses a small risk of wound botulism. However, in none of the many reports published on the clinical usage of honey on open wounds was the honey that was used sterilized, yet there are no reports of any type of infection resulting from the application of honey to wounds. If spores germinated, any vegetative cells of clostridia, being obligate anaerobes, would be unlikely to survive in the presence of the hydrogen peroxide that is generated in diluted honey. But the use of honey as a wound dressing has been argued against, however, on the grounds that the risk of it possibly causing wound botulism is unacceptable. This objection can be overcome by the use of honey that has been treated by gamma-irradiation, which kills clostridial spores in honey without loss of any of the antibacterial activity. The problem of attraction of flies and ants to honey dressings, not commonly noted, can be overcome by using effective secondary dressings so that the honey is prevented from leaking out or being exposed to insects.

Advantages of Using Honey as a Wound Dressing
Honey provides a moist healing environment yet prevents bacterial growth even when wounds are heavily infected. It is a very effective means of quickly rendering heavily infected wounds sterile, without the side-effects of antibiotics, and it is effective against antibiotic-resistant strains of bacteria. Its antibacterial properties and its viscosity also provide a barrier to cross-infection of wounds. It also provides a supply of glucose for leucocytes, essential for the 'respiratory burst' that produces hydrogen peroxide, the dominant component of the antibacterial activity of macrophages. Furthermore it provides substrates for glycolysis, which is the major mechanism for energy production in the macrophages, and thus allows them to function in damaged tissues and exudates where the oxygen supply is often poor. The acidity of honey (typically below pH 4) may also assist in the antibacterial action of macrophages, as an acid pH inside the vacuole is involved in killing ingested bacteria. Whether it is through this action, or through preventing the toxic unionized form of ammonia from existing that is involved, topical acidification of wounds promotes healing. The high glucose levels that the honey provides would be used by the infecting bacteria in preference to amino acids from the serum and dead cells, and thus would give rise to lactic acid instead of ammonia and the amines and sulphur compounds that are the cause of malodor in wounds.

Honey gives a fast rate of tissue regeneration and suppression of inflammation, oedema, exudation and malodor in wounds, as evidenced in clinical observations and the results of animal studies and clinical trials. The antibacterial properties clearing infection could alone account for these effects by preventing the production of the products of bacterial metabolism which are responsible for the contrary conditions. But honey has a direct trophic and anti-inflammatory effect on wound tissues, as evidenced by the results of animal studies in which there was no bacterial infection involved, particularly in those where the honey was administered systemically.

Honey can be expected to have a direct nutrient effect on regenerating tissue because it contains a wide range of amino acids, vitamins and trace elements in addition to large quantities of readily assimilable sugars. (The vitamin C content of honey, which is typically more than three times higher than that in serum, and may be many times higher, could be of particular importance as because of the essential role of this vitamin in collagen synthesis.) In addition, the high osmolarity of honey causes an outflow of lymph which serves to provide nutrition for regenerating tissue which otherwise can only grow around points of angiogenesis (seen as granulation): healing is delayed if the circulation to an area is poor, or if a patient is poorly nourished. Also it has been suggested that the decreased turgor resulting from the application of honey may increase oxygenation of tissues.

There is also an economical advantage to using honey as a wound dressing. This is seen both in the direct cost savings when compared with conventional treatments, and in the savings in ongoing costs when consideration is given to the more rapid healing rates that are achieved. Other observations on cost savings have been: use of antibiotics ceased, length of hospitalization reduced (by at least half). In addition there are the savings in the costs of surgery where debridement and skin grafting become unnecessary when honey is used.

Honey is also an ideal first-aid dressing material, especially for patients in remote locations when there could be time for infection to have set in before medical treatment is obtained: it is readily available and simple to use. It would be particularly suitable for first-aid treatment for burns, where emergency dousing or cooling frequently involves the use of contaminated water which then leads to heavy infection of the traumatized tissue. As well as providing an immediate anti-inflammatory treatment the honey would provide an antibacterial action and a barrier to further infection of the wound.