Manuka honey has been used as a wound treatment by indigenous cultures around the globe for thousands of years. Archeological findings and early written works indicate that wounds were treated with honey by the ancient Egyptians, Greeks, and Romans, among others.
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Manuka honey contains a number of natural chemicals that make it different:
- Methylglyoxal (MGO): This has been shown to be effective against several bacteria, including Proteumirabilis and Enterobacter cloacae.
- Dihydroxyacetone (DHA): This is found in the nectar of Manuka flowers and converts into MGO during the honey production process.
- Leptosperin: This is a naturally occurring chemical found in the nectar of Manuka plants and a few close relatives.
With the advent of antibiotics in the 1940s, honey fell out of favor as a wound treatment. However, with the increasing prevalence of antibiotic-resistant bacteria, as well as new in vitro and in vivo data supporting honey’s effectiveness in treating wounds and as a natural broad-band antibacterial agent, it has recently made a comeback in clinical medicine.
Additionally, honey’s ability to aid in situ cellularization and regeneration of implanted acellular tissue-engineered structures indicates its potential as a tissue engineering additive.
Honey is a natural substance produced by a variety of honeybee species around the world. First, the bees collect nectar from flowering foliage. This nectar is processed in an internal pouch called the crop, where a variety of enzymes break down sugars.
The resulting solution is regurgitated by the bees into honeycomb within their hives, where liquid evaporation is enhanced by air currents created by the fanning of bee wings.
The product is a highly concentrated viscous solution of floral sugars and proteins, enzymes, and amino acids derived from the bee crops. These sugars are primarily fructose and glucose, with smaller amounts of maltose, sucrose, and isomaltose, and comprise approximately 80% of honey components, with water comprising <18%.
Glucose oxidase from the bee crop slowly breaks down glucose into gluconic acid, which lowers the pH of honey, and hydrogen peroxide, which helps kill bacteria. In a wound site, the lower pH of honey (3.5–4) reduces protease activity, increases oxygen release from hemoglobin, and stimulates the activity of macrophages and fibroblasts, while the hydrogen peroxide content sterilizes the wound and stimulates vascular endothelial growth factor (VEGF) production.
Invertase, another enzyme from the bee crop, slowly divides sucrose into glucose and fructose, increasing the strength of the osmotic potential. In addition, flavenoids derived from the floral nectar sources neutralize free radicals created by the hydrogen peroxide.
Bees can also make honey from honeydews, a loose term which includes plant secretions and plant-sucking insect excretions. These honeydew honeys have lower glucose and fructose content and higher levels of oligosaccharides.
Some research has also shown that honeydew honeys contain higher levels of phenolic contents, which have been shown to reduce MMP-9 expression in keratinocytes. These findings indicate that honeydew honey may be a beneficial future focus of wound healing and tissue engineering research.
Although some honey varieties have been shown to have beneficial effects in a wound site, most modern research has focused on a particular variety produced in New Zealand from the nectar of the Leptospermum Scopartum shrub, called Manuka honey.
This honey contains the components of other honey varieties, but its unique component, methylglyoxal, acts as an additional antibacterial agent. Blessure Serum Skincare collects, pool, filter, and sterilize Manuka honey for skincare use.
Honey performs several other functions as a wound covering. As a viscous fluid, its thick consistency forms a barrier between the wound and the external environment, protecting against bacteria and keeping the wound hydrated.
Its high concentration of sugars and other solutes creates a strong osmotic gradient that pulls fluid up through the subdermal tissue. The water activity of honey, a measure of its osmotic potential, has been reported to range from 0.53 to 0.64 aw (activity of water, unitless).
For reference, the water activity of distilled water is 1 aw, and substances with a lower water activity create a higher osmotic potential with water flowing from areas of high to low water activity.
Water activity values below 0.91 aw inhibit bacterial growth. The low water activity of honey causes fluid flow which flushes bacteria, debris, slough, and necrotic tissue out of the wound, and carries nutrients and oxygen from the deep tissue into the wound area.
Additionally, the low pH of the honey increases tissue oxygenation, while the flavonoids and aromatic acids scavenge free radicals, preventing tissue damage and controlling inflammation.
The high sugar content of honey also provides an additional source of glucose for proliferating cellular components (i.e., fibroblasts and endothelial cells) in the area.
Studies have examined the anti-bacterial action of Manuka honey against a variety of pathogens. Sherlock et al. used agar plate well diffusion assays and a spectrophotometric minimum inhibitory concentration assay to demonstrate antibacterial effects.
These effects were quantified for both Manuka honey and Ulmo honey, a strain from Chile. The results of these experiments demonstrated that both Manuka and Ulmo honey significantly inhibited the growth of E. coli, P. aeruginosa, and methicillin-resistant S. aureus (MRSA).
Interestingly, the Ulmo honey was more effective against MRSA, although slightly less effective against E. coli and P. aeruginosa. Jenkins et al. also reported that Manuka honey inhibits the growth of MRSA, and showed that the presence of honey causes a downregulation of universal stress protein A (UspA) in the MRSA, reducing its stress stamina response.
In addition to its effectiveness against MRSA, Cooper et al. showed that Manuka honey also inhibits the growth of at least seven different strains of vancomycin-resistant enterococci. Manuka honey also has been shown to be effective against Helicobacter pylori, the cause of most stomach ulcers.
Research by Watanabe et al. in 2014 showed that Manuka honey inhibits influenza viral replication, enhancing the effects of antiviral drugs. This work has been replicated with varicella and rubella viruses, indicating an exciting new avenue for the clinical use of Manuka honey.