Bardy, J., Molassiotis, A., Ryder, W.D., Mais, K., Sykes, A., Yap, B., … Lee, L. (2011). A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis. The British Journal of Oral & Maxillofacial Surgery, 50(3), 221–226.

To assess the effect of active manuka honey on the grade and duration of mucositis

Patients were randomly allocated by a computer-generated list of random numbers to be given active manuka honey or placebo (golden syrup) mixed with 2% sodium alginate, which increased the contact time by ensuring that the substance adhered sufficiently to the oral and oropharyngeal mucosa. They were shown the technique and given verbal and written instructions to rinse the mouth with 20 ml of the allocated substance and to swallow it slowly, 4 times per day for the duration of the radiotherapy (4 weeks) and for 2 weeks after treatment (42 days in total). To assess compliance, they were also asked to record daily on a card when they took the substance.

The patients were all to receive 4 weeks (20 fractions) of accelerated radiotherapy at a dose between 50 and 55 Gy. Synchronous or induction chemotherapy, or both, was permitted.

Since both substances in the study are known to be cariogenic in patients being treated by radiotherapy, all patients were seen by the hospital dentist before beginning treatment and were provided with fluoride toothpaste and a soft toothbrush and given written and verbal dental hygiene instructions. 

Inter-rater reliability was measured between assessors and found to be higher using the modified scale.

Weekly assessments of mucositis were undertaken during radiotherapy (four weeks) and every two weeks thereafter until the mucositis resolved. Weight was assessed at each assessment.

Swabs were taken from the throat to assess for bacterial and fungal infections. These were taken at baseline and during and after radiotherapy, and the process was overseen by a microbiologist consultant.

• The sample consisted of 131 patients, with 64 in the experimental arm and 63 in the control arm.
• The experimental arm was 83% male and 17% female. The control arm was 92% male and 8% female. 
• The mean age patients in the experimental arm was 59 years old. The mean age of patients in the control arm was 58 years.
• Patients were drawn from a consecutive sample who had either oral or oropharyngeal cancer.

Patients were recruited from an outpatient clinic at a cancer center in northwest England.

Patients were undergoing the active treatment phase of care.

This was a double-blind, randomized, controlled study. The treatment allocation was by minimization with an allocation probability of 2/3 to the arm that would yield a lower imbalance score.

A modified acute radiation toxicity scale of mucositis by the Radiation Therapy Oncology Group was used.

Primary analysis revealed no significant differences in the incidence of grade 3 mucositis or severity or duration of mucositis between the two groups. 

Ninety-eight percent of the patients managed at least 1 week of the intervention, and 67 patients managed more than 2 weeks. Median compliance was 2 weeks for both groups.

The incidence of pathogenic bacteria in both arms was similar to reported baseline values, which indicated that the levels of bacterial colonization were similar to those of an unirradiated mouth. It also confirms the previous findings that honey has a bacteriostatic effect, which might be the result of its hyperosmolar properties, as golden syrup had a similar effect.

No significant differences were found in either the primary or the secondary outcome measures when honey was compared with placebo. The results of the study did not agree with the findings of other trials.

• Poor compliance affected the potential impact of the intervention. Patients reported problems with the taste and texture of the product and cited the effort required to take them as reason for discontinuation.
• Compliance might have been hampered by the use of the carrier agent (sodium alginate).
• The intervention required too much volume and was too sweet for the subjects to be expected to use it daily.
• A different formulation of honey should be used for future studies, using only the active ingredient and using a more liquid formulation.
• This was a single institution study.
• No measurement for or discussion of the use of opioids for pain control in the results and discussion segment of the report, even though this topic was listed as a secondary outcome.
• The article was poorly written with several grammatical errors that hampered understanding.
• The authors did not specify if chemotherapy was given, and, if so, which drugs, amounts, and durations, all of which can influence the development of mucositis.
• Further research is needed to determine methods that are successful in treating grade 3-4 mucositis during radiotherapy.
• The study was not very practical if the median compliance was only half of the study treatment duration. The patients were to swallow 20 ml of honey 4 times a day for the duration of the study, which was too difficult for the participants to accomplish. This intervention is unlikely to be used in clinical practice.

Well-documented bacteriostatic properties of honey exist; further research needs to be done to determine feasibility in the realm of preventing oral mucositis.