ReviewHoney in modern wound care: A systematic review
Introduction
Since ancient times, as discovered in the tomb of King Tut (14th century BC), honey has occupied an important place in traditional medicine and has been mentioned as a medicinal product in countless works [1], [2], [3], [4], [5]. Probably the first deliberate mentioning of honey as a wound treatment was found in the “Edwin Smith papyrus” (2600–2200 BC) [6]. Not only the Egyptians but also the ancient Greeks and Romans used honey, not only in combination with vegetable or animal fat but also as part of all sorts of ointments, which were used to prevent wounds from festering [4], [6], [7], [8]. Avicenna (980–1037), the most famous of the Arab doctors of Islam, advised the use of astringents such as cooked honey and myrrh to reduce the amount of exudate in wounds with tissue loss [9]. From the early Middle Ages to the late 19th century, there were several descriptions of the use of honey to cleanse and heal chronic and traumatic wounds, in particular gunshot wounds in the 17th and 18th century [9], [10]. In more recent times, during World War I, honey was used by the Russians and the Germans [4], [11] and remained popular until the advent of antibiotics in 1940 [1], [12]. However, due to the ever-increasing resistance against antibiotics and the growing awareness for natural remedies, the interest in the antimicrobial and wound healing properties of honey have shown a revival [1], [3], [13].
Honey is a viscous, hypersaturated sugar solution coming from nectar which has been collected and modified by the honey bee, Apis [6]. The bees collects the nectar of the plants, transform and combine it with substances of their own. The honey is stored in the honey comb to ripen and mature [14]. Honey primarily contains sugar (75–79%) and water (20%) [7]. Other components of honey are proteins, vitamins of the B complex, minerals and antioxidants such as flavonoids, ascorbic acid, catalase and selenium [11], [15]. Organic acids make up 0.57% of the honey and are responsible for its acidity [15], [16]. The main enzymes in honey are invertase, amylase and glucose oxidase [16]. The specific percentages of all these different components may vary depending on the plant origin, the geographical location, the season in which the honey was collected, the treatment of honey since its harvesting, and its age [8].
Honey is easily contaminated during its production process [16], [17]. Therefore, a medical grade honey should be sterilized, not by heating, but by means of gamma irradiation [8]. Through the process of gamma irradiation, micro-organisms are killed without jeopardizing the antibacterial activity of the medical honey [8], [18], [19].
The antibacterial effect of honey is based on several mechanisms. First, hydrogen peroxide is produced by the enzyme glucose oxidase when the honey is diluted by wound exudate [1], [11], [16], [17]. Hydrogen peroxide activates the neutrophils through the nuclear transcription factor NF-kB. Hereby genes are activated that produce cytokines which strengthen the inflammatory response by recruiting and activating leucocytes [14], [20], [21], [22].
Phytochemicals, also called flavonoids, are a second antibacterial mechanism of honey [11], [16], and are present in Manuka honey and Medihoney [8], [23], [24]. By their direct inhibition of phagocytosis, these antioxidants prevent the formation of the superoxide free radicals, protecting the tissues from further damage [14].
A third effect of honey relates to the fact that bacterial growth requires a water activity (amount of ‘free’ water) of 0.94–0.99. However, since honey has a low water activity of 0.56–0.62, this prevents the growth of bacteria [11], [18]. The high sugar content of honey draws fluid from the wound by osmosis and hereby extracts water from the bacteria resulting in bacterial death [8], [23].
Finally, the acidity of honey (with a pH between 3.2 and 4.5) further inhibits the growth of micro-organisms, since the optimal pH for the majority of these organisms lies between 7.2 and 7.4 [3], [23], [25].
Apart from its antibacterial effect, a lot of other properties have been attributed to honey. It has also been shown to reduce inflammation, to avoid the need for surgical debridement, to neutralize bad smells, and to accelerate tissue growth and wound healing [3].
In clinical practice, mainly Manuka honey and Medihoney are being used. Manuka honey is a mono-floral honey that comes from the Leptospermum scoparium tree in New Zealand and Australia and is particularly interesting because its antibacterial activity is independent of the peroxide activity [26], [27], [28], [29]. Medihoney is a standard mix of Australian and New Zealand honeys, predominantly of the Leptospermum species (Manuka) [4], [30], [31]. It has an antibacterial activity that corresponds to a phenol acid strength of at least 18, which makes it currently the strongest antibacterial medical honey available [4]. Besides mono-floral honey, also multi-floral honey is used in clinical practice.
Honey, an ancient therapy, has known a revival in recent times and is frequently used nowadays for a very wide range of conditions. Despite its universal use, especially in the treatment of burn wounds and difficult to heal chronic ulcers, it is not clear to date what exactly the level of evidence is for honey in wound management [1], [3], [11], [18], [23], [32]. The aim of this systematic review is to evaluate the use of honey in modern wound care based on the published literature to date. It examines the role of honey in wound care, the wound categories in which honey is applied, and provides a critical evaluation of the reported benefits of using honey.
Section snippets
Methods
This study was designed as a systematic review of published randomized controlled trials (RCTs), clinical controlled trials (CCTs), clinical trials (CTs) and case reports (CRs).
The search strategy was developed in two electronic databases: PubMed and ISI Web of Science by the first and the second author. Both databases were selected in order to cover most of the published peer-reviewed literature.
A search filter composed of four items: “Honey”, “Wound healing”, “Design” and “Language” was
Description of the included studies
The search strategies in PubMed (PM) and Web of Science (WOS) resulted in a total of 55 unique publications (Fig. 1).
In three of the included publications a clarification regarding the selection of design is indicated.
The publication of Moolenaar et al. is actually a letter to the editor, but in this review it was selected as an RCT because it describes a fully randomized controlled study performed by the authors. The reporting was limited, but of sufficient value to include [33].
The
Outcomes
The results of the included studies were examined and classified by wound aetiology.
Outcomes of the included studies
Looking at all three described wound categories, it is clear that honey is a dressing with properties that are beneficial to wound healing. However, the evidence for its deodorizing, debridement, anti-inflammatory, and wound pain reducing properties is rather limited.
The evidence for its antibacterial property is strongest in the studies on burns. However, one RCT reported that TE with subsequent grafting leads to a better result [36]. But it is incorrect to compare the effect of topical honey
Conflict of interest statement
The authors, Lynn Vandamme, Alexander Heyneman, Hendrik Hoeksema, Jozef Verbelen and Stan Monstrey do not have any interests that might be interpreted as influencing the review. This review did not receive any support from industry or private corporations.
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Both authors are shared first authors of this publication.