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Anti-stress effect of theanine on students during pharmacy practice: Positive correlation among salivary α-amylase activity, trait anxiety and subjective stress

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... Unno et al. [26] Senescence-accelerated mice prone 10 (SAMP10) and ddY mice 6 mg/kg (20 g/mL in normal tap water) ...
... Salivary amylase activity (sAA) has been considered as an stress level [26]. Elevated sAA is a biomarker of autonomic nervous system excitation reactivity to stress. ...
... Elevated sAA is a biomarker of autonomic nervous system excitation reactivity to stress. In a single-blind study on the university students (n = 20) during an 11-week pharmacy practice, L-theanine (400 mg/day) was able to alleviate the initial stress and anxiety as shown by the decreased level of pre-practice sAA (P = 0.032) and subjective stress measured by visual analogue scales (P = 0.020) [26]. ...
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Tea (Camellia sinensis) is widely considered to promote feelings of calming and soothing. This effect is attributed to L-theanine (L-γ-glutamylethylamide) in tea, a non-protein amino acid mainly derived from tea leaves. As a naturally occurring structural analogue of glutamate, L-theanine competes for the receptors with glutamate and is able to pass the blood-brain barrier to exert its relaxation effect. This review focuses on the relaxation effect of L-theanine, including animal models and the latest human trials as well as the potential molecular mechanisms regarding neuron stem cells. The biological efficacy of dietary L-theanine in the food matrix has been further discussed in this review in relation to the physiological changes in the gastrointestinal tract and bindings of L-theanine with other food components.
... It has been previously observed that the adrenal glands are enlarged and the thymu gland is atrophied in stressed mice [15]. The wet weight of the adrenal glands and thymu gland were measured in the mice injected with LPS. ...
... It has been previously observed that the adrenal glands are enlarged and the thymus gland is atrophied in stressed mice [15]. The wet weight of the adrenal glands and thymus gland were measured in the mice injected with LPS. ...
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Being in a prolonged depressed state increases the risk of developing depression. To investigate whether green tea intake is effective in improving depression-like moods, we used an experimental animal model of depression with lipopolysaccharide (LPS) and clarified the effects of green tea on the biological stress response and inflammation in the brain. Regarding the stress reduction effect of green tea, we found that the sum of caffeine (C) and epigallocatechin gallate (E) relative to the sum of theanine (T) and arginine (A), the major components of green tea, or the CE/TA ratio, is important. The results showed that depression-like behavior, adrenal hypertrophy as a typical stress response, and brain inflammation were suppressed in mice fed green tea components with CE/TA ratios of 2 to 8. In addition, the expression of Npas4, which is reduced in anxiety and depression, was maintained at the same level as controls in mice that consumed green tea with a CE/TA ratio of 4. In clinical human trials, the consumption of green tea with CE/TA ratios of 3.9 and 4.7 reduced susceptibility to subjective depression. These results suggest that the daily consumption of green tea with a CE/TA ratio of 4–5 is beneficial to improving depressed mood.
... For example, it has been reported that theanine has a relaxing effect, as alpha waves have been observed to significantly increase in the brain after its ingestion [3]. In addition, animal experiments and clinical studies in humans have shown that theanine offers excellent stress-relieving effects [4][5][6][7][8][9]. Theanine acts via glutamate receptors but binds rather tightly to glutamine receptors [10]. ...
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Group rearing is a common housing condition, but group-housed older mice show increased adrenal hypertrophy, a marker of stress. However, the ingestion of theanine, an amino acid unique to tea leaves, suppressed stress. We aimed to elucidate the mechanism of theanine’s stress-reducing effects using group-reared older mice. The expression of repressor element 1 silencing transcription factor (REST), which represses excitability-related genes, was increased in the hippocampus of group-reared older mice, whereas the expression of neuronal PAS domain protein 4 (Npas4), which is involved in the regulation of excitation and inhibition in the brain, was lower in the hippocampus of older group-reared mice than in same-aged two-to-a-house mice. That is, the expression patterns of REST and Npas4 were found to be just inversely correlated. On the other hand, the expression levels of the glucocorticoid receptor and DNA methyltransferase, which suppress Npas4 transcription, were higher in the older group-housed mice. In mice fed theanine, the stress response was reduced and Npas4 expression tended to be increased. These results suggest that Npas4 expression was suppressed by the increased expression of REST and Npas4 downregulators in the group-fed older mice, but that theanine avoids the decrease in Npas4 expression by suppressing the expression of Npas4 transcriptional repressors.
... Through this mechanism, theanine is thought to exert physiological effects. Previous clinical trials have reported that theanine has psychological effects such as anxiolytic and anti-stress, as well as improving memory and cognitive functions [7][8][9][10]. ...
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L-theanine (theanine), one of the ingredients of green tea, had been proven to have anti-anxiety, anti-stress, memory, cognitive, and sleep improvement effects in most clinical trials. However, these effects have shown efficacy at a dose of 200–400 mg of theanine a day. In this study, we explored the sleep-improving effects of a lower dose (100 mg/day) of theanine. A double-blind, randomized crossover study was conducted on 25 middle-aged and older males. Participants were randomly assigned to Groups A and B. Group A took theanine first, and Group B took theanine later in the intervention period. The participants took theanine/placebo for one week. Electroencephalogram (EEG) parameters were measured with a monitoring device during sleep, and subjective sleep quality after waking up was evaluated using a questionnaire. Following the statistical analysis between interventions, subgroup analyses according to the participants’ background information were conducted on the representative sleep parameters of non-REM sleep, REM sleep, and wakefulness. Of the 25 participants, three withdrew from this study. In the sleep analysis, there was no significant difference in all sleep parameters between the theanine and placebo periods. In particular, the difference in the percentage of nonREM sleep in stage 2 per sleep duration was not significant (p = 0.053). However, subgroup analysis of the results showed that the percentage of non-REM sleep in stage 2 in groups aged <50 years was higher in theanine than that of the placebo, and in groups with green tea consumption habit of <3 to 4 days per week (p = 0.018, 0.048). The intake of 100 mg/day of theanine does not have an effect on sleep improvement. However, subgroup analyses showed that theanine had an improved effect in stage 2 non-REM sleep according to age and green tea consumption habit.
... For instance, L-theanine increases alpha-wave activity, indicating effects in increasing relaxing and reducing anxiety [8]. L-theanine is expected to exert these psychological effects [9], but also physical effects such as reduction of sympathetic overactivity [10] and oxidative stress [11]. ...
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Chronic sympathetic hyperactivity is known to affect metabolism and cause various organ damage including bladder dysfunction. In this study, we evaluated whether L-theanine, a major amino acid found in green tea, ameliorates bladder dysfunction induced by chronic sympathetic hyperactivity as a dietary component for daily consumption. Spontaneously hypertensive rats (SHRs), as an animal model of bladder dysfunction, were divided into SHR–water and SHR–theanine groups. After 6 weeks of oral administration, the sympathetic nervous system, bladder function, and oxidative stress of bladder tissue were evaluated. The mean blood pressure, serum noradrenaline level, and media-to-lumen ratio of small arteries in the suburothelium were significantly lower in the SHR–theanine than in the SHR–water group. Micturition interval was significantly longer, and bladder capacity was significantly higher in the SHR–theanine than in the SHR–water group. Bladder strip contractility was also higher in the SHR–theanine than in the SHR–water group. Western blotting of bladder showed that expression of malondialdehyde was significantly lower in the SHR–theanine than in the SHR–water group. These results suggested that orally administered L-theanine may contribute at least partly to the prevention of bladder dysfunctions by inhibiting chronic sympathetic hyperactivity and protecting bladder contractility.
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We investigated the inhibitory actions of oral noncentrifugal cane brown sugar (Kokuto) on mental stress in healthy subjects. When the subjects orally consumed 5 g of Kokuto before a 15-min Uchida-Kraepelin psychodiagnostic test (pre-task group), the salivary levels of stress biomarkers, including chromogranin A, α-amylase, secretory immunoglobulin A, dehydroepiandrosterone, and testosterone, were lower at 5 min after the test compared with those in the control group. However, Kokuto intake after the stress task (post-task group) showed little inhibitory effects. Subjective ratings for mental state using the visual analog scale were significantly lower in the pre-task group than in the control group, while the post-task group showed no significant differences. Moreover, Profile of Mood States scores showed a positive influence on the five negative mood states, which consequently improved vigor, in the pre-task group. These results suggest that oral intake of 5 g of Kokuto may efficiently suppress mental stress.
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Objectives: Sleepiness is associated with decreased cognitive abilities and remains one of the main causes of fatal road accidents. The tools currently available to assess sleepiness, such as questionnaires, are subject to intra- and inter-individual variability, while multiple sleep latency tests are only feasible in few sleep laboratories. The main objective of this study was to explore new potential markers (neurocognitive, biological) to objectively assess sleepiness in drivers. Methods: A total of 186 drivers (median age 44 years, range 20–74 years, 73% men, 14% obese) were included during a break at a highway service area, in the morning, while on the road for vacation. Questionnaires on sleepiness and sleep characteristics (habitual and on the night before travel), the Bron-Lyon Attention Stability Test (BLAST), and two salivary samples (α-amylase and oxalate) were collected. Associations between measures of sleepiness [Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS)], sleep characteristics, neurocognitive, and biological markers were tested using regression models adjusted for confounding factors. Results: The night before travel, 83% of the drivers reduced their sleep time and 30% slept 5 h or less. The higher the number of miles to be traveled, the higher the decrease, and the shorter the sleep time. The night before travel, 18 and 24% of the drivers complained of poor sleep quality and difficulty falling asleep. The sleep characteristics on the night before travel were associated with the habitual sleep characteristics. At the time of the test, 47% of the drivers scored pathologically on the SSS. Poor sleep quality and difficulty falling asleep the night before travel were associated with increased sleepiness as assessed by the SSS and decreased attentional ability as assessed by the BLAST. No association between salivary markers and acute sleepiness was observed. Conclusions: The sleep characteristics of the night before travel were associated with sleepiness and attentional performance. The SSS and the BLAST could be used by individual drivers in a self-evaluation context. Biological markers showed a high variability and limited association with sleep parameters across subjects, emphasizing the need for within-subject designs to assess their usefulness.
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Myriad evidence attests to the health-promoting benefits of tea drinking. While there are multiple factors of tea influencing the effective biological properties, tea polyphenols are the most significant and valuable components. The chemical characterization and physical characteristics of tea polyphenols have been comprehensively studied over the previous years. Still the emergence of new chemistry in tea, particularly the property of scavenging reactive carbonyl species (RCS) and the newly discovered flavoalkaloid compounds, has drawn increasing attention. In this review, we summarize recent findings of a new class of compounds in tea - flavonoid alkaloids (flavoalkaloids), which exist in fresh tea leaves and can be generated during the process of post-harvesting, and also postulate the formation mechanism of flavoalkaloids between catechins and theanine-derived Strecker aldehyde. Additionally, we detail the up-to-date research results of tea polyphenols regarding their ability to trap RCS and their in vivo aminated metabolites to suppress advanced glycation ends products (AGEs). We further raise questions to be addressed in the near future, including the synthetic pathways for the generation of flavoalkaloids and AGEs in fresh tea leaves before processing and the concentrations of tea polyphenols that affect their RCS scavenging capability due to their pro-oxidant nature. More intensive research is warranted to elucidate the mechanisms of action underlying the biological activity of flavoalkaloids and the pharmacological application of tea polyphenols in scavenging RCS and impeding detrimental AGEs.
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Tea (Camellia sinensis) has enthralled both consumers and researchers, due to its taste, aroma and its medicinal attributes. Tea consumers concern themselves with the quality of tea in particular, its taste and aroma based on which consumers are willing to pay premium prices for the best quality teas. The quality of tea is undeniably affected by variations in its metabolite composition. In this study, two groups of black tea cultivars were compared using a metabolomics approach. Data were generated via GC–MS and 1H-NMR. The GC–MS differentiated between the two groups, based on carbohydrates. The 1H-NMR differentiated between the two groups, based on caffeine, catechins and amino acids. These metabolites applicability in the discrimination of newly developed cultivars into potentially commercialisable and non-commercialisable groups at an early stage in the tea improvement programme is demonstrated. This may help tea breeders to select promising high quality tea cultivars either for release or further field evaluations.
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The anti-stress effect of theanine (γ-glutamylethylamide), an amino acid in tea, was investigated using mice that were psychosocially stressed from a conflict among male mice under confrontational housing. Two male mice were housed in the same cage separated with a partition to establish a territorial imperative. Then, the partition was removed and mice were co-housed confrontationally (confrontational housing). As a marker for stress-response, changes in the adrenal gland were studied in comparison to group-housed control mice (6 mice in a cage). Significant adrenal hypertrophy was observed in mice under confrontational housing, which was developed in 24 h and persisted for at least 1 week. The cell size in the zona fasciculata of the adrenal gland, from which glucocorticoid is mainly secreted, increased (ca. 1.11 times) in mice under confrontational housing, which was accompanied by the flattened diurnal rhythm of corticosterone and ACTH in blood. The ingestion of theanine (>5 μg/ml) prior to confrontational housing significantly suppressed adrenal hypertrophy. An anti-depressant paroxetin similarly suppressed adrenal hypertrophy in mice under confrontational housing. In mice that ingested theanine, behavioral depression was also suppressed and a diurnal rhythm of corticosterone and ACTH was observed, even when mice were under confrontational housing. Furthermore, the daily dose of theanine (40 μg/ml) blocked the counteracting effects of caffeine (30 μg/ml) and catechin (200 μg/ml). The present study demonstrated that theanine prevents and relieves psychosocial stress through the modulation of HPA axis activity.
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The purpose of this study was to investigate the efficacy and safety of L-theanine as an aid to the improvement of objectively measured sleep quality in a population of 98 male children formally diagnosed with attention-deficit/hyperactivity disorder (ADHD). A randomized, double-blind, placebo-controlled trial was conducted involving boys, ages 8-12 years, who had been previously diagnosed with ADHD. An experienced physician confirmed the diagnosis of ADHD in each subject. Randomization was stratified based upon current use of stimulant medication to ensure an equal distribution of stimulant/non-stimulant treated subjects into active and placebo treated groups. Participants consumed two chewable tablets twice daily (at breakfast and after school), with each tablet containing 100 mg of L-theanine (total 400 mg daily Suntheanine®, Taiyo Kagaku, Yokkaichi, Japan) or identical tasting chewable placebo for six weeks. Subjects were evaluated for five consecutive nights using wrist actigraphy at baseline, and again at the end of the six-week treatment period. The Pediatric Sleep Questionnaire (PSQ) was completed by parents at baseline and at the end of the treatment period. Actigraph watch data findings indicated that boys who consumed L-theanine obtained significantly higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep (defined as less time awake after sleep onset) compared to those in the placebo group. Sleep latency and other sleep parameters were unchanged. The PSQ data did not correlate significantly to the objective data gathered from actigraphy, suggesting that parents were not particularly aware of their children's sleep quality. L-theanine at relatively high doses was well tolerated with no significant adverse events. This study demonstrates that 400 mg daily of L-theanine is safe and effective in improving some aspects of sleep quality in boys diagnosed with ADHD. Since sleep problems are a common co-morbidity associated with ADHD, and because disturbed sleep may be linked etiologically to this disorder, L-theanine may represent a safe and important adjunctive therapy in childhood ADHD. Larger, long-term studies looking at the wider therapeutic role of this agent in this population are warranted.
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Objective: Previous data from our group and others have shown that salivary alpha-amylase activity increases in response to stress. It has been suggested that salivary alpha-amylase may be a marker for adrenergic activity. Less is known about other determinants of salivary alpha-amylase activation. The objective of the current study was to describe the diurnal pattern of salivary amylase and its determinants. Methods: Saliva samples were collected immediately after waking-up, 30 and 60 min later, and each full hour between 0900 and 2000 h by 76 healthy volunteers (44 women, 32 men). Compliance was controlled by electronic monitors. In order to control factors which might influence the diurnal profile of salivary alpha-amylase (such as momentary stress, mood, food, or body activity), at each sampling time point the subjects filled out a diary examining the activities they had carried out during the previous hour. Results: Salivary alpha-amylase activity shows a distinct diurnal profile pattern with a pronounced decrease within 60 min after awakening and a steady increase of activity during the course of the day. Mixed models showed a relative independence of diurnal salivary alpha-amylase from momentary stress and other factors, but significant associations with chronic stress and mood. Conclusions: Our results suggest that diurnal profiles of salivary alpha-amylase are relatively robust against momentary influences and therefore may prove useful in the assessment of sympathetic nervous system activity. The findings underscore the need to control for time of day in studies using salivary alpha-amylase as a dependent variable.
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In the present study, we employ a longitudinal design and a generalizability framework to examine the sources of variance in the diurnal rhythm of salivary α-amylase (sAA). The sample consisted of 122 first-year law students (55% male, mean age=23.9 years), who collected five saliva samples on each of three consecutive days at each of five data collection waves. In total, over 6900 saliva samples were collected, which allowed us to examine the properties of diurnal variation in sAA in great detail. Systematic individual differences accounted for 15-29% of the variability in the awakening response and diurnal slope, and for 61-65% of the variation in overall daily levels (i.e., diurnal mean, area under the curve with respect to ground [AUCg]). Although less than 1% of the variation was due to differences between waves and between days, the generalizability analyses revealed that between 16% and 17% of the variance in the diurnal mean, slope and AUCg is due to person by wave interactions, indicating that individuals vary in their biological sensitivity to environmental influences. In sum, this study documents sufficient stability and variation in diurnal sAA to warrant future studies on the origins and consequences of alterations in the diurnal rhythm of sAA worthwhile, and proposes guidelines on obtaining reliable measures.
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The authors propose a theoretical model linking achievement goals and achievement emotions to academic performance. This model was tested in a prospective study with undergraduates (N = 213), using exam-specific assessments of both goals and emotions as predictors of exam performance in an introductory-level psychology course. The findings were consistent with the authors' hypotheses and supported all aspects of the proposed model. In multiple regression analysis, achievement goals (mastery, performance approach, and performance avoidance) were shown to predict discrete achievement emotions (enjoyment, boredom, anger, hope, pride, anxiety, hopelessness, and shame), achievement emotions were shown to predict performance attainment, and 7 of the 8 focal emotions were documented as mediators of the relations between achievement goals and performance attainment. All of these findings were shown to be robust when controlling for gender, social desirability, positive and negative trait affectivity, and scholastic ability. The results are discussed with regard to the underdeveloped literature on discrete achievement emotions and the need to integrate conceptual and applied work on achievement goals and achievement emotions.
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In posttraumatic stress disorder (PTSD), chronic activation of the sympathetic nervous system (SNS) has been suggested. No study so far has investigated diurnal secretion patterns of salivary alpha-amylase (sAA) in PTSD, a promising candidate for non-invasive assessment of SNS activity. We compared sAA diurnal profiles between a group of Bosnian War refugees with PTSD and a healthy control group, and further analyzed for associations with psychiatric symptoms and glucocorticoid (GC) sensitivity of inflammatory regulation. PTSD patients showed a sAA awakening response profile that was opposite to those seen in healthy controls, i.e. an increase instead of a sharp decrease. Patterns of sAA secretion were further positively associated with psychiatric symptoms of PTSD. Finally, higher sAA awakening responses were associated with higher GC sensitivity of inflammatory cytokine production. These findings are in line with altered SNS function in PTSD, and lend further support for employing assessment of diurnal sAA profiles as non-invasive biomarkers in stress-related disease.
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Salivary alpha amylase (sAA) has been proposed as a marker of autonomic nervous system activity. Few studies have examined sAA basal activity and reactivity in naturalistic settings, or developmental changes in sAA. In 50 adolescents, diary-reported moods and sAA levels were gathered across two typical weekdays. As in adults, basal sAA levels were low at waking and increased across the day. More advanced pubertal development was associated with higher waking sAA levels; males had smaller sAA increases across the day. High arousal positive emotions (feeling strong, active, excited) were associated with acute sAA increases; high arousal negative emotions (angry, stressed, nervous, worried) predicted sAA increases among youth with high average levels of these emotions. Findings suggest that basal sAA levels increase with puberty, and that acute sAA increases may reflect levels of emotional arousal, including high arousal positive emotions, rather than being specific to stress or emotions of negative valence.
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Theanine (γ-glutamylethylamide) characteristically present in tea leaves (Camellia sinensis). It has a similar chemical structure to glutamate, which is a neurotransmitter related to memory. Theanine passes through the blood-brain barrier and has been shown to have a cerebroprotective effect and a preventive effect on neuronal cell death after transient cerebral ischemia. The neuroprotective effect is partly due to the antagonistic action of theanine on glutamate receptor subtype AMPA and kainate receptors, but the affinity is very low. Theanine also acted on glutamine (Gln) transporter strongly and inhibited the incorporation of extracellular Gln into neurons, which in turn suppressed the conversion of Gln to glutamate by glutaminase, a reaction required for condensation into synaptic vesicles to form a neurotransmitter pool responsible for subsequent exocytotic release upon stimuli. In an investigation of elderly persons with normal or slight cognitive dysfunction, volunteers who ingested powdered green tea containing a high theanine concentration (equivalent to 47.5mgday(-1) of theanine) showed significantly lower decline in cognitive function compared with that of the placebo group. This result suggested that theanine might have improved a slight cognitive dysfunction in elderly persons.
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To evaluate the psychosocial effect on lifespan and cognitive function, this study investigated the effect of confrontational housing on mice because conflict among male mice is a psychosocial stress. In addition, it investigated the anti-stress effect of theanine (γ-glutamylethylamide), an amino acid in tea. Mice were housed under confrontation. That is, two male mice were separately housed in the same cage with a partition for establishing the territorial imperative in each mouse. Then, the partition was removed and mice were co-housed confrontationally (confront-housing) using a model mouse of accelerated-senescence (SAMP10) that exhibited cerebral atrophy and cognitive dysfunction with ageing. It was found that mice began to die earlier under confront-housing than group-housed control mice. Additionally, it was found that cerebral atrophy, learning impairment and behavioural depression were higher in mice under the stressed condition of confront-housing than age-matched mice under group-housing. Furthermore, the level of oxidative damage in cerebral DNA was higher in mice housed confrontationally than group-housed control mice. On the other hand, the consumption of purified theanine (20 μg/ml, 5-6 mg/kg) suppressed the shortened lifespan, cerebral atrophy, learning impairment, behavioural depression and oxidative damage in cerebral DNA. These results suggest that psychosocial stress accelerates age-related alterations such as oxidative damage, lifespan, cognitive dysfunction and behavioural depression. The intake of theanine might be a potential candidate for suppression of disadvantage under psychosocial stress.