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P. C. Molan, Honey Research Unit, University of Waikato, Hamilton, New Zealand

Honey - an ancient remedy "rediscovered"

Overview

manuka_honeybeesThe usage of honey as a medicine is referred to in the most ancient written records, it being prescribed by the physicians of many ancient races of people for a wide variety of ailments (Ransome 1937). An editorial in the Journal of the Royal Society of Medicine (Zumla and Lulat 1989) discussing this expressed the opinion "The therapeutic potential of uncontaminated, pure honey is grossly underutilized.” Some examples of the reports being published are given here:

Wound Healing

Cavanagh et al. (1970) described 12 cases of wound breakdown after radical vulvectomy being dressed with honey. The wounds, of a type notoriously difficult to keep free from infection, were found to become sterile in 3– 6 days, have a clean healthy granulating (healing) appearance, required the minimum of surgical removal of dead tissue, and to not need skin grafting as would normally be required. Honey was found to be non-irritant and much more effective than topical antibiotics, the time in hospital being reduced from the usual 7–8 to 3–4 weeks.

Wound and Skin Ulcers

Efem (1988) reported clinical observations on the healing with honey of 59 cases of wounds and skin ulcers that had not been healing for 1–24 months with conventional treatment. The wounds were found to become sterile and odourless in 1 week, pus and gangrenous tissue separating by themselves painlessly. Swelling and exudation of lymph subsided rapidly and there was rapid development of new tissue to repair the wounds. The honey caused no adverse reactions.

Gangrene

Efem (1993) reported a trial where 20 cases of Fournier's gangrene (a form of necrotising fasciitis) were treated by daily application of honey with no surgery, compared with 21 similar cases treated by surgical removal of infected tissue and systemic antibiotics. Similar outcomes were achieved with both treatments but with a faster response to treatment withhoney, the wounds becoming sterile within 1 week with honey, and with the group treated with honey not requiring plastic surgery.

Burns

Subrahmanyam (1991) reported a randomised controlled trial in which honey was compared with silver sulfadiazine for efficacy as a dressing for burns. With silver sulfadiazine, the most widely used agent to prevent or clear infection in burns, 7% of the patients had infection in the burns controlled within 7 days, whereas with honey 91% of the wounds were sterile within 7 days. Honey was observed to remove dead tissue and offensive smell from the burns. Healthy granulation tissue was observed to appear nearly twice as fast with honey, and new skin cover developed faster also. There was better relief of pain, less exudation of lymph, and less irritation with honey. Honey also gave a lower incidence of raised scars and contractures.

Gastroenteritis in Children

Haffejee and Moosa (1985) reported a clinical trial in which honey was used in place of glucose in a rehydration fluid (solution of electrolytes) given to infants and children admitted into hospital with gastroenteritis. The treatment with honey gave a statistically significant reduction in the duration of diarrhoea caused by bacterial infection (58 hours cf 93 hours).

Dyspepsia and Peptic Ulcers

Salem (1981) reported a clinical trial in which 45 patients with dyspepsia were given no medication other than 30ml of honey before meals 3 times daily. After treatment with honey the number of patients passing blood (from peptic ulcers) in their faeces had decreased from 37 to 4; the number of patients with dyspepsia had decreased from 41 to 8; the number of patients with gastritis or duodenitis seen on endoscopy had decreased from 24 to 15; the number of patients with a duodenal ulcer seen on endoscopy had decreased from 7 to 2.

Eye Disorders

Emarah (1982) reported treating with honey 102 patients with a variety of ophthalmological disorders not responding to conventional treatment, such as keratitis, conjunctivitis and blepharitis. The honey was applied under the lower eyelid as eye ointment would be applied. Improvement was seen in 85% of the cases, with no deterioration seen in any of the other 15%. There was reported a transient stinging sensation and redness of the eye soon after putting honey in the eye, but never enough to stop the treatment in any of the cases.

Sore throats.

Laboratory studies are showing the UMF property in UMF Manuka Honey is effective, in vitro, against the bacteria streptococcus pyogenes (causes sore throats). The honey has an anti-inflammatory action as well as an antibacterial action. Therefore Manuka Honey is a 100% natural product and has no known side effects. Active Manuka Honey has antibacterial properties that are known to kill all bacteria including the streptococcus that causes sore throat.

Hancock B M: Microbiology Dept., Waikato Hospital, Hamilton, New Zealand: unpublished findings.
Bacterial Species Manuka Honey Other Honey
Escherichia coli 3.7 7.1
Proteus mirabilis 7.3 3.3
Pseudomonas aeruginosa 10.8 6.8
Salmonella typhimurium 6.0 4.1
Serratia marcescens 6.3 4.7
Staphylococcus aureus 1.8 4.9
Streptococcus pyogenes 3.6 2.6

The bioactivity of honey in wound healingDoctor

There are many reasons why honey has such a good therapeutic effect on wounds, particularly on infected non healing wounds. These have been discussed in detail by Molan (2001b), and are just briefly outlined here:
  • viscosity provides a protective barrier which prevents cross-infection.
  • osmolarity draws fluid out from tissues and creates a moist healing environment. That gives optimum healing as tissue growth not slowed by drying.
  • The sugar content of honey also aids in the rapid removal of malodour from wounds
  • Honey contains the enzyme glucose oxidase which becomes active when honey is diluted and produces hydrogen peroxide (Molan 1992a).
The hydrogen peroxide produced in honey would also be a factor responsible for the rapid rate of healing observed when wounds are dressed with honey. Additional to this nutritional optimisation of the body's immune system, honey enhances immunity through a bioactive effect. Abuharfeil et al. (1999) have found that concentrations of honey as low as 0.1% stimulate the proliferation of lymphocytes in cell culture and activate phagocytes from blood, and Tonks et al. (2001) have found that that honey at a concentration of 1% stimulates monocytes in cell culture to release cytokines which activate the many facets of the immune response to infection. Tonks et al. (2001) also found that monocytes already activated by exposure to mitogens had their production of reactive oxygen species reduced by honey. This is an important bioactivity of honey, as a feedback loop (see Figure 1) allows the reactive oxygen species produced as a consequence of the inflammatory response to destroy bacteria to initiate a greater inflammatory response which can be very deleterious to the healing process. Apart from inflammation creating pain, it causes opening of the circulation which leads to exudation of lymph from open wounds which can be difficult to manage, and oedema in surrounding tissue which can restrict circulation through capillaries and increase diffusional distances from capillaries to tissue cells. This reduces the availability of oxygen and nutrients to cells and thus restricts the cell growth necessary to replace tissues to repair wounds.

Anti Inflammatory property of honey

bee_manuka_flowerIt is probably the very effective anti-inflammatory activity of honey that is responsible for the minimisation of scarring by honey dressings on wounds, although it may also be the antioxidants in honey removing free radicals that is involved. Honey has a direct anti-inflammatory effect, not a secondary effect resulting from the antibacterial action removing inflammation-causing bacteria.

The antibacterial activity of honey

The antibacterial activity of honey was first recognised in 1892, by van Ketel (Dustmann 1979). The studies carried out on this since have been reviewed by Molan (1992b, 1992a). It has been found that mostly the activity is due to the hydrogen peroxide produced enzymically in honey, but there have been some reports of minor additional antibacterial components.

This was unique amongst the many reports on other honeys around the world in that this non-peroxide component was a major contributor to the antibacterial activity, although a subsequent survey of 340 samples of Australian honeys from 78 different floral sources (C. Davis, Queensland Departmentof Primary Industries: personal communication) made a similar finding for honey from jellybush (Leptospermum polygalifolium). This novel antibacterial activity has been subsequently studied to determine the potential usefulness of manuka honey as a therapeutic agent. In this research it has been compared with honey that has the usual type of antibacterial activity due to hydrogen peroxide. In the survey carried out by Allen et al. (1991) a large number of the samples of honey from the different floral sources were found to be of low activity (36% of the samples had activity near or below the level of detection in an agar diffusion assay), the rest having almost a Gaussian distribution over a thirty-fold range of activity. The non-peroxide activity in the samples of manuka honey was found to be similarly distributed. Consequently in the studies on the effectiveness of the antibacterial activity a representative manuka honey and a honey with activity due to hydrogen peroxide were selected to be each near the median level of their respective type of activity. The manuka honey was also selected to have a low level ofactivity due to hydrogen peroxide, and in some of the studies catalase was added to break down any hydrogen peroxide that may have been formed. The results are summarised as follows, expressed as the minimum concentration of honey (% v/v) that will completely stop the growth of each species of microorganism:

Seven common wound-infecting species of bacteria (Willix et al. 1992):
manuka honey: 1.810.8% other honey: 2.67.1%

20 isolates of Pseudomonas from infected wounds (Cooper and Molan 1999):
manuka honey: 5.5–8.7% other honey: 5.8–9.0%

58 clinical isolates of Staphylococcus aureus (Cooper et al. 1999):
manuka honey: 2–3% other honey: 3–4%

82 epidemic strains of MRSA (Allen et al. 2000):
manuka honey: 4–7% other honey: 3–7%

56 strains of VRE (Allen et al. 2000):
manuka honey: 5–10% other honey: 8–20%

20 strains of Burkholderia cepacia isolated from the sputum of cystic fibrosis patients (Cooper et al. 2000):
manuka honey: 2.1–5.0% other honey: 2.8–5.3%

Seven species of dermatophytes commonly causing tineas (Brady et al. 1997):
manuka honey: 10–50% other honey: 520%

7 isolates of Helicobacter pylori from biopsies of gastric ulcers(Al Somai et al. 1994):
manuka honey: 5% other honey: >40%

Twelve species of bacteria commonly causing gastroenteritis(Brady NF and Molan PC: paper in preparation):
manuka honey: 2–11% other honey: 3–8%

Seven species of bacteria commonly causing mastitis in dairy cattle (Allen and Molan 1997):
manuka honey: 5–10% other honey: 5–10%

These results all show that the activity is sufficient to expect a good therapeutic antibacterial action if the honey were used clinically.

Results from clinical usage of manuka honey

Using manuka honey with a 'Unique Manuka Factor' rating of 12, have reported healing wounds infected with MRSA (Dunford et al. 2000b, Betts and Molan 2001b, Natarajan et al. 2001). Another, also using manuka honey with a 'Unique Manuka Factor', rating of 12, reported rapidly healing widespread serious skin ulcers resulting from meningococcal septicaemia that were heavily infected with Pseudomonas, Staphylococcus aureus and Enterococcus and had not responded to all modern conventional treatments over a period of 9 months in intensive care (Dunford et al. 2000a). Also, Cooper et al. (2001) have reported a case of hidradenitis suppuritiva that had been giving recurrent abscesses for 22 years and had given a non-healing wound for the past 3 years that had had three attempts at surgical removal of infected tissue and a wide range of antibiotics, antiseptics and wound dressings. This was healed (with no recurrence of infection in the two years since) within 1 month by dressing with manuka honey with a 'Unique Manuka Factor' rating of 13.

Another case reported was of a large wound from surgical removal of an area of necrotising fasciitis which was heavily infected with Pseudomonas after surgery so could not have a skin graft applied: this was rapidly cleared of infection by application of a dressing of manuka honey with a 'Unique Manuka Factor' rating of 12 then successfully skin grafted (Robson et al. 2000). Betts and Molan (2001b) have reported a trial using manuka honey with a 'Unique Manuka Factor' rating of 12 on a wider range of types of infected wounds (venous leg ulcers, leg ulcers of mixed aetiology, diabetic foot ulcers, pressure ulcers, unhealed graft donor sites, abscesses, boils, pilonidal sinuses, and infected wounds from lower limb surgery). Infection was rapidly cleared and all wounds were healed successfully other than ones where there was an underlying failure in arterial blood supply creating non-viable tissue.

Conclusions from the Waikato Honey Research Unit

bee_manukaThe establishment by research that there are bioactive components in honey, and the wide dissemination of this knowledge, has led to a general acceptance that honey is a respectable therapeutic agent, and to a rapidly increasing uptake of its usage by clinicians as well as by the general public. The finding that there are multiple bioactive components involved in the therapeutic action makes it a much more attractive option to use the natural product rather than to attempt to identify individual active components and use synthesised copies of those.