1. food and drink
2. food
3. condiments and dressings

Science, Practice and Education
Efficacy of honey gel
in the treatment of chronic lower
leg ulcers: A prospective study
ABSTRACT
Chronic leg ulcers are a common medical
problem among elderly patients and have a
dramatic impact on quality of life as a result
of pain, disability, and social isolation.
Regardless of their cause, chronic leg ulcers
remain difficult to treat. In recent years, there
has been increasing interest in the use of
honey as a therapeutic agent.
Objective: To evaluate the efficacy of honeybased dressings in the treatment of chronic
leg ulcers.
Methods: Ten patients with chronic (mean
duration 3.3 years) leg ulcers who had
received non-honey based treatments with
no improvement were included in this study.
A honey gel dressing was applied twice a
week as the only treatment.
Results: Seven patients experienced complete healing of their leg ulcers. The remaining three patients showed a significant
reduction in wound size, which was achieved
in a mean time of 101 days (range 28-174
days).
Conclusion: Honey-based dressings appear
to be an efficient and easy to use treatment
for leg ulcers.
Key words: Chronic lower leg ulcer, venous
leg ulcer, dressings, honey gel
INTRODUCTION
Lower leg ulcers affect 15-18 out of 10,000 adults in developed countries, with venous leg ulcers (VLUs) representing up to 84% of all leg ulcer cases (Watson, 2011).
These ulcers have an important impact on the quality of
life and health of patients (Cullum, 2000). Treatment of
VLU patients also has a significant economic impact; the
annual cost of treatment of VLUs in the UK and Sweden
is estimated to be between 1,300-2,500 Euros per patient.
Costs increase for lesions with long healing times or for
larger ulcerations, as well as for ulcers that are defined as
“difficult to treat” (Ragnarson Tennvall, 2005). Difficult
to treat cases can cause significant morbidity (Faria, 2011),
seriously impact the patient’s quality of life (GonzálezConsuegra, 2011), and consequently increase treatment
costs.
Evidence-based treatment options for VLUs include leg
elevation, compression therapy, topical (active) dressings,
pentoxifylline, and aspirin therapy. Surgical management
can be considered for ulcers that are large, of prolonged
duration, or refractory to conservative measures (Collins,
2010).
In clinical practice surgery is rarely an option due to
the nature of the pathology in the lower limb.
Instead, common treatment options include compression therapy as standard care in combination with a variety
of dressings, although meta-analyses have not yet identified the ideal dressing type (Palfreyman, 2006; O’Meara,
2009). The recent resurgence of the use of honey in wound
management (Al-Waili, 2011) triggered our prospective
study of the efficacy of honey-based treatment in the management of venous leg ulcers.
STUDY DESIGN
In this prospective study we evaluated the efficacy of a
honey gel dressing in a group of patients with difficult to
treat VLUs. Patients with lower leg ulcers who presented
at the University Hospital between February and October 2010 were recruited for this study. All patients with
chronic lower leg ulcers, regardless of ulcer depth, area,
or presence of infection, were included. Patients were randomly selected for treatment as outpatients with consultation or for inpatient treatment. Exclusion criteria were
EWMA JOURNAL
2013 VOL 13 NO 2
Oscar Tellechea
M.D., Ph.D. 2
Ana Tellechea, D.Sc.1
Vera Teixeira, M.D.2
Fatima Ribeiro, RN2
1Neurosciences and Cellbiology centre, University
of Coimbra, Coimbra,
Portugal
2Dermatology
Service,
Hospitals of the University
of Coimbra, Coimbra,
Portugal
Correspondence:
[email protected]
Conflict of interest: none
䊳
35
Table 1: Clinicopathological characteristics of patients and ulcers
General information Underlying pathology
Etiology
2
75 Y
F
X Polycythemia vera
1
0
3
65 Y
M
Smoker
0
0
0
0
4
65 Y
M
X
CRI, dialysis,
awaiting kidney
transplant
5
75 Y
F
1
0
6
81 Y
F
X
1
0
7
78 Y
F
X
TEP (pulmonary
1
0
thromboembolism)
8
57 Y
M
0
0
9
10
83 Y
67 Y
Y: years old
M
F
F: female
unlikelihood of wound improvement due to cutaneous
necrotizing vasculitis, lower limb cellulitis, or severe lower
limb arterial insufficiency.
PATIENTS
The study included ten patients: six females and four
males with an average age of 73 years (age range 57-83).
Underlying pathologies included diabetes mellitus (n=3),
hypertension (n=4), and a range of other factors that influence wound healing (Table 1). Seven patients had venous
ulcers, one had a mixed venous and arterial ulcer, one had a
post-trauma ulcer, and one had an ulcer related to diabetes
mellitus (Table 1). Standard criteria for the diagnosis of
leg ulceration were used.
Leg ulcers had been present in these patients for an
average of 3.3 years (range: 2 months-5 years). During that
period, patients were treated with a range of products and
techniques in primary care centres without improvement
(Tables 2 & 3). For our study, the patients themselves
before initiation of the honey gel treatment were used as
controls. To ensure that application of honey gel was the
only variable, the same wound management regimen that
was followed in the pre-study treatment period was applied
during our study, except that honey gel was now used as
a topical dressing (Moghazy, 2010). Patients consented
to the honey gel regimen prior to the start of the study.
During the treatment period no compression therapy was
performed in any patient.
MATERIALS
The honey gel (L-Mesitran Soft, Triticum, NL) used in this
study contains 40% medical-grade honey, ultra-purified
hypoallergenic medical grade lanolin (Medilan), polyethylene glycol, and Vitamins C and E. All of these ingredients
have individual beneficial effects on wound management
and healing (Cutting, 2005) and the honey product as a
whole has proven antibacterial efficacy (Stephen-Haynes,
2011).
36
X
X
-
1
1
0
0
0
1
0
0
0
1
0
0
0
X
X
X
0
0
0
0
0
0
0
0
0
X
X
0
0
0
0
0
0
post
trauma
0
0
X
X
M: male
Fig 1. Patient 3. Ulcer pathology before honey gel treatment.
Fig 2. Patient 3. Complete healing of the wound after
7 months of honey gel treatment.
METHODS
Patients were treated only with honey gel. The honey gel
was applied twice weekly d directly over the wound and
covered with a sterile cotton dressing. Compression was
not used during the period of treatment with the honey
gel.
During the observation period the patients were seen
for consultation at weeks 2, 4, and on a monthly basis
thereafter. Ulcer size was measured using the Opsite Flexigrid® system.
EWMA JOURNAL
2013 VOL 13 NO 2
Science, Practice and Education
Lateral, posterior (right side)
1,2,3,4,5
z1
Left internal malleolus
1,2,3,4,5,9 23
Left external malleolus
1,2,3,4,5 29,6
Injury next to the lap of the 1st metatarsal
4,5,8
1,5
Left supramaleolar
1,4,7,10
2,5
Right external malleolus
1,3,4,6
3,6
One-third distal right leg, circumferential
3,4,5
67,6
One-third distal right leg, anterior
1,2,3,4
1
Right internal malleolus
3,4
6,9
Right internal malleolus
1,4,5,9
54,3
2013 VOL 13 NO 2
2
Calcium Alginate
3
Allevyn
4
Aquacel AG
5
Activated charcoal
6
Fat gauze
7
Vaseline salicylated 10%
8
Silver sulfadiazine
9
HZN Reducol Gel
10
2006; Stephen-Haynes, 2011). It is particularly important
that the honey used for wound care is free from residues
and sterilized, because honey can contain clostridial spores
in addition to non-pathogenic Bacillus spp. Only gamma
irradiation effectively sterilizes honey without reducing
its efficacy (Postmes, 1993; Molan, 1996) and the use of
non-sterilized honey samples cannot be justified (Cooper,
2009).
The honey gel used in this study may also have a direct
positive effect on wound healing. Du Toit (2009) examined the cell morphological effects of honey- and silverimpregnated dressings on two key cellular components
of wound healing, keratinocytes and fibroblasts, using an
䊳
Period of treatment
with honey gel (days)
Reduction in wound size
Fold acceleration of
healing time
Table 4: Honey gel treatment
End of the treatment
DISCUSSION
A primary factor contributing to the chronic nature of
VLUs is poly-microbial biofilm infection, where several
bacterial species colonize the wound. The most common
organisms found in VLU biofilms include various anaerobes, Staphylococcus (Wolcott, 2009), and Pseudomonas
aeruginosa (Jacobsen, 2011). The honey-based product
used in our study has a known broad-spectrum antibacterial effect, which could have contributed to the accelerated
healing. In vitro research using antibiotic-resistant clinical isolates and extended spectrum b-lactamase (ESBL)producing strains of bacteria showed that this honey gel
is highly effective and has stronger antibacterial activity
than other honey products (Manuka) (Stobberingh, 2010;
Stephen-Haynes, 2011). The efficacy of honey in wound
healing is further attributed to its low pH, its ability to produce hydrogen peroxide, and its osmotic action (Molan,
1
Hydrocolloid
Wound size at the end
of the treatment (cm2)
RESULTS
A reduction in wound size was observed in all patients in
a mean time of 101 days (range: 28-174 days) (Table 4).
Seven patients showed complete healing of the wound
and the mean degree of reduction of ulcer extension was
90%, ranging from less than 10% to 100% (Table 4).
Patient 7, who showed the smallest reduction in wound
size, complained of pain after application of the honey gel
and abandoned the study.
Hydrogel
Initiation of treatment
Dermocorticoids (betametasone valerate cream) and
emollients were applied to the peri-wound area when necessary. No topical or systemic antibiotics were used.
Adverse reactions, including subjective unfavourable
symptoms, were registered when present.
EWMA JOURNAL
Wound size at the start of
honey gel treatment (cm2)
1,825
1,278
1,825
730
730
1,460
1,825
61
1,095
1,095
Previous Treatment
Patient #
Presence of ulcers prior to
honey gel treatment (days)
5.0
3.5
5.0
2.0
2.0
4.0
5.0
0.2
3.0
3.0
Table 3
Previous treatments
Presence of ulcers prior to
honey gel treatment (years)
1
2
3
4
5
6
7
8
9
10
Location
Patient #
Table 2: Characteristics of ulcer at initiation of honey treatment
1
2
3
4
5
6
7
8
9
10
16-06-2010
04-10-2010
18-03-2010
25-05-2010
08-02-2010
15-04-2010
15-06-2010
18-05-2010
06-04-2010
26-05-2010
0
8.4
0
0
0
0
59.7
0
0
27
29-09-2010
25-11-2010
28-10-2010
01-07-2010
30-05-2010
25-10-2010
20-07-2010
16-06-2010
30-09-2010
26-07-2010
103
51
220
36
112
190
35
28
174
60
100%
63%
100%
100%
100%
100%
12%
100%
100%
50%
18
25
8
20
7
8
52
2
6
18
37
Table 5: Previous studies on the efficacy of honey in VLU tretament
Author
Type of study
Olabanji (2000)
Natarajan
(2001)
Alcaraz
(2002)
Dunford (2004)
Comparative study
Case report
Case report
Four-centre feasibility
Number
Study
of patients period
50
4 weeks
1
until
healing
1
until
healing
40
12 weeks
Schumacher
Case report
(2004)
van der Weyden Case report
(2005)
6
Timmons
(2008)
Case report
1
Jull (2008)
Community-based, open-label
randomised trial
Case report
368
Gethin (2009)
Prospective, multicentre, open
label randomised controlled trial
108
Kegels (2011)
Retrospective study
22
Sare (2008)
1
3
in vitro tissue explant culture model and found that the
honey-impregnated dressings promoted new tissue regeneration. A second study comparing silver-sulphadiazine
with the honey gel used in our study reported similar
findings; the honey gel significantly stimulated re-epithelialisation, whereas silver sulphadiazine significantly reduced
it (Boekema, 2013). In support of these findings, Rossiter
et al. (2010) showed that honey products stimulated angiogenesis in vitro in an investigation of the influence of
honey on growth of the tubular length of rat aorta.
Several previous studies (Table 5, 601 patients) have reported that honey-based wound management has positive
effects on wound healing, ulcer size, and patient comfort.
However, when compared to standard methods or other
comparative methods, honey has not been shown to superior to these methods significant difference in wound
healing. This might reflect the type of honey used in these
studies (Jull, 2008), the study design (Firth, 2010), and
the complexity of VLU management.
However, we did see a significant improvement in
wound healing in our study. The patients’ previous treatments were less effective (Table 2) than honey treatment
(Table 4), with an observed shortening of healing time
from an average of 3.3 years to 101 days. The honey gel
was used in monotherapy. Only emollients and, when
indicated, topical corticosteroids were allowed as complementary treatment on the peri-ulcerous skin, and in no
circumstance were antibiotics or antiseptics used.
38
Outcome
Reduction in wound size was significantly different.
MRSA was eradicated from the ulcer and rapid
healing was successfully achieved.
The patient’s wounds improved with the
honey-based dressing.
Overall, ulcer pain and size decreased significantly,
and odorous wounds were deodorised promptly.
until
No significant difference from conventional methods
healing recorded.
until
Honey was found to be an effective antibacterial,
healing anti-inflammatory, and deodorizing dressing,
with total healing of the ulcer achieved.
until
Honey promoted the removal of slough, encouraging
healing the formation of granulation tissue and epithelial
tissue growth
12 weeks Honey-impregnated dressings promoted healing,
however, not significantly more than usual care.
until
Promotion of healing occurred in all instances with
healing a reduction in the incidence of infection, reduction
in pain, and the provision of comfort.
12 weeks Increased incidence of healing, effective
desloughing, and a lower incidence of infection
than the control.
until
Infected wounds were controlled within a few days.
healing All the wounds progressed to healing without any
adverse effects.
Similar results were obtained in a recent retrospective
study in which 22 patients with lower extremity ulcerations had delayed healing, in part attributed to application
of povidone iodine or fusidic acid, and 50% of the wounds
were infected. After treatment with honey-based products,
all cases progressed to healing (Kegels, 2011).The use of
honey may therefore have a place in VLU treatment (Jull,
2013). Antibiotics are not recommended because there is
no evidence that the routine use of systemic antibiotics
promotes VLU healing. In addition, in light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial
preparations should only be used in cases of clinical infection and not for bacterial colonisation (O’Meara, 2010).
Honey gel treatment may also be superior to traditional
treatments because it is easier for patients to administer.
The patients in our study showed low compliance with
compression bandage treatment during the pre-study
treatment period because a lack of local health facilities,
advanced patient age, and the low economic status of the
patients often precluded maintenance of correct compression treatment. In contrast, application of honey gel to the
wound surface was easy and could be accomplished by the
patients themselves or by a relative without specialised
skills, as previously reported (Smaropoulos, 2011). Patients were therefore able to follow the treatment protocol
provided no adverse effects occurred.
Another advantage of honey-based treatment is that
it requires fewer materials and the procedure is less time
EWMA JOURNAL
2013 VOL 13 NO 2
Science, Practice and Education
consuming than traditional methods, which has the potential to reduce treatment costs. The reduction in health
care costs might be expected when the faster healing times
are taken into consideration. In addition, although the
present study did not analyse quality of life data, the patients welcomed the faster wound healing with honeybased treatment. We therefore believe that honey-based
treatments of VLUs should be more seriously considered
for the treatment of leg ulcer patients.
Limitations
The small number of patients and the use of the patients
themselves as the treatment controls are limitations of this
study.
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CONCLUSION
We believe that honey gel treatment may provide a practical and well-tolerated treatment for the management of
lower leg venous ulcers, particularly when patient compli䡵
ance with compression therapy is poor.
Read our author guidelines at
www.ewma.org/english/authorguide
Acknowledgement
The authors wish to thank the patients who volunteered
in this study.
References
Alcaraz A, Kelly J. (2002) Treatment of an infected
venous leg ulcer with honey dressings. Br J Nurs.
11(13):859-60, 862, 864-6
Al-Waili N, Salom K, Al-Ghamdi AA (2011) Honey for
wound healing, ulcers, and burns; data supporting its use
in clinical practice. Scientific World Journal 11:766-87
Boekema B, Pool L, Ulrich M (2013) The effect of a
honey based gel and silver sulphadiazine on bacterial
infections of in vitro burn wounds. Burns 39(4):754-759
Collins L, Seraj S (2010) Diagnosis and treatment of
venous ulcers. Am Fam Physician. 81(8):989-96
Cooper RA, Jenkins L (2009) A comparison between
medical grade honey and table honeys in relation to
antimicrobial efficacy. Wounds 21(2):29-36
Cullum N, Nelson EA, Fletcher AW, Sheldon TA (2000)
Compression bandages and stockings for venous leg ulcers. Cochrane Database Syst Rev. 2000;(2):CD000265.
Jacobsen JN, Andersen AS, Sonnested MK, Laursen I, Jorgensen B, Krogfelt KA (2011) Investigating the humoral
immune response in chronic venous leg ulcer patients
colonised with Pseudomonas aeruginosa. Int Wound J.
8(1):33-43 doi: 10.1111/j.1742-481X.2010.00741.x.
Epub 2010 Nov 19
Postmes T, Van den Boogaard T, Hazen M (1993) Honey
for wounds, ulcers and skin graft preservation. The Lancet
Vol 341; March 20:756-757
Jull A, Walker N, Parag V, Molan P, Rodgers A (2008)
Randomized clinical trial of honey-impregnated dressings for venous leg ulcers British Journal of Surgery 95:
175-182
Rossiter K, Cooper AJ, Voegeli D, Lwaleed B (2010)
Honey promotes angiogeneic activity in the rat aortic ring
assay. Journal of Wound Care 19(10):440-446
Jull AB, Walker N, Deshpande S (2013) Honey as a
topical treatment for wounds. Cochrane Database Syst
Rev. 2013 Feb 28;2:CD005083. doi: 10.1002/14651858.
CD005083.pub3.
Kegels F (2011) Clinical evaluation of honey-based products for lower extremity wounds in a home care setting.
Wounds UK 7(2):46-53
Cutting K, Davies P (2005) Natural therapeutic agents for
the topical management of wounds. Wounds UK Supplement 1(3):4-13
Moghazy AM, Shams ME, Adly OA, Abbas AH, El-Badawy
ME, Elsakka DM, Hassan SA, Abdelmohsen WS, Ali OS,
Mohamed BA (2010) The clinical and cost effectiveness
of bee honey dressing in the treatment of diabetic foot ulcers. Diabetes Research and Clinical Practice 89:276-281
Dunford CE, Hanano R (2004) Acceptability to patients
of a honey dressing for non-healing venous leg ulcers. J
Wound Care 13(5):193-7
Molan PC, Allen KL (1996) The effect of gammairradiation on the antibacterial activity of honey. J Pharm
Pharmacol. 48(11):1206-9
DuToit DF, Page B (2009) An in vitro evaluation of the
cell toxicity of honey and silver dressings. Journal of
Wound Care 18(9):383-389
Molan PC (2006) The evidence supporting the use of
honey as a wound dressing. Int J Low Extrem Wounds
5(1); 40-54
Faria E, Blanes L, Hochman B,Mesquita Filho M, Ferreira
L (2011) Health-related Quality of Life, Self esteem, and
Functional Status of Patients With Leg Ulcers. Wounds
23(1):4-10
Natarajan S, Williamson D, Grey J, Harding KG, Cooper
RA (2001) Healing of an MRSA-colonized, hydroxyureainduced leg ulcer with honey. J Dermatolog Treat.
12(1):33-6
Firth J, Nelson EA, Hale C, Hill J, Helliwell P (2010) A
review of design and reporting issues in self-reported
prevalence studies of leg ulceration. J Clin Epidemiol.
63(8):907-13
Olabanji JK, Tijani LA, Oluwatosin OM, Onyechi HU,
Oluwatosin OA (2000) A comparison of topical honey and
phenytoin in the treatment of chronic leg ulcers. African
Journal of Medicine and Medical Sciences 29(1):31-34
Gethin G, Cowman S (2009) Manuka honey vs. hydrogel-a prospective, open label, multicentre, randomised
controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers. J Clin Nurs. 18(3):466-74.
Epub 2008 Aug 23.
O’Meara S, Cullum NA, Nelson EA. (2009) Compression for venous leg ulcers. Cochrane Database Syst Rev.
21;(1):CD000265
González-Consuegra RV, Verdú J (2011). Quality of
life in people with venous leg ulcers: an integrative
review. J Adv Nurs. 67(5):926-44. doi: 10.1111/j.13652648.2010.05568.x
EWMA JOURNAL
2013 VOL 13 NO 2
O’Meara S, Al-Kurdi D, Ologun Y, Ovington LG (2010)
Antibiotics and antiseptics for venous leg ulcers. Cochrane
Database Syst Rev. 20;(1):CD003557
Palfreyman SJ, Nelson EA, Lochiel R, Michaels JA. (2006)
Dressings for healing venous leg ulcers. Cochrane Database Syst Rev. Jul 19;3:CD001103
Ragnarson Tennvall G, Hjelmgren J (2005) Annual costs
of treatment for venous leg ulcers in Sweden and the
United Kingdom. Wound Repair Regen. 13(1):13-8
Sare JL (2008) Leg ulcer management with topical
medical honey. Br J Community Nurs. 13(9):S22, S24,
S26 passim.
Schumacher HH (2004) Use of medical honey in patients
with chronic venous leg ulcers after split-skin grafting. J
Wound Care 13(10):451-2
Smaropoulos E, Romeos S, Dimitriadou C (2011) Honeybased therapy for paediatric burns and dermal trauma
compared to standard hospital protocol. Wounds UK
7(1):33-40
Stephen-Haynes J, Callaghan R (2011) Properties of
honey: its mode of action and clinical outcomes. Wounds
UK 7(1):54-57
Stobberingh EE (2010) Antibacterial activity of honey
against ESBL -producing strains. Report by the department of Medical Microbiology University of Maastricht,
The Netherlands.
Timmons J (2008) Treatment of a bilateral necrotic leg
ulcer with Mesitran. Wounds UK 4(4):129
van der Weyden EA (2005) Treatment of a venous leg
ulcer with a honey alginate dressing. Br J Community
Nurs. Suppl:S21, S24, S26-7
Watson JM, Kang’ombe AR, Soares MO, Chuang LH,
Worthy G, Bland JM, Iglesias C, Cullum N, Torgerson D,
Nelson EA; VenUS III team (2011) VenUS III: a randomised controlled trial of therapeutic ultrasound in the
management of venous leg ulcers. Health Technol Assess.
15(13):1-192
Wolcott RD, Gontcharova V, Sun Y, Dowd SE (2009)
Evaluation of the bacterial diversity among and within
individual venous leg ulcers using bacterial tag-encoded
FLX and Titanium amplicon pyrosequencing and
metagenomic approaches. BMC Microbiology 9:226
doi:10.1186/1471-2180-9-226
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