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Medical Mycology May 2006, 44, 289 /291

Short Communication

Honey has an antifungal effect against Candida species


JULIE IRISH*, DEE A. CARTER*, TAHEREH SHOKOHI$ & SHONA E. BLAIR*
*School of Molecular and Microbial Biosciences, University of Sydney, New South Wales, Australia, and $Department of
Medical Mycology and Parasitology, Mazandaran University of Medical Sciences, Sari, Iran

The incidence of Candida infections is escalating worldwide. The serious nature of


these infections is compounded by increasing levels of drug resistance. We report
that certain honeys have significant antifungal activity against clinical isolates of
Candida species. Importantly, the minimum inhibitory concentration of these
honeys would be achievable in a clinical setting.
Keywords

honey, Candida, antifungal effect

Introduction
Honey has been used as a medicine for thousands of
years, and has been found to be an effective antimicrobial agent [1]. This antimicrobial activity stems
primarily from the production of hydrogen peroxide
from glucose and oxygen by glucose oxidase, a beederived enzyme [2]. Honey from certain species of
Leptospermum flora native to Australia and New
Zealand contains additional phytochemical components that further enhance its antibacterial activity
[3]. The precise nature of these components is yet to be
identified.
Although several in vitro studies have demonstrated
the antibacterial properties of honey [3 /5], few have
examined the action against fungi. The incidence of
fungal infections is increasing in both the community
and hospital environments, with Candida spp. among
the leading organisms. Candida albicans causes oral
infections, over 50% of candidaemia cases [6 /9]
and more than 90% of vaginal candidiasis [10,11].
Recently there have been increased reports of non-C.
albicans Candida species in clinical studies. Candida
glabrata has become the dominant non-C. albicans
Candida species involved in bloodstream and vaginal
infections [9,12/14], while Candida dubliniensis is often
implicated in oropharyngeal candidiasis [15]. Infection

Received 8 August 2005; Accepted 17 October 2005


Correspondence: Julie Irish, School of Molecular and Microbial
Biosciences, Building G08, University of Sydney, New South Wales,
2006, Australia. Tel: /61 2 9351 6041; Fax: /61 2 9351 4571; E-mail:
j.irish@mmb.usyd.edu.au

2006 ISHAM

with non-C. albicans Candida species has important


clinical implications, as many are resistant to conventional triazole-based antifungal therapy. Other conventional antifungal therapies are either toxic or of limited
efficacy, and there is a growing need for new potent
antifungal agents. The aim of the current study was to
determine the efficacy of various honeys against clinical
isolates of C. albicans, C. glabrata and C. dubliniensis.

Materials and methods


Clinical isolates of C. albicans, C. glabrata and C.
dubliniensis were tested against four different honeys:
an unprocessed Jarrah honey with hydrogen peroxide
activity (total antibacterial activity (as described in
[16]) equivalent to 30.2% phenol [17]); Medihoney
Antibacterial Honey Barrier, a proprietary blend of
Leptospermum and hydrogen peroxide honeys (phytochemical activity ]/18% phenol equivalent); Comvita
Wound Care 18/, a pure Leptospermum honey
(phytochemical activity ]/18% phenol equivalent);
and an artificial honey, used to simulate the high sugar
levels found in honey (7.5 g sucrose, 37.5 g maltose,
167.5 g glucose, and 202.5 g fructose in 85 ml of sterile
water).
The minimum inhibitory concentration (MIC) of
each honey was determined based on the NCCLS
microdilution method [18]. Fifty percent (w/v) stock
solutions of honey in RPMI-1640 medium (with
glutamine and without bicarbonate (Sigma)) were
prepared immediately before each assay and filter
sterilised through 0.2 mm pore filters (Millipore). Stock
solutions were further diluted with RPMI-1640
DOI: 10.1080/13693780500417037

290

Irish et al.

medium in 96-well microtitre plates to give final


honey concentrations that increased in 1% (w/v)
increments. Suspensions of Candida isolates were
prepared in sterile 0.85% saline and transmittance at
530 nm was adjusted to 80/88%. Suspensions were
diluted in RPMI-1640 medium, and 25 ml was added to
each well of the microtitre plate immediately after
preparation of the honey solutions, resulting in a final
inoculum of 0.5 /2.5 /103 cfu/ml. Following incubation at 35oC for 24 h, the MIC was recorded as the
lowest concentration of honey that prevented visible
growth. Each Candida isolate was tested in duplicate
and the assays were repeated on a separate day. The
Mann-Whitney U test was used to evaluate statistically
significant groups. Correlations were performed using
the Spearman rank-order test.

Results
Results of the susceptibility of C. albicans, C. glabrata ,
and C. dubliniensis to various honeys are shown in
Table 1. Jarrah honey was significantly more active
against the three Candida species (P B/ 0.00001). The
antifungal activities of the floral honeys were significantly greater than the artificial honey against C.
albicans and C. glabrata (P B/ 0.002), but for C.
dubliniensis, only Jarrah honey was significantly more
active (P B/ 0.00001). C. dubliniensis was more susceptible to the osmotic effect of all honeys, and to the
antifungal effects of Jarrah honey, exhibiting significantly lower MICs than the other species (P B/
0.00001). C. glabrata , which is innately less susceptible
to many conventional antifungals [19], was the least
susceptible to the honeys tested (P B/ 0.00001).
Drug resistance profiles were available for 20 of the
isolates. Twelve of these were either resistant or
Table 1 Susceptibility of Candida species to different honey typesa
Candida species (n )

Jarrah
Medihoney
Antibacterial
Honey Barrier
Comvita Wound
Care 18/
Artificial honey
a

C. albicans
(18)

C. glabrata
(10)

C. dubliniensis
(10)

18.59/2.7**
38.29/2.9**

29.99/2.8**
43.19/4.2*

15.49/2.8**
34.69/2.5

39.99/1.7**

42.69/2.8**

33.49/2.5

42.69/1.8

44.79/2.7

34.39/2.4

Values show mean minimum inhibitory concentration (% (w/v)


honey)9/standard deviation.
*PB/ 0.002; **PB/ 0.00001. P values assessed in comparison to
artificial honey.

susceptible-dose dependent to itraconazole and/or fluconazole. All of these isolates were inhibited by honey,
with no statistical relationship between antifungal
susceptibility and sensitivity to honey (P / 0.05).

Discussion
Limited observations have found honey to have an
inhibitory effect against C. albicans in vitro [20 /22],
however none of these studies used standardized
honeys or assay methods. Only one published study
has used honey with known phenol-equivalent activity
to examine antifungal activity [23]. In this study the
effects of pasture honey were compared with Leptospermum honey against dermatophyte fungi. In accordance with the results of the current study the hydrogen
peroxide-type honey was found to have a greater
antifungal effect.
The current study found no statistical relationship
between antifungal susceptibility and sensitivity to
honey. This is of particular importance considering
the increasing rate of resistance to azole drugs among
Candida isolates [8,24,25], and the finding that azolebased prophylaxis increases the risk of infection with
non-C. albicans Candida species, which may be less
responsive to usual drug dosages [6,24].
Although this study demonstrates the antifungal
effect of honey in vitro there are some practical
considerations for its use in vivo. Firstly, honey is
limited to topical treatments, and could not be used to
treat candidaemia, the most serious form of candidiasis. However, as the leading risk factor for bloodstream
infection is colonization or infection of external sites,
such as indwelling catheters, or the oral or vaginal
mucosae [19], honey may be used prophylactically to
prevent more serious infections. Whole honey placed
directly around catheters was found to be at least as
effective as povidone iodine [26] or mupirocin [27] in
preventing exit site infection. Secondly, as honey is
water soluble, it may be diluted or removed by body
fluids, particularly saliva in the oral cavity. A pilot
study by English et al . [28] found a significant
reduction in mean plaque scores and bleeding sites in
patients given a chewable honey leather; this same
technique could be applied for the treatment of oral
candidiasis. At other body sites, regular application of
100% honey would maintain a concentration well
above the desired MIC. Honey could also be incorporated into a pessary for the treatment of vaginal
candidiasis. Another practical issue is the presence of
catalase in body fluids that has the potential to reduce
hydrogen peroxide activity. However, case reports and
clinical trials suggest sufficient activity is retained to
2006 ISHAM, Medical Mycology, 44, 289 /291

Antifungal effects of honey against Candida

allow honey to be effective in the clinical setting [29,30].


The results of the current study argue for controlled
clinical trials to establish honey as a topical antifungal
agent.

12

13

Acknowledgements
This work was supported by the Rural Industries
Research and Development Corporation Honeybee
Committee grant number US-128. Clinical isolates
were kindly provided by Westmead Hospital Institute
of Clinical Pathology and Medical Research, Sydney,
Australia; and Mazandaran University of Medical
Sciences, Sari, Iran. Honey samples were kindly
provided by Medihoney Pty. Ltd., Queensland, Australia; Comvita Medical Ltd., Te Puke, New Zealand;
and the Western Australian Beekeepers Association.

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