Stimulation of healing

Wounds dressed with honey often have a rapid rate of healing. Honey is also able to start the healing process in dormant wounds. Honey has been reported to promote the formation of granulation tissue and to stimulate the growth of epithelium over wounds. It has also been reported that honey is a reliable alternative to conventional dressing for the management of skin excoriation around stomas ( ileostomy and colostomy), giving a more rapid epithelialisation of the raw surface (Aminu et al, 2000). These clinical observations of the stimulatory effect of honey on tissue growth in wounds have been confirmed by measurements and histological observations in studies of experimental wounds in animals (Burlando, 1978; Bergman et al, 1983; Gupta et al, 1992; Kumar et al, 1993; Suguna et al, 1993; Postmes et al, 1997), where honey treatment has been shown to give statistically significant improvements. In these experimental wounds, honey has also been shown to stimulate the synthesis of collagen (Suguna et al, 1992) and other connective tissue components (Suguna et al, 1993), and to stimulate angiogenesis (development of new blood vessels) (Gupta et al, 1992; Kumar et al, 1993).

Stimulation of angiogenesis is an important feature for promotion of healing, as the supply of oxygen is the rate-limiting factor in tissue repair (Silver, 1980), granulation tissue being granules of fibroblasts growing where new capillary beds form. The anti-inflammatory activity of honey would also assist by decreasing oedema and, consequently, the pressure on capillaries which restricts blood flow and the supply of oxygen to the regenerating wound tissues. The acidity of honey would also help with oxygenation, as acidification of wounds speeds the rate of healing by increasing the release of oxygen from haemoglobin (Kaufman et al, 1985).The newly-formed capillaries supply essential nutrients to growing fibroblasts, another factor limiting the rate of healing — it has been demonstrated that wounds heal faster if a nutrient mixture is applied topically (Viljanto and Raekallio, 1976; Niinikoski et al, 1977; Silvetti, 1981; Kaufman et al, 1984). There is a wide range of minerals, including the trace elements of nutrition, and of amino acids and vitamins contained in honey (Haydak et al, 1975; White, 1975). Although these are present in amounts too low to be of nutritional significance when compared with the recommended daily intake, they are, on average, present at levels like those circulating in the blood. This topical supply of nutrients would be augmented by the osmotic action of honey drawing lymph from the underlying capillaries, thus creating a constant flow of nutrients for cells which may be somewhat distant from the functioning capillaries deeper down. Another way in which honey may promote healing is by supplying glucose to the epithelial cells, as these have to build up an internal store of carbohydrate to provide the energy they need to migrate across the surface of a wound to restore skin cover (Silver, 1980). The level of glucose in the wound fluid of chronic wounds is very low (Schultz et al, 2003). The sugars in honey would also provide an energy source for the macrophages working in the wound, as glycolysis is their major mechanism for energy production, and is dependent on a supply of glucose or fructose. Glycolysis is the only means of cells obtaining energy in the absence of oxygen, so the supply of sugars from honey would allow them to function in damaged tissues where the oxygen supply is often poor (Ryan and Majno, 1977).

Another possible way that honey may work to stimulate wound repair is through its production of hydrogen peroxide, as hydrogen peroxide activates the insulin receptor complexes on cells (Czech et al, 1974; Helm and Gunn, 1986; Koshio et al, 1988). Activation triggers a chain of molecular events in the cell that stimulates the uptake of glucose and amino acids, and promotes anabolic metabolism, giving cell growth. Topical or intravenous application of insulin to wounds, stimulates the rate of wound healing (Lopez and Mena, 1968; Belfield et al, 1970; Pierre et al, 1998). By this mechanism, honey may stimulate the uptake and anabolic metabolism of the nutrients it supplies to wound tissues.

The stimulation of angiogenesis by honey, that has been observed experimentally when honey is applied to wounds, could also be via its production of hydrogen peroxide, as topical application of hydrogen peroxide has been found to enhance cutaneous blood recruitment in ischaemic ulcers (Tur et al, 1995). In vascular, smooth muscle cells, hydrogen peroxide is endogenously produced as part of the process of response to stimulation by platelet-derived growth factor, and exogenous hydrogen peroxide in the concentration range of 0.1 to 1.0 mmol/l will also function in the response (Rao and Berk, 1992). The promotion of formation of granulation tissue by honey may also be via the stimulation of growth of fibroblasts by the hydrogen peroxide produced in honey, as hydrogen peroxide has been found to stimulate the proliferation of fibroblasts (Chung et al, 1993). There is a large amount of evidence that hydrogen peroxide is involved in many cell types in the body as a stimulus for cell multiplication, by acting at various points in the mechanisms of the cells that control the cycle of cell growth and division (Burdon, 1995). It has been proposed that low concentrations of hydrogen peroxide might be used to stimulate wound healing in place of the expensive cell growth factors used for this purpose (Burdon, 1995; Postmes and Vandeputte, 1999). However, this is feasible only if the concentration could be carefully controlled to avoid tissue damage (Chung et al, 1993). This is possible with the controlled sustained release of hydrogen peroxide that occurs in honey.

Another possibility is that the stimulation of tissue repair is a down-stream effect of the stimulation by honey of cytokine production by leukocytes. The production of cytokines, as part of the initial inflammatory response, normally starts off the healing process. There is good evidence for the ability of honey in quite dilute solution to stimulate such a response in leukocytes in cell culture.

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