Effects of Denture Treatment on Salivary Metabolites: A Pilot Study.

Symptoms of oral discomfort such as dry mouth are common in older people wearing dentures. Such symptoms are mainly treated symptomatically. Many of these symptoms are related to saliva, and associations with salivary volume have been reported. Although denture treatment improves symptoms by increasing the amount of saliva, the effects on salivary components remain unclear. This study aimed to investigate the effects of denture treatment on salivary metabolite changes based on salivary metabolome analyses. We enrolled 21 patients requiring denture treatment. At the first visit, and after completion of denture treatment, saliva outflow was measured under resting and stimulated conditions, samples for salivary metabolite analysis were collected, and masticatory efficiency was tested. In all participants, masticatory efficiency increased after denture treatment. Moreover, the amounts of resting and stimulated saliva were increased. Using salivary metabolome analysis, 61 salivary metabolites were detected. Substantial concentration changes were observed for 4 and 21 metabolites in resting and stimulated saliva, respectively. The four metabolites common to both saliva tests had significantly lower concentrations after treatment. These results suggest that the improvement in masticatory function by dentures is related not only to salivary secretion volume, but also to salivary metabolite composition.

Comparison of digital and silicone impressions for single-tooth implants and two- and three-unit implants for a free-end edentulous saddle.

BACKGROUND: The use of intraoral scanners (IOS) has facilitated the use of digital workflows for the fabrication of implant-supported prostheses not only for single missing teeth, but also for multiple missing teeth. However, the clinical application of IOS and computer-aided design/manufacturing (CAD/CAM) in implant-supported prosthodontics remains unclear. This study aimed to compare the accuracy of digital and silicone impressions for single-tooth implants for bounded edentulous spaces and two-unit and three-unit implant-supported fixed dental prostheses for free-end edentulous spaces. METHODS: This study enrolled 30 patients (n = 10 for each of the three groups) with an average age of 61.9 years. Conventional silicone-based and digital IOS-based impressions were made for all patients, and the implant superstructures were fabricated. We measured the scan-body misfit and compared the accuracy of the impressions for single-unit, two-unit, and three-unit implant prostheses with a bounded edentulous space by superimposing the standard triangulated language (STL) data obtained from IOS over the STL data of the plaster model used for final prosthesis fabrication. The scan bodies of the superimposed single-molar implant, two-unit implant prosthesis without teeth on the mesial side, two-unit implant prosthesis without teeth on the distal side, three-unit implant prosthesis without teeth on the mesial side, and three-unit implant prosthesis without teeth on the distal side were designated as A, B1, B2, C1, and C2, respectively. The misfit for each scan body was calculated and the accuracies were compared using the Tukey-Kramer method. RESULTS: The average scan-body misfit for conditions A, B1, B2, C1, and C2 was 40.5 ± 18.9, 45.4 ± 13.4, 56.5 ± 9.6, 50.7 ± 14.9, and 80.3 ± 12.4 µm, respectively. Significant differences were observed between the accuracies of A and B2, A and C2, and C1 and C2 (P < 0.001). CONCLUSIONS: IOS and CAD/CAM can find clinical applications for implant-supported prostheses of up to three units for a bounded edentulous saddle. The use of IOS could render implant treatment easier, benefiting both the surgeons and patients. Prosthesis maladjustment may lead to peri-implantitis and prosthetic fracture. Therefore, further validation of the accuracy of IOS impressions is required in patients with multiple missing teeth in long-span implant prostheses.

The effect of masticatory behaviour on generalized attention in heathy volunteers.

AIM: As our society ages, the number of people living with dementia also steadily increases. Some work has focused on masticatory behaviour as a form of daily health care that could help prevent cognitive impairment and dementia. However, it is not yet clear how masticatory behaviour influences various cognitive functions. Therefore, the purpose of this study was to examine the effect of masticatory behaviour on the decline of generalized attention, an important cognitive function. METHODS: Participants were 35 healthy, dentulous individuals without stomatognathic abnormalities (24 men, 11 women; mean age: 56.8 ± 4.8 years). All participants completed three interventions: mastication, foot-stepping, and none (control). Pre- and post-intervention measures of generalized attention were measured by using neuropsychological tests to examine general attention; the results were then compared. Simultaneously, during the generalized attention task, the functional activity of the prefrontal cortex was observed on functional near-infrared spectroscopy. RESULTS: Response time of generalized attention improved in both the masticatory and foot-stepping interventions. There was a transient increase in oxyhaemoglobin activity in the right and left prefrontal cortices in the masticatory intervention. CONCLUSIONS: Masticatory behaviour may be involved in a partial improvement of generalized attention and may induce prefrontal cortex activity in middle-aged and older adults.

Effect of Ultraviolet Irradiation of the Implant Surface on Progression of Periimplantitis--A Pilot Study in Dogs.

OBJECTIVE: The objective of this study was to investigate morphologically the progression of periimplantitis around an ultraviolet (UV)-light-irradiated implant in dogs. MATERIALS AND METHODS: Pure titanium implants (3.3 mm in diameter and 8 mm long) were placed into dog jawbone bilaterally. Implants on one side were irradiated with UV light for 15 minutes using a photodevice immediately before placement (UV group), whereas those on the other side were not irradiated (non-UV group). Osseointegration was confirmed 90 days after implant placement by radiography. Experimental periimplantitis was induced by the application of dental floss over 90 days. Clinical and radiographic examination and micro-computed tomography (micro-CT) were performed after 90 and 180 days, and bone resorption was measured. The bone-implant interface in tissue sections was examined by light microscopy. RESULTS: Bone resorption around the UV-irradiated implant was less pronounced than around the non-UV-irradiated implant in the ligature-induced periimplantitis model. Tissue section images revealed no contact and partial destruction at the bone-implant interface. CONCLUSION: Within the limitations of this preliminary investigation, it is suggested that UV-light-irradiated implants suppress spontaneous progression of periimplantitis.

Effect of denture adhesives on masticatory performance: Multicenter randomized controlled trial.

PURPOSE: The purpose of this study is to investigate the effects of denture adhesives on masticatory performance via a 10-center, parallel, randomized, controlled trial of complete denture wearers in Japan. METHODS: The trial was conducted between September 2013 and October 2016. The inclusion criteria were complete edentulism, willingness to undergo new complete denture treatment, and willingness to return for recall treatment. The exclusion criteria were age 90 years or older, presence of severe systemic illness, inability to understand the questionnaires, wearing metal base complete dentures, denture adhesive user, wearing prosthetics for maxillofacial defects, wearing complete dentures with tissue conditioners, and severe xerostomia. Randomization of the powder-type denture adhesive (powder), cream-type denture adhesive (cream), and control (saline) groups was performed using a sealed envelope system. Masticatory performance was measured using color-changeable chewing gum. Intervention blinding was not feasible. RESULTS: Sixty-seven control, 69 powder, and 64 cream participants are analyzed using the intention-to-treat principle. The participants in all groups show significantly improved masticatory performance at post-intervention (paired t-test with Bonferroni correction P < 0.0001). However, no significant difference in masticatory performance is detected among the three groups (one-way analysis of variance). A significant negative correlation between pre- and post-changes in masticatory performance and intraoral condition scores is observed (Pearson's correlation coefficient, P < 0.0001). CONCLUSIONS: Although denture adhesives improved the masticatory performance of complete denture wearers, their clinical effects are comparable to those of saline solution. The use of denture adhesives is more effective in complete denture wearers with unsatisfactory intraoral conditions.

Effects of denture adhesives on denture retention and occlusal forces in complete denture wearers: A multicenter, randomized controlled trial.

PURPOSE: This study aimed to determine the effects of denture adhesives on denture retention and occlusal force in complete denture wearers in a multicenter, randomized, parallel-group controlled trial. METHODS: Two hundred edentulous patients wearing complete dentures were allocated to three groups: powder-type denture adhesive, cream-type denture adhesive, and control (saline solution). Denture adhesives and saline solution were applied to the dentures for 4 days. The retentive force of the dentures and occlusal force were measured using a force transducer occlusal force meter at baseline and after 4 days of intervention. In addition to between-group comparisons, subgroup analyses of denture retention and occlusal force were performed based on the level of difficulty of the edentulism treatment. The levels were ranked as I (easy), II, III, and IV (difficult). RESULTS: Cream-type denture adhesives significantly improved the retentive force of the dentures (P<0.01) and occlusal force (P<0.05), with no significant differences between baseline and post-intervention forces in the powder-type denture adhesive and control groups. In within-group comparisons, cream-type denture adhesives improved both the retentive and occlusal forces at Level II (P<0.05), and powder-type denture adhesives improved the occlusal force at Level II (P<0.01). CONCLUSIONS: Application of cream-type denture adhesives effectively improves the denture retention and occlusal force in complete denture wearers with a moderate degree of difficulty during edentulism treatment.

A Preliminary Pilot Study: Metabolomic Analysis of Saliva in Oral Candidiasis.

Early detection of oral candidiasis is essential. However, most currently available methods are time-consuming and useful only for screening patients. Previous studies on the relationship between oral candidiasis and saliva have focused on saliva volume and not on its components. Therefore, to clarify the effects of oral candidiasis on salivary metabolites, the relationship between salivary components and oral candidiasis was investigated by comparing the salivary metabolites of oral candidiasis patients and those not previously diagnosed with candidiasis. Forty-five participants visiting our university hospital were included and classified into two groups, the Candida group and the control group, based on the Candida detection test results. The unstimulated saliva was collected using the spitting method over 15 min, and the stimulated saliva was collected using the gum-chewing method over 10 min. The saliva volume was measured, and the saliva samples were frozen and analyzed metabolomically. Metabolome analysis revealed 51 metabolites with peak detection rates exceeding 50%. There was no significant difference in age and sex between the Candida and control groups. In the Candida group, five metabolites (tyrosine, choline, phosphoenolpyruvate, histidine, and 6-phosphogluconate) were significantly elevated in the unstimulated, two (octanoic acid and uridine monophosphate(UMP)) were significantly increased, and four (ornithine, butyrate, aminovalerate and aminolevulinate) were significantly decreased in the stimulated saliva. This study suggests the possibility of identifying metabolites specific to patients with oral candidiasis, which could aid prompt diagnosis.

Application of multi-directionally forged high-strength titanium to dental implants in beagle dogs.

Pure titanium is widely used as a material in dental implants. However, it possesses inferior mechanical strength. This study aimed to elucidate the efficacy of acid treated multi-directionally forged (MDF) pure titanium in vivo. We verified the temporal changes until osseointegration in beagle dogs. Using two types of experimental materials (conventional pure titanium or MDF pure titanium), new bone formation was assessed using morphological examinations, and the bone-to-implant contact (BIC) value was evaluated at each time point (14, 30, and 90 days after the operation). As such, new bone formation was observed around the acid-etched MDF group, in which the BIC value was highest, followed by that in the acid-etched pure titanium group. MDF pure titanium implants showed early promotion of new bone formation compared to conventional titanium implants. The new acid-treated MDF made of pure titanium could be applied to humans in the future to prove its practicality.

Patient satisfaction with conventional dentures vs. digital dentures fabricated using 3D-printing: A randomized crossover trial.

PURPOSE: Evidence regarding the performance of digital dentures (DDs) fabricated using 3D printing is insufficient. This study aimed to evaluate patient satisfaction with conventional dentures (CDs) and DDs fabricated using 3D printing. METHODS: This randomized controlled trial was conducted between November 2017 and May 2020. In the CD-DD group, CDs were fabricated before DDs, while the protocol was reversed in the DD-CD group. The primary outcome was patient satisfaction, quantified using a 100-mm visual analog scale, which assessed chewing efficiency, pain, stability, retention, comfort, esthetics, ease of cleaning, phonetics, and general satisfaction. Secondary outcomes were quality of life (QOL), number of visits, time required for definitive denture fabrication, number of adjustment appointments, and time required for denture stabilization after denture delivery. RESULTS: Patient satisfaction with CDs was superior in terms of phonetics, ease of cleaning, stability, comfort, and general satisfaction. Secondary outcomes such as social disability and the number of clinic visits were significantly lower in patients with DDs. However, the two groups showed no significant differences in the other outcomes. Although patient satisfaction with DDs was inferior to that with CDs, 20% of patients preferred and used DDs (12 patients preferred CDs, and three patients opted for DDs). CONCLUSION: Although patient satisfaction or QOL with DDs may be somewhat inferior to that with CDs, 20% of patients preferred and used DDs daily. Thus, DDs fabricated using 3D printing may have comparable practicality and efficacy to CDs.

Clinical efficacy of mandibular complete dentures with a resilient liner: study protocol for a multicenter randomized controlled trial.

BACKGROUND: During restoration of poorly fitting complete dentures (CDs) in edentulous patients, liners are used to reconstruct the concave surfaces of CDs with a new base material. These relining materials are classified into resilient liners (RLs) and non-resilient liners (NRLs), but the clinical effects of these liners and their selection criteria remain unclear. The purpose of this study is to evaluate the clinical efficacy of relining mandibular CDs using RL and NRL and to conduct a follow-up study. METHODS: The study is currently being conducted at eight centers, and a parallel-group randomized controlled trial (RCT) is underway. One hundred thirty-two edentulous patients with poorly fitting mandibular CDs will be assigned to two groups based on whether they will receive RL or NRL. Participants will have an RL or NRL applied for relining their CDs using an indirect method of dynamic impressions. Data will be recorded at 1 week and 3, 6, and 12 months after denture delivery. The primary outcome will be assessment of the patients' general satisfaction by using a 100-mm visual analog scale (VAS). Secondary outcomes will be measured as patient-reported outcomes, including food intake status and oral hygiene-related quality of life. Masticatory performance and the number of sore spots on the oral mucosa will also be recorded. Comparisons between the two groups and within-subject comparisons of pre- and post-intervention measurements will be conducted. DISCUSSION: For dentists and prosthetic researchers in Japan, this RCT will provide information on the clinical efficacy of RL materials in comparison to RNL in CD wearers. The new evidence regarding the use of RL materials in an aging population will also be useful to dentists in other countries in their routine clinical practice. TRIAL REGISTRATION: This clinical trial has been registered at the University Hospital Medical Information Network (UMIN) Center (UMIN000041950).

Positive Effects of Saliva on Oral Candidiasis: Basic Research on the Analysis of Salivary Properties.

The major causes of oral candidiasis include decreased salivary flow rate and the use of ill-fitting dentures. However, the relationships among prosthetic treatment, saliva, and Candida albicans have not been elucidated. This study aimed to examine the effects of prosthetic treatment and changes in saliva (mainly the salivary flow rate) on oral candidiasis symptoms. Participants requiring prosthetic treatment underwent testing for C. albicans, salivary flow rate, intraoral symptoms, and bite force at the initial visit and four months after treatment to evaluate pretreatment and post-treatment changes. The relationships among C. albicans, salivary flow rate, dentures, and intraoral symptoms were analyzed using multiple regression analysis. Denture treatment improved activity against C. albicans as well as the salivary flow rate, intraoral symptoms, and masticatory function. Multiple regression analysis revealed that changes in the stimulated salivary flow rate due to prosthetic treatment significantly improved C. albicans detection (p = 0.011), intraoral symptoms (p = 0.037), and bite force (p = 0.031). This study showed that prosthetic treatment improved salivary flow and intraoral symptoms and confirmed the influence of stimulated salivary flow rate changes.

Accuracy of guided surgery using the silicon impression and digital impression method for the mandibular free end: a comparative study.

BACKGROUND: Implant treatment using guided surgery is becoming widespread in clinical dental practice. Furthermore, the development of digital technology has enabled the use of intraoral scanners (IOSs) to fabricate surgical guide plates. The objective of this study was to compare the accuracy of guided surgery using the silicone impression method with a three-dimensional (3D) scanner and the digital impression method with IOS for one side of the mandibular free end. In addition, we compared the accuracy of tooth-supported vs tooth/mucosa-supported surgical guide plates. RESULTS: The accuracy of the tooth-supported surgical guide plate using the new IOS method instead of the method of obtaining impressions with conventional silicone resulted in better measurements of 3D deviation at the crest, 3D deviation at the apex, and angular deviation. In terms of the accuracy of the tooth/mucosa-supported surgical guide plate, there were no significant differences in all measurements. The surgical guide plate using an IOS and the tooth/mucosa-supported surgical guide plate may enable more accurate guided surgery. CONCLUSION: Tooth/mucosa-supported guided surgery involving preparation with an IOS may result in more accurate implant surgery.

Application of multi-directional forged titanium for prosthetic crown fabrication by CAD/CAM.

Titanium are often used as dental materials, pure titanium present low strength and titanium alloy is reported poor biocompatibility, respectively. To overcome the problem, we fabricated high-strength multi-directional forged (MDF) titanium with improved mechanical properties without changing the chemical composition and evaluated its applicability in prosthetic crowns. Cutting tests: the average absolute value of the difference before and after cutting was calculated as the uncut amount. Surface evaluations: MDF titanium, pure titanium, and the Ti-6Al-4V alloy were the surface properties (the surface roughness, the contact angles, glossiness) of the samples were evaluated. The fitness test used digital data. These demonstrated that the good workability of high-strength MDF titanium. The surface-roughness and contact-angle properties of MDF titanium and pure titanium were similar. The fitness test showed no significant differences between MDF titanium and pure titanium crowns. These results suggest that MDF titanium is promising for fabricating prosthetic crowns in dental applications.

Multivariate analysis reveals oral health-related quality of life of complete denture wearers with denture adhesives: a multicenter randomized controlled trial.

Purpose To investigate the difference in improvement of oral health-related quality of life (OHR-QoL) depending on the oral and denture conditions of a complete denture wearer when using a cream or powder type denture adhesive in a 10-center parallel randomized clinical trial.Methods Two hundred edentulous subjects who wore complete dentures were allocated to each of the three groups according to denture adhesive type: cream, powder, and control (saline solution). The materials were applied to the mucosal surface of the dentures for 4 days, and baseline data and data after the intervention were collected. OHR-QoL was assessed using the Japanese version of the modified Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT-J) scale for outcome. Multivariate analysis was used to investigate improvements in OHR-QoL according to participant characteristics among complete denture wearers using these materials.Results OHIP-EDENT-J scores were significantly decreased in all groups after the intervention (p < 0.05); however, there were no statistically significant differences among the groups. Multiple logistic regression analysis revealed a significant association between the vertical height of the maxillary and mandibular alveolar ridge and OHIP-EDENT-J scores in the cream-type denture adhesive group. In contrast, there were no significant association between participant characteristics and OHIP-EDENT-J scores in the powder-type adhesive and control groups.Conclusions The use of denture adhesives could improve OHR-QoL for complete denture wearers. The cream-type denture adhesives may be expected to improve OHR-QoL in patients with poor residual ridge conditions compared with patients with good residual ridge conditions.

In vitro evaluation of a removable partial denture framework using multi-directionally forged titanium.

PURPOSE: This study evaluated the availability of multi-directionally forged (MDF) titanium (Ti) as a component of removable partial dentures (RPDs). MDF-Ti remarkably improved the mechanical properties of RPDs due to its ultrafine-grained structure. MATERIALS AND METHODS: The wear resistance, plaque adhesion, and machinability of MDF-Ti were tested. As controls, commercially pure (CP) titanium was used for wear, plaque adhesion, and machinability tests. For wear resistance, the volume losses of the titanium teeth before and after wear tests were evaluated. Plaque adhesion was evaluated by the assay of Streptococcus mutans. In the machinability test, samples were cut and ground by a steel fissure bur and carborundum (SiC) point. An unpaired t-test was employed for the analysis of the significant differences between MDF-Ti and the control in the results for each test. RESULTS: Wear resistance and plaque adherence of MDF-Ti similar to those of CP-Ti (P>.05) were indicated. MDF-Ti exhibited significantly larger volume loss than CP-Ti in all conditions except 100/30,000 g/rpm in machinability tests (P<.05). CONCLUSION: Although the wear resistance and plaque adherence of MDF-Ti were comparable to those of controls, MDF-Ti showed better machinability than did CP-Ti. MDF-Ti could be used as a framework material for RPDs.

Effect of denture adhesives on oral moisture: A multicenter randomized controlled trial.

PURPOSE: The purpose of this study was to investigate the effect of denture adhesives on oral moisture in a 10-center parallel randomized clinical trial. METHODS: Two hundred edentulous subjects wearing complete dentures were allocated into three groups: cream-type adhesive, powder-type adhesive and control groups. The adhesives (and saline solution in the control group) were applied to the mucosal surface of the dentures for 4 days, and baseline data and data after the intervention for eight meals over 4 days were obtained. For the main outcome, oral moisture was measured with a moisture checking device. Secondary outcomes were denture satisfaction, masticatory performance, denture retention, and occlusal force. In addition to between-group and within-group comparisons of oral moisture, investigations for secondary outcomes were undertaken in subgroups classified according to the degree of oral moisture at baseline (normal subgroup and dry mouth subgroup). Intention-to-treat analysis was also performed. RESULTS: Between-group and within-group comparisons of oral moisture showed no significant differences. The cream-type and powder-type denture adhesives were significantly effective in the dry mouth group for denture satisfaction ratings of ability to masticate, stability, retention, and comfort of mandibular dentures (p<0.05). The masticatory performance and retentive force of the dry mouth denture adhesive using groups were significantly improved after intervention (p<0.05). CONCLUSIONS: The oral moisture of complete denture wearers was not influenced by the use of denture adhesives. Our findings showed that denture adhesives improved subjective denture satisfaction, masticatory performance, and retention for complete denture patients with oral dryness.

Electrochemical property and corrosion behavior of multi-directionally forged titanium in fluoride solution.

Multi-directional forging (MDFing) can improve the various properties of metals and alloys due to the evolution of an ultrafine-grained structure. In the present study, electrochemical properties and corrosion behaviors in a fluoride solution of MDFed pure titanium (MDF-Ti) were evaluated by comparing with conventional coarse-grained pure titanium (Ti). The Eopen value of MDF-Ti was significantly higher than that of Ti. However, similar potentiodynamic polarization profiles were obtained for Ti and MDF-Ti. Immersion in NaF solution caused no severe corrosion to Ti or MDF-Ti. However, immersion in acidulate phosphate fluoride solution (APF) revealed that MDF-Ti had better corrosion resistance than Ti at shorter time immersion periods and was more susceptible to corrosion for longer immersion. Significantly less release of titanium was observed for MDF-Ti in shorter immersion periods in APF. In conclusion, MDF-Ti showed similar electrochemical behaviors to Ti and less susceptible to corrosion in shorter time APF immersion.

Effects of inter-day and intra-day variation on salivary metabolomic profiles.

BACKGROUND: Salivary secretion is an important parameter reflecting the health status of an individual and has been used clinically for the diagnosis of various oral diseases, such as xerostomia. Salivary metabolomic profiling is considered an emerging potential tool for the detection of various systemic diseases. To our knowledge, this is the first study to investigate the quantitative relationship between salivary secretion volume and salivary metabolomic profile. METHODS: To evaluate inter- and intra-day variations in salivary secretion, 234 saliva samples were collected three times per day for three days from 13 subjects and analyzed. Capillary electrophoresis-mass spectrometry was used for non-targeted quantification of water-soluble metabolites. RESULTS: No significant inter- or intra-day variations were observed in salivary secretion volume. No significant inter-day variations were observed in metabolomic patterns. In contrast, significant intra-day variations were observed in salivary metabolomic profiles. The difference was more obvious for stimulated saliva than for unstimulated saliva. These profile changes were independent of salivary secretion volume. CONCLUSIONS: Our results indicated that diurnal change had a greater effect on salivary metabolomic profiles than the other factors. Hence, sampling time should be tightly controlled to minimize unexpected bias in the clinical use of salivary metabolomics.

Influence of ultraviolet irradiation treatment on porcelain bond strength of titanium surfaces.

To determine the effect of titanium (Ti) surface modification by ultraviolet irradiation (UVI) on the bond strength between Ti and porcelain. Grade 2 Ti plates were allotted to five groups: sandblasted (SA), 15 min UVI (UV), SA+5 min UVI (SA+UV5), SA+10 min UVI (SA+UV10), and SA+15 min UVI (SA+UV15). After surface treatment, porcelain was added. A precious metal (MC) was used for comparison with Ti. The effects of 24-h storage at room temperature versus thermal cycling only at 5 and 55°C in water were evaluated. Subsequently, the tensile strength of each sample was tested. Data were analyzed using one-way analysis of variance and the Tukey test. In both the room temperature and thermal cycling groups, the MC and SA+15 min UVI samples showed significantly greater bond strengths than the other samples (p<0.05). UVI processing efficiently increases the bond strength between porcelain and the Ti surface.

Effect of masticatory stimulation on the quantity and quality of saliva and the salivary metabolomic profile.

BACKGROUND: This study characterized the changes in quality and quantity of saliva, and changes in the salivary metabolomic profile, to understand the effects of masticatory stimulation. METHODS: Stimulated and unstimulated saliva samples were collected from 55 subjects and salivary hydrophilic metabolites were comprehensively quantified using capillary electrophoresis-time-of-flight mass spectrometry. RESULTS: In total, 137 metabolites were identified and quantified. The concentrations of 44 metabolites in stimulated saliva were significantly higher than those in unstimulated saliva. Pathway analysis identified the upregulation of the urea cycle and synthesis and degradation pathways of glycine, serine, cysteine and threonine in stimulated saliva. A principal component analysis revealed that the effect of masticatory stimulation on salivary metabolomic profiles was less dependent on sample population sex, age, and smoking. The concentrations of only 1 metabolite in unstimulated saliva, and of 3 metabolites stimulated saliva, showed significant correlation with salivary secretion volume, indicating that the salivary metabolomic profile and salivary secretion volume were independent factors. CONCLUSIONS: Masticatory stimulation affected not only salivary secretion volume, but also metabolite concentration patterns. A low correlation between the secretion volume and these patterns supports the conclusion that the salivary metabolomic profile may be a new indicator to characterize masticatory stimulation.