|Year : 2022 | Volume
| Issue : 2 | Page : 141-145
Effectiveness of topical application of honey in the management of radiation induced oral mucositis
Karthikeya Patil, CJ Sanjay, S Viveka, Nagabhushana Doggalli, R Aishwarya
Department of Oral Medicine and Radiology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
|Date of Submission||07-Jan-2022|
|Date of Decision||27-Apr-2022|
|Date of Acceptance||08-May-2022|
|Date of Web Publication||22-Jun-2022|
C J Sanjay
Department of Oral Medicine and Radiology, JSS Dental College and Hospital, JSS Academy of Higher Education and Research, Mysore – 570 015, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background and Objective: Most patients with oral cancer receive chemoradiotherapy with or without surgery for treatment and develop oral mucositis, a debilitating adverse. Currently, there is no standard regimen for the management of radiation-induced mucositis. This study aims to evaluate the effect of honey on radiation-induced mucositis. Methods: The study consisted of 204 subjects of both genders, diagnosed and treated by radiotherapy for head and neck carcinoma and who had developed oral mucositis. The control group (n = 102) received 0.9% normal saline while the interventional group (n = 102) received honey as a topical application. Both groups were evaluated by the World Health Organization oral mucositis assessment scale at baseline (I visit) and four follow-up visits. Results: A decrease in the progression of the lesion and symptomatic relief were found in the interventional group. There was neither symptomatic relief nor a decrease in mucositis grade in the control group. Conclusion: Within the limits of this study, the results showed that the topical application of honey could be used to alleviate the symptoms in the management of radiation mucositis as it is easily available, simple, and economical.
Keywords: Apitherapy, healing, honey, oral mucositis, radiotherapy, ulceration
|How to cite this article:|
Patil K, Sanjay C J, Viveka S, Doggalli N, Aishwarya R. Effectiveness of topical application of honey in the management of radiation induced oral mucositis. J Indian Acad Oral Med Radiol 2022;34:141-5
|How to cite this URL:|
Patil K, Sanjay C J, Viveka S, Doggalli N, Aishwarya R. Effectiveness of topical application of honey in the management of radiation induced oral mucositis. J Indian Acad Oral Med Radiol [serial online] 2022 [cited 2022 Jul 1];34:141-5. Available from: https://www.jiaomr.in/text.asp?2022/34/2/141/347909
| Introduction|| |
Malignancies are the second most common cause of death globally. About 60,000 new cases of oral cancer are reported every year in India. Around 90% of oral carcinomas occur in middle-aged men, with most of them being squamous cell carcinomas. Its management protocol includes surgery, radiotherapy, and chemotherapy. Patients with head and neck carcinoma receive an accumulative dose of 60-70 Gy of radiation for primary treatment. Its immediate side effects include mucositis, oral ulcerations, nausea, and alopecia. Oral mucositis refers to the erythematous and ulcerative lesions in the oral cavity commonly seen in patients undergoing cancer therapy. Effective management of oral mucositis is of prime concern as there are no drugs to avoid or mitigate radiation-induced mucositis.
Medicine in the 21st century is an era of artificial intelligence, lasers, etc. However, the indigenous ways of treatment are still accepted and practised by people worldwide with strong beliefs. One such example is apitherapy, in which bee products are used to treat diseases.
Honey is an age-old remedy that dates to Egyptian civilization, but it has found a place lately in symptomatic management protocols. Honey has potential anti-inflammatory and antibacterial properties that enhance epithelisation and wound healing. Therefore, honey is regarded as an agent that holds promise in reducing ulceration and inflammation of the mucosa.
| Methodology|| |
In vitro and in vivo experiments have adequately investigated honey's beneficial effects on mucositis, but any intervention appraisal is incomplete without evaluating its impact on human life quality. The aim and objective of the study were to evaluate the efficacy of natural honey in the management of radiation-induced oral mucositis and recommend natural honey as an effective adjunct in the management of radiation-induced oral mucositis if found effective.
Natural honey is a product with rich nutritional qualities that could be a pleasant, simple, and economic modality for the prevention and management of chemo-radiation-induced mucositis.
The protocol was approved by the Institutional Human Ethics Committee of HCG-Bharath Hospital & Institute of Oncology ethical committee (HCG-BHIO ETHICS COMMITTEE – IECREF Number: ECM/06/19). Written informed consent was taken from all the patients, and the data was kept disclosed according to the principles of the Helsinki Declaration. The study was conducted on patients who reported to the oncology centre from January 2021 to December 2021. All subjects were recruited for the study by random sampling.
- INCLUSION CRITERIA: Patients with biopsy-proven head and neck carcinoma were planned for external beam radiotherapy with a total radiation dose ranging between 60 and 70 Gy and presented with oral mucositis. Patients aged 40–70 years with no other comorbidities such as diabetes and hypertension.
- EXCLUSION CRITERIA: Patients with systemic diseases like diabetes and hypertension. Patients experiencing xerostomia and oral sores due to ill-fitting dentures.
Two hundred and four patients were selected for the study and divided into randomly selected interventional and control groups. There were two investigators in our study. The principal investigator was blinded and distributed the amber-coloured bottles to the patients. The randomization of the groups was carried out by a computer-generated random method by the second investigator, who had no other role. All patients were strictly instructed to avoid smoking, chewing pan and spicy foods and maintain oral hygiene during the study.
The principal investigator, who was blinded, evaluated the severity of lesions clinically using the WHO oral mucositis assessment scale. Symptoms were assessed on a verbal basis at baseline and each follow-up visit.
In the interventional group, 20 mL of commercially available Dabur natural honey (manufactured by Dabur India Limited, one of India's largest Ayurvedic medicine and natural consumer products manufacturers) labelled as “A” in an amber-colored bottle was given to subjects, and they were instructed to apply using a cotton pellet topically four times per day after radiation (a total of 20 ml/day). This management protocol for honey was followed from day 1 of radiotherapy till the end of the 6th week, for which the observations of mucositis were made. They were instructed to take meals in the early morning, noon, and at night and not to interfere in such a manner with the ingestion of honey. Similarly, 20 ml of 0.9% normal saline mixed with methylcellulose in an amber-coloured bottle was labelled as B, given to the control group, and instructed to rinse it for 3 min, four times per day, starting on day 1 of radiotherapy and continuing till the end of 6 weeks.
The study was conducted for 40 days, including four follow-ups of 10 days each. The investigator evaluated the severity of lesions clinically using the WHO oral mucositis assessment scale. The WHO assessment scale monitored patient compliance.
Furthermore, patients in both groups were instructed not to swallow the oral rinses. All the patients who participated in the study were informed by their consultants about oral hygiene, including using a soft toothbrush and high-fluoride toothpaste. Furthermore, they were given written and verbal instructions about oral hygiene and its crucial importance. A coordinator was responsible for a simple reminder call to all the patients to fortify their adherence to the intervention.
WHO oral mucositis assessment scale by the WHO handbook (1979).
Grade 1: Soreness with or without erythema
Grade 2: Erythema, ulcers, patients can swallow solid food.
Grade 3: Ulcers with extensive erythema; the patient is unable to swallow.
Grade 4: Mucositis to the extent that alimentation is not possible.
None of the patients reported adverse effects of us from natural honey or 0.9% normal saline, and there were no dropouts in the study.
The collected data was tabulated and analysed using the SPSS 22.0 software for Windows. Descriptive statistics included frequency and percentage [Table 1]. The Pearson's Chi-square test was used in the present study to test the within subject effects.
|Table 1: Mucositis grading in interventional and control groups at baseline and during various visits|
Click here to view
| Results|| |
The application of natural honey for oral mucositis in the patients for 40 days showed promising results. Progression in the grade of oral mucositis was observed among patients from the interventional group with grade I and grade II mucositis when natural honey was topically applied from the first visit to the fourth visit [Graph 1], [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Interventional group pre-intervention (b): Interventional group post-intervention|
Click here to view
[Table 1] depicts the comparative distribution of subjects in the intervention and control groups between various visits of various mucositis gradings (G0, G1, G2, G3). At the second visit, the percentage of subjects with grade III mucositis was 2% in the interventional group, which is significantly less than in the control group (21.6%) (p < 0.005). At the final visit, the percentage of subjects with grade II mucositis was 7.8% in the interventional group, which is significantly less than in the control group (49%, P 0.005). In grade III, in the final visit, the percentage of subjects was 0% in the interventional group, which is significantly less than in the control group (51.0%) (p < 0.005).
Most patients with grade I and II mucositis experienced clinical alleviation during the first ten days and a gradual decrease in erythema [Figure 2]a and [Figure 2]b. Individuals treated with 0.9% normal saline demonstrated neither clinical alleviation nor a suspension in the condition's progression. As a result, the condition increased mucositis grades at each follow-up visit.
|Figure 2: (a) Interventional group pre-intervention (b): Interventional group post-intervention|
Click here to view
| Discussion|| |
Radiation therapy causes significant damage to the normal oral mucosa, tongue, salivary glands, alveolar bone, and tumour cells. The oral mucosa has a high rate of mitosis, which leads to the debilitating condition called oral mucositis.
Typically, the oral mucosa cells regenerate rapidly every 7–14 days. Radiation therapy hinders cellular mitosis and limits the oral mucosa's ability to regenerate. Due to an increased cell production rate from the surviving cells, a steady state between mucosal cell death and regeneration may arise as radiation therapy continues. However, cell regeneration cannot keep up with cell death in most cases, resulting in partial or total denudation. Patchy or confluent mucositis is a symptom of this condition. Pseudomembranes and ulceration occur as the mucositis progresses. A lack of nutrition impedes mucosal regeneration by limiting cell migration and renewal.,
Effective management of oral mucositis is of prime concern as there are no drugs for the avoidance or mitigation of radiation-induced mucositis. Local antibiotics are given in the form of tablets, which help prevent bacterial colonisation and reduce inflammation of damaged mucosa. Low-energy laser treatment with He/Ni may make mucosal cells grow and heal wounds, so it should be used to treat chemotherapy- or radiation-induced mucositis.
Honey has been used as a healing agent since the classical era, but recently there has been a newfound interest in utilising it to treat wounds. Honey is a heterogeneous mixture of proteins, flower nectar sugars, and glandular secretions produced by honeybees. Honey is formed from the transformation and concentration of nectar from flowers by two processes, interaction with the upper digestive tract secretion of honeybees and concentration due to water loss in beehives. There are different varieties of honey, like avocado honey, basswood honey, beechwood honey, blueberry honey, etc. In the present study, commercially available Dabur honey was used as it is easily available and standardised by FSSAI (Food Safety and Standards Authority of India). Honey exhibits antibacterial, analgesic, and tissue nutritive factors to stimulate re-epithelisation in damaged mucosa; thereby, it can be considered a competent agent in radiation mucositis. It has a significant impact on B- and T-lymphocyte proliferation as well as macrophage activation.
Important factors such as its hygroscopic nature, acidic pH, and inhibin converted from glucose oxidase; gluconic acid, enzymes, and tissue-nutritive minerals and vitamins aid in direct tissue repair. Honey averts the inflammatory lesion involved in radiation mucositis by stimulating granulation tissue formation, promoting angiogenesis, rapid epithelisation, and proliferation of fibroblasts, and stimulating re-epithelisation of damaged mucosa, which plays an important role in the healing process because of enhanced epithelisation of the mucosa. Honey-derived natural resin acts as a potent inhibitor of human colon adenocarcinoma cell growth and carcinogenic induction. Honey-derived natural resin inhibits human colon adenocarcinoma cells' development and carcinogenic induction. Honey is also non-cytotoxic to host cells, unlike other antimicrobials, even in high quantities.
Hussein et al. demonstrated the molecular basis of Gelam honey's anti-inflammatory effect in a mouse model. In radiation-induced mucositis, the NF-kB pathway is important. Gelam honey was found to stop nuclear translocation and activation of the NF-kB pathway, which is important.
The results of our study were consistent with those of Biswal et al., where the study group undergoing radiotherapy was treated with a topical application of natural honey. In our study, patients were advised to apply honey four times a day post-radiotherapy. In contrast, Biswal et al., in their study, advised consumption of honey before radiotherapy and consumption and topical application of honey post-radiotherapy. There was a substantial reduction in the occurrence of symptomatic grade III and grade IV mucositis among honey-treated patients compared to controls. Similar results were obtained by Rashad U M et al. where patients were administered honey topically, and no patients in the study group developed grade 4 mucositis. The observation was consistent with that of M. Motallebnejad et al., although patients were instructed to consume honey rather than apply it topically. The outcomes of their study were similar, with the mucositis score after each week being considerably lower than in the control group.
The study's shortcomings include the inability to anticipate honey contact time in patients. Furthermore, this was a single-site investigation, and a multi-centre experiment is needed to confirm the findings further.
| Conclusion|| |
In the presence of widely different standards of care for radiation-induced mucositis available, which vary from different countries and treatment centres, it is important to use economic, practical, locally available, and culturally acceptable interventions. Although with mixed results, honey showed a modest improvement in mucositis scores. The current study found that honey can be used as an aid in the management of radiation-induced mucositis symptoms.
We are grateful to the patient who gave us written consent to write this story. We would like to express our gratitude to our colleagues who supported us throughout this project.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Scully C, Epstein JB. Oral health care for the cancer patient. Eur J Cancer B Oral Oncol 1996;32:281-92.
Naidu GS, Shukla S, Nagi R, Jain S, Makkad RS. Evaluation of oral health-related quality of life in subjects diagnosed with head and neck malignancies undergoing chemotherapy, radiotherapy, and surgery. J Indian Acad Oral Med Radiol 2019;31:228-33. [Full text]
Sonis ST. New thoughts on the initiation of mucositis. Oral Dis 2010;16:597-600.
Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al
. Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004;100:1995–25.
Dorr W, Noack R, Spekl K, Farrell CL. Modification of oral mucositis by keratinocyte growth factor: Single radiation exposure. Int J Radiat Biol 2001;77:341–7.
Song JJ, Salcido R. Use of honey in wound care: An update. Adv Skin Wound Care 2011;24:40-4.
De Vries A, Sprinzl G, Reich K, Gunczler P, Thumfart W, Lukas P. GM CSF-mouthwash for treatment of chemotherapy patients with advanced head and neck cancer: A clinical trial. Ann Oncol 2001;11:409.
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47:207-14.
Wymenga AN, van der Graaf WT, Hofstra LS, Spijkervet FK, Timens W, Timmer-Bosscha H, et al
. Phase I study of transforming growth factor ß3 mouthwash for prevention of chemotherapy induced mucositis. Clin Cancer Res 1999;5:1363-8.
Soni P, Garlapati K, Kammari A, Guduru H. Growth factors in the treatment of oral mucositis in patients receiving treatment for head and neck cancers – A review. J Indian Acad Oral Med Radiol 2019;31:162-6. [Full text]
Amanat A, Ahmed A, Kazmi A, Aziz B. The effect of honey on radiation-induced oral mucositis in head and neck cancer patients. Indian J Palliat Care 2017;23:317–20.
] [Full text]
Jayachandran S, Balaji N. Evaluating the effectiveness of the topical application of natural honey and benzydamine hydrochloride in the management of radiation mucositis. Indian J Palliat Care 2012;18:190–5.
] [Full text]
Sela M, Maroz D, Gedalia I. Streptococcus mutant in saliva of normal subjects and neck and head irradiated cancer subjects after consumption of honey. J Oral Rehabil 2000;27:269–70.
Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res 1995;55:2310–11.
Sedighi I, Molaee S, Amanati A, Khoeinipourfar H, Nouri S. Antimicrobial activity of natural honey: Topical application of pure natural honey in prevention of chemotherapy induced oral mucositis. J Compr Pediatr 2013;4:138-42.
Hussein SZ, Mohd Yusoff K, Makpol S, Mohd Yusof YA. Gelam honey attenuates carrageenan-induced rat paw inflammation via NF-kB pathway. PloS One 2013;8:e72365.
Biswal BM, Zakaria A, Ahmad NM. Topical application of honey in the management of radiation mucositis. Support Care Cancer 2003;11:242-8.
Rashad UM, Al-Gezawy SM, El-Gezawy E, Azzaz AN. Honey as topical prophylaxis against radiochemotherapy-induced mucositis in head and neck cancer. J Laryngol Otol 2009;123:223-8.
Motallebnejad M, Akram S, Moghadamnia A, Moulana Z, Omidi S. The effect of topical application of pure honey on radiation-induced mucositis: A randomized clinical trial. J Contemp Dent Pract 2008;9:40-7.
[Figure 1], [Figure 2]