ONC: Honey (2006)


Biswal BM, Zakaria A, Ahmad NM. Topical application of honey in the management of radiation mucositis. A preliminary study. Support Care Cancer. 2003;11:242-248

Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To study the effect of honey on the oral mucosa of radiation patients compared to control radiation patients.
Inclusion Criteria:
  • Patients undergoing radiation therapy using a 6-MV linear accelerator with external beam radiation at a rate of 2 Gy per fraction, 5 fractions per week for 6-7 weeks to the head and neck, AND
  • Signed informed consent prior to radiation therapy, AND
  • Enrolled from November 2000 to October 2001
Exclusion Criteria:
  • Prior or concurrent chemotherapy, OR
  • Presence of systemic disease, OR
  • Prior radiation therapy
Description of Study Protocol:

Recruitment Patients about to undergo XRT to the head and neck were invited to participate in this study.


Design Forty patients were randomly assigned by a computer generated number to the study (n=20) or control arm (n=20).  Study participants were instructed to consume 20 ml of natural honey three times a day for the duration of their radiation therapy.


Patients in the study arm were instructed throughout the XRT treatment to rinse natural honey (from the tea plant, Camellia sinensis, found on the Cameron Highland peninsula of Malaysia and filtered and tested for this study) on oral mucosa and slowly swallow to allow it to coat the oral and pharyngeal mucosa, timing as directed:

  • 20 ml 15 minutes before XRT
  • 20 ml 15 minutes after XRT
  • 20 ml six hours after XRT

Both study and control arms were instructed on adequate fluid intake, consumption of high-protein diet and appropriate oral care. (Unsure of when instructed and how frequently).

Statistical Analysis

Descriptive statistics using Microsoft Excel for morbidity scores, treatment-related scores and demographics.

Chi square analysis was used for differences in nutritional parameters, treatment breaks, total duration of mucositis and morbidities, etc.

Data Collection Summary:

Timing of Measurements

1. Before and after radiation therapy

  • Oro-dental evaluation
  • Lab values include liver function tests, kidney function and blood sugar

2. Weekly assessment

  • tumor response and development of complications
  • body weight
  • full blood count
  • mucositis by clinical and mirror examinations, graded by the Radiation Therapy Oncology Group (RTOG) scoring system
  • treatment delays/gaps from intolerable mucositis

RTOG mucositis grades

Mucositis grade

Status of oral/pharyngeal mucosa

Further directions

0 No change
1 Mucosal erythema
2      Studded mucositis
3 Confluent mucositis
4 Ulceration Requires a treatment break

Dependent Variables

  • Mucositis score (measured by RTOG scale)
  • Body weight 
  • Length of treatment delay

Independent Variables

Consumption of honey 20 ml three times a day


Control Variables

None provided


Description of Actual Data Sample:

Initial N: 40 patients total- 20 in study arm, 20 in control arm

M:F ratio    15:5 study arm, 8:12 control arm

Attrition (final N): no change

Age: study arm- median 63 years (range- 19-89)

        control arm- median 54 years (range: 14-78)

Ethnicity: Not indicated but study completed in Malaysia

Other relevant demographics:

Mean radiation field: Study arm- 53.4 cm2 , control arm- 32 cm2

Stage of disease

Study arm

Control arm

T1 1 0
T2 1 1
T3 3 5
T4 12 12
Metastasis 2 0

Anthropometrics: Body weight was measured in kilograms

  • Study arm: Median 52 kg, Mean 50 kg, range 28-75 kg
  • Control arm: Median 45 kg, Mean 46.5 kg, range 33-68 kg

Location: Division of Radiotherapy and Oncology, Universiti Sains Malaysia, Kelantan, Malaysia


Summary of Results:



Study arm


Control arm


Statistical Significance of Group Difference

Patients with mucositis




Patients with grade 3/4 mucositis 4 (20%) 15 (75%) 0.0005

Mean grade of mucositis




Median grade of mucositis 1 2

Mean onset of mucositis (week)

3     3 NS
Mean duration of mucositis (days) 7 7 NS
Evaluation of weekly weight loss +9 to -8 kg +2 to -9 kg not evaluated
Number of patients with weight gain 55% 20% 0.05

Number of patients with mucositis-related treatment interruptions





Other Findings

Of control patients who experienced treatment interruptions, the range of the treatment delay in days was 4-9 days. These patients required nutritional support, topic anesthetics and analgesics.

Author Conclusion:
Although this is a small study, the authors concluded that honey is useful in management of radiation mucositis. The honey application could have potential in the management of chemotherapy and BMT induced mucositis/stomatitis. Further randomised studies are needed. Natural honey needs to undergo further quality assurance to guarantee similar products. 
Funding Source:
University/Hospital: University Sains Malaysia
Reviewer Comments:

Research was sponsored by a research grant form the Universiti Sains Malaysia.


  • Length of XRT not indicated (could be different lengths of treatment, therefore different total dosing of honey)
  • Not indicated in other forms of analgesics/topical agents were taken by patients
  • Did not indicate how honey was supplied to patients (daily, weekly, etc and storage)
  • What about weekends without treatment
  • Did not verify amount patients took or if followed prescribed regimen (compliance)
  • Differences in ages and sex of study and control arms not discussed or evaluated for statistical significance (however pretty representative of head and neck cancer population)
  • Smoking and drinking status not indicated (could affect mucositis)
  • Appears the radiation area is significantly different between groups, not discussed
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) No
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) No
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? No
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes