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Honey is a mixture of sugars, water, and other compounds, the specific composition depending largely on the mix of flowers consumed by the bees. It has been reported that approximately 181 substances are present in honey (Terrab et al., 2003). A typical honey analysis is shown in Figure 1 according to the U.S. National Honey Board, where it has an average composition of fructose 38.2%, glucose 31 %, sucrose 1.5%, maltose 7.2% and 17-20% water. In addition, acids, minerals, enzymes, vitamins and proteins also found (Sharquie & Najim, 2004). About 18 free amino acids are known to occur in honey. However, they are present in small amounts although proline is the most common (White, 1979; Atrouse et al., 2004).
The composition of honey is varying from honey to other depending on several factors. These factors are the floral source as the nectar from different plants will contain different composition of the main sugars and the trace elements. These composition are influenced by soil type, climate conditions and the environment surrounding the plant (Crane, 1975)
Many plants like flowers and trees are excellent sources of nectar for honey. The colour and flavour of honey can vary depending on the nectar source. Colours range from almost water white to dark brown as darker honey has more antioxidant potential and strong flavour. The flavours vary from delectably mild to distinctively bold, depending on where the honeybees worked (http://www.fao.org).
Figure 1: Diagram represents the chemical composition of U.S honey
(Adopted from the website http://www.nhb.org)
Raw honey contains several enzymes that help in its digestion. These enzymes are invertase (that converts sucrose into glucose and fructose), amylase (diastase) and glucose oxidase (that produces gluconic acid and hydrogen peroxide from glucose in diluted honey). Other enzymes which also present in the honey are catalase and acid phosphatase. In addition, honey contains several B vitamins such as riboflavin, niacin, folic acid, and B6. Antioxidants and traces of pollen also present in the honey (Atrouse et al., 2004). Moreover, honey contains a number of minerals such as calcium, iron, zinc, potassium, phosphorus, magnesium, selenium, chromium and manganese (White, 1975; Atrouse et al., 2004).
Evidence of Antimicrobial Activity of Honey
The antibacterial activity of honey was first recognised in 1892, by Van Ketel (Dustmann, 1979). Since then there have been many researches proved the antibacterial activity of honey against many bacterial pathogens and fungi (Efem 1992, Molan, 1992a, Cooper 1999).
A survey of 345 samples of New Zealand honey was carried out to assess the antibacterial activity of honey. Four types of honey were shown to have high antibacterial activity equivalent to phenol standard. In this assay most of the honeys showed no detectable antibacterial activity when catalase was added to remove hydrogen peroxide. However, manuka and vipers bugloss honeys showed measurable amount of hydrogen peroxide which believed to aid antibacterial activity (Allen et al., 1991)
Efem (1992) found that undiluted honey prevented the growth of Candida albicans. Wahdan (1998) showed that undiluted honey could be used in the treatment of superficial fungal infections such as ringworm and superficial candidiases.
Cooper (1999) showed that honey has a significant antibacterial activity against the major wound infecting species including methicillin-resistant Staphylococcus aureus (MRSA). In the same year cooper et al., compared pasture and manuka honey and found out that the antibacterial activity of honey against Staph.aureus was not wholly due to its high osmolarity. It has been shown that there is not much different in sensitivity to honey between methicillin-sensitive and methicillin-reisitant staphylococci. In 2000 Cooper et .,al also reported the sensitivity of multi-resistant strains of Burkholderia cepacia isolated from cystic fibrosis patients to manuka honey at concentrations below 6% (v/v). Six commercial honey samples were tested against control organisms, Staph.aureus, Escherichia coli, Pseudomonas aeruginosa and various clinical isolates it was found that some samples have high broad- spectrum antimicrobial activity which resist refrigeration temperature for six months and being boiled for 15 minutes (Nezeako & Hamdi 2000)
Cooper et al (2002b) showed the antimicrobial activity of manuka and pasture honey against 18 strains of MRSA isolated from wounds and strains of vancomycin-sensitive enterococci (VSE). MIC for both honeys was below 10% (v/v) compared to artificial honey, which required a concentration 3 times higher to inhibit the growth. In 2002c Cooper et al compared the antimicrobial activity of two honeys, a pasture and manuka honey against 17 strains of Pseudomonas aeruginosa isolated from burns. Both honeys maintained bactericidal activity when diluted more than 10-fold.
Al-Jabri et al (2002) compared the antibacterial activity of 16 honeys from different parts of Oman and 8 from different countries in Africa against three control organisms Staph.aureus, Escherichia coli, Pseudomonas aeruginosa. It was found that Dhofar honey (Oman) and Eucalyptus honey (Uganda) had highest level of activity against all the three control organisms.
Anti-Staphylococcal activity of thirty types of Omani honey was tested alone and in combination with gentamicin. It was observed thirteen of the Omani honey showed excellent anti-Staphylococcus aureus activity. The best honey had killing rate of 38% of Staphylococcus aureus at 50% concentration in 30 minutes. Gentamicin (4Âµg/ml) killed 70% while the killing rate for the combination of honey and gentamicin was superior with 92% killing in the same duration (Al-Jabri et al., 2005)
The first Study of the ability of honey to prevent bacterial adherence in vitro was done by Al-Naqdy et al., 2005. Four different types of Omani honey were used to in this study for growth inhibition. Bacterial adherence was assayed using of Salmonella interitidis cells that had been incubated first with honey and then with intestinal epithelial cells. Results showed decreased in number of bacteria attached to the treated epithelial cells from 25.6Â±6.5 to 6.7Â±3.3 bacteria per epithelial cell (P<0.001).
The primary host defence is the physical barrier afforded by the skin and mucous membrane; once this barrier is breached it provides a route for entry of bacteria into the body. Infection can be from patients own flora, infectious material from carriers or other infected individuals that may reach the wound. Microorganisms associated with wound infection could be bacteria, fungi or viruses. The most frequently isolated wound pathogens are Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Enterobacteroceas (Bowler et al., 2001). A study done on the prevalence of wound infection showed that surgical wounds and skin infections were two of four largest categories of hospital acquired infections (Emmerson et al., 1996). The management of infected wounds costs a considerable amount of money, Plowman et al., (2000) reported that the cost per case of hospital-acquired infection ranges between £1,618 and £2,398 per person.
Honey and wound healing process:
Honey is an effective treatment of wounds because it is non- irritating, non-toxic, self-sterile, easy and simple application, bactericidal, anti-inflammatory, nutritive, and more comfortable than other dressings.
Clinical Evidence of Effectiveness:
In order to whether honey does stimulate wound healing an investigation was undertaken and evidence has been derived from several sources: animal studies, cell line in vitro studies, clinical observations with case studies, cohorts of patients and clinical trails.
Honey has been used to treat infections in a wide range of wound types. These include burns, leg ulcers, diabetic foot ulcers and pressure sores. Cavanagh et al. (1970) observed 12 cases of wound damage after radical vulvectomy being dressed with honey. The wounds became sterile after 3-6 days. In (1981) Salem performed a clinical trial of 45 patients diagnosed with dyspepsia improved after treatment with only 30mls of honey before each meal. Emarah (1982) observed improvement of patients suffering from eye infection after applying honey as an eye ointment. Moreover, Honey reported to reduce the duration of diarrhoea in clinical trials done for infants with gastroenteritis in which honey was used insted of glucose in rehydration fluid (Haffejee & Moosa 1985)
In 1988, Efem reported first large clinical cohort study involving 59 patients who had a variety of wounds ranging from Fournier's gangrene, burns and a range of ulcers. Unprocessed honey was applied on cleaned wound daily. The use of honey on these patients resulted successful wound healing and clearance of infection. Suprahmanyam (1993, 1994. 1996 & 1998) reported a clinical trials on burns patients with honey compared to different treatments e.g. polyurethane film (Opsite), potato peelings and amniotic membrane. Honey was superior to all other treatments and healing time was shorter. Tonks et al (2001) showed that pasture and manuka honey were found to down regulate the ROIs (reactive oxygen intermediate) synthesis from MM6 cells. ROIs are known as toxic by-products of various cellular O2 consuming redox processes which are responsible for causing symptoms of oxidative damage if ROI production exceeds the capacity of ROI scavenging reactions. Honey aids in controlling the ROIs which required for wound healing.
How does honey promote wound healing?
Although the water activity of honey is very low it provides a moist environment for optimum healing conditions. The tissue does not get dehydrated because of the osmotic effect of honey it draws the fluid through the wound tissue from the underlying circulation (Chirife et al., 1983). The topical application of nutrients to wounds has been shown to increase the growth rate of granulation tissue (Kaufman, 1984). The viscosity of honey provides a protective barrier to prevent cross-infection of wound (Efem, 1988). Honey has been proved to have a deodorising property on wound. It thought to be due to high glucose content uptake by infecting bacteria as an alternative to amino acids, resulting in production of lactic acid rather than malodorous compounds such as ammonia, sulphur compounds and amines (Molan, 1998). Moreover, acidification of wound (pH 3-4) causes more oxygen to be released from haemoglobin, thus promotes healing (Efem, 1988).
Some researchers observed that honey promotes tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells (Efem 1988, 1993 & Subrahmanyam 1994, 1998), therefore quick healing can minimise the need for skin graft (Subrahmanyam 1998).
Due to poor blood supply that limited availability of oxygen and nutrients to the cells in a skin necrotic lesion. The osmotic effect (high glucose) and mixture content of vitamins, minerals and amino acids in honey plays a role to overcome these limitations (Molan, 1999).
In addition, after honey is applied to the wound it forms a film of liquid between the wound and the dressing that prevents the dressing from sticking to the wound without pain and without damaging the newly formed cells. As honey has no adverse effects on tissue, it can be used safely on wound and introduce into cavities and sinuses to clear infection (Molan, 2000).