Honey is a carbohydrate compound made by bees. Most microorganisms do not grow in honey because of its osmotic pressure, and its local application has been examined for its effects on wound healing. Honey has been examined in patients with cancer for the management of mucositis as an oral rinse and for radiodermatitis as a dressing. Various formulations of medical and nonmedical grade honey have been used.
Cho, H.K., Jeong, Y.M., Lee, H.S., Lee, Y.J., & Hwang, S.H. (2015). Effects of honey on oral mucositis in patients with head and neck cancer: A meta-analysis. The Laryngoscope, 125, 2085–2092.
PHASE OF CARE: Active antitumor treatment
APPLICATIONS: None stated
Administration of Honey Versus Control (Mucositis-Related Adverse Effects)
This study demonstrated the potential efficacy of honey administration in the prevention of oral mucositis and weight loss during radiotherapy and chemotherapy in patients with head and neck cancer.
Co, J.L., Mejia, M.B., Que, J.C., & Dizon, J.M. (2016). Effectiveness of honey on radiation-induced oral mucositis, time to mucositis, weight loss, and treatment interruptions among patients with head and neck malignancies: A meta-analysis and systematic review of literature. Head and Neck, 38, 1119–1128.
STUDY PURPOSE: To synthesize the available literature to determine the role of honey in reducing oral mucositis, time to onset of mucositis, weight loss, and treatment interruptions among patients with head and neck cancers undergoing radiation with or without concomitant chemotherapy
TYPE OF STUDY: Meta analysis and systematic review
PHASE OF CARE: Active antitumor treatment
Honey was significantly better in lowering the risk for treatment interruptions and probably less weight loss but did not decrease the rate of the peak mucositis score. The results for prolonged onset of mucositis is favorable with the honey intervention in two studies, but one study did not show a significant difference.
The results showed that the honey intervention is effective in reducing treatment interruption. Other measures (weight loss, peak mucositis score, time to mucositis) need further meta-analysis to establish. Further well-designed research is needed to confirm the usefulness of honey preparations.
Song, J.J., Twumasi-Ankrah, P., & Salcido, R. (2012). Systematic review and meta-analysis on the use of honey to protect from the effects of radiation-induced oral mucositis. Advances in Skin & Wound Care, 25, 23–28.
To investigate whether the use of honey provides protection from the effects of radiation-induced mucositis
Databases searched were PubMed, MEDLINE via OVID, EMBASE, CINAHAL via EBSCO, and Cochrane.
Keywords searched were honey and mucositis or stomatitis.
Studies were included in the review if they
Studies were excluded if they
A total of 15 references were retrieved. Four trials reported on the protective effects of honey. One of these was nonblinded. The remaining three were randomized examiner-blinded, and these three trials were assessed for overall risk of bias using the Cochrane method. Three of the four studies met the inclusion and exclusion criteria for the meta-analysis.
All patients were undergoing the active treatment phase of care.
Meta-analysis of the of the three trials reported that honey appeared to have protective effects against radiation-induced mucositis by 80% compared to the control group. Overall relative risk of developing mucositis was almost 80% lower (risk ratio, 0.19; 95% confidence interval, 0.098–0.371) in the honey treatment group than in the control group.
Trials were fairly homogeneous (I² = 0%, p = 0.39), so meta-analysis used a fixed-effects model (Mantel-Haenszel method) to calculate a pooled risk ratio.
Further research is needed to strengthen the current evidence prior to any clinical recommendations for practice. They suggested blinding the assessor in future studies.
Worthington, H.V., Clarkson, J.E., Bryan, G., Furness, S., Glenny, A.M., Littlewood, A., … Khalid, T. (2011). Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews (Online), 4(4), CD000978.
To evaluate the evidence for prophylactic agents in management of oral mucositis in patients with cancer receiving treatment
Databases searched were MEDLINE, CANCERLIT, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature (LILACS), System for Information on Grey Literature in Europe (SIGLE), and the Cochrane Database.
An extensive list of search terms and strategies used per database was provided in the article.
Studies were included in the review if they
A total of 383 references were retrieved. Risk of bias was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions. Studies were categorized as low, unclear, or high risk of bias. Studies were labeled using the GRADES system for evaluating quality of evidence.
Findings support the benefits of cryotherapy and keratinocyte growth factor. The low quality of evidence in most of the other interventions points to the need for ongoing, well-designed research in this area. The presentation of findings in many publications made meta-analysis impossible.
The rationale for the authors' summaries of findings was not entirely clear. Similar RR ratio results with similar evidence quality levels were identified differently in terms of potential benefit. Although the review was inclusive and extensive, interpretation of results was inconsistent. High heterogeneity existed in most interventions, and most studies were either at high or unclear risk of bias with low GRADES scoring. Studies did not always differentiate between mucositis and candidiasis, which would affect recommendations.
This article suggests strong support for use of cryotherapy and keratinocyte growth factor for mucositis prevention. It suggests possible benefit from aloe vera, amifostine, IV glutamine, G-CSF, honey, laser, and antibiotic lozenges. Sucralfate may reduce the severity of mucositis. These findings should be interpreted with caution, given the relatively low quality of overall evidence and high heterogeneity across studies included in meta-analysis, as well as the fact that treatments and sample characteristics were highly varied.
STUDY PURPOSE: To determine the prophylactic effects of honey on radiation- and chemotherapy-induced mucositis
TYPE OF STUDY: Meta-analysis and systematic review
PHASE OF CARE: Active antitumor treatment
Honey treatment reduced the incidence of oral mucositis in the honey group by 65% compared to the control group. The type of radiation therapy (source, dose) may have influenced the results.
Mostly low quality/high risk of bias studies
Honey prevents the incidence of mucositis compared to no intervention. However, more randomized, controlled trials are needed to determine the prophylactic effects of honey on patients receiving radiation or radiation and chemotherapy.
Abdulrhman, M., El Barbary, N.S., Ahmed Amin, D., & Saeid Ebrahim, R. (2012). Honey and a mixture of honey, beeswax, and olive oil-propolis extract in treatment of chemotherapy-induced oral mucositis: A randomized controlled pilot study. Pediatric Hematology and Oncology, 29, 285–292.
To evaluate the effect of topical use of honey and a mixture of honey, olive oil-propolis extract, and beeswax (HOPE) as natural products in the treatment of chemotherapy-related oral mucositis
Patients were randomly assigned to one of three groups, with 30 patients in each group. All patients used routine oral care, which included toothbrushing with a soft brush and normal saline rinses three times daily before topical treatment. All treatments were done three times daily to affected oral mucosa until healing or for 10 days, whichever came first. Topical treatments in each group were performed by the resident or nursing staff under researcher supervision.
The study was conducted at a single site, inpatient setting at Hematology-Oncology of Children's Hospital of Ain Shams University in Egypt.
This was a randomized, non-blinded, controlled, clinical phase II trial.
The superiority of topical honey alone may be related to the amount of honey used as well as better distribution in the oral cavity.
Mucositis is a significant debilitating side effect of cancer therapy. Effective interventions to reduce or eliminate the severity of this symptom are needed. Further research is needed in all patient populations.
Al Jaouni, S.K., Al Muhayawi, M.S., Hussein, A., Elfiki, I., Al-Raddadi, R., Al Muhayawi, S.M., . . . Harakeh, S. (2017). Effects of honey on oral mucositis among pediatric cancer patients undergoing chemo/radiotherapy treatment at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia. Evidence-Based Complementary and Alternative Medicine (eCAM), 2017, 5861024.
To evaluate the effects of honey on severe oral mucositis
Patients were randomized to the honey or control group. The experimental group was given a topical application of honey before the development of mucositis. Both groups received routine oral hygiene with lidocaine, mycostatin, daktarin mouth gel, and mouthwash.
Open-label, randomized, controlled trial
Analysis showed an absolute risk reduction for the development of grade 3–4 mucositis of 35% among those using honey (p = 0.02). Less Candida colonization (p = 0.003) and bacterial colonization (p = 0.003) were seen in the honey group.
Honey may have some benefit in the management of oral mucositis.
There may be some benefit from the use of honey to coat oral mucosa in the management of chemotherapy-induced oral mucositis. This study had several limitations.
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.
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.
Well-documented bacteriostatic properties of honey exist; further research needs to be done to determine feasibility in the realm of preventing oral mucositis.
Francis, M., & Williams, S. (2013). Effectiveness of Indian turmeric powder with honey as complementary therapy on oral mucositis: A nursing perspective among cancer patients in Mysore. Nursing Journal of India, 105, 258–260.
To test the effectiveness of the application of a mixture of turmeric and honey on treatment-induced oral mucositis in patients receiving chemotherapy and radiation therapy
Patients were randomly assigned to receive the mixture of turmeric and honey or to a control group that did not receive the intervention. The mixture was applied for five minutes before treatment and again five minutes after treatment. Study measures were obtained on days 2, 4, and 6 of treatment.
The mucositis score was significantly lower at all post measurements in the experimental group (p < 0.05). Scores were similar between groups at baseline, but subsequent measures were lower in the experimental group.
The combination of turmeric and honey may provide some protection against the development of oral mucositis and may provide benefit for treatment.
The results of this study suggest that turmeric and honey may have some promise in the management of oral mucositis, but this study has several substantial limitations. Further well-designed research is needed. One of the basic needs for preventing and managing oral mucositis is regular mouth care, the foundation of any intervention.
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.
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.
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.
Jayachandran, S., & Balaji, N. (2012). Evaluating the effectiveness of topical application of natural honey and benzydamine hydrochloride in the management of radiation mucositis. Indian Journal of Palliative Care, 18(3), 190–195.
To evaluate the effect of honey and 0.15% benzydamine hydrochloride on the onset and severity of radiation mucositis when compared to 0.9% normal saline
This was a single site, outpatient study conducted in Chennai, India.
Patients were undergoing the active antitumor treatment phase of care.
This was a three-group, randomized, controlled trial.
Patients were assess via clinical exam.
The onset of mucositis and progression to grades 2, 3, and 4 were noted for each group. Group I had a later onset of grades 1, 2, 3, and 4 mucositis compared to Groups II and III. The difference was statistically significant (p < 0.001).
Honey can be an effective agent in managing radiation-induced oral mucositis. It is simple, inexpensive, and readily available. Further randomized studies are essential to validate the findings.
Mucositis during RT for oral malignancy is a continuing challenge for patients. Further testing of honey is needed. The availability and cost are benefits. The treatment is not complex or impractical.
Maiti, P.K., Ray, A., Mitra, T.N., Jana, U., Bhattacharya, J., & Ganguly, S. (2012). The effect of honey on mucositis induced by chemoradiation in head and neck cancer. Journal of the Indian Medical Association, 110, 453–456.
To evaluate the use of natural honey for treatment of radiation mucositis
Patients were randomly assigned to the honey treatment or control group. Patients in the intervention group were instructed to take 20 ml of honey 15 minutes before radiation therapy, 15 minutes after radiation therapy, and at bedtime. On days when they had no radiation treatment, they were to take the same amount of honey 3 times per day. Patients were evaluated at baseline, weekly during treatment, and at 3 and 6 weeks after completion of radiation therapy.
The study was conducted at a single outpatient site in India.
Patients were undergoing the active antitumor treatment phase of care.
This was a randomized controlled trial.
The authors reported that honey delayed the onset of severe mucositis in about 80% of the intervention group, while 63% of the control group developed severe mucositis. Grade 3 mucositis developed in 11 patients in the control group and 5 patients in the study group. No statistical analysis was done.
This study suggests that honey may help to delay the onset of mucositis in patients with head and neck cancer during radiation therapy; however, multiple limitations in this report make it impossible to draw firm conclusions.
Findings as reported from this study are inconclusive regarding any effect of honey on the development of mucositis.
Motallebnejad, M., Akram, S., Moghadamnia, A., Moulana, Z., & Omidi, S. (2008). The effect of topical application of pure honey on radiation-induced mucositis: A randomized clinical trial. Journal of Contemporary Dental Practice, 9(3), 40–47.
Patients received 20 mL pure, natural honey 14 minutes before radiotherapy, then 20 mL 15 minutes and six hours after radiotherapy. Honey was rinsed and gradually swallowed to coat the oral and pharyngeal mucosa.
OMAS scores were significantly lower for the honey group than the control group for all weeks (p = 0.000). Significant differences were noted during week six of therapy. Mean weight loss was significantly higher in the control group (p = 0.000).
Raeessi, M.A., Raeessi, N., Panahi, Y., Gharaie, H., Davoudi, S.M., Saadat, A., . . . Jalalian, H. (2014). \"Coffee plus Honey\" versus \"topical steroid\" in the treatment of chemotherapy-induced oral mucositis: A randomised controlled trial. BMC Complementary and Alternative Medicine, 14, 293-6882-14-293.
To draw a comparison between the therapeutic effects of treatment modalities (topical steroid, honey, honey plus coffee) in patients with oral mucositis
Patients were randomized to one of three groups that each received a 600 g syrup solution. The solution in the steroid group (S) contained 20, 8 mg Betamethasone solution ampoules. The solution in the honey plus coffee group (HC) contained 300 g of honey plus 20 g of instant coffee. The solution in the honey group (H) contained 300 g of honey. Every three hours for one week, patients were instructed to sip 10 ml of their solution and swallow it. Data were collected prior to the initiation of the intervention and one week later. Patients were not allowed to use any other anti-inflammatory agents during the study. Patients and providers were blinded to the groups.
Double-blinded, randomized clinical trial
All three regimens significantly reduced oral mucositis at the end of the intervention week (p < .05).
A steroid solution, honey plus coffee solution, or honey only solution reduced the severity of oral mucositis after one week of treatment.
Further investigation is needed on this intervention taking into account participants' diseases and chemotherapy regimens received.
Rashad, U.M., Al-Gezawy, S.M., El-Gezawy, E., & Azzaz, A.N. (2009). Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. Journal of Laryngology and Otology, 123, 223–228.
Patients smeared 20 mL of pure, natural honey (acidic with a pH of about 3.9) on the inside of their mouths 15 minutes before, 15 minutes after, and six hours after radiation. Patients rinsed honey on oral mucosa and then swallowed it slowly. Patients were randomized to the treatment or control group. Patients also used benzydamine HCL plus supportive oral care measures. A solubility-reducing factor present in honey can activate in the absence of saliva.
Yarom, N., Ariyawardana, A., Hovan, A., Barasch, A., Jarvis, V., Jensen, S.B., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of natural agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21, 3209–3221.
PURPOSE: Review evidence and provide guidelines for use of natural agents in the prevention and management of oral mucositis in cancer
TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy, radiation therapy, or stem cell transplant
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Systematic review of evidence, quality rating using Hadorn criteria, and level of evidence classified via Somerfield criteria
DATABASES USED: MEDLINE
KEYWORDS: Alternative, complementary, homeopathic, aloe vera, beta carotene, chamomile, chines herbal, folic acid, and numerous other specific natural agents
INCLUSION CRITERIA: Not specified, other than use of a natural agent
EXCLUSION CRITERIA: Not specified
PHASE OF CARE: Active antitumor treatment
Ninety-nine papers were identified, and, of these, 49 papers were included in the review.
Findings do not support efficacy of currently studied natural herbal agents and other agents for prevention of oral mucositis. Systemic zinc supplementation may be helpful for patients with oral cancer receiving treatment. Glutamine is not recommended in patients undergoing cell transplant. Further, well-designed research in this area continues to be needed.