Honey and Antibiotics

on Sunday, 21 April 2013. Posted in Honey Research

The indiscriminate use of antibiotics has made many microorganisms develop resistance to them...

The indiscriminate use of antibiotics has made many microorganisms develop resistance to them. This has created immense clinical problems in the treatment of infectious diseases. Therefore, there is a need to develop alternative antimicrobial agents for the treatment of infectious diseases. Non-antibiotic approaches to the treatment and prevention of infection includes the application of honey. Milk naturally contains an array of bioactivities due to lysozyme, lactoferrin, immunoglobulins, growth factors, and hormones, which are secreted in their active form by the mammary gland. The combination of milk and honey may prove to be important source of nutrition and for protection against microbial infection. In this review article we discuss the importance of honey, and its ability to provide protection from infection.

INTRODUCTION
Antibiotics are molecules that stop microbes (both bacteria and fungi) from growing or killing them outright. However, antibiotics are sometimes associated with adverse effects on host which include hypersensitivity, depletion of beneficial gut and mucosal microorganisms, immunosuppression and allergic reactions. There is, therefore, a need to develop alternative antimicrobial agents for the treatment of infectious diseases. There are already several non-antibiotic approaches to the treatment and prevention of infection including the use of honey. Bovine and human milk have also been reported to possess antimicrobial activities. Milk is an established and healthy food source for energy, proteins, vitamins, and minerals. In addition to its value as a nutrient source, interest has arisen in the ability of milk to kill bacteria and how this knowledge can be applied to human health. A number of proteins like immunoglobulins found in milk under various conditions exhibit antimicrobial activity and can confer passive immunity from mother to the neonate. The young of many mammalian species are not born with an effective immune system. The immunoglobulins protect the neonate from infection until their own immune system is developed. The use of honey, milk and combination of both may reduce the indiscriminate use of antibiotics.

In this article, we review our knowledge of the antimicrobial effect of honey, milk and combination of both. We also discuss our own experience from in vitro tests on the benefit of combining milk and honey against bacterial infection. We will start by giving a brief review of the antimicrobial activity of honey, then of milk and thereafter we will discuss combination of honey with milk and with antibiotics.

ANTIMICROBIAL ACTIVITY OF HONEY

Honey is acceptable in the medical profession as an antibacterial agent for the treatment of some diseases and infections resulting from wounds and burns. In many cases, it is used with success on infections not responding to standard antibiotic and antiseptic therapy. Its effectiveness as an antibacterial agent is widely reported. Honey is the substance made when the nectar and sweet deposits from plants are gathered, modified and stored in the honeycomb by honey bees. The definition of honey depends upon who defines it. Most people think of honey as excellent food, but some others consider it an elixir, and still others as medicine. Essentially, honey is an invert sugar (a mixture of glucose and fructose) dissolved in 14 to 20% water with minor amounts of organic acids, along with traces of minerals and vitamins. Honey is derived from the nectar of flowering plants which the honey bee collects. Nectar consists primarily of 10 to 50% sucrose, glucose, and fructose, and 50 to 90% water. The source of honey determines many of the attributes of honey such as aroma, flavor, color and composition.

Hydrogen peroxide, a component of honey is well known as an antibacterial agent, although it is mostly used as an antiseptic rather than antibacterial agent. It has been out of favor with the medical profession since it first came into use in the late 19th century. It has been suggested that it readily decomposes in solutions containing traces of catalytic metals such as iron or copper. This may be the reason why hydrogen peroxide went out of favor as an antiseptic after initially being hailed as an antibacterial and cleansing agent when first introduced. There was an upsurge of interest in its use later when stabilized preparations became available, with good germicidal activity being reported. But in more recent times, it has again gone out of favor as awareness has developed of its inflammatory properties and damage caused to tissue by its oxygen free radicals. However, the hydrogen peroxide concentration produced in honey activated by dilution is typically around 1 mmol/l, about one thousand times the level in the 3% solution that is commonly used as an antiseptic. There is also a potential for honey to sequester and inactivate the metal ions which catalyse the formation of oxygen radicals from hydrogen peroxide, and the antioxidant components of honey to mop up any free radicals that may be formed.

In almost all studies in which more than one type of honey has been used, differences in the antibacterial activity of honey have been observed. The degree of difference observed has in some cases been very large and in many others very small. The differences are attributable to limited range of testing rather than variation in the activity of the honeys.

THERAPEUTIC PROPERTIES OF HONEY

The antimicrobial activity of honey is very important therapeutically, especially in situations where the body’s immune response is insufficient to clear infection. Bacteria often produce protein-digesting enzymes, which can be very destructive to tissues and can destroy the protein growth factors that are produced by the body to stimulate the regeneration of damaged tissues in the healing process. Furthermore, some bacteria produce toxins that kill tissue cells. Additional damage is often caused by bacteria carrying antigens that stimulate a prolonged inflammatory immune response which give excessive production of free radicals that are very damaging to tissues. Bacteria in wounds can also consume oxygen, and thus make the level of oxygen available in wound tissues drop to a point where tissue growth is impaired. The consequences of bacterial infection are; non-healing of wounds; increase in size of wounds and development of ulcers and abscesses; failure of skin grafts; and inflammation causing swelling and pain. All these can be avoided by administering honey to clear infection. In addition to having a direct antibacterial action, honey may clear infection through a number of properties including boosting the immune system, its anti-inflammatory action, its antioxidant activity and stimulation of cell growth.

It has been reported that honey stimulates Tlymphocytes in cell culture to multiply, and activates neutrophils. It has also been reported that honey stimulates monocytes in cell cultures to release the cytokines TNF-alpha, IL-1 and IL-6, the cell ‘messengers’ that activate the many facets of the immune response to infection. In addition to stimulation of these leucocytes, honey provides a supply of glucose, which is essential for the ‘respiratory burst’ in macrophages that produce hydrogen peroxide, the dominant component of their bacteria-destroying activity. Furthermore, it provides substrates for glycolysis, which is the major mechanism for energy production in the macrophages, and thus allows them to function in damaged tissue and exudates where the oxygen supply is often poor. The acidity of honey may also assist in the bacteria-destroying action of macrophages, as an acid pH inside the phagocytotic vacuole is involved in killing ingested bacteria.

The anti-inflammatory properties of honey have been well established. It has been observed clinically that when honey is applied to wound, it visibly reduces inflammation. It has also been observed to reduce oedema around wounds and exudates from wounds, both of which result from inflammation. Pain is another feature of inflammation, and honey has been observed to be soothing when applied to wounds. A histological study of biopsy samples from wounds has also shown that there are fewer of the leucocytes associated with inflammation present in the wound tissues. What is responsible for these observations is a direct anti-inflammatory effect, not a secondary effect resulting from the antibacterial action removing inflammation-causing bacteria. The anti-inflammatory effects of honey have been demonstrated in histological studies of wounds in animals where there was no infection involved.

The anti-inflammatory action of honey is potentially very important therapeutically, as the consequences of inflammation can be major. Although inflammation is a vital part of the normal response to infection or injury, when it is excessive or prolonged it can prevent healing or even cause further damage. The anti-inflammatory action of honey has been found in a clinical trial to prevent partial-thickness burns from converting to full thickness burns which would have needed plastic surgery.

The reduction in keloids and scarring that is a feature of the dressing of wounds with honey, and the cosmetically good results obtained, are probably due to the anti-inflammatory action of honey. Thus, there are significant benefits to be derived from therapeutic use of anti-inflammatory substances. However, the pharmaceutical ones have serious limitations: corticosteroids suppress tissue growth and suppress the immune response, and the non-steroidal anti-inflammatory drugs are harmful to cells, especially in the stomach. But honey has an anti-inflammatory action free from adverse side effects.

It has been observed clinically that when honey is used as a wound dressing it promotes rapid healing of wounds. It has been reported by many clinicians that honey promotes the formation of clean healthy granulation tissue (the clusters of fibroblasts around new capillary beds that is the regenerating connective tissue). It has also been reported that honey hastens epithelialization of the wound (coverage with a new outer layer of skin), making skin grafting unnecessary. It is likely that it is the stimulation of cell growth by honey that is responsible for ‘kick-starting’ the healing process observed in chronic wounds which have remained non-healing for long periods.

HARMLESSNESS OF HONEY

Honey has no adverse effects other than a stinging sensation experienced by some people when it is applied to open wounds. A transient stinging sensation and redness of the eye soon after applying honey in the eye, but never enough to stop the treatment, was reported in the 102 cases in a trial of honey for opthalmological use. Over the thousands of years, honey has been used on open wounds and in the eyes. It has not gained any reputation for adverse effects, and this is borne out by histological examination of wound tissues that have been treated with honey. In papers describing the application of honey to open wounds it is reported to be soothing, to relieve pain, be non-irritating, cause no pain on dressing, and give no secondary reactions. Although allergy to antibiotics is fairly common, allergy to honey is rare and it may be a reaction to either the pollen or the bee proteins in honey. There is a hypothetical risk of infection of wounds resulting from the application of honey, as honey sometimes contains viable spores of Clostridia. However, in none of the many reports published on the clinical usage of honey on open wounds there are no reports of any type of infection resulting from the application of honey to wounds. Spores germinate of Clostridia, being obligate anaerobes, would be unlikely to survive in the presence of the hydrogen peroxide that is generated in diluted honey. But any concern about risk of infection can be overcome by the use of honey that has been treated by gamma-irradiation, which kills clostridial spores in honey without loss of any of the antibacterial activity.

There is a hypothetical risk of blood glucose levels in diabetics being raised through glucose being absorbed from honey across the bed of large wounds, but in cases where this has been checked there has been no sign of this happening. Where honey is taken by mouth by diabetics for treatment of gastrointestinal infections the risk is greater, but research has shown that honey gives a lower peak of blood glucose than table sugar does because the absorption from the gut is slower.