Honey-Based Dressings and Wound Care: An Option for Care in the United States

Honey-Based Dressings and Wound Care: An Option for Care in the United States
Barbara Pieper Journal of Wound, Ostomy and Continence Nursing
January/February 2009
Volume 36 Number 1
Pages 60 - 66





Abstract
Honey-based wound dressings have been used worldwide since ancient times. A honey product received US Federal Drug Administration approval in 2007, making this dressing an option for wound care. Honey has been found to exert anti-inflammatory and antibacterial effects without antibiotic resistance, promote moist wound healing, and facilitate debridement. However, it may cause a stinging pain. As is true of any wound dressing, its use must be carefully selected and monitored. Continued research is needed to add to its evidence base. This article provides a summary of the current evidence base for the use of honey and a review of its therapeutic effects and discusses implications for WOC nursing practice.
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Introduction
Referenced in ancient medical writings of Egypt, Greece, and parts of India, honey is considered to be the oldest wound dressing.1,2 In 2007, the US Food and Drug Administration gave clearance to market a honey-based wound dressing product (Medihoney, Derma Sciences, Toronto, Ontario, Canada).3 The product uses active Manuka honey (Leptospermum scoparium), derived from tea plants, and Leptospermum polygalifolium, known as the jelly bush.4 Manuka is the name of the floral source of the honey L scoparium.1 This article summarizes the current evidence base for the use of honey, its therapeutic effects, and implications for WOC nursing practice.
Composition of Honey
Honey consists of multiple components derived from plants and bees during the maturation processes. It is a product obtained from bees of the genera Apis and Meliponinae.5 Bees collect nectar from flowers; nectar has a sugar content ranging from 5% to 60%. The resulting compound is composed of sucrose, glucose, and fructose.6 Nectar is processed by bees and deposited in the wax cells of the hive. The water content of honey is reduced to 17% by evaporation from the warmth of the hive and fanning of bees. The bees also add enzymes to the honey including invertase (which converts sucrose into glucose and fructose) and glucose oxidase (which oxidizes glucose and produces gluconic acid). Production of gluconic acid lowers honey's pH and contributes to hydrogen peroxide production.6 The resulting compound is converted to glucose and fructose, and the glucose is converted to gluconic acid and hydrogen peroxide by glucose oxidase. Culinary honeys undergo heat treatment, which destroys the enzyme responsible for producing hydrogen peroxide. In contrast, honey used for wound care does not undergo heat treatment. Instead, it is sterilized by [gamma]-radiation, thus retaining its biologic activity.1 The resulting honey is a supersaturated solution whose pH ranges from 3.2 to 4.2.1,6
Therapeutic Effects of Honey Dressings
WOC nurses should be knowledgeable of the therapeutic effects of a dressing when selecting it for wound care. This section reviews the anti-inflammatory and antimicrobial effects of honey, its ability to support moist wound healing, debride the wound bed, and control odor, and its effects on scar formation.
Anti-inflammatory Effects
Excessive inflammation can prevent healing or cause further tissue damage by increasing reactive oxygen species or free radicals.2 Honey has been shown to reduce both acute and chronic inflammation.7 Although the mechanism for the anti-inflammatory action of honey is not entirely understood,1 multiple effects have been reported. For example, histological studies of biopsy specimens show a reduced number of inflammatory cells when exposed to honey.2,8 Honey has also been shown to modulate the activity of immunocompetent cells such as monocytes in the wound.1 In addition, honey may stimulate peripheral blood B and T lymphocytes in cell culture and activate phagocytes from the blood.2,8 Honey has been reported to stimulate monocytes in cell culture to release cytokines tumor necrosis factor-1, interleukin (IL)-1, and IL-6, which act as intermediates in the immune response.2 Honey also supplies glucose that is critical for the “respiratory burst” in macrophages needed to generate hydrogen peroxide, and it provides substrates for glycolysis for energy production in macrophages.2
The potential benefits of honey's anti-inflammatory effect include alleviation of the pain associated with inflammation. A reduction in edema provides other positive effects. The pressure from edema restricts the blood flow of oxygen and nutrients, which leukocytes need to fight infection and fibroblasts need for connective tissue synthesis.2,8 Thus, reducing edema not only alleviates associated pain but also improves microcirculation and increases the availability of dissolved oxygen and nutrients needed for tissue repair and regeneration.
The anti-inflammatory effects of honey reduce hypertrophic scarring during the maturation phase of wound healing.2 The free radicals formed when excessive or prolonged inflammation is present stimulate the fibroblasts that produce the collagen fibers of a scar. The anti-inflammatory effects of honey reduce formation of reactive oxygen species, thus decreasing the fibroblast and collagen production needed to create a hypertrophic scar.
Antibacterial Effects
Honey has a broad spectrum of bactericidal and bacteriostatic activities.1,2 Although the antibacterial effects of honey have long been known,2 there is currently increased interest in these properties, partly due to the emergence of antibiotic-resistant strains of microorganisms. Medical honey has not been observed to foster bacterial resistance.9,10 Instead, honey is hypothesized to inhibit bacterial growth primarily due to its high osmolarity.2,10,11 However, some researchers contend that this effect is lost once the wound drainage dilutes the honey. Other factors thought to contribute to the antibacterial effects of honey are the phytochemicals in the nectar collected by the bees. This has been demonstrated for honey from the Leptospermum species from Australia and New Zealand. The antibacterial activity of honey may vary as many as 100-fold based on the type of honey and how it was processed.2,10 Producers have a registered trademark (UMF—Unique Manuka Factor) to measure the antibacterial potency of honey.12 The higher the number, the more potent the honey's antibacterial activity. The highest rating is 18.12
Other antibacterial effects of honey are associated with its acidic pH (range, 3.2–4.5), which may prevent biofilm formation and cross-contamination.4 Honey's ability to prevent cross-contamination is linked to its high osmolarity; it draws fluids into the wound, resulting in a viscous solution that provides a protective barrier against cross-infection.1
Hydrogen peroxide, produced in honey by the enzyme glucose oxidase, is an important source of honey's antibacterial activity.13 The amount of hydrogen peroxide in a wound varies over time, based on rates of production, destruction, and dilution by exudate. The hydrogen peroxide produced by honey is not cytotoxic. The amount produced is 1,000 times lower than a hydrogen peroxide 3% solution rinse.1,2,7 This low concentration of hydrogen peroxide may act as a “messenger” in promoting healing, and it may stimulate both fibroblasts and epithelial cells.1
Research has shown that honey exerts antibacterial activity against clinical isolates of Staphylococcus aureus, methicillin-resistant S aureus, vancomycin-resistant enterococci, [beta]-hemolytic streptococci, and vancomycin-sensitive enterococci.2,9–11,14,15 Examples of microorganisms that honey may inhibit are given in Table 1. Lusby and colleagues 16 reported that only Serratia marcescens and Candida albicans were not inhibited by honey. However, as noted earlier, the precise mechanisms that account for these antimicrobial effects are not entirely understood. It is known that honey's antibacterial activity acts much more slowly than traditional antiseptics that decrease bacterial counts within minutes.9 Honey also differs from other antiseptics because it retains its bactericidal activity in vitro even after dilution.11,14,15 Researchers are seeking to more clearly understand honey's antimicrobial activity because it persists irrespective of bacterial resistance to antibiotics. The clinical relevance of this is apparent as clinicians continue to grapple with the growing problem of antimicrobial resistance.

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TABLE 1. Examples of Microorganisms Against Which Honey Is Effectivea
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Gethin 17 examined bacteriologic findings associated with the use of Manuka honey. She noted (1) a small number of clinical trials but a multitude of case reports and observational reports, (2) a lack of research rigor, and (3) a paucity of trials on the use of topical honey in wound management of people with diabetes. Based on this review, Gethin concluded that honey may help reduce bacterial burden, but its floral source should be specified in all studies because it profoundly influences honey's effectiveness as an antibacterial agent.
Debridement Properties
Honey may facilitate wound debridement through several mechanisms. It enables the autolytic action of tissue proteases.2 Because of its strong osmotic action, honey pulls lymph fluid from the wound tissues to add moisture needed for autolytic debridement. The osmotic action washes the wound base from beneath, removing debris and painlessly lifting off slough and necrotic tissue.2,8 The production of hydrogen peroxide may also contribute to debridement.1 Matrix metalloproteases of connective tissue and neutrophil serine proteases may be activated by hydrogen peroxide.2 Although high protease activity is strongly associated with impaired wound healing, this has not been shown to be the case with honey, possibly because the anti-inflammatory effect of honey tempers this situation.2 Honey may provide a more comfortable and cost-effective method of debridement than mechanical or surgical excision.2
Odor Control Properties
Decreased wound odor has been reported when honey dressings were used to treat abscesses, diabetic foot ulcers, leg ulcers, and fungating wounds.1 Honey reduces wound odor via 2 mechanisms. First, malodor is attributed to the presence of anaerobic bacteria such as Bacteroides spp, Peptostreptococcus spp, and Prevotella spp. Honey exerts antibacterial action in vivo and in vitro against these anaerobes, reducing their presence in the wound bed and subsequent ability to produce odor. Second, honey provides glucose as an alternative to the amino acids created when serum and dead cells are metabolized by bacteria.18 As a result, lactic acid is produced as compared to the malodorous ammonia, amines, and sulfur compounds typically formed by the metabolism of amino acids from decomposed serum and tissue proteins when honey is not present.1,2,8,18
Wound Healing Effects
Honey has been reported to promote wound healing through several mechanisms. It promotes a moist wound environment by drawing lymph into the wound through osmosis and preventing the dressing from adhering to the wound bed.18 In addition, the levulose and fructose contained in honey may improve local nutrition and promote epithelialization.1,2 The acidic nature of honey provides an optimal environment for fibroblast activity.1 Molan 2 noted that honey (1) stimulates angiogenesis, thus increasing oxygen and nutrients to the wound and promoting healthy granulation tissue; (2) hastens epithelialization, possibly decreasing the need of skin grafting; and (3) stimulates collagen synthesis and improves tensile strength.
Honey's effect on wound healing has been examined with various wound types (Table 2). Gunes and Eser 18 completed a randomized clinical trial comparing honey dressing (n = 15) versus an ethoxy-diaminoacridine plus nitrofurazone dressing (n = 11) on pressure ulcer healing. The investigators were not blinded to treatment group. Wounds were traced and evaluated with the Pressure Ulcer Scale for Healing tool. Both groups had decreased scores over the course of the study, but the honey group had 4 times the rate of healing of the control group.

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TABLE 2. Types of Wounds for Which Honey Dressings Have Been Useda
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Gethin and Cowman 19 examined healing of leg ulcers with Manuka honey in an 8-patient case series. Mean reduction in wound area across all wounds was 54.8% over the 4-week period. This improvement, in part, might have been attributable to renewed interest and compliance in wound care. Dunford and Hanano 20 examined the effects of honey for the treatment of venous leg ulcers that had not healed after 12 weeks of compression therapy. This prospective, nonrandomized study reported on 40 patients from 4 centers. Thirteen patients (32.5%) dropped from the study primarily because of an increased stinging ulcer pain (n = 6, 15%), deterioration in health (n = 3), and deterioration in the ulcer condition (n = 2). Overall, pain levels decreased in 50% of participants, wound odor decreased in 24 patients, wound area decreased significantly, and 7 ulcers healed.
Ahmed and colleagues 21 examined the use of honey dressings with 21 patients with chronic wounds, 23 with complicated surgical wounds, and 16 with acute traumatic wounds. Treatment lasted for 1 to 28 weeks; all wounds had failed previous treatments. All but one patient (who dropped due to pain) completed the study, and 57 of 59 patients (96.6%) achieved healing of their wounds. During treatment, they noted decreased edema and wound exudate, enhanced debridement, decreased odor, and advanced epithelialization. No allergic reactions occurred. Stephen-Haynes 22 evaluated a Manuka-impregnated dressing on 20 patients with nonhealing wounds. She reported that the honey dressing was easy to apply (65%), was easy to remove (75%), stayed in place (85%), improved the wound bed (80%), and was comfortable (65%).
Honey has been used on damaged skin associated with radiation therapy for cancer. Moolenaar and colleagues 23 initiated a prospective randomized controlled study in Caucasian women who received radiotherapy to the breast or the thoracic wall and developed grade 3 radiation-induced dermatitis. In 21 women, 24 skin reactions were evaluated: 12 were treated with a honey dressing and 12 with paraffin dressings. No statistically significant difference in time to healing and closure was found when treatments were compared. However, subjects managed with the honey dressing had a trend toward less pain, itching, and irritation. Neither treatment resulted in relevant side effects.
Topical honey has also been examined in the management of radiation-induced mucositis for head and neck cancers.24 Twenty patients received the radiation therapy alone and 20 received 20 mL of pure honey applied to the mucosa 15 minutes pretreatment, 15 minutes posttreatment, and 6 hours postradiation therapy. The honey-treated patients had a significant reduction in symptomatic grade 3/4 mucositis and had either no change or a positive change in body weight.
Subrahmanyam 25 randomly assigned 50 burn patients to early tangential excision and skin grafting (n = 25) versus honey treatment (n = 25). The honey-treated group had less blood volume replaced. After 3 months, the graft group had significantly better functional and cosmetic results than the honey-treated group. In fact, 3 of the honey-treated patients had significant contractures. The authors concluded that early tangential excision and skin grafting was superior to topical honey treatment.25
Misirlioglu and colleagues 26 compared honey- impregnated gauze with 3 other dressings (hydrocolloid, paraffin gauze, and saline-soaked gauze) on split-thickness, skin-graft donor sites. Eighty-eight patients' grafts were treated half with the honey-based dressing and half with 1 of the other 3 dressings. The honey-treated sites showed a faster epithelialization time and lower pain compared to the paraffin and saline-soaked dressings. However, these differences did not persist when the honey dressing was compared to the hydrocolloid dressing. They concluded that the honey dressing was safe and could be an alternative dressing for split-thickness, skin-graft donor sites.26
Systematic Reviews of Wound Healing
The results of 3 systematic reviews illustrate existing evidence pertaining to the effectiveness of honey dressings in chronic wound healing. Fox 27 searched 5 databases, literature from companies, and the Internet. She identified 6 studies that examined the use of honey in wound management for adults with chronic wounds. None were randomized controlled trials or comparative studies of honey treatment versus usual treatment. All were found to have major design flaws. Despite this paucity of research-based evidence, 5 of the 6 articles described honey as a superior treatment option, thus creating a dilemma for clinicians who are questioned by patients about the use of a honey dressing. Fox 27 concluded that there is a paucity of high-quality literature related to the use of topical honey in adults with chronic wounds and recommended caution in the use of honey-based dressings. Moore and colleagues 28 reported a systematic review of 7 nonblinded, randomized controlled trials that used honey as a wound dressing for superficial burns (n = 6) and infected postoperative wounds (n = 1). All of the studies compared honey to other active therapies, but the alternative interventions included atypical treatments such as potato peelings and amniotic membrane. The main outcomes of the studies were healing time and infection rate. In all of the studies, honey was associated with a shorter healing time, eradication of infection, decreased use of antibiotics, and decreased hospitalization. Nevertheless, since 6 of the studies were done by the same researcher, Moore and colleagues 28 suggest caution when interpreting these findings. In contrast, Molan 29 analyzed research from 17 randomized controlled trials with 1,965 participants, 5 clinical trials involving 95 participants, and 16 trials on 533 wounds on experimental animals. He concluded that honey could promote wound healing when other dressings have failed.29 He also noted that trials examining the efficacy of honey dressings were rarely blinded because the odor of honey is easily recognizable to both investigators and subjects.
Scar Formation
Topham 30 reported scarless healing when honey was used in some cavity wounds. He suggested 3 potential mechanisms resulting in this outcome: (1) saccharides at the wound surface may encourage the production of hyaluronic acid from glucose, which simultaneously suppresses the formation of fiber-forming collagens; (2) glucose at the wound bed creates an environment that enables wound-healing proteoglycans to exert their effects without producing excessive quantities of collagens; and (3) the mechanism by which sugar attaches to collagen may change its structure.
Use of Honey in Children
Honey dressings have also been used in children. Simon and colleagues 31 described 16 wound care situations in 14 patients with impaired wound healing due to the toxicity of chemotherapy and radiation therapy, persistent or intermittent immunosuppression, malnutrition from nausea, vomiting, or mucositis, or infection. Honey was found to be a nonadherent dressing. One child experienced local pain, resulting in discontinuation of the honey dressings. Although measurement methods were not presented, the authors reported a high acceptance by patients and their families that positively impacted patient satisfaction. Vardi and coworkers 32 described 9 neonates who had undergone major operations and presented with chronic open wounds that failed to heal with conventional treatment after 14 days. The conventional treatment included systemic antibiotics, cleaning the wound twice daily, and applying an ointment. Swab cultures were taken daily. Conventional treatment failure was defined as after 14 days of systemic antibiotics and local treatment, the wound was still open, oozing pus, and swab cultures were positive. The honey-based dressing resulted in improved wound healing in all neonates after 5 days of treatment, and all of the wounds closed within 21 days. Systemic adverse events (ie, hyperglycemia, electrolyte imbalance, or significant irritation of surrounding tissue) did not occur. Okeniyi and colleagues 33 examined healing of 43 incised pyomyositis abscess wounds with honey in 32 Nigerian children. The most common cause of this infection was S aureus, which was attributed to the hot and humid tropical climate, poor hygiene, and malnutrition. All children received antibiotics, but the hospital length of stay was shorter and wounds healed faster in the honey-treated group. No wound required secondary wound closure and no side effects were seen in either group.
Bell 6 reviewed the literature from 1996 to 2006 and 2 studies using honey for treating wounds or skin damage in children. One study evaluated the use of honey for treatment of wound infections in neonates 32 and the other reported honey for treatment of diaper dermatitis. The second study that Bell summarized combined honey with beeswax and olive oil in the treatment of 12 infants with incontinence-associated dermatitis. A swab culture for C albicans was taken before therapy and at the end of treatment. Rash severity was rated on a 5-point scale. The honey mixture was applied to the affected areas 4 times per day for a maximum of 7 days. By day 7, 10 of the 12 infants had mild or no incontinence-associated dermatitis. Based on these studies, Bell 6 concluded that the evidence of using honey was interesting, but evidence supporting its use in infants and neonates is weak and recommended that randomized controlled clinical trials with sufficient power should be completed to provide more definitive data. Weaknesses in the available evidence included variability in honey preparations, small sample sizes in the 2 studies identified, and absence of cultures for subjects in the dermatitis study.
Although microbes cannot grow in honey, Clostridium botulinum spores are a theoretical concern in raw products meant for infants. Specifically, the gastric environment in infants is less acidic, and it may provide less effective protection against Clostridium spores than the gastric lumen of an adult. Nevertheless, C botulinum has not been reported yet with honey dressings.6
Clinical Considerations
WOC nurses should make decisions about the use of honey dressings based on current best evidence and research-based knowledge of principles of topical wound care (Table 3). This process begins with an assessment of wound type. White 8 identified the use of honey for (1) chronic wounds such as leg ulcers and pressure ulcers, (2) wounds with delayed healing and local infection, (3) acute wounds such as burns and locally infected wounds without cellulitis, and (4) wound bed preparation for grafting. Honey also may be used as a compassionate treatment option for patients whose care has failed other treatments.9

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TABLE 3. Considerations for Honey-Based Dressingsa
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The type of honey dressing product should match the wound type. Honey gel/ointment may be applied directly to the wound or an appropriate dressing placed on the wound. The gel/ointment is covered with an occlusive dressing so as to maintain a moist environment to keep the preparation from drying out on the wound bed.8 A practical challenge associated with the use of a liquid/gel honey application is ensuring that it remains in place on vertical wounds such as leg ulcers or abdominal wounds.9,34 If the honey-based product is not available in this format, soaking an alginate dressing with honey and covering with a gauze layer followed by a transparent dressing may help maintain contact with the wound. The alginate honey dressing is especially attractive because it has been found to be malleable, easy to apply, nonadherent to the wound base, and less painful on removal.12
The frequency of dressing change needs to be based on the amount of drainage. If the outer dressing becomes moist with exudate, it must be removed to prevent contamination and maceration of periwound skin. As the drainage decreases, the dressing can be left on for longer periods (4–7 days), thus decreasing the frequency of dressing changes.12 Strike-through of the honey dressing should be avoided because it leaves a sticky residue on affected surfaces.34 A heavy flow of drainage that washes honey to the outer surface may also allow the dressing to stick to the wound, necessitating more frequent dressing changes.35 If a nonadherent dressing is used on the wound base, it should be sufficiently porous to allow components of the honey to diffuse to the wound.35
Relative and absolute contraindications for using a honey dressing also must be considered. These include the following: (1) using a honey product that is not indicated for wound care; (2) sensitivity to bee venom/stings or honey; (3) dry, necrotic wounds; (4) dressings that cannot be changed within a specific time; (5) wounds requiring surgical debridement; and (6) following incision and drainage of an abscess.31,36 Although Stephen-Haynes 22 noted that dressings made from animal products have the potential to provoke an immune reaction, Simon and colleagues 31 observed that no reports of anaphylaxis have ever been associated with the use of honey products for wound care. In addition, since honey is a potential source of glucose absorption, patients with diabetes may be at a slightly greater risk of hyperglycemia.22
Although honey has antibacterial properties, systemic antibiotics may still be needed. For example, this is true of oncology patients with profound neutropenia 31 and any situation in which there is invasive infection, including those with cellulitis.
Some patients experience pain associated with the use of honey dressings. Transient stinging reported as pain may occur for around an hour after its application.8 Blaser and associates 9 reported that 1 of 7 patients stopped treatment due to severe pain, but the pain in this case was later found to be related to opioid resistance. The cause of the transient pain often seen with the use of honey dressings is not fully understood, but it may be related to its osmotic effect (ie, drawing fluid from the wound) or its acidic pH.9 Honey-associated wound pain can be treated with an analgesic or a more dilute honey preparation.8 In some patients, the use of a gel preparation that contains wax ester and ethoxylated oil has been found effective.9
As with any topical therapy, the WOC nurse must assess the effectiveness of a honey-based dressing. Anderson 36 identified key questions to be used when assessing outcomes of a honey dressing:
1. Is there a reduction in redness and swelling in terms of inflammation indicating positive changes in the wound? Has the infection resolved?
2. What is the person's pain description? Has it increased or decreased with the honey dressing? Is it pain the person is willing to tolerate with the dressing?
3. What is the condition of the surrounding skin and is it improving?
4. Is the number of dressing changes decreasing over time? (If dressing frequency is not decreasing, the honey may not be effective due to the amount of drainage and the amount of honey may need to be increased.)
5. Is there a reduction in necrotic tissue?
6. What are the patient's and the clinician's rating of wound odor and is it decreasing?
7. Considering the wound and other dressings, is it cost-effective?
Summary
Honey dressing products have been used worldwide for many years, and a honey-based dressing is not available in the United States. A review of existing research reveals increasing evidence regarding the efficacy of honey-based products for healing selected chronic wounds. Honey has been used with adults and children and on acute and chronic wounds. It exerts an antibacterial effect without the risk of antibiotic resistance. Some patients report pain reduction, but stinging or increased pain has also been reported. As with any wound care treatment, prospective randomized controlled studies are needed to provide a more robust and informative evidence base concerning its use in wound care.
ACKNOWLEDGMENT
The authors have no significant interest, financial or otherwise, in any company that might have an interest in the publication of this educational activity.
KEY POINTS
[check mark] Honey wound care products have a long historical use worldwide and have been recently approved by the Food and Drug Administration in the United States.
[check mark] Honey-based dressings should be considered with other wound dressings in patient care decisions. WOC nurses should be aware of recommendations for not using these products such as an allergy to honey or bee products.
[check mark] Honey dressings have anti-inflammatory and antibacterial effects. They promote moist wound healing and facilitate debridement. They may cause a stinging pain in some patients.
[check mark] Only honey products approved for wound care should be used.
[check mark] Clinician/patient/family teaching on the proper use of this product is critical.
[check mark] Evaluation of the outcomes of a honey-based dressing should be done as it is done for other dressings.