Manuka Honey Bibliography

Allen, K. L., Molan P.C. & Reid G.M. (1991). “A survey of the antibacterial activity of some New Zealand honeys.” Journal Of Pharmacy and Pharmacology 43(12), 817-822. Abstract. To assess the variation in antibacterial activity of honey a survey was carried out on 345 samples of unpasteurized honey obtained from commercial apiarists throughout New Zealand. Most of the honeys were considered to be monofloral, from 26 different floral sources. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay, with reference to phenol as a standard. Antibacterial activity was found to range from the equivalent of less than 2% (w/v) phenol to 58% (w/v) phenol, with a median of 13.6 and a standard deviation of 12.5. Neither the age of the honey samples nor whether they had been processed by the apiarist was associated with lower activity. However, the difference between floral sources in the antibacterial activity was very highly significant. Kanuka (Kunzea ericoides (A. Rich.) J. Thompson. Family: Myrtaceae), manuka (Leptospermum scoparium J. R. et G. Forst. Family: Myrtaceae), ling heather (Calluna vulgaris (L.) Hull. Family: Ericaceae) and kamahi (Weinmannia racemosa Linn. f. Family: Cunoniaceae) were shown to be sources likely to give honey with high antibacterial activity. When antibacterial activity was assayed with catalase added to remove hydrogen peroxide, most of the honeys showed no detectable antibacterial activity. Only manuka and vipers bugloss (Echium vulgare L. Family: Boraginaceae) honeys showed this type of activity in a significant proportion of the samples. The high antibacterial activity of manuka honey was in many cases due entirely to this non-peroxide component.

Betts, J.A. & Molan, P.C. (2002) " Results of a pilot trial of manuka honey as a dressing for infected chronic wounds." - a paper presented at the 4th Australian Wound Management Association Conference, Adelaide, Australia.

Bignall J. (2003) "Honey & Heliobacter" The Lancet 342(8875), 858.

Brady N.F., Molan P.C. & Harfoot C.G. (1996) “The Sensitivity of Dermatophytes to the Anti-Microbial Activity of Manuka Honey & Other Honey.” Pharm. Sciences 2(10), 471-473. Abstract. Honey has been reported to have anti-fungal activity and so was tested against clinical isolates of the common dermatophyte species which cause tineas in man. A honey with an average level of hydrogen peroxide and a manuka (Leptospermum scoparium J.R. & G. Forst, Fam. Myrtaceae) honey with an average level of non-peroxide antibacterial activity were used. An agar well diffusion assay was used, the contents of the wells being replaced with freshly prepared honey solutions at 24h intervals over 3-4 days of incubation. The lowest concentrations (% v/v, in steps of 5%) of manuka honey with catalase added to remove hydrogen peroxide, and of the other honey (without catalase) showed that the inhibition of growth around the walls were, repectively Epidermophyton floccosum 25%,10%, Microsporum canis 25%,15%, Microsporum gypseum 55%, 20%, Trichophyton mentagrophytes var. interdigitale 45%, 15%, Trichophyton mentagrophytes var. mentagrophytes 25%,15%, Trichophyton rubrum 20%, 5%, Trichophyton tonsurans 25%, 20%. No inhibitory activity was detected with the other honey at 50% (v/v) with catalase added. The results of this investigation show that the common dermatophytes are sensitive to the antimicrobial activity of honey, indicating that clinical evaluation of honey in the treatment of tineas is warranted. This would determine whether the hydrogen peroxide or the non-peroxide antifungal agent diffuses better into the skin.

Casey G. & van Rij A. (1997) “Manuka honey & leg ulcers.” New Zealand Med. J. 110(1045), 216.

Chambers J. (2006). “Topical manuka for MRSA-contaminated skin ulcers.” Palliat Med. 20(5), 557.

Cooper R.A. & Molan P.C. (1999). “The use of honey as an antiseptic in managing Pseudomonas infection.” J. Wound Care 8(4), 161-164. A laboratory study was undertaken to extend existing knowledge about the effectiveness of the antibacterial properties of honey against pseudomonads. To date, sensitivity testing has used non-standardised honeys, which may vary greatly in their antibacterial potency. Pure cultures of Pseudomonas spp, isolated from swabs from 20 infected wounds, were inoculated on the surface of nutrient agar plates containing various concentrations of honey in the medium. Two types of honey were used, a manuka honey and a pasture honey, each selected to have antibacterial activity close to the median for each type. The minimum inhibitory concentration of the manuka honey for the 20 isolates ranged from 5.5-8.7% (v/v) (mean 6.9% (v/v), standard deviation 1.3). The minimum inhibitory concentration of the pasture honey for the 20 isolates ranged from 5.8-9.0% (v/v) (mean 7.1% (v/v), standard deviation 1.0). Honeys with an average level of antibacterial activity could be expected to be effective in preventing the growth of pseudomonads on the surface of a wound even if the honey were diluted more than ten-fold by exudation from the wound.

Cooper R.A. Molan P.C. & Harding K.G. (1999). “Anti-bacterial activity of honey against strains of Staphylococcus aureus from infected wounds.” J. R. Soc. Med. 92(6), 283-285. Abstract.The antibacterial action of honey in infected wounds does not depend wholly on its high osmolarity. We tested the sensitivity of 58 strains of coagulase-positive Staphylococcus aureus, isolated from infected wounds, to a pasture honey and a manuka honey. There was little variation between the isolates in their sensitivity to honey: minimum inhibitory concentrations were all between 2 and 3% (v/v) for the manuka honey and between 3 and 4% for the pasture honey. Thus, these honeys would prevent growth of S. aureus if diluted by body fluids a further seven-fold to fourteen-fold beyond the point where their osmolarity ceased to be completely inhibitory. The antibacterial action of the pasture honey relied on release of hydrogen peroxide, which in vivo might be reduced by catalase activity in tissues or blood. The action of manuka honey stems partly from a phytochemical component, so this type of honey might be more effective in vivo. Comparative clinical trials with standardized honeys are needed.

Cooper R.A., Molan P.C., Krishnamoorthy L. & Harding K.G. (2001) “Manuka honey used to heal a recalcitrant surgical wound.” Eur J. Clin. Micobiol Infect Dis. 20(10), 758-9.

Cooper R.A. Molan P.C. & Harding K.G. (2002) “The `sensitivity to honey of Gram-positive cocci of clinical significance isolated from wounds.” J. Applied Microbiol 93(5), 857-63. Abstract.AIMS: To determine the sensitivity to honey of Gram-positive cocci of clinical significance in wounds and demonstrate that inhibition is not exclusively due to osmotic effects. METHODS AND RESULTS: Eighteen strains of methicillin-resistant Staphylococcus aureus and seven strains of vancomycin-sensitive enterococci were isolated from infected wounds and 20 strains of vancomycin-resistant enterococci were isolated from hospital environmental surfaces. Using an agar incorporation technique to determine the minimum inhibitory concentration (MIC), their sensitivity to two natural honeys of median levels of antibacterial activity was established and compared with an artificial honey solution. For all of the strains tested, the MIC values against manuka and pasture honey were below 10% (v/v), but concentrations of artificial honey at least three times higher were required to achieve equivalent inhibition in vitro. Comparison of the MIC values of antibiotic-sensitive strains with their respective antibiotic-resistant strains demonstrated no marked differences in their susceptibilities to honey. CONCLUSIONS: The inhibition of bacteria by honey is not exclusively due to osmolarity. For the Gram-positive cocci tested, antibiotic-sensitive and -resistant strains showed similar sensitivity to honey. SIGNIFICANCE AND IMPACT OF THE STUDY: A possible role for honey in the treatment of wounds colonized by antibiotic-resistant bacteria is indicated.

Cooper R.A., Halas E. & Molan P.C. (2002) “The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns.” J. Burn Care Rehab. 23(6), 366-370. Abstract. Because there is no ideal therapy for burns infected with Pseudomonas aeruginosa there is sufficient need to investigate the efficiency of alternative antipseudomonal interventions. Honey is an ancient wound remedy for which there is modern evidence of efficacy in the treatment of burn wounds, but limited evidence for the effectiveness of its antibacterial activity against Pseudomonas. We tested the sensitivity of 17 strains of P. aeruginosa isolated from infected burns to two honeys with different types of antibacterial activity, a pasture honey and a manuka honey, both with median levels of activity. All strains showed similar sensitivity to honey with minimum inhibitory concentrations below 10% (vol/vol) both honeys maintained bactericidal activity when diluted more than 10-fold. Honey with proven antibacterial activity has the potential to be an effective treatment option for burns infected or at risk of infection with P. aeruginosa.

Dixon B. (2003) “Bacteria can’t resist honey.” The Lancet Infectious Diseases 3(2), 116.

English H.K., Pack A.R. & Molan PC. (2004). “The effects of manuka honey on plaque & gingivitis: a pilot study.” J. Int. Acad. Peridontol. 6(2), 63-67. Abstract: Research has shown that manuka honey has superior antimicrobial properties that can be used with success in the treatment of wound healing, peptic ulcers and bacterial gastro-enteritis. Studies have already shown that manuka honey with a high antibacterial activity is likely to be non-cariogenic. The current pilot study investigated whether or not manuka honey with an antibacterial activity rated UMF 15 could be used to reduce dental plaque and clinical levels of gingivitis. A chewable "honey leather" was produced for this trial. Thirty volunteers were randomly allocated to chew or suck either the manuka honey product, or sugarless chewing gum, for 10 minutes, three times a day, after each meal. Plaque and gingival bleeding scores were recorded before and after the 21-day trial period. Analysis of the results indicated that there were statistically highly significant reductions in the mean plaque scores (0.99 reduced to 0.65; p=0.001), and the percentage of bleeding sites (48% reduced to 17%; p=0.001), in the manuka honey group, with no significant changes in the control group. Conclusion: These results suggest that there may be a potential therapeutic role for manuka honey confectionery in the treatment of gingivitis and periodontal disease.

French V.M. Cooper R.A. & Molan P.C. (2005) “The anti-bacterial action of honey against coagulase-negative Staphylococci. “ J. Antimicrob. Biochem. 56(1), 228-231. Abstract. OBJECTIVES: Development of anti-biotic resistant strains of coagulase-negative Staphylococci has complicated the management of infections associated with the use of invasive medical devices, and innovative treatment and prophylactic options are needed. Honey is increasingly being used to treat infected wounds, but little is known about its effectiveness against coagulase-negative Staphylococci. The aim of this study was to determine the minimum active dilution of two standardised representative honeys for 18 clinical isolates of coagulase-negative Staphylococci. METHODS: An agar incorporation technique was used to determine the minimum active dilution, with dilution steps of 1% (v/v) [or steps of 5%v/v of a sugar syrup matching the osmotic effects of honey]. The plates were inoculated with 10 microl. spots of cultures of the isolates. RESULTS: The honeys were inhibitory at dilutions down to 3.6 +/- 0.7% (v/v) for the pasture honey, 3.4 +/- 0.5% (v/v) for the manuka honey, and 29.9 +/- 1.9 for the sugar syrup. CONCLUSIONS: Typical honeys are about eight times more potent against coagulase-negative Staphylococci than if bacterial inhibition was due to their osmolarity alone. Therefore, honey applied to the skin at the insertion points of medical devices may have a role in the treatment or prevention of infections by coagulase-negative Staphylococci.

Gethin G. & Cowman S. (2005) “Case series of use of Manuka honey in leg ulceration.” Int. Wound. J. 2(1), 10-15. Abstract. The historical and current literature reports the successful use of honey to manage a diversity of wound aetiologies. However, only in the last 40 years is research on its mode of action and contribution to wound healing being investigated. The challenge of managing chronic non healing wounds generated interest in researching non standard therapies. The aims of the study were to gain insight into the practical use of Manuka honey in wound management. The objective was to test the feasibility of further rigorous research into the use of honey in the management of chronic wounds. Instrumental case series were used to examine the use of Manuka honey in eight cases of leg ulceration. To collect the necessary data, photographs, acetate tracings, data monitoring and patient comments and observations were used to add greater reliability and validity to the findings. The wounds were dressed weekly with Manuka honey. The results obtained showed three males and five females with ulceration of different aetiologies were studied. A mean initial wound size for all wounds of 5.62 cm(2) was obtained. At the end of four-week treatment period, the mean size was 2.25 cm(2). Odour was eliminated and pain reduced. The conclusions drawn were that the use of Manuka honey was associated with a positive wound-healing outcome in these eight cases. Arterial wounds showed minimal improvement only.

Lusby P.E. Coombes A. & Wilkinson J.M. (2002) “Honey: a potent agent for wound healing?” J. Wound Ostomy Continence Nurs. 29(6), 273-274. Abstract. Although honey has been used as a traditional remedy for burns and wounds, the potential for its inclusion in mainstream medical care is not well recognized. Many studies have demonstrated that honey has antibacterial activity in vitro, and a small number of clinical case studies have shown that application of honey to severely infected cutaneous wounds is capable of clearing infection from the wound and improving tissue healing. The physicochemical properties (e.g. osmotic effects and pH) of honey also aid in its antibacterial actions. Research has also indicated that honey may possess anti-inflammatory activity and stimulate immune responses within a wound. The overall effect is to reduce infection and to enhance wound healing in burns, ulcers, and other cutaneous wounds. It is also known that honeys derived from particular floral sources in Australia and New Zealand (Leptospermum spp.ma) have enhanced antibacterial activity, and these honeys have been approved for marketing as therapeutic honeys (Medihoney and Active Manuka honey). This review outlines what is known about the medical properties of honey and indicates the potential for honey to be incorporated into the management of a large number of wound types.

Lusby P.E., Coombes A.L. & Wilkinson J.M. (2005). “Bacterial activity of different honeys against pathogenic bacteria.” Arch. Med. Res. 36(5), 464-467. Abstract. Renewed interest in honey for various therapeutic purposes including treatment of infected wounds has led to the search for new antibacterial honeys. In this study we have assessed the antibacterial activity of three locally produced honeys and compared them to three commercial therapeutic honeys (including Medihoney and manuka honey). METHODS: An agar dilution method was used to assess the activity of honeys against 13 bacteria and one yeast. The honeys were tested at five concentrations ranging from 0.1 to 20%. RESULTS: Twelve of the 13 bacteria were inhibited by all honeys used in this study with only Serratia marcescens and the yeast Candida albicans not inhibited by the honeys. Little or no antibacterial activity was seen at honey concentrations <1%, with minimal inhibition at 5%. No honey was able to produce complete inhibition of bacterial growth. Although Medihoney and manuka had the overall best activity, the locally produced honeys had equivalent inhibitory activity for some, but not all, bacteria. CONCLUSIONS: Honeys other than those commercially available as antibacterial honeys can have equivalent antibacterial activity. These newly identified antibacterial honeys may prove to be a valuable source of future therapeutic honeys.

McGovern D.P., Abbas S.Z., Vivian G. & Dalton H.R. (1999) “Manuka honey against Heliobacter pyroli.” J.R. Soc. Med. 92(8), 439.

McIntosh C.D. & Thomson C.E. (2006) “Honey dressing vs. paraffin tulle gras after toe nail surgery.” J. Wound Care 15(3), 133-136. Abstract. OBJECTIVE: Anecdotal reports suggest that certain honey dressings have a positive effect on wound healing. However there is limited empirical evidence supporting its use. This double-blind randomised controlled trial investigated the effect of a honey dressing on a wound healing following toenail surgery with matrix phenolisation. METHOD: Participants (n=100) were randomly assigned to receive either an active manuka honey dressing (n=52) or paraffin-impregnated tulle gras (n=48). The primary outcome was time (days) taken for complete re-epithelisation of the nail bed. RESULTS: Mean healing times were 40.30 days (SD 18.21) for the honey group and 39.98 days (SD 25.42) for the paraffin tulle gras group. Partial avulsion wounds healed statistically significantly faster (p=0.01) with paraffin tulle gras (19.62 days, SD 9.31) than with the honey dressing (31.76 days, SD 18.8) but no significant difference (p=0.21) was found following total avulsion when comparing honey (45.28 days, SD 18.03) with paraffin tull gras dressings (52.03 days, SD 21.3. CONCLUSION: The results suggest that patients may benefit more from paraffin tulle gras dressings than the honey dressings following partial toenail avulsion. No statistically significant difference was found for healing times after total toenail avulsion., although marginal benefits of the honey dressing on these healing times warrants further investigation.

Moar N.T. (1985) “Pollen analysis of New Zealand hone”. New Zealand J of Agric Res. 28(1), 39-70.

Molan P.C., Allen, K. L., Tan, S. T. & Wilkins, A. L. (1989) "Identification of components responsible for the antibacterial activity of Manuka and Viper's Bugloss honeys" paper presented at the Annual Conference of the New Zealand Institute of Chemistry.

Molan P.C. & Allen K.L. (1996) “The effect of gamma-irradiation on the antibacterial activity of honey.” J. Pharm. Pharmacol. 48(11), 1206-1209. Abstract.There is increasing usage of honey as a dressing on infected wounds, burns and ulcers, but there is some concern that there may be a risk of wound botulism from the clostridial spores sometimes found in honey. It is well-established that the antibacterial activity is heat-labile so would be destroyed if honey were sterilized by autoclaving, but the effect of gamma-irradiation on the antibacterial activity of honey is not known. Therefore an investigation was carried out to assess the effect on the antibacterial activity of honey when the honey was subjected to a commercial sterilization procedure using gamma-irradiation (25 kGy). Two honeys with antibacterial activity due to enzymically-generated hydrogen peroxide and three manuka honeys with non-peroxide antibacterial activity were investigated. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay. There was no significant change found in either type of antibacterial activity resulting from this form of sterilization of honey, even when the radiation was doubled (to 50 kGy). Testing of honey seeded with spores of Clostridium perfringens and C. tetani (10000 and 1000 spores g-1 of honey, respectively) showed that 25 kGy of gamma-irradiation was sufficient to achieve sterility.

Molan P.C. (1999) "The unique properties of manuka honey" Bee Informed (The Journal of the American Apitherapy Society) 6 (1): 5-6.

Natajaran S, Williamson D., Grey J., Harding K.G. & Cooper R.A. (2001) "Healing of an MRSA-colonized, hydroxyurea-induced leg ulcer with honey." J. Dermatol. Treat. 12(1), 33-36. Abstract. BACKGROUND: With the ever increasing emergence of antibiotic-resistant pathogens, in particular methicillin-resistant Staphylococcus aureus (MRSA) in leg ulcers, a means of reducing the bacterial bioburden of such ulcers, other than by the use of either topical or systemic antibiotics, is urgently required. METHODS: We report the case of an immunosuppressed patient who developed a hydroxyurea-induced leg ulcer with subclinical MRSA infection which was subsequently treated with topical application of manuka honey, without cessation of hydroxyurea or cyclosporin. RESULTS: MRSA was eradicated from the ulcer and rapid healing was successfully achieved. CONCLUSION: Honey is recognized to have antibacterial properties, and can also promote effective wound healing. A traditional therapy, therefore, appears to have enormous potential in solving new problems.

Patton T., Barret J., Brennan J. & Moran N. (2005). “Use of a spectrophotometric assay for determination of microbial sensitivity to manuka honey.” J. Microbiol Methods 64(1), 84-95. Abstract. The antimicrobial activity of manuka honey has been well documented (Molan, 1992a,b,c, (1997)) [Molan, P.C. (1992). “The antibacterial activity of honey. 1: the nature of the antibacterial activity.” Bee World 73 (1) 5-28; Molan, P.C. (1992). “The antibacterial activity of honey. 2: variation in the potency of the antibacterial activity.” Bee World 73(2) 59-76; Molan, P.C. (1992). “Medicinal uses for honey.” Beekeepers Quarterly 26; Molan, P.C. (1997). “Finding New Zealand honeys with outstanding antibacterial and antifungal activity.” New Zealand Beekeeper 4(10) 20-26]. The current bioassays for determining this antimicrobial effect employ a well diffusion (Ahn & Stiles, 1990) [Ahn, C. & Stiles, M.E. (1990). “Antibacterial activity of lactic acid bacteria isolated from vacuum-packed meats.” Journal of Applied Bacteriology 69, 302-310], (Weston et al., 1999) [Weston, R.J., Mitchell, K.R., Allen, K.L., 1999. “Antibacterial phenolic components of New Zealand manuka honey.” J. Food Chem. 64, 295-301] or disc diffusion (Taormina et al., 2001) Taormina, P. J., Niemira B.A. & Beuchat L.R. (2001). “Inhibitory activity of honey against food borne pathogens as influenced by the presence of hydrogen peroxide and level of antioxidant power. Int. J. Food Microbiol. 69, 217-225] assay using zones of inhibition as indicators of bacterial susceptibility. The development of a 24-h spectrophotometric assay employing 96-well microtiter plates, that is more sensitive and more amenable to statistical analysis than the assays currently employed, was undertaken. This simple and rapid assay permits extensive kinetic studies even in the presence of low honey concentrations, and is capable of detecting inhibitory levels below those recorded for well or disc diffusion assays. In this paper, we compare the assay to both well and disc diffusion assays. The results we obtained for the spectrophotometric method MIC values show that this method has greater sensitivity than the standard well and disc diffusion assays. In addition, inter- and intra-assay variance for this method was investigated, demonstrating the methods reproducibility and repeatability.

Price S.B. (M.Sc.) Isolation of antibacterial components from manuka honey. (Thesis, 1991).

Russell K.M., Molan P.C. & Wilkins A.L. (1990) “Identification of some antibacterial constituents of New Zealand manuka honey.” J. Agric. Food Chem. 34, 10-13.

Sealey D.F (M.Sc.) Chromatographic investigations of the antibacterial activity in manuka honey. (Thesis 1988)

al Somal N., Coley K.E., Molan P.C. & Hancock B.M. (1994) “Susceptibility of Heliobacter pylori to the anti-bacterial activity of manuka honey.” J.R. Soc. Med. 87(1), 9-12. Abstract. Honey is a traditional remedy for dyspepsia, and is still used for this by some medical practitioners although there is no rational basis for its use. The finding that Helicobacter pylori is probably the causative agent in many cases of dyspepsia has raised the possibility that the therapeutic action of honey may be due to its antibacterial properties. Consequently, the sensitivity of Helicobacter pylori to honey was tested, using isolates from biopsies of gastric ulcers. It was found that all five isolates tested were sensitive to a 20% (v/v) solution of manuka honey in an agar well diffusion assay, but none showed sensitivity to a 40% solution of a honey in which the antibacterial activity was due primarily to its content of hydrogen peroxide. Assessment of the minimum inhibitory concentration by inclusion of manuka honey in the agar showed that all seven isolates tested had visible growth over the incubation period of 72 h. prevented completely by the presence of 5% (v/v) honey.

Snow M.J. & Manley-Harris M. (2004) “On the nature of non-peroxide antibacterial activity in New Zealand manuka honey.” Food Chemistry 84(1), 145-147. Abstract. Some conclusions, which exist in the literature about the nature of non-peroxide antibacterial activity in manuka honey, have been revisited. The stability of non-peroxide antibacterial activity in manuka honey at basic pH was investigated. At pH 11 antibacterial activity was immediately and irreversibly destroyed. This indicates that it is not possible to carry out chromatography of honey solutions at elevated pH with the intent to isolate the active fraction. The effect of 10-fold excess of catalase upon the antibacterial assay was examined. No statistical difference in the outcome was observed between the normal amount of catalase and the 10-fold excess. This indicates that non-peroxide antibacterial activity in manuka honey is not likely to be due to residual hydrogen peroxide.

Stephen-Haynes J. (2004) "Evaluation of a honey-impregnated tulle dressing in primary care." Br. J. Community Nurs. June 2004 (Suppl), 21-27. Abstract: Honey has been used for its healing properties for centuries and has been used to dress wounds with favourable results. The emergence of antibiotic resistance and growing interest in "natural" or "complementary" therapies has led to an interest in honey dressings. Much of the research to date has been related to honey's antibacterial properties. However, the healing properties claimed for honey also include stimulating new tissue growth, moist wound healing, fluid handling and promoting epithelialization. Until recently, honey had not been developed as a wound management product and was not a certified pharmaceutical device. Activon Tulle is a sterile, non-adherent dressing impregnated with Leptospermum scoparium honey. The claimed properties of honey dressings would make this a valuable addition to the dressing currently available in the primary care setting. An evaluation was undertaken involving 20 patients with a variety of wounds. A conclusion is drawn that while further research is needed, medical grade honey does appear to be a valuable addition to the wound management formulary.

Tan S.T., Holland P.T., Wilkins A.L., Molan P.C. (1988) “Extractives from New Zealand honeys. White clover, manuka & manuka unifloral honeys.” J. Agric. Food Chem. 36, 453-460. Abstract. Ether extracts were made from aqueous solutions of manuka (Leptospermum scoparium),kanuka (Leptospermumericoides),and clover (Trifolium repens)honeys with use of a continuous liquid/liquid extractor. The components of the extracts were methylated before being separated and identified by gas chromatography and massspectrometry, and alsoby preparative thin-layer chromatography followed by 'H and 13C NMR analyses. A total of 61 different compounds were detected, and 56 of these were

identified. Their concentrations ranged from 0.1 to4000 pg/g. Classes of compounds detected included hydrocarbons (C21-C33) and straight-chain-

monobasic (C8-C23) dibasic, and aromatic acids. The concentration of aromatic acids in manuka and kanuka honeys was much higher than in clover honey. These acids were not present in a chloroform extract of manuka flowers, which contained many terpenes, none of which were present in manuka honey. Compounds reported for the first time in honey include 2-decenedioic, decanedioic, nonanedioic, and octanedioic acids.

Tonks A.J., Cooper R.A., Jones K.P., Blair S., Parton J. & Tonks A. (2003) “Honey stimulates inflammatory cytokine production from monocytes.” Cytokine 21(5), 242-247. Abstract.Clinical observations indicate that honey may initiate or accelerate the healing of chronic wounds and has, therefore, been claimed to have anti-inflammatory properties. The aim of this study was to investigate the effects of honey on the activation state of immunocompetent cells, using the monocytic cell line, MonoMac-6 (MM6), as a model. We investigated the effect of each of the three honeys (manuka, pasture and jelly bush) on the release of important inflammatory cytokines from MM6 cells. These honeys, together with a sugar syrup control (artificial honey), were incubated with MM6 cells at a concentration of 1% (w/v) for 0-24h. Cell culture supernatants were tested using specific ELISA assays for tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta and IL-6. All honeys significantly increased the TNF-alpha, IL-1beta and IL-6 release from MM6 cells (and human monocytes) when compared with untreated and artificial-honey-treated cells (P<0.001). Jelly bush honey significantly induced the maximal release of each cytokine compared with manuka, pasture or artificial honeys (P<0.001).These results suggest that the effect of honey on wound healing may in part be related to the stimulation of inflammatory cytokines from monocytic cells. Such cell types are known to play an important role in healing and tissue repair.

Tonks A.J., Cooper R.A., Price A.J., Molan P.C. & Jones K.P. (2001). “Stimulation of TNF-alpha release in monocytes by honey.” Cytokine 14(4), 240-242. Abstract. Although evidence exists for the antibacterial effects of honey there is limited objective evidence for direct promotion of healing. We investigated the effect of manuka, pasture and an artificial honey on macrophage function. Reactive oxygen intermediate (ROI) production was accessed by luminal enhanced chemoluminescence & tumour necrosis factor (TNF-alpha) release was determined by immunoassay. ROI production was significantly (p<0.001) decreased by pasture honey & manuka honey. TNK-alpha release was significantly enhanced (p<0.001) in unprimed MM6 cells by manuka & pasture honey but was not altered in prime cells. These results could explain the suggested therapeutic properties of honey in promoting wound healing.

Visser F.R., Allen J.R et al. (1988). “The effect of heat on the volatile flavour fraction from a unifloral honey.” J Apicultural Res. 27(3), 175-181

Weston R.J. & Brocklebank R.K. (1999) "The oligosaccharide composition of some New Zealand honeys." Food Chem. 64(1), 33-37. Abstract. The oligosaccharide fraction of samples of manuka (Leptospermum), heather (Calluna), clover (Trifolium) and beech honeydew (Nothofagus) honeys from New Zealand was separated from the monosaccharides and then analysed by high performance anion-exchange chromatography with pulsed amperometric detection (hpaec-pad). Significant oligosaccharide components of manuka honey were isomaltose (or maltulose), kojibiose, turanose (or gentiobiose), nigerose and maltose which was the major component. The composition of clover honey was identical to that of manuka, while heather honey differed from these two only because isomaltose was the major component. Beech honeydew honey was characterised by the complexity of the oligosaccharide composition. The trisaccharides melezitose and panose were the most abundant components. No differences were observed between the oligosaccharide compositions of manuka honeys which did or did not exhibit non-peroxide residual antibacterial activity. Manuka honey was shown to be derived from nectar and not honeydew as has been suggested.

Weston R.J., Mitchell K.R. & Allen K.L (1999) “Anti-bacterial phenolic components of New Zealand manuka honey.” Food Chem 64, 295-301. Abstract. This paper describes several methods for isolation of the antibacterially active phenolic fraction of honey derived from the native New Zealand manuka tree, Leptospermum scoparium (Myrtaceae). This fraction consists of phenolic derivatives of benzoic acids, cinnamic acids and flavonoids, all of which have been identified previously in honeys which do not exhibit non-peroxide residual antibacterial activity. The flavonoids had not previously been identified in manuka honey. Furthermore, the flavonoids were different from those found in the leaves of manuka trees but were the same as those found in European honeys and propolis. While most of these phenolic products possess antibiotic activity, they do not individually or collectively account for the antibacterial activity of ‘active' manuka honey. Essentially all of this activity is associated with the carbohydrate fraction of the honey.

Weston R.J., Brocklebank L.K. & Lu Y. (2000) “Identification & quantitative levels of antibacterial components of some New Zealand honeys.” Food Chem 70(4), 427-435. Abstract.High performance liquid chromatograms of the phenolic fraction of 19 samples of New Zealand manuka honey, some with high levels of non-peroxide antibacterial activity and some with no such activity, were identical, which indicated that phenolic components of this honey are not responsible for the presence or absence of this activity in manuka honey. Similarly, the result showed that geography does not influence the phenolic composition of manuka honey. Antibacterial bee peptides and the antibacterial β-triketone leptospermone were not detected in manuka honey. Methyl syringate constituted approximately 70% w/w of the phenolic fraction of manuka honey and can be regarded as a floral marker for this honey. High performance liquid chromatographic profiles of the phenolic components of manuka, heather, clover and beech honeydew honeys were significantly different and could be used to differentiate honeys if they can be shown to be as consistent as those of manuka honey.

Weston R.J. (2000) “The contribution of catalase & other natural products to the antibacterial activity of honey: a review.” Food Chem 71(2), 235-239. Abstract. Several natural products are collected or manufactured by bees to construct their hive and produce honey. These include beeswax, flower volatiles, nectar, pollen, propolis and honey itself. Some of the components of these materials possess antibacterial properties and are discussed briefly to ascertain their contribution to the antibacterial activity of honey. New Zealand's manuka honey is known to possess a high level of "non-peroxide" antibacterial activity and research to identify the origin of this activity is briefly reviewed. Finally a hypothesis is advanced to explain the phenomenon of "non-peroxide" antibacterial activity in honey. The author concludes that this activity should be interpreted as residual hydrogen peroxide activity, which is probably due to the absence of plant-derived catalase from honey, an idea first suggested by Dustman in 1971. [Dustman, J. H. (1971). “Über die Katalaseaktivität in Bienenhonig aus der Tracht der Heidekrautgewächse (Ericaceae).” Zeitschrift für Lebensmittel-Untersuchung und Forschung, 145, 292–295].

Wilkins, A. L., Lu, Y. & Molan, P. C. (1993) "Extractable organic substances from New Zealand unifloral manuka (Leptospermum scoparium) honeys." Journal of Apicultural Research 32 (1): 3-9.

D.J. Willix (M.Sc.Tech.) A comparitive study of the antibacterial action spectrum of manuka honey and other honey. (1992) - Thesis.

Willix D.J., Molan P.C. & Harfoot C.G. (1992) “A comparison of the sensitivity of wound-infecting species of bacteria to the anti-bacterial activity of manuka honey & other honeys.” J. Appl. Bacteriol. 73, 388-394. Abstract. Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non-peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v).

Wilkins A.L., Lu Y. & Molan P.C. (1993) “Extractable organic substances from New Zealand unifloral manuka Leptospermum scoparium honeys.” J. Agric. Res. 32, 3-9.

Wilkinson J.M. & Cavanagh H.M.A. (2005). “Antibacterial activity of 13 honeys against Escherichia coli & Pseudomonas aeruginosa.” J. of Medicinal Food 8(1), 100-103. Abstract. In this study the activity of 13 honeys, including 3 commercial antibacterial honeys, against Escherichia coli & Pseudomonas aeruginosa was determined. Antibacterial activity of the honeys was assayed using standard well diffusion methods. All honeys, and an artificial honey, were tested at four concentrations (10%,5%,2.5% & 1% wt/vol) against E. coli & P. aeruginosa, and zones of inhibition were measured. All honeys tested had an inhibitory effect on the growth of E. coli & P. aeruginosa, with one honey still having activity against E. coli and three having activity against P. aeruginosa at 2.5%. No honey was active at 1% concentration. E. coli was more susceptible to inhibition by the honeys used in this study than P. aeruginosa. In this study we have demonstrated that several honeys, in addition to the commercial honeys, can inhibit E. coli & P. aeruginosa and may have potential as therapeutic honeys.

Wood B. et al. (1997) “Manuka Honey: a low cost leg ulcer dressing.” New Zealand Medical J. 110(1040), 107.

Yao L., Datta N., Francisco A. Tomás-Barberán F.F., Ferreres M.I. & Singanusong R. (2003). “Flavonoids, phenolic acids and abscisic acid in Australian and New Zealand Leptospermum honeys.” Food Chemistry 81(2),159-168. Abstract. Flavonoids, phenolic acids and abscisic acid of Australian and New Zealand Leptospermum honeys were analyzed by HPLC. Fifteen flavonoids were isolated in Australian jelly bush honey (Leptospermum polygalifolium), with an average content of 2.22 mg/100 g honey. Myricetin (3,5,7,3’,4’,5’-hexahydroxyflavone), luteolin (5,7,3’4’-tetrahydroxyflavone) and tricetin (5,7,3’,4’,5’-pentahydroxyflavone) were the main flavonoids identified. The mean content of total phenolic acids in jelly bush honey was 5.14 mg/100 g honey, with gallic and coumaric acids as the potential phenolic acids. Abscisic acid was quantified as twice the amount (11.6 mg/100 g honey) of the phenolic acids in this honey. The flavonoid profile mainly consisted of quercetin (3,5,7,3’,4’-pentahydroxyflavone), isorhamnetin (3,5,7,4’-tetrahydroxyflavone 3’-methyl ethyl), chrysin (5,7-dihydroxyflavone), luteolin and an unknown flavanone in New Zealand manuka (Leptospermum scoparium) honey with an average content of total flavonoids of 3.06 mg/100 g honey. The content of total phenolic acids was up to 14.0 mg/100 g honey, with gallic acid as the main component. A substantial quantity (32.8 mg/100 g honey) of abscisic acid was present in manuka honey. These results showed that flavonoids and phenolic acids could be used for authenticating honey floral origins, and abscisic acid may aid in this authentication.

Manuka Honey Related Articles.

Mundo M.A., Padilla-Zakour O.I. & Worobo R.W. (2004) “Growth inhibition of foodborne pathogens & food spoilage organisms by select raw honeys.” Int. J. Food. Microbiol. 97(1), 1-8.

Therapeutic Manuka Honey: No Longer So Alternative

Dee A. Carter,1,* Shona E. Blair,2 Nural N. Cokcetin,2 Daniel Bouzo,2 Peter Brooks,3 Ralf Schothauer,4 and Elizabeth J. Harry2

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ESBL	extended spectrum β-lactamase
MBC	minimum bactericidal concentration
MGO	methyl glyoxal
MIC	minimum inhibitory concentration
MRSA	methicillin-resistant Staphylococcus aureus
MRSE	methicillin-resistant Staphylococcus epidermis
NPA	non-peroxide activity
VRE	vancomycin-resistant Enterococcus

Manuka Honey Bibliography

Manuka Honey Related Articles.

Therapeutic Manuka Honey: No Longer So Alternative

Abstract

Introduction

Chemical Analyses of Active Manuka Honey

The Inhibition of Pathogens by Honey

Taking Honey Into Mainstream Medicine: Recent Experimental and Mechanistic Studies Shed Light on How Honey Works

Ultrastructural Studies of Bacterial Cells and Communities Treated by Honey

‘Omics Analyses Assess the Whole-Cell Response to Inhibition by Honey

Interactions Between Honey and Conventional Antibiotics

Evidence of Efficacy From Animal Studies, Case Reports, and Clinical Trials

Gaps and Emerging Opportunities in the Study of Honey

Author Contributions

Conflict of Interest Statement

Abbreviations

Footnotes

References

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