Currently, chemoradiotherapy-induced OM benefits from a multitude of pharmacological and non-pharmacological therapeutic options. Although numerous agents exposed in the present study are available, researchers have not yet reached a consensus regarding the prevention and treatment of this toxicity [50]. There are many studies in the literature on the usefulness of honey in the prevention and treatment of OM based on the biological properties of this agent. As an anti-inflammatory and antimicrobial agent and immunomodulator, this natural product has a great impact on OM [8,9,10,11,13,51,52]. For example, Pradip Kumar Maiti et al. conducted a study on 50 patients diagnosed with head and neck cancer who were radiotreated and divided into two study groups. The study arm was given 20 mL of honey 15 min before, 15 min after treatment, and a similar amount at bedtime. After evaluation, there was a significant reduction in grade 3 or 4 OM in the honey arm from 18% to 41% in the control arm [53]. The working method is similar to Howdler et al.’s, mentioned in this paper. Both Pradip Kumar Maiti et al. and Howdler conclude that honey is an inexpensive, readily available, effective agent for treating OM. The difference between these studies is in the oncological treatment applied to the patients, i.e., radiotherapy alone versus radiochemotherapy in combination with cisplatin-based chemotherapy. Not all studies specify the type of honey used. Howdler et al. used 20 mg of fresh, organic, unprocessed honey and in the study by Pradip Kumar Maiti et al. honey of unspecified origin was used but the recommendations of the studies are similar [39,53]. On the other hand, Motallebnejad M et al. conducted a double-blind randomized clinical trial in which 40 patients randomly assigned to two groups are examined. The study protocol is similar to the studies described above. However, the type of honey used is specified, this being pure natural honey obtained mainly from Thymus and Astragale in the Alborz Mountains, northern Iran. It is assumed that the beneficial effect of honey is based not only on its antibacterial properties but also on its geographical location, pollen source, season, type of bee, or other factors influencing its quality [10,11,54]. In contrast in the subspecialty review of Tharakan, T et al. [43], in which oncology patients are administered thyme honey, polyfloral honey, Ziziphus honey, pure or diluted honey oral rinse with satisfactory results, Karsten Münstedt [19] evaluated the efficacy of conventional bee honey and Manuka honey on radiochemotherapy-induced OM. Conventional honey has been shown to be more beneficial than Manuka honey, which requires caution when administered [11] for example due to adverse effects (severe nausea, vomiting, and severe burning sensations in the mouth) it was necessary to change the protocol in a study conducted by Parsonset et al. [11,54,55]. On the other hand, Hunter et al.’s study also found adverse effects of Manuka honey in a group treated with this type of honey [11] compared to Bardy et al., who conducted a double-blind, placebo-controlled, randomized trial with 131 patients. Consequently, a different form of honey presentation is recommended using a more liquid formula with active ingredients [11,56]. In other respects in the systematic reviews and meta-analyses [37,42,44,45] introduced in the present study, reference is made to honey combined locally and systemically, “natural” honey, royal jelly, honey extracted from Camellia sinensis, Thymus, and Astragale, from the Western Ghats forests, from Trifolium alexandrenum, pure natural honey, manuka, local honey, or unspecified honey applied locally or administered systemically. The results of studies are positive, honey administered either in dilution or in pure form has beneficial effects on OM [43,46,47]. Although the literature, as we have extensively exposed in this study, supports the benefits of bee honey in preventing and treating OM in patients with head and neck cancer, this topic is still controversial. Effective management of this toxicity is needed, but in neoplastic patients who are given different types of treatments such as pain relievers and anti-inflammatory drugs, which may influence the results of the research, these studies sometimes seem inconsistent [44]. On the other hand, it is very difficult to control the purity of honey, as it differs depending on a multitude of factors. In order to avoid inconsistent results in future research, it is necessary to specify and recognize the differences between different types of honey or to identify the active substances of this agent responsible for its beneficial effect on OM [19]. Despite these pros and cons, there is sufficient evidence and scientific studies conducted by researchers recommending bee honey to be included in the guidelines responsible for the management of this post-radiochemotherapy toxicity [34,36,37,38,42].

Despite its many benefits, honey consumption is still limited. Many researchers also warn patients about potential health problems caused by the excessive consumption of honey. Although honey has extraordinary anti-inflammatory, antibacterial, antiviral, anticancer, and tissue-repairing properties, caution is still required in its consumption [52]. Moreover, honey is a food subject to adulteration. In its composition there must not be any other ingredient, flavor, or foreign substance. Honey must not be overheated in order not to lose its properties. Pure honey can be altered either directly by adding adulterants, indirectly by feeding bees, or by mixing honey with other low-quality products [57]. Apart from the nutrients and compounds that give it these beneficial physicochemical properties, there may be contaminants in the composition of honey, such as pesticides, antibiotics, heavy metals, or other toxic agents, caused by exposure to the environment, faulty handling by beekeepers, or even the presence of numerous bee diseases that can ultimately affect the quality of honey. Honey can be contaminated by various chemicals or pathogens, which is why it is recommended that before consumption honey should be sterilized in order to remove contaminated agents without losing the therapeutic properties of honey. The use of honey should not be recommended for cancer patients with associated diabetes.

Another important problem is the presence of allergens that can cause severe anaphylactic reactions. Honey can also be a factor in the development of dental caries, therefore careful care of the oral cavity is recommended, especially during antineoplastic treatment.

Given the benefits but also the contraindications, manufacturers are encouraged to label each beekeeping product appropriately, especially honey [52].