Manuka Honey Science


Manuka honey is produced predominantly in New Zealand by European honey bees (Apis mellifera) feeding on the Manuka tree flower (Leptospermum scoparium) nectars (Adams 2009).  According to the New Zealand Ministry for Primary Industries, Manuka-type honey has the following, naturally produced, characteristics (NZMPI 2015): 

  1. A color greater than 62 mm pfund. 

  1. A conductivity range of 347-867 µS/cm. 

  1. A flavor typical of Manuka-type honey (mineral, slightly bitter). 

  1. An aroma typical of Manuka-type honey (damp earth, heather, aromatic). 

  1. Presence of Manuka-type pollen. 

  1. Presence of dihydroxyacetone (DHA) and methylglyoxal (MG) 

Manuka Honey Production 
Manuka honey is mainly produced in New Zealand by approximately 3800 bee keepers and over 400,000 hives (Leake 2013).   Figure 2 illustrates a typical Manuka honey apiary, found adjacent to heavily wooded areas.  Some farmers use helicopters to find areas with dense Manuka bushes to aid in hive placement (Leake 2013).  According to Unique Manuka Factor™ Honey Association (UMFHA) data, approximately 1,700 tons of Manuka honey are produced annually in New Zealand, representing almost all of the world's production (Leake 2013).   However, approximately 10,000 tons are being sold internationally as Manuka honey, including 1,800 tons in the UK alone (Leake 2013). Counterfeit issues have become a significant concern with Manuka honey; in one publication, 41 of 73 Manuka honey samples tested from Britain, China and Singapore showed no non-peroxide activity, which is a key feature of Manuka honey (Leake 2013).  


Assessing Manuka Honey’s Purity and Potency  
There are various methods reported for determining and documenting the potency and purity of Manuka honey. Unfortunately, there is a lack of standardization in regards to labeling of Manuka honey, making interpretation and comparison very confusing. In order to better standardize labeling of Manuka honey, new interim guidelines have recently been released by New Zealand’s Ministry for Primary Industries ( ; NZMPI 2015).  Most Manuka honeys are currently labeled with a grading system that include a numerical value and a potency descriptor. Examples of potency descriptors include: active, bioactive, total activity, total peroxide activity, total non-peroxide activity, unique Manuka factor™ (UMF™), and methylglyoxal levels (NZMPI 2015). Third party test results to substantiate label claims are typically not readily available. Recent guidelines have suggested that terms such as “Non-Peroxide Activity”, “Total Peroxide Activity”, “Peroxide Activity”, “Total Activity” and “Active” should be removed from labels and advertising, as these terms involve a therapeutic claim that suggest an antimicrobial effect (NZPMI 2015). Methylglyoxal is thought to be the major contributor to Manuka honey’s non-peroxide antimicrobial activity (Adams 2009).  Levels in honey are typically reported in mg/kg. References to methylglyoxal are permitted on honey labels provided they’re not used to imply antibacterial effects (NZPMI 2015). 

One of the most well-known grading systems for Manuka honey is the Unique Manuka Factor® (UMF®) grade, which is a trademark of the Unique Manuka Factor Honey Association.  The UMFHA is a group of certified licensees (currently 67) that can use the UMF trade mark on their products. To receive a UMF® grading, a honey must have the presence of DHA (dihydroxyacetone), methylglyoxal, and leptosperin. Values typically range from UMF® 5+ to UMF® 28+ that vary with the methylglyoxal level in the honey (see Table 1, UMFHA 2015).  

Manuka Honey Rating (UMF) »

Table 1 – Methylgloxal level and correlating UMF® grading (UMFHA 2015) 

Methylgloxal Level 

UMF™ Grade 

≥83 mg/kg 


≥263 mg/kg 


≥514 mg/kg 


≥573 mg/kg 


≥696 mg/kg 


≥829 mg/kg 


≥1200 mg/kg 


≥1449 mg/kg 



Melissopalynology is the study of pollen in honey. Manuka honey can contain Manuka and Kanuka pollens, which can be difficult to differentiate.  Recent research by NZPMI indicates that although morphological differences between Manuka and Kanuka pollens may be subtle, the two can be differentiated using direct light microscopy and Classifynder™ (NZMPI 2015).   In order for Manuka honey to be classified as a monofloral honey, it must contain >70% Manuka pollens (NZPMI 2015). Manuka pollens alone are not sufficient for the identification of Manuka honey as high pollen counts do not always correlate with contribution of Manuka nectar to the honey (NZPMI 2015). 

A recent publication found that leptosperin, a novel glycoside that is specific to manuka honey, is stable during storage and its measurement may be applicable for Manuka honey authentication (Kato 2014). Leptosperin testing has recently become available to commercial honey producers as a method of determining Manuka honey purity.  PCR testing to detect DNA of L.scoparium is currently being developed and refined to be used on a commercial level for identification of Manuka honey (NZPMI 2015) 

Antioxidant Activity: 
Manuka honey’s antioxidant effects are due to specific scavenging activity for superoxide anion radicals (Inoue 2005).   Methyl syringate has been found to be responsible for part of Manuka honey’s potent antioxidant activity (Inoue 2005) 

Antimicrobial Activity of Manuka Honey 

Significant research has been conducted on the antimicrobial activity of Manuka honey; these studies are limited to either topical application of the honey or to its in vitro antimicrobial activity.  The antimicrobial effects of Manuka honey were first described by Molan and Russell in 1988 and attributed to the honey’s non-peroxide activity.  Honeys have been shown to exhibit their antimicrobial effects through various mechanisms including: osmotic effects, honey acidity, peroxide activity, non-peroxide activity, biofilm inhibition and other antimicrobial compounds including phytochemicals (Molan 1992). 
Osmotic effects 
Osmotic effects from the high level of sugars (including sucrose, glucose, levulose (fructose), and maltose) in honey result in rupture of bacteria (Molan 1992).  In one study on Manuka honey against coagulase negative Staphylococci, the antibacterial activity of natural Manuka honey was approximately 8 times more potent than if bacterial inhibition were due to the osmotic effect alone (French and Cooper 2005).  Several other studies have also illustrated that the antimicrobial effect of Manuka honey is independent of its sugar content (Cooper and Hasisas et al. 2002, Copper and Molan et al. 2002, Henriques et al. 2010)  


Peroxide Activity 

Hydrogen peroxide is proposed to be the main antibacterial compound found in most honeys (Molan 1992). Hydrogen peroxide is generated by action of glucose oxidase in honey. With time, glucose oxidase can become inactivated by heat and light. Therefore, peroxide activity has shorter term stability compared to non-peroxide activity (Molan 1992). 

Non-Peroxide Activity 
Non-peroxide activity is a unique property of Manuka honey and is mainly due to high levels of methylglyoxal (Attrot et al 2012, Mavric et al 2008, Adams 2009).  Methylglyoxal originates from the high levels of dihydroxyacetone present in the nectar of Manuka flowers (Adams 2009).  Methylglyoxal is unique in that it has long- term stability in honey and its levels typically increase with time (Adams 2009).  Methylglyoxal is reported to be the main antimicrobial agent in Manuka honey (Attrot et al 2012, Mavric et al 2008).  However, if methylglyoxal is neutralized, the honey still has antimicrobial effects on various bacterial isolates including E.coliBacillus subtilis and Pseudomonas aeruginosa, but not S.aureus (Kwakman 2011). Also, non-Manuka honeys with methylglyoxal added do not have the same antimicrobial effects as Manuka honey (Jenkins 2011). Methylglyoxal/non-peroxide activity is not inactivated by irradiation; therefore Manuka honey can be sterilized by irradiation for use as a wound dressing (Maddocks 2013). 

Biofilm Inhibition 
Biofilm is an assemblage of surface-associated microbial cells that is enclosed in an extracellular polymeric substance matrix (Alandejani et al. 2009). Conventional oral antimicrobial therapies are often ineffective in eliminating bacteria located in the biofilm and topical therapies may also be ineffective depending on type. Biofilm has been shown to play an important role in the pathogenicity of bacteria like Pseudomonas and Staphylococcus that are commonly incriminated in cutaneous/wound infections (Alandejani et al 2009).   Manuka honey has been shown to inhibit biofilm in various species of bacteria including Staphylococcus aureus, MRSA, C.difficleStreptococcus pyogenesStreptococcus mutansProteus mirabilis, and Enterobacter cloacae (Alandejani et al 2009Maddocks 2012). Methylglyoxal requires other components in Manuka-type honeys for this anti- biofilm activity (Maddocks 2012). Manuka honey have been found to be cidal to 82% of Staph aureus, 67% of MRSA and 91% Pseudomonas biofilms (Alandejani et al 2009). 

Microorganisms Killed by Manuka Honey 
Manuka honey has been shown to have antimicrobial effect against a variety of organisms including Staphylococcus aureus, MRSA, PseudomonasE.coliStreptococcus, Campylobacter, Clostridium dificile and various fungi (dermatophytes and Candida) (Molan 1992, Lin et al 2009, Hammon and Donkor 2013).  The reported MIC (and MBC when available) levels for Manuka honey against various microorganisms are reported below in Table 2.    

Table 2: MIC/MBC levels for Manuka honey against various microorganisms 


MIC (% v/v unless indicated) 

MBC (% v/v unless indicated) 


Clostridium dificle 



Hammon and Donkor 2013 

Pseudomonas aeruginosa 



Cooper et al. 2002 

Pseudomonas aeruginosa 

5.5% - 8.7%  


Cooper and Molan 1999 

Pseudomonas aeruginosa 



Sherlock et al 2010 

Pseudomonas aeruginosa 

9.5% w/v 

12% w/v 

Henriques 2010 

Pseudomonas aeruginosa 

12% w/v 

16% w/v 

Roberts 2012 

Pseudomonas aeruginosa 

15.3% w/v 

15.7 w/v 

Cooper 2010 

Campylobacter jejuni/coli 



Lin et al 2009 




Wilkinson and Cavanagh 




Sherlock et al 2010 




Lin et al 2011 


16.2% w/v 

18% w/v 

Cooper 2010 

Enterobacter aerogenes, Enterobacter cloacae 



Lin et al 2011 

Yersinia enterocolitica 



Lin et al 2011 

Salmonella typhimurium 



Wilkinson and Cavanagh 

Salmonella typhimurium, Mississippi, enteritidis 



Lin et al 2011 

Proteus mirabilis  



Wilkinson and Cavanagh 

Staphylococcus aureus 



Cooper 1999 

Staphylococcus aureus 



Wilkinson and Cavanagh 

Coagulase negative Staphylococci (methicillin resistant and sensitive) 



French and Cooper 2005 

S. epidermidis 

5.7% w/v 

8.3 w/v 

Cooper 2010 




Sherlock et al 2010 


6% w/v 


Jenkins and Cooper 2012 




Cooper 1999, Cooper 2002 


5.83% w/v 

8.5% w/v 

Cooper 2010 

Streptococcus spp and Enterococcus spp 



Cooper 2011 


Manuka Honey’s Anti-Staphylococcal Activity 

The Minimum inhibitory concentration of Manuka honey for Staph aureus varies with the strain and publication (see table 2); Cooper et al.1999 first reported the MIC of 58 Staphylococcus aureus isolates from infected wounds to be 2 - 3% (v/v).   For Staphylococcus aureus, Manuka honey has a bactericidal mode of inhibition (Henriques 2010). Manuka honey prevents cell division of Staph bacteria, resulting in a failure of progression through the cell cycle and accumulation of fully formed septa within the bacteria visible with transmission electron microscopy; the staphylococcal target site of Manuka honey involves the cell division machinery (Henriques 2010).  


Manuka honey has also been shown to be active against coagulase negative Staphylococci, with inhibitory concentrations ranging from 2.7-5% v/v (French 2005).  In that study, there was no significant difference in susceptibility to honey between antibiotic sensitive and antibiotic resistant isolates (French 2005).  In vitro clinical isolates of methicillin-susceptible and methicillin-resistant staphylococci were shown to be equally susceptible to Manuka honey with MICs reported as 3% (v/v) [equivalent to 41000 mg/L or 4.1% (w/v) (Cooper 1999, Cooper 2002); however, other publications report higher MIC levels for MRSA (see table 2).  A decrease in expression of virulence genes has been demonstrated in MRSA isolates exposed to Manuka honey (Jenkins et al. 2013).  Exposure of MRSA to inhibitory concentrations of Manuka honey has been shown to down-regulate mecR1 (Jenkins and Cooper 2012).   Interestingly, sub inhibitory concentrations of honey in combination with oxacillin restored oxacillin susceptibility to MRSA (Jenkins and Cooper 2012).  MRSA isolates exposed to Manuka honey all had impaired cell division similar to what is reported in methicillin sensitive isolates (Jenkins 2011).   


Manuka Honey’s Anti-Pseudomonal Activity 
The MIC (and MBC) of Manuka honey for various Pseudomonas aeruginosa strains has been reported in several publications (Cooper and Molan  1999, Cooper et al. 2002, Henriques 2010).  Manuka honey has bactericidal activity against Pseudomonas as it causes a loss of structural integrity and destabilization of the cell wall resulting in lysis (Henriques 2011).   OprF, an outer membrane protein that is involved in cell wall stability, diffusion and virulence, has been implicated as a possible genetic target for Manuka honey’s activity against Pseudomonas and decreased expression of this protein has been found in Manuka honey treated bacteria (Roberts 2012). Additionally, Manuka honey inhibits siderophore production in Pseudomonaslimiting its ability to capture iron (Kronda 2013).  Manuka honey has also been shown to decrease the adhesion of Pseudomonas to human keratinocytes (Maddock 2013).  Exposure of P. aeruginosa to Manuka honey has also been shown to reduce swarming and swimming motility (Roberts 2015).  This decreased motility was found to be due to de-flagellation of the bacterial cell, correlating with decreased expression of the major structural flagellin protein, FliC, and concurrent suppression of flagellin-associated genes, including fliAfliCflhFfleNfleQ and fleR (Roberts 2015). 

Resistance to Manuka honey 
A recent study (Henriques 2010) evaluated the possibility of Manuka honey resistant by continuously exposing resistant clinical strains of bacteria (MRSA, Pseudomonas and E.coli) from wound infection cases in people to sub-lethal concentrations of Manuka honey for up to 28 days. No honey resistant mutants developed in any of the isolates and viable bacteria were not recovered above the starting MIC values upon repeat exposure (Henriques 2010). 

Manuka honey is produced predominantly in New Zealand by European honey bees (Apis mellifera) feeding on the Manuka tree flower (Leptospermum scoparium) nectars.  High levels of DHA in Manuka flower nectars are converted into methylglyoxal in Manuka honey; the levels of MG increase with time.   Methylglyoxal is the main contributor to non-peroxide activity of Manuka honey, but other compounds and properties of Manuka honey also contribute to its potent antimicrobial effects against a variety of microorganisms commonly encountered in cutaneous infections and wounds.    



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