L-Theanine

This systematic review ansd meta-analysis aimed to evaluate the effects of L-theanine, a non-proteinogenic amino acid found in tea, on sleep outcomes. Literature searches were conducted in five electronic databases (APA PsycINFO, CINAHL, Medline, Scopus, Web of Science), and one register (Cochrane Central Register of Controlled Trials) from inception until September 2024. Randomised controlled trials investigating the effects of L-theanine supplementation on sleep quality in humans of all ages and health status were included. Nineteen articles (N = 897 participants) were selected and 18 included in the meta-analysis. L-theanine was shown to significantly improve subjective sleep onset latency (SMD = 0.15, 95 % CI [0.01, 0.29], p = 0.04; n = 10 studies), subjective daytime dysfunction (SMD = 0.33, 95 % CI [0.16, 0.49], p < 0.001; n = 9 studies), and overall subjective sleep quality score (SMD = 0.43, 95 % CI [0.04, 0.83], p = 0.03; n = 12 studies). The findings indicate the potential use of L-theanine in the management of sleep disturbances; however, the lack of studies on "pure" L-theanine warrants further investigation. Future studies are needed to determine the adequate dose and duration of L-theanine supplementation for improving and maintaining sleep quality in healthy and clinical populations.

BACKGROUND: Caffeine is a well-known ergogenic aid that can enhance physical and cognitive performance. However, it often induces side effects, such as anxiety and overstimulation, which can be problematic in high-pressure sports like wrestling. L-theanine, a non-stimulant amino acid found in tea, may help mitigate these effects by promoting a calm yet focused mental state. This study aimed to investigate the acute effects of caffeine, L-theanine, and their combination on physical performance, cognitive function, and anxiety in elite male wrestlers. METHODS: In a double-blind, placebo-controlled, crossover design, 12 elite male wrestlers (21.8 ± 2.1 years) completed four test sessions under randomized conditions: placebo (PLA), caffeine (CAF; 3 mg/kg), L-theanine (THE; 3 mg/kg), and caffeine + L-theanine (CAF+THE; 3 mg/kg each). After 60 minutes, athletes performed the wall-squat test, vertical jump height (VJH), medicine ball throw (MBT), handgrip strength, and the Specific Wrestling Fitness Test (SWFT). Cognitive function was assessed pre- and post-SWFT using a computerized Stroop test. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI), and side effects were recorded. RESULTS: CAF+THE outperformed PLA in wall-squat time (p = 0.001), MBT (p = 0.005), VJH (p = 0.011), and grip strength (p = 0.004). SWFT throw count was highest in CAF+THE versus all other conditions (p < 0.001). Post-SWFT Stroop reaction time was faster in CAF+THE than PLA (p = 0.004) and THE (p = 0.036), and accuracy was also higher (p = 0.009 vs PLA). CAF alone increased state anxiety compared to PLA (p = 0.021), while CAF+THE reduced anxiety to below placebo levels (8% incidence vs 33%). Trait anxiety was lower in CAF+THE compared to CAF (p = 0.018). The prevalence of caffeine-induced tachycardia (92%) was notably reduced under CAF+THE (17%). CONCLUSION: CAF+THE (3 mg/kg each) enhances elite wrestlers' strength, endurance, cognitive speed, and accuracy while reducing anxiety and physiological side effects commonly associated with caffeine alone. This combination represents a safe, practical supplement strategy for combat sports athletes who must maintain explosive performance

L-theanine, an amino acid found in tea, and caffeine, found in tea and coffee, are claimed to enhance attention. We conducted a double-blind, placebo-controlled, counterbalanced, two-way crossover trial to determine the acute effects of a high-dose L-theanine-caffeine combination on neurobehavioural (reaction time) and neurophysiological (P3b cognitive event-related potential (ERP)) measures of selective attention in acutely sleep-deprived healthy adults. Thirty-seven overnight sleep-deprived healthy adults (aged 22-30 years, twenty-one men) completed a computerised traffic-scene-related visual stimulus discrimination task before and 50 min after ingesting 200 mg L-theanine-160 mg caffeine combination or a placebo. The task involved selectively responding to imminent accident scenes (20 % probability) while ignoring randomly intermixed, more frequent safe scenes (80 % probability). A 32-channel electroencephalogram was recorded concurrently to derive ERP. The L-theanine-caffeine combination significantly improved the hit rate (P = 0·02) and target-distractor discriminability (P = 0·047), compared with the placebo. Although both L-theanine-caffeine combination (△ = 52·08 ms, P < 0·0001) and placebo (△ = 13·97 ms, P = 0·024) improved reaction time to accident scenes, the pre-post-dose reaction time improvement of the L-theanine-caffeine combination was significantly greater than that of placebo (△ = 38·1 ms, P = 0·003). Compared with the placebo, the L-theanine-caffeine combination significantly increased the amplitudes and reduced the latencies of P3b ERP component. Our findings suggest that L-theanine-caffeine combination improves the accuracy and speed of deploying selective attention to traffic scenarios in sleep-deprived individuals. This improvement is brought about by greater and faster neural resource allocation in the attentional networks of the brain.

BACKGROUND: L-theanine is a non-protein-forming amino acid found in tea. Limited evidence suggests that it improves selective attention. Sleep deprivation impairs attention and psychomotor reactions, affecting automobile driving. We aimed to determine whether L-theanine improves neurobehavioral measures of visual attention in acutely sleep-deprived healthy adults in a traffic-scene-based attention task. METHODS: In a double-blind, placebo-controlled, counterbalanced, two-way crossover study, we compared the effects of a 200-mg dose of L-theanine with a placebo (150 ml of distilled water) on a computerised, traffic-scene-based visual recognition reaction task in 24 healthy volunteers (age 20-25 years; 13 males) sleep-deprived overnight. The participants made speeded button-presses to imminent accident scenes (i.e. hits), while ignoring safe scenes. They were tested pre-dose and 45 min post-dose, each treatment administered one week apart. RESULTS: Hit rates were more than 90% in all sessions, and were similar in two treatments, pre- vs post-dose. L-theanine significantly reduced false alarms (i.e. responses to safe scenes) (p = 0.014) and increased A' (i.e. target-distractor discriminability) (p = 0.009), whereas placebo did not (p > 0.05). L-theanine reduced hit reaction time by 38.65 ms (p = 0.007), and placebo by 19.08 ms (p = 0.016), however reaction time changes from baseline were not significantly different between treatments (p > 0.05). CONCLUSIONS: L-theanine in high doses appears to improve selective visual attention by concurrently improving information processing speed and target-distractor discriminability in acutely sleep-deprived individuals. This is consistent with previous functional neuroimaging findings, where L-theanine suppressed distractor-processing and default-mode-network activity in visual selective attention tasks.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge. The cognitive challenge involved a Stroop challenge and mental arithmetic. Eighty subjects (age = 21 ± 2.6 yrs; male = 46; female = 34) were randomly assigned L-tyrosine (n = 28; 2000 mg), L-theanine (n = 25; 200 mg), or placebo (n = 27) prior to MSC exposure. Saliva samples, state-anxiety inventory (SAI) scales, and heart rate (HR) were collected before and after exposure to the MSC. Saliva was analyzed for stress markers α-amylase (sAA) and secretory immunoglobulin A (SIgA). The MSC resulted in significant increases in sAA, SIgA, HR, and SAI. Ingestion of L-theanine and L-tyrosine did not impact markers of stress. However, the L-tyrosine treatment demonstrated significantly lower missed responses compared to the placebo treatment group during the Stroop challenge. These data demonstrate that ingestion of L-theanine or L-tyrosine does not impact markers of stress in response to a MSC but may impact cognitive performance. This study was pre-registered as a clinical trial ("Impact of supplements on stress markers": NCT05592561).

This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semiprofessional male soccer players (n = 12, age: 22 ± 3 years, stature: 1.78 ± 0.06 m, mass: 75 ± 9 kg) performed 120-min soccer-specific exercise on two occasions. In a triple-blind, randomized, crossover design, players chewed caffeinated (200 mg; caffeine) or control (0 mg; placebo) gum for 5 min following 90 min of soccer-specific exercise. Perceptual-cognitive skills (i.e., passing accuracy, reaction time, composure, and adaptability) were assessed using a soccer-specific virtual reality simulator, collected pre- and posttrial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15 and 30 m) were measured at pretrial, half-time, 90 min, and posttrial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8 AU to post: 90.7 ± 0.8 AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8 AU to post: 88.2 ± 0.8 AU; p < .01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8 AU to post: 65.9 ± 0.8 AU) versus placebo (pre: 68.8 ± 0.8 AU to post: 68.3 ± 0.8 AU; p < .01). Caffeine gum did not influence any other variables (p > .05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions.

In this randomised, placebo-controlled trial, adults with impaired sleep (Pittsburgh Sleep Quality Index ≥ 5) were randomly assigned using a minimization algorithm to receive a formulation containing L-theanine plus lemon balm, valerian, and saffron extracts, or placebo, during 6 weeks. Objective sleep quality parameters were measured using an actigraphy device. We enrolled and randomised 64 individuals, 31 from the active group and 27 from the placebo group completed the 6 week follow-up. Mean sleep efficiency remained unmodified in the active group, and increased by 3% in the placebo group, the between-group difference in the change was not statistically significant (p = 0.49). Total sleep time also improved more with placebo (13.0 vs. 1.33 min, p = 0.66). Time wake after sleep onset (WASO) decreased more in the active group (4.6% vs. 2.4%), but the difference was not significant (p = 0.33). Mean PSQI decreased by 3.11 points (32.3%) in the active group, and by 3.86 points (39.5%) in the placebo group (p = 0.41). SF-36 increased more with placebo (+ 18.3 in active, + 32.1 in placebo, p = 0.68). Salivary cortisol remained unchanged in both groups. No serious adverse events were reported. Among adults with impaired sleep, a nutraceutical combination did not improve objective or subjective sleep parameters more than a placebo infusion. © 2024. The Author(s).

PURPOSE: Previous studies have investigated the effect of single or combined caffeine (CAF) and L-theanine (THE) intake on attention performance. However, its effect on shooting performance and cognitive performance in a sport is unknown. The aim of this study was to investigate the hypothesis "Does single or combined CAF and THE supplementation have an effect on shooting and cognitive performance in elite curling athletes?." It is predicted that over the next decade, studies based on nutritional ergogenic supplements in the developing sport of curling will continue to increase, leading to a significant increase in studies examining the effects of CAF and THE supplementation, alone or in combination, on throwing and cognitive performance in elite curling athletes. METHODS: In this double-blind, randomized controlled crossover study, twenty-two elite national curling athletes (age 20.20 ± 1.61 and sports age 6.20 ± 0.51 years, height 174.10 ± 7.21 cm, BMI 21.80 ± 3.47 kg/m2) were randomly assigned to CAF (6 mg/kg single dose CAF), THE (6 mg/kg single dose THE), CAF*THE (6 mg/kg CAF and 6 mg/kg THE combined) and PLA (400 mg maltodextrin) groups at each of four sessions. 60 minutes after taking the supplement, the athletes were first given the Stroop test and then asked to shoot. RESULTS: Our main findings have shown that the performance of athletes in guard (F=3.452, P < .001, ηp2 = .842), draw (F=1.647, P < .001, ηp2 = .485), and take-out (F=3.121, P < .001, ηp2 = .743) shot styles significantly improved when comparing the combined intake of CAF and THE to the PLA. Regarding cognitive performance evaluation through the Stroop test, during the NR task (F=4.743, P = .001, ηp2 = .653), the combined intake of CAF and THE significantly improved reaction times compared to the intake of single CAF, THE, or PLA. The best reaction times during the CR and ICR (respectively; F=2.742, P = .004, ηp2 = .328; F = 1.632, P < .001, ηp2 = .625) tasks were achieved with the combined CAF and THE intake, showing a significant improvement compared to PLA. During the NER (F=2.961, P < .001, ηp2 = .741), task, the combined intake of CAF and THE significantly improved error rates compare

Adaptogens are a group of substances capable to increase the nonspecific resistance of the organism to a wide range of harmful effects and stress. However, only limited data exist on their use in the composition of foods for special dietary uses. The aim of the study was to evaluate the effect of a diet that included vegetable-fat spread enriched with 5-hydroxytryptophan, L-theanine and γ-aminobutyric acid on memory, general well-being and emotional status of healthy volunteers. Material and methods. The single-center, single-blind randomized prospective trial that enrolled persons without signs of significant organic pathology have been performed. Participants were randomly allocated to receive either 45 g/day standard spread enriched with 5-hydroxytryptophan (0.67%), L-theanine (0.56%) and γ-aminobutyric acid (0.45%) (main group, MG) or 45 g/day standard spread (control group, CG) for 10 days. Beside this, all participants followed a standard diet. Initially, as well as on the 10th day after the start of using the diet, the emotional state was assessed using the HADS anxiety and depression scale and Beck's depression inventory (BDI), general well-being by SAN questionnaire, memory according to the Lurie method; reaction time and attention concentration were assessed using the Krepelin counting test and the Burdon correction test. A 5-point Likert visual-analogue scale was used to assess the palatability (pasting) of the product, the severity of feelings of hunger and satiety at the baseline and on the 10th day of the study. All tests were performed under the supervision of staff. During the study, daily monitoring of the presence of adverse events was performed. Results. There were 70 subjects in MG and 70 in CG. Lurie memory score significantly increased in the MG (59.9±6.7 vs 58.1±7.4 points at the baseline; p=0.001), but not in the CG (58.0±6.9 vs 57.3±7.3 points, p>0.05). According to the SAN questionnaire, significant increase of well-being values (46.9±13.4 vs 44.2±13.5 points; p=0.01) and mood (49.9±12.6 vs 47.4±12.9 points; p=0.01) was found in MG, while in CG there was an increase of the mood category only (54.4±10.8 vs 52.2±12.1, p=0.04). At the end

RATIONALE: Inadequate responses to current schizophrenia treatments have accelerated research into novel therapeutic approaches. OBJECTIVES: This study investigated the efficacy and tolerability of adjunctive L-theanine, an ingredient with neuroimmunomodulatory and neuroprotective properties, for chronic schizophrenia. METHODS: Eighty chronic schizophrenia inpatients were equally assigned to receive risperidone (6 mg/day) plus either L-theanine (400 mg/day) or matched placebo in this 8-week, randomized, parallel-group, double-blind, placebo-controlled trial. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS) by recording the results of subscales at baseline and weeks 4 and 8 to measure treatment efficacy. Additionally, the participants were assessed for the Hamilton Depression Rating Scale (HDRS) and adverse events, including the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: Sixty patients, 30 in each group, were included in the analyses. All baseline demographic and clinical characteristics were comparable between the groups (p-values > 0.05). The reduction rates from baseline to endpoint in negative, general psychopathology, and total scores of PANSS were greater in the L-theanine group (p-values = 0.03, 0.01, and 0.04, respectively). Regarding general psychopathology scores, the reduction in the L-theanine group was also greater until week 4 (p-value < 0.01). The time × treatment interaction effect was significant on negative (p-value = 0.03), general psychopathology (p-value < 0.01), and total (p-value = 0.04) scores of PANSS, indicating additional improvements in the L-theanine group. The HDRS and side effects were comparable between the groups (p-values > 0.05). CONCLUSIONS: L-Theanine adjunct to risperidone safely and tolerably outperformed adjunctive placebo for schizophrenia, and promising evidence indicated its effects on primary negative symptoms, which need to be scrutinized in further studies. TRIAL REGISTRATION: The study protocol was registered and published prospectively in the Iranian Registry of Clinical Trials ( http://www.irct.ir ; registration number: IRCT20090117001556N133) on 2020-12-12. © 2023. T

Sleep is a crucial component of health, and insomnia is among the most common and vexing of life-habit-related disorders. While dietary sleep-support supplements can improve sleep, choosing an effective dietary supplement can be challenging for users due to the wide variety of options available and the varying effects experienced by different individuals. In this study, to identify new criteria for estimating the effects of dietary supplements, we examined the relationships among the dietary supplements, the pre-conditions (PCs; defined as the life habits and sleep conditions before supplementation), and the sleep problems of subjects before supplementation. An open, randomized, cross-over intervention trial enrolling 160 subjects was conducted to test the efficacy of each dietary supplement (Analysis 1) and the relationships among dietary supplements, the PCs, and sleep problems (Analysis 2). To this end, l-theanine (200 mg/day), γ-aminobutyric acid (GABA) (111.1 mg/day), Apocynum venetum leaf extract (AVLE) (50 mg/day), and l-serine (300 mg/day) were administered to subjects. Before the first intervention period, life habits and sleep conditions were surveyed to identify each subject's PCs. For each combination of supplements and sleep problems, PCs were compared between subjects whose sleep problems were improved and subjects whose sleep problems were not improved via supplementation. All the tested supplements were found to ameliorate sleep problems significantly (Analysis 1). In Analysis 2, the PCs specific to improved subjects were found to differ depending on the dietary supplements and sleep problems. In addition, subjects who consumed dairy products often showed improvement in their sleep problems with all the tested supplements. This study suggests the possibility of personalizing sleep-support supplementation based on personal life habits, sleep conditions, and sleep problems, in addition to the known efficacy of dietary supplements.

Natural products are gaining attention as α-glucosidase (α-GLU) inhibitors owing to their safety and multifunctionality. L-theanine (THE) and epigallocatechin gallate (EGCG) in tea have inhibitory effects, but whether their synergistic inhibition of α-GLU remains unclear. This study investigated the synergistic mechanism of THE and EGCG in inhibiting α-GLU activity using spectral analysis and computational simulation. The results showed that a combination of 1.6 mM THE and 0.11 mM EGCG significantly enhanced α-GLU inhibition. Fluorescence quenching experiments revealed that EGCG did not alter the static quenching pattern of THE on α-GLU. However, it promoted enzyme conformational changes. Multi-spectral analysis and molecular dynamics simulations further demonstrated that THE and EGCG interacted non-covalently with key α-GLU residues (ASP-242, PHE-303, and PRO-312, etc.), disrupting the active site structure, reducing its catalytic efficiency. These findings provide valuable insight into the synergistic inhibition of α-GLU by natural active ingredients, with potential applications in functional foods.

With the increasing prevalence of diabetes, the search for natural compounds with potential anti-hyperglycemic effects has become a key focus in food and nutrition research. L-theanine (THE) and epigallocatechin gallate (EGCG) from tea are gaining attention due to their antioxidant and metabolic regulation properties. Although they have been shown to have an effect on glucose metabolism, their synergistic effect on starch digestive properties and the mechanism remain unclear. Here, we explored that THE and EGCG synergistically regulated starch digestive properties in ultrasound treatment through two different perspectives. At specific THE/EGCG ratios (THE/EGCG1:1), maize starch granules exhibited significant aggregation and densification. THE promoted the ordered arrangement of starch molecular chains through hydrogen bonding, and the polyphenolic structure of EGCG further stabilised this ordered structure, thus enhancing the crystallinity and short-range ordering of starch. It meant that THE and EGCG further reduced starch digestibility by synergistically modulating the multi-scale structure of starch. In addition, THE and EGCG exhibited significant synergistic inhibition of α-amylase activity (1.6 mM THE and 0.05 mg/mL EGCG). The multi-spectral results showed that the addition of THE and EGCG enhanced the conformational change of the enzyme, leading to the change of the secondary structure, and the synergistic effect might originate from the multiple interactions of THE and EGCG with different amino acid residues in the digestive enzyme (e.g., THR-163, GLN-63, ASP-197, etc), which strengthened the inhibition, and the molecular dynamics simulations further supported the findings. This work promotes the further development and utilisation of endogenous substances in tea and provides some references for the development of food ingredients with potential hypoglycaemic functions.

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.

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.

CONTEXT: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits. OBJECTIVE: This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture. MATERIALS AND METHODS: Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes. RESULTS: GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit. CONCLUSIONS: GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.

In general, preparations of coffee, teas, and cocoa containing high levels of polyphenols, L-theanine and other bioactive compounds selectively enhance mood and cognition effects of caffeine. This review summarizes the bioactive components of commonly consumed natural caffeine sources (e.g. guayusa, mate and camellia teas, coffee and cocoa) and analyzes the psychopharmacology of constituent phytochemicals: methylxanthines, polyphenols, and L-theanine. Acute and chronic synergistic effects of these compounds on mood and cognition are compared and discussed. Specific sets of constituent compounds such as polyphenols, theobromine and L-theanine appear to enhance mood and cognition effects of caffeine and alleviate negative psychophysiological effects of caffeine. However, more research is needed to identify optimal combinations and ratios of caffeine and phytochemicals for enhancement of cognitive performance.

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η2p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η2p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

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.

Tea is one of the most widely consumed non-alcoholic beverages in the world next to water. It is classified as Camellia sinensis and non-Camellia sinensis (herbal teas). The common bioactive compounds found mainly in green teas are flavan-3-ols (catechins) (also called flavanols), proanthocyanidins (tannins) and flavonols. Black tea contains theaflavins and thearubigins and white tea contains l-theanine and gamma-aminobutyric acid (GABA), while herbal teas contain diverse polyphenols. Phytochemicals in tea exhibit antimicrobial, anti-diabetic and anti-cancer activities that are perceived to be helpful in managing chronic diseases linked to lifestyle. Many of these phytochemicals are reported to be biologically active when combined. Knowledge of the synergistic interactions of tea with other teas or herbs in terms of biological activities will be of benefit for therapeutic enhancement. There is evidence that various types of teas act synergistically in exhibiting health benefits to humans, improving consumer acceptance and economic value. Similar observations have been made when teas and herbs or medicinal drugs were combined. The aim of this review is to highlight potential beneficial synergies between combinations of different types of teas, tea and herbs, and tea and medicinal drugs. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p < 0.05), theanine accentuated local processing (p < 0.05), and the combination did not differ from placebo. Caffeine reduced flanker conflict difference scores on the Attention Network Test (p < 0.05), theanine increased difference scores (p < 0.05), and the combination did not differ from placebo. Thus, under emotional arousal, caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

INTRODUCTION: The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality. METHODS: Forty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed. RESULTS: No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group. CONCLUSION: These results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep dur

Objective: Sleep problems are a common complaint among adults worldwide, however, the use of prescription and over-the-counter products may not always be an appropriate or desirable solution. L-theanine is a naturally occurring, non-protein amino acid that can be found in the leaves of the tea plant Camellia sinensis. Previous studies have reported that consumption of L-theanine can help to aid relaxation, without causing sedation or adversely impacting cognitive function. Building on these calming effects and results from recent pre-clinical studies, the aim of this review was to systematically appraise the scientific literature to establish whether dietary supplementation with L-theanine can also help to support sleep in humans.Methods: Electronic database searches of Ovid MEDLINE, PsycINFO, Embase, CENTRAL and Google Scholar were conducted from inception to 3rd February 2025. Retrieved articles were independently reviewed by three authors.Results: Thirteen eligible trials (n = 550) that examined the effect of L-theanine (50-900 mg/day) as a standalone intervention on sleep-related outcome measures were identified. This included two single-arm, open-label trials and eleven randomised controlled trials.Discussion: Based on the current evidence, supplementation with 200-450 mg/day of L-theanine appears to be a safe and effective way to support healthy sleep in adults. Among the included trials, beneficial effects were reported on both objective and participant-reported outcomes, including measures linked to sleep latency, maintenance and efficiency, perceived sleep satisfaction and feelings of refreshment and recovery on waking. Further high-quality trials using objective measures, into the mechanisms underlying these effects, and among those with clinical insomnia would provide further useful insights.

OBJECTIVE: This review aims to assess the efficacy and safety of different supplements, such as L-theanine, caffeine, Ginkgo biloba L., and Bacopa monnieri for improving ADHD symptoms, to determine the most effective supplement and provide insight for medical practice. METHODS: International databases (PubMed/MEDLINE and Scopus) were searched for English-language RCTs, open-label studies, and cross-sectional studies. RESULTS: Studies on L-theanine, caffeine, Ginkgo biloba L., and Bacopa monnieri have shown various effects on ADHD symptoms. L-theanine improved sleep efficiency but not other sleep parameters. Caffeine showed no significant benefits, although its combination with L-theanine may enhance attention. Bacopa monnieri consistently improved inattention, hyperactivity, and memory, whereas Ginkgo biloba L. reduced ADHD symptoms, particularly inattention, but was less effective than methylphenidate. CONCLUSIONS: The evidence revealed the potential use of supplements as complementary ADHD treatments under clinical guidance. The limited effect of supplements cannot replace the well-documented efficacy of stimulants for ADHD treatment. Additional studies are needed to ascertain the most effective dosages and the safety of these supplements as adjunctive treatments for ADHD.

CONTEXT: The bioactive compounds found in tea from Camellia sinensis, namely theanine, caffeine, and polyphenols, can potentially improve short-term and long-term health outcomes. OBJECTIVE: The aim of this study was to assess the effects of tea, theanine alone, or theanine plus caffeine on cognition, mood, and sleep outcomes, using data from randomized controlled trials (RCTs) in healthy participants. DATA SOURCES: The Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, and Ovid Medline were searched up to and including August 2023. DATA EXTRACTION: Data relevant to the participants, interventions, comparisons, outcomes (ie, cognition, mood, and sleep), and study design were extracted. DATA ANALYSIS: Fifty RCTs were included in the review, of which 15 were eligible for at least 1 meta-analysis, most commonly performed by use of standardized mean differences (SMD), in random effects models. After intake of theanine plus caffeine, and of placebo, small-to-moderate differences were found between these interventions in the first hour (h1) and second hour (h2), that favoured theanine plus caffeine, with regard to cognition and mood outcomes such as choice reaction time (h1: SMD, -0.48; 95% CI, -1.01, 0.05), digit vigilance task accuracy (h2: SMD, 0.20; 95% CI, 0.02, 0.38), attention switching task accuracy (h2: SMD, 0.33; 95% CI, 0.13, 0.54), and overall mood (h2: SMD, 0.26; 95% CI,-0.10, 0.63). There was a small-to-moderate difference between the effects of theanine and placebo that favored theanine on choice reaction time (h1: SMD, -0.35; 95% CI,-0.61, -0.10). The CIs frequently highlighted the uncertainty surrounding the direction and magnitude of these differences. CONCLUSIONS: This meta-analysis provides evidence that theanine plus caffeine, and theanine alone, could be beneficial for cognitive and mood outcomes. More research using tea beverages or tea-equivalent bioactive doses and research in free-living participants is needed. PROSPERO REGISTRATION NO: CRD42022351601. © The Author(s) 2025. Published by Oxford University Press on behalf of the International Life Sciences Institute.

BACKGROUND: When utilized as an adjunct with antidepressants, antipsychotics, and other psychopharmacological drugs, certain amino acids, such as L-Theanine (LT), have shown potential effectiveness in enhancing the symptomatic outcomes of patients with mental disorders. Despite this, there is a lack of previous systematic reviews examining these associations. Therefore, we conducted a systematic review of randomized controlled trials examining these relationships. METHODS: A comprehensive systematic review was conducted, scouring six electronic databases (PubMed, Scopus, PsycINFO, Web of Science, CINAHL Complete, and Cochrane) from their inception up to June 2023, specifically focusing on randomized controlled trials that investigated the effects of LT supplementation on the outcomes of patients with mental health disorders. The Cochrane Risk of Bias Tool for Randomized Trials was employed to assess the quality of the included studies. RESULTS: Among the 419 publications identified, 11 studies from six countries - Israel, Iran, the USA, Japan, Australia, and Italy - were included in the final analysis. These studies covered a range of mental disorders, including schizophrenia, Attention-Deficit/Hyperactivity Disorder (ADHD), Obsessive-Compulsive Disorder (OCD), Major Depressive Disorder (MDD), sleep disorders, Generalized Anxiety Disorder (GAD), and Tourette syndrome. The findings demonstrated that LT supplementation reduced psychiatric symptoms more effectively than control conditions in individuals with schizophrenia, anxiety disorders, and ADHD. CONCLUSIONS: The findings from this systematic review suggest that LT supplementation significantly reduced psychiatric symptoms more effectively than control conditions in individuals with schizophrenia, anxiety disorders, and ADHD. However, further studies are essential to validate these findings, deepen the understanding of the observed effects, and explore the mechanisms underlying these associations. © 2024. The Author(s).

OBJECTIVE: The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD). DATA SOURCE: A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide. DATA SYNTHESIS: The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency. CONCLUSIONS: The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable. OBJETIVO: Analisar a interferência do tratamento farmacológico no padrão de sono das crianças com transtorno do déficit de atenção com hiperatividade (TDAH). FONTES DE DADOS: Busca eletrônica de alta sensibilidade nas bases de dados Cochrane Library, Medical Literature Analysis and Retrieval System Online (MEDLINE) via United States National Library of Medicine (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) via Biblioteca Virtual em Saúde (BVS), Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) e Web of Science, de acordo com o preconizado pelo Cochrane Handbook, de artigos que passaram pela revisão por pares segundo o Guia PRESS. SÍNTESE DOS DADOS: Os estudos que contemplaram o uso das drogas atomoxetina (ATX), guanfacina, metilfenidato (MPH), dasotralina, L-teanina e lisdexanfetamina mostraram eficiência na redução dos sintomas do TDAH, embora todos os medicamentos, exceto a atomoxetina, tenham afetado a qualidade do sono — reduzindo REM total, fase não REM, tempo de sono de ondas lentas e maior latência de início do sono. CONCLUSÕES

BACKGROUND: Anxiety disorder is a common psychiatric illness. Medicinal herbs have become a field of interest in the treatment of anxiety. This study aimed to evaluate and compare the efficacy and acceptability of all possible medicinal herbs for the treatment of anxiety. METHODS: A Bayesian network meta-analysis was conducted for adults with diagnosed or subthreshold anxiety in randomized controlled trials identified in PubMed, EMBASE, the Cochrane Library, and Web of Science, searched between Jan 1, 1987, and Dec 31, 2021. The outcomes included efficacy (measured by endpoint Hamilton Anxiety Scale [HAMA] Scores) and acceptability (discontinuation by ineffectiveness, worsening of the symptoms, or adverse events). RESULTS: A total of 29 trials were reviewed, comparing 12 medicinal herbs. Silexan (mean difference [MD]: -3.84, 95% credible interval [CrI]: -6.31 to -1.34) displayed a significant effect on anxiety, and possibly benefitted the treatment of depression (standard mean difference [SMD]: -0.37, 95% confidence interval [CI]: -0.53 to -0.20) and insomnia (SMD: -0.48, 95% CI: -0.76 to -0.21). Kava was found to be an effective anxiolytic (MD: -2.46, 95% CrI: -4.47 to -0.32) but possibly ineffective in patients with generalized anxiety disorder (MD: -0.17, 95% CrI: -2.55 to -1.97). Ginkgo biloba (MD: -4.63, 95% CrI: -9.01 to -0.23) and Withania somnifera (MD: -4.90, 95% CrI: -9.70 to -0.17) were efficacious, as measured by HAMA scores but the trials were limited by their small sample sizes. Galphimia glauca (MD: -1.23, 95% CrI: -4.68 to 2.23) and Manasamitravn Vataka (MD: -1.35, 95% CrI: -7.39 to 4.68) exhibited the same anxiolytic effect as standard treatments, but both were absent from trials that were rated low risk, highlighting that confidence in their ability to provide an anxiolytic effect requires additional study. Conversely, although Passionflower (MD: -4.20, 95% CrI: -8.82 to 0.16) and Saffron (MD: -2.71, 95% CrI: -6.06 to 0.57) did not reduce HAMA scores significantly in the summary network, both were worthy of further study because of support from separate networks. There was insufficient evidence to confirm the effectiveness of Valerian (MD: 0.95

The green tea amino acid, L-theanine (L-THE) is associated with several health benefits, including improvements in mood, cognition and a reduction of stress and anxiety-like symptoms. This systematic review evaluated the effect of pure L-THE intake, in the form of orally administered nutritional supplements, on stress responses and anxiety levels in human randomised controlled trials. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 9 peer-reviewed journal articles were identified where L-THE as a supplement was compared to a control. Our findings suggest that supplementation of 200-400 mg/day of L-THE may assist in the reduction of stress and anxiety in people exposed to stressful conditions. Despite this finding, longer-term and larger cohort clinical studies, including those where L-THE is incorporated into the diet regularly, are needed to clinically justify the use of L-THE as a therapeutic agent to reduce stress and anxiety in people exposed to stressful conditions.

Beyond the well-known effects on cognitive impairment of the Mediterranean diet, a number of studies have investigated the possible action on cognitive decline of different botanicals and phytochemicals, most of which are well-known anti-inflammatory or antioxidant agents with a good tolerability and safety profile. In particular, the current literature supports the use of Ginkgo biloba, resveratrol, epigallocatechin-3-gallate and l-theanine, Theobroma cacao, Bacopa monnieri, Crocus sativus and curcumin, which might have a positive impact on cognitive impairment used alone or in combination with other nutraceuticals or traditional drugs. Then, the aim of the present study was to review and comment the available evidence on botanicals and phytochemicals with a clinically demonstrable effect on cognitive decline. For this reason, we carefully reviewed studies published in English language from 1970 to April 2017 on botanicals and phytochemical claiming to show an effect on cognitive impairment in humans. Thus, the terms 'botanicals', 'dietary supplements', 'herbal drug', 'nutraceuticals', 'phytochemical', 'cognitive impairment', 'Alzheimer's disease', 'clinical trial', and 'humans', alone and in combinations, were incorporated into an electronic search strategy in both MEDLINE (National Library of Medicine, Bethesda, MD) and the Cochrane Register of Controlled Trials (The Cochrane Collaboration, Oxford, UK). As it emerges from this systematic review, the use of some phytochemicals and botanicals seems to be very promising in order to delay the onset and progression of neurodegenerative and other age-related diseases. However, further well-designed clinical research is certainly needed to finally confirm the efficacy and safety profile of these compounds.