(Jurnal Plastik Rekonstruksi 2016; 2:45-51) WOUND

HONEY AS A TREATMENT FOR DIABETIC FOOT ULCER: A

SYSTEMATIC REVIEW

Ide Bagoes Insani, Nurina Widayanti, Aliyya Rifki

Research Assistant of Lingkar Studi Bedah Plastik, Jakarta, Indonesia

ABSTRACT
Background : Increased number of antibiotic-resistance bacteria has made honey widely reused as a modern wound
treatment, including for Diabetic Foot Ulcer (DFU) treatment. Researchers have studied mean duration of wound
healing and effectivity of honey dressing compared to other substances, such as povidone iodine, normal saline or
alginate. This systematic review was conducted to objectively evaluate mean duration of wound healing using topical
honey dressing compared to other substances in the treatment of DFU.
Method : All RCT and CCT trials were collected from 4 electronic databases using keywords “Honey”, “Honey
dressing”, “Diabetic foot ulcer”, and “Diabetic ulcer”. We included all English literatures with year of publication from
January 2006 to November 2016; studies comparing honey with other substances; and patients with DFUs. Qualitative
assessment of these studies were scored using Jadad Scale.
Result : A total of 5 studies involving 517 participants were included. None of 5 studies obtained full Jadad score in
quality assessment due to lack of description on randomization method, blinding and dropouts. Three studies reported
significantly shorter mean duration of wound healing in honey dressing compared to normal saline and alginate
dressing. Other 2 studies reported insignificant difference compared to povidone iodine, although honey still has
shorter mean duration of wound healing. Two studies reported less pain during dressing changes in honey dressing
group.
Conclusion : Honey dressing was superior than control group (normal saline, alginate, and povidone iodine) in
reducing mean duration of wound healing in DFU patients. It was also proven to cause less pain during dressing
changes. Due to high heterogeneity we are unable to carry out a meta-analysis.
Keywords: diabetic foot ulcers; honey dressing; duration of wound healing; systematic review

Latar Belakang: Meningkatnya jumlah bakteri yang resisten terhadap antibiotik membuat madu kembali digunakan
dalam pengobatan luka modern, termasuk kasus Ulkus Kaki Diabetik (UKD). Para peneliti telah mempelajari rerata
durasi penyembuhan luka dan efektivitas dressing madu dibanding zat lain, seperti povidone iodine, salin normal atau
alginate. Review sistematik ini dibuat untuk mengevaluasi secara objektif rerata durasi penyembuhan luka dengan
madu topikal dibandingkan dengan zat lain dalam pengobatan UKD.
Metodologi: Seluruh penelitian RCT dan CCT diambil dari 4 database elektronik dengan menggunakan kata kunci
“Honey”, “Honey dressing”, “Diabetic foot ulcer”, dan “Diabetic ulcer”. Kami memasukkan seluruh penelitian
berbahasa Inggris dengan tahun publikasi antara Januari 2006 hingga November 2016; penelitian yang
membandingkan madu dengan zat lain; dan pasien dengan UKD. Penilaian kualitas dari penelitian tersebut
menggunakan Jadad Scale.
Hasil: Terdapat total 5 studi dengan 517 peserta. Dari kelima studi tersebut, tidak ada yang mendapatkan nilai Jadad
yang sempurna karena tidak menyebutkan metode randomisasi, penyamaran dan drop out. Tiga penelitian melaporkan
bahwa rerata durasi penyembuhan luka pada dressing madu lebih pendek secara signifikan dibandingkan dengan
dressing larutan salin dan alginate. Dua penelitian lainnya melaporkan bahwa tidak ada perbedaan yang signifikan
antara dressing madu dengan povidon iodin, walaupun dressing madu tetap menunjukkan rerata durasi penyembuhan
luka yang lebih singkat. Dua penelitian melaporkan penggantian dressing madu menimbulkan rasa nyeri yang lebih
ringan. Tidak ada yang mendapatkan nilai penuh dalam penilaian kualitatif karena kurangnya penjelasan mengenai
metode acak, buta dan dropout.
Kesimpulan: Dressing madu lebih unggul dibandingkan grup kontrol (larutan salin, alginate, dan povidone iodine)
dalam menurunkan rerata durasi penyembuhan luka pada pasien UKD. Terbukti pula bahwa rasa nyeri yang
ditimbulkan saat penggantian dressing madu lebih ringan dibanding substansi lain. Heterogenitas muncul akibat
kurangnya jumlah penelitian yang diterbitkan dan tidak adanya standarisasi metode aplikasi madu terhadap luka,
oleh karena itu kami menyarankan penelitian lebih lanjut dalam bidang ini.
Kata Kunci : diabetic foot ulcers; honey dressing; duration of wound healing; systematic review.

Received: 5 September 2016, Revised: 19 September 2016, Accepted: 1 November 2016

ISSN 2089-6492 ; E-ISSN 2089-9734
This Article can be viewed at www.jprjournal.com
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INTRODUCTION However, we are still lacking systematic review on

Honey has been used in wound care since the use of topical honey for diabetic foot ulcers
ancient times. The Egyptians started using honey for treatment. According to this reason, the authors
wound treatment at least since 3000 years BC and it planned this review.
became an important part of the ancient Egyptians
wound care methods1. The introduction of METHOD
antibiotics in modern medicine led to a decrease use The aim of this study was to review and to analyze
of topical honey as wound treatment until recent published randomized controlled trials (RCTs) and
studies reported that antibiotic-resistance bacteria clinical controlled trial (CCTs). The search strategy
including Methicillin Resistant Staphilococcus Aureus was developed in four electronic databases9:
(MRSA) were found in infected wound in the last PubMed, ProQuest, Mendeley, and
few years. As the consequence of misused Perpusnas.go.id. Search terms composed of four
antibiotics and antibiotics resistance, honey is items: “Honey”, “Honey dressing”, “Diabetic foot
widely reused as modern wound treatment. Several ulcer”, and “Diabetic ulcer”. These phrases were
modern studies have proven the benefits of honey combined using Boolean operators “OR” and
for wound treatment. Based on study published by “AND”. Filters have been used to restrict non-
Jurnal Plastik Rekonstruksi (JPR) in 2012, honey has english language publication and to specify year
antibacterial effect towards bacteria such as of publication. All trials were screened by title and
Pseudomonas A., Staphylococcus A. and MRSA2. Due abstract, retrieved potentially relevant articles in
to its moisturizing nature, honey can also accelerate full text, and assessed them for the inclusion
migration of fibroblast, keratinocyte and criteria.
macrophage into the wound3,4. Antibacterial effect Trials eligible for inclusion in this review
of honey is one of the main characteristics profitable were: RCTs and CCTs with year of publication
for wound treatment as it has low osmolarity, low from January 2006 to November 2016 of any
acidity level (pH) and low hydrogen peroxide authors or participating institutions; English
activity2. There are also other benefits of honey as literature; studies comparing between honey (any
wound treatment, such as : inhibits inflammation, resources and concentration) versus other
absorbs exudate and eliminates odors1. substances (pyodine dressing, normal saline
On the other hand, some epidemiological dressing, saline soaked gauze dressing, povidone
studies show tendency of increased incidence and iodine solution 10% diluted with normal saline,
prevalence of Diabetes Mellitus type-I and type-II and alginate dressing); and patient with diabetic
around the world including Indonesia5. WHO foot ulcers. Exclusion criteria in this review
predicts that the number of diabetic patients will includes: (1) Animal and in-vitro studies, (2)
increase in the next few years. In Indonesia Review articles, intervention protocol, discussion
population, WHO predicts that the number of papers, case report, case series, quasi experimental
people with Diabetes Mellitus will increased from study, case-control and retrospective studies, (3)
8.4 million in 2000 to 21.3 million in 20306. Studies involving diabetic patients with pressure
Uncontrolled blood glucose level will lead to ulcer, venous ulcer or other chronic wounds.
complications (15-25%) such as infection, gangrene The quality of all trials were evaluated
and soft tissue-hard tissue (bone) damaged. Diabetic using Jadad Scale. Those articles were assessed for
Foot Ulcer (DFU) is one of the most common randomization, double blinding, and
complications among diabetic patients and it may withdrawals/dropouts. Total score ranged from 0
lead to amputation of the lower leg which will have to 5, with 0 as the lowest score and 5 as the highest
a negative impact on the patient’s quality of life7. score.
DFU also imposes huge burden to the worldwide
health care system with at least 33% of all costs for
diabetic complication treatment was spent for the
treatment of DFU8. Topical honey - for its benefits
(wound healing properties and cost effectiveness) -
is widely used to treat wounds including diabetic Disclosure: The authors have no financial interest to
foot ulcers. There are several randomized controlled disclose.
trials and controlled clinical trial reporting the use of
topical honey for diabetic foot ulcer treatment.

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Outcome parameters of all trials were METHOD

systematically included in the detailed analysis From 311 studies searched through
using RevMan 5.3 from The Cochrane electronic databases, any duplication was
Community and methodological strengths or removed and 276 studies were screened (Figure
weaknesses were identified. Mean duration of 1). We found 45 relevant articles based on their
healing in days were compared as continuous titles and abstracts. From those 45 articles, we
variable. In these studies included, healing was excluded the following: review articles and
judged by focusing on whether the wound was editorial articles (n=12); quasi-experimental (n=1);
clean and ready for closure10,14; complete case report/case series (n=3); in-vitro and
epithelialization with no discharge12; sterile from preclinical studies (n=6); venous ulcer, pressure
microorganisms on swab cultures14; and ulcers ulcer, burn wound (n=14); and studies with no
size (cm2)12. If standard deviations and means comparison (n=1). Eight full text articles assessed
were not provided in the manuscript, we assume for eligibility and 3 full text articles were
the data were normally distributed. excluded (Figure 1) due to incomparable
Consequently, we calculate standard deviation outcomes as such: 1 text article analyzed wound
and mean based on data range and median area per m2 as the outcome and 2 other articles
provided. Heterogeneity was assessed with I2 analyzed infection clearence as the outcome.
recommended by The Cochrane Collaboration. Finally, 5 studies were eligible for qualitative and

Table 1. Database and Research Terminology

No Databases Results Search Term

1 Pubmed 45 ((("diabetic foot ulcer") OR "diabetic ulcer") AND honey) OR "honey

dressing"

3 Mendeley 73 title:Honey abstract:"diabetic foot ulcer" or "diabetic ulcer" or ulcer

discipline:medicine

4 ProQuest 58 ("diabetic foot ulcer" OR " diabetic ulcer") AND honey

5 Perpusnas.go.id 135 ((TitleCombined:(honey)) OR (honey dressing)) AND ((diabetic foot

ulcer) OR (diabetic ulcer))

Table 2. Characteristic of surgery

Jadad Score

Randomised Double Withdraw -1 if use -1 if use

No Study Total
Blind als/ innapropriate use innapropriate
Dropouts of randomization method of
blinding

1 Agarwal, 2015 1 0 0 0 0 1
10

2 Eldeen, 2012 11 1 0 0 0 0 1

3 Imran, 2015 12 2 0 1 0 0 3

4 Kamaratos, 1 1 0 -1 0 1
2012 13

5 Shukrimi, 2008 1 0 0 0 0 1
14

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Records identified through

electronic database searching
(n=311)

Records after duplication Articles excluded (n=37):

removed (n=276) • Review articles and
editorial (n=12)
• Quasi-experimental
(n=1)
• Case report/case series
(n=3)
Records screened • In-vitro and preclinical
(n= 45) studies (n=6)
• Venous ulcer, pressure
ulcer, burn wound
(n=14)
• No comparison (n=1)

Full-text articles assessed for Full-text articles excluded

eligibility (n=8) with reasons (n=3) due to
incomparable outcome
parameters

Studies included in qualitative

synthesis (n=5)

Studies included in quantitative

synthesis (meta-analysis)
(n=5)

Figure 1. Study flow diagram of search results, studies identified and included in this review

Quality of these studies were analyzed using wound healing for honey treatment groups11,12,13.
Jadad Scale (Table 2). Total score varied from 1-3. The other two studies reported that honey versus
None of them had full score due to lack of povidone iodine dressing showed insignificant
description on randomization method, blinding, difference in mean duration of wound healing,
and dropouts. We also had to deduct one point in but the mean duration of wound healing in honey
one of the studies because of its inappropriate group still showed shorter period10,14. Two studies
randomization sequence. From 5 studies reported that patients in honey treatment group
included, a total of 517 patients were reported. had experienced less pain during dressing
Two studies compared honey dressing with changes10,14 (Table 3). All of the studies have
normal saline dressing; 2 studies compared similarity in reporting their results of wound
honey dressing with povidone iodine dressing; healing duration, which was using days as an
and 1 study compared honey dressing with outcome parameter.
alginate dressing. Three studies reported there
are significant reduction in mean duration of

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Table 2. Characteristic of surgery

Study Design Sample Size and Type of Honey DFU Outcome

Treatment Groups used Classification

Agarwal, RCTs n=36; Non-sterile pure Grade II Wagner Mean duration for wound healing
2015 Honey impregnated honey classification showed insignificant difference,
dressing versus however all patients in honey group
Povidone iodine 10% experienced less pain

Eldeen, RCTs Honey dressing n=20; Pedyphar Grade II Wagner Honey treatment group has
2012 Alginate dressing n=20 ointment classification significantly shorter wound healing
duration compared to alginate

Imran, RCTs Honey dressing n=179; sterilised Beri Grade I and II Honey impregnated dressing
2015 Normal saline dressing (Ziziphus jujuba) Wagner significantly reduced the duration of
n=169 honey classification wound healing in diabetic foot ulcer
patients

Kamaratos, RCTs Honey dressing n=32; Manuka honey Grade I and II Duration of healing in patients treated
2012 Saline dressing n=31 impregnated Wagner with honey were significantly shorter
dressing classification

Shukrimi, RCTs n=30; Non-sterile pure Grade II Wagner Ulcer healing was not significantly
2008 Honey dressing versus honey classification different in both study groups. All
10% povidone iodine patients in honey group experienced
dressing less pain during dressing

DISCUSSION also reported that intra-oral honey application

Outcome of Studies significantly precipitates faster epithelialization
Although there are two studies reported process.
that honey gives insignificant results, mean
duration for wound healing were shorter in honey Bacteria Colonization
dressing group. Agarwal10 mentioned that mean Honey posses several benefits in treating
duration for wound healing in honey group was diabetic foot ulcer. Especially in wounds
14.2 days (range 6-25 days) compared to 15.5 days contaminated with Pseudomonas A, Staphylococcus
(range 9-37 days) in povidone iodine group. A, and MRSA2. Based on study conducted by
Shukrimi14 mentioned that mean duration in Pemayun in Semarang17, out of positive cultured
honey group was 14.4 days (range 7-26 days) specimen of DFU patients admitted in RSUD
compared to 15.4 days (range 9-36 days) in Kariadi, 70.8% were positive for gram-negative
povidone iodine group. They also reported that bacilli, 20.8% for gram-positive, and 4.3% for
honey dressing has better result in decreasing anaerobic bacteria. Most of anaerobic bacteria
wound oedema10,14, reducing wound discharge10 were cultured from gangrenous specimens.
and reducing malodorous discharge14. Both studies In Indonesia, patients tend to assume that DFUs
reported less pain during dressing changes10,14 in are common just like wounds in non-diabetic
honey dressing group. This is due to the ability of cases17. They try to treat their ulcers with
honey to maintain the moisture of the wound traditional treatments such as dried in sunlight
without adhesion to the granulating surface14. exposure or soaked in hot water. After the
The other three significant studies reported that traditional treatments failed, they started to seek
honey dressing group gave better result in: mean medical attention. Due to this delay of medical
duration of wound healing11,12,13, eradication of treatment, their ulcer has become infected or even
gangrenous which are mandatory for surgical
infection11, granulation tissue11, and experience of
debridement or amputation.
pain11. Faster healthy granulation tissue on honey
Hydrogen peroxide activity in honey has been
dressing treatment is similar to Subrahmanyam
described by White in 196318. This property is very
study in 199115. Other experimental study by
important in inhibiting the growth of anaerobic
Kreshanti et al in 201216
bacteria that can cause gangrene.

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Most types of honey can generate H2O2 with the Strength and Limitation of This Review
activation of glucose oxidase which oxidizes The strength of this review lies in the fact
glucose to gluconic acid and H2O219. Nevertheless, that all trials was done in different parts of the
the presence of heat or catalase can breakdown world (Greece, India, Malaysia, Pakistan and
this activity. Egypt) so they were hoped to represent different
In 5 of our subjected articles, there are 2 articles race of the patients involved.
assessed wound healing by the eradication of Limitations of this review include the
microorganisms on swab cultures13,14. Kamaratos13 inability to carry out a meta-analysis. Forest Plot
showed healing duration of diabetic foot ulcers in of all trials showed statistically significant effect
patients treated with honey-impregnated dressing favouring honey as diabetic foot ulcer treatment,
was significantly shorter than patients treated but as we tried to calculate the pooled mean
with normal saline dressing, which was marked difference based on mean duration of wound
by sterile wounds from any microorganisms, such healing from each studies, it was to no success due
as: Pseudomonas, E. coli, MRSA and Proteus sp. to heterogeneity of the included studies. This
Other article also said that mean duration of heterogeniety due to: unstandardized clinical
wound healing in honey dressing group was assessment to determine healed wound;
shorter (although not significantly) than unstandardized age of participants; and
povidone-iodine dressing group, which was unstandardized honey application.
marked by negative culture of Staphylococcus and
Streptococcus14.
Recommendation for Future Research
Application of Honey Dressing To upgrade the evidence on honey in
Debridement was carried out prior to modern wound care, standardized and validated
honey application in these 5 included studies. measurement tools are needed, as well as reliable
Currently, there are no standardized method for cost-effectiveness analysis, as they will allow a
applying honey dressing. Even in this review, we valid comparison with current practice.
found different methods of honey application. Conducting more trials with sufficiently larger
Three trials was using pure undiluted honey10,12,14, sample size and standardization of honey
while other two was using standardized honey application are needed to determine its statistical
medication (Pedyphar Ointment and significance as wound dressing. We do hope that
Medihoney)11,13. However, given the promising those trials could determined honey application
evidence, there are several pharmacies that have protocols in the future.
started to produce standardized honey
impregnated dressings. Unfortunately,
standardized medical honey is not available yet in
our country. DISCUSSION
Unstandardized honey application is one of Honey dressing was proven to be effective
obstacles in using honey for wound dressing. in reducing mean duration of wound healing
Sudjatmiko4 proposed that manually prepared compared to Normal Saline dressing and Alginate
honey impregnated dressing should be changed at Dressing. Although it showed insignificant
least once daily or more in presence of excessive difference compared to Povidone Iodine dressing,
exudate. This standardization of honey mean duration of wound healing in honey
application is concluded based on: (1) its dressing groups were still shorter. On the other
hygroscopic properties—honey could easily hand, honey dressing was also proven to cause
liquefied (decreased viscosity) in contact to body less pain in dressing changes. The mean difference
temperature, (2) dry honey dressing can cause of wound healing duration between honey
gauze to adhere to wound surface thus induce dressing and other substances cannot be pooled
pain in dressing changes, (3) honey can give due to low number of the studies and substansial
unpleasant smell if the dressing does not be heterogeniety. We suggested more studies
changed in 3 days. We do hope that there will be analyzed honey as diabetic foot ulcer treatment as
more protocols of honey application in the future. well as its standardized method of application.

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Corresponding author : 10. Agarwal A, et al. A Control Trial of Honey-

Ide Bagoes Insani impregnated and Povidone Iodine Dressings in
[email protected] The Treatment of Diabetic Foot Ulcers among
North Indian Subjects. Indian J.Sci.Res. 2015. 6(2):
7-10.
11. Eldeen M, Fathey R, Hasaballah A, Basal A.
Acknowledgement
Topical Honey versus Alginate as Dressing for
We would like to show our gratitude to dr.Gentur Management of Wagner Type 2 Diabetic Foot
Sudjatmiko, SpB, SpBP-RE(K) for sharing his Ulcer. Journal of American Science. 2012. 8(9).
pearls of wisdom with us during the course of this 12.Imran M, Hussain MB, Baig M. A Randomized,
research. Controlled Clinical Trial of Honey-Impregnated
Dressing for Treating Diabetic Foot Ulcer. Journal
of The College of Physicians and Surgeons Pakistan.
2015. 25(10):721-725.
13. Kamaratos AV, et al. Manuka honey-
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