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Cochrane Database of Systematic Reviews

Honey as a topical treatment for wounds

Information

DOI:
https://doi.org/10.1002/14651858.CD005083.pub4Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 06 March 2015see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Wounds Group

Copyright:
  1. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Andrew B Jull

    Correspondence to: School of Nursing, University of Auckland, Auckland, New Zealand

    [email protected]

  • Nicky Cullum

    School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK

  • Jo C Dumville

    School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK

  • Maggie J Westby

    School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK

  • Sohan Deshpande

    Kleijnen Systematic Reviews, York, UK

  • Natalie Walker

    National Institute for Health Innovation, University of Auckland, Auckland, New Zealand

Contributions of authors

Andrew Jull: designed and co‐ordinated the review. Extracted data (first review), reviewed risk of bias assessments and data extraction (this update). Analysed or interpreted data and performed statistical analysis, wrote to study author/experts/companies, completed or reviewed the drafts, revisions, and the final review (first review and this update). He is guarantor of the review.

Nicky Cullum: checked others' data extraction and extracted data (this update); checked others' risk of bias assessment and conducted risk of bias assessments (this update). Analysed and interpreted data; constructed summary of findings tables (this update); completed drafts and revisions of the review and approved the final version of this update prior to publication.

Jo Dumville: checked others' data extraction and extracted data (this update); checked others' risk of bias assessment and conducted risk of bias assessments (this update). Analysed and interpreted data; constructed summary of findings tables (this update); completed drafts and revisions of the review and approved the final version of this update prior to publication.

Maggie Westby: checked others' data extraction and extracted data (this update); checked others' risk of bias assessment and conducted risk of bias assessments (this update). Analysed and interpreted data; constructed summary of findings tables (this update); completed drafts and revisions of the review and approved the final version of this update prior to publication.

Natalie Walker: designed the review and checked studies to be included, checked risk of bias assessment and the quality of statistical analysis (first review), performed part of writing or editing of the review (first review and first update). Approved final review prior to submission (first review and all updates).

Sohan Deshpande: checked studies to be included, extracted data, performed risk of bias assessments and contributed to writing (first update).

Contributions of editorial base:

Nicky Cullum: for the original review and first update ‐ edited the review, advised on methodology, interpretation and review content; approved the final review prior to submission.
Liz McInnes, Editor: approved the first review update prior to submission.
Sally Bell‐Syer: co‐ordinated the editorial process; advised on methodology, interpretation and content; edited the review and the updated versions of the review.
Ruth Foxlee: designed the search strategy and edited the search methods section.

David Tovey (Editor in Chief) approved the final version of this updated review (second update).
Toby Lasserson (Senior Editor) of the Cochrane Editorial Unit advised on the Summary of Findings Tables and approved the final version of this updated review (second update).

Sources of support

Internal sources

  • Senior Health Research Scholarship, University of Auckland, New Zealand.

  • School of Nursing, Midwifery and Social Work, University of Manchester, UK.

External sources

  • This project was supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to Cochrane Wounds. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health, UK.

  • The Douglas Senior Fellowship in Heart Health (Prevention), New Zealand.

Declarations of interest

Andrew Jull, Natalie Walker and Anthony Rodgers were investigators in the Honey as Adjuvant Leg ulcer Treatment (HALT) trial (ISRCTN 06161544), one of the trials included in this review. The Clinical Trials Research Unit, which employed Andrew Jull, Natalie Walker and Antony Rodgers received a small, unconditional cash contribution from a manufacturer of honey dressings for the conduct of the HALT trial.
Dr Walker is supported by a Heart Foundation Douglas Senior Fellowship in Heart Health (Prevention). She has provided consultancy to the manufacturers of smoking cessation medications, received honoraria for speaking at a research meeting and received benefits in kind and travel support from a pharmaceutical company that makes smoking cessation medications. She has also received product in kind from a pharmaceutical company that makes smoking cessation medications, for use in an investigator initiated phase III clinical trial.  She has been contracted by two companies to undertake clinical trials for them ‐ one company wanted her to evaluate a treatment for leg ulcers (but this was not honey) and the second was an asthma trial for a New Zealand Crown entity that decides, on behalf of District Health Boards, which medicines and pharmaceutical products are subsidised for use in the community and public hospitals. 

Acknowledgements

The review authors would like to thank the following referees for their comments on the review, Wounds Group Editors: Mieke Flour, Andrea Nelson and Gill Worthy, referees: Margaret Harrison, Lois Orton, Consumer referee: Durhane Wong‐Rieger. Anthony Rodgers contributed to the original review but was not involved in the updating of the review, we would like to acknowledge his contribution. Elizabeth Royle copy edited the updated review.

The review authors would also like to thank David Tovey and Toby Lasserson of the Cochrane Editorial Unit for their advice and review of this updated review.

Dr Walker is supported by a Heart Foundation Douglas Senior Fellowship in Heart Health (Prevention).

Version history

Published

Title

Stage

Authors

Version

2015 Mar 06

Honey as a topical treatment for wounds

Review

Andrew B Jull, Nicky Cullum, Jo C Dumville, Maggie J Westby, Sohan Deshpande, Natalie Walker

https://doi.org/10.1002/14651858.CD005083.pub4

2013 Feb 28

Honey as a topical treatment for wounds

Review

Andrew B Jull, Natalie Walker, Sohan Deshpande

https://doi.org/10.1002/14651858.CD005083.pub3

2008 Oct 08

Honey as a topical treatment for wounds

Review

Andrew B Jull, Anthony Rodgers, Natalie Walker

https://doi.org/10.1002/14651858.CD005083.pub2

2004 Apr 19

Honey as a topical treatment for wounds

Protocol

Andrew B Jull, Anthony Rodgers, Natalie Walker

https://doi.org/10.1002/14651858.CD005083

Differences between protocol and review

In the first version of the review, two trials that compared active interventions allocated wounds to the interventions rather than participants (Oluwatosin 2000; Okeniyi 2005). The participants had multiple wounds in many cases, and some participants would have received both interventions. In this update, a trial that required participants to have two burns (Malik 2010), and a trial that may have randomised participants but appears to have reported healing by pressure injury rather than by participant (Yapucu Gunes 2007), were excluded. The data in these trials were presented by wound and thus could not be combined (if possible) with trials where data were presented by participant in both the first version of the review and this update. Such methods were not foreseen in the protocol, where it was assumed that data would be presented by participant. Randomising by wound breaches the assumption of independence that underpins inferential testing, increases the weight of a study inappropriately if included in a meta‐analysis (by doubling the denominator) and thereby artificially improves the precision of the confidence interval for the summary statistic. Additionally, a trial requiring participants to have two wounds that randomises one wound to each treatment is not clinically generalisable as it has reduced between‐patient variability. Between‐patient variability in pragmatic trials drives external validity. The inclusion criteria have been adjusted in this update to reflect this change.

Notes

The authors have carefully considered and incorporated the observations and items of feedback submitted through the “Submit Comments” facility on the Cochrane Library for this review. These comments and the replies from the authors have been retained in this version of the review. This is to enable readers to follow the exchange and to form their own interpretation of the evidence that is now available.

During the updating of this review the review authors became aware that the publication Gethin G, Cowman S. Manuka honey vs. hydrogel ‐ a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers. Journal of Clinical Nursing 2009;18(3):466‐74 (http://onlinelibrary.wiley.com/doi/10.1111/jocn.12652/abstract) has been retracted by agreement between the journal Editor‐in‐Chief, the authors and John Wiley & Sons, Ltd. The retraction has been agreed due to errors in the data analysis which affect the article's findings. The review authors would like to confirm that the data in this updated review is taken from the source: Gethin G. Manuka honey versus hydrogel ‐ a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers. Unpublished PhD thesis 2007.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 1 Time to healing.
Figures and Tables -
Analysis 1.1

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 1 Time to healing.

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 2 Adverse events.
Figures and Tables -
Analysis 1.2

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 2 Adverse events.

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 3 Infection.
Figures and Tables -
Analysis 1.3

Comparison 1 Minor acute wounds: honey vs. no honey (conventional dressings), Outcome 3 Infection.

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 1 Time to healing (days).
Figures and Tables -
Analysis 2.1

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 1 Time to healing (days).

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 2 Adverse events.
Figures and Tables -
Analysis 2.2

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 2 Adverse events.

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 3 Negative swab at Day 7‐8.
Figures and Tables -
Analysis 2.3

Comparison 2 Partial thickness burns: honey vs no honey (conventional dressings), Outcome 3 Negative swab at Day 7‐8.

Comparison 3 Burns: honey with delayed graft PRN vs early excision & grafting (no honey), Outcome 1 Time to healing (days).
Figures and Tables -
Analysis 3.1

Comparison 3 Burns: honey with delayed graft PRN vs early excision & grafting (no honey), Outcome 1 Time to healing (days).

Comparison 3 Burns: honey with delayed graft PRN vs early excision & grafting (no honey), Outcome 2 Mean duration of antibiotic therapy (days).
Figures and Tables -
Analysis 3.2

Comparison 3 Burns: honey with delayed graft PRN vs early excision & grafting (no honey), Outcome 2 Mean duration of antibiotic therapy (days).

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 1 Time to healing (days).
Figures and Tables -
Analysis 4.1

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 1 Time to healing (days).

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 2 Proportion burns completely healed.
Figures and Tables -
Analysis 4.2

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 2 Proportion burns completely healed.

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 3 Adverse events.
Figures and Tables -
Analysis 4.3

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 3 Adverse events.

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 4 Negative swab at Day 7.
Figures and Tables -
Analysis 4.4

Comparison 4 Burns: honey vs silver sulfadiazine (SSD), Outcome 4 Negative swab at Day 7.

Comparison 5 Burns: honey vs. no honey (atypical dressings), Outcome 1 Time to healing (days).
Figures and Tables -
Analysis 5.1

Comparison 5 Burns: honey vs. no honey (atypical dressings), Outcome 1 Time to healing (days).

Comparison 6 Mixed acute and chronic wounds, Outcome 1 Time to healing (days).
Figures and Tables -
Analysis 6.1

Comparison 6 Mixed acute and chronic wounds, Outcome 1 Time to healing (days).

Comparison 6 Mixed acute and chronic wounds, Outcome 2 Negative swab at Day 7.
Figures and Tables -
Analysis 6.2

Comparison 6 Mixed acute and chronic wounds, Outcome 2 Negative swab at Day 7.

Comparison 7 Chronic wounds, Outcome 1 Proportion healed.
Figures and Tables -
Analysis 7.1

Comparison 7 Chronic wounds, Outcome 1 Proportion healed.

Comparison 7 Chronic wounds, Outcome 2 Time to healing (days).
Figures and Tables -
Analysis 7.2

Comparison 7 Chronic wounds, Outcome 2 Time to healing (days).

Comparison 7 Chronic wounds, Outcome 3 Venous ulcers: proportion healed at 12 weeks.
Figures and Tables -
Analysis 7.3

Comparison 7 Chronic wounds, Outcome 3 Venous ulcers: proportion healed at 12 weeks.

Comparison 7 Chronic wounds, Outcome 4 Venous ulcers: infection.
Figures and Tables -
Analysis 7.4

Comparison 7 Chronic wounds, Outcome 4 Venous ulcers: infection.

Comparison 7 Chronic wounds, Outcome 5 Mixed wounds: proportion healed.
Figures and Tables -
Analysis 7.5

Comparison 7 Chronic wounds, Outcome 5 Mixed wounds: proportion healed.

Summary of findings for the main comparison. Honey compared with conventional dressings for minor acute wounds

Honey compared with conventional dressings for minor acute wounds

Patient or population: patients with Minor acute wounds
Settings: Any
Intervention: Honey
Comparison: Conventional dressings

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Conventional dressings

Honey

Complete healing (time to healing)(days)

The mean complete healing (time to healing) in the intervention groups was
2.26 higher
(3.09 lower to 7.61 higher)

213
(3 studies)

⊕⊝⊝⊝
very low1,2,3

Adverse events

Study population

RR 1.19
(0.69 to 2.05)

82
(1 study)

⊕⊝⊝⊝
very low1,2,4

357 per 1000

425 per 1000
(246 to 732)

Infection

Study population

RR 0.91
(0.13 to 6.37)

151
(3 studies)

⊕⊝⊝⊝
very low1,2,5

14 per 1000

13 per 1000
(2 to 88)

Costs
Average dressing cost per patient

The mean cost of dressing materials per patient was 0.49 ZAR in the honey

group and 12.06 ZAR in the control (hydrogel) group

82
(1 study)

⊕⊝⊝⊝
very low7,8,9

Quality of Life6

Not reported

N/A

N/A

N/A

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded due to risk of bias (one level): High risk of attrition bias in all three included studies
2 Downgraded due to inconsistency (one level): the patient populations and comparator interventions differed between the studies
3 Downgraded due to imprecision (two levels): The plausible range of effects extends from a three day reduction in healing time with honey up to a more than seven day extension in healing time
4 Downgraded due to imprecision (two levels): The 95% confidence interval ranges from 0.69 and 2.05
5 Downgraded due to imprecision (two levels): The relative risk of infection for honey‐treated wounds compared with conventional dressings lies somewhere between 0.13 and 6.37
6 None of the studies reported quality of life
7 ITT analysis not done; cost data from withdrawn patients not included
8 Only report cost of dressing material not other related costs e.g., nursing care, other treatments
9 Only one small study reported costs: honey a non‐proprietary product in this study

Figures and Tables -
Summary of findings for the main comparison. Honey compared with conventional dressings for minor acute wounds
Summary of findings 2. Honey compared with conventional dressings for burns

Honey compared with conventional dressings for burns

Patient or population: patients with Burns
Settings: Any
Intervention: Honey
Comparison: conventional dressings

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Conventional dressings

Honey

Complete healing (time to healing)(days)
Mean time to healing
Follow‐up: median 4 weeks

The mean complete healing (time to healing) in the intervention groups was
4.68 lower
(5.09 to 4.28 lower)

992
(2 studies)

⊕⊕⊕⊕
high

Adverse events
Follow‐up: median 4 weeks

Study population

RR 0.56
(0.15 to 2.06)

992
(2 studies)

⊕⊝⊝⊝
very low1,2

206 per 1000

115 per 1000
(31 to 424)

Negative wound swab
Follow‐up: median 8 days

Study population

RR 1.31
(1.01 to 1.7)

92
(1 study)

⊕⊝⊝⊝
very low3,4

630 per 1000

826 per 1000
(637 to 1000)

Costs5

Not reported

Not estimable5

N/A

N/A

Quality of life5

Not reported

Not estimable5

N/A

N/A

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded due to inconsistency (one level): High heterogeneity was detected with an I‐squared of 70%
2 Downgraded due to imprecision (two levels): The 95% confidence interval ranges from 0.15 to 2.06
3 Downgraded due to indirectness (one level). The outcome of a negative wound swab at 8 days is only a proxy for clinical infection and difficult to interpret
4 Downgraded for imprecision (two levels): this outcome is only reported for one study involving 92 participants
5 Neither study reported costs or quality of life

Figures and Tables -
Summary of findings 2. Honey compared with conventional dressings for burns
Summary of findings 3. Honey compared with silver sulfadiazine for burns

Honey compared with silver sulfadiazine for burns

Patient or population: patients with Burns
Settings: Any
Intervention: Honey
Comparison: Silver sulfadiazine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Silver sulfadiazine

Honey

Complete healing
Follow‐up: 4‐6 weeks

Study population

RR 1.00
(0.98 to 1.02)

462
(6 studies)

⊕⊕⊕⊕
high

1000 per 1000

1000 per 1000
(980 to 1000)

Mean time to complete healing (days)
Follow‐up: 21‐60 days

The mean time to complete healing in the intervention groups was
5.12 lower
(9.51 to 0.73 lower)

332
(4 studies)

⊕⊝⊝⊝
very low1,2

Adverse events
Follow‐up: 4‐6 weeks

Study population

RR 0.29
(0.2 to 0.42)

412
(6 studies)

⊕⊕⊕⊕
high

413 per 1000

120 per 1000
(83 to 174)

Negative wound swab
Follow‐up: median 7 days

Study population

RR 3.92
(1.32 to 11.63)

412
(5 studies)

⊕⊝⊝⊝
very low3,4,5

236 per 1000

923 per 1000
(311 to 1000)

Costs
Cost of dressing per percent TBSA affected

The cost of dressing treatment per % TBSA affected was 0.75 PKR for honey and 10 PKR for silver sulfadiazine.

50
(1 study)

⊕⊕⊝⊝
low7,8

Quality of Life6

Not reported

N/A

N/A

N/A

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded due to inconsistency (two levels): Very high level of statistical heterogeneity (I squared of 93%)
2 Downgraded due to imprecision (one level): Although the direction of effect is consistently in favour of honey, the confidence interval around the mean difference ranges from a reduction in healing time of less than one day up to nearly 10 days
3 Downgraded two levels due to inconsistency: Very high level of statistical heterogeneity (I squared of 94%)
4 Downgraded due to indirectness (one level) since the outcome of a negative wound swab at 7 days is only an indirect measure of wound infection.
5 Downgraded due to imprecision (one level): The risk of a negative swab at 7 days favour honey however the confidence interval is extremely wide
6 Quality of life not reported in any of the studies
7 Only cost of dressing materials reported not other associated health care costs
8 Only one small study reported cost of materials

Figures and Tables -
Summary of findings 3. Honey compared with silver sulfadiazine for burns
Summary of findings 4. Honey for venous leg ulcers

Honey for venous leg ulcers

Patient or population: patients with Venous leg ulcers
Settings: Any
Intervention: Honey

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Honey

Complete healing (time to healing)
Follow‐up: 12 weeks

Study population

HR 1.1
(0.8 to 1.5)

368
(1 study)

⊕⊕⊝⊝
low1,2

497 per 1000

531 per 1000
(423 to 644)

Complete healing (proportion wounds healed)

Study population

RR 1.15
(0.96 to 1.38)

476
(2 studies)

⊕⊕⊝⊝
low3,4

460 per 1000

529 per 1000
(441 to 634)

Adverse events

Study population

RR 1.28
(1.05 to 1.56)

368
(1 study)

⊕⊕⊝⊝
low1,5

464 per 1000

594 per 1000
(487 to 724)

Infection
Follow‐up: 12 weeks

Study population

RR 0.71
(0.49 to 1.04)

476
(2 studies)

⊕⊕⊝⊝
low6

221 per 1000

157 per 1000
(108 to 230)

Costs
Incremental cost effectiveness ratio
Follow‐up: 12 weeks

The mean cost in the intervention group was
9.45 NZD lower
(95%CI 39.63 NZD lower to 16.07 NZD higher)7

368
(1 study)

⊕⊝⊝⊝
very low8,9

The ICER was sensitive to the inclusion

of hospitalisation costs. Hospitalisation

unlikely related to treatment and when

these were excluded the ICER was in favour of control.

Quality of Life
SF‐36 PCS
Follow‐up: 12 weeks

The mean PCS in the intervention group was
1.1 higher (95% CI 0.8 lower to 3 higher)

368
(1 study)

⊕⊕⊕⊝
moderate10

Quality of Life
SF‐36 MCS
Follow‐up: 12 weeks

The mean MCS in the intervention groups was
0.7 higher (95% CI 1.1 lower to 2.4 higher)

368
(1 study)

⊕⊕⊕⊝
moderate10

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; HR: Hazard ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded due to risk of bias (one level): Unblinded outcome assessment
2 Downgraded due to imprecision (one level): The confidence interval around the estimate of the hazard ratio ranges from a 20% reduction to a 50% increase in the hazard for healing with honey
3 Downgraded due to risk of bias (one level): Neither study used blinded outcome assessment
4 Downgraded due to imprecision (one level): The result is consistent with there being no important difference between the dressings up to honey increasing the risk of healing by just over a third
5 Downgraded due to imprecision (one level): Wide confidence intervals; only one study
6 Downgraded due to risk of bias (two levels): The diagnosis of infection is partly subjective: both trials were open label
7 Including hospitalisation costs (and $11.34 (‐$2.24 to $26.25) in favour of usual care when hospitalisation costs excluded.
8 Large difference in rates of hospitalisations and therefore associated costs between arms unlikely to be related to treatments. ICER sensitive to inclusion/exclusion of hospitalisation costs
9 Large uncertainty on cost data
10 Patients not blinded to treatment

Figures and Tables -
Summary of findings 4. Honey for venous leg ulcers
Table 1. Frequency of adverse events reported in venous ulcer trial (Jull 2008)

Adverse event

Honey treatment

Control treatment

Ulcer pain

47/187

18/181

Bleeding

3/187

3/181

Dermatitis

8/187

8/181

Deterioration of ulcer

19/187

9/181

Erythema

6/187

4/181

Oedema

4/187

1/181

Increased exudate

5/187

1/181

Deterioration of surrounding skin

5/187

3/181

New ulceration

16/187

15/181

Other

6/187

3/181

Cardiovascular

4/187

3/181

Cancer

2/187

2/181

Neurological

4/187

1/181

Gastrointestinal

4/187

2/181

Injury

10/187

9/181

Musculoskeletal

13/187

9/181

Respiratory

6/187

3/181

Other

3/187

8/181

Figures and Tables -
Table 1. Frequency of adverse events reported in venous ulcer trial (Jull 2008)
Comparison 1. Minor acute wounds: honey vs. no honey (conventional dressings)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing Show forest plot

3

213

Mean Difference (IV, Random, 95% CI)

2.26 [‐3.09, 7.61]

2 Adverse events Show forest plot

1

82

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.69, 2.05]

3 Infection Show forest plot

2

151

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.13, 6.37]

Figures and Tables -
Comparison 1. Minor acute wounds: honey vs. no honey (conventional dressings)
Comparison 2. Partial thickness burns: honey vs no honey (conventional dressings)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing (days) Show forest plot

2

992

Mean Difference (IV, Fixed, 95% CI)

‐4.68 [‐5.09, ‐4.28]

2 Adverse events Show forest plot

2

992

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.15, 2.06]

3 Negative swab at Day 7‐8 Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figures and Tables -
Comparison 2. Partial thickness burns: honey vs no honey (conventional dressings)
Comparison 3. Burns: honey with delayed graft PRN vs early excision & grafting (no honey)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing (days) Show forest plot

1

46

Mean Difference (IV, Fixed, 95% CI)

13.60 [9.82, 17.38]

2 Mean duration of antibiotic therapy (days) Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

16.0 [8.85, 23.15]

Figures and Tables -
Comparison 3. Burns: honey with delayed graft PRN vs early excision & grafting (no honey)
Comparison 4. Burns: honey vs silver sulfadiazine (SSD)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing (days) Show forest plot

4

Mean Difference (Random, 95% CI)

Subtotals only

1.1 Time to healing (days)

4

332

Mean Difference (Random, 95% CI)

‐5.12 [‐9.51, ‐0.73]

2 Proportion burns completely healed Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Burns: honey vs SSD at 4 to 6 weeks

6

462

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.98, 1.02]

3 Adverse events Show forest plot

5

412

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.20, 0.42]

4 Negative swab at Day 7 Show forest plot

5

412

Risk Ratio (M‐H, Random, 95% CI)

3.92 [1.32, 11.63]

Figures and Tables -
Comparison 4. Burns: honey vs silver sulfadiazine (SSD)
Comparison 5. Burns: honey vs. no honey (atypical dressings)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing (days) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

Figures and Tables -
Comparison 5. Burns: honey vs. no honey (atypical dressings)
Comparison 6. Mixed acute and chronic wounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Time to healing (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

2 Negative swab at Day 7 Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 6. Mixed acute and chronic wounds
Comparison 7. Chronic wounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion healed Show forest plot

6

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

1.1 Infected post‐op wounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Pressure ulcers (grade I and II) at 10 days

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.3 Leishmaniasis at 4 months (16 weeks)

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.4 Venous leg ulcers at 12 weeks

2

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.5 Diabetic foot ulcers

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Time to healing (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

2.1 Fournier's gangrene

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

3 Venous ulcers: proportion healed at 12 weeks Show forest plot

2

476

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.96, 1.38]

4 Venous ulcers: infection Show forest plot

2

476

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.49, 1.04]

5 Mixed wounds: proportion healed Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

5.1 Mixed wounds healing 2' intention at 12 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.2 Mixed wounds healing 2' intention at 24 weeks

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figures and Tables -
Comparison 7. Chronic wounds