Propolis, or bee glue, is a resin-like material made by bees to coat the inside of the hive. Propolis is derived from the buds of poplar and cone-bearing toma trees and is believed to have antioxidant and anti-inflammatory properties. Propolis has been studied in patients with cancer for treatment of mucositis.
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.
Akhavan-Karbassi, M.H., Yazdi, M.F., Ahadian, H., & SadrAbad, M.J. (2016). Randomized double-blind placebo-controlled trial of propolis for oral mucositis in patients receiving chemotherapy for head and neck cancer. Asian Pacific Journal of Cancer Prevention, 17, 3611–3614.
To test the effectiveness of propolis as a mouthwash to reduce chemotherapy-induced oral mucositis
Patients were randomized to receive a propolis mouth rinse (30% extract) or sterile water placebo rinse. Patients were to swish 5 ml of the rinse in the mouth for 60 seconds, gargle, and expectorate. Rinses were used three times daily for seven days.
PHASE OF CARE: Active antitumor treatment
Double-blind, randomized, controlled trial
World Health Organization (WHO) mucositis grading
By day seven, erythema, wounding, and general mucositis grades were lower in the propolis group (p < 0.006). Mucositis grades were lower in the propolis group.
The findings suggest that propolis mouth rinses may be helpful to manage oral mucositis in patients with head and neck cancer receiving chemotherapy and radiation therapy. Well designed research is needed to confirm these findings.
This study report has multiple flaws and provided only weak evidence of the potential effectiveness of propolis for the reduction of oral mucositis. Well designed research is needed to further evaluate the potential effects of this intervention.
Augusto Souza Noronha, V.R., Araujo, G.S., Gomes, R.T., Iwanaga, S.H., Barbosa, M.C., Abdo, E.N., ... Santos, V.R. (2014). Mucoadhesive propolis gel for prevention of radiation-induced oral mucositis. Current Clinical Pharmacology, 9(4), 359–364.
To determine the efficacy of propolis gel on radiation-induced oral mucositis
Patients applied a coffee spoon (10 g) of propolis gel 5.0% three times a day (every 8 hours) beginning 24 hours before radiation began, continuing throughout radiation treatment, and two weeks post-treatment. The propolis gel was created following Brazilian safety guidelines. Propolis gel was applied on the tongue and then spread on the oral mucosa. Patients could use a swab or a finger covered with a latex glove to spread the gel if they had difficulty moving their tongue. Mucositis, food intake, and pain were measured at a weekly follow-up. Exfoliative cytology of buccal mucosa, palate, and tongue was performed to confirm the absence of Candida-related mucositis.
83.33% of patients did not develop oral mucositis; 8.33% developed grade I and 8.33% developed grade II oral mucositis. Patients reported no pain associated with the propolis gel. More than 80% of patients who participated in the study were satisfied with the product and would recommend its use.
Mucoadhesive propolis gel could be a useful topical alternative for prevention of radiation-induced oral mucositis. In this study, no participants developed severe mucositis. Patients found the propolis gel used in this study to be acceptable and did not report pain or discomfort associated with the application of this product.
At this time, evidence is limited for the use of propolis/bee glue in the prevention and treatment of oral mucositis. In this study, patients found the mixture of propolis gel 5.0% to be an acceptable intervention. The majority of patients in this study did not develop severe mucositis; however, the study has many flaws, including a lack of randomization, no control group, and a small sample size. Additionally, the dose of radiation varied among participants. More research is needed to determine the effectiveness of propolis/bee glue on the prevention and treatment or oral mucositis.
Eslami, H., Pouralibaba, F., Falsafi, P., Bohluli, S., Najati, B., Negahdari, R., & Ghanizadeh, M. (2016). Efficacy of Hypozalix spray and propolis mouthwash for prevention of chemotherapy-induced oral mucositis in leukemic patients: A double-blind randomized clinical trial. Journal of Dental Research, Dental Clinics, Dental Prospects, 10, 226–233.
To evaluate Hypozalix artificial saliva and propolis mouthwash efficacy for the prevention of chemotherapy-induced oral mucositis in patients with leukemia.
Double-blind RCT with patients assigned to three groups. The control group used the CHX mouthwash and fluconazole. Group 1 and 2, Hypozalix and propolis mouthwashes, respectively, added to combination therapy used in control group. Results compared between three groups after 14 days.
Double-blind RCT, one control and two intervention groups.
Descriptive two-part questionnaire checklist and OM severity checklist. The tool used to collect data was a two-part questionnaire and a checklist to determine the severity of mucositis. The two-part questionnaire was used to collect demographic data (age and gender) and consisted of questions on the type of disease, history of chemotherapy, presence or absence of systemic disease other than malignancy, and the presence or absence of skin or respiratory allergy. The second part of the questionnaire consisted of questions on the severity of xerostomia, ease of mastication and swallowing, the severity of burning sensation, the quality of sleep during the night, and the tendency to continue to use the medications; the patients completed this part before and after the intervention. In addition, in order to determine the severity of oral mucositis, a checklist was used, which was designed based on the criteria of WHO; based on these criteria, oral mucositis is divided into five distinct grades from 0 to 4.17. To determine validity of the questionnaire, content validity method was used. To determine reliability of the questionnaire, simultaneous observation technique was used. To this end, observations were carried out by two observers with similar characteristics, using similar guidelines on 10 samples, which yielded a correlation coefficient of 0.94. Then, the questionnaire was completed using interviews and patient files.
After 14 days, 50% of patients in the control group (CHX mouthwash and fluconazole) exhibited signs of recovery from xerostomia. For group 2 (propolis mouthwash and CHX mouthwash and fluconazole), 50% of patients exhibited some signs of recovery from xerostomia. 95.8% patients in group 1 (CHX mouthwash and fluconazole and Hypozalix spray) reported recovery from xerostomia. Chi-squared test statistically significant (p = 0.0006). At the end of the study, 29.17% in control group, 87.5% in group 1, and 70.83% in group 2 exhibited easy mastication. Chi-squared test significant statistically (p = 0.0001). 33.3% in control group, 63.3% in group 1, and 87.5% of patients in group 2 exhibited easy swallowing. Chi-squared test statistically significant (p < 0.0001). At end of study, 33.3% in control group, 58.3% in group 1, and 91.6% in group 2 were interested in continuing to use the product. Chi-squared test statistically significant (p = 0.0002). 16.67% of patients in control group, 25% in group 1, and 62.5% in group 2 exhibited more full night’s sleep and less waking up. Chi-squared test statistically significant (p = 0.0018). In relation to an improvement in oral burning sensation, 8.33% of patients in control group, 25% in group 1, and 91.67% in group 2 exhibited decrease in burning sensation. Chi-squared test significant statistically (p < 0.0001). 62.5% of patients in control group, 62.5% in group 1, and 95.8% in group 2 had a higher rate of feeling comfortable. Chi-squared test was significant (p = 0.0103). A clinical examination of patients five days after using the medications showed 8.33% of patients in control group, 12.5% in group 1, and 50% in group 2 were free of mucositis. However, 25% of patients in control group and 16.6% in group 1 had grade 4 mucositis. None in group 2 exhibited grade 4 mucositis. Chi-squared test significant (p = 0.0007). A clinical examination of patients 10 days after using the medications showed 25% of patients in control group, 33.3% in group 1, and 50% in group 2 were free of mucositis. 12.5% of patients in control group and 4.17% in group 1 had grade 4 mucositis. None in group 2 had grade 4 mucositis. However, chi-squared test indicated that the difference was not statistically significant (p = 0.1135).
50% of patients in control group, 95.8% of patients who received Hypozalix, and 50% who received Propolis exhibited decrease in xerostomia severity. 29.17% of patients in control group, 87.5% in Hypozalix group, and 70.83% in Propolis group exhibited easy mastication. 33.3% of patients in control group, 63.3% of patients in Hypozalix group, and 87.5% of patients in Propolis group exhibited easy swallowing. 91.6% of patients in propolis group were interested in continuing to use product. The lowest tendency was seen in control group patients, followed by those in Hypozalix group. 62.5% of patients in propolis group exhibited less waking up at night and 95.8% of them had a higher rate of feeling comfortable. The lowest burning sensation was detected in that group. Propolis resulted in significantly greater decrease in severity of mucositis compared to Hypozalix and control group five days after using medications. These contradictory results might be attributed to differences in study designs and in Propolis origins. In many cases, use of Propolis mouthwash yielded significantly better results, and patients exhibited a greater tendency to continue to use it. If results of this study are confirmed by other studies, treatment with Propolis can reduce secondary oral infections and mucositis caused by chemotherapy. Since Propolis and Hypozalix had positive effects on decreasing mucositis induced by chemotherapy in this study, toothpastes may be designed with propolis base. Hypozalix spray or propolis mouthwash in association with CHX mouthwash and fluconazole simultaneously at the start of chemotherapy resulted in decrease in chemotherapy complications after 14 days. Propolis mouthwash yielded better results and the patients exhibited greater tendency to continue to use it.
Tomazevic, T., & Jazbec, J. (2013). A double blind randomised placebo controlled study of propolis (bee glue) effectiveness in the treatment of severe oral mucositis in chemotherapy treated children. Complementary Therapies in Medicine, 21, 306-312.
To assess the efficacy of propolis versus placebo for the treatment of chemotherapy-induced severe oral mucositis (OM) treatment as a complementary and alternative medicine to alleviate severe OM from cancer therapy in the pediatric population. Propolis is a resinous material collected by bees from various plant sources and mixed with the bee’s salivary enzymes and beeswax. Recent scientific evidence suggests that honeybee products include anti-inflammatory, antioxidant, and antimicrobial properties.
The pediatric patients randomly were assigned to two groups: propolis or placebo. The oral care protocol consisted of teeth brushing.
The propolis or placebo was applied twice a day—once in the morning and once in the evening. The patients' OM was assessed according to the modified Eilers Oral Assessment Guide (OAG) twice a week when the patients were in the hospital. Patients were followed for the period of the chemotherapy or the first six months of the chemotherapy. An average of 0.38 g of propolis or placebo was used for each application. Each patient was given an information folder to reinforce cooperation and help them remember the protocol. A protocol follow-up regarding side effects and efficacy was assessed by questionnaire.
OM was clinically assessed using a dental mirror and portable head light. OM was scored according to the modified Eilers OAG twice a week.
The study assessed OM episode frequency, duration, and severity. The OM episode frequency and OM mean duration were assessed. The frequency of severe OM and duration of OM were not statistically significant between the study groups. Thus, the findings found that severe OM was of slightly shorter duration and of a lesser extent in the propolis group. The study results demonstrated that almost half of the patients enrolled in the study suffered from severe OM. Severe OM was seen in 18 (45%) patients. In the propolis group, 8 of 19 (42%) patients had OM, while in the placebo group, the corresponding number was 10 of 21 (48%). Twenty-four episodes of severe OM were recorded—10 (42%) in the propolis group and 14 (58%) in the placebo group.
The authors do not recommend propolis in severe OM as a treatment plan. Because of the limitations in the study design, further clinical studies are needed to verify whether the use of propolis in OM treatment truly is not justified.
The study was limited to the pediatric population in one hospital. Therefore, there is a need to replicate it with a different study population and multiple settings to establish regular use and guidelines.