Hawley, P., Hovan, A., McGahan, C.E., & Saunders, D. (2014). A randomized placebo-controlled trial of manuka honey for radiation-induced oral mucositis. Supportive Care in Cancer, 22, 751–761.

To determine if honey swished, held, and swallowed reduced the severity of radiation-induced oral mucositis (ROM)

Honey and placebo gel were provided in 5 mL packets to be taken after salt/bicarbonate oral rinses four times a day after meals and after radiotherapy or approximately the same time on non-treatment days. Participants were to pour the product into their mouth, circulate it for 30 seconds, and swallow. Subjects were instructed not to eat, drink, or rinse their mouth for 30 minutes following swallowing the honey or placebo. Treatment started on the first day of radiation and continued for seven days following the last radiation treatment. Visits to the oral oncology/dentistry department were scheduled weekly until mucositis was resolved. During each visit, an oral examination was done for mucositis severity rating, a brief questionnaire was conducted, and weight was obtained. Unused treatment medication was collected at the last visit to measure compliance.

• N = 81  
• MEAN AGE: Honey arm: 56.8 years, placebo arm: 59.5 years
• MALES: Honey arm: 81%, placebo arm: 84%; FEMALES: Honey arm: 19%, placebo arm: 16%
• KEY DISEASE CHARACTERISTICS: Head and neck cancer—hypopharynx, larynx, nasopharynx, oral cavity, oropharynx
• OTHER KEY SAMPLE CHARACTERISTICS: Radiation therapy of ≥ 50 Gy; 62% had concurrent chemotherapy; Caucasian

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Vancouver and Sudbury, Canada

• PHASE OF CARE: Active antitumor treatment

• Double-blind, randomized, placebo-controlled, investigator-initiated

• Sialometry and mucositis severity scales from the Radiation Therapy Oncology Group (RTOG)
• World Health Organization (WHO) Oral Mucositis Scale

There were no differences found between the treatment and placebo arms for any of the three outcome assessment scales of mucositis for quality of life, symptom scores, or sialometry. Both the honey (35%) and placebo (43%) groups had lower than expected rates of ≥ grade 3 mucositis.

The honey, when used as directed in this study, did not significantly decrease the severity of ROM. The treatment and placebo groups were well matched, and the blinding was effective. The dropout rate was high (honey: 57%, placebo: 52%, those receiving concurrent chemotherapy: 59%). Most of the dropouts were related to nausea. Patients receiving radiation only had a dropout rate of 48%. Only 48 patients had complete weekly mucositis assessments.

• Small sample (< 100)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: The initial plan for the study was to enroll 180 subjects. The study was terminated at planned interim analysis when 106 patients had been recruited.

There have been varied outcomes in studies of honey for the treatment of mucositis. Differences in methodology could explain at least part of the variability. In this study, the subjects tolerated the honey poorly because of nausea and gagging, and a couple patients experienced a burning sensation. The authors referenced a study from New Zealand in which a honey mouthwash was used because undiluted honey caused extreme nausea, vomiting, and stinging sensations. Potential reasons for the lack of efficacy seen could be that the mucositis tools may not have had adequate sensitivity to reveal any clinical difference between or the osmotic effect of the honey and placebo. Also, Christian areas like Canada, New Zealand, and Great Britain, where honey does not have any special significance, may differ from Muslim areas that have the Koran’s references to honey’s healing powers.