Effects of Hydrogen Water Gargling on Oral Mucositis and Pain in Head and Neck Cancer Patients: A Randomized Controlled Pilot Study

Abstract

Background

Traditional, complementary, and integrative medicine (TCIM) is an evolving field in oncology focused on managing cancer symptoms. Hydrogen water (HW) has gained attention for its antioxidant and anti-inflammatory properties, yet its clinical effectiveness needs further exploration. This randomized controlled trial aimed to assess the impact of gargling with HW on oral mucositis severity, pain levels, oral frailty, and quality of life in head and neck cancer patients undergoing radiotherapy or concurrent chemo-radiotherapy.

Methods

In this single-center, single-blind, parallel-group randomized controlled trial, patients were randomly assigned to receive either HW or distilled water (DW) for gargling. Oral mucositis (OM) severity, pain, oral frailty, and quality of life (QoL) were assessed using the World Health Organization Oral Mucositis Grading Criteria (WHO-OMGC), the Brief Pain Inventory-Taiwan (BPI-T), the Oral Frailty Checklist (OFC), and the EORTC QLQ-H&N35 questionnaire. Assessments were conducted at baseline (T0) and on Days 1 (T1), 3 (T2), 7 (T3), and 14 (T4) post-treatment.

Results

The HW group showed significant OM improvement at Day 7 (p = 0.04) and Day 14 (p = 0.002). Pain decreased significantly in the HW group at Day 14 (p = 0.02). QoL improved in the HW group (p = 0.03), while OFC scores showed no significant difference between groups (p = 0.74).

Conclusion

HW gargling significantly alleviated OM severity and pain and improved QoL in head and neck cancer (HNC) patients undergoing radiotherapy or CCRT. HW gargling may serve as a simple, well-tolerated, and effective complementary and integrative therapy during cancer treatment.

Introduction

Head and neck cancer (HNC) is the seventh most common malignancy worldwide and the sixth most prevalent cancer in Taiwan, with an incidence rate of 6.79%, making Taiwan one of the countries with the highest global incidence of HNC.^1-3 Treatment guidelines for advanced HNC include concurrent chemoradiotherapy (CCRT), postoperative adjuvant chemotherapy, and postoperative radiotherapy.^4,5 These treatment modalities are often accompanied by a range of adverse effects, such as oral mucositis (OM), pain, dysphagia, impaired mastication, and taste alterations. Developing and testing Traditional Complementary and Integrative Medicine (TCIM) interventions to address cancer symptoms and treatment-related side effects, such as pain, insomnia, fatigue, and psychological distress, is an emerging focus in cancer care. ⁶ However, while hydrogen water (HW) is known for its antioxidant properties, the effectiveness of this complementary treatment in alleviating the adverse effects caused by cancer therapies remains unclear.

Patients with head and neck cancer manage a variety of symptoms at home on an outpatient basis. OM is particularly burdensome. OM affects approximately 80% of patients undergoing radiotherapy and up to 90% of those receiving CCRT.^7,8 Severe OM can lead to intense pain and difficulty with oral intake, potentially causing nutritional deficits, an increased risk of local and systemic infections, treatment interruptions, and reduced quality of life (QoL).^8-10 Patients with OM experience a twofold increase in the risk of infection and a fourfold increase in mortality compared to those without OM.^11,12

Oral frailty, defined as a decline in oral function characterized by tooth loss, poor oral hygiene, and dysfunction in chewing and swallowing, is also prevalent among HNC patients—particularly those with a history of smoking or alcohol consumption.^13,14 Furthermore, surgery, radiotherapy, and chemotherapy often result in structural damage or fibrosis in the oral and pharyngeal regions, which can further compromise oral function.^11,12

Pain is another common and distressing symptom in patients with HNC, with a prevalence of approximately 70%, increasing to 90% in those with advanced disease or tumors involving the oral cavity or tongue.^15,16Cancer-related pain arises from both direct tumor invasion and inflammation. ¹⁷ These inflammatory processes can result in anorexia, fatigue, depression, anxiety, and cognitive impairment in cancer patients. ¹⁸

Hydrogen has been shown to possess antioxidant, anti-apoptotic, cytoprotective, and anti-inflammatory properties. ¹⁹ HW can rapidly diffuse into tissues, scavenge excessive reactive oxygen species (ROS), and reduce oxidative stress. ²⁰ Clinical and preclinical studies have suggested that HW improves the healing of oral ulcers and QoL.^21,22 Due to its safety, minimal side effects, and rapid metabolism into water following redox reactions, HW is emerging as an innovative supportive treatment in complementary medicine. ²³ HW has emerged as a potential health-enhancing agent owing to its ability to scavenge reactive oxygen species. Given the central role of antioxidant therapies within the TCIM, HW is increasingly being considered as a supportive strategy for mitigating oxidative stress and maintaining physiological balance.^19,24,25 To date, no clinical study has specifically evaluated the efficacy of HW in alleviating oral mucositis, pain, oral frailty, and QoL in patients undergoing cancer treatment. Accordingly, this study aimed to assess the therapeutic potential of HW gargling in patients with HNC receiving radiotherapy or CCRT. We hypothesized that HW gargling would significantly reduce the severity of oral mucositis and pain and enhance oral function and QoL in this patient population.

Materials and Methods

Study Design and Participants

This single-center, single-blind, parallel-group randomized controlled trial enrolled patients who were blinded to group allocation, while investigators remained unblinded. To adhere to the principle of informed consent, all participants were thoroughly informed about their involvement in the study prior to enrollment. Participants were randomly assigned to either the experimental or control group using a computer-generated block randomization sequence, with a 1:1 allocation ratio. Stratification was performed based on treatment modality (radiotherapy alone or CCRT). Chemotherapy regimens were predominantly cisplatin-based, and radiotherapy was administered at a dose of 60 to 70 Gy, following standard clinical protocols. Inclusion criteria were as follows: age ≥ 20 years, histologically confirmed HNC, an Eastern Cooperative Oncology Group performance status of 0–2, ability to communicate in Mandarin, and receipt of radiotherapy or CCRT. The main exclusion criterion was undergoing surgery for HNC within the two months preceding enrollment.

Study Procedure and Data Collection

Upon completion of radiotherapy, baseline assessments of OM, pain, QoL, and oral frailty were conducted in each group. The final day of radiotherapy was defined as T0 (baseline), and the intervention began the following day (T1). Follow-up assessments were performed on Days 3 (T2), 7 (T3), and 14 (T4). At baseline (T0), participants completed pre-treatment assessments, including: (1) a demographic and medical information questionnaire, (2) the World Health Organization Oral Mucositis Grading Scale (WHO-OMGC), (3) the Taiwanese version of the Brief Pain Inventory (BPI-T), (4) the Oral Frailty Checklist (OFC), and (5) the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for head and neck cancer (EORTC QLQ-H&N35). Participants in the experimental group received hydrogen water (HW) prepared using a commercially available hydrogen water generator equipped with a microporous hydrogen-gas bubbling device (HW-N2; Ohta Hydrogen Biotechnology Co., Ltd., Kaohsiung, Taiwan). This device generates nano-hydrogen water (nano-HW) by shearing hydrogen bubbles in purified water. The size distribution and concentration of hydrogen nanobubbles were characterized using nanoparticle tracking analysis (NTA). Within 1 hour of preparation, the nanobubbles exhibited a mean diameter of approximately 145 nm, a concentration ranging from 2.79 to 4.89 × 10⁸ bubbles/mL, and a D90 value of 217.8 nm. ²⁶ Participants in the control group used distilled water (DW) for gargling over the same two-week period. Each participant was provided with 20 mL of HW or DW and instructed to gargle for 30–60 seconds every four hours, at least three times per day.

The same questionnaires were administered at each follow-up time point (T1–T4) to evaluate changes in clinical outcomes. Participants in the control group continued to receive usual care and were regularly monitored throughout the study period. To minimize potential bias, participants in different groups were scheduled at separate times to prevent interaction and the potential exchange of information.

The study investigator explained the purpose and procedures of the study to all participants and obtained written informed consent prior to enrollment. A 24-hour contact phone number was provided to allow participants to seek clarification or consultation at any time during the study. Each interview was conducted in person and lasted approximately 25 minutes. Following the interview, a blank copy of the research questionnaire was sent individually to participants via the LINE messaging app, contingent upon their willingness to share their contact information. Throughout the study period, the investigator refrained from initiating any unsolicited communication with participants via the app.

Measurements

This study followed the CONSORT 2010 guidelines ²⁷ to ensure standardized and transparent reporting of the randomized controlled trial.

Demographic and Medical Information Questionnaires

A demographic information sheet was used to collect basic patient data, including age, education level, sex at birth, marital status, smoking status, alcohol consumption, and betel nut chewing habits. A medical information sheet recorded each patient’s diagnosis, cancer stage, types of cancer treatment received, radiotherapy dosage, types of analgesics used, and any adverse effects associated with HW.

World Health Organization Oral Mucositis Grading Scale (WHO-OMGC)

The WHO Oral Mucositis Grading Scale (WHO-OMGC) is a standardized and widely used tool for assessing the severity of oral mucositis in cancer patients, ranging from Grade 0 (normal mucosa) to Grade 4 (life-threatening mucositis). Higher oral mucositis grades indicate greater severity, with Grade 1 indicating mild erythema and soreness without ulceration; Grade 2 representing moderate ulceration with pain but tolerable solid intake; Grade 3 denoting severe ulceration requiring a liquid diet and systemic analgesics; and Grade 4 involving extensive ulceration or necrosis preventing oral intake and necessitating nutritional support. Owing to its simplicity, reproducibility, and clinical relevance, the WHO- OMGC remains one of the most frequently applied instruments, alongside the NCI-CTCAE, for evaluating treatment-related oral complications.^28,29

Oral Frailty Checklist (OFC)

Oral frailty was assessed using the Chinese version of the Oral Frailty Checklist (OFC), developed by the Japanese Dental Association and validated in Taiwanese populations. The OFC ranges from 0 to 11, with lower scores indicating better oral function.^28,29

Brief Pain Inventory-Taiwan (BPI-T)

The Taiwanese version of the Brief Pain Inventory (BPI-T) is a validated self-administered tool for assessing pain severity and its interference with daily functioning. It consists of four severity items and seven interference items rated on a 0–10 numeric scale, with higher scores indicating more severe pain. ³⁰

European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head & Neck (EORTC QLQ-H&N35)

Quality of life was assessed using the Chinese version of the EORTC QLQ-H&N35, a 35-item questionnaire specifically designed for patients with head and neck cancer. Scores range from 0 to 100, with higher scores indicating greater symptom burden or functional impairment. The reliability and validity of the Chinese version have been well established.^31-34

Statistical Analysis

Sample size estimation was conducted using G*Power 3.1 software, ³⁵ based on an F-test with a moderate effect size of 0.25, a type I error rate (α) of 0.05, and a statistical power of 0.80. This resulted in a required sample size of 22 participants, with 11 in each group. Statistical tests included Mann–Whitney U test, and the Wilcoxon signed-rank test. To assess the practical significance of the findings, nonparametric effect size post hoc tests were employed. Additionally, rank-biserial correlation was used with the Wilcoxon tests to interpret the effect size. ³⁶ All statistical analyses were carried out using IBM SPSS version 23.0 (IBM Corp., Armonk, NY, USA).

Results

The randomized controlled trial was analyzed using a per-protocol (PP) approach (Figure 1). Most participants were male and had a history of current or former smoking, alcohol consumption, or betel nut chewing. Twelve patients received radiotherapy alone, while the remaining 19 received concurrent chemoradiotherapy (CCRT). Baseline demographic and clinical characteristics, including oral mucositis grade, pain scores, quality of life (QoL), and oral frailty (OFC) scores, as well as treatment-related variables, were well balanced between groups and are presented descriptively in Table 1.

Figure 1.

Flowchart of participants recruitment and allocation

Table 1.

Demographic and Clinical Characteristics of Participants (N=31)

Characteristic	Total (N=31)	Experimental (n=16)	Control (n=15)
Age (years), mean ± SD
​	56.20 ± 10.15	53.88 ± 10.86	58.67 ± 9.05
Sex, n (%)
Male	27	13 (81.3)	14 (93.3)
Female	4	3 (18.8)	1 (6.7)
Smoking status, n (%)
Former	9	7 (43.8)	2 (13.3)
Current	11	6 (37.5)	5 (33.3)
Quit >6 months	11	3 (18.8)	8 (53.3)
Alcohol consumption, n (%)
Former	11	6 (37.5)	5 (33.3)
Current	9	5 (31.3)	4 (26.7)
Quit >6 months	11	5 (31.3)	6 (40.0)
Betel nut chewing, n (%)
Former	12	8 (50.0)	4 (26.7)
Current	5	2 (12.5)	3 (20.0)
Quit >6 months	14	6 (37.5)	8 (53.3)
Primary site, n (%)
Nasopharyngeal	5	3 (18.8)	2 (13.3)
Oropharyngeal	15	9 (56.3)	6 (40.0)
Oral cavity	9	3 (18.8)	6 (40.0)
Hypopharyngeal	1	1 (6.3)	0 (0.0)
Laryngeal	1	0 (0.0)	1 (6.7)
Stage at study, n (%)
Stage 1	4	3 (18.8)	1 (6.7)
Stage 2	4	3 (18.8)	1 (6.7)
Stage 3	3	1 (6.3)	2 (13.3)
Stage 4	20	9 (56.3)	11 (73.3)
Type of treatment, n (%)
Radiotherapy	12	6 (37.5)	6 (40.0)
Concurrent chemoradiotherapy	19	10 (62.5)	9 (60.0)
Analgesic medication, n (%)
Yes	27	15 (93.8)	12 (80.0)
No	4	1 (6.3)	3 (20.0)
OM, n (%)
Grade 0	0	0 (0.0)	0 (0.0)
Grade 1	1	1 (6.3)	0 (0.0)
Grade 2	14	8 (50.0)	6 (40.0)
Grade 3	13	4 (25.0)	9 (60.0)
Grade 4	3	3 (18.8)	0 (0.0)
OM grade, median (IQR)	​	2.0 (2.0, 3.0) a	3.0 (2.0, 3.0) a
Pain (BPI-T)	​	3.0 (2.0, 4.5) a	4.0 (2.0, 5.0) a
QoL	​	36.7(25.0, 51.1) a	37.8 (28.9, 48.9) a
OF	​	7.0 (6.0, 8.5) a	8.0 (7.0, 9.0) a

Note. OM = oral mucositis; Pain (BPI-T) = Brief Pain Inventory–Taiwan version; QoL = quality of life; OF = oral frailty; CCRT = concurrent chemoradiotherapy; IQR = interquartile range. Baseline (T0) characteristics are presented as n (%), mean ± SD, or median (IQR). OM is presented as n (%) by grade, with median (IQR) additionally provided as a descriptive summary.

^aMedian (IQR).

Effect of HW on Oral Mucositis

Based on the WHO-OMGC questionnaire, the experimental group showed a significant improvement in oral mucositis beginning at T3 (p = 0.04), which persisted through T4 (p = 0.002) when compared with T0. In contrast, the control group did not show significant improvement until T4 (Table 2 and Figure 2). For additional detail, the proportions of WHO-OM grades at each time point for both groups are provided in Table S1 and Figure S1.

Table 2.

Oral Mucositis Score Changes Over Time (WHO-OMGC)

Change of score	Experimental arm (n=16) Median [IQR]	P value	Control arm (n=15) Median [IQR]	P value
T1–T0	0 [-1, 0.5]	0.97	0 [0, 1]	0.53
T2–T0	0 [-1, 0]	0.34	0 [0, 1]	1.00
T3–T0	-1 [-1, 0]	0.04*	0 [0, 1]	0.65
T4–T0	-1 [-2, -0.5]	0.002**	-1 [-1, 0]	0.02*

Note. WHO-OMGC = World Health Organization Oral Mucositis Grading Scale; IQR = interquartile range. Within-group changes from baseline (T0) were analyzed using the Wilcoxon signed-rank test.

^*P < .05.

^**P < .01.

Figure 2.

Changes in WHO oral mucositis scores over time

Effect of HW on Pain Severity

Using the BPI-T, pain levels were evaluated from T0 through T4. At T4, the median change in pain score was −1.0 (IQR: −2.5 to −0.3) in the experimental group and −0.5 (IQR: −2.3 to −0.3) in the control group, with a statistically significant difference (p = 0.02). These findings indicate that HW gargling provided more effective pain relief than DW (Table 3 and Figure 3). For additional reference, the raw pain scores from T0 to T4 are provided in Table S2.

Table 3.

Pain Scores Changes Over Time

Change of score	Experimental arm (n=16) Median [IQR]	P value	Control arm (n=15) Median [IQR]	P value
T1–T0	0.9 [-0.8, 2.1]	0.26	0.5 [0, 1.3]	0.12
T2–T0	0.5 [-0.9, 1.5]	0.46	0.8 [-0.5, 3.5]	0.14
T3–T0	-0.3 [-1.4, 0.9]	0.52	-0.3 [-0.8, 0.8]	0.97
T4–T0	-1.0 [-2.5, -0.3]	0.02*	-0.5 [-2.3, -0.3]	0.11

Note. BPI-T = Brief Pain Inventory – Taiwan version; IQR = interquartile range. Within-group changes from baseline (T0) were analyzed using the Wilcoxon signed-rank test.

^*P < .05.

Figure 3.

Changes in pain scores (BPI-T) over time

Effect of HW on QoL

QoL was evaluated using the EORTC QLQ-H&N35 throughout the study period. Changes in QoL scores at each time point were compared to baseline (T0). A significant improvement in QoL was observed at T4 in the HW group (p = 0.03), whereas no significant change was detected in the DW group after two weeks of intervention (Table 4 and Figure 4). For additional reference, the raw QoL scores from T0 to T4 are provided in Table S2.

Table 4.

EORTC QLQ-H&N35 Score Changes Over Time

Change of score	Experimental arm (n=16) Median [IQR]	P value	Control arm (n=15) Median [IQR]	P value
T1-T0	5.0(-6.7,16.7)	0.22	5.6(2.2,20)	0.05
T2-T0	1.7(-2.8,8.9)	0.50	2.2(-4.4,18.9)	0.19
T3-T0	-6.1(-10.6,6.1)	0.27	-1.1(-8.9,15.6)	0.59
T4-T0	-7.8(-15.6,-2.8)	0.03*	-3.3(-12.2,12.2)	0.73

Note. EORTC QLQ-H&N35 = European Organization for Research and Treatment of Cancer Head and Neck Module. Within-group changes from baseline (T0) were analyzed using the Wilcoxon signed-rank test.

^*P < .05.

Figure 4.

Changes in EORTC QLQ-H&N35 scores over time

Effect of HW on Oral Frailty

After 14 days of treatment, no substantial improvement in oral frailty was observed, and the median OFC scores did not differ significantly between the two groups at T1, T2, T3, or T4 (Table 5 and Figure 5). For additional reference, the raw OFC scores from T0 to T4 are provided in Table S2.

Table 5.

Oral Frailty Scores Changes Over Time (OFC)

Change of score	Experimental arm (n=16) Median [IQR]	P value	Control arm (n=15) Median [IQR]	P value
T1–T0	0 [-1, 1]	1.00	0 [-1, 1]	0.35
T2–T0	0 [-1, 1]	0.77	0 [-1, 0]	0.18
T3–T0	0 [-0.5, 1]	0.56	0 [-1, 1]	0.59
T4–T0	0 [-1.5, 1]	0.74	-1 [-1, 1]	0.14

Note. OFC = Oral Frailty Checklist; IQR = interquartile range. Within-group changes from baseline (T0) were analyzed using the Wilcoxon signed-rank test.

Figure 5.

Changes in oral frailty scores over time

Discussion

To the best of our knowledge, this study is the first to specifically assess the effects of HW on reducing the severity of OM and pain and improving QoL in patients with HNC, followed up 2 weeks after radiotherapy or concurrent CCRT completion. This study demonstrated significant improvements in the experimental group in WHO-OMGC, pain, and QoL. The effect sizes of the oral mucositis, pain, and QoL are 0.74, 0.54, and 0.54. No change was observed in oral frailty. Compared to hydrogen inhalation, HW offers greater convenience for patients, as it can be stored in a bottle and easily used as a mouthwash. Notably, no adverse events associated with HW were observed throughout the study. Mechanistically, although HW was administered orally, partial exposure of the oropharyngeal mucosa during gargling may have contributed to the observed symptom relief.

Hydrogen gas exhibits potent antioxidant properties that help regulate reactive oxygen species (ROS) production and modulate inflammatory responses. In murine models, hydrogen gas inhalation has been shown to be effective in treating coronary artery dilatation. ³⁷ HW has also demonstrated anti-inflammatory effects due to its ability to efficiently diffuse into tissues and cells, reducing ROS levels and enhancing antioxidant activity. ³⁸ Previous studies have suggested that HW selectively reduces excessive ROS without impairing the antitumor efficacy of radiotherapy. ³⁹

In animal studies, rats consuming HW exhibited increased expression of the transcription factor Nrf2, which was associated with downregulation of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines, accelerated oral wound healing, and reduced iNOS expression in hard palate tissue. ²¹ Evidence in humans further supports the antioxidant effects of HW. ⁴⁰ Dobashi et al demonstrated that HW consumption attenuated the decline in total antioxidant capacity following several days of high-intensity exercise in physically active men, suggesting that HW may help preserve systemic redox homeostasis under oxidative stress.

Radiotherapy remains a cornerstone of treatment for patients with HNC, particularly those with localized tumors.^20,41 Although effective in eradicating cancer cells, radiotherapy alters the tumor microenvironment and increases ROS production, leading to both acute and chronic side effects that negatively impact patients’ QoL.^42,43 Among these side effects, OM is one of the most common and debilitating.^44,45 Pain resulting from OM not only disrupts QoL but also increases the risk of infection and malnutrition. Severe pain may lead to treatment interruption or discontinuation, ultimately worsening patient prognosis. Therefore, strategies that mitigate the severity of OM are essential not only for improving QoL but also for optimizing treatment outcomes.

Inhalation of hydrogen has been approved for clinical use and has shown excellent tolerability in individuals with confirmed SARS-CoV-2 infection. ⁴⁶ Additionally, hydrogen gas inhalation combined with CCRT has been demonstrated to be both feasible and safe in patients with locally advanced HNC. ⁴⁷ A randomized, placebo-controlled trial evaluated the effects of consuming HW for six weeks in patients receiving radiotherapy for malignant liver tumors. The results indicated that hydrogen-rich water reduced reactive oxygen metabolites in the blood and maintained serum oxidation potential. Moreover, QoL scores during radiotherapy were significantly improved in patients treated with HW compared to controls. ⁴⁸

In this study, patients with head and neck cancer (HNC) who had recently completed radiotherapy or CCRT were enrolled. After two weeks of HW gargling, improvements were observed in the severity of oral mucositis (OM), pain intensity, and QoL by the end of the intervention period (T4), compared to baseline (T0). In contrast, no significant improvements were observed in the control group. Although OM generally improves over time, patients in the HW group experienced more rapid pain relief. Early reduction in pain may contribute to enhanced QoL and facilitate a quicker return to daily activities. This improvement may also help reduce the risk of complications such as infection, odynophagia, and malnutrition.

However, the study did not demonstrate a significant benefit of HW in improving oral frailty. This may be attributed to the multifactorial nature of oral health, which encompasses structural, functional, and systemic components such as age, comorbidities, and nutritional status. Many patients with HNC undergo multimodal treatments and may already exhibit baseline oral frailty. A short-term intervention with HW may not be sufficient to reverse anatomical deficits caused by surgery or the delayed effects of radiotherapy, which often manifest months or even years after treatment. ⁴⁹

Implication for Clinical Practice

Hydrogen water gargling has potential as an adjunct therapy for patients with head and neck cancer undergoing radiotherapy or concurrent chemoradiotherapy. Hydrogen water can be prepared using a commercially available hydrogen water generator, making it a simple and accessible intervention in clinical practice. Usage instructions: Patients may gargle with 20 mL of hydrogen water for 30 to 60 seconds each time. It is recommended that gargling be performed at least three times a day, ideally once every four hours. For optimal results, this routine should be followed for a minimum of two weeks. This practice may help alleviate symptoms such as oral mucositis and pain.

Limitations

This study has several limitations. The sample size is limited due to case numbers, time constraints, and budget limitations. The average age of participants was 56.2, which is comparable to the national median age of 58 for patients with head and neck cancer (HNC) in Taiwan. However, the generalizability of these findings to other age groups remains uncertain. Additionally, the two-week follow-up period may have been too brief to capture long-term outcomes. Pain assessment was limited to measuring intensity using the Brief Pain Inventory-Taiwan version (BPI-T), without evaluating qualitative pain characteristics. This restriction limits the comprehensiveness of the pain evaluation. Dose-response relationships of large-sample-size RCTs are recommended for the future. Finally, at baseline, some imbalance in the distribution of oral mucositis (OM) grades was observed between the two groups. The experimental group had a higher proportion of severe OM cases, with 18.8% of patients presenting with Grade 4 OM compared with none in the control group. As participants were randomized without stratification by OM grade, this imbalance may have occurred by chance and may have influenced the interpretation of treatment effects.

Conclusion

Integrating HW gargling into complementary and integrative care for patients with head and neck cancer (HNC) undergoing radiotherapy or concurrent chemoradiotherapy (CCRT) is safe, well tolerated, and may be effective. We observed a reduction in the severity of oral mucositis (OM) and pain and improvements in quality of life (QoL) within one to two weeks of the intervention. Future research should explore the effects of earlier interventions and investigate the preventive potential of HW for oral-related side effects.

ORCID iDs

Hui-Ting Tsai https://orcid.org/0000-0002-8760-176X

Kun-Ming Rau https://orcid.org/0000-0002-1209-3043

Pi-Ling Chou https://orcid.org/0000-0001-6316-1002

Ethical Considerations

The study protocol was approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-F(I)-20230082) and registered on ClinicalTrials.gov (NCT05913895). All procedures were conducted in accordance with the principles of the Declaration of Helsinki and relevant ethical guidelines and regulations. Participants received a comprehensive explanation of the study’s objectives, procedures, potential risks and benefits, and their right to withdraw at any time without penalty. Written informed consent was obtained from all participants prior to enrollment.

Data Availability Statement

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.*