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The efficacy of honey or olive oil on the severity of oral mucositis and pain compared to placebo (standard care) in children with leukemia receiving intensive chemotherapy: A randomized controlled trial (RCT)
Clinical Educator-Clinical and Professional development Center, American University of Beirut Medical Center, Riad El Solh, PO Box: 11 0236, Beirut 1107 2020, Lebanon
In this RCT with 42 children, children who received the Manuka honey or the olive oil had less severe oral mucositis compared to the control group. Children in the honey group had the least severe oral mucositis than the olive oil group or the control group.
•
Children who received the honey or the olive oil had less pain than the control group, with the honey group having the least pain.
•
Compared to standard treatment honey is economical, well tolerated by children and can be used as an alternative medicine especially in low and middle-income countries
Abstract
Background
Oral mucositis (OM) is a significant complication occurring in approximately 40 to 80% of patients receiving chemotherapy regimens. Although a wide variety of agents have been tested to prevent OM or reduce its severity, none have provided conclusive evidence.
Objectives
To determine the efficacy of honey or olive oil on the severity and OM pain in children with leukemia and suffering from OM compared to placebo (standard care) and, to assess which of the two interventions is more beneficial.
Methods
A single blind randomized controlled study (RCT) was used to evaluate the effect of Manuka honey or olive oil, in the treatment of chemotherapy-related OM in 42 children with leukemia. The primary outcome was the severity of mucositis, using the World Health Organization (WHO) scale and the secondary outcome was the pain assessed using the Visual analogue scale (VAS).
Results
Children who received the honey had less severe OM (assessed on the (WHO) scale), p = 0.00 and less pain (assessed on the VAS scale), p = 0.00, compared to the control group. Children who received the olive oil had less pain than the control group, p = 0.00), although not lower than the honey group.
Conclusion
Manuka honey or olive oil can be used as alternative therapies by nurses to children with leukemia and suffering from OM, especially in low and middle-income countries where more expensive therapies may not be available or economical.
Practice implications
Pediatric nurses may recommend Manuka honey to treat OM in children with leukemia as it is safe and inexpensive compared to other treatment modalities.
Oral mucositis (OM), is an inflammatory condition of the oral and oropharyngeal mucosa that occurs in the majority of patients on chemotherapy and/or radiotherapy (Lalla et al., 2014;
). It can be mild or severe, however in severe OM, patients present with deep ulcerations and severe pain, which requires opioid analgesics. Due to the severe pain, nutritional intake is compromised leading to weight loss, systemic infectious and decreased quality of life (
The incidence of OM varies depending on the type of cancer and how it is treated. For example, it affects 20–40% of patients receiving conventional chemotherapy and close to 80% of patients undergoing hematopoietic stem cell transplantation and receiving high doses of chemotherapy (Miranzadeh et al., 2015; Lalla et al., 2014;
). Furthermore, OM is affected by several risk factors, such as age, malnutrition, gender, pre-existing medical conditions, genetic and ethnic differences, poor dental health, and mucosal trauma (
). A recent systematic review of 1197 publications by the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) (
Mucositis guidelines leadership group of the multinational association of supportive care in cancer and international society of oral oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.
) recommended 24 evidence-based guidelines for treating OM. However, the authors of this review suggested that there are many clinical settings and geographic areas where there may be no recommended intervention. Also, the results of this review have shown that further research is required to document the benefits and risks expected from using different treatment methods,
Interventions that have been evaluated with the aim of reducing the severity of OM include, but are not limited to: oral hygiene care with mouth rinses and antimicrobial agents, sodium bicarbonate rinses, chlorhexidine rinses, the use of anti-inflammatory drugs, topical and systemic analgesics, topical antioxidants; mucosal-coating agents; ice chips, cryotherapy, herbal compounds, saliva stimulants/inhibitors, probiotics, and honey (
Mucositis guidelines leadership group of the multinational association of supportive care in cancer and international society of oral oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.
Mucositis study group of the multinational association of supportive care in cancer / international society of oral oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.
The purpose of this study was to assess the benefits of Manuka honey or olive oil in children with leukemia, receiving chemotherapy and suffering from OM. Studies to date have not provided conclusive evidence for the benefits of Manuka honey or olive oil in the prevention and treatment of mucositis in children. The primary objective of this study was to assess the efficacy of Manuka honey or olive oil compared to placebo (standard care) on the severity of OM in children and to determine which of the two interventions was more beneficial. The secondary objective was to assess the efficacy of Manuka honey or olive oil compared to placebo (standard care) on the pain from OM in children and to determine which of the two interventions was more beneficial in decreasing pain.
Honey is one of the oldest known natural remedies regarded as a health-giving substance (
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.2012; 29: 285-292
). Its medical use is recorded from around 3000 BCE onward and is addressed as a curative substance in the holy Bible. According to some studies, honey has antibacterial properties as well as antioxidants that can increase cytokine release which can cure wounds and ulcers (Maiti et al., 2012;
Mucositis study group of the multinational association of supportive care in cancer / international society of oral oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.
of 49 studies including 12 RCTs, concluded that honey used as a topical application or combined with systemic administration is beneficial in preventing the incidence, or limiting the progression of OM (
Mucositis study group of the multinational association of supportive care in cancer / international society of oral oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.
Mucositis study group of the multinational association of supportive care in cancer / international society of oral oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.
is that the source of the honey varied between these studies. Four intervention studies were found that used local honey to treat OM in children with cancer. These studies were conducted in Egypt (
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.2012; 29: 285-292
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.2017; 5861024
). All four studies reported the beneficial effect of the local honey in reducing pain and limiting the progression of OM. While the above mentioned studies used local honey, we used Manuka honey imported from New Zealand that has the registered trade mark Unique Manuka Factor (UMF) which is a guarantee that the honey has the special antibacterial activity and is manufactured in accordance with rigorous quality standards. https://manukahoney.co.uk/info/faqs.html.
Manuka pollen is collected by honey bees from the manuka tree (Leptospermum scoparium) and has potent antibacterial effects attributed to the phytochemical component methylglyoxal. It grows abundantly throughout New Zealand and has been a part of traditional medicine since the earliest times. It has been used by the indigenous populations of New Zealand and Australia as topical preparations for wounds, cuts, sores and skin diseases and as inhalations for colds and (
Evaluating the effects of the essential oils Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) on radiotherapy induced mucositis: A randomized, placebo controlled feasibility study.
A randomized phase 2 trial of prophylactic Manuka honey for the reduction of chemoradiation therapy-induced esophagitis during the treatment of lung cancer: Results of NRG oncology RTOG 1012.
International Journal of Radiation Oncology, Biology and Physicist.2017; 97: 786-796
; Parsons et al., 2012) studying the topical application of Manuka honey did not show positive effects on OM. Yaron and colleagues (2019) argue that “it is unclear if a combined topical and systemic application of Manuka honey will be effective in preventing OM” (p. 2468). Only three studies in the past decade used Manuka honey in children (
Effectiveness of three mouthwashes – Manuka honey, raw honey, and chlorhexidine on plaque and gingival scores of 12–15-year-old school children: A randomized controlled field trial.
Journal of the Indian society of Periodontology.2018; 22: 34-39
Effectiveness of three mouthwashes – Manuka honey, raw honey, and chlorhexidine on plaque and gingival scores of 12–15-year-old school children: A randomized controlled field trial.
Journal of the Indian society of Periodontology.2018; 22: 34-39
used manuka honey on 10 pediatric oncology patients between the ages of 9 months and 17 years and noted that children who used the honey paste had healing of the OM within 3 days.
Olive oil is derived from the fruit of the olive tree (Olea europaea), which grows in the east Mediterranean region and is one of the earliest botanicals used by mankind. The unique molecule that provides olive oil with its health benefits is “oleuropein” which is produced abundantly in the leaves as well as in the olive fruit itself (
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.2012; 29: 285-292
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.2012; 29: 285-292
Olive leaf extract as a new topical management for oral mucositis following chemotherapy: A microbiological examination, experimental animal study and clinical trial.
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
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.2012; 29: 285-292
) noted that olive oil reduced the severity of OM in 90 children with ALL compared to the control group. However, in this latter study olive oil was mixed with honey and beeswax precluding its sole efficacy. Another study in Iraq assessed the benefits of olive leaf extract in 54 adults and children undergoing cancer treatment (
Olive leaf extract as a new topical management for oral mucositis following chemotherapy: A microbiological examination, experimental animal study and clinical trial.
). Although the authors do not provide the number so children or adults in this study, they did report that the application of topical olive leaf extract was effective in treating OM and in decreasing pain compared to the benzydamine HCl and placebo groups. A third RCT in Syria (
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
) with 36 children with acute lymphoblastic leukemia aged between 6 and 9 years and suffering from grade 3 or 4 oral mucositis, were randomly divided into three groups. The results indicated that both Aloe Vera and olive oil applied topically resulted in a significant decrease in OM grades compared to the standard sodium bicarbonate (
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
Although, the benefits of both honey and olive oil are in general promising, the data are limited with insufficient evidence to recommend a ‘magic bullet’ for oncology nurses. In addition, there is a need for well-designed trials to arrive at a consensus for the benefits and harms of natural products in reducing OM. No study to date compared the benefits of olive oil or Manuka honey when swallowed in children with leukemia and suffering from OM. Olive oil in particular grows abundantly in the Mediterranean region, is used in the majority of Mediterranean dishes, and is relatively inexpensive. Thus, the use of honey and olive oil in this study was expected to be easy.
The hypotheses were as follows:
1)
Children who receive honey (group 1) or olive oil (group 2) will have less severe OM assessed by the World Health Organization assessment scale (WHO) scale compared to the control group (the primary outcome)
2)
Children who receive Manuka honey (group 1) or olive oil (group 2) will have less pain assessed by the Visual analogue 10 cm scale (VAS) than the control group (pain is the secondary outcome).
Materials and methods
Design
This was a single blinded randomized controlled clinical trial phase II (RCT) according to the CONSORT statement with three parallel-groups conducted on 46 children with leukemia receiving high dose chemotherapy.
Setting
Participants were recruited from two university hospitals in the Middle East. Data were collected from July 2017 to December 2020.
Sample
Based on a significant difference between honey and placebo in a previous study (
Evaluating the effects of the essential oils Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) on radiotherapy induced mucositis: A randomized, placebo controlled feasibility study.
), a power of 80%, significance level of <0.05 and an attrition rate of 5%, the sample size was calculated to be 20 in each group. The inclusion criteria were based on previous similar studies (eg.
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.2012; 29: 285-292
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.2017; 5861024
Children with Acute Lymphocytic Leukemia (ALL) receiving intensive (high dose) chemotherapy treatment such as myeloablative, doxorubicin or methotrexate during induction, consolidation and re-induction therapy.
2.
Children between the ages of 5–17 years
3.
Absence of any home remedy for mucositis
4.
Children with grades 1–4 OM based on the WHO grading system.
Children were excluded if, they had advanced or severe periodontitis (patients with periodontal pockets of 6 mm or more) if they had a cognitive disability which may not enable them to assess their pain, and if they had a history of allergy to honey or olive oil. A summary of recruitment and interventions in this trial are shown in Fig. 1. Although we aimed at having 20 children in each group, we reached significance with 42 children.
Fig. 1Flow diagram of the study: recruitment and final analysis of participants.
Either parent signed a consent form while children signed an assent form. The study was approved by the IRB of the university (NU04) and registered in clinicaltrials.gov (NCT03399331). The IRB committee recommended the use of Manuka oil compared to the standard honey used locally in order to prevent possible botulism in immunocompromised children.
Procedure
Potential subjects were identified through reviewing daily census in the units. Participates were screened for eligibility and were excluded if they have any condition that may affect the efficacy of treatment as listed in the exclusion criteria. After approval from their attending physician, and if interested in participating, parents and children were approached directly by one of the investigators in this study during their hospital stay. The investigator(s) explained the study, answered all their questions and concerns and informed them about the study benefits/potential risks. If either parent approved to participate in the study, he/she signed an informed consent and children older than 7 years singed an assent form. Children were randomly assigned to 1 of 3 groups, using a paper list-generated random assignment sequence by a statistician not involved in the trial. The numbers for each group assignment were placed in an opaque envelope which was to be opened when parents and their children signed the consent and assent forms. Based on group assignment, participants received a different compound applied to the oral mucosa 3 times daily by their assigned nurse until healing, or for 7 days, whichever comes first. All children were treated based on the standard St. Jude protocol for leukemia.
Group 1 received 2.5 cc of Manuka honey imported from New Zealand which is certified and. For every participant in the study, the honey was drawn in syringes and kept in a dark cool place.
Group 2 received 2.5 cc of extra virgin olive oil directly from a local distributor in south Lebanon. The olive oil is made by pressing the olive s in the old traditional methods that preserve most of the biological benefits of the olive s. It was drawn in syringes for every participant and stored in a dark cool place.
Group 3 served as control, which at our institution is 5 cc of 3% sodium bicarbonate and 5 cc Rinsidin. Children in groups 1 and 2 were instructed to slowly swish the honey or olive oil in their mouths for one minute then swallow it 3 times a day. This was in order for the honey or olive oil to contact the oral mucosa and the pharyngeal mucosa. For group 3, children were instructed to swish the mixture then spit it out 3 times a day. The attending physician wrote the order for the different solution in each medical record and the nurse caring for the child observed the child taking the solution and documented it on the flowsheet. Routine oral care was performed for all children in the three groups and consisted of tooth brushing using a soft toothbrush followed by oral normal saline rinse 3 times daily. At the time of enrollment, all patients had the following recorded:
(1)
Pain assessment by the nurses.
(2)
Physical examination with oral and dental assessment (normal/abnormal)
(3)
Grading of oral mucositis using the World Health Organization Mucositis Assessment Index (WHO) scale.
(4)
Results of their blood analysis found in their medical records (ANC levels).
(5)
Use of antibiotics (yes/ no).
(6)
Risk category of risk of leukemia.
(7)
Height and weight (BMI).
Each participant was assessed daily for signs of healing or progression to a more severe grade of mucositis. When a participant deteriorated, or was transferred to the Intensive Care Unit, due to a worsening medical condition, the treatment was interrupted upon discretion of the attending physician.
Outcomes
The primary outcome was the severity of OM measured by the severity of the OM from the day the first treatment began until healing or day 7 assessed by four trained nurses on a daily basis and who are blinded to the study group using the scale designed by the World Health Organization. The WHO scale assesses OMs development, and recovery. Scale measurements are: 0 indicated (no mucositis), 1 slight degree of mucositis, 2 moderate degree of mucositis, 3–4 (severe mucositis). The WHO scales is widely used for cancer patients to assess the degree of OM (
Olive leaf extract as a new topical management for oral mucositis following chemotherapy: A microbiological examination, experimental animal study and clinical trial.
). The WHO scale is based upon the ability to eat and drink combined with objective signs of mucositis, namely erythema and ulceration which was recorded daily by visualization of the oral cavity. Although the WHO scale is routinely used in most of our hospitals, the Co-Principal investigator [Co- PI) (RS) established inte-rater reliability with the four nurses before the study began by assessing patients on the WHO scale. Each nurse conducted the assessment and compared her/his results with the PI, until a reliability of r≥0.80 was achieved.
The secondary outcome was pain assessed as per the institution's policy using the Visual analogue 10 cm scale (VAS). A score of 1 on the VAS indicates no mouth or throat pain and 10 indicates the most severe mouth or throat pain. The construct, convergent and predictive validity of the VAS has been widely published (
Pain scores of the OM were conducted twice a daily for study purposes by nurses blinded to group assignment and which was documented in the patient charts twice per day at 8 am and at 8 pm (even in the absence of pain).
Statistical analysis
The characteristics of the three subject groups were described using means and standard deviations (SDs) for continuous variables and frequencies and percentages for categorical variables. Baseline differences between the two groups were tested using ANOVA for continuous data, and the Chi-square for categorical data. The three groups were compared based on the initial treatment assignment and not on the treatment eventually received. ANOVA tests were used to find the association between group assignment and the pain scores on the VAS scale as well as the association between group assignment and the severity of OM on the WHO scale. This was followed by post hoc Tukey-Kramer tests, to assess which of the three treatment was the most effective (
). For ease of analysis, days 1, 3 and 7 were compared. Data were analyzed on 42 children (23 males and 19 females) out of the 46 randomized ones, as two children were discharged three days after being in the study and could not be followed up, one refused to take the olive and was dropped from the study and one child was transferred to the pediatric intensive care unit (PICU), two days after the treatment was initiated.
Results
On enrollment, there were no significant differences between groups in terms of age, gender, BMI, Pain level, blood values, OM grading, severity of leukemia and antibiotics received. Table 1 provides the characteristics of children in each group. Honey was well accepted by all children in group 1 without any complaint while children in group 2 did not like the taste of olive oil. None of the children, developed any gastrointestinal adverse effects or an allergic reaction as a result of swallowing the compound.
Table 1Characteristics of participants in the three groups.
For hypothesis one or the primary outcome, at day 7 children who received honey (group 1) or olive oil (group 2) had less severe OM, based on the WHO scale, compared to the control group on, F = 5.18, p = 0.01. The result of the Tukey post hoc test indicated that group 1 (honey group) was significantly lower than group 3 (control group), p = 0.00, and group 2 (olive oil) was significantly lower than group 3 (the control group), p = 0.00. Table 2 shows the results for days 1, 3 and 7.
Table 2Differences between the three groups in terms of OM grade and pain level.
For hypotheses two or the secondary objective, at day 3 children who received the honey (group) or the olive oil (group 2) had less pain than the control group, F = 7.22, p = 0.002. The results of the Tukey post hoc analysis showed that the honey group had significantly least pain, p = 0.002 than group 3 (the control group). At day 7 there was a significant difference between groups F = 14.18, p = 0.00. The results of the Tukey test indicated that group 1 (the honey group) had less pain than group 3 (the control group), p = 0.00 and that group 2 (the olive oil group) had less pain than group 3 (the control group), p = 0.00. Table 2 shows the results on days 1, 3 and 7.
Discussion
Discussion, limitations, conclusion, I still do not see practice implications in the discussion section
Because OM is an unwanted outcome of cancer chemotherapy resulting in pain, and inability to eat or drink in children, we conducted this RCT to assess the benefits of Manuca honey or olive oil in comparison to the standard treatment of 5 cc of 3% sodium bicarbonate and 5 cc Rinsidin. The results reveal that both Manuka honey and olive oil were superior to the standard treatment albeit children did not like the taste of olive oil. In contrast to previous studies, which assessed the benefits of Manuka honey or olive oil, in our study children were instructed to swish the solution in their mouth then swallow it allowing for increased contact with the oral mucosa and helping in the healing of the oral cavity lesions, and any mucosal inflammation in the oropharynx, and esophagus. This method may have been responsible for the positive results obtained. Of note is the fact that the children tolerated the Manuka honey probably due to the small amount (2.5 cc) they received which is unlike a previous study where the author indicated that patients did not tolerate the taste and texture of the product (
). We found that Manuka honey was superior to both olive oil and the standard treatment. Our results are in contrast to four earlier studies, which showed little benefit to using Manuka honey with adults, receiving radiation therapy or chemotherapy (
A randomized phase 2 trial of prophylactic Manuka honey for the reduction of chemoradiation therapy-induced esophagitis during the treatment of lung cancer: Results of NRG oncology RTOG 1012.
International Journal of Radiation Oncology, Biology and Physicist.2017; 97: 786-796
A randomized phase 2 trial of prophylactic Manuka honey for the reduction of chemoradiation therapy-induced esophagitis during the treatment of lung cancer: Results of NRG oncology RTOG 1012.
International Journal of Radiation Oncology, Biology and Physicist.2017; 97: 786-796
), or the study had a very small sample size (Parsons et al., 2012). No studies have been conducted in children suffering from OM and treated with Manuka honey imported from New Zealand, which was not irradiated and was swallowed. It is thus necessary to conduct future studies with large samples to confirm the results of this study.
Although the exact mechanism of action of “honey” is not well established, osmolality, acidity, and the production of hydrogen peroxide have been proposed to be the main factors. Manuka honey specifically has natural antimicrobial, immuno-stimulant and wound healing properties due to a number of ingredients it contains mostly methylglyoxal (MGO) which is found in high concentrations and is a potent antimicrobial agent as compared to other honeys (
Manuka honey microneedles for enhanced wound healing and the prevention and/or treatment of methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection.
Despite the fact that olive oil is a common household ingredient in the Middle East and used daily in cooking and in salads, children did not like the taste of it. The benefits of olive oil in helping heal OM is supported by earlier studies that have found that olive oil may have anti-inflammatory properties, and a substantial role in decreasing mucosal injury (
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
Identifying antioxidant and antimicrobial activities of the phenolic extracts and mineral contents of virgin olive oils (Olea europaea L. cv. Edincik Su) from different regions in Turkey.
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.2012; 29: 285-292
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
Olive leaf extract as a new topical management for oral mucositis following chemotherapy: A microbiological examination, experimental animal study and clinical trial.
reported that olive oil was effective in treating OM in children with leukemia albeit, the olive oil was applied topically. Thus, the benefits of olive oil applied topically or systemically is worth further research especially that the former mentioned studies did not assess pain.
Practice implications
Pediatric nurses working with children with cancer may recommend Manuka honey to treat OM in children with leukemia as it is safe and children liked its taste compared to other treatment modalities. While we used Manuka honey in this study which was imported from New Zealnd at 99$ per 100 cc, local honey which costs much less can be used and has been tested in studies in developing countries and found to be safe (
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.2012; 29: 285-292
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.2017; 5861024
). Local honey or olive oil are especially proposed in developing countries where the cost of alternative medications such as sodium bicarbonate and Rinsdin at a cost of around 30$ per 100 cc, are either not available or expensive.
Limitations
Although this is the first study to report the benefits of Manuka honey or olive oil on OM in children with leukemia, there are limitations worth noting. First, the sample size was small especially in the olive oil group, which may have affected the results indicating the need for a larger controlled trial to confirm the effect of honey or olive oil on pain and the severity of OM. Second, the nurses taking care of the children and the treating physicians were not blinded to the study arm, which may have affected their decisions to report pain severity or to prescribe opioids. Finally, the Manuka oil used was imported from New Zealand which makes it difficult for daily clinical use, local honey as documented in several previous studies could be more practical to use and less expensive.
Conclusion
Oral mucositis may be successfully treated by Manuka honey or olive oil. Albeit, children did not like the taste of olive oil. Compared to standard treatment, honey is economical, well tolerated by children and can be used as an alternative medicine especially in low and middle-income countries. Further RCTs are warranted to provide conclusive evidence to the efficacy of both Manuka honey and olive oil to treat OM in children receiving chemotherapy for leukemia.
CRediT authorship contribution statement
Lina Kurdahi Badr: Conceptualization. Rebecca El Asmar: Data curation, Supervision, Project administration. Sarah Hakim: Investigation. Rima Saad: Investigation, Supervision, Visualization. Roni Merhi: Investigation. Ammar Zahreddine: Investigation. Samar Muwakkit: Resources.
Conflict of interest
The authors of this study certify that they have no affiliations with, or involvement in, any organization or entity with any financial interest or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
References
Abdulrhman M.
Elbarbary N.S.
Ahmed Amin D.
Saeid Ebrahim R.
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.2012; 29: 285-292
Olive leaf extract as a new topical management for oral mucositis following chemotherapy: A microbiological examination, experimental animal study and clinical trial.
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.2017; 5861024
Assessing the topical application efficiency of two biological agents in managing chemotherapy-induced oral mucositis in children: A randomized clinical trial.
Journal of Oral Biology and Craniofacial Research.2021; 11: 373-378
Identifying antioxidant and antimicrobial activities of the phenolic extracts and mineral contents of virgin olive oils (Olea europaea L. cv. Edincik Su) from different regions in Turkey.
Mucositis guidelines leadership group of the multinational association of supportive care in cancer and international society of oral oncology (MASCC/ISOO). MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.
A randomized phase 2 trial of prophylactic Manuka honey for the reduction of chemoradiation therapy-induced esophagitis during the treatment of lung cancer: Results of NRG oncology RTOG 1012.
International Journal of Radiation Oncology, Biology and Physicist.2017; 97: 786-796
Manuka honey microneedles for enhanced wound healing and the prevention and/or treatment of methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection.
Evaluating the effects of the essential oils Leptospermum scoparium (manuka) and Kunzea ericoides (kanuka) on radiotherapy induced mucositis: A randomized, placebo controlled feasibility study.
Effectiveness of three mouthwashes – Manuka honey, raw honey, and chlorhexidine on plaque and gingival scores of 12–15-year-old school children: A randomized controlled field trial.
Journal of the Indian society of Periodontology.2018; 22: 34-39
Mucositis study group of the multinational association of supportive care in cancer / international society of oral oncology (MASCC/ISOO). Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: Honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.
Group 1 vs Group 3: Diff = 1.16, 95% CI = 0.46 to 1.85, p = 0.00, Group 2 vs Group 3: Diff = 1.03, 95% CI = 0.29 to 1.76, p = 0.00.
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