Abstract
Background:
Radiation-induced xerostomia is a common complication in head and neck cancer (HNC) patients, significantly impairing oral health, nutrition, and quality of life. Salivary substitutes such as Biotene and Xerostom have been developed to manage symptoms, but clinical evidence comparing their effectiveness is limited.
Aim:
The aim is to evaluate and compare the efficacy of Biotene and Xerostom salivary systems in improving salivary properties and reducing caries susceptibility in postradiotherapy (RT) HNC patients.
Methods:
Sixty-six patients with radiation-induced xerostomia were randomly assigned to three groups: Biotene (n = 22), Xerostom (n = 22), and placebo (n = 22). Interventions were used for 28 days. Salivary flow rate, pH, buffering capacity, mucin-7 (MUC7), β-defensin-2, Streptococcus mutans count, and oral mucositis (OM) were assessed at baseline, 1, 3, and 6 months. Data were analyzed using repeated measures analysis of variance and Chi-square tests.
Results:
Both Biotene and Xerostom significantly improved salivary flow (Biotene: 1.26 ± 0.22 mL/min; Xerostom: 1.00 ± 0.25 mL/min) compared to placebo (0.76 ± 0.27 mL/min) at 6 months. pH and buffering capacity also improved in both intervention groups. MUC7 levels were higher in Biotene (77.71 ± 9.38 ng/mL) and Xerostom (74.92 ± 6.76 ng/mL) compared to placebo (61.48 ± 4.96 ng/mL), indicating enhanced mucosal protection. β-defensin-2 levels were lower in treatment groups, suggesting balanced immune activity. S. mutans counts were significantly reduced in Biotene (9.20 ± 8.50 CFU/mL) and Xerostom (12.5 ± 12.82 CFU/mL) versus placebo (118.75 ± 60.61 CFU/mL), reflecting reduced caries risk. OM severity was also lower in treated groups.
Conclusion:
Both Biotene and Xerostom improved salivary function, reduced microbial load, and enhanced oral mucosal protection in HNC patients with radiation-induced xerostomia. Biotene demonstrated marginally superior outcomes. These systems may serve as effective interventions for xerostomia management post-RT.
Keywords: Biotene salivary system, caries susceptibility, head and neck cancer, irradiation-induced xerostomia, radiotherapy, Xerostom salivary system
INTRODUCTION
Head and neck cancer (HNC) is the sixth-most common cancer globally, accounting for approximately 2.8% of all malignancies, with over 630,000 new cases and 350,000 deaths annually.[1] With global cancer incidence expected to rise, radiotherapy (RT) continues to play a central role in HNC management. While effective in tumor control, RT often causes collateral damage to healthy tissues, particularly the salivary glands, leading to xerostomia.
Saliva plays a vital role in oral health, aiding in mastication, swallowing, speech, buffering acids, remineralization, and antimicrobial defense. Despite their low mitotic index, salivary glands are highly radiosensitive. Radiation induces apoptosis and membrane disruption in acinar cells, resulting in reduced salivary output.[2] Xerostomia and hyposalivation are reported in over 80% of patients receiving RT for HNC. Salivary flow may decrease by 50%–60% within the 1st week of therapy and reach its lowest level by the second or third week.[3] This reduction severely compromises quality of life, leading to malnutrition, social difficulties, and general health decline.[4]
RT alters saliva composition by increasing viscosity, reducing buffering capacity, and disrupting antimicrobial function. Levels of mucins – especially MUC7 – and other glycoproteins decline, impacting lubrication, tissue adhesion, and microbial interactions.[5] Reduced MUC7 levels post-RT have been linked to increased caries risk. Similarly, human beta-defensins (HBDs), particularly HBD-2, are antimicrobial peptides vital for oral immunity. A decline in these peptides weakens mucosal defense and increases susceptibility to infection and caries.[6] Radiation caries is a rapidly progressive condition affecting up to 24% of RT patients, often destroying dentition within a year.[5]
Lesions may appear as early as 3 months posttreatment. Changes in salivary flow and composition, coupled with a shift in oral microbiota toward acidogenic and cariogenic species such as Streptococcus mutans, Lactobacillus, and Candida, contribute significantly. Effective management of xerostomia is essential for improving patient comfort and health outcomes.
Treatment strategies include stimulation of residual salivary function, symptom relief through hydration, and use of salivary substitutes. Commercial substitutes come in forms such as gels, toothpastes, and mouthwashes. Most are based on carboxymethyl cellulose or animal-derived mucins. While mucin-based products offer slightly better efficacy, they may cause allergic reactions and are unsuitable for some patients.[7,8] Newer salivary systems aim to replicate natural saliva and support the oral immune system. The Biotene system contains lactoperoxidase, glucose oxidase, xylitol, hydroxyethyl cellulose, and antimicrobial proteins such as lysozyme and lactoferrin.[9] Xerostom system includes olive oil for lubrication and anti-inflammatory effects, betaine as a moisture-preserving osmoprotectant, and xylitol for salivary stimulation and anticaries action.[10] These formulations aim not only to relieve symptoms but also to enhance the protective functions of saliva. Despite the availability of these products, clinical evidence regarding their effectiveness remains limited. To date, no study has thoroughly evaluated their impact on salivary properties and caries susceptibility in patients with RT induced xerostomia. This study aims to fill that gap by comparing the efficacy of Biotene and Xerostom systems in improving salivary flow, pH, buffering capacity, and assessing salivary biomarkers, including beta-defensin, MUC7, and S. mutans levels in post-RT HNC patients.
METHODOLOGY
This randomized, prospective study was conducted in collaboration with Dharamshila Narayana Superspeciality Hospital, New Delhi, and the Centre for Advanced Research at I.T.S. Centre for Dental Studies and Research, Ghaziabad. Ethical approval was obtained from the I.T.S Institutional Ethics Committee (Ref No. ITSCDSR/Director-Principal/2023/L/076), and the trial was registered with the Clinical Trial Registry of India (CTRI/2024/11/077083). Informed consent was obtained from all participants.
A total of 120 HNC patients, aged ≥18 years, who had completed RT within the past year and were clinically diagnosed with xerostomia, were screened. Inclusion criteria were: RT completed ≥2 weeks prior,≥60 Gy dose involving major and minor salivary glands, oral nutrient intake,≥10 natural teeth, and an ICDAS score of 1 or 2. Exclusion criteria included: stimulated salivary flow rate >1 ml/min; use of salivary stimulants or hyposalivation therapy; severe dysphagia; RT dose <60 Gy; or radiation fields excluding the jaws.
After eligibility screening, 66 participants were enrolled. Random allocation was performed by an independent researcher using Random Allocation Software. Participants were assigned to one of three groups via the Sequentially Numbered, Opaque, Sealed Envelope method to ensure allocation concealment. Sample collection was performed by a single operator at four intervals: baseline (2 weeks post-RT), 1 month, 3 months, and 6 months.
According to randomization, the groups are as follows:
Group A: Biotene salivary system (N = 22)
Group B: Xerostom salivary system (N = 22)
Group C: Placebo (N = 22).
Groups A and B used Biotene and Xerostom moisturizing gel (1–2 cm applied five times daily, especially at night) and Biotene and Xerostom toothpaste thrice daily for 28 days. Group C used regular toothpaste (Colgate) without gel, following the same schedule. Clinical assessments were done on day 0 and day 28.
To measure the salivary pH, indicator strips were used. Buffering capacity was assessed by mixing 150 µl 5 mM HCl with 50 µl saliva, incubating for 10 min (Ericsson’s method), then measuring pH. Buffering capacity was deemed as low (≤4), moderate (4.1-5.5), or high (>5.6) for the final pH value.
Salivary human β-defensin-2 (hβD-2) levels were quantified using a Human DEFB ELISA kit (BT Lab, Cat. No. E0345Hu) according to the manufacturer’s instructions. After preparing all reagents and samples, 40 µL of saliva and 10 µL of anti-DEFB antibody were added to the sample wells, followed by 50 µL of streptavidin-HRP. Plates were incubated at 37°C for 60 min, washed five times, and treated with substrate solutions A and B (50 µL each). After a 10-min incubation in the dark, 50 µL of stop solution was added, and absorbance was measured at 450 nm. hβD-2 concentrations were expressed in µg/mL.
Salivary MUC7 levels were quantified using a high-sensitivity ELISA kit (BT Lab, Cat. No. E1613Hu) according to the manufacturer’s instructions. Samples (40 µL) were combined with 10 µL anti-MUC7 antibody and 50 µL streptavidin-HRP, incubated at 37°C for 60 min, and washed five times. Substrate solutions A and B (50 µL each) were added, followed by a 10-min incubation in the dark. After adding the stop solution, absorbance was measured at 450 nm. Reactions were also read at 492 nm post 2N H2SO4 addition. All samples were analyzed in triplicate, and mean optical density values and coefficient of variation were calculated.
For S. mutans detection, undiluted saliva samples were plated on mitis salivarius agar with 10% sucrose and bacitracin, then dried and incubated. Colonies were counted under a dissecting microscope to determine bacterial concentration (organisms/ml). Levels 10[5] or higher indicated high caries risk.
Assessment of oral mucositis (OM) as a secondary outcome was done, and grades were given according to the World Health Organization Scale as mentioned below:
Grade 1: Soreness with or without erythema
Grade 2: Ulcers with erythema without dysphagia to solid foods
Grade 3: Ulcers with extensive erythema and dysphagia to solid foods
Grade 4: Mucositis with complete dysphagia.
Statistical analysis
Data were analyzed using IBM SPSS Statistics version 25.0 (Armonk, New York, United States). Descriptive statistics were reported as mean ± standard deviation. Normality of the data was assessed using the Shapiro–Wilk test. For intragroup comparisons across time intervals (baseline, 1 month, 3 months, and 6 months), repeated measures analysis of variance (ANOVA) with Bonferroni post hoc test was applied. Intergroup comparisons among the three groups (Biotene, Xerostom, and placebo) were conducted using one-way ANOVA followed by Tukey’s HSD test for pairwise comparisons. Categorical data, including OM grades, were analyzed using the Chi-square test. A significance level of P < 0.05 was considered statistically significant.
RESULTS
At 6 months post-RT, patients using Biotene and Xerostom demonstrated significantly improved salivary parameters compared to the placebo group. Mean salivary flow rates were highest in the Biotene group (1.26 ± 0.22 mL/min), followed by Xerostom (1.00 ± 0.25 mL/min), and placebo (0.76 ± 0.27 mL/min). Salivary pH and buffering capacity also followed this trend, with Biotene showing slightly better outcomes.
Both interventions improved mucosal conditions, with reduced OM scores (Biotene: 1.4 ± 0.5, Xerostom: 1.5 ± 0.69) compared to placebo (2.6 ± 0.5). Mucin-7 levels increased significantly in both intervention groups (Biotene: 77.71 ± 9.38 ng/mL; Xerostom: 74.92 ± 6.76 ng/mL) relative to placebo (61.48 ± 4.96 ng/mL), while β-defensin-2 levels were lower in treated groups, suggesting improved antimicrobial efficiency. S. mutans CFU counts were markedly reduced in Biotene (9.20 ± 8.50 CFU/mL) and Xerostom (12.5± 12.82 CFU/mL) versus placebo (118.75 ± 60.61 CFU/mL).
Overall, both Biotene and Xerostom significantly enhanced salivary flow, composition, antimicrobial activity, and reduced caries risk, with Biotene showing marginally superior outcomes across most parameters.
DISCUSSION
Radiation therapy is a standard modality for managing HNC, but it often results in xerostomia and salivary hypofunction due to collateral damage to the salivary glands. These effects emerge as early as the 1st week of treatment and may persist or only partially recover over the next 6–24 months, depending on gland preservation and radiation dose.[6] The current study compared two commercially available, sodium lauryl sulfate-free salivary systems – Biotene and Xerostom – for their efficacy in restoring salivary function, improving oral biomarkers, and reducing caries susceptibility in post-RT patients.
Our study demonstrated that Biotene significantly enhanced salivary flow rates, followed by Xerostom, with placebo performing the least, which was statistically significant. This aligns with the findings of Jasmer et al., who attributed persistent xerostomia to radiation-induced fibrosis and apoptosis of acinar and ductal cells.[10] Biotene’s superior effect may be due to its unique composition, which includes enzymes (glucose oxidase, lactoferrin, and lactoperoxidase), humectants, and xylitol. The latter, as shown by Warde et al., stimulates salivary flow via muscarinic receptor activation and AQP5 expression, which regulates intracellular calcium and water transport in glandular cells.[11]
Xerostom, although slightly less effective, still produced a significant improvement in salivary output. Its effectiveness can be attributed to ingredients such as olive oil, betaine, and xylitol, all of which offer mucosal protection and lubrication.[9] Martin et al. and Ship et al. showed that betaine has osmoprotective properties, reduces mucosal irritation, and enhances epithelial barrier integrity – critical for xerostomia management.[12,13]
Post-RT patients frequently experience a shift toward acidic salivary pH and reduced buffering, which promotes an environment conducive to dental caries. Our findings revealed that both Biotene and Xerostom significantly improved these parameters, likely due to the combined effects of increased salivary volume and alkalinizing ingredients such as xylitol and sodium bicarbonate. These results are consistent with Podunavac et al., who demonstrated improved pH profiles following the use of xylitol-based saliva substitutes.[14]
All the parameters and their respective findings are summarised in Table 1 and depicted in Figure 1. Arrifin et al. reported a 44% reduction in buffering capacity in irradiated patients, which significantly increased caries risk. Our results show that Biotene and Xerostom restored buffering capacity to near-normal values, supporting their role in re-establishing oral pH balance and preventing enamel demineralization.[15] Beta-defensins (hBD-1 and hBD-2) are antimicrobial peptides secreted by ductal cells in response to microbial presence. Our study found significantly lower beta-defensin levels in the Biotene and Xerostom groups compared to the placebo. This contrasts with the findings of Jurczak et al., who noted elevated hBD levels in individuals with active caries.[16]
Table 1.
Comparative analysis of salivary parameters and bio markers at baseline, 1 month, 3 months, and 6 months among subjects treated with Biotène, Xerostom, and placebo
| Biotene (mean±SD) | Xerostom (mean±SD) | Placebo (mean±SD) | |
|---|---|---|---|
| Salivary flow | |||
| Baseline | 0.41±0.24a,b,c | 0.38±0.21a,b,c | 0.43±0.24 a,b,c |
| 1 month | 0.68±0.27a,b,c | 0.60±0.25a,b,c | 0.55±0.23c,a,b,c |
| 3 month | 1.06±0.26 | 0.82±0.22 | 0.62±0.22c |
| 6 month | 1.26±0.22 | 1.00±0.25 | 0.76±0.27c |
| Salivary pH | |||
| Baseline | 5.03±0.55a,b,c | 4.95±0.58a,b,c | 5.00±0.51a,b,c |
| 1 month | 5.55±0.43a,b,c | 5.58±0.59a,b,c | 5.35±0.49c,a,b,c |
| 3 months | 6.38±0.43 | 6.13±0.63 | 5.63±0.39c |
| 6 months | 7.03±0.41 | 6.70±0.59 | 5.75±0.41c |
| Buffer capacity | |||
| Baseline | 5.20±0.76a,b,c | 5.01±0.61a,b,c | 4.90±0.65a,b,c |
| 1 month | 5.74±0.81 | 5.32±0.69 | 5.14±0.47 |
| 3 months | 6.21±0.75 | 5.71±0.68 | 5.20±0.57 |
| 6 months | 6.76±0.70 | 6.42±0.49 | 5.42±0.48 |
| β-defensin levels | |||
| Baseline | 20.45±5.09a,b,c | 22.42±5.18a,b,c | 24.08±6.74a,b,c |
| 1 month | 15.30±6.85a,b,c | 15.44±4.82a,b,c | 18.12±5.57a,b,c |
| 3 months | 9.69±4.73 | 9.33±4.05 | 15.06±5.06 |
| 6 months | 5.96±3.07 | 6.33±3.42 | 10.13±5.60 |
| MUC7 protein levels | |||
| Baseline | 53.25±7.88a,b,c | 51.72±6.78a,b,c | 48.84±4.50a,b,c |
| 1 month | 60.68±7.76 | 58.68±7.39 | 54.03±6.57 |
| 3 months | 67.89±8.17 | 65.65±7.49 | 57.62±6.13 |
| 6 months | 77.71±9.38 | 74.92±6.76 | 61.48±4.96 |
| Colony-forming units | |||
| Baseline | 61.75±40.22a,b,c | 60.85±53.47a,b,c | 58.25±47.22a,b,c |
| 1 month | 31.25±18.13 | 32.45±21.71 | 79.05±51.95 |
| 3 months | 20.25±14.17 | 21.20±15.09 | 101.90±60.30 |
| 6 month | 9.20±8.50 | 12.50±12.82 | 118.75±60.61 |
| Oral mucositis scores | |||
| Baseline | 3.10±0.79a,b,c | 3.20±0.89a,b,c | 3.50±0.61a,b,c |
| 1 month | 2.55±0.69 | 2.55±0.76b | 3.10±0.55c |
| 3 months | 1.85±0.59a | 2.10±0.72b | 2.80±0.52c |
| 6 months | 1.40±0.50a | 1.50±0.69 | 2.60±0.50c |
*P<0.05 indicates statistically significant differences, #SD values are presented as mean±SD. Upper-case letters indicate no significant difference between the intergroup analysis at a time interval. Lower-case letter indicates no significant difference between the various time intervals in intragroup comparison. SD: Standard deviation
Figure 1.
The colony-formin g unit culture of Streptococcus mutans (Groups a-Biotene, b-Xerostom, and c-Placebo), depicting the maximum colony-formin g unit count in placebo, and the least count in the Biotene group
The reduction in our study may indicate decreased microbial burden and restored immune homeostasis, rather than a compromised defense. Notably, beta-defensins serve as markers of inflammatory activation, and their normalization may reflect improved oral immunity. Mucin-7, a salivary glycoprotein essential for lubrication and microbial aggregation, was significantly elevated in both treatment groups, with Biotene showing slightly higher levels. MUC7 protects hydroxyapatite by forming a protective barrier and preventing microbial colonization. Studies by Frenkel et al. and Situ et al. confirm that MUC7 selectively binds to S. mutans via sialic acid residues, inhibiting its adherence and biofilm formation. The observed increase in mucin levels suggests these systems not only lubricate but also actively restore protective salivary functions.[17,18] Caries susceptibility was assessed through CFU counts of S. mutans, the primary etiological agent in radiation-related caries. Placebo patients showed the highest bacterial counts, consistent with post-RT microbiome shifts favoring acidogenic species. Both Biotene and Xerostom significantly reduced S. mutans counts, with Biotene exhibiting greater suppression, but it was statistically nonsignificant when compared with Xerostom.
The antimicrobial enzymes in Biotene – lactoperoxidase and lactoferrin – likely played a role in disrupting bacterial metabolism and reducing virulence, as also reported by Kristila et al. and Tenovuo et al. in similar settings.[19,20] These findings align with Hegde et al., who demonstrated that radiation enhances S. mutans virulence by upregulating glucosyltransferases (Gtfs), contributing to extracellular polysaccharide production and robust biofilms. Our study’s CFU reductions in the intervention groups suggest that enzyme-xylitol-based salivary systems may counteract radiation-induced dysbiosis and offer caries prevention.[21] OM, a painful complication of RT, arises from mucosal atrophy, ulceration, and inflammation. In this study, both Biotene and Xerostom significantly reduced OM severity compared to placebo, with no significant difference between the two. Ingredients like glycerin, betaine, and olive oil, common to both products, are known for their soothing, lubricating, and anti-inflammatory effects.
This is supported by Shetty et al., who described how mucosal hydration and epithelial barrier integrity can mitigate mucositis symptoms.[22] The glycerin content, in particular, appears to play a central role, given its shared presence and similar effect across both treatment groups. These results suggest that both salivary systems provide symptomatic relief for OM and may prevent its progression in irradiated patients.[23] Over time, placebo participants showed a decline in salivary flow, consistent with long-term post-RT damage. In contrast, Biotene and Xerostom users showed progressive improvement, suggesting a dual benefit: Natural recovery of gland function and therapeutic stimulation by the salivary systems. However, no significant intragroup changes were observed for mucin or beta-defensin, indicating that a longer follow-up period may be necessary to observe biomarker shifts.
While our findings are encouraging, the short duration limits evaluation of long-term caries development and glandular recovery. Moreover, patient variability in radiation exposure and baseline oral health may have influenced biomarker expression. However, the study’s strengths include strict inclusion/exclusion criteria, standardized interventions, and sensitive biomarker detection using ELISA, as supported by Pradeep et al., who emphasized ELISA’s precision in low-concentration biomarker assays.[24] This study is among the first to directly compare Biotene and Xerostom in a clinical setting while assessing their effects on salivary physiology, immune biomarkers, and caries risk. Both systems offer clear benefits, with Biotene showing marginally superior outcomes in salivary flow and microbial control. These findings underscore their utility in xerostomia management and caries prevention in RT-treated patients.
CONCLUSION
Within the study’s limitations, both Biotene oral balance and Xerostom salivary system effectively improved salivary function, enhanced salivary biomarkers, and reduced caries risk in patients with radiation-induced xerostomia. These results support their use in managing xerostomia in irradiated patients, though further research is needed to assess long-term efficacy and potential combination therapies.
Study approval statement
This study protocol was reviewed and approved by the institutional ethical clearance committee under protocol number ITSCDSR/Director-Principal/2023/L/076.
Consent to participate statement
A written consent was obtained from participants for using their saliva samples to participate in the study.
Author contributions
Alam A: Concept, design, data acquisition, analysis, manuscript preparation; Taneja S: Concept, design, supervision, manuscript review and editing (Guarantor); Kumar A: Clinical studies, data acquisition, methodology; Dheer A: Data analysis, manuscript editing, review; “Dr. Sonali Taneja is the guarantor of this work and takes responsibility for the integrity of the study.”
Data availability statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Winter C, Keimel R, Gugatschka M, Kolb D, Leitinger G, Roblegg E. Investigation of changes in saliva in radiotherapy-induced head neck cancer patients. Int J Environ Res Public Health. 2021;18:1629. doi: 10.3390/ijerph18041629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Rahman QB, Iocca O, Kufta K, Shanti RM. Global burden of head and neck cancer. Oral Maxillofac Surg Clin North Am. 2020;32:367–75. doi: 10.1016/j.coms.2020.04.002. [DOI] [PubMed] [Google Scholar]
- 3.Jasmer KJ, Gilman KE, Muñoz Forti K, Weisman GA, Limesand KH. Radiation-induced salivary gland dysfunction: Mechanisms, therapeutics and future directions. J Clin Med. 2020;9:4095. doi: 10.3390/jcm9124095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Grundmann O, Mitchell GC, Limesand KH. Sensitivity of salivary glands to radiation: From animal models to therapies. J Dent Res. 2009;88:894–903. doi: 10.1177/0022034509343143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr 2019. 2019:lgz016. doi: 10.1093/jncimonographs/lgz016. [DOI] [PubMed] [Google Scholar]
- 6.Gupta N, Pal M, Rawat S, Grewal MS, Garg H, Chauhan D, et al. Radiation-induced dental caries, prevention and treatment-a systematic review. Natl J Maxillofac Surg. 2015;6:160–6. doi: 10.4103/0975-5950.183870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Szkaradkiewicz-Karpińska AK, Ronij A, Goślińska-Kuźniarek O, Przybyłek I, Szkaradkiewicz A. MUC7 level as a new saliva risk factor for dental caries in adult patients. Int J Med Sci. 2019;16:241–6. doi: 10.7150/ijms.29027. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Jurczak A, Kościelniak D, Papież M, Vyhouskaya P, Krzyściak W. A study on β-defensin-2 and histatin-5 as a diagnostic marker of early childhood caries progression. Biol Res. 2015;48:61. doi: 10.1186/s40659-015-0050-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Martín M, Marín A, López M, Liñán O, Alvarenga F, Büchser D, et al. Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia. Rep Pract Oncol Radiother. 2017;22:71–6. doi: 10.1016/j.rpor.2016.09.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Jasmer KJ, Gilman KE, Muñoz Forti K, Weisman GA, Limesand KH. Radiation-induced salivary gland dysfunction: mechanisms, therapeutics and future directions. J Clin Med. 2020;9:4095. doi: 10.3390/jcm9124095. [doi:10.3390/jcm9124095] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy. Oral Oncol. 1999;35:132–7. doi: 10.1016/s1368-8375(98)00109-2. [doi:10.1016/S1368-8375(98)00109-2] [DOI] [PubMed] [Google Scholar]
- 12.Ship JA, McCutcheon JA, Spivakovsky S, Kerr AR. Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth. J Oral Rehabil. 2007;34:724–32. doi: 10.1111/j.1365-2842.2006.01718.x. [doi:10.1111/j.1365-2842.2006.01718.x] [DOI] [PubMed] [Google Scholar]
- 13.Martín M, Marín A, López M, Liñán O, Alvarenga F, Büchser D, et al. Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia. Rep Pract Oncol Radiother. 2017;22((1)):71–76. doi: 10.1016/j.rpor.2016.09.008. [doi:10.1016/j.rpor.2016.09.008] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Podunavac I, Hinić S, Kojić S, Jelenčiakova N, Radonić V, Petrović B, et al. Microfluidic platform for examination of effect of chewing xylitol gum on salivary pH, O2, and CO2. Appl Sci. 2021;11:2049. [doi:10.3390/app11052049] [Google Scholar]
- 15.López-Jornet MP, García-Teresa G, Viñas M, Vinuesa T. Clinical and antimicrobial evaluation of a mouthwash and toothpaste for xerostomia. J Dent. 2011;39:757–63. doi: 10.1016/j.jdent.2011.08.007. [DOI] [PubMed] [Google Scholar]
- 16.Vijayan A, Asha ML, Babu S, Chakraborty S. Prospective phase ii study of efficacy of transcutaneous electrical nerve stimulation in post-radiation patients Clin Oncol. 2014;26:743–7. doi: 10.1016/j.clon.2014.09.004. [DOI] [PubMed] [Google Scholar]
- 17.Frenkel ES, Ribbeck K. Salivary mucins protect surfaces from colonization by cariogenic bacteria. Appl Environ Microbiol. 2015;81:332–8. doi: 10.1128/AEM.02573-14. [doi:10.1128/AEM.02573-14] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Situ H, Bobek LA. MUC7 20-mer: investigation of antimicrobial activity, secondary structure, and possible mechanism of antifungal action. Antimicrob Agents Chemother. 2003;47:643–52. doi: 10.1128/AAC.47.2.643-652.2003. [doi:10.1128/AAC.47.2.643-652.2003] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Kirstilä V, Lenander-Lumikari M, Söderling E, Tenovuo J. Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia. Acta Odontol Scand. 1996;54:391–7. doi: 10.3109/00016359609003557. [doi:10.3109/00016359609003557] [DOI] [PubMed] [Google Scholar]
- 20.Tenovuo J. Clinical applications of antimicrobial host proteins lactoperoxidase, lysozyme and lactoferrin in xerostomia: efficacy and safety. Oral Dis. 2002;8:23–9. doi: 10.1034/j.1601-0825.2002.1o781.x. [doi:10.1034/j.1601-0825.2002.1o781.x] [DOI] [PubMed] [Google Scholar]
- 21.Hegde MN, Attavar SH, Shetty N. Saliva as a biomarker for dental caries: A systematic review. J Conserv Dent. 2019;22:2–6. doi: 10.4103/JCD.JCD_531_18. [doi:10.4103/JCD.JCD_531_18] [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Hegde MN, Hegde ND, Ashok A, Shetty S. Biochemical indicators of dental caries in saliva: An in vivo study. J Conserv Dent. 2014;17:300–4. doi: 10.1159/000355580. [DOI] [PubMed] [Google Scholar]
- 23.Shetty V, Hegde AM, Bhandary S. Salivary factors and dental caries experience in children: A clinical correlation study. J Conserv Dent. 2013;16:170–3. [Google Scholar]
- 24.Rai K, Hegde AM, Jose N. Salivary biomarkers in caries risk assessment among children: A comparative study. J Conserv Dent. 2012;15:335–9. [Google Scholar]
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Data Availability Statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.