Synergistic Effect of Aloe Vera Gel and Manuka Honey on Radiation Induced Oral Mucositis in Head and Neck Cancer Patients: Randomized Controlled Clinical Trial

Head and neck cancer is the eighth common type among all cancer types all over the world [1] The treatment comprises surgery, radiotherapy, chemotherapy or a combination escorted by restoration therapy, and social support [2] Radiotherapy leads to irreversible loss of the reproductive integrity, the cell cycle necessary for cell growth, apoptosis, and necrosis of cancer cells [3] Conventional fraction size ranges from 1.8 to 3 Grays (Gy) per fraction over 4-6 weeks [4] The accumulative dose of radiation for the primary treatment of head and neck cancer treatment is 60-70 Gy, depending on the irradiation of the tumor [5].

Radiation affects malignant cells and is also absorbed by the oral mucosa and gastrointestinal mucosa, especially in rapidly dividing cells [6] Oral mucositis is the most frequent, distressing, painful, clinical side effect of radiotherapy [7] It is defined as an inflammatory lesion of oral mucosa resulting from the cancer therapy typically manifesting as atrophy, swelling, erythema, ulceration, and pseudomembrane formation [8,9] It is described in five overlapping stages: initiation, upregulation, message generation, ulceration, and healing [9,10].

Radiation-induced oral mucositis shows hyperkeratosis of the oral mucosa after the dose of 10-20 Gy [6,8] Erythema is the first clinical sign seen on the oral mucosa, and severity of mucositis reaches at a dose of 30 Gy. After the completion of radiotherapy, the symptoms abate in 2-6 weeks [11,12] Effective management of oral mucositis is very important [13,14].

Honey is an important traditional medicine and prophylactic agent that has numerous beneficial health properties including its ability to facilitate healing.[15,16] Honey helps in the reduction of ulceration and inflammation of the biological process of mucositis.[17,18] Honey has been used to manage burns, oral infections, surgical wounds, and pressure wounds.[19,20]. Honey was applied to the oral mucosa of patients undergoing radiotherapy which is beneficial in limiting the severity of oral mucositis. Honey is a natural product with rich nutritional properties that is economical and a pleasant agent for managing mucositis [21].

Manuka honey is a monofloral honey, produced from the nectar of flowers of Manuka tree. This variety is produced from the Apis mellifera honey bees, using New Zealand Manuka plants producing specific floral-variety named as Leptospermum scoparium [22]. Manuka honey is usually rated using a classification system known as the Unique Manuka Factor (UMF), which reflects the equivalent concentration of phenol (%, w/v) required to produce the same antibacterial activity as honey.