Honey-Based Dressings: Can They Have An Impact For Diabetic Foot Ulcers?

     Honey is an ancient wound remedy that is reappearing in clinical practice in developed countries. The availability of licensed wound care products in Europe, New Zealand and Australia is prompting healthcare practitioners in conventional medicine to consider the use of honey within their treatment armamentarium. Ulcer remedies such as honey are necessary as the prevalence of diabetes rises.      The American Diabetes Association has estimated that about 7 percent of the population had diabetes.1 It is an increasing problem that has serious implications and a high degree of morbidity. In 2005, 1.5 million new cases in the U.S. were diagnosed in people over 20 years of age.      Foot ulcers are a frequent and complex complication in diabetes and researchers have estimated the prevalence of foot ulceration in this population to be approximately 6 percent.2 Diabetic foot ulcers are often present for long periods of time and have poor healing rates.3 These poor healing rates lead to the worst case scenario — amputation — and diabetes remains the most common cause of lower extremity amputation in the Western world.      There are a variety of factors that lead to the development of ulceration in the diabetic foot. In addition to complex sensory, motor and autonomic neuropathy, other contributory factors include the duration of diabetes, circulatory status, blood glucose levels, age, height, limited joint mobility and the high plantar pressures that are often present as a result of structural deformities in the foot.4-6 When these underlying factors are present, relatively minor traumatic incidents, such as ill fitting footwear or knocking a toe against a firm object, wind up instigating the causal chain that all too frequently leads to amputation.      Diabetic foot ulcers often become chronic and difficult to heal. Wound healing is a multifaceted event and any single intervention is likely to be of little value unless clinicians identify and address all the factors with the potential to delay wound healing.      Indeed, one needs to consider the factors that promote healing. These factors include glycemic control, appropriate management of tissue, whether surgical revascularization is indicated and the correction of defined biological abnormalities.7      In terms of appropriate wound care, one must debride the ulcer itself of all necrotic and callused tissue until the full extent of the ulceration is evident.8 Seemingly simple ulcers are often complicated by sinuses and tracking, and clinicians need to identify and treat these appropriately.

Understanding The Compliance Limitations Of Offloading

     It has been suggested that trauma during ambulation may not only create a wound but also keep it in the chronic inflammatory phase. Perhaps the single most significant factor in promoting healing of such an ulceration is the reduction of the high pressure loading caused by limited joint mobility in an insensate foot.9 Rest, elevation and relief of pressure have been confirmed as the essential components of treatment. Accordingly, clinicians should emphasize these components at the very outset of treatment.10      Offloading strategies include the use of bed rest, walking aids and various types of casts and walkers. The most popular interventions are the use of casts and special walkers. Total contact casts are in the form of plaster of Paris or fiberglass cast material applied to the foot and leg. Such casts are not removable and rely on frequent and regular visits to specialist technicians for removal and reapplication of the cast.      However, this is costly in terms of time and materials. This facilitated the introduction of removable, reusable cast walkers, which include items such as the Bledsoe Walker (Bledsoe Brace Systems) and the Aircast walker (Aircast). While the rationale behind their design and use is sound, patients are able to remove the devices themselves. These devices have proven to be effective in achieving ulcer healing but only if they are worn. Advise patients that they may remove cast walkers overnight but should wear them at all other times.      It is interesting to note that while patients consider that they are wearing such devices as directed, a study by Armstrong in 2003 followed 21 patients who were each fitted with a removable cast walker and a computerized accelerometer/pedometer. This device measured activity over time. The study identified that nearly 75 percent of the steps taken by this study population were taken without the cast walker and, accordingly, there was a lack of adequate pressure relief on the site of their ulcer.11 Remember that these neuropathic patients have lost the normal warning signal of pain as an indicator that they should rest the affected part. Therefore, they have no “built-in reminder” that they are sustaining further damage to their ulcer site each time they take a step without the prescribed offloading device.

A Lack Of Definitive Evidence On Agents For Delayed Wound Healing

     It is no wonder then that the complexity of the presenting factors leads to delayed healing in the diabetic foot. Unhealed ulcers frequently lead to additional complications such as infections that may in turn lead to osteomyelitis.12 Infection is often the final pathway that leads to amputation.13      The early detection of infection in diabetic foot ulcers is essential if clinicians are to prevent lower limb amputations. However, a recent systematic review has indicated that the evidence is too weak to draw any reliable implications for practice on the effectiveness of diagnostic tests to identify infection in diabetic foot ulcers. Additionally, with respect to treatment, it was unclear whether systemic or local antibiotics were better or whether any one agent was better than another.14 A parallel systematic review investigated the effectiveness and cost-effectiveness of antimicrobial agents.15 The study concluded there is no strong evidence to suggest that any specific antimicrobial agent is particularly effective in preventing amputation, the resolution of infection or the healing of a diabetic foot ulcer. Therefore, there is a need for innovative interventions.

What The Research Reveals About Honey’s Healing Properties

     When it comes to the use of honey in wounds, there has been ample anecdotal evidence for thousands of years. Yet the extent of recent documented clinical evidence has been underestimated.      A review by Molan has shown that 17 randomized controlled trials involving more than 1,965 patients have now been published. The addition of cohort studies and case reports bring the total to more than 2,000.16 Evidence from animal models and cell lines is also available. Much of that evidence supports the use of honey although the design of some of the trials has been questioned.17      Essentially the properties of honey that are relevant to wounds are an ability to inhibit a broad spectrum of microbial species and the ability to stimulate healing. Antimicrobial activity to more than 80 species has been reported with honey and both antibiotic-resistant and antibiotic-sensitive strains of bacteria are equally susceptible to honey.18-20 Studies have demonstrated inhibition of dermatophytes as well as Candida.21-22 Contrary to popular belief, the inhibition of bacteria is not attributed solely to sugars.18,20 There are increasing reports of cases in which eradication of methicillin-resistant Staphylococcus aureus (MRSA) has been achieved by utilizing honey in wounds.23-25      The ways in which honey promotes healing are known and practical advice on using honey is available.26 Therapeutic properties described for honey include antiinflammatory activity, debriding action, reduction of edema, elimination of malodors, the promotion of granulation tissue and rapid reepithelialization.      There are reportedly a wide variety of wounds that benefit from topical application of honey. These wounds include burn wounds, pressure sores, traumatic wounds, surgical wounds, meningococcal septicaemia lesions, necrotizing fasciitis and ulcers. Various researchers have been able to achieve successful treatment of a small number of diabetic ulcers with honey.26-30 Often, researchers seem to have used honey as a last resort, for example, when amputation was threatened.31      The need to use sterile, quality assured medical devices in dressing wounds is readily recognized today. However, many of the trials and studies using honey to date have been conducted in India or Africa, where proprietary products were not available.      Honey is a natural product with a complex composition. It varies according to floral source, geographical location, age and storage conditions. Raw honey usually contains bacteria and yeasts, possibly sporing organisms such as Clostridium botulinum.32 The need to utilize high potency honey from traceable sources is recognized and traces of chemical residues, antibiotics and plant toxins must be absent.33 Modern wound care products (such as honey in tubes, wound gels, impregnated tulle and honey and alginate dressings) are being developed in New Zealand, Australia, Holland and the United Kingdom.      Clinical trials are in progress in these countries and additional trials are underway in Ireland, Denmark and South Africa. Many employ honey of proven high potency such as from Leptospermum species (manuka or jellybush). All utilize gamma irradiated sterile products that have been licensed by the relevant regulatory authorities.      Despite containing approximately 33 percent glucose, topical application of honey has not been reported to affect blood glucose levels. Slight stinging sensation on initial application has been reported but this would not be an issue in neuropathic patients.34      Contraindication to the use of honey is allergy to pollen or bee venom, which is rare. An advantage of using sterile honey that is supplied in single use tubes is that one can introduce it to the entire ulcer, including undermined tracts or sinuses. Honey-impregnated dressings are sufficiently flexible so one could use them with cast walkers. However, clinicians may need to apply secondary dressings to cope with excess exudate.

How Does Honey Facilitate Healing?

     To date, the mechanisms by which honey affects wound healing are not yet fully explained. Antiseptic properties are derived from multiple factors. High sugar content, low water content and acidity prevent microbial growth in all undiluted honey samples. Topical application of honey to wounds causes increased exudation by osmotic effect. For some honeys, contrary to expectation, dilution enhances antibacterial activity. This paradox was explained when glucose oxidase was discovered in honey.35 This is an enzyme secreted into nectar by the bee during deposition in the hive. It is inactive in concentrated honey but becomes activated during dilution when it catalyzes the formation of hydrogen peroxide from glucose.36      Hydrogen peroxide inhibits bacteria and stimulates fibroblasts and keratinocytes, although concentration is critical.37 Not all honeys generate hydrogen peroxide and antibacterial potency is not constant. A survey of 345 New Zealand honeys demonstrated that potency was restricted to sugars and acids for some whereas others had activity due to hydrogen peroxide on dilution. Some had activity on dilution that persisted after hydrogen peroxide had been enzymically destroyed by catalase.38 Such honeys (manuka and jellybush) are known as non-peroxide honeys and are thought to contain phytochemicals that confer antimicrobial properties.38      The potency of hydrogen peroxide generating honeys can be destroyed by inactivation of glucose oxidase during exposure to elevated temperature. Accordingly, honeys destined for medical use are routinely tested for potency relative to a phenol standard.39 Activity of manuka honey tested in the presence of catalase is expressed as UMF (or unique manuka factor) and higher factors indicate higher potency.

In Conclusion

     Ancient physicians recognized that honeys from different floral origins had varying therapeutic characteristics and selected their medicinal honey wisely. The variety of proven honey at present is small but some countries are investigating whether honey has therapeutic potential. It is to be expected that further honey will be discovered. In the meantime, the current interest in modern wound care products that contain honey is likely to provide more clinical evidence on efficacy.      Since diabetic foot ulcers present problems in terms of their potential for infection and their recalcitrance to healing, a topical agent that can influence both aspects offers real promise as a therapeutic agent.           Dr. Tyrrell is a Podiatry Consultant and Principal Lecturer at the Cardiff School of Health Sciences, University of Wales Institute Cardiff in Cardiff, U.K.      Dr. Cooper is a Microbiologist at the Cardiff School of Health Sciences, University of Wales Institute Cardiff in Cardiff, U.K.
 

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