Although I use honey for things like coughs etc until recently I never had reason to use Honey on a wound
I was bitten by a ordinary spider several weeks ago [here in the UK] for some days the wound continued to blister and fester, so my friend, a nurse speacialising in wound care gave me a wound dressing which initially helped draw out any nasties but didn't make any other impact, on day 17 I decided to steam the wound which caused the eschar to raise from the wound and I removed it with little discomfort, I the put honey into the wound and was amazed at the difference the next day, the wound is decreasing in size and the new skin growth is strong. 5 days later the wound continues to improve and heal with twice daily applications of honey.
Honey will deffo always be my first choice of wound care from now on. Curious to find out how honey works on wounds I found this great information yesterday - see below
The concerted action of the various physical properties and bioactivities in honey explains the remarkable results obtained clinically, especially when sufficient honey is held in place on the wound for these factors to work. The use of honey over a period of more than 4,000 years, with no adverse effects coming to light, is evidence of its effectiveness as a healing agent.
Mode of action
Honey is a substance produced by bees to store as a sugar food source collected as nectar from flowers (and occasionally from the sap of plants). Since the earliest recorded times, humans have taken this honey for use, not only as a food product, but also as a medicine, especially for wound care.
The bees concentrate the dilute sugar solutions they collect from the plants by evaporating off most of the water. (Honey is typically 17% water, 80% sugars.) They also add enzymes, so that as the honey ripens in the comb its composition changes and it becomes impossible for microbes to grow in it and spoil the stored food. One of these enzymes converts sucrose, the major sugar in nectar and sap, into a more soluble mixture of glucose and fructose. This makes the saturated or supersaturated solution of sugars that is stored as honey. (The difference in texture between liquid honey and solid or ‘creamed’ honey is due to fine crystals of solidified glucose being suspended in the saturated syrup.)
The sugar molecules in solution bind up water molecules, thereby denying microbes the water that is essential for their survival. Another enzyme added is glucose oxidase. This converts some of the glucose to gluconic acid, making honey too acidic for microbes to grow (honey has a pH of about 3.5) and, as a by-product of this reaction, forms hydrogen peroxide. This is a sporicidal antiseptic that sterilises the honey that is sealed in the comb. (When subsequently extracted from the comb, honey can be contaminated with microbial spores as the enzyme that produces hydrogen peroxide is inactive at that time because there is insufficient free water. These can survive the acidity and high sugar content.) These factors, which ensure the preservation of honey in the comb, are also useful in suppressing microbial growth when honey is applied to a wound.
Additionally, there are ‘herbal’ factors present which may be of benefit in wound care. Being the concentrated juice from plants, honey contains the various nutrients and herbal chemicals that come from the plants, such as: amino acids, other organic acids, enzymes, vitamins, acetylcholine, flavonoids, carotenoids, polyphenols, minerals and a wide variety of organic chemicals in trace quantities. These are what give different honeys their characteristic colours, flavours and aromas.
The colour of honey is also due to products of the Maillard reaction1 and caramelisation of its sugars, hence it gets darker in colour as it ages. Some of the plant-derived chemicals have antioxidant properties and some are known to have antibacterial properties.
It is for topical treatment of infections that honey has been most widely used as a medicine throughout history, and now that its use as a wound dressing has been ‘rediscovered’ by the medical profession, it is on infected wounds that it is mostly being used.
The clinical definition of infection is that the area of the wound is showing the classical signs of inflammation (redness, swelling and pain). The clinical focus in treating wounds is to remove the cause of the inflammation by killing the infecting bacteria and removing any pus or dead tissue that provide a medium for their growth. Inflammation in a wound causes many problems, such as making the wound uncomfortable and difficult to manage, but the major problem is that it prevents the tissue repair processes from healing the wound. The various bioactivities of honey work through all of these facets to give rapid healing — honey rapidly debrides wounds (ie. cleans the wound by releasing pus or dead tissue), kills bacteria, directly suppresses inflammation, and stimulates the growth of the various types of cells involved in the production of new tissue to repair the wound.
The scourge of excessive inflammation
Inflammation is a vital part of the normal response to infection or injury, and is what starts the healing process. It normally lasts for one day but, if it is prolonged or if the inflammatory response is excessive in intensity, it can prevent healing or even cause further damage to tissues. Prolonged inflammation, at a level below that which causes damage, is the cause of fibrosis, seen as hypertrophic scarring in wounds. Inflammation in wounds also causes discomfort for patients and problems in dressing the wounds, because of the large amounts of exudate associated with it.
The prostaglandins are part of the inflammatory response. They give rise to pain and cause small arteries to open, increasing blood pressure locally and giving rise to oedema in the area of the wound, and exudation of plasma from the wound. Suppression of inflammation, as well as reduction of pain, reduces the oedema and exudate. The pressure building up in tissues from oedema can slow the healing process, as it restricts the flow of blood through the capillaries, thus starving the tissues of the oxygen and nutrients that are vital for leukocytes to fight infection and for fibroblasts to multiply for wound healing. The swelling also increases the distance for diffusion of oxygen and nutrients from the capillaries to the cells
The inflammatory response is initiated by the reaction of leukocytes when in contact with substances from bacterial cells, or to tissue factors released when there is physical damage. (In the case of burn injuries, there are large quantities of these tissue factors released, which accounts for the severe inflammation associated with burns.) Phagocytes that are activated as part of the initial inflammatory response produce hydrogen peroxide to destroy the bacteria and debris that they engulf. Some of this hydrogen peroxide leaks out of the cells, which serves to give a feed-back amplification of the inflammatory response, as the hydrogen peroxide attracts and stimulates other leucocytes to proliferate. If this continues unchecked, the feed-back amplification can result in a vicious cycle that gives excessive levels of inflammation. Hydrogen peroxide was once widely used as an antiseptic, but has gone out of favour because it causes this inflammation. Although the hydrogen peroxide produced in honey may have the potential to cause inflammation, it is produced at very low levels, equivalent to about one thousandth of that in the 3% solution of hydrogen peroxide used as an antiseptic. However, there is also protection via the anti-inflammatory properties of honey.
The hydrogen peroxide released by phagocytes can also be converted to reactive oxygen species ( free radicals) in the tissues. These free radicals are very reactive and can break down proteins, nucleic acids and cell membrane lipids, thus damaging or destroying tissue. Far greater damage to tissues results from the activation of proteases in the wound tissues by reactive oxygen species. These protein-digesting enzymes are normally present in an inactive form (in the case of the matrix metalloproteases), or are kept inactive by the presence of an inhibitor (in the case of the neutrophil serine protease). But, once activated, can destroy wound tissue. Thus, a wound can become ulcerated and a partial thickness burn can become full-thickness. These activated proteases also have the potential to destroy the tissue growth factors which, being proteins, are essential for activation of the repair process.
In the case of reperfusion injury, hydrogen peroxide produced by a biochemical process is the initiator of the inflammatory response and the ongoing vicious cycle. When tissues are deprived of oxygen through obstruction of circulation, production of xanthine and alteration of the enzyme xanthine dehydrogenase to catalyse an oxidase type of reaction
occurs. When the circulation is subsequently restored and the tissue is reperfused, the oxygen now available is used by the enzyme to oxidise xanthine, setting up production of hydrogen peroxide and reactive oxygen species. This mechanism of initiation accounts for the inflammation in pressure ulcers (where circulation is cut off by pressure on the tissues then restored by relief of the pressure), and in varicose ulcers (where circulation is restricted by venous stasis then restored by elevating the legs), with the subsequent activation of proteases by the inflammatory reaction contributing to ulceration of the tissue.
Where the inflammation is less severe and insufficient to give erosion of tissue by activation of wound proteases, it can give excessive activation of fibroblasts, causing fibrosis, hypertrophic scarring and contractures. ( Fibroblasts are the precursors of muscle cells, and use the same contractile fibres as muscle cells to pull the edges of a wound together. They also produce collagen fibres which form scar tissue.) Although excessive or prolonged inflammation is a major problem in wounds, pharmaceutical anti-inflammatory substances are not generally used in wound treatment because they can impair healing through adverse effects on proliferating cells. Honey, however, has a potent anti-inflammatory action that not only has no adverse effects on the growth of cells, but actually gives a positive stimulation of their growth.
Anti-inflammatory properties of honey
Many clinical observations have been reported of reduced symptoms of inflammation when honey is applied to wounds and of it having a soothing effect when applied to wounds. The reduction of exudate in wounds dressed with honey is a great help when managing inflamed wounds. The anti-inflammatory action of honey is also seen in the reports of reducing scarring and contractures.
As well as these clinical observations, it has been demonstrated in animal models that honey gives reduced inflammation compared with various controls; histological studies finding reduced numbers of inflammatory cells present in deep and superficial burns and in full-thickness wounds. These effects are due to components other than the sugar in honey. Similar evidence has also come from a study of biopsy samples from burn wound tissue of hospital patients
The anti-inflammatory action of honey is not just a consequence of removing the stimulus for inflammation by clearing infection and debriding the wound, as has been observed in experimental wounds in which there were few or no bacteria present There has also been a direct demonstration of the anti-inflammatory properties of honey in a standard test for anti-inflammatory agents, where it decreased the stiffness of inflamed wrist joints of guinea pigs It has also been reported that, when given orally, honey lowers plasma prostaglandin concentrations in normal individuals
The component of honey responsible for its anti-inflammatory activity has not been identified, but it may be due to the antioxidant activity of honey. There are significant levels of antioxidants in honey (including some which complex with iron to stop it catalysing the Fenton reaction2. This reaction forms free radicals from hydrogen peroxide; these free radicals serve to recruit more leukocytes into areas of inflammation, as a self-amplification of the inflammatory response. The mechanism of this self-amplification of the inflammatory response is oxidative activation of the nuclear transcription factor NF-?B, which then promotes the production of pro-inflammatory cytokines by leukocytes and stimulate the activity of the fibroblasts, thus giving hypergranulation and fibrosis
It is the free radicals formed from hydrogen peroxide, rather than hydrogen peroxide itself, that are responsible for the activation of the transcription factor NF-?B and this activation can be prevented by antioxidants. A study carried out on burn wounds has shown that application of antioxidants to mop up free radicals reduces inflammation. In a clinical trial it was found that honey dressings prevented partial-thickness burns from converting to full-thickness burns which would have needed plastic surgery
Clearance of infection
Applying honey dressings to wounds has been reported to:
Clear infection rapidly
Heal deeply infected surgical wounds
Halt advancing necrotising fasciitis
Wounds not responding to conventional therapy with antibiotics and antiseptics have been healed by application of honey dressings ( including wounds infected with methicillin-resistant Staphylococcus aureus (MRSA) Pseudomonas aeruginosa and other bacteria resistant to antibiotics
The laboratory evidence for the potent broad-spectrum antimicrobial activity of honey is covered in Chapter 2, as is the stimulatory action of honey on leukocytes — another mechanism by which honey may work to clear infection from wounds. There is no clear evidence of the ability of the antibacterial activity of honey to diffuse down into wound tissue when applied as a wound dressing. But, the suppression by honey of growth of any bacteria already present on the surface of the wound means that there is not the problem of malodorous dressings when hydrocolloid dressings are used.
Being a source of toxins and pyrogens, honey also removes the problem of bacteria growing on the wound surface. However, the rapid clearance of a deep-seated infection and of boils with unbroken skin by topical application of honey indicates that the antibacterial activity of honey probably does diffuse though skin. If this is so, it is important to use a honey with a high level of antibacterial activity to achieve an effective level of antibacterial activity below the surface. When diffusion occurs, there is a gradient formed of decreasing concentration from the source (in this case, the dressing on the surface of the wound).
The minimum concentration of antibacterial component that will stop bacterial growth will be deeper down in the wound tissue if the source has a higher concentration. It is also important to keep a substantial quantity of honey on the surface (eg. by using a dressing pad soaked with honey), so that the concentration of antibacterial activity on the surface does not become low through dilution by exudate, or depletion by diffusion into the underlying tissue.
Honey rapidly deodorises wounds. On fungating (malignant) wounds where no other treatment could control the malodour, dressing the wound with honey was found to remove the malodour within twenty-four hours. Honey is now being used routinely at Waikato Hospital on fungating wounds, not only for odour control, but also because it reduces the inflammation and level of exudate that is a common problem with this type of wound.
The rapid deodorising of wounds from honey dressings is probably due to more than just antibacterial action. The malodorous substances that bacteria produce in wounds, such as, ammonia, amines and sulphur compounds, are formed from the metabolism of amino acids derived from decomposed serum and tissue proteins. Bacteria metabolise glucose in preference to amino acids, thus, in the presence of honey (composition of 30%–40%), the malododorous compounds are not formed
The high viscosity of honey provides a physical barrier to infection of wounds from external contamination, the effectiveness of which is increased by the antibacterial activity of the honey (as long as the honey used is selected to have good antibacterial activity). This feature is particularly useful where it is preferable to avoid occluding highly exudative wounds, such as burn wounds, and thus encourage growth of bacteria, particularly Pseudomonas spp, in the moist conditions created. Prophylactic use of honey dressings has been found to solve a problem of skin grafts frequently becoming infected with Pseudomonas spp. This raises the suggestion of using honey dressings routinely on surgical wounds to protect at-risk patients from acquiring nosocomial infection with MRSA — the demonstrated sensitivity of MRSA to honey and the reports of honey dressings healing wounds already infected with MRSA indicate that it is likely to be effective as a prophylactic treatment. It is also likely to be effective as a prophylactic treatment for the other major route of nosocomial infection with MRSA, ie. sites where medical devices penetrate the skin, as indicated by the favourable results reported from a trial conducted on central vein catheter exit sites
Provision of the optimum moist healing environment
Honey dressings on wounds provide a moist healing environment: a feature sought in most modern wound dressings to obtain conditions necessary for optimum growth of the cells involved in the repair process. But, unlike other dressings, honey does this without the associated problems of encouraging microbial growth and maceration of surrounding skin that can result from the moist conditions.
The antibacterial activity of honey prevents bacterial growth without any cytotoxic effects which could otherwise slow healing; and the osmotic action of its high sugar content will tend to draw fluid out from skin rather then let it soak in, even if honey gets diluted by large amounts of exudate.
This means that there is no need to trim honey dressings to the shape of the wound bed or to use protective coverings on peri-wound skin, and there is no restriction on using occlusive secondary dressings. It has been suggested that the osmotic effect would dehydrate wound tissues but, in a paper on the use of sugar as a wound dressing, it has been pointed out that where there is a circulation of blood underneath to replace fluid lost from cells, the osmotic effect of sugar on the surface just creates an outflow of fluid
Also, unlike other dressings, honey dressings are easy to remove causing no pain on changing dressings. This is because the outflow of fluid from the wound bed created by the osmotic action of the honey forms a layer of diluted honey in contact with the wound bed. This fluid interface allows the dressings to be lifted off painlessly, preventing the tearing away of newly regenerated tissue which can happen when an adherent wound dressing is pulled off.
There are many reports that wounds dressed with honey are rapidly debrided to give a clean granulating wound bed, slough and necrotic tissue painlessly lifting off. Although induction of autolytic debridement is a feature of all wound dressings that give a moist environment, the debriding action of honey is faster than with other dressings and, on sloughy wounds, is about as rapid as that experienced using maggots. Where there is hard eschar, maggot therapy provides a faster method of debridement as the maggots appear to burrow under the edges of the eschar, but honey dressings will remove hard eschar, especially if this is scored to aid penetration of the honey, and if the honey is diluted with water or saline so that it softens the eschar. Furthermore, using honey instead of maggots, removes the problems of obtaining a supply of freshly prepared material, of ensuring that the wound is not too wet (causing drowning) or too dry (killing by dehydration), or of keeping the maggots in place, and of overcoming patients’ unease with the squirming movement of the maggots.
The debriding action of maggots is due to the proteolytic enzyme activity they secrete, but with honey there does not appear to be a direct proteolytic activity involved: the existence of protein-digesting enzyme activity in honey has not been reported. Therefore, there must be a mechanism by which honey activates dormant proteolytic enzyme activity within the wound tissue, but in a controlled way so as not to cause unwanted digestion of the tissue. There is a strong association between high protease activity and impaired wound healing, and dressings are now being produced that inhibit or bind up and inactivate excessive protease activity in wounds that would otherwise be digesting wound tissue
As mentioned earlier, the tissue-digesting collagenase and elastase enzyme activity in wounds is activated by oxidation. The antioxidant activity of honey can be expected to suppress this, just as the anti-inflammatory activity suppresses the infiltration of elastase-secreting neutrophils. This decreases the amount of enzyme released and, subsequently, the activity of that enzyme.
The most likely explanation of the debriding activity induced by honey is that it promotes conversion of inactive plasminogen in the wound matrix to the active form, plasmin. This is an enzyme that functions to break down fibrin clots which attach slough and eschar to the wound bed. This action of honey could also be attributed to its anti-inflammatory activity, as inflammation causes inhibition of fibrinolysis by elevating the level of PAl-1 (plasminogen activator inhibitor and thus preventing plasminogen from being converted to the active enzyme plasmin Fibrin is very common in chronic wounds (The enzyme streptokinase that is often used to debride wounds functions by activating plasminogen.)
The osmotic action of honey may also assist, as drawing out lymph from the wound tissues gives a constantly replenished supply of plasminogen at the interface of the wound bed and the overlying slough. Another advantage of this osmotic action of honey is that it washes the surface of the wound bed from beneath. This would account for the long-known feature of honey dressings to remove dirt with the dressing making such dressings an excellent way of cleaning up grazes in which grit has become embedded.
Stimulation of healing
Wounds dressed with honey often have a rapid rate of healing.
Honey is also able to start the healing process in dormant wounds. Honey has been reported to promote the formation of granulation tissue and to stimulate the growth of epithelium over wounds. It has also been reported that honey is a reliable alternative to conventional dressing for the management of skin excoriation around stomas ( ileostomy and colostomy), giving a more rapid epithelialisation of the raw surface.
These clinical observations of the stimulatory effect of honey on tissue growth in wounds have been confirmed by measurements and histological observations in studies of experimental wounds in animals where honey treatment has been shown to give statistically significant improvements. In these experimental wounds, honey has also been shown to stimulate the synthesis of collagen and other connective tissue components, and to stimulate angiogenesis (development of new blood vessels)
Stimulation of angiogenesis is an important feature for promotion of healing, as the supply of oxygen is the rate-limiting factor in tissue repair, granulation tissue being granules of fibroblasts growing where new capillary beds form. The anti-inflammatory activity of honey would also assist by decreasing oedema and, consequently, the pressure on capillaries which restricts blood flow and the supply of oxygen to the regenerating wound tissues. The acidity of honey would also help with oxygenation, as acidification of wounds speeds the rate of healing by increasing the release of oxygen from haemoglobin. The newly-formed capillaries supply essential nutrients to growing fibroblasts, another factor limiting the rate of healing — it has been demonstrated that wounds heal faster if a nutrient mixture is applied topically.
There is a wide range of minerals, including the trace elements of nutrition, and of amino acids and vitamins contained in honey. Although these are present in amounts too low to be of nutritional significance when compared with the recommended daily intake, they are, on average, present at levels like those circulating in the blood. This topical supply of nutrients would be augmented by the osmotic action of honey drawing lymph from the underlying capillaries, thus creating a constant flow of nutrients for cells which may be somewhat distant from the functioning capillaries deeper down.
Another way in which honey may promote healing is by supplying glucose to the epithelial cells, as these have to build up an internal store of carbohydrate to provide the energy they need to migrate across the surface of a wound to restore skin cover. The level of glucose in the wound fluid of chronic wounds is very low. The sugars in honey would also provide an energy source for the macrophages working in the wound, as glycolysis is their major mechanism for energy production, and is dependent on a supply of glucose or fructose. Glycolysis is the only means of cells obtaining energy in the absence of oxygen, so the supply of sugars from honey would allow them to function in damaged tissues where the oxygen supply is often poor
Another possible way that honey may work to stimulate wound repair is through its production of hydrogen peroxide, as hydrogen peroxide activates the insulin receptor complexes on cells. Activation triggers a chain of molecular events in the cell that stimulates the uptake of glucose and amino acids, and promotes anabolic metabolism, giving cell growth. Topical or intravenous application of insulin to wounds, stimulates the rate of wound healing. By this mechanism, honey may stimulate the uptake and anabolic metabolism of the nutrients it supplies to wound tissues.
The stimulation of angiogenesis by honey, that has been observed experimentally when honey is applied to wounds, could also be via its production of hydrogen peroxide, as topical application of hydrogen peroxide has been found to enhance cutaneous blood recruitment in ischaemic ulcers. In vascular, smooth muscle cells, hydrogen peroxide is endogenously produced as part of the process of response to stimulation by platelet-derived growth factor, and exogenous hydrogen peroxide in the concentration range of 0.1 to 1.0 mmol/l will also function in the response.
The promotion of formation of granulation tissue by honey may also be via the stimulation of growth of fibroblasts by the hydrogen peroxide produced in honey, as hydrogen peroxide has been found to stimulate the proliferation of fibroblasts. There is a large amount of evidence that hydrogen peroxide is involved in many cell types in the body as a stimulus for cell multiplication, by acting at various points in the mechanisms of the cells that control the cycle of cell growth and division.
It has been proposed that low concentrations of hydrogen peroxide might be used to stimulate wound healing in place of the expensive cell growth factors used for this purpose. However, this is feasible only if the concentration could be carefully controlled to avoid tissue damage. This is possible with the controlled sustained release of hydrogen peroxide that occurs in honey.
Another possibility is that the stimulation of tissue repair is a down-stream effect of the stimulation by honey of cytokine production by leukocytes. The production of cytokines, as part of the initial inflammatory response, normally starts off the healing process. There is good evidence for the ability of honey in quite dilute solution to stimulate such a response in leukocytes in cell culture.
Safety in use
Honey is extremely safe to use. In the 500-plus cases reported in publications on using honey on wounds, and the 140-plus cases reported of using honey in ophthalmology, there has been no mention of any adverse effects. A large number of other cases that have not been published are known to the author and, again, there have been no adverse effects observed in any of these, with the exception of one case where there appeared to be an allergic reaction on the skin around the wound. With honey, there are no reported cytotoxic effects that would slow the healing process, whereas all antiseptics in common use can be harmful to body tissues, including silver as released from nanocrystalline silver dressings
There have been reports of honey causing a stinging pain when applied to wounds. This appears to be due to the acidity of honey, as pain is not experienced when neutralised honey is used, The pain experienced does not seem to be indicative of damage being done to the wound, as wounds have healed rapidly in cases where patients have endured the pain to benefit from the stimulation of healing that they see, and in cases where analgesia has been used (personal communications from numerous clinicians). There is evidence that honey stimulates nocioceptors, nerve endings that create a pain sensation in response to heat, acidity and some organic chemicals such as those in ginger and chilli. It is of interest that patients have been reported to experience a ‘peppery’ sensation from application of honey to their ulcers. It may be that it is not a direct effect of the acidity of honey, as neutralising honey could affect the ionisation of some of its components and make them unable to fit in the nocioceptors. It is possible that in some patients these nerve endings are sensitised and are more responsive to the acidity and/or the component organic chemicals of honey.
However, there are many reports of honey relieving pain. In a trial in which pain was measured on a visual analogue scale, the pain experienced with a honey-soaked gauze dressing was found to be one-third less than with saline-soaked gauze and paraffin gauze, but slightly more than with a hydrocolloid dressing. In another trial, where the comfort of honey dressings on chronic venous leg ulcers was investigated, six patients experienced a transient stinging pain, and eight experienced a lasting pain, but only some of the times the dressing was applied. However, in this trial, the overall result was that pain was significantly reduced by the honey dressings, and the patient satisfaction with the honey dressings was high.
Other cases where honey is reported to cause pain are few. In one of these, there was pain experienced by the patient for the first twenty to thirty minutes. In another case, a patient experienced moderate pain for fifteen to thirty minutes after honey was applied.
In a clinical trial of honey dressings, one of the sixty patients treated with honey withdrew because the dressings caused pain. In a pilot trial in which the author participated, six of the twenty patients recruited withdrew because of the pain caused by honey on the wound. This probably reflects the recruitment criterion of infected or heavily colonised wounds for the trial, as it was observed that pain was experienced only in inflamed wounds. Patients who found honey very painful when their wounds were inflamed experienced no problem with pain once the inflammation had subsided.
Similarly, in the trial where the comfort of honey dressings on chronic venous leg ulcers was investigated, the six patients who withdrew from the trial because of the honey being painful (out of a total of forty participants), had a higher than average pain level before the start of the honey dressings
For full list of References and morehttp://www.medicalhoney.com/mode_of_action/stimulation_of_healing.php
Also from Honey as a topical agent
Honey is a traditional topical treatment for infected wounds. It can be effective on antibiotic-resistant strains of bacteria.
Honey is produced from many different floral sources and its antibacterial activity varies with origin and processing. Honey selected for clinical use should be evaluated on the basis of antibacterial activity levels determined by laboratory testing.
The antibacterial properties of honey include the release of low levels of hydrogen peroxide. Some honeys have an additional phytochemical antibacterial component.
Many authors support the use of honey in infected wounds and some suggest its prophylactic use on the wounds of patients susceptible to MRSA and other antibiotic-resistant bacteria.
Honey is an ancient remedy for the treatment of infected wounds, which has recently been 'rediscovered' by the medical profession, particularly where conventional modern therapeutic agents are failing. There are now many published reports describing the effectiveness of honey in rapidly clearing infection from wounds, with no adverse effects to slow the healing process; there is also some evidence to suggest that honey may actively promote healing.
In laboratory studies, it has been shown to have an antimicrobial action against a broad spectrum of bacteria and fungi. However, further research is needed to optimise the effective use of this agent in clinical practice.
Honey was used to treat infected wounds as long ago as 2000 years before bacteria were discovered to be the cause of infection. In c.50 AD, Dioscorides described honey as being "good for all rotten and hollow ulcers".
More recently, honey has been reported to have an inhibitory effect to around 60 species of bacteria including aerobes and anaerobes, gram-positives and gram-negatives. An antifungal action has also been observed for some yeasts and species of Aspergillus and Penicillium, as well as all the common dermatophytes. The current prevalence of antibiotic-resistant microbial species has led to a re-evaluation of the therapeutic use of ancient remedies, including honey.
The antibacterial property of honey was first recognised in 1892 by van Ketel. It has often been assumed that this is due entirely to the osmotic effect of its high sugar content. Honey, like other saturated sugar syrups and sugar pastes, has an osmolarity sufficient to inhibit microbial growth, but when used as a wound contact layer, dilution by wound exudate reduces the osmolarity to a level that ceases to control infection. However, it has been shown that wounds infected with Staphylococcus aureus are quickly rendered sterile by honey Honeys selected to have a median level of antibacterial activity have been found to prevent growth of Staphylococcus aureus if diluted by a further 7-14 fold beyond the point where their osmolarity ceases to be inhibitory.
The fact that the antibacterial properties of honey are increased when diluted was clearly observed and reported in 1919. The explanation for this apparent paradox came from the finding that honey contains an enzyme that produces hydrogen peroxide when diluted. This agent was referred to as 'inhibine' prior to its identification as hydrogen peroxide; the term 'inhibine number' was coined as a measure of the relative antibacterial potency of different honeys, it being the number of steps by which a honey could be diluted and still inhibit bacterial growth.
The importance of the additional antibacterial activity of honey is demonstrated in comparisons between the therapeutic effects of honey and sugar. In an experimental study conducted on burns created on the skin of pigs, there were fewer bacterial colonies seen histologically in wounds treated with honey compared with those treated with sugar, fewer micro-pustules in the neo-epidermis, and fewer bacteria seen in the eschar of the honey-treated wounds.
There has also been a clinical case report of a discharging deep pressure sore not responding to various treatments, including dressing with sugar, which was completely healed in six weeks when dressed with honey. Frequent changes of sugar dressings are also necessary to maintain a therapeutic action, compared with fewer changes of honey dressings.
Hydrogen peroxide activity
Hydrogen peroxide is a well-known antimicrobial agent, initially hailed for its antibacterial and cleansing properties when it was first introduced into clinical practice . In more recent times it has lost favour because of inflammation and damage to tissue.
However, the hydrogen peroxide concentration produced in honey activated by dilution is typically around 1 mmol/l, about 1000 times less than in the 3% solution commonly used as an antiseptic. The harmful effects of hydrogen peroxide are further reduced because honey sequesters and inactivates the free iron which catalyses the formation of oxygen free radicals produced by hydrogen peroxide and its antioxidant components help to mop up oxygen free radicals.
Studies in animal models have demonstrated that honey reduces inflammation (seen histologically), compared with various controls, in deep and superficial burns and in full-thickness wounds
Although the level of hydrogen peroxide in honey is very low it is still effective as an antimicrobial agent. It has been reported that hydrogen peroxide is more effective when supplied by continuous generation with glucose oxidase than when added in isolation. A study with Escherichia coli exposed to a constantly replenished stream of hydrogen peroxide, showed that bacterial growth was inhibited by 0.02-0.05 mmol/l hydrogen peroxide, a concentration that was not damaging to fibroblast cells from human skin.
In some honeys treated with catalase to remove the hydrogen peroxide activity, additional non-peroxide antibacterial factors have been identified. Manuka (Leptospermum scoparium) honey from New Zealand has been found to have substantial levels of non-peroxide antibacterial activity. This is associated with an unidentified phytochemical component, although further investigations are still to be completed. A similar finding has been made in honey from an unidentified Leptospermum species in Australia, 'jellybush'
Increased lymphocyte and phagocytic activity
The clearing of infection seen when honey is applied to a wound may reflect more than just antibacterial properties. Recent research shows that the proliferation of peripheral blood B-lymphocytes and T-lymphocytes in cell culture is stimulated by honey at concentrations as low as 0.1%; and phagocytes are activated by honey at concentrations as low as 0.1%.
Honey (at a concentration of 1%) also stimulates monocytes in cell culture to release cytokines, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6, which activate the immune response to infection.
In addition, the glucose content of honey and the acid pH (typically between pH3 and pH4) may assist in the bacteria-destroying action of macrophages.
Honey is produced from many different floral sources and its antimicrobial activity varies with origin and processing. Dioscorides (c.50 AD) stated that a pale yellow honey from Attica was the best; Aristotle (384-322 BC), when discussing different honeys, referred to pale honey as being "good as a salve for sore eyes and wounds".. Today, the strawberry-tree honey of Sardinia is valued for its therapeutic properties; in India lotus honey is said to be a panacea for eye diseases; honey from the Jirdin valley of Yemen is revered in Dubai for its therapeutic properties; and manuka honey has a long-standing reputation in New Zealand folk-lore for its antiseptic properties.
The failure to take into account the large variance in antibacterial potency of different honeys may contribute, in part, to the large discrepancy in results reported between hospitals using honey in similar ways. Some have reported rapid clearance of infection in a range of different types of wound, with all wounds becoming sterile in 3-6 days ,7 days or 7-10 days. Others have reported bacteria still present in wounds after 2 weeks, 3 weeks and 5 weeks.
The only studies that give a reasonable indication of the likely usefulness of honey for treatment of infected wounds are those conducted with standardised honeys.
Two types of standardised honey have been subjected to laboratory investigations. These are a typical (near median activity) manuka honey from New Zealand, with activity due to a phytochemical component and a typical (near median activity) multifloral honey with activity due to hydrogen peroxide. In one study the hydrogen peroxide component was removed from the manuka honey, but generally manuka honey was selected for its phytochemical component and low hydrogen peroxide component. The antibacterial potency of these two honeys are described below.
The non-peroxide antibacterial activity of the typical (near median activity) manuka honey was tested against seven species of bacteria and compared with the typical (near median activity) honey with hydrogen peroxide activity. The MIC (minimum inhibitory concentration) of the honeys was found to range from 1.8% to 10.8% (v/v), indicating that the honeys had sufficient antibacterial potency to stop bacterial growth if diluted at least nine times, and up to 56 times in the presence of Staphylococcus aureus, the most common wound pathogen. In another study with 58 clinical isolates of Staphylococcus aureus the MIC ranged from 2% to 4% (v/v). In a study of 20 isolates of Pseudomonas from infected wounds the MIC of these two honeys was found to range from 5.5% to 9.0%.
Antibiotic-resistant strains have also been studied and found to be as sensitive to honey as the antibiotic-sensitive strains of the same species. The MIC for 82 epidemic strains of methicillin-resistant staphylococcus aureus (MRSA) was found to range from 3% to 8% (v/v) In this study 56 strains of vancomycin-resistant enterococci (VRE) were also examined, and the MIC values were found to range from 5% to 10% (v/v) for the manuka honey and from 8% to 20% for the second honey.
In a further study the MIC values for eight strains of MRSA isolated from swabs collected from acute and chronic wounds, and 16 strains of VRE isolated from the hospital environment were all below 10% (v/v) for both honeys, as were the MIC values for 15 strains of beta-haemolytic streptococci, and seven strains of vancomycin-sensitive enterococci isolated from swabs collected from acute and chronic wounds
Overall in these studies, other than those with enterococci, there was no marked difference in effectiveness between the two types of honey used. However, further research is needed to fully evaluate the effectiveness of these results.
Honey has been used to treat infections in a wide range of wound types. These include burns, venous leg ulcers, leg ulcers of mixed aetiology, diabetic foot ulcers, pressure ulcers, unhealed graft donor sites, abscesses, boils, pilonidal sinuses, infected wounds from lower limb surgery necrotising faciitis and neonatal postoperative wound infection. In many of these and other cases, honey has been used to heal wounds not responding to treatment with conventional antibiotics and One study, for example, reported treatment with honey dressings of 59 patients with recalcitrant wounds and ulcers, 47 of which had been treated for between one month to two years with no signs of healing. Some had increased in size. The ulcers had been treated with a chlorinated lime and boric acid solution (Eusol) and dressed with acriflavine, framycetin-impregnated dressing (Sofra-Tulle) or neomycin-zinc bacitracin (Cicatrin). Swabs from the 51 wounds with bacteria present became sterile within one week and the others remained sterile. All but one wound (a Buruli ulcer) showed signs of healing.
Another study used honey on nine infants with large infected surgical wounds that failed to heal with intravenous antibiotics, cleaning the wound with aqueous 0.05% chlorhexidine solution and application of fusidic acid ointment Marked clinical improvement was seen in all cases after five days of treatment with honey, and all wounds were closed, clean and free of infection after 21 days of application of honey.
In a randomised control trial 26 patients with postoperative wound infections had their wounds treated with honey and 24 had their wounds washed with 70% ethanol and povidone iodine applied. The group treated with honey had infection eradicated and achieved complete healing in less than half the time compared with the antiseptic-treated group.
Wounds infected with Pseudomonas, not responding to other treatment, have been rapidly cleared of infection using honey, allowing successful skin grafting
In patients with wounds infected with antibiotic-resistant strains of bacteria, not responding to antibiotic therapy, good results have been achieved after five weeks of application of honey. The bacteria infecting the wounds were found to be resistant to ampicillin, oxytetracycline, gentamicin, chloramphenicol and cephadine. Wounds infected with MRSA have also been cleared of infection and healed by application of honey
Allergic reactions to honey are rare and have been attributed in some cases to a reaction to a specific pollen in the honey. Honey processed for use in wound care is passed through fine filters which remove most of the pollen. In more than 500 published reports on the clinical usage of honey in open wounds, there have been no adverse reactions noted other than a localised stinging sensation described by some patients. This may be due to the acidity of honey as it has not been reported when the acidity is neutralised
A transient stinging sensation was also observed in 102 cases in a trial of honey for ophthalmological use, although this was never severe enough to stop treatment. In papers describing the application of honey to open wounds it has been reported to be soothing, to relieve pain, be non-irritating, be pain free on application, and with no adverse effects. A number of histological studies examining wound tissues also support the safe use of honey
Substantial amounts of honey need to be applied to a wound to achieve adequate potency. Although it may be very viscous or even solid at room temperature, honey becomes very fluid at body temperature and even more fluid if diluted with proportionally small volumes of exudate. It is therefore very important that sufficient honey is applied to a wound and it is kept in place if a good therapeutic effect is to be obtained. For the optimal MIC of the antibacterial components of honey to be reached at the deepest sites of infection there needs to be the highest concentration possible on the surface, and a 'reservoir' of sufficient quantity that it is not substantially depleted by diffusion into the wound tissues.
Practical considerations for the clinical use of honey
The amount of honey required on the wound relates to the amount of fluid exuding from the wound diluting it. The frequency of dressing changes required will depend on how rapidly the honey is being diluted by exudate. If there is no exudate, dressings need to be changed twice-weekly to maintain a 'reservoir' of antibacterial components as they diffuse into the wound tissues.
To achieve best results the honey should be applied to an absorbent dressing prior to application. If applied directly to the wound, the honey tends to run off before a secondary dressing is applied to hold it in place.
Honey will not soak readily into absorbent dressings. Soaking is facilitated by warming the honey to body temperature and/or adding 1 part water to 20 parts honey to make the honey more fluid.
In some situations a 'blister' of honey can be held on a wound using an adhesive film dressing. Honey can be used to treat cavity wounds in this way, although this approach is not suitable for heavily exuding wounds.
For moderately to heavily exuding wounds, a secondary dressing may be needed to contain seepage of diluted honey from the primary dressing. An occlusive dressing such as polyurethane film is best, as an absorbent secondary dressing tends to draw the honey away from the wound surface.
A low-adherent dressing helps prevent the honey dressing sticking to the wound in cases where this is a problem. This dressing is placed between the wound and the honey dressing, but must be porous to allow the antibacterial components of the honey to diffuse freely into the wound bed.
Alginate dressings impregnated with honey are a good alternative to cotton/cellulose dressings, as the alginate converts into a honey-containing soft gel.
Any depressions or cavities in the wound bed need to be filled with honey in addition to using a honey-impregnated dressing. This is to ensure the antibacterial components of the honey diffuse into the wound tissues.
Honey can safely be inserted into cavities and sinuses. It is water-soluble and easily rinsed out; any residues are bio-degradable (honey filtered in processing does not contain any foreign bodies). For sinuses with small openings a catheter on a syringe filled with honey is an effective way of applying honey.
Since infection may lie in the tissues underlying the wound margins, honey dressings need to extend beyond the inflamed area surrounding a wound.
The use of honey to treat infected wounds, is viewed with sceptism by some. For example, an editorial in the Archives of Internal Medicine in 1976 on medical folk-lore ridiculed the use of honey, placing "honey from selected geographic areas" in the category of "worthless but harmless substances". However, it is excepted that the clinical significance of the antibacterial activity in honey will be unequivocally proven only if a clinical trial is conducted to compare dressings of sugar and selected honeys.
A recent review on the successful usage of honey as a dressing on infected wounds shows that many authors support the use of honey in infected wounds and some suggest the prophylactic use of honey on the wounds of patients susceptible to MRSA and other antibiotic-resistant bacteria. Whichever honey is used on a wound, consideration needs to be given to its quality and further evidence and understanding of the therapeutic and chemical properties of honey is needed to optimise the use of this product in the clinical management of wounds.
Peter Charles Molan PhD
Associate Professor of Biochemistry and Director of the Honey Research Unit
Department of Biological Sciences, University of Waikato
Private Bag 3105, Hamilton, New Zealand
For full article seehttp://www.worldwidewounds.com/2001/november/Molan/honey-as-topical-agent.html