Honey as a medicine

Honey has been prized both as a food and medicine since the earliest times.^(1,2)  Traditional medicine practices from around the world have long valued its therapeutic properties, particularly as a remedy for burns, cataracts, ulcers and wound healing.

All honeys are rich in antioxidant, anti-inflammatory and antimicrobial flavonoids, phenolic acids and other bioactive compounds cleverly extracted and manufactured by bees. These contribute to honey’s anti-inflammatory, antibacterial, antiviral, immunomodulatory and anti-allergic activities.^(3-5)

While applications for wound care have become quite well known, clinical trials have also reported beneficial effects of honey intake on cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, and coughs in children.^(6,7)

Different types of honey are classified depending on the floral source and/or the geographical regions from which they derive.

Mānuka honey

Mānuka honey is honey made by bees using nectar from flowers of Leptospermum scoparium, a small native tree which grows abundantly throughout Aotearoa New Zealand. Mānuka is an important plant in rongoā Māori and for medical herbalists here, with its bark, foliage and seeds used to compound preparations for wounds, cuts, sores and skin diseases, colds, coughs and gastrointestinal conditions.^(8,9) Its essential oil, also has multiple anti-inflammatory, antimicrobial and other bioactivities.⁽¹⁰⁾

Apart from being a rich source of glucose, fructose and flavonoids such as quercetin and chrysin found in other honeys, Mānuka honey contains unique chemical compounds such as methylglyoxal (MGO), dihydroxyacetone, leptosperin glyoxal, methyl syringate and leptosin.⁽¹¹⁾

While once regarded as being inferior to other culinary honeys in terms of its taste profile, interest in the medicinal properties of Mānuka honey began to grow during the 1980’s. Its reputation as a health promoting food grew rapidly, a key catalyst being research in the early 1980’s which showed Mānuka honey to have potent antibacterial activities. 

Antimicrobial properties

These were reported against a wide range of different human pathogens, but antibacterial properties against Staphylococcus aureus and the gut pathogen Helicobacter pylori, attracted particular interest for Mānuka honey.^(11-14) With stomach problems being a common human complaint, this research together with anecdotal reports of improvement in various gastrointestinal problems when taking Mānuka honey, lead to increasing demand.

Mānuka honey impregnated dressings have been developed and shown to be effective in wound care and infection management. Successful applications include for diabetic and venous leg ulcers^(16-18) and hospital acquired pressure injuries in critically ill children.⁽¹⁹⁾  These dressings are now being increasingly used by wound care nurse practitioners in Aotearoa New Zealand.

On a global level, much research is ongoing into the antibacterial activities of Mānuka and other honeys.  Numerous scientific papers involving the potential infection control and antimicrobial activities of Mānuka honey have been published over the past year, with several encouraging findings.^(20-26)

Research into the use of medical grade Mānuka honey as a post surgical wound application also continues in a number of countries outside of Aotearoa New Zealand, with encouraging findings.^(28-30) Applications in oral surgery and dentistry, are also receiving increased attention.^{(31, 32)}

Mānuka honey at low concentrations has been reported to kill multidrug-resistant and extensively drug-resistant clinical strains of Salmonella Typhi.⁽²²⁾  Saudi Arabian researchers have also reported activity against carbapenem-resistant Enterobacterales.⁽²¹⁾  Medical researchers in Sweden, have found topical Mānuka honey to reduce the bacterial count of Staphylococcus aureus in a comparable way to an intramuscular antibiotic.⁽³³⁾  They have also advocated potential applications for Mānuka honey as an immediate treatment for war wounds in the field of combat.

 A clinical trial to compare the use of a medical grade honey with the antifungal drug fluconazole for vaginal thrush is currently underway in the Netherlands, and the results will be interesting.⁽³⁴⁾

Honey and Cancer

With rates of cancer increasing steadily as the global population increases and people live longer, research into interventions to help reduce the treatment burden has become more compelling. Interest in potential applications of honey in cancer therapy go back a long way. In fact there are now more than 800 papers and several reviews on honey and cancer in the scientific literature, many with encouraging findings.^(35-42)

In vitro antiproliferative and apoptotic effects for honey have been reported against a large number of different cancer cell types. These include bladder cancer, colon, melanoma, breast, cervical, oral, prostate, hepatic and osteosarcoma cancer.  Several different honey types including Mānuka, thyme, gelam and acacia honeys, have shown such activities.^(43-50) Relevant activities have also been reported in studies involving rat and mice models of different forms of cancer, including breast, colon, bladder and Ehrlich Ascite carcinoma.^{(46, 47, 51-54)}

Mānuka Honey & cancer

Potential applications of Mānuka preparations in cancer patients, were first reported for a gargle using a mix of mānuka and kānuka essential oils diluted in water, bringing relief to mucositis of the oropharyngeal area as a result of radiation treatment for head and neck cancers.⁽⁵⁵⁾

In vitro research by a number of different researchers has found anti-proliferative effects of Mānuka honey on breast, colorectal, breast and melanoma cell lines. Researchers from United Arab Emirates found that Mānuka honey had potent on all three cancer cell lines in a time- and dose-dependent manner, and was effective at concentrations as low as 0.6% (w/v).^{(53, 54)}

They’ve also found improved survival rates of mice with melanoma when Mānuka honey was administered as an injection, alongside treatment with the chemotherapy drug paclitaxel.⁽⁵³⁾ Subject to future parenteral product development and human clinical studies, this study suggests exciting potential applications as an adjunct in cancer chemotherapy.  

Enhanced anti-tumour responses against colorectal cancer in mice have been shown following oral administration of Mānuka honey over a four week period.⁽⁵⁶⁾ These effects were correlated with immunomodulatory activities and changes in the gut microbiota.

In 2017, Malaysian researchers reported inhibitory effects on tumour development for Mānuka and Tualang honeys in a rat model of breast cancer.⁽⁵⁷⁾  Recently American researchers have also revealed inhibitory effects on human breast cancer progression in preclinical models for Mānuka honey. Mānuka honey reduced the proliferation of MCF-7 breast cancer cells but not that of non-malignant human mammary epithelial cells. Antitumor activity was in a similar range to that exerted by treatment of MCF-7 cells with the oestrogenic antagonist tamoxifen, widely used in the management of breast cancer. ⁽⁵⁸⁾

An Italian team has undertaken a considerable amount of research into Mānuka honey’s potential preventive effects against colon cancer. They reported strong inhibitory effects on human colon cancer cells in a dose-dependent manner.⁽⁵⁹⁾  Anti-metastatic impacts on colon cancer stem-like cells, a reduction in the ability of colorectal cancer cells to migrate, and downregulation of pro-angiogenic factors, were revealed as likely mechanisms of Mānuka honey’s activity.^{(60, 61, 62)}

Possible protective effects against prostate cancer cell metastases, have been reported for New Zealand thyme, mānuka and honeydew honeys. Both their phenolic and sugar components, were shown to reduce the cellular adhesion abilities of cancer cells, in this in vitro study.⁽⁶³⁾

With these types of cancers having a high risk of metastases, while clinical studies are needed, these anti-metastatic effects of Mānuka honey, offer much promise.

Mechanisms of action

Several potential mechanisms of action are evident for potential preventive effects of Mānuka honey against cancer development. Oxidative stress and increased levels of free radicals is involved in cancer formation, and Mānuka honey is rich in antioxidant phenolic acids and polyphenols with in vitro antiproliferative activity against several types of cancer.^{(41, 54)}

A low immune status is well known to increase the risk of cancer development. Italian research showing an ability of Mānuka honey to modulate the immune system by inducing immunostimulatory and anti-inflammatory effects, could potentially help with chemoprevention.⁽⁶⁴⁾  It’s antimicrobial actions may also be useful, given that chronic infections such as Epstein-Barr virus, human papilloma virus and Helicobacter pylori, are also associated with a higher risk of cancer development.

Possible Chemotherapy adjunct?

Recent research involving an international team of researchers, has provided evidence of sensitising effects of Mānuka honey to chemotherapy  against colon cancer cells.⁽⁶²⁾ Mānuka honey was associated with downregulation of pro-angiogenic factors, and enhanced the cytotoxicity of 5-fluorouracil. This and other studies by the Italian team suggest a potential of Mānuka honey as an adjunctive intervention to increase the efficacy of this and potentially other anticancer drugs against colon cancer cells.^{(59, 61, 62)}

Protective effects of honey against cisplatin-induced renal toxicity, has been shown both in animals and in patients with cancer.⁽⁶⁵⁾  A recent review found significant evidence for an ability of honey to mitigate toxicity from anticancer chemotherapy toxicity, with multiple mechanisms for this being evident. These included inhibition of oxidative stress and NF-κB-mediated inflammation, the dampening of caspase-dependent apoptosis cascades, and several other potential molecular mechanisms.⁽⁴²⁾  

Oral mucositis

Oral mucositis (stomatitis) is a serious complication of cancer chemotherapy resulting in pain, an inability to eat or drink, and often weight loss. It occurs in a large proportion of paediatric patients being treated for cancer, and in patients undergoing treatment with radiotherapy or chemotherapy for head, neck and breast cancers, and is difficult to treat in clinical practice.

At least fifteen clinical trials have now taken place involving Mānuka and several other honey types from around the world as an oral application for oral mucositis, with most finding positive results.^(66-69) These include a clinical trial using Mānuka honey in children with leukaemia suffering from chemotherapy-induced oral mucositis.⁽⁷⁰⁾

Summary

Honey is a natural product used since ancient times for its nutritive and therapeutic value.  Despite this extensive history, and a huge body of laboratory data now implicating its usefulness for a large number of serious health conditions in humans, clinical applications have been limited until recently, by there being few human trials, and widespread variability in honey quality.

Research is increasingly providing compelling evidence for preventative as well as potential clinical applications of different types of Mānuka honey, in modern medicine. This research, mostly undertaken outside of Aotearoa New Zealand, suggests exciting therapeutic value particularly in the management of infectious disease and cancer, both highly prevalent and expensive conditions which have a high burden on patients and healthcare systems.

Aotearoa New Zealand was the first country in the world to successfully produce and commercialise grades of honey suitable to be prescribed and sold or dispensed for serious medical conditions. Several other countries are now developing or have already developed their own medical honeys, and are putting these through clinical trials for a range of conditions.

In order to retain and further build Aotearoa New Zealand’s international reputation as a country producing some unique health promoting honeys, significant investment and a world class regulatory environment is needed. Therapeutic claims should be legally possible for products which have achieved clinical trial validation and meet quality standards. Without this, further innovation and product development may be compromised, while other countries forge ahead with developments, in what is certain to continue to be a growing global industry.

Given the extent of the many promising preclinical findings into the potential of Mānuka and other honeys to improve outcomes in cancer patients, more controlled clinical studies are needed. They should involve further work on animal models of cancer, as well as pilot clinical studies using phytochemically characterised types of honey, as an adjunctive treatment in patients receiving chemotherapy or radiotherapy.⁽⁹⁾

While much of the Mānuka honey industry here has gone through difficult times in the aftermath of Covid-19 and challenges in export markets, new and ongoing research suggests there is much more to this treasured local natural product, than just its value as a food.

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