Honey has many beneficial effects that make it an ideal wound dressing. Its wide spectrum of antimicrobial activity and immunomodulatory effects on the wound healing process exceed many currently available dressings.
Wound healing is a complex process. It involves inflammatory, debridement, repair, and maturation phases, which ultimately lead to a scar or restoration of the original tissue. Honey, the modified secretion of flower nectars and honeydews from the bees of the genus Apis, possesses numerous bioactive properties that make it a useful tool for wound care involving chronic and traumatic wounds, as well as burns.1 In fact, several randomized controlled studies have demonstrated statistically significant beneficial effects of honey on wounds in both animals and humans.2,3
With the discovery of antibiotics, the medical use of honey fell out of favor.2 However, honey has a 4,000-year-old record of historical usage for its medicinal properties.4 And with the rise of antibiotic resistance, the focus on honey for its antimicrobial and wound healing properties has been the spotlight of several recent studies,5 and a 2016 article was published in JAMA Dermatology examining the role of honey in wound treatment.6 Its usefulness has been extensively examined and used in human medicine due to the prevalence of chronic wounds, but there are also several animal studies focusing on honey and wound care, and a variety of medical honey products are available for veterinarians.1,2,3,7,8,9
Properties: how does honey help?
Honey is a complex mixture of over 200 components.10 Monosaccharides, primarily fructose, comprise nearly 80% (w/v), while its water content varies between 15% to 21% (w/v).10 Honey also contains proteins, vitamins, minerals, phenolic compounds, organic acids, and volatile compounds that all contribute to its bioactivity.10 The composition and thus the bioactivity of honey varies based on its geographical origin and floral source (Figure 1).11
Manuka honey, for example, is a monofloral honey originating in New Zealand from the flowers of Leptospermum scoparium trees. Manuka honey is recognized for its high levels of an antibiotic substance called methylglyoxal (MGO), or unique manuka factor (UMF).12 MGO is not necessarily unique to manuka honey, and other honey varieties such as kanuka and other European honeys, contain this chemical.5,13
Licensed medical grade honey products tend to use manuka honey products and rate its antibiotic activity based on the concentration of UMF. Because honey contains particulate contaminants, such as pollens, and microorganisms from the honeybee gastrointestinal tract, most notably Clostridium botulinum spores, a medical-grade, filtered, gamma-irradiated product is recommended for wound treatment. Unlike pasteurization, gamma-irradiation preserves the bioactive compounds lost due to heat treatment.14
Honey exerts a multifaceted antimicrobial effect that has been shown to inhibit gram-positive and gram-negative bacteria, yeast, and fungi.15,16 It is an acidic substance with a pH of between 3.2 and 4.5, due to the presence of organic acids, that inhibits the growth of many microorganisms.15 The osmotic effect, due to the high osmolarity from honey’s high sugar content, dehydrates and inactivates bacteria.15 Honey has been shown to affect bacteria through multiple mechanisms, such as changing their cell structure, decreasing membrane potential, disrupting the cell-cycle and metabolism, decreasing cellular growth, affecting efflux pump mechanisms, disrupting quorum sensing, and disrupting biofilms.5 Studies have shown a bactericidal or bacteriostatic effect against many wound pathogens such as multidrug-resistant Staphylococcus aureus, methicillinresistant Staphylococcus pseudintermedius, Pseudomonas, Pasteurella multocida, Enterococcus, Proteus, and Escherichia coli.16,17 The minimum inhibitory concentrations of various honeys range anywhere from greater than 50% down to 0.25%.18
bioactive components. Leptospermum scoparium is the manuka tree
Honeys are classified into hydrogen peroxide (H2O2) dependent or non-H2O2 dependent antimicrobial pathways. H2O2 is thought to be slowly generated in honey due to the deposition of glucose oxidase into the honey by the bee. Although phenolic compounds possess antimicrobial qualities, the phenolic concentrations found in H2O2-dependent honey are too low to exert an antimicrobial effect. Instead, it is thought that the phenolic compounds and minerals found in honey synergize together and with H2O2 produce an antimicrobial effect.5 H2O2 is present in honey at a concentration that is 900 times less than the conventional 3% H2O2 antiseptic, yet it exhibits antimicrobial activity while simultaneously preventing tissue damage through various mechanisms.19
Non-H2O2 dependent honeys utilize other antimicrobial mechanisms, such as the high concentrations of phenolic compounds found in Malaysian multifloral meliponini honey.20 The most studied of these non-H2O2 dependent honeys is manuka honey, whose antimicrobial effect is due to high levels of MGO, a breakdown product of dihydroxyacetone contained in the nectar of the manuka tree flower.12 Although the mechanisms of action on bacteria have yet to be fully understood, MGO has shown to disrupt bacterial fimbriae, flagellum, and other bacterial cell structures.5 Honey has also been reported to synergize its antimicrobial effects with the use of antibiotic administration.5 There have been reports of antimicrobial resistance to manuka honey in biofilm-producing bacteria, but it appears that synergism with antibiotics negates these findings thus far.5
Honey and wounds
Wounds are assessed and classified at presentation for their degree of contamination (clean, clean-contaminated, contaminated, or dirty).21 A treatment plan is then created that involves first, second, or third intention healing process. In clean wounds, first intention healing is always preferred; however cost, health status of the animal, failure of first intention healing, infection, and surgical limitations might limit the veterinarian to select the second intention method. This method leaves the wound open, covered by bandages, to allow for granulation, re-epithelization, and contraction.22 The phases of wound healing are summarized in Table 1.
When applied to the wound as a part of the wound dressing honey forms a physical barrier and maintains a moist environment while preventing bandages from adhering to the wound bed; this has been shown to accelerate granulation and healing.22 Due to its high osmolarity, honey decreases wound edema and pulls exudates away from the wound bed.1 This effect activates autolytic debridement of the wound bed through osmotic action by drawing water out of the wound, and may also activate plasminogen, which breaks down wound fibrin.26
On the wound bed, honey also exerts several anti-inflammatory and immune-modulating effects that result in reduced healing time,27 scarring,28 edema,29 exudate,30 and increased wound tensile strength.31 Honey has been shown to neutralize reactive oxygen species during the inflammatory phase of healing, stimulate or inhibit macrophages and fibroblasts, and stimulate keratinocytes, depending on the chronicity of the wound.32 Unlike common wound antiseptics such as chlorhexidine,23 iodine, and silver-ion, honey is non-cytotoxic to the wound bed.33
During the repair phase, honey has been shown to stimulate angiogenesis, formation of granulation tissue, and re-epithelialization.32 Due to its high density of sugars, vitamins, and minerals, honey delivers nutrition to the healing tissues. Honey has been reported to help reduce pain due to its anti-inflammatory effects, but there are reports of pain upon application in some human patients with highly inflamed wounds.34
Licensed medical-grade honey (MGH) products
Multiple honey products for human and animal medicine are available for wound management. Thus far, there have been no reports of botulism through the topical application of raw honeys, but again, a gamma-irradiated medical-grade honey product is recommended for wound treatment.5 These honeys are strictly regulated, collected from organic regions, and must be free from contaminants like pesticides, herbicides, heavy metals, and spores.5
Manuka MGHs are classified based on their UMF content. The UMF rating correlates with the MGO concentration. For example, UMF-10 manuka honey contains an MGO rating of 263mg/kg.35 A compound unique to manuka honey, leptosperin, has been recently discovered; it contributes to manuka honey bioactivity, and is now incorporated into the UMF rating.35 A rating of no less than UMF-10 should be selected for wound treatment.35 However, as pointed out in a 2020 study by Bucekova et al,36 due to the unreliability of the UMF rating, medical-grade manuka honeys also utilize MGO concentration (e.g. Manuka Vet®), percentage of pure honey (e.g. KRUUSE Manuka products), and non-peroxide activity (e.g. Integra MediHoney®) to indicate the degree of antibacterial activity.
Manuka honey products are available in natural, gel, paste, ointment, and cream forms that are directly applied to the wound bed for wounds with pockets, sinuses, tunneling, and undermining. In addition, medical-grade manuka impregnated bandages such as tulle (gauze), foams, hydrogel colloidal sheets, hydrogel sheets, and calcium alginate are available (Figure 2). The type of bandage should be selected based on the amount of exudate the wound is producing; e.g. for heavy exudative wounds, a calcium alginate bandage should be selected. Alternatively, the veterinarian can create MGH impregnated bandages by applying at least 30 cc of MGH to a 10 cm x 10 cm cotton gauze.7 Any pockets or sinuses should be filled with MGH honey.7 A three-layer bandage should then be applied over the wound.
Bandage change protocols
Honey will maintain its bioactive effects until it is diluted by wound exudates up to 45 to 60 times its volume.34 According to a recommendation by Molan and Betts,38 bandages might initially require changing up to three times daily until wound exudates subside. Ensure that the honey application extends beyond the margins of the wound bed. Afterwards, a bandage change may only be necessary every two to three days. If the bandages adhere to the wound, more frequent bandage changes are required. Molan and Betts also recommend that non-adherent bandages, such as those impregnated with paraffin, should be chosen to allow the honey to diffuse into the wound.38
Conflicting information exists on the duration and type of MGH recommended in veterinary medicine. A 2011 study of wounds of the equine distal limb by Bischofberger et al8 recommended using manuka honey up to 12 days with daily bandage changes, followed by a thin topical application of manuka honey gel two to three times daily for up to 21 days. A 2018 review by Kennedy39 recommended using honey only during the inflammatory phase (no more than five days) and until a healthy granulation bed is seen, with bandages being left on for up to five days. A 2018 study in mice by Sawazaki et al also recommended only using MGH during the inflammatory phase of wound healing, due to the low pH of honey delaying the re-epithelialization process of traumatic wounds, but this was thought to occur because of the application of a pure rather than diluted MGH.40 A technical review for Manuka Vet® products recommends selecting a MGH with a concentration greater than 500 mg/kg, following the protocol presented by Bischofberger et al for horses, or using the protocol outlined by Kennedy for dogs and other species.41
References
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