This is not the most recent version of the article. View current version (6 MAR 2015)

Intervention Review

You have free access to this content

Honey as a topical treatment for wounds

  1. Andrew B Jull1,*,
  2. Natalie Walker2,
  3. Sohan Deshpande3

Editorial Group: Cochrane Wounds Group

Published Online: 28 FEB 2013

DOI: 10.1002/14651858.CD005083.pub3


How to Cite

Jull AB, Walker N, Deshpande S. Honey as a topical treatment for wounds. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD005083. DOI: 10.1002/14651858.CD005083.pub3.

Author Information

  1. 1

    University of Auckland, School of Nursing, Auckland, New Zealand

  2. 2

    University of Auckland, Clinical Trials Research Unit, Auckland, New Zealand

  3. 3

    Kleijnen Systematic Reviews, York, UK

*Andrew B Jull, School of Nursing, University of Auckland, Private Bag 92019, Auckland, New Zealand. a.jull@auckland.ac.nz.

Publication History

  1. Publication Status: Edited (no change to conclusions), comment added to review
  2. Published Online: 28 FEB 2013

SEARCH

This is not the most recent version of the article. View current version (06 MAR 2015)

 
Characteristics of included studies [ordered by study ID]
Al Waili 1999

MethodsSingle-centred, 2-armed parallel group RCT.


Participants50 participants who had had Caesarean sections or hysterectomies.
Setting: hospital.
Country: United Arab Emirates.
Inclusion criteria: acute post-operative bacterial wound infections confirmed by culture and sensitivity.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 26): Yemeni honey.
Group 2 (n = 24): 70% ethanol with povidone-iodine.
Treatment duration: not reported, dressing changed 12-hourly.


OutcomesComplete healing:
Group 1: 22/26 (84.6%);
Group 2: 12/24 (50.0%).


NotesAll participants received systemic antibiotics. The authors have not responded to requests for additional information.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After informed consent the patients were allocated randomly into two groups”.
Comment: method of generating the random schedule not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Table 6 shows that all the randomised participants completed follow-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but, since there were no drop-outs reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskQuote: “Both groups were comparable with regards to age, sex, and duration of symptoms, type and severity of bacterial infections, clinical signs and symptoms and use of systematic antibiotics”.
Comment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Baghel 2009

MethodsSingle-centered, 2-arm parallel group RCT.


Participants78 participants admitted to burn unit of MY hospital Indore over a period of 2 years (June 2006-June 2008).
Setting: hospital.
Country: India.
Inclusion criteria: 10-50 years of age, with 1st- and 2nd-degree burns, burn area < 50% of TBSA.
Exclusion criteria: patients on chemotherapy, with renal and/or liver failure, immuno-compromised state and those with bronchial asthma.


InterventionsGroup 1 (n = 37): honey dressing applied daily.
Group 2 (n = 41): SSD applied daily.
Treatment duration: not reported, duration of follow-up 2 months.


OutcomesComplete healing:
Group 1: 30/37 (81.1%);
Group 2: 15/41 (36.6%).

Mean time to healing:
Group 1: 18.1 days (No SD);
Group 2: 32.6 days (No SD).


NotesComplete healing included healing without scarring or contractures. Formation of soft scar, hypertrophic scar and/or contracture was counted as incomplete recovery. The authors have not responded to requests for additional information.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After taking consent from the patients/parents or guardians, patients were randomly attributed into two study groups; Honey group and SSD group . . .”.
Comment: method of generation of the random sequence not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Tables 3 and 5 showed there were no drop-outs, all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: although the baseline characteristics were broadly similar, a greater proportion of patients treated with honey were admitted to hospital within 1-8 h of the burn (65%) compared to the SSD group (11%). The study seemed to be free from other forms of bias.

Gethin 2009

MethodsMulti-centred, 2-armed, open label RCT.


Participants108 participants recruited February 2003-January 2006.
Setting: hospital and community leg ulcer clinics.
Country: Ireland.
Inclusion criteria: > 18 years, wound area < 100 cm2, > 50% of wound covered by slough, able to provide written informed consent.
Exclusion criteria: current wound infection, medicated with antibiotics or steroids for any reason, cavity or malignant lesion.


InterventionsGroup 1 (n = 54): monofloral (manuka) honey (Woundcare 18+) + compression at dose of 5 g/20 cm2 applied weekly.
Group 2 (n = 54): hydrogel (IntraSite) + compression at dose of 3 g/20 cm2 applied weekly.

Treatment duration: 4 weeks, dressing changed with compression.


OutcomesComplete healing at 12 weeks:
Group 1: 24/54 (44.4%);
Group 2: 18/54 (33.3%).


NotesHealing was a secondary outcome. The primary outcome was change in area of slough at 4 weeks (no significant difference).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “The allocation sequence was generated using serially numbered, sealed, opaque envelopes, prior to the study by two persons independent of the study”.
Comment from study author (personal communication): the sequence was generated in two stages each of which was independent of the researcher. A number of coloured cards either treatment or controls were prepared for the total number of participants required for recruitment. These were then shuffled and placed in sealed envelopes. The sealed envelopes were then shuffled again and were sequentially numbered. This process was completed by two people who were not involved in the study.

Allocation concealment (selection bias)Low riskQuote: “patients were randomised via remote phone allocation to either treatment group”.
Comment: centrally randomised via remote phone allocation.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskQuote: “This prospective, open label, 12 week, multicentre, randomised controlled trial was conducted . . .”.
Comment: open label RCT, so blinding of participants not done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “This prospective, open label, 12 week, multicentre, randomised controlled trial was conducted . . .”.
Comment: open label RCT, so blinding of healthcare providers not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
High riskQuote: “Blinded outcome assessment was not possible because of obvious difference in the colour and presentation of the products, specifically orange staining of the peri-wound skin when [manuka honey] was used”.
Comment: primary outcome assessors were not blinded.
Quote: “All statistician analyses were performed using SPSS version 14 and Stata 9.2 by a statistician blinded to the treatment allocations on the intention-to-treat population”.
Quote: “The laboratory was blinded to the treatment allocation”.
Comment: Secondary outcome assessors were blinded.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Figure 1 shows that no patients were lost to follow-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskQuote: “All patients were included in the final analysis”.
Comment: ITT analysis had been done, as all the randomised participants were included in the final results. 

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskQuote: “There were no statistical baseline differences between groups”.
Comment: ulcers in the honey group were larger (5.4 vs 4.2 cm2), present for longer (39.5 vs 29.9 weeks) and had a greater area covered by slough (85.5% vs 78.2%), however, these factors would affect the likelihood of healing in the honey group. The study seems to be free from other forms of bias.

Ingle 2006

MethodsSingle-centred, 2-armed, double-blind, parallel group RCT.


Participants87 participants with shallow wounds recruited September 1995-July 1996.
Setting: community.
Country: South Africa.
Inclusion criteria: patients with wounds < 2 cm deep, abrasions 10 cm2-100 cm2 (including donor sites for skin grafting and partial-thickness burns).
Exclusion criteria: patients with wounds > 100 cm2; unwilling to have an HIV test; infected wound; genital or malignant ulcers; wounds on legs, perineum, fingers or toes that would make measurement difficult; systemic disease; chronic alcoholism.


InterventionsGroup 1 (n = 40): monofloral (Aloe vera) honey applied daily.
Group 2 (n = 42): hydrogel (IntraSite) applied daily.
Treatment duration: until complete healing (abrasion) or wound < 3 cm2 (shallow wound).


OutcomesMean time to healing (all wounds) - information supplied by authors:
Group 1: 16.48 days (SD 8.40);
Group 2: 16.88 days (SD 11.31).


NotesDiet supplemented with zinc sulphate and vitamins A, B and C for all participants. 5 participants excluded from analysis after randomisation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “then randomised (using random permuted blocks of size 10) to treatment with either honey or IntraSite Gel”.
Comment: method of generation of random schedule reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskQuote: “A prospective, randomised, double-blind controlled trial was carried out by authors . . . Patients did not know which agent was being used”.
Comment: whilst reported as double-blind, the information given was insufficient to permit judgement regarding how blinding of participants was maintained.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskQuote: “A prospective, randomised, double-blind controlled trial was carried out by authors . . . Patients did not know which agent was being used”.
Comment: whilst reported as double-blind, the information given was insufficient to permit judgement as it did not state whether the healthcare providers were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “A prospective, randomised, double-blind controlled trial was carried out by authors . . . When the healing endpoint was approaching [KP] measured the surface area daily, still blinded, the applied agent from the previous day having been washed off with normal saline”.
Comment: blinding of outcome assessor judged to be adequate. 

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskQuote: “Of 87 patients enrolled, 5 were excluded from the analysis . . . ”.
Comment: the loss to follow-up was less than 10%, and judged to be acceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
High riskQuote: “Of 87 patients enrolled, 5 were excluded from the analysis . . .”.
Comment: ITT analysis was not done, as 5 of the 87 patients defaulted, and were not included in the results.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskQuote: “The composition of the groups did not differ significantly in terms of recorded characteristics”.
Comment: there was no imbalance in the baseline characteristics and the study seemed to be free of other forms of bias.

Jull 2008

MethodsMulti-centred, 2-armed, parallel group RCT.


Participants368 participants with venous or mixed venous/arterial leg ulcers recruited May 2004-September 2005.
Setting: community nursing services.
Country: New Zealand.
Inclusion criteria: venous ulcer (clinical presentation + AB I > 0.8) or mixed venous/arterial ulcer (clinical presentation + ABI > 0.7), receiving compression, able to provide informed consent, residing in one of 4 study regions.
Exclusion criteria: diagnosis of diabetes, rheumatoid arthritis or significant peripheral arterial disease, allergy to honey or calcium alginate, currently using honey treatment.


InterventionsGroup 1 (n = 187): monofloral (manuka) honey-impregnated calcium alginate dressing (ApiNate) + compression bandaging system normally available at study centre.
Group 2 (n = 181): usual care: choice of any dressing clinically indicated + compression system normally available at study centre.

Treatment duration: until healing or 12 weeks, dressing changed with compression.


OutcomesComplete healing at 12 weeks:
Group 1: 104/187 (55.6%);
Group 2: 90/181 (49.7%).


NotesNo difference between groups for time to healing, change in ulcer area, incidence of infection or health-related quality of life.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “The allocation sequence was stratified by study centre and Margolis index using minimization”.
Comment: sequence generated using minimization technique.

Allocation concealment (selection bias)Low riskQuote: “Participants were randomly assigned to one of two groups by an independent central telephone service”.
Comment: allocation concealed using an independent central telephone service.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskQuote: “open-label, multicentre randomised controlled trial was conducted”.
Comment: open label RCT, so blinding of participants not done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “open-label, multicentre randomised controlled trial was conducted”.
Comment: open label RCT, so blinding of healthcare providers not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
High riskQuote: “The primary outcome measure was the proportion of participants with completely healed reference ulcers at 12 weeks, as determined by the research nurse. The research nurse was not blind to allocation”.

Comment: primary outcome assessor not blinded.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskQuote: “Loss to follow-up was similar between the two groups, although withdrawal from the study differed significantly (31 participants in the honey-treated group compared with none in the usual care group) . . . All participants who withdrew were followed up at 12 weeks”.
Comment: outcome data was collected for all participants unless lost to follow-up. 6 participants (< 2%) were lost to follow-up, all in the control group. The loss to follow-up was < 10% and judged to be acceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskQuote: “The primary analysis was by intention to treat, with all participants included, and participants lost to follow-up deemed treatment failures”.
Comment: ITT analysis was done, as all the randomised participants were included in the final results. 

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results. The trial was registered in a publicly available trials register (ISRCTN06161544).

Other biasLow riskQuote: “Baseline data were similar for both study groups”.
Comment: there was no imbalance in the baseline characteristics and the study seemed to be free from other forms of bias.

Marshall 2005

MethodsSingle-centred, 2-armed, single-blind, parallel group RCT.


Participants51 participants.
Setting: outpatient clinic.
Country: England.
Inclusion criteria: patients suitable for toenail removal (unilateral or bilateral, partial or total) with matrix phenolisation.
Exclusion criteria: unable to give informed consent, unable to attend follow-up clinics, peripheral vascular disease, peripheral neuropathy.


InterventionsGroup 1 (n = 27): monofloral (jarrah) honey dressing daily.
Group 2 (n = 24): iodine (Inadine) dressing daily.
Treatment duration: until complete epithelialisation of nail bed.


OutcomesMean time to healing:
Group 1: 33.4 days (SD 15.71);
Group 2: 25.3 days (SD 8.70).


NotesImbalance in numbers of diabetics in honey group compared to comparison treatment (9 vs 4) and in total avulsions (16 vs 7) both of which favoured the comparison treatment.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “random tables were used to determine group allocation”.
Comment: method of generation of random schedule reported.

Allocation concealment (selection bias)Low riskQuote: “Those given written informed consent were randomly assigned to the intervention groups by telephone randomisation. This involved a phone call to an independent assistant located outside of the clinical settings with no prior knowledge of the participants”.
Comment: allocation concealed using an independent central telephone service.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskQuote: “The study was single blind trial. While the operating clinician and the patients could not be blinded to the intervention . . .”.
Comment: blinding of participants not done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “The study was single blind trial. While the operating clinician and the patients could not be blinded to the intervention . . .”.
Comment: blinding of healthcare providers not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “ . . . the outcome assessor was unaware of group allocation”.
Comment: blinding of outcome assessors was done, and it was unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
High riskQuote: “A total of 7/51 participants withdrew from the trial: 4/27 in the honey group, of which 2/4 were lost to follow up and 2/4 were withdrawn due to non-compliance. In the iodine group, 3/24 withdrew from the trial; 1/3 lost to follow up, 1/3 withdrawn for non-compliance, and 1/3 required further surgical intervention.”
Comment: reasons for drop-outs were given, but the rate was > 10%, and judged to be unacceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
High riskQuote: “All the seven participants were excluded from the primary analysis.”
Comment: ITT analysis not done, as the randomised participants were not all included in the final analyses.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasHigh riskQuote: “In respect of prognostic factors randomisation allocated more patients who smoked (7 vs 3), and more patients with diabetes (9 vs 4) to the honey group”.
Comment: there was baseline imbalance with respect to demographics, as more participants who smoked and had diabetes were allocated to the honey group.

Mashood 2006

MethodsSingle-centered, 2-armed, parallel group RCT.


Participants50 participants recruited September 2002-August 2003.
Setting: hospital.
Country: Pakistan.
Inclusion criteria: patients of all ages who sustained superficial and partial-thickness burns of < 15% TBSA, and with no co-morbidities present.
Exclusion criteria: patients with deep burns and those who sustained burns of > 15% TBSA, whether was superficial or deep.


InterventionsGroup 1 (n = 25): honey.
Group 2 (n = 25): 1% SSD.
Treatment until healed.
Duration of follow-up: 6 months.


OutcomesComplete healing in weeks:
Group 1: 2 weeks = 13/25, 4 weeks = 25/25;
Group 2: 2 weeks = 5/25, 4 weeks = 15/25, 6 weeks = 25/25.


NotesPatients with deep partial-thickness burns were included. The authors have not responded to requests for additional information.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “They were randomly assigned to two groups. Each group contained 25 patients”.
Comment: method of generating the random sequence not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Tables 1 and 2 show that there were no drop-outs; all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information to judge whether any other important form of bias existed.

McIntosh 2006

MethodsSingle-centred, 2-armed, double-blind, parallel group RCT.


Participants100 participants.
Setting: outpatient clinic.
Country: England.
Inclusion criteria: patients suitable for toenail surgery (unilateral or bilateral, partial or total) with matrix phenolisation.
Exclusion criteria: age < 16 years, unable to give informed consent, unable to attend follow-up clinics, communication barriers, unsuitable for toenail surgery (patients with peripheral vascular disease, unstable diabetes, or where local anaesthetic was contra-indicated).


InterventionsGroup 1 (n = 52): monofloral (manuka) honey-impregnated calcium alginate (ApiNate) twice weekly.
Group 2 (n = 48): paraffin-impregnated gauze (Jelonet), twice weekly.

Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 40.30 days (SD 18.21);
Group 2: 39.98 days (SD 25.42).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “Random tables were used to determine intervention allocation”.
Comment: method of generation of random schedule reported.

Allocation concealment (selection bias)Low riskQuote: “Participants were assigned to intervention groups by remote randomisation. This involved a telephone call to an independent assistant located outside of the study setting who had no prior knowledge of the participants”.
Comment: allocation concealed using an independent central telephone service.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Low riskQuote: “This was a double blind study. Both the outcomes assessors and participants were blind to the intervention throughout. Removal and application of all dressings were performed in a treatment group with only the investigator and participant present; a screen concealed the participant’s feet during dressing removal and application”.
Comment: blinding of participants was done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “Removal and application of all dressings were performed in a treatment group with only the investigator and participant present”.
Comment: blinding of healthcare providers not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “This was a double blind study. Both the outcomes assessors and participants were blind to the intervention throughout ... All evidence of the intervention was removed and wounds were irrigated before the outcome assessors entered the room”.
Comment: blinding of outcome assessors was done.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
High riskQuote: “A total of 13/100 participants withdrew from the trial: 5/52 from the honey group (one was lost to follow-up and four withdrew because of non-concordance) and 8/48 from the paraffin tulle gras group (five were lost to follow-up and three withdrew due to non-concordance)".
Comment: Reasons for drop-outs were given, but the rate was more than 10% and judged to be unacceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
High riskQuote: “All 13 withdrawals were excluded from primary analyses”.
Comment: ITT analysis not done, as not all the randomised participants were included in the final analyses.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasHigh riskQuote: “There were disparities in baseline demographics. Established prognostic factors differed between groups: more smokers were assigned to the paraffin tulle gras group, and more diabetics to the honey group.”.
Comment: whilst the study report stated that there were more smokers assigned to the paraffin tulle gras group, the data in table 1 (baseline demographics) stated that more smokers were assigned to the honey group.

Memon 2005

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants80 participants with superficial-dermal, mid-dermal or deep-dermal burns recruited January 2002-December 2003.
Setting: hospital.
Country: Pakistan.
Inclusion criteria: age 4-62 years, TBSA burnt 10-40%.
Exclusion criteria: patients with chemical or electrical burns, full-thickness burns or burns involving > 40% TBSA.


InterventionsGroup 1 (n = 40): natural, unprocessed honey-gauze dressings every other day.

Group 2 (n = 40): SSD-gauze dressings every other day.
Treatment duration: not reported.
Follow-up duration: until healed.


OutcomesNumber healed:
Group 1: by day 16 (n = 20), by day 26 (n = 12), by day 30 (n = 8). Mean 15.3 days (no SD).
Group 2: by day 20 (n = 16), by day 36 (n = 18), by day 46 (n = 6). Mean 20.0 days (no SD).


NotesThe authors have not responded to requests for additional information.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “The patients were allotted at random in two different groups”.
Comment: in addition, it was reported in the abstract that the design was "a quasi-experimental study". The method for generating the random sequence was not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Tables 4 and 5 showed there were no drop-outs; all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.   

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasHigh riskComment: there was a baseline imbalance in demographics such as % TBSA and depth of burn. More participants with burns 16-25% TBSA were randomised to the SSD group (20 vs 14). The honey group had more participants with burns 10-15% TBSA (18 vs 12). More participants in the SSD group had deep-dermal burns (20 vs 16), whereas more participants in the honey group had superficial-dermal burns (18 vs 12).

Mphande 2007

MethodsSingle-centred, 2-armed, quasi-randomised controlled trial.


Participants40 participants with open or infected wounds (chronic osteomyelitis n = 7, post-surgical n = 14, ulcer n = 8, trauma n = 9, abscess n = 2) recruited February-November 2005.
Setting: hospital with outpatient follow-up.
Country: Malawi.
Inclusion criteria: not reported.
Exclusion criteria: lived too far from hospital for follow-up.


InterventionsGroup 1 (n = 22): honey-soaked gauze daily; frequency reduced after 1 week if wound healing progressing.
Group 2 (n = 18): sugar covered with gauze dressing; frequency reduced after 1 week if wound healing progressing.
Treatment duration: not reported.
Follow up duration: not reported.


OutcomesMedian time to complete healing:
Group 1: 31.5 days (no SD);
Group 2: 56.0 days (no SD).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuote: “Patients were randomised to receive a honey or sugar dressing. They were allocated to one of the two groups on an alternating basis at admission”.
Comment: method of generating sequence was not random and, therefore, not adequate.

Allocation concealment (selection bias)High riskQuote: “They were allocated to one of the two groups on an alternating basis at admission”.
Comment: allocation was judged to have been inadequately concealed, as alternation was used.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Unclear riskComment: the study did not state whether there were any drop-outs, or whether all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Unclear riskComment: no drop outs or withdrawals were reported. The total numbers of participants assessed were also not reported. We cannot judge whether an ITT analysis was conducted.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskQuote: “The honey group comprised 22 patients (13 males and nine females) with a mean age of 12.7 years (range 1–39). The sugar group comprised 18 patients (12 males and six females) with a mean age of 13.8 years (range 3–53).There was a range of causes of wounds, but their distribution was similar between the two groups.”.
Comment: age, sex and types of wounds similar between the two groups, but no information was reported on other baseline characteristics.

Nilforoushzadeh 2007

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants100 participants with confirmed cutaneous Leishmaniasis.
Setting: skin disease and Leishmaniasis research centre.
Country: Iran.
Inclusion criteria: patients with confirmed cutaneous Leishmaniasis with direct smear, no history of systemic or topical therapy for cutaneous Leishmaniasis, absence of malnutrition or severe predisposing disease such as cardiac, renal or hepatic disease and other contraindication for glucantime.
Exclusion criteria: pregnant and lactating women, lesions < 3 months old, and patients treated with drugs that interact with glucantime.


InterventionsGroup 1 (n = 45): intralesional injection of meglumine antimoniate (glucantamine) once weekly and dressed with honey-soaked gauze twice daily.
Group 2 (n = 45): intralesional injection of meglumine antimoniate (glucantamine) once weekly.
Treatment duration:until complete healing of wounds, or maximum 6 weeks.


OutcomesComplete healing:
Group 1: 23/45 (51.1%);
Group 2: 32/45 (71.1%).

Mean time to healing in days:
Group 1: 7.04 (± 3.09);
Group 2 : 6.30 (± 2.29).


NotesThis RCT reported that, initially, 100 patients were confirmed with cutaneous Leishmaniasis and were randomised into two groups. Further on, in the results section, the authors report that each group had 45 patients and stated that 10 patients left the study. They also reported that 23 patients in the honey-treated group achieved complete cure, whilst in the glucantime alone group 32 patients achieved complete cure. 13 patients from the honey-treated group left the study, as did 10 patients from the glucantime group.     


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “The patients were randomised into 2 groups, using Random allocation software. (version 1.0, may 2004; Saghaei)”.
Comment: method of generation of random sequence reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “Diameter of the lesion and size of the erythema, induration and ulcer were measured by use of the millimetre papers. These evaluations performed [sic] by the investigators who were blinded to the type of treatment”.
Comment: blinding of outcome assessors was done.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
High riskQuote: "Overall, in the topical honey treated group, 13 patients left out [sic] the study. One patient (7.7%) left out the study because of contact dermatitis to honey and 12 patients left out of the study because of progression of their lesions. In the glucantime treated group, 10 patients left out [sic] the study because of progression of their lesions".
Comment: reasons for drop-outs provided, but the rate was > 10%, and judged to be unacceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
High riskComment: the study stated that 100 participants were randomised, but there were only 45 included in each arm (see table 1 baseline demography). Percentages were inaccurate because the denominators used were 45.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: age, sex, number and location of lesions similar between the two groups, but no information reported on potentially prognostic baseline characteristics, such as size of lesions.

Robson 2009

MethodsSingle-centred, parallel group, open-label RCT.


Participants105 participants recruited September 2004-May 2007.
Setting: large district hospital.
Country: United Kingdom.
Inclusion criteria: patients with a wound healing by secondary intention.
Exclusion criteria: patients with: diabetes, history of neuroses, psychoses or dementia, known allergy to bee/honey products, venous ulcers of < 12 week duration, Grade 1 or Grade 4 pressure ulcers (EPUAP grades), wounds containing exposed tendon, muscle or bone, or wounds where malignancy was present or suspected; patients with an existing wound infection requiring systemic antibiotics and those who had received antibiotic therapy in the preceding 2 weeks.


InterventionsGroup 1 (n = 52): manuka honey.
Group 2 (n = 53): conventional treatment.
Duration of treatment 24 weeks.


OutcomesHealing rate at 24 weeks:

Group 1: 72.7%;

Group 2: 63.3%.

Healing rate at 12 weeks:

Group 1: 46.2%;

Group 2: 34.0%.

Median time to heal:
Group 1: 100 days;

Group 2: 140 days.

Time to heal in days (Time to event):
Group 1: 0 days = 50, 50 days = 30, 100 days = 20, 150 days = 12, 200 days = 1.
Group 2: 0 days = 51, 50 days = 36, 100 days = 25, 150 days = 15, 200 days = 1.


Notes52 patients were randomized to receive honey and 53 to receive conventional treatment. 2 patients randomized to the honey group (3.8%) did not receive honey (1 as a result of the patient’s decision, 1 as a result of a clinical decision), and 6 allocated to the conventional treatment group (11.3%) received honey (all except 1 as a result of a clinician’s decision).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: “Allocation to treatment was determined using blocked randomisation (with sequence produced using computer software (STATA version 8.2; StataCorp, College \station, TX, USA) with randomly varying block size), stratified by two factors, age (< 40 and ≥ 40 year old) and size of wound (< 10 and ≥ 10 cm2)”.
Comment: method of generation of random schedule reported.

Allocation concealment (selection bias)Low riskQuote: “Sealed, opaque, serially numbered envelopes were produced from the randomisation sequence for each stratum separately, and an independent third party with access to the envelopes was contacted by telephone to determine treatment allocation as patients were recruited”.
Comment: allocation concealed using sealed, opaque, serially numbered envelopes and an independent central telephone service.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskQuote: “The study was designed as a single centre, open-label, randomized controlled trial”.
Comment: open label RCT, so blinding of participants not done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “The study was designed as a single centre, open-label, randomized controlled trial”.
Comment: open label RCT, so blinding of healthcare providers not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
High riskQuote: “The study was designed as a single centre, open-label, randomized controlled trial”.
Comment: open label RCT, so blinding of outcome assessors not done.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskQuote: “One patient in the honey group (1.9%) was lost to follow up (as they moved to an alternative hospital) and one patient died in each group (1.9% in each group)”.
Comment: drop-out rate < 10%, and judged to be acceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskQuote: “Statistical analysis was carried out on an intention to treat (ITT) basis, retaining patients in their randomised treatment groups regardless of the actual treatment received and including protocol violators and ineligible patients”.
Comment: ITT analysis was done, as all the randomised participants were included in the final results.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Shukrimi 2008

MethodsSingle-centered, 2-armed, parallel group RCT.


Participants30 participants.
Setting: hospital.
Country: Malaysia.
Inclusion criteria: all non-Insulin dependent diabetes mellitus patients (NIDDM) with Wagner grade II ulcers who were admitted for surgery were enrolled if the following parameters were met: age 35-65, transcutaneous oxygen tension > 30 mmHg and serum albumin level of > 35 g/dl.
Exclusion criteria: multiple medical co-morbidity, steroid therapy, neutrophil count < 2000/mm3.


InterventionsGroup 1: honey applied daily.
Group 2: povidone-soaked gauze applied daily.
Duration: until wound closure.


OutcomesMean time to heal in days:
Group 1: 14.4 (no SD);
Group 2: 15.4 (no SD).


NotesThe study did not state the number of participants randomised to each arm, or the percentage of wounds healed in each group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “The patients were randomised to two dressing arms; honey dressing group and standard dressing group”.
Comment: method of generating the random schedule not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “All the wounds were assessed every other day by a surgeon blinded to the material of dressing”.
Comment: blinding of outcome assessors was done and it was unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Unclear riskComment: the study did not report the numbers allocated to each treatment, drop-outs, or state whether all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Unclear riskComment: the study did not report the numbers allocated to each treatment, drop-outs or withdrawals. The total numbers of participants assessed were not reported either. We cannot judge whether an ITT analysis was conducted.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information to judge whether any important form of bias existed.

Subrahmanyam 1991

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants104 participants with burns < 40% TBSA recruited July 1988-December 1989.
Setting: hospital.
Country: India.
Inclusion criteria: superficial burns.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 52): unprocessed, undiluted honey dressings daily.
Group 2 (n = 52): SSD-impregnated gauze daily.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 9.4 days (SD 2.3);
Group 2: 17.2 days (SD 3.2).


NotesInformation on allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing were provided by the author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “The cases were allocated at random to two groups”.
Comment: method of generating random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear how this method works.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered, sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 2 showed there were no drop-outs, and that all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 1993a

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants92 participants with burns < 40% TBSA recruited January 1990-January 1991.
Setting: hospital.

Country: India.
Inclusion criteria: treated within 6 h of injury, partial-thickness burns.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 46): unprocessed, undiluted, honey-impregnated gauze daily.
Group 2 (n = 46): polyurethane film (OpSite) left intact until day 8, unless evidence of infection, excessive exudate or leakage.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 10.8 days (SD 3.93);
Group 2: 15.3 days (SD 2.98).


NotesInformation on allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial management, patients were allotted at random to two groups”.
Comment: method of generation of random sequence not reported. Author informed us that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was via sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded, but not patients.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 1 showed that there were no drop-outs, and that all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information available to judge whether any important form of bias existed.

Subrahmanyam 1993b

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants100 participants with burns or ulcers recruited January 1989-January 1990.
Setting: hospital.
Country: India.
Inclusion criteria: not reported.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 50): unprocessed, undiluted, honey-impregnated gauze daily.
Group 2 (n = 50): SSD-impregnated gauze daily.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 9.5 days (SD 6.2);
Group 2: 22.5 days (SD 5.2).


NotesInformation on allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “Patients were divided into two groups and they were distributed at random”.
Comment: method of generating random sequence was not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered, sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Table 3 showed there were no drop-outs, and that all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: there was no baseline imbalance with respect to patients' age between two groups, however, other baseline characteristics were not reported, so there was insufficient information to judge whether any important form of bias existed.

Subrahmanyam 1994

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants100 participants with partial-thickness burns recruited June 1991-July 1992.
Setting: hospital.
Country: India.
Inclusion criteria: treated within 6 h of injury, TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 50): unprocessed, undiluted, honey-impregnated gauze changed every 2nd day.
Group 2 (n = 50): amniotic membrane left intact until day 8, and then changed every 2nd day.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 9.4 days (SD 2.52);
Group 2: 17.5 days (SD 6.66).


NotesInformation about allocation method, allocation concealment, blinding, and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial treatment, patients were allotted to two groups at random”.
Comment: method of generating the random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered, sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: Tables 2 and 3 show that there were no drop-outs, all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 1996a

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants900 participants with partial-thickness burns recruited July 1987-December 1993.
Setting: hospital.
Country: India.
Inclusion criteria: TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 450): pure, unprocessed, undiluted, honey-impregnated gauze every 2nd day.
Group 2 (n = 450): Soframycin (90 participants), Vaseline-impregnated gauze (90 participants), OpSite (90 participants), sterile gauze (90 participants) or left exposed (90 participants). "Dressings were replaced on alternative days, except in the case of OpSite, which was continued until the wounds healed... sterile linen changed at frequent intervals." Frequency of dressing change is not mentioned with respect to the sterile gauze group.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 8.8 days (SD 2.1);
Group 2: 13.5 days (SD 4.1).


NotesInformation about allocation method, allocation concealment, blinding, and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial treatment, the cases were divided at random into a study group treated with honey dressing and a control group treated with conventional dressing”.
Comment: method of generating the random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered, sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 1 showed that there were no drop-outs; all the randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information to judge whether any important form of bias existed.

Subrahmanyam 1996b

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants100 participants with partial-thickness burns recruited July 1992-December 1993.
Setting: hospital.

Country: India.
Inclusion criteria: treated within 6 h of injury, TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 50): pure, unprocessed, undiluted honey every 2nd day.
Group 2 (n = 50): potato peel bandages every 2nd day.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 10.4 days (SD 2.2);
Group 2: 16.2 days (SD 2.3).


NotesInformation about allocation method, allocation concealment, blinding, and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial management, patients were allotted at random to two groups”.
Comment: method of generating the random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 1 showed that there were no drop-outs; all randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 1996c

MethodsSingle-centred, 2-armed, blinded, parallel group RCT.


Participants84 participants with partial-thickness burns recruited January 1993-June 1994.
Setting: hospital.

Country: India.
Inclusion criteria: treated within 6 h of injury, TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 42): pure, unprocessed, undiluted honey changed every 2nd day.
Group 2 (n = 42): pure, unprocessed, undiluted honey with added vitamins C and E, and polyethylene glycol 4000 changed every 2nd day.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 8.3 days (SD 2.4);
Group 2: 6.4 days (SD 3.6).


NotesInformation about allocation method, allocation concealment, blinding and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial management, patients were allotted at random to two groups”.
Comment: method of generation of random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 2 showed that there were no drop-outs; all randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 1998

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants50 participants with superficial thermal burns recruited June 1995-December 1996.
Setting: hospital.

Country: India.
Inclusion criteria: present within 6 h of injury, TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 25): pure, unprocessed, undiluted honey every 2nd day.
Group 2 (n = 25): SSD-impregnated gauze daily.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 4.92 days (SD 3.61);
Group 2: 8.22 days (SD 8.31).


NotesInformation about allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “After initial management, patients were allotted at random to two groups”.
Comment: method of generation of random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment:  Table 2 showed that there were no drop-outs; all randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis not reported, but since no drop-outs were reported, and all randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 1999

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants50 participants with mixed-depth (partial- and full-thickness) burns recruited January 1996-December 1997.
Setting: hospital.

Country: India.
Inclusion criteria: aged 10-40 years, haemodynamically stable, no systemic illness or smoke inhalation injury, TBSA burnt < 30%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 25): unprocessed honey every 2nd day, with autologous skin grafting as required.
Group 2 (n = 25): early tangential excision and skin grafting 3-6 days after admission.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 32.0 days (SD 8.1);
Group 2: 18.4 days (SD 4.2).


NotesInformation about allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing provided by author.
3 participants in the honey-treated group died, and 1 in the early tangential excision group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “Twenty five patients were randomly assigned to the TE group”.
Comment: method of generation of the random sequence was not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskQuote: “One TE patient died, from status asthaticus, while 3 HT patients died with septicaemia”.
Comment: overall the number of drop-outs was < 10%, however, drop-outs were due to death, which is of some concern given that the burns were described as “moderate”.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Unclear riskComment: the study did not state whether all the randomised participants were followed-up and included in the final analysis, hence, we cannot judge if an ITT analysis was conducted.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information available to judge whether any important form of bias existed.

Subrahmanyam 2001a

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants100 participants with mixed-depth (partial- and full-thickness) burns recruited June 1998-December 1999.
Setting: hospital.

Country: India.
Inclusion criteria: treated within 6 h of injury, TBSA burnt < 40%.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 50): unprocessed, undiluted, monofloral (Jambhul) honey every 2nd day.
Group 2 (n = 50): SSD-impregnated gauze every 2nd day.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 15.4 days (SD 3.2);
Group 2: 17.2 days (SD 4.3).


NotesInformation about allocation method, allocation concealment, blinding, and standard deviation for mean time to healing provided by author.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “The patients were allocated at random to two groups, the initial management being the same”.
Comment: method of generation of random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially-numbered sealed envelopes, although it is not clear whether the envelopes were opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskComment: not stated in study report, but author responded to request for further information by stating the patients were not blinded.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated in study report, but author responded to request for further information by stating the investigators and outcome assessors were blinded. How blinding was achieved was not described in the response.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskQuote: “Thus, all the patients in this group, the wound healed by day 21” (patients treated with honey).
Quote:  “In the group treated with sulphur sulphadiazine, the wounds healed in 4 patients by day 7, in 22 patients by 14 day, and in 24 patients by day 21”.
Comment: no drop-outs, as all the participants randomised were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Low riskComment: ITT analysis was not reported, but since no drop-outs were reported, and all the randomised participants completed the study, ITT analysis was assumed to have been done and to be acceptable.  

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasLow riskComment: there was no imbalance in the baseline characteristics, and the study seemed to be free from other forms of bias.

Subrahmanyam 2004

MethodsSingle-centred, 2-armed, blinded (outcome assessor), parallel group RCT.


Participants30 consecutive males with Fournier's gangrene recruited April 2001-May 2003.
Setting: hospital.

Country: India.
Inclusion criteria: not reported.
Exclusion criteria: not reported.


InterventionsGroup 1 (n = 14): unprocessed, undiluted, monofloral (Jamun) honey daily.
Group 2 (n = 16): Edinburgh Solution of Lime- (EUSOL) soaked gauze daily.
Treatment duration: until healed.


OutcomesMean time to healing:
Group 1: 18.5 days (SD 2.1);
Group 2: 26.5 days (SD 3.2).


NotesInformation about allocation method, allocation concealment, blinding, mean time to healing and standard deviation for mean time to healing provided by author.
3 participants died: 1 in the honey-treated group and 2 in the EUSOL-treated group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “For assessing the beneficial effects of local dressings, the patients were divided into two groups by randomisation”.
Comment: method of generating the random sequence not reported. Author provided information that the sequence was generated by the "chit method", but it is not clear what this method is.

Allocation concealment (selection bias)Unclear riskComment: not stated, but author provided information that allocation concealment was by means of sequentially numbered envelopes, although it is not clear whether they were sealed or opaque.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
High riskQuote: “The assessor was not aware of the treatment given (single blind)”.
Comment: blinding of participants was not done.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
High riskQuote: “The assessor was not aware of the treatment given (single blind)”.
Comment: blinding of providers was not done.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Low riskQuote: “The assessor was not aware of the treatment given (single blind)”.
Comment: blinding of outcome assessors was done and it was unlikely that the blinding could have been broken.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Low riskComment: 3 deaths reported: 1 in the honey-treated group and 2 in the EUSOL-treated group. The causes of death were not mentioned, but the drop-out rate was < 10%, which was acceptable.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Unclear riskComment: the information available was not sufficient to judge whether an ITT analysis had been conducted.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasUnclear riskComment: the baseline characteristics were not reported, so there was insufficient information available to judge whether any important form of bias existed.

Weheida 1991

MethodsSingle-centred, 2-armed, parallel group RCT.


Participants40 participants with grade I or II pressure ulcers.
Setting: hospital.

Country: Egypt.
Inclusion criteria: orthopaedic patients aged ≥ 21 years, ulcer ≥ 2 cm in diameter, ulcer uninfected, haemoglobin ≥ 10 g/dL, oral temperature ≤ 37.5 oC, restricted to bed or wheelchair for at least 2 weeks
Exclusion criteria: debilitant co-morbidities e.g. diabetes, cancer.


InterventionsGroup 1 (n = 20): honey dressing changed daily.

Group 2 (n = 20): saline-soaked gauze changed daily.
Treatment duration: 10 days.
Follow-up duration: three months.


OutcomesMean time to healing:
Group 1: 8.20 days (SD 1.44);

Group 2: 9.93 days (SD 0.27).


NotesGrade I ulcer defined as moist irregular partial-thickness ulcer confined to epidermis and dermis. Grade II ulcer defined as full-thickness ulcer descending into subcutaneous tissue.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: “Subjects of the study were randomly recruited to one of the two treatment groups”.
Comment: method of generation of randomisation schedule not reported.

Allocation concealment (selection bias)Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of participants? All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of healthcare providers?All outcomes
Unclear riskComment: not stated.

Blinding (performance bias and detection bias)
Blinding of outcome assessors? All outcomes
Unclear riskComment: not stated.

Incomplete outcome data (attrition bias)
Drop-out rate described and acceptable -All outcomes
Unclear riskComment: the study did not state whether there were any drop-outs or whether all randomised participants were followed-up.

Incomplete outcome data (attrition bias)
ITT analysis -All outcomes
Unclear riskComment: the study did not state whether all randomised participants were followed-up and included in the final analysis, hence, we cannot judge whether an ITT analysis was conducted.

Selective reporting (reporting bias)Low riskComment: the study protocol was not available, but the important outcome measures stated in the methods section were reported in the results.

Other biasHigh riskQuote: “Eighty percent of group I had ulcers grade I before treatment ... For group II, all the subjects had ulcers grade I, and all of which were completely healed after treatment [sic]”.
Comment: there was a baseline imbalance in ulcer grades between 2 groups; all grade II ulcers were in the saline dressing group, while all ulcers in the honey dressing group were grade I ulcers. Therefore, the ulcers in the saline dressing group were more severe.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Abdelatif 2008Not a randomised or controlled clinical trial.

Ahmed 2003Not a randomised or controlled clinical trial.

Al Waili 2003Participants did not have wounds; trial of honey mixture for atopic dermatitis or psoriasis.

Al Waili 2004aAnimal-model study.

Al Waili 2004bAnimal-model study.

Al Waili 2004cNot a randomised or controlled clinical trial.

Al Waili 2005Not a randomised or controlled clinical trial.

Albietz 2006Participants did not have wounds.

Bangroo 2005Insufficient information on healing - no response to attempts to contact corresponding author.

Berchtold 1992Did not use honey.

Biswal 2003Participants did not have wounds; trial of honey for radiation-induced mucositis.

Bose 1982Not a randomised or controlled clinical trial.

Calderon Espina 1989Could not be obtained for assessment.

Chokotho 2005No information on healing. No response to attempts to contact investigator.

Dunford 2004Not a randomised or controlled clinical trial.

Freeman 2010Not a randomised or controlled clinical trial.

Gad 1988No information on healing. No response to attempts to contact investigator.

Gethin 2005Not a randomised or quasi-randomised controlled trial.

Jeffery 2008No information on healing.

Johnson 2005Participants did not have wounds; trial of honey to prevent catheter-associated infections in haemodialysis patients.

Lund-Nielsen 2011No information on healing.

Lusby 2002Not a randomised or quasi-randomised controlled trial.

Malik 2010Unit of analysis issue - wounds randomised, not patients.

Marshall 2002Not a randomised or quasi-randomised controlled trial.

Misirligou 2003Not a randomised or controlled clinical trial.

Molan 2002Not a randomised or controlled clinical trial.

Molan 2006Not a randomised or controlled clinical trial.

Muller 1985Did not use honey.

Mwipatayi 2004Not a randomised or controlled clinical trial.

Nagane 2004Not a randomised or controlled clinical trial.

Okeniyi 2005Unit of analysis issue - wounds randomised, not participants. 32 participants had 43 wounds and individual participants may have been treated by both honey and the comparator (EUSOL). Healing rate provided by wound, not by participant.

Oluwatosin 2000Unit of analysis issue. No information on healing.

Quadri 1998Participants did not have wounds; trial of honey to prevent catheter-associated infections in haemodialysis patients. Duplicate study.

Quadri 1999Participants did not have wounds; trial of honey to prevent catheter-associated infections in haemodialysis patients.

Rivero Varona 1999Could not be obtained.

Robson 2002Not a randomised or controlled clinical trial.

Rogers 2010Insufficient information on healing.

Rucigaj 2006Insufficient information on healing - corresponding author unwilling to provide information until study published.

Schumacher 2004Not a randomised or controlled clinical trial.

Subrahmanyam 1993Not a randomised or controlled clinical trial.

Subrahmanyam 2001bAnimal-model study.

Subrahmanyam 2003No data on healing - biochemical data only.

Thurnheer 1983Not a randomised or controlled clinical trial.

Tostes 1994Not a randomised or controlled clinical trial.

Visscher 1996Not a randomised or controlled clinical trial.

Yapucu Gunes 2007Unit of analysis issue - outcomes reported by pressure injury, not by participant.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Maghsoudi 2011

MethodsSingle-centred, 2-armed, parallel group RCT

Participants100 participants with partial-thickness burns recruited March 2010-March 2011.
Setting: hospital.
Country: Iran.
Inclusion criteria: TBSA burnt < 40%.
Exclusion criteria: not reported.

InterventionsGroup 1 (n = 50): 16-30 ml unprocessed, undiluted honey dressings changed on alternate days.
Group 2 (n = 50): mafenide acetate-impregnated gauze changed daily.
Treatment duration: until healed.

OutcomesMean time to healing and standard deviation not available.

NotesAttempting to contact authors.

 
Comparison 1. Minor acute wounds

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing3213Mean Difference (IV, Fixed, 95% CI)1.55 [-1.91, 5.00]

 
Comparison 2. Partial-thickness burns - honey vs conventional dressings

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing (days)2992Mean Difference (IV, Fixed, 95% CI)-4.68 [-5.09, -4.28]

 
Comparison 3. Burns - honey vs early excision & grafting

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Early excision & grafting150Mean Difference (IV, Fixed, 95% CI)13.60 [10.02, 17.18]

 
Comparison 4. Burns - honey vs silver sulfadiazine (SSD)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing (days)3254Mean Difference (IV, Random, 95% CI)-4.37 [-8.94, 0.19]

 
Comparison 5. Burns - honey vs unconventional dressings

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing (days)3Mean Difference (IV, Random, 95% CI)Totals not selected

 
Comparison 6. Mixed acute and chronic wounds

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing (days)1100Mean Difference (IV, Fixed, 95% CI)-13.0 [-15.24, -10.76]

 2 Proportion healed1105Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.88, 1.48]

 
Comparison 7. Chronic wounds

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Time to healing (days)3Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Infected postoperative wounds
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Pressure ulcers
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Fournier's gangrene
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Proportion healed3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Leishmaniasis
190Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.51, 1.01]

    2.2 Venous leg ulcers
2476Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.96, 1.38]

 
Comparison 8. Adverse events

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 All adverse events12Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Minor acute wounds
182Risk Ratio (M-H, Random, 95% CI)1.37 [0.77, 2.45]

    1.2 Burns
71390Risk Ratio (M-H, Random, 95% CI)0.77 [0.31, 1.92]

    1.3 Infected post-operative wounds
150Risk Ratio (M-H, Random, 95% CI)0.31 [0.11, 0.82]

    1.4 Fournier's gangrene
130Risk Ratio (M-H, Random, 95% CI)0.57 [0.06, 5.65]

    1.5 Venous leg ulcers
1368Risk Ratio (M-H, Random, 95% CI)1.28 [1.05, 1.56]

    1.6 Wounds healing by secondary intention
1105Risk Ratio (M-H, Random, 95% CI)2.04 [0.39, 10.65]

 
Comparison 9. Incidence of infection

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Incidence of clinically diagnosed infection4627Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.50, 1.04]

 2 Burns patients with positive swab cultures at admission rendered sterile after 7 days treatment7522Risk Ratio (M-H, Random, 95% CI)5.31 [1.75, 16.18]

 
Table 1. Frequency of adverse events reported in burns trials (Memon 2005; Subrahmanyam 1991, 1993a, 1994, 1996a, 1999, 2001a)

Adverse eventHoneyControl treatment

Hypergranulation8/54817/548

Contracture11/25321/237

Minor scarring28/45087/450

Hypertrophic scarring0/527/52

 
Table 2. Frequency of adverse events reported in venous ulcer trial (Jull 2008)

Adverse eventHoney treatmentControl treatment

Ulcer pain47/18718/181

Bleeding3/1873/181

Dermatitis8/1878/181

Deterioration of ulcer19/1879/181

Erythema6/1874/181

Oedema4/1871/181

Increased exudate5/1871/181

Deterioration of surrounding skin5/1873/181

New ulceration16/18715/181

Other6/1873/181

Cardiovascular4/1873/181

Cancer2/1872/181

Neurological4/1871/181

Gastrointestinal4/1872/181

Injury10/1879/181

Musculoskeletal13/1879/181

Respiratory6/1873/181

Other3/1878/181