Journal of Industrial Hygiene Journal of Occupational Health 2010; 52: 172–181 Neurophysiological effects of flavoring and caffeine-added toothpaste Hidetoshi Sadat, Yoshinori Murakami, Manabu Hosoya, and Yukihiro Yada Kao Corporation Tokyo Research Laboratory Abstract: Neurophysiological effects of toothpaste containing flavoring ÿ. introduction ingredients and caffeine: Hidetoshi Sadatoshi et al. Kao Corporation Tokyo Research Laboratory - Objective: We have previously reported that In recent years, bathing and coffee drinking have been commonly adopted toothbrushing can be used as a form of active rest to reduce fatigue. In this as methods for reducing and alleviating fatigue, while research has shown study, we focused on toothpaste to enhance the fatigue-reducing effect of that aromatherapy and acupressure are more widely recognized as toothbrushing. Subjects and Methods: The effects of adding flavoring effective1 ). Meanwhile, we have been investigating the application of tooth ingredients and caffeine were examined using flicker values, event-related brushing to active rest2,3). As a result, we reported that tooth brushing potentials P300, and mood scales. First, 13 healthy adults (6 men, 7 women, increased flicker values4) and changed mood scales5–9 ), suggesting that mean age ± standard deviation; 28.2 ± 6.5 years) were asked to perform a tooth brushing may be a useful method for reducing fatigue through active 25-minute calculation task on a computer. After that, they brushed their teeth rest10). However , although tooth brushing has been proposed as a possible with the toothpaste and performed the calculation task again. Results: method for reducing and alleviating fatigue, there are Compared to toothpaste without flavoring or caffeine, toothpaste containing few studies that have examined in detail the evaluation of the active flavoring and caffeine significantly shortened the P300 peak latency (p < ingredients that enhance its effect or the conditions of use. In addition, our 0.01), and significantly inhibited the extension of the P300 peak latency after investigation into the application of tooth brushing to active rest only the calculation task (p < 0.01 ). Furthermore, the rate of correct answers in suggested one possibility as a method for reducing and alleviating fatigue the calculation task tended to increase (p < 0.1). In the mood scale, there that has been previously reported. was a tendency for a decrease in "overall fatigue" (p < 0.1), a significant decrease in "fatigue" (p < 0.05), and a significant increase in "exhilaration" and "clear mind" ( p < 0.01, p < 0.05, respectively) . Discussion: These Not enough. Therefore, in this study, we focused on dentifrice to improve the effect of results suggest that toothpaste containing flavoring and caffeine is useful for reducing fatigue caused by tooth brushing. A typical dentifrice contains the reducing fatigue. (Sanhygienist Journal 2010; 52: 172-181) basic ingredients of a humectant (e.g., sorbitol solution), a cleaning agent (e.g., calcium carbonate), a binder (e.g., xanthan gum), a foaming agent (e.g., lauryl sulfate), and a base (e.g., purified water). In some cases, it may also contain a viscosity adjuster (e.g., silicic anhydride), medicinal ingredients (e.g., polyethylene glycol), flavoring agents (fragrances), cooling agents Keywords : Active rest, Event-related potentials, (menthol), and coloring agents (e.g., titanium oxide). In particular, flavoring Mood scale, P300, Toothpaste ingredients play an important role in providing a feeling of oral hygiene through a refreshing sensation and preventing bad breath, and are expected to have a mood-changing effect due to the refreshing feeling after brushing teeth11 ). Furthermore, flavor ingredients act on the autonomic and central nervous systems, and it has been reported that they have the effect of increasing sympathetic nervous activity, which is seen in increased blood Received January 15, 2010; Accepted March 30, 2010 pressure12), the effect of affecting mood and work efficiency13 ), the effect J-STAGE Early Release Date: April 28, 2010 Contact: Hidetoshi Sado 2-1-3 Bunka, Sumida-ku, Tokyo 131-8501, Japan of promoting recovery from stress reactions and the effect of awakening14 ), Kao Corporation Tokyo Research and even the effect of suppressing the decline in information processing Laboratory (email: sadachi.hidetoshi@kao.co.jp) ability due to work stress15). Therefore, by incorporating flavor ingredients with an awakening effe
Sadatatsu et al.: Neurophysiological effects of toothpastes containing flavoring ingredients and caffeine 173 The subjects were given either the 1 or 2 condition once a day, for a total of two It is expected that this will enhance the fatigue-reducing effect of active rest. Furthermore, it is thought that the incorporation of caffeine17,18), which has been trials. The room temperature was set at 25 degrees Celsius and the humidity at confirmed to have a direct arousing effect on the cerebral cortex16), may additively 50% Rh. After measuring the resting state (Rest), the subjects were asked to and synergistically enhance the fatigue-reducing effect of toothpaste . In this study, perform the first calculation task (Load1) for 25 minutes. After Load1, the subjects in order to brushed their teeth (Care), and then performed the second calculation task (Load2). clarify whether the flavor components of toothpaste and caffeine enhance the The subjects were asked to complete the flicker test immediately after Rest brain's information processing ability and whether they can suppress the decline in (preLoad1), immediately after Load1 (postLoad1), immediately after Care information processing ability due to mental fatigue, in addition to subjective (preLoad2), and immediately after Load2 (postLoad2), and then answered three evaluation and flicker value measurement , we also performed neurophysiological types of questionnaires about their mood at that time. After filling out the verification by newly adding measurements of the peak latency and amplitude of the questionnaires, the subjects were asked to perform an auditory oddball task. The related potential P300, which has previously been suggested to be closely event- related to information processing ability19-21 ) . experimental procedure is shown in Fig. 1. 1) Toothpaste formulations A dentifrice (test formulation) was used that was based on a commercially available dentifrice (containing base (purified water), humectant II. Subjects and methods (sorbitol solution), sweetener (sodium saccharin), binder (sodium 1. Subjects carboxymethylcellulose), foaming agent (lauryl sulfate), cleaning agent (calcium Fourteen healthy male and female subjects (7 males, 7 females, mean age 28.2 carbonate, anhydrous silicic acid), and medicinal ingredients (sodium ± 6.3 years, right-handed) who reported that their hearing and vision (including monofluorophosphate, etc.)) and contained citrus flavoring ingredients (1.4%) corrected vision) were normal were used as subjects. In addition, it was confirmed (hereafter referred to as flavoring ingredients) and anhydrous caffeine (1.0%). As by self-report that there was no obvious trauma in the oral cavity of the subjects, a control, a dentifrice that did not contain flavoring ingredients or anhydrous and that their teeth and gums were not currently undergoing treatment. Before the caffeine (control formulation) was used. In both conditions, 1 g of dentifrice experiment, the contents of the experiment were explained to each subject, and (containing flavoring ingredients: 14 mg, anhydrous caffeine: 10 mg) was applied consent forms for participation were obtained. Ultimately, the results of 13 subjects to a toothbrush and the teeth and gums were brushed. The tooth brushing time who had little artifact contamination in the EEG and could be analyzed in all auditory was set to 1 minute, after which the subjects were asked to rinse their mouths oddball tasks were analyzed. In addition, the protocol of this experiment was several times with a cup of 150 cc of water. 2) Auditory oddball task approved by the Kao Corporation Human Research Ethics Committee and was carried out. 2. Methods Thirteen subjects were divided into two groups (seven subjects in the test An auditory oddball task was performed using 1 kHz and 2 kHz sound stimuli. formulation group first, and six subjects in the control formulation group first), and The duration was 100 ms, the rise and fall time was 10 ms, the stimulus interval all subjects underwent experiments under both the test formulation and control was 1,500 ms, and the inter-stimulus interval had a random rate of 25%. The 2 kHz formulation conditions. The experiment started at 13:00, one hour after lunch and sound stimuli were presented as low-frequency stimuli (p = 0.20) and the 1 kHz break, taking into account the influence of lunch. The experiment was a crossover sound stimuli were presented as high-frequency stimuli (p = 0.80). The subjects randomized comparative study, in which subjects were randomly assigned to the were asked to choose the stimuli that they could enjoy the low-frequency stimuli. test formulation and the control formulation in a single-blind manner. Fig. 1. Experimental protocol of this study. Flicker test, ERPs (Event-Related Potentials) and subjective questionnaires using VAS (Visual Analogue Scale), MMS (Multiple Mood Scale) and SSS (Stanford Sleepiness Scale) are shown by arrows (ÿ). A continuous calculation task was done for 25 min, shown by the closed box ( ). Tooth brushing is shown by the open box ( ). Rest is shown by the hatched box ( ).
174 Journal of Industrial Hygiene, Vol. 52, 2010 The subjects were instructed to press the button as quickly and accurately The signals were amplified using a filter (0.16–30 Hz) and recorded on a as possible, and to suppress blinking and eye movements as much as laptop computer (NEC VersaPro VY16E/R-1) at a sampling frequency of 1 possible. The reaction time when the button was pressed correctly was used kHz. ERP waveforms were obtained by averaging the 1,000 ms interval from for the analysis. 200 ms before the presentation of the auditory stimulus to 800 ms after the 3) Flicker test First, the subjects were asked to gaze at a target (ÿ8.7 mm) of a green light-emitting stimulus. Trials in which artifacts such as blinking were visible were excluded from the averaging process. The baseline was set to the average potential for diode (dominant wavelength: 555 nm) flickering at 70 Hz using a handy flicker the 200 ms interval before the stimulus was presented. The obtained (NEITZ Handy Flicker HF-II) (distance between the target and the subject's waveforms were processed by moving averaging for 31 data sets using eye: approximately 25 cm, visual angle: approximately 2°), and to confirm Matlab 6.0 software. that they did not sense flicker. Next, the subjects were asked to press the button with their right thumb and release their finger when they sensed flicker. The frequency at that time was calculated as the flicker value. Five 3. Statistical analysis Repeated measures ANOVA was used to compare each item consecutive trials were performed in one test, and the average value of the before and after each calculation task between the two conditions (test and three trials, excluding the maximum and minimum values, was used for the control) and within each condition (P300 peak latency and amplitude: 3 analysis. 4) factors (condition (test/control) × task (pre/post) × site (Fz/Cz/Pz)), ERP button Calculation task press reaction time, flicker value, mood scale: 2 factors (condition (test/control) In order to control the degree of fatigue of the subjects, the calculation task software we developed was performed for 25 minutes. This software × task (pre/post)). Fisher's PLSD method was used for sub-tests. Changes in the rate of correct answers and average reaction time of the calculation task imitates the Uchida-Kraepelin test format, where one-digit numbers are based on Load1 were used for analysis, and Student's paired t -test was used displayed randomly and participants are asked to calculate two numbers for comparison between conditions. StatView (5.0) was used for analysis, and according to addition or multiplication symbols that are also displayed all ANOVAs and t- tests were used. The significance level was set at 5%. randomly, and to enter only the first digit of the answer using the numeric keypad. Before the task, participants were instructed to enter the answers as quickly and accurately as possible. 5) Questionnaires This study used the following three types of questionnaires. Note that subjects were instructed in advance to fill out the questions intuitively without careful consideration. ÿ. result Ta. 1. Visual Analogue Scale (VAS)5,6): Seven items were used, namely "general fatigue ," "perceived stress," "boredom," "mental clarity," "concentration," "motivation," and "exhilaration." 2. Short version of the Scale for 1ÿERP Figure 2 shows the grand averages for both conditions at Fz, Cz, and Pz. ERP waveforms were shown. In both conditions, large positive potentials occurred Multiple Emotional States7,8 ): Twenty items were used across four in the latency period of 200–700 ms, and were predominant in the parietal region. subscales, namely "depression/anxiety," "fatigue," "active pleasure," and Based on the polarity, distribution, and latency patterns, these components were "inactive pleasure." Subjective evaluation was conducted on a four-point identified as P300. scale ranging from "not at all" (1) to "definitely felt" (4). 1 to 4 were simply added up, and the higher the total score, the higher the feelings for each item. 3. The Japanese 2. P300 dive time Figure 3 shows the P300 peak latency before and after Load1 (pre/post translation of the Stanford Sleepiness Scale ( SSS)9) was used to assess Load1). First, to examine the effect of Load1, which was performed to control subjective sleepiness on a 7-point scale ranging from (1) “full of energy and the degree of fatigue, the response under each condition was confirmed in energy, wide awake” to (7) “unable to keep eyes open, likely to fall asleep the oddball task. An ANOVA was performed for condition (test formulation/ immediately.” 6) ERP recording EEG was derived from three points, Fz, Cz, control formulation) x task (pre/post) x site (Fz/Cz/Pz), and a main effect of and Pz, based on the right mastoid process (A1), task was observed (p < 0.0001). At post Load1, the P300 peak latency for the according to the entire oddball task was significantly extended at three sites under both International 10-20 system. A plate-shaped silver-silver chloride electrode conditions. However, no site differences were obtained, so the average values was attached to the forehead as the ground electrode. Biosignals were for the three sites are shown in Figure 3. Furthermore, the P300 peak latency recorded using a portable multipurpose bioamplifier (Polymate AP1000, for the oddball task before and after Load2 (pre/post Digitex Laboratory Co., Ltd.) with a time constant of 1.0 s and a high-frequency cutoff frequency of 30 Hz (band-pass filter). Load2) was compared between the test formulation and the control formulation. An ANOVA for condition x task x site was performed.
Sadatatsu et al.: Neurophysiological effects of toothpastes containing flavoring ingredients and caffeine 175 Fig. 2. Average waveform of event-related potentials (ERPs) of 3 areas elicited by a target stim-) toothpaste. ulus before and after the use of the test ( ) or control ( Fig. 3. P300 latency (ms) before and after (pre / post) calculation (Load1 / Load2) before and after using the test (•) or control (•) toothpaste. Mean ± S.D., N=13, ****p<0.0001, ***p<0.001. The main effects of condition and task were found. Compared to the In the ball-ball task, the control preparation delayed the P300 peak control formulation, the test formulation significantly shortened the P300 latency, but the test preparation did not (test preparation: ns, control peak latency (p < 0.001). Furthermore, compared to pre-Load2, post- preparation: p < 0.0001). In addition, multiple comparisons using the Load2, the P300 peak latency was significantly prolonged (p < 0.0001 ). average values of the three sites showed that the P300 peak latency of However, as with the results for Load1, no main effect of site was found, the test preparation (355 ms) was significantly shorter than that of the so the average values for the three sites are shown in Figure 3. An control preparation (386 ms) only at post-Load2 (p < 0.0001). interaction between condition and task was also found (p < 0.001). The odds ratio before and after Load2 (pre/post-Load2) was significantly increased (p < 0.0001) .
176 Journal of Industrial Hygiene, Vol. 52, 2010 3. P300 A main effect of location and task was obtained (task; p < 0.0001, Amplitude Figure 4 shows the P300 peak amplitude before and after Load1 (pre/post Load1). First, to examine the effect of Load1, site; p < 0.01). In both conditions, the P300 peak amplitude was significantly larger at Pz than at Fz (p < 0.001), and the P300 peak which was administered to control the degree of fatigue, we confirmed amplitude at Cz was significantly larger than at Fz (p < 0.01). At Post the response under each condition in the oddball task. Load2, the amplitude was significantly smaller in both conditions and at all sites. ANOVA revealed main effects of task and site (task; p < 0.01, site; p Ta. < 0.01). In both conditions, the P300 peak amplitude was significantly larger at Pz than at Fz (p < 0.01), and the P300 peak amplitude was significantly larger at Cz than at Fz (p < 0.05). At Post Load 1, it was significantly smaller in both conditions and at all sites. 4. Auditory oddball task Figure 5 shows the button press reaction time (RT) for the oddball task during ERP measurement before and after Load1 (pre/post Load1). First, to examine the effect of Load1, which was administered Next, to examine the effects of the two conditions on Load2, to control for the degree of fatigue, we confirmed the response under The P300 peak amplitudes of these two toothpastes in the oddball each condition in the oddball task. First, we performed an ANOVA of task before and after Load2 (pre/post Load2) were compared. condition × task, and found a tendency for a main effect of task, with the response increasing in both conditions after post Load1. Fig. 4. P300 amplitude (V) before and after (pre / post) calculation (Load1 / Load2) before and after using the test (ÿ, ÿ, •) or m control (ÿ, ÿ, •) toothpaste. Mean, N=13, ****p<0.0001, **p<0.01. ÿ, ÿ: Fz, ÿ, ÿ: Cz, •, •: Pz. Fig. 5. Reaction time (ms) of oddball paradigm before and after (pre / post) calcula-tion (Load1 / Load2) before and after using the test (•) or control (•) tooth-paste. Mean ± S.D., N=13, (+) p<0.1.
177 Sadatatsu et al.: Neurophysiological effects of toothpastes containing flavoring ingredients and caffeine There was a tendency for the time to be extended (p < 0.1). An ANOVA was performed on the condition × task, and the main To examine the effect of the two conditions on Load2, Only the effect was observed, and Load2 was observed in both conditions. In the oddball task (pre/post Load2) Flicker values were significantly reduced (p < 0.05). A comparison was made. An ANOVA was performed on condition × task. 6. Computing topics Only a tendency for the main effect of task was observed. A tendency for reaction times to be longer was observed in the following cases (p < 0.05) . Table 1 shows the percentage of correct answers and reaction times for the calculation tasks. 0.1ÿÿ The change in response between the two conditions (Load2 - Load1) was shown. 5. Flicker value There was a tendency for the correct answer rate to increase compared to the control formulation. No difference was observed in time, but the correct answer rate was higher for the test preparation. Figure 6 shows the flip-flops before and after Load1 (pre/post Load1). ÿp ÿ 0.1ÿÿ First, the effect of conditions on Load1 was investigated. 7. Mood score To examine the effect of the condition on the task, an ANOVA was performed. Only the main effect of the subject was observed, and the effect was greater in Load1 in both conditions. Tables 2 and 3 show the results of each questionnaire based on pre-Laod1. The change (difference) in the mood scores obtained was shown. The flicker value was significantly reduced by the addition of the 100% 15 ... To examine the effect of the two conditions on Load2, before and after Load2 To examine the effect of the two conditions on Load1, we compared condition × task (pre A comparison of the two toothpastes (pre/post Load2) was performed. When ANOVA was performed on the 1st and 2nd loads (post Load1), all items Only the main effect of the task was observed for “general fatigue” and "Perceived stress", "Feeling of boredom", "Fatigue", "Active pleasure", The feeling of "sleepiness" significantly increased, while "motivation," "concentration," and "refreshment" decreased. "Pleasure", "Clearness of mind", "Depression/anxiety", "Inactivity pleasure" The feelings of fatigue and subjective stress significantly decreased. "Stress", "sleepiness", "motivation", "concentration", "refreshment", "brainstorming" Table 1. Change value and standard deviations of calcula-tion reaction time (RT) and percentage of correct answers (CA) from Load1 after using the test or control toothpaste p RT (ms) AC (%) Control –0.09 ± 0.18 0.30 ± 2.28 Test –0.13 ± 0.15 1.51 ± 3.27 p (+) Fig. 6. Flicker fusion threshold (Hz) before and after (pre / post) calculation (Load1 / Load2) before and after Mean ± S.D., N=13. p: Student’s paired t-tests were used to using the test (• ) or control (• ) toothpaste. examine the difference between test and control toothpaste. Mean ± S.D., N=13, ***p<0.001, *p<0.05. (+) p<0.1. Table 2. Change value and standard deviation of VAS (Visual Analogue Scale) from rest before and after using the test or control toothpaste Load1 Load2 post Control pre Test well Control post Test well Control Test General fatigue 35.2 ± 26.2 30.8 ± 25.0 28.5 ± 25.4 3.9 ± 21.0 37.8 ± 31.4 23.6 ± 23.9 Subjective stress 33.8 ± 26.4 32.7 ± 28.8 26.6 ± 24.4 11.2 ± 26.1 36.6 ± 28.8 27.2 ± 30.2 Boredom 12.5 ± 37.3 21.7 ± 24.6 –0.5 ± 21.7 14.3 ± 22.6 13.1 ± 25.0 28.2 ± 26.2 b so, Eagerness –27.8 ± 26.1 –16.8 ± 18.4 –16.7 ± 15.6 –0.5 ± 17.9 –25.3 ± 26.3 –16.7 ± 19.3 Concentration power –28.2 ± 23.7 –33.4 ± 23.2 –10.6 ± 15.1 2.7 ± 18.9 –23.1 ± 19.5 –17.5 ± 19.6 –9.0 ± 16.3 27.2 ± 28.9 (#) –22.9 ± 18.8 –21.1 ± 27.8 Feeling of being refreshed (#) –8.1 ± 15.7 Feeling of clear-headedness –23.5 ± 25.6 –32.2 ± 22.2 Mean ± S.D., N=13. a 11.8 ± 25.1 ** * p: two-factor repeated measure ANOVA was used to examine the difference between test and control b toothpaste in pre or post: **p<0.01, *p<0.05. p: two-factor repeated measure ANOVA was used to examine the difference between test and control toothpaste in Load2: ###p<0.01, (#) p<0.1. –19.3 ± 18.0 1.4 ± 30.3 –19.8 ± 15.6 –15.8 ± 32.8 (#) *, ###
178 Journal of Industrial Hygiene, Vol. 52, 2010 Table 3. Change value and standard deviation of MMM (Multiple Mood Scale) and sleepiness by SSS (Stanford Sleepiness Scale) from rest before and after using the test or control toothpaste Load1 Load2 post pre Control Test pa post Control Control Test pa –0.5 ± 1.6 –1.1 ± 1.8 –1.2 ± 1.5 –1.1 ± 2.0 Lassitude 2.2 ± 2.2 1.8 ± 2.2 1.3 ± 2.1 –0.1 ± 2.7 Active comfort 0.5 ± 1.2 0.8 ± 1.6 0.5 ± 1.6 –2.1 ± 2.8 –1.9 ± 1.8 Depression/Anxiety Passive comfort 1.6 ± 1.0 Sleepiness Mean ± S.D., N=13. 1.6 ± 1.0 –1.2 ± 2.0 * Test pb –1.4 ± 1.6 1.9 ± 2.6 1.7 ± 2.9 –0.2 ± 1.4 0.2 ± 2.5 –0.2 ± 1.4 –1.2 ± 2.6 –1.2 ± 2.2 –2.5 ± 3.2 –2.4 ± 2.8 0.6 ± 0.8 –0.2 ± 0.7 1.4 ± 1.0 1.0 ± 0.8 ## a p: two-factor repeated measure ANOVA was used to examine the difference between test and control toothpaste in pre or post: *p<0.05. and control b p: two-factor repeated measure ANOVA was used to examine the difference between test toothpaste in Load2: ##p<0.05. "Feeling refreshed"; p < 0.0001, "Feeling bored"; p < 0.05, "Feeling tired"; The effect was significantly higher in the control group than in the control group, and the effect was sustained (p < 0.05). "lazy"; p ÿ 0.001, "quick in activity"; p ÿ 0.05, "depression·unable to IV. Investigation "An"; p ÿ 0.05, "inactive fast"; p ÿ 0.001). Next, to examine the effects of the two conditions on Load2, First, to equalize the degree of fatigue in both conditions, we adjusted the mental load. A comparison was made between the two conditions before and after Load2 (pre/post Load2). As a result, the P300 When we performed an ANOVA on condition × task, we found that Significant prolongation of peak latency, significant decrease in P300 amplitude, ERP A main effect of task was observed for all tasks except for “anxious” and “actively pleasant.” A significant increase in button press reaction time was observed. "General fatigue", "perceived stress", "boredom", "fatigue", There was a significant decrease in flicker value, an increase in fatigue, and a feeling of refreshment. "Sleepiness" significantly increased, while "motivation," "concentration," "refreshment," A significant decrease in positive mood, such as pleasure, was observed. "Clearness of mind" and "comfort from inactivity" significantly decreased This suggests that he is definitely in a state of fatigue. ("General fatigue": p < 0.001, "Perceived stress": This fatigue state was observed in the test and control preparations . p < 0.01, "boredom"; p < 0.001, "fatigue"; p < 0.001, "Sleepiness", "concentration", "clear mind"; p < 0.0001, The effects of the formulations were compared. Next, regarding the oddball task before and after the calculation task (Load 2), "Desire"; p ÿ 0.001, "pleasure"; p ÿ 0.001, "inactive" We analyzed the peak latency and amplitude of the stimuli. "Feeling refreshed" and "sleepiness" were significantly higher than those of the control group ( p < 0.01). Active stimulus processing leads to high amplitudes in the centro-parietal regions. A main effect of condition was observed, and the “feeling of refreshment” was significantly higher than that of the control formulation. 23, 24), but in this study , All scores were significantly higher for the test formulation (p < 0.01), with The maximum amplitude was recorded at Cz, and a similar amplitude was recorded at Cz. was significantly lower for the test formulation than for the control formulation. The result was that the amplitude was smallest at Fz. (p < 0.05). In addition, "general fatigue," "boredom," and "motivation" No difference was observed between the test and control formulations for the problem. A tendency for the condition to have a main effect was observed in "general fatigue" Although no significant difference was observed in the results, the use of the test formulation compared with the control formulation The test formulation had a lower "feeling of boredom" than the control formulation. The peak latency was earlier, indicating that the information On the other hand, there was a tendency for "motivation" to increase. It is possible that processing speed was accelerated and selective attention was strengthened. A tendency toward fatigue was observed ("general fatigue": p < 0.1, "boredom": p < 0.1). This suggests that the P300 reflects the updating of cognitive context. " Feeling of being able to do something"; p < 0.1, "Motivation"; p < 0.1). This is consistent with the report on the cognitive interpretation that An interaction between the condition and the task was observed in the sense of "sense of freedom." On the other hand, when the control preparation was used, the P300 peak latency Furthermore, the conditions and tasks were alternating between "exhilaration" and "fatigue." Since a delay was confirmed, the calculation task (Load 2) There was a tendency for the two to use the same device ("feeling clear headed"; p < 0.05, The information processing speed in the brain is suppressed by mental stress. "Exhilaration": p < 0.1, "Fatigue": p < 0.1). It was presumed that this was due to the condition of the When the effect of conditions was examined at and after Load2, In addition, the effect of the button press reaction time on the oddball task was The "refreshing feeling" and "refreshing feeling" were the same as those of the control product at pre-Load2. Since no effect of the test formulation was observed, the calculation task The test formulation was significantly higher than the control, and fatigue was significantly As a result of being temporarily affected by the mental stress caused by (Load2) ("Clear head": p < 0.05, "Refreshing": p < 0.05) This may be due to the fact that the oddball task "Feeling of refreshment" ; p < 0.01, "fatigue"; p < 0.05). The button press reaction time in the The test formulation showed a higher solubility than the control formulation even at post Load2. This was a task that placed little strain on working memory.
Sadatatsu et al.: Neurophysiological effects of toothpastes containing flavoring ingredients and caffeine 179 It is possible that it was difficult to obtain a difference from the control formulation. It was also revealed that toothpaste also had an effect on improving work efficiency do. and changing mood in the course of daily activities. These results of improved work According to our previous findings, when teeth brushing was not performed, the efficiency and mood changes are consistent with the effects on arithmetic performance flicker value did not return to its original state even after resting, and remained reported so far8,30-32 ). The finding that toothpaste may have a fatigue-reducing effect decreased. The cause of this decrease in flicker value reflects a decrease in perceptual using indicators of brain information processing in this study is thought to provide function, and can be interpreted as a decrease in the ability of visual information in the insight into the usefulness of toothpaste in improving fatigue and changing mood in perceptual association cortex. 25, 26) On the other hand, the flicker value increased industrial hygiene, in addition to its original purpose of optimizing the oral environment. when teeth brushing was performed, which suggests that the act of brushing teeth enhanced the activity of the cerebral cortex and exerted the effect of active rest. In From the above results, it is believed that the factor that causes the fatigue-reducing addition, since the effect of the test preparation was not observed in the measurement effect of toothpaste such as this test formulation is due to the combined effect of the of flicker value in this study, it is presumed that the mental load of the calculation task citrus flavoring ingredients and caffeine contained in this test formulation. For example, (Load 2) was temporarily affected, similar to the button pressing in the oddball task. it is believed that the results obtained are similar to those reported in the report on the Therefore, it is considered that the test preparation was not able to suppress the inhibitory effect of grapefruit scent on the decline in information processing ability due decrease in visual information ability. to work stress15). Furthermore , since the stimulation of the olfactory nerve by the flavoring ingredients of toothpaste is thought to be due not only to the scent from the nasal cavity (nasal aroma) but also to the scent directly from the oral cavity (back Regarding the efficiency of the calculation task, reaction time was shortened under aroma)33-35), it is possible that the inhibitory effect was stronger than the effect of both conditions. Furthermore, it was revealed that the test formulation tended to simply smelling the flavoring ingredients alone36,37). On the other hand, the effect of increase the rate of correct answers. The increase in efficiency may be due to recovery caffeine on cognitive function, such as shortening the peak from fatigue caused by the mental load of the calculation task, or the suppression of the effects of that fatigue. latency of P300, has been reported when a low-concentration (0.032% by weight) caffeine-containing beverage is consumed.38) This suggests that caffeine may have been absorbed directly into the body through the oral mucosa when it was added to In the subjective questionnaire, the mood scale showed a tendency for the test toothpaste, affecting the brain's information processing ability. However, at present, formulation to decrease "overall fatigue". "Motivation" and "boredom" tended to sufficient evidence has not been obtained, so further investigation will be necessary in increase, but "refreshment" in particular increased significantly. Furthermore, the future. Meanwhile, there are very few reports on neurophysiological research on "refreshment" was significantly higher than in the control formulation from immediately active rest, although there are some reports that use electroencephalograms as an after brushing to after the calculation task, and "mental clarity" was also significantly indicator39). This new higher immediately after brushing. On the other hand, "boredom" increased, similar to the results of our previous research on tooth brushing behavior10). Although boredom neurophysiological knowledge of active rest has been obtained by capturing neural activity by electroencephalograms using the event-related potential P300. This is is known to be positively correlated with low educational grades and poor thought to be one of the very important indicators for elucidating the mechanism of performance27 ), positive aspects such as increased desire for creativity and increased fatigue reduction and for future applied research. In other words, the evaluation of desire for diversity due to awareness of boredom28,29 ) have also been reported. active rest against mental fatigue does not only show the effect in changes in subjective Therefore, the result of an increase in "boredom" in this study does not necessarily mood, but it is becoming increasingly important to verify physiological evaluation at the negate the mood-changing effect of the test formulation. No effect of the test brain function level. However, in this study, we only evaluated a formulation that formulation was observed on subjective stress. Furthermore, while the test formulation combined flavoring ingredients and caffeine with a commercially available toothpaste, had no effect on "depression/anxiety," "active comfort," or "inactive comfort," the test and first discovered its potential. In the future, it will be necessary to examine in detail formulation significantly reduced "fatigue" and "drowsiness" immediately after brushing. the mechanism of action, including the concentration dependency of these ingredients. From these results, it is believed that the test formulation had a mood-altering effect, Furthermore, from the perspective of industrial hygiene, it will be important to verify the suppressing fatigue caused by mental stress and enhancing a sense of refreshment. fatigue-reducing effect of using it in daily activity situations. In this study, the test drug shortened the P300 peak latency. This is thought to Acknowledgements: We would like to express our sincere gratitude to Professor Ichiro Shimoyama indicate that the brain's information processing ability was enhanced and selective of the Department of Brain Function Measurement and Analysis Research, Frontier Medical attention was improved.20 ) Furthermore, the drug was shown to activate the cerebral Engineering Research Center, Chiba University, for his guidance and proofreading of this research. cortex, increasing the rate of correct answers in a calculation task and the sense of exhilaration.
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