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1.
Effects of single-dose L-theanine on motor cortex excitability.
Yuan, S, Brown, JC, Gold, M, Tirrell, E, Jones, RN, Carpenter, LL
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2021;(9):2062-2064
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Protective effect of the oral administration of cystine and theanine on oxaliplatin-induced peripheral neuropathy: a pilot randomized trial.
Kobayashi, M, Sato, R, Komura, T, Ichikawa, H, Hirashima, T, Otake, S, Akazawa, N, Yazawa, T, Abe, T, Okada, T, et al
International journal of clinical oncology. 2020;(10):1814-1821
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Abstract
BACKGROUND Oxaliplatin, one of the key cytotoxic drugs for colorectal cancer, frequently causes peripheral neuropathy which leads to dose modification and decreased patients' quality of life. However, prophylactic or therapeutic measures have not yet been established. Orally administered amino acids, cystine and theanine, promoted the synthesis of glutathione which was one of the potential candidates for preventing the neuropathy. The aim of this study was to determine whether daily oral administration of cystine and theanine attenuated oxaliplatin-induced peripheral neuropathy (OXLIPN). METHODS Twenty-eight colorectal cancer patients who received infusional 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) therapy were randomly and evenly assigned to the cystine and theanine group and the control group. OXLIPN was assessed up to the sixth course using original 7-item questionnaire as well as Common Terminology Criteria for Adverse Events (CTCAE) grading scale. RESULTS Neuropathy scores according to our original questionnaire were significantly smaller in the cystine and theanine group at the fourth (p = 0.026), fifth (p = 0.029), and sixth course (p = 0.038). Furthermore, significant differences were also observed in CTCAE neuropathy grades at the fourth (p = 0.037) and the sixth course (p = 0.017). There was one patient in each group who required dose reduction due to OXLIPN. Except for neurotoxicity, no significant differences were noted in the incidence of adverse events, and the total amount of administered oxaliplatin. CONCLUSION The results demonstrated the daily oral administration of cystine and theanine attenuated OXLIPN.
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Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.
Kahathuduwa, CN, Wakefield, S, West, BD, Blume, J, Dassanayake, TL, Weerasinghe, VS, Mastergeorge, A
Scientific reports. 2020;(1):13072
Abstract
We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.
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Effects of acute caffeine, theanine and tyrosine supplementation on mental and physical performance in athletes.
Zaragoza, J, Tinsley, G, Urbina, S, Villa, K, Santos, E, Juaneza, A, Tinnin, M, Davidson, C, Mitmesser, S, Zhang, Z, et al
Journal of the International Society of Sports Nutrition. 2019;(1):56
Abstract
BACKGROUND A limited amount of research has demonstrated beneficial effects of caffeine and theanine supplementation for enhancement of mental performance. The purpose of this investigation was to determine whether the acute ingestion of a supplement containing caffeine, theanine and tyrosine improves mental and physical performance in athletes. METHODS Twenty current or former male collegiate athletes (age: 20.5 ± 1.4 y; height: 1.82 ± 0.08 m; weight: 83.9 ± 12.6 kg; body fat: 13.8 ± 5.6%) completed this randomized, double-blind, placebo-controlled crossover trial. After familiarization, each participant completed two identical testing sessions with provision of a proprietary dietary supplement (SUP) containing caffeine theanine and tyrosine or a placebo (PL). Within each testing session, participants completed assessments of mental and physical performance before and after provision of SUP or PL, as well as after two rounds of exercise. Assessments were performed using a performance testing device (Makoto Arena) that evaluated multiple aspects of mental and physical performance in response to auditory and visual stimuli. Testing was performed both with the body in a static position and during dynamic movement. General linear models were used to evaluate the effects of SUP and PL on performance. RESULTS Changes in movement accuracy during performance assessment were greater following SUP ingestion as compared to PL for both static and dynamic testing (SUP: + 0.4 to 7.5%; PL: - 1.4 to 1.4% on average; p < 0.05). For dynamic testing, the change in number of targets hit was higher and the change in average hit time was lower with SUP as compared to PL (p < 0.05). However, there were no differences between conditions for the changes in number of targets hit or average hit time during static testing. There were no differences in changes of subjective variables during either condition, and performance measures during the two rounds of exercise did not differ between conditions (p > 0.05). DISCUSSION The present results indicate that a combination of a low-dose of caffeine with theanine and tyrosine may improve athletes' movement accuracy surrounding bouts of exhaustive exercise without altering subjective variables. Based on this finding, supplementation with caffeine, theanine and tyrosine could potentially hold ergogenic value for athletes in sports requiring rapid and accurate movements. TRIAL REGISTRATION NCT03019523. Registered 24 January 2017.
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l-Theanine and caffeine improve target-specific attention to visual stimuli by decreasing mind wandering: a human functional magnetic resonance imaging study.
Kahathuduwa, CN, Dhanasekara, CS, Chin, SH, Davis, T, Weerasinghe, VS, Dassanayake, TL, Binks, M
Nutrition research (New York, N.Y.). 2018;:67-78
Abstract
Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed.
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Acute effects of theanine, caffeine and theanine-caffeine combination on attention.
Kahathuduwa, CN, Dassanayake, TL, Amarakoon, AMT, Weerasinghe, VS
Nutritional neuroscience. 2017;(6):369-377
Abstract
OBJECTIVE l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. DESIGN In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. RESULTS Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude. DISCUSSION A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.
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Anti-Stress, Behavioural and Magnetoencephalography Effects of an L-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, Crossover Trial.
White, DJ, de Klerk, S, Woods, W, Gondalia, S, Noonan, C, Scholey, AB
Nutrients. 2016;(1)
Abstract
L-theanine (γ-glutamylethylamide) is an amino acid found primarily in the green tea plant. This study explored the effects of an L-theanine-based nutrient drink on mood responses to a cognitive stressor. Additional measures included an assessment of cognitive performance and resting state alpha oscillatory activity using magnetoencephalography (MEG). Thirty-four healthy adults aged 18-40 participated in this double-blind, placebo-controlled, balanced crossover study. The primary outcome measure, subjective stress response to a multitasking cognitive stressor, was significantly reduced one hour after administration of the L-theanine drink when compared to placebo. The salivary cortisol response to the stressor was reduced three hours post-dose following active treatment. No treatment-related cognitive performance changes were observed. Resting state alpha oscillatory activity was significantly greater in posterior MEG sensors after active treatment compared to placebo two hours post-dose; however, this effect was only apparent for those higher in trait anxiety. This change in resting state alpha oscillatory activity was not correlated with the change in subjective stress response or the cortisol response, suggesting further research is required to assess the functional relevance of these treatment-related changes in resting alpha activity. These findings further support the anti-stress effects of L-theanine.
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Increased pain and muscle glutamate concentration after single ingestion of monosodium glutamate by myofascial temporomandibular disorders patients.
Shimada, A, Castrillon, EE, Baad-Hansen, L, Ghafouri, B, Gerdle, B, Wåhlén, K, Ernberg, M, Cairns, BE, Svensson, P
European journal of pain (London, England). 2016;(9):1502-12
Abstract
BACKGROUND A randomized, double-blinded, placebo-controlled study was conducted to investigate if single monosodium glutamate (MSG) administration would elevate muscle/serum glutamate concentrations and affect muscle pain sensitivity in myofascial temporomandibular disorders (TMD) patients more than in healthy individuals. METHODS Twelve myofascial TMD patients and 12 sex- and age-matched healthy controls participated in two sessions. Participants drank MSG (150 mg/kg) or NaCl (24 mg/kg; control) diluted in 400 mL of soda. The concentration of glutamate in the masseter muscle, blood plasma and saliva was determined before and after the ingestion of MSG or control. At baseline and every 15 min after the ingestion, pain intensity was scored on a 0-10 numeric rating scale. Pressure pain threshold, pressure pain tolerance (PPTol) and autonomic parameters were measured. All participants were asked to report adverse effects after the ingestion. RESULTS In TMD, interstitial glutamate concentration was significantly greater after the MSG ingestion when compared with healthy controls. TMD reported a mean pain intensity of 2.8/10 at baseline, which significantly increased by 40% 30 min post MSG ingestion. At baseline, TMD showed lower PPTols in the masseter and trapezius, and higher diastolic blood pressure and heart rate than healthy controls. The MSG ingestion resulted in reports of headache by half of the TMD and healthy controls, respectively. CONCLUSION These findings suggest that myofascial TMD patients may be particularly sensitive to the effects of ingested MSG. WHAT DOES THIS STUDY ADD?': Elevation of interstitial glutamate concentration in the masseter muscle caused by monosodium glutamate (MSG) ingestion was significantly greater in myofascial myofascial temporomandibular disorders (TMD) patients than healthy individuals. This elevation of interstitial glutamate concentration in the masseter muscle significantly increased the intensity of spontaneous pain in myofascial TMD patients.
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Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients.
Tsuchiya, T, Honda, H, Oikawa, M, Kakita, T, Oyama, A, Oishi, H, Tochikubo, K, Hashimoto, T, Kurihara, S, Shibakusa, T, et al
International journal of clinical oncology. 2016;(6):1085-1090
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Abstract
BACKGROUND Nutritional therapy is used to reduce the adverse events (AEs) of anticancer drugs. Here, we determined whether the amino acids cystine and theanine, which provide substrates for glutathione, attenuated the AEs of S-1 adjuvant chemotherapy. METHODS Patients scheduled to receive S-1 adjuvant chemotherapy were randomized to the C/T or the control groups. The C/T group received 700 mg cystine and 280 mg theanine orally 1 week before the administration of S-1, which then continued for 5 weeks. Each group received S-1 for 4 weeks. Blood sampling was performed and AEs were evaluated (CTCAE ver. 4.0) before and after the administration of S-1. S-1 was discontinued when AEs ≥ grade 2 occurred. RESULTS The incidences of AEs of any grade and those over grade 2 were lower in the C/T group than in the controls. The incidence of diarrhea (G ≥ 2) was significantly less (p < 0.05) in the C/T group (3.1 %) than in the controls (25.8 %). The duration and completion rate of the S-1 adjuvant chemotherapy were significantly longer (p < 0.01) and higher (p < 0.01), respectively, in the C/T group (complete ratio: 75.0 %, duration: 24.8 ± 5.8 days) than in the controls (complete ratio: 35.5 %, duration: 20.0 ± 7.7 days). CONCLUSIONS The oral administration of cystine and theanine attenuated the AEs of S-1 adjuvant chemotherapy and increased the S-1 completion rate, suggesting that cystine and theanine is a useful supportive care for chemotherapy.
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Differential effects of repetitive oral administration of monosodium glutamate on interstitial glutamate concentration and muscle pain sensitivity.
Shimada, A, Baad-Hansen, L, Castrillon, E, Ghafouri, B, Stensson, N, Gerdle, B, Ernberg, M, Cairns, B, Svensson, P
Nutrition (Burbank, Los Angeles County, Calif.). 2015;(2):315-23
Abstract
OBJECTIVE The aim of this study was to determine the relationship of high daily monosodium glutamate (MSG) consumption with glutamate concentrations in jaw muscle, saliva, and serum, and muscle pain sensitivity in healthy participants. METHODS A randomized, double-blinded, placebo-controlled study was conducted to investigate the effect of repetitive consumption of high-dose MSG on glutamate concentration in the masseter muscles measured by microdialysis and muscle pain sensitivity. In five contiguous experimental daily sessions, 32 healthy participants drank MSG (150 mg/kg) or NaCl (24 mg/kg) diluted with a 400 mL soda. The concentrations of glutamate before and after the ingestion were assessed in dialysate and plasma samples on the first and last days. Saliva glutamate concentration was assessed every day. Pressure pain threshold, pressure pain tolerance, autonomic parameters (heart rate, systolic and diastolic blood pressures) and reported side effects also were assessed. RESULTS No significant change was noted in the baseline concentration of glutamate in the masseter muscle, blood, or saliva, but the peak concentration in the masseter muscle increased significantly between day 1 and 5. A statistically significant increase in systolic and diastolic blood pressures after MSG administration was observed, as well as a significantly higher frequency of reports of nausea and headache in the MSG group. No robust effect of MSG on muscle sensitivity was found. CONCLUSION Interstitial glutamate concentration in the masseter muscle is not highly disturbed by excessive repetitive intake of MSG in healthy man.