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Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial

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Nutrients
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This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.
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nutrients
Article
Eects of L-Theanine Administration on
Stress-Related Symptoms and Cognitive Functions in
Healthy Adults: A Randomized Controlled Trial
Shinsuke Hidese 1, Shintaro Ogawa 1, Miho Ota 1, Ikki Ishida 1, Zenta Yasukawa 2,
Makoto Ozeki 2and Hiroshi Kunugi 1, *
1
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology
and Psychiatry, 4-1-1, Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; shidese@ncnp.go.jp (S.H.);
sogawa@ncnp.go.jp (S.O.); ota@ncnp.go.jp (M.O.); iishida@ncnp.go.jp (I.I.)
2Department of Research and Development, Nutrition Division, Taiyo Kagaku Co. Ltd, 1-3, Takara-machi,
Yokkaichi, Mie 510-0844, Japan; zyasukawa@taiyokagaku.co.jp (Z.Y.); mozeki@taiyokagaku.co.jp (M.O.)
*Correspondence: hkunugi@ncnp.go.jp; Tel.: +81-42-346-1714; Fax: +81-42-346-1714
Received: 20 August 2019; Accepted: 29 September 2019; Published: 3 October 2019


Abstract:
This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine
the possible eects of four weeks L-theanine administration on stress-related symptoms and cognitive
functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age:
48.3 ±11.9 years
) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets
were randomly and blindly assigned for four-week administration. For stress-related symptoms,
Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index
(PSQI) scores decreased after L-theanine administration (p=0.019, 0.006, and 0.013, respectively).
The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced
after L-theanine administration, compared to the placebo administration (all p<0.05). For cognitive
functions, verbal fluency and executive function scores improved after L-theanine administration
(
p=0.001
and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (
p=0.002
),
especially letter fluency (p=0.002), increased after L-theanine administration, compared to the placebo
administration, in individuals who were sub-grouped into the lower half by the median split based
on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote
mental health in the general population with stress-related ailments and cognitive impairments.
Keywords: cognition; emotion; L-theanine; sleep; stress
1. Introduction
L-theanine (
γ
-glutamylethylamide) is a unique non-protein amino acid found in green tea
(Camellia sinensis), a widely consumed beverage associated with human health [
1
3
]. As the structure
of L-theanine resembles that of L-glutamic acid, its mechanism of action may be potentially mediated
through glutamate receptors [
4
], a possibility supported by its partial co-agonistic eect on the
N-methyl-D-aspartate receptor [
5
,
6
]. Given that L-theanine is a phytochemical ingested in daily life,
it has the potential to become a nutraceutical ingredient that mitigates and prevents stress-related
psychic confusion in modern society [710].
In rodents, L-theanine has been proposed as a neuroprotective and cognitive-enhancing
agent [
11
]. Peripherally and centrally administered L-theanine has been reported to act on the
brain [
12
,
13
], to modulate monoamine levels in the central nervous system [
14
17
], and glutamate and
glycine neurotransmissions [
18
,
19
]. L-theanine has been also reported to influence hippocampal
synaptic plasticity, improving performance in recognition tasks in stressed young rats [
20
,
21
].
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Nutrients 2019,11, 2362 2 of 13
Furthermore, in behavioral experiments in mice, L-theanine has been reported to have anti-stress or
antidepressant-like eects [
22
26
], which has been associated with an increase in the expression of
brain-derived neurotrophic factor in the hippocampus [
6
], while anxiolytic eects of L-theanine have
been observed in Wistar Kyoto rats, where it enhances hippocampal activity in positron emission
tomography [27].
In humans, L-theanine has been reported to modulate alpha activity and play a role in attentional
tasks in electroencephalogram studies [
28
30
], as well as provide beneficial eects on mental state [
31
],
including sleep quality [
32
]. To our knowledge, however, only its acute eects have been investigated
in healthy individuals. The anti-stress eects of L-theanine (200 mg/day) have been observed following
once- [
33
,
34
] and twice daily [
35
] administration, while its attention-improving eects have been
observed in response to treatment of 100 mg/day on four separate days [
36
] and 200 mg/day single
administration [
37
], which was further supported by decreased responses in functional magnetic
resonance imaging [
38
]. Moreover, L-theanine has been suggested to have potential therapeutic eects
in psychiatric disorders [
39
]. In accordance with this, we have reported multiple favourable eects of
four weeks L-theanine administration (250 mg/day) in patients with major depressive disorder (MDD),
although this was an open-label study [40].
With the except of Hidese et al. [
40
], most human studies have focused on the eects of acute
L-theanine administration. The present study aimed to examine the eects of four weeks L-theanine
administration (200 mg/day, four weeks) in a healthy population, i.e., individuals without any major
psychiatric disorder. Namely, the population of this study comprised individuals suering from some
non-clinical symptoms (e.g., emotion, sleep, and cognition). In order to obtain valid data, this study
was designed to be a randomized, placebo-controlled, crossover, and double-blind trial.
2. Materials and Methods
2.1. Participants
Thirty individuals (Nine men and 21 women; mean age: 48.3
±
11.9 years [range: 20–69]), without
any major psychiatric illness and enrolled after a screening by a trained psychiatrist, participated in the
study. The sample size was determined by using G*Power software (3.1 version, Franz Faul, University
of Kiel, Kiel, Germany) [
41
,
42
]. The current sample (30 L-theanine and 30 placebo) had a power of
>0.80, based on the eect size (0.61) of L-theanine on depression score in our previous study [
40
].
Individuals who had been treated for any psychiatric disorder, assessed according to the criteria of
the Japanese version of the Mini-International Neuropsychiatric Interview [
43
,
44
] and the Diagnostic
and Statistical Manual of Mental Disorders, 5th edition [
45
], were excluded. Individuals who did
not have any psychiatric disorders were included, while those who had severe physical illnesses
or pregnant women were excluded. We obtained the information about current drinking alcohol
and smoking habits. All participants were recruited randomly through prepared advertisements in
the local community and announcements in a free magazine or on our website. Written informed
consent was obtained from every participant. Confidentiality of personal information was consistently
preserved by anonymizing data obtained by using code corresponding to personal identification
information. The protocol was approved by the ethics committee at the National Center of Neurology
and Psychiatry, and primary and secondary endpoints were complied with, accordingly. The study
protocol was registered at the university hospital medical information network—clinical trials registry
(UMIN 000028603) and carried out according to the Declaration of Helsinki [
46
]. This randomized
study adhered to the Consolidated Standards of Reporting Trials extensions [47].
2.2. L-theanine Administration
An enzymatic synthetic product L-theanine (200 mg/day; Suntheanine, Taiyo Kagaku Co., Ltd,
Mie, Japan) or placebo tablets were orally self-administered before sleep each night for four weeks,
while the compliance was checked only verbally. Placebo tablet was the same as L-theanine tablet in
Nutrients 2019,11, 2362 3 of 13
terms of appearance and taste. This dose was chosen because it was found to be eective in a previous
study [
48
], which was normal dose as also used in other studies [
33
35
,
37
]. However, the dose was
relatively high compared to the median amount of L-theanine per cup of green tea (8–30 mg) [
49
].
The tablets were allocated to the participants in a randomized manner, using a table of random numbers
to generate the sequence for randomization, by a representative assignee who was not an intervention
practitioner. After a two-week wash-out period, which was justified based on the half-life of L-theanine
plasma concentration reported around 65 min in humans [
50
], participants received the other tablets
for a further four weeks, according to the crossover method. Participants were instructed not to alter
their usual intake of green tea or other beverage contained L-theanine during the intervention period,
although it was not actually tracked. In accordance with double-blind procedures, the identity of
the active or placebo tablets was not disclosed to participants or research conductors at the National
Center of Neurology and Psychiatry until all the statistical analyses had been completed. The tablets
were labeled only as either A or B at the time of supply to the participants. After performance of
the statistical analyses by an outcome evaluator, the identity of the tablets was finally disclosed by
a researcher at Taiyo Kagaku Co., Ltd. All the data collection and analysis were thus performed by
blinded investigators. After removing anonymity, L-theanine and placebo were found to have been
administered to 16 and 14 participants, respectively, between weeks zero and four. Following the
two-week wash-out period, subjects were administered tablets in a crossover manner between weeks
six and ten.
2.3. Clinical Assessments (Primary Outcome)
Clinical assessments were performed at baseline, and four, six, and ten weeks into the trial.
The Japanese version of the Self-rating Depression Scale (SDS) [
51
,
52
], the State-Trait Anxiety Inventory
(STAI) [
53
,
54
], and the Pittsburgh Sleep Quality Index (PSQI) [
55
,
56
] were used to evaluate depression,
anxiety, and sleep quality, respectively. Cognitive functions were evaluated by a research psychiatrist
using the Trail-Making Test [
57
], the Stroop test [
58
], and the Japanese version of the Brief Assessment
of Cognition in Schizophrenia (BACS) [
59
,
60
]. The Stroop test was conducted on a computer using
two separate PowerPoint files for control and experimental conditions, composed of four colored
words (blue, red, yellow, and black). After practice with the control condition, wherein the color and
word were matched, response latency (msec) and error rate (%) were calculated in the experimental
condition, in which the colour and word were dierent. Two dierent versions (A and B) of the Stroop
and BACS tests were used alternately at each assessment to exclude the possibility of any learning
eect. All assessments completed on the same day from 10:00 to 12:00.
2.4. Laboratory Tests (Secondary Outcome)
Fasted venous blood and salivary samples were obtained between 12:00 and 13:00 after the clinical
assessments at baseline and four, six, and ten weeks into the trial. Serum and plasma samples were
prepared by centrifuging blood for ten minutes at 2000
×
g, while salivary supernatants were prepared
by centrifuging saliva impregnated in mesh (Salimetrics, LLC., Carlsbad, California, United States
of America) for 15 min at 1000
×
g(Kubota Corp., Tabletop Centrifuge Model 4000, Tokyo, Japan).
In addition to general serum measures, plasma glucose and haemoglobin-A1c, and whole blood count
levels, serum cortisol and immunoglobulin-A levels were measured at SRL Co., Ltd. (Tokyo, Japan).
Salivary cortisol and immunoglobulin-A levels were measured at our laboratory using Salivary enzyme
immunoassay kits (1-3002 and 1-1602; respectively, Salimetrics, LLC., Carlsbad, California, United
States of America). Serum L-theanine concentrations were measured using a high-performance liquid
chromatography system based on the AccQ
·
Tag method [
61
], using commercially available reagents
(Waters Corp., Tokyo, Japan) and equipment (Shimazu Corp., Kyoto, Japan) at Taiyo Kagaku Co., Ltd.
(Mie, Japan) The anonymity of the participants was preserved throughout the biochemical tests.
Nutrients 2019,11, 2362 4 of 13
2.5. Statistical Analyses
The crossover data during the intervention period were combined to a total period (i.e., the sum
of baseline-four and six-ten weeks) of four weeks L-theanine and placebo administration. Clinical
variables were compared between baseline and after four weeks of administration, using the Wilcoxon
signed-rank test. Changes in clinical variables between pre- and post-treatment were compared
between the L-theanine and placebo administrations, using the Mann-Whitney U test. The eect
sizes were calculated using r values from the Wilcoxon signed-rank and Mann-Whitney U tests. For
comparison of the BACS scores, we performed analyses stratified by the median split based on the
mean pretreatment scores (i.e., dividing the 30 subjects into two groups [N=15 each] based on the
average of the scores at week zero and that of week six) for each cognitive function. Changes in BACS
scores were compared between L-theanine and placebo administrations in the high and low score
groups, separately. All statistical tests were two-tailed and p<0.05 was deemed statistically significant.
Statistical analyses were performed using the Statistical Package for the Social Sciences version 25.0
(IBM Corp., Tokyo, Japan).
3. Results
3.1. Participants
The clinical characteristics of the participants are shown in Table 1. The data collection period
was from 7th June 2017 to 7th August 2018. There was no participant drop-out (i.e., trial compliance of
100%), and adverse events were not apparent during the intervention period.
Table 1. The clinical characteristics of the participants.
Variables Mean ±Standard Deviation Range
Age (years) 48.3 ±11.9 20–69
Sex, female: n(%) 21 (70)
Education (years) 14.5 ±2.0 10–18
Height (cm) 161 ±8.0 148–180
Weight at baseline (kg) 58.6 ±12.7 44–102
Body mass index at baseline (kg/m2)22.5 ±3.9 17.1–31.5
Drinking alcohol habit: n(%) 20 (66.7)
Smoking habit: n(%) 8 (26.7)
n=30, frequency (percentage).
3.2. Symptom Scores
The stress-related symptom scores after 4 weeks L-theanine or placebo administration are shown
in Table 2. The SDS, STAI-trait (T), and PSQI scores were significantly improved after L-theanine
administration (p=0.019, 0.006, and 0.013, respectively; Figure 1). Among the PSQI subscales,
the scores of “sleep latency” and “daytime dysfunction” significantly improved in response to
L-theanine administration (p=0.036 and 0.022, respectively). In contrast, there was no significant
dierence after placebo administration. When score reductions in the stress-related symptoms were
compared between L-theanine and placebo administrations, changes in the PSQI sleep latency, sleep
disturbance, and use of sleep medication subscales were significantly greater (p=0.0499, 0.046,
and 0.047, respectively), while those in the SDS and PSQI scores showed a non-statistically significant
trend towards greater improvement (p=0.084 and 0.073, respectively), during the L-theanine period
compared to placebo.
Nutrients 2019,11, 2362 5 of 13
Table 2. The stress-related symptom scores after 4 weeks L-theanine or placebo administration.
Symptoms Pretreatment Posttreatment Wilcoxon Signed-Rank Test Pretreatment Posttreatment Wilcoxon Signed-Rank Test Score Changes Mann-Whitney U Test
L-theanine Placebo L-theanine Placebo
Self-rating Depression Scale 45.8 ±7.38 43.2 ±7.47 W=83.5, p=0.019,
r=0.43 45.8 ±7.41 45.7 ±6.77 W=216.0, p=0.77,
r=0.06 2.53 ±5.38 0.07 ±6.60 U=333.5, p=0.084,
r=0.22
State-Trait Anxiety
Inventory-state 48.6 ±9.32 46.1 ±9.51 W=158.5, p=0.20,
r=0.23 50.6 ±9.86 49.9 ±11.2 W=181.5, p=0.44,
r=0.14 2.47 ±9.26 0.67 ±8.75 U=435.0, p=0.82,
r=0.03
State-Trait Anxiety
Inventory-trait 51.9 ±9.66 48.5 ±10.4 W=74.0, p=0.006,
r=0.51 51.4 ±10.3 52.1 ±11.2 W=184.0, p=0.90,
r=0.02 3.37 ±8.13 0.77 ±7.52 U=348.0, p=0.13,
r=0.20
Pittsburgh Sleep Quality Index 9.67 ±2.71 8.3 ±2.45 W=78.5, p=0.013,
r=0.46 9.63 ±2.24 9.60 ±2.84 W=132.0, p=0.85,
r=0.03 1.37 ±2.81 0.03 ±2.08 U=330.0, p=0.073,
r=0.23
C1 (sleep quality) 1.77 ±0.73 1.50 ±0.73 W=10.0, p=0.052,
r=0.36 1.73 ±0.69 1.63 ±0.56 W=30.0, p=0.44,
r=0.14 0.27 ±0.74 0.10 ±0.71 U=403.0, p=0.42,
r=0.11
C2 (sleep latency) 1.67 ±1.12 1.23 ±1.01 W=34.0, p=0.036,
r=0.38 1.63 ±0.93 1.63 ±0.93 W=27.5, p=1.00,
r=0.00 0.43 ±1.04 0.00 ±0.59 U=330.0, p=0.0499,
r=0.25
C3 (sleep duration) 3.00 ±0.00 3.00 ±0.00 W=0.0, p=1.00,
r=not applicable 3.00 ±0.00 3.00 ±0.00 W=0.0, p=1.00,
r=not applicable 0.00 ±0.00 0.00 ±0.00 U=450.0, p=1.00,
r=0.00
C4 (habitual sleep eciency) 0.50 ±0.94 0.50 ±0.86 W=30.0, p=0.93,
r=0.02 0.63 ±0.96 0.53 ±0.90 W=22.0, p=0.57,
r=0.11 0.00 ±0.98 0.10 ±0.92 U=435.0, p=0.79,
r=0.03
C5 (sleep disturbances) 1.27 ±0.45 1.10 ±0.40 W=10.0, p=0.096,
r=0.31 1.17 ±0.59 1.27 ±0.64 W=20.0, p=0.26,
r=0.21 0.17 ±0.53 0.10 ±0.48 U=345.5, p=0.046,
r=0.26
C6 (use of sleeping medication) 0.27 ±0.78 0.13 ±0.57 W=0.0, p=0.18,
r=0.25 0.13 ±0.57 0.27 ±0.78 W=3.0, p=0.18,
r=0.25 0.13 ±0.57 0.13 ±0.57 U=392.0, p=0.047,
r=0.26
C7 (daytime dysfunction) 1.20 ±1.00 0.83 ±0.79 W=32.0, p=0.022,
r=0.42 1.33 ±0.84 1.27 ±0.91 W=115.0, p=0.67,
r=0.08 0.37 ±0.81 0.07 ±0.87 U=374.0, p=0.23,
r=0.15
Values are represented as mean ±standard deviation. Significant p-values are shown in bold cases.
Nutrients 2019,11, 2362 6 of 13
Figure 1.
Stress-related symptom scores after 4 weeks L-theanine or placebo administration.
The Wilcoxon signed-rank test revealed that the Self-rating Depression Scale, State-Trait Anxiety
Inventory-trait, and Pittsburgh Sleep Quality Index scores were significantly decreased in the L-theanine
administration (n=30), while there was no significant change in the placebo administration (n=30).
*p<0.05, ** p<0.01. N.S., not significant.
3.3. Cognitive Function Scores
The cognitive function scores after 4 weeks L-theanine or placebo administration are shown
in Table 3. The BACS verbal fluency, especially letter fluency (p=0.001), and executive function
scores were significantly increased after L-theanine administration (p=0.001 and 0.031, respectively;
Figure 2), while the Trail Making Test A and B scores were significantly improved after placebo
administration (p=0.042 and 0.038, respectively). When score changes were compared between
the L-theanine and placebo administrations, no significant dierence was found for any cognitive
function. We then performed analyses stratified by the median split based on the mean pretreatment
scores for each cognitive function (Table 4). We found that improvement in the BACS verbal fluency
(p=0.002)
, especially letter fluency (p=0.002), score was significantly greater during the L-theanine
period than the placebo period among those individuals who were sub-grouped into the lower half
by the median split (n=15). In addition, the BACS executive function score improvement tended
to be greater in the L-theanine period than in the placebo period among the lower half of the group
(p=0.062)
. Furthermore, we repeated the analyses with subjects restricted to those aged 40 years or
more, since cognitive decline typically begins at, or after, middle age. The results were essentially
unchanged (
n=21
; verbal fluency: p=0.023, letter fluency: p=0.040, and executive function:
p=0.048
;
Supplementary Table S1).
Figure 2.
Cognitive function scores after 4 weeks L-theanine or placebo administration. The Wilcoxon
signed-rank test revealed that the Brief Assessment of Cognition in Schizophrenia (BACS) verbal fluency
and executive function scores were significantly decreased in the L-theanine administration (
n=30
),
while there was no significant change in the placebo administration (n=30). * p<0.05,
** p<0.01
. N.S.:
Not significant.
Nutrients 2019,11, 2362 7 of 13
Table 3. The cognitive function scores after 4 weeks L-theanine or placebo administration.
Cognitive functions Pretreatmnent Posttreatment Wilcoxon
Signed-Rank Test Pretreatment Postreatment Wilcoxon
Signed-Rank Test Score Changes Mann-Whitney U Test
L-theanine Placebo L-theanine Placebo
Trail Making Test A (sec) 27.4 ±9.78 25.9 ±10.2 W=170.5, p=0.31,
r=0.19 29.1 ±10.7 25.9 ±10.3 W=123.5, p=0.042,
r=0.37 1.57 ±9.68 3.27 ±7.48 U=410.0, p=0.55,
r=0.08
Trail Making Test B (sec) 62.4 ±22.0 59.6 ±24.8 W=136.5, p=0.13,
r=0.28 63.9 ±22.9 58.6 ±20.4 W=121.5, p=0.038,
r=0.38 2.83 ±18.5 5.23 ±14.9 U=428.0, p=0.75,
r=0.04
Stroop test response
latency (msec) 1176 ±219 1159 ±228 W=149.0, p=0.50,
r=0.12 1188 ±259 1140 ±217 W=154.5, p=0.27,
r=0.20 16.7 ±158 47.9 ±183 U=422.5, p=0.68,
r=0.05
Stroop test error rate (%) 1.04 ±1.62 1.81 ±2.37 W=130.0, p=0.15,
r=0.26 0.83 ±1.51 1.32 ±2.35 W=74.0, p=0.42,
r=0.15 0.76 ±2.41 0.49 ±2.10 U=426.0, p=0.71,
r=0.05
Brief Assessment of
Cognition in Schizophrenia
verbal memory 52.2 ±7.68 52.5 ±7.74 W=183.0, p=0.85,
r=0.04 52.7 ±9.05 51.5 ±9.69 W=182.0, p=0.63,
r=0.09 0.30 ±8.57 1.20 ±9.53 U=414.5, p=0.60,
r=0.07
working memory 20.9 ±4.14 21.5 ±4.43 W=194.5, p=0.39,
r=0.16 21.5 ±4.91 21.4 ±4.83 W=158.5, p=0.91,
r=0.02 0.57 ±3.87 0.03 ±3.31 U=397.0, p=0.43,
r=0.10
motor speed 83.7 ±12.6 84.0 ±12.5 W=193.5, p=0.65,
r=0.08 83.2 ±13.0 83.6 ±13.3 W=204.5, p=0.71,
r=0.07 0.37 ±7.80 0.43 ±7.94 U=439.5, p=0.88,
r=0.02
verbal fluency 50.3 ±13.0 54.9 ±10.4 W=364.5, p=0.001,
r=0.58 52.3 ±9.80 54.7 ±12.2 W=299.5, p=0.076,
r=0.33 4.57 ±7.13 2.33 ±7.26 U=336.5, p=0.22,
r=0.20
category fluency 21.9 ±5.87 23.1 ±5.30 W=271.5, p=0.12,
r=0.29 22.4 ±4.48 23.3 ±5.49 W=244.0, p=0.35,
r=0.17 1.20 ±4.23 0.90 ±5.91 U=442.5, p=0.91,
r=0.02
letter fluency 28.4 ±8.43 31.7 ±6.94 W=348.5, p=0.001,
r=0.61 29.9 ±7.28 31.4 ±9.68 W=283.5, p=0.29,
r=0.19 3.37 ±4.63 1.43 ±5.83 U=344.0, p=0.12,
r=0.20
attention 64.4 ±11.6 62.9 ±11.7 W=139.0, p=0.53,
r=0.12 62.6 ±11.3 62.9 ±10.1 W=204.0, p=0.47,
r=0.13 1.47 ±7.37 0.33 ±4.97 U=308.5, p=0.30,
r=0.13
executive function 17.4 ±2.71 18.5 ±1.72 W=208.5, p=0.031,
r=0.40 18.2 ±1.77 18.5 ±1.63 W=205.0, p=0.24,
r=0.21 1.10 ±2.52 0.33 ±1.81 U=397.0, p=0.43,
r=0.10
Values are represented as mean ±standard deviation. Significant p-values are shown in bold cases.
Nutrients 2019,11, 2362 8 of 13
Table 4.
Comparisons of BACS score changes between 4 weeks L-theanine and placebo administrations
stratified by the median split based on mean pretreatment score.
L-theanine Placebo Mann-Whitney U Test
Verbal memory 0.30 ±8.57 1.20 ±9.53 U =414.5, p=0.60, r =0.07
Upper half 3.13 ±9.36 3.07 ±10.0 U =108.0, p=0.85, r =0.04
Lower half 3.73 ±6.27 0.67 ±8.93 U =95.0, p=0.47, r =0.13
Working memory 0.57 ±3.87 0.03 ±3.31 U =397.0, p=0.43, r =0.10
Upper half 0.47 ±3.50 0.80 ±3.38 U =80.0, p=0.17, r =0.25
Lower half 0.67 ±4.34 0.73 ±3.15 U =111.0, p=0.95, r =0.01
Motor speed 0.37 ±7.80 0.43 ±7.94 U =439.5, p=0.88, r =0.02
Upper half 0.67 ±7.10 0.27 ±6.24 U =104.0, p=0.72, r =0.07
Lower half 0.07 ±8.69 0.60 ±9.58 U =112.0, p=0.98, r =0.00
Verbal fluency 4.57 ±7.13 2.33 ±7.26 U =336.5, p=0.22, r =0.20
Upper half 1.20 ±6.30 4.53 ±7.36 U =81.5, p=0.20, r =0.24
Lower half 7.93 ±6.42 0.13 ±6.69 U =37.5, p=0.002, r =0.57
category fluency 2.65 ±4.18 1.13 ±4.17 U =101.5, p=0.32, r =0.18
letter fluency 6.00 ±3.41 0.07 ±5.31 U =44.0, p=0.002, r =0.56
Attention 1.47 ±7.37 0.33 ±4.97 U =308.5, p=0.30, r =0.13
Upper half 3.67 ±9.57 1.20 ±3.95 U =100.0, p=0.60, r =0.10
Lower half 0.73 ±3.24 1.87 ±5.53 U =80.5, p=0.18, r =0.24
Executive function 1.10 ±2.52 0.33 ±1.81 U =397.0, p=0.43, r =0.10
Upper half 0.07 ±1.49 0.40 ±1.55 U =88.5, p=0.30, r =0.19
Lower half 2.27 ±2.84 0.27 ±2.09 U =68.0, p=0.062, r =0.34
Values are represented as mean
±
standard deviation. Significant p-value are shown in bold cases. Median values
for verbal memory, working memory, motor speed, verbal fluency, attention, and executive function were 53.5, 21.5,
84.0, 52.8, 62.8, and 18.3, respectively. BACS: Brief Assessment of Cognition in Schizophrenia.
3.4. Biochemical Data
Body mass index and biochemical data after 4 weeks L-theanine or placebo administration are
shown in Supplementary Table S2. The serum L-theanine concentration was significantly increased after
L-theanine administration (p=0.002), while it was not significantly altered after placebo administration.
There was a significant dierence in the serum L-theanine concentration between the L-theanine and
placebo administrations (p=0.028). No other significantly altered indices were found after either
L-theanine or placebo administration.
4. Discussion
In this placebo-controlled study, stress-related symptoms assessed with SDS, STAI-T, and PSQI
scores decreased, while BACS verbal fluency and executive function scores improved following four
weeks L-theanine administration. Reductions in PSQI subscales were greater, and improvement in BACS
verbal fluency, especially letter fluency, was higher during the L-theanine administration, compared
to the placebo, among those who showed poorer baseline functions. These results suggest that four
weeks L-theanine administration has positive eects on stress-related symptoms and cognitive function
in a healthy population. To our knowledge, this is the first study that has examined stress-related
symptoms and cognitive functions simultaneously in healthy adults.
For stress-related symptoms, SDS, STAI-T, and PSQI scores decreased after four weeks L-theanine
administration. These findings are consistent with previous studies in rodents [
6
,
22
27
], acute eects
reported in healthy humans [
31
35
], and chronic eects in patients with MDD [
40
]. Additionally,
this trial suggests, for the first time, that 4 weeks L-theanine administration is eective in improving
stress-related symptoms in healthy adults. The eects on stress-related symptoms were broad among
the symptom indices presented in the study, although a comparison to the placebo administration
somewhat limits the ecacy of L-theanine administration for some sleep disturbance measurements.
For cognitive functions, BACS verbal fluency and executive function scores improved after
four weeks L-theanine administration. These findings are consistent with previous preclinical
Nutrients 2019,11, 2362 9 of 13
studies [
11
,
20
,
21
] and our clinical trial for MDD [
40
], whereas they are inconsistent with the acute
attention-improving eects reported in healthy humans [
28
30
,
36
38
]. Considering the comparison
to the placebo administration, the current study suggests that the score for the BACS verbal fluency,
especially letter fluency, but not the Trail Making Test, Stroop test, or other BACS parameters,
significantly changes in response to the 4 weeks eects of L-theanine. In contrast to our previous
study [
40
], the present study was performed on individuals without clinical depression, which may
have resulted in inconsistency concerning the cognitive-enhancing eects. This is partly consistent
with the finding that the present verbal fluency enhancement occurred in the subgroup in which
cognitive function was poorer at pretreatment.
There was no significant alteration in body mass index or biochemical data after four weeks
L-theanine administration. It should also be noted that there were no significant adverse events,
demonstrating the safety of four weeks of L-theanine administration. Although psychotropic eects
were observed in the current study, four weeks L-theanine administration had no significant eect
on cortisol or immunoglobulin A levels in the saliva or serum, which was inconsistent with previous
studies reporting that salivary cortisol [
34
] and immunoglobulin A [
33
] levels were reduced after
acute L-theanine administration. Considering this inconsistency, the reduction of salivary cortisol
and immunoglobulin A levels may be short term, recoverable eect of L-theanine administration.
As expected, changes in serum L-theanine concentrations were higher in the L-theanine administration
compared to the placebo administration, which validated the compliance of the participants in
this intervention.
L-theanine may act as a partial agonist for the N-methyl-D-aspartate receptor [
5
], resulting
in its four weeks psychotropic (i.e., antidepressant, anxiolytic, sleep aid, and cognitive-enhancing)
eects. The modulation of the monoamine [
14
17
] and glutamic acid and glycine [
18
,
19
] systems
may also contribute to these four weeks psychotropic eects. Hippocampal function may be related
to cognitive-enhancing eects as suggested in our prior studies [
6
,
27
]. In addition to the possible
ecacy in the treatment of clinical depression [
40
], the present study suggests that L-theanine may
be a psychoactive reagent broadly useful to improve mental health in humans. Moreover, our data
support the translational value of L-theanine considering its multiple psychoactive eects which have
been observed in animal studies.
There are several limitations to the study. First, this trial was conducted in a real-world setting and
possible biases (e.g., green or other kind of tea consumption, medicine intake, diet, intake nutrients,
and type of work) were not accounted for, which may rather impact the ecacy of L-theanine in daily
life. Second, only about 20% of symptoms (the PSQI subscales) and cognitive functions (the BACS
verbal fluency, especially letter fluency and executive function) scores showed significant changes after
L- theanine administration compared to the placebo administration, suggesting that the eects are not
large on daily function of the participants. Third, any psychotropic eects of L-theanine may have
been relatively inconspicuous as our participants had no psychiatric disorders, whereas these eects
may be more significant in severe clinical cases. In this context, the study was conducted on a small
population and the number of the participants (n=30) may have been insucient, which is subject
to type II errors, although the sample size had been determined according to the eect size from our
previous study in patients with MDD [
40
]. Finally, one might suspect that a tighter age range and
one sex population may have been more appropriate. However, we had no solid information on any
specific age range or sex in which L-theanine is eective. We therefore included subjects of a relatively
wider range of age and both sexes. Further studies are warranted to confirm the presented eects in
much larger sample size.
5. Conclusions
Stress-related symptom (i.e., depression, anxiety-trait, and sleep) scores decreased and cognitive
function (i.e., verbal fluency and executive function) scores improved after four weeks of L-theanine
administration. The reduction in sleep quality problems (disturbances in sleep latency, sleep disturbance,
Nutrients 2019,11, 2362 10 of 13
and use of sleep medication) was greater in the L-theanine administration compared to the placebo
administration, while verbal fluency, especially letter fluency, was improved in the L-theanine
administration among individuals who showed relatively low performance at pretreatment. Moreover,
L-theanine administration was safe and well complied with. Therefore, L-theanine may be a suitable
nutraceutical ingredient for improving mental conditions in a healthy population.
Supplementary Materials:
The following are available online at http://www.mdpi.com/2072-6643/11/10/2362/s1,
Table S1: Comparisons of BACS score changes between 4 weeks L-theanine and placebo administrations in
participants aged 40 years or more (n=21), Table S2: Body mass index and biochemical data after 4 weeks
L-theanine or placebo administration.
Author Contributions:
S.H. and M.O. (Miho Ota) designed, and H.K. supervised the study. S.O. prepared and
measured salivary samples, supported by S.H. and Z.Y. carried out high performance liquid chromatography
analysis to measure L-theanine concentration. M.O. (Makoto Ozeki) provided information about L-theanine and
critical comments on the manuscript. I.I. was involved in the recruitment of the participants. S.H. evaluated
stress-related symptoms and cognitive functions. S.H. performed statistical analyses and wrote the manuscript.
All authors read and approved the final version of the manuscript.
Funding: This study was supported by funding received from Taiyo Kagaku Co., Ltd., Mie, Japan.
Acknowledgments:
We thank Jun Ogura for anonymizing data to protect personal information. We also thank
Yuuki Yokota, Moeko Hiraishi, and Junko Matsuo for their assistance in the recruitment and clinical assessments
of the participants. This paper was proofread by a native medical editor who the manuscript at the Editage Co.,
Ltd., Tokyo, Japan.
Conflicts of Interest:
Yasukawa Z. and Ozeki M. are employees of Taiyo Kagaku Co., Ltd. which supplied the
L-theanine and placebo tablets used in this trial.
References
1.
Vuong, Q.V. Epidemiological evidence linking tea consumption to human health: A review. Crit. Rev. Food
Sci. Nutr. 2014,54, 523–536. [CrossRef]
2.
Saeed, M.; Naveed, M.; Arif, M.; Kakar, M.U.; Manzoor, R.; El-Hack, M.E.A.; Alagawany, M.; Tiwari, R.;
Khandia, R.; Munjal, A.; et al. Green tea (Camellia sinensis) and l-theanine: Medicinal values and beneficial
applications in humans—A comprehensive review. Biomed. Pharmacother. 2017,95, 1260–1275. [CrossRef]
3.
Sharma, E.; Joshi, R.; Gulati, A. l-theanine: An astounding sui generis integrant in tea. Food Chem.
2018
,242,
601–610. [CrossRef]
4.
Kakuda, T. Neuroprotective eects of theanine and its preventive eects on cognitive dysfunction. Pharmacol.
Res. 2011,64, 162–168. [CrossRef]
5.
Sebih, F.; Rousset, M.; Bellahouel, S.; Rolland, M.; de Ferreira, M.C.J.; Guiramand, J.; Cohen-Solal, C.;
Barbanel, G.; Cens, T.; Abouazza, M.; et al. Characterization of l-theanine excitatory actions on hippocampal
neurons: Toward the generation of novel N-Methyl-d-aspartate receptor modulators based on its backbone.
ACS Chem. Neurosci. 2017,8, 1724–1734. [CrossRef]
6.
Wakabayashi, C.; Numakawa, T.; Ninomiya, M.; Chiba, S.; Kunugi, H. Behavioral and molecular evidence
for psychotropic eects in l-theanine. Psychopharmacology 2012,219, 1099–1109. [CrossRef]
7.
Cooper, R. Green tea and theanine: Health benefits. Int. J. Food Sci. Nutr.
2012
,63 (Suppl. 1), 90–97.
[CrossRef]
8.
Mancini, E.; Beglinger, C.; Drewe, J.; Zanchi, D.; Lang, U.E.; Borgwardt, S. Green tea eects on cognition,
mood and human brain function: A systematic review. Phytomedicine 2017,34, 26–37. [CrossRef]
9.
Camfield, D.A.; Stough, C.; Farrimond, J.; Scholey, A.B. Acute eects of tea constituents l-theanine, caeine,
and epigallocatechin gallate on cognitive function and mood: A systematic review and meta-analysis. Nutr.
Rev. 2014,72, 507–522. [CrossRef]
10.
Einother, S.J.; Martens, V.E. Acute eects of tea consumption on attention and mood. Am. J. Clin. Nutr.
2013
,
98, 1700S–1708S. [CrossRef]
11.
Nathan, P.J.; Lu, K.; Gray, M.; Oliver, C. The neuropharmacology of l-theanine(N-ethyl-l-glutamine):
A possible neuroprotective and cognitive enhancing agent. J. Herb. Pharmacother.
2006
,6, 21–30. [CrossRef]
12.
Kimura, R.; Murata, T. Influence of alkylamides of glutamic acid and related compounds on the central
nervous system. I. Central depressant eect of theanine. Chem. Pharm. Bull.
1971
,19, 1257–1261. [CrossRef]
Nutrients 2019,11, 2362 11 of 13
13.
Terashima, T.; Takido, J.; Yokogoshi, H. Time-dependent changes of amino acids in the serum, liver, brain
and urine of rats administered with theanine. Biosci. Biotechnol. Biochem. 1999,63, 615–618. [CrossRef]
14.
Yokogoshi, H.; Terashima, T. Eect of theanine, r-glutamylethylamide, on brain monoamines, striatal
dopamine release and some kinds of behavior in rats. Nutrition 2000,16, 776–777. [CrossRef]
15.
Yokogoshi, H.; Mochizuki, M.; Saitoh, K. Theanine-induced reduction of brain serotonin concentration in
rats. Biosci. Biotechnol. Biochem. 1998,62, 816–817. [CrossRef]
16.
Yokogoshi, H.; Kobayashi, M.; Mochizuki, M.; Terashima, T. Eect of theanine, r-glutamylethylamide, on
brain monoamines and striatal dopamine release in conscious rats. Neurochem. Res.
1998
,23, 667–673.
[CrossRef]
17.
Kimura, R.; Murata, T. Eect of theanine on norepinephrine and serotonin levels in rat brain. Chem. Pharm.
Bull. 1986,34, 3053–3057. [CrossRef]
18.
Yamada, T.; Terashima, T.; Okubo, T.; Juneja, L.R.; Yokogoshi, H. Eects of theanine, r-glutamylethylamide,
on neurotransmitter release and its relationship with glutamic acid neurotransmission. Nutr. Neurosci.
2005
,
8, 219–226. [CrossRef]
19.
Yamada, T.; Terashima, T.; Kawano, S.; Furuno, R.; Okubo, T.; Juneja, L.R.; Yokogoshi, H. Theanine,
γ
-glutamylethylamide, a unique amino acid in tea leaves, modulates neurotransmitter concentrations in the
brain striatum interstitium in conscious rats. Amino Acids 2009,36, 21–27. [CrossRef]
20.
Tamano, H.; Fukura, K.; Suzuki, M.; Sakamoto, K.; Yokogoshi, H.; Takeda, A. Preventive eect of theanine
intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.
Brain Res. Bull. 2013,95, 1–6. [CrossRef]
21.
Takeda, A.; Tamano, H.; Suzuki, M.; Sakamoto, K.; Oku, N.; Yokogoshi, H. Unique induction of CA1 LTP
components after intake of theanine, an amino acid in tea leaves and its eect on stress response. Cell. Mol.
Neurobiol. 2012,32, 41–48. [CrossRef]
22.
Unno, K.; Iguchi, K.; Tanida, N.; Fujitani, K.; Takamori,N.; Yamamoto, H.; Ishii, N.; Nagano, H.; Nagashima,T.;
Hara, A.; et al. Ingestion of theanine, an amino acid in tea, suppresses psychosocial stress in mice. Exp.
Physiol. 2013,98, 290–303. [CrossRef]
23.
Tian, X.; Sun, L.; Gou, L.; Ling, X.; Feng, Y.; Wang, L.; Yin, X.; Liu, Y. Protective eect of l-theanine on chronic
restraint stress-induced cognitive impairments in mice. Brain Res. 2013,1503, 24–32. [CrossRef]
24.
Yin, C.; Gou, L.; Liu, Y.; Yin, X.; Zhang, L.; Jia, G.; Zhuang, X. Antidepressant-like eects of l-theanine in the
forced swim and tail suspension tests in mice. Phytother. Res. 2011,25, 1636–1639. [CrossRef]
25.
Unno, K.; Fujitani, K.; Takamori, N.; Takabayashi, F.; Maeda, K.; Miyazaki, H.; Tanida, N.; Iguchi, K.;
Shimoi, K.; Hoshino, M. Theanine intake improves the shortened lifespan, cognitive dysfunction and
behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic. Res.
2011
,45,
966–974. [CrossRef]
26.
Takarada, T.; Nakamichi, N.; Kakuda, T.; Nakazato, R.; Kokubo, H.; Ikeno, S.; Nakamura, S.; Hinoi, E.;
Yoneda, Y. Daily oral intake of theanine prevents the decline of 5-bromo-2
0
-deoxyuridine incorporation in
hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with
severe traumatic stress. J. Pharmacol. Sci. 2015,127, 292–297. [CrossRef]
27.
Ogawa, S.; Ota, M.; Ogura, J.; Kato, K.; Kunugi, H. Eects of l-theanine on anxiety-like behavior, cerebrospinal
fluid amino acid profile, and hippocampal activity in Wistar Kyoto rats. Psychopharmacology
2017
. [CrossRef]
28.
Gomez-Ramirez, M.; Kelly, S.P.; Montesi, J.L.; Foxe, J.J. The eects of l-theanine on alpha-band oscillatory
brain activity during a visuo-spatial attention task. Brain Topogr. 2009,22, 44–51. [CrossRef]
29.
Nobre, A.C.; Rao, A.; Owen, G.N. l-theanine, a natural constituent in tea, and its eect on mental state. Asia
Pac. J. Clin. Nutr. 2008,17 (Suppl. 1), 167–168.
30.
Gomez-Ramirez, M.; Higgins, B.A.; Rycroft, J.A.; Owen, G.N.; Mahoney, J.; Shpaner, M.; Foxe, J.J. The
deployment of intersensory selective attention: A high-density electrical mapping study of the eects of
theanine. Clin. Neuropharmacol. 2007,30, 25–38. [CrossRef]
31.
Turkozu, D.; Sanlier, N. l-theanine, unique amino acid of tea, and its metabolism, health eects, and safety.
Crit. Rev. Food Sci. Nutr. 2017,57, 1681–1687. [CrossRef] [PubMed]
32.
Rao, T.P.; Ozeki, M.; Juneja, L.R. In search of a safe natural sleep aid. J. Am. Coll. Nutr.
2015
,34, 436–447.
[CrossRef] [PubMed]
33.
Kimura, K.; Ozeki, M.; Juneja, L.R.; Ohira, H. l-theanine reduces psychological and physiological stress
responses. Biol. Psychol. 2007,74, 39–45. [CrossRef] [PubMed]
Nutrients 2019,11, 2362 12 of 13
34.
White, D.J.; de Klerk, S.; Woods, W.; Gondalia, S.; Noonan, C.; Scholey, A.B. Anti-stress, behavioural
and magnetoencephalography eects of an l-theanine-based nutrient drink: A randomised, double-blind,
placebo-controlled, crossover trial. Nutrients 2016,8, 53. [CrossRef] [PubMed]
35.
Unno, K.; Tanida, N.; Ishii, N.; Yamamoto, H.; Iguchi, K.; Hoshino, M.; Takeda, A.; Ozawa, H.; Ohkubo, T.;
Juneja, L.R.; et al. Anti-stress eect of theanine on students during pharmacy practice: Positive correlation
among salivary α-amylase activity, trait anxiety and subjective stress. Pharmacol. Biochem. Behav. 2013,111,
128–135. [CrossRef]
36.
Foxe, J.J.; Morie, K.P.; Laud, P.J.; Rowson, M.J.; de Bruin, E.A.; Kelly, S.P. Assessing the eects of caeine
and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology
2012
,62,
2320–2327. [CrossRef] [PubMed]
37.
Kahathuduwa, C.N.; Dassanayake, T.L.; Amarakoon, A.M.T.; Weerasinghe, V.S. Acute eects of theanine,
caeine and theanine-caeine combination on attention. Nutr. Neurosci.
2017
,20, 369–377. [CrossRef]
[PubMed]
38.
Kahathuduwa, C.N.; Dhanasekara, C.S.; Chin, S.H.; Davis, T.; Weerasinghe, V.S.; Dassanayake, T.L.; Binks, M.
l-theanine and caeine improve target-specific attention to visual stimuli by decreasing mind wandering: A
human functional magnetic resonance imaging study. Nutr. Res. 2018,49, 67–78. [CrossRef]
39.
Lardner, A.L. Neurobiological eects of the green tea constituent theanine and its potential role in the
treatment of psychiatric and neurodegenerative disorders. Nutr. Neurosci. 2014,17, 145–155. [CrossRef]
40.
Hidese, S.; Ota, M.; Wakabayashi, C.; Noda, T.; Ozawa, H.; Okubo, T.; Kunugi, H. Eects of chronic l-theanine
administration in patients with major depressive disorder: An open-label study. Acta Neuropsychiatr.
2017
,
29, 72–79. [CrossRef]
41.
Faul, F.; Erdfelder, E.; Lang, A.G.; Buchner, A. G*Power 3: A flexible statistical power analysis program for
the social, behavioral, and biomedical sciences. Behav. Res. Methods
2007
,39, 175–191. [CrossRef] [PubMed]
42.
Faul, F.; Erdfelder, E.; Buchner, A.; Lang, A.G. Statistical power analyses using G*Power 3.1: Tests for
correlation and regression analyses. Behav. Res. Methods 2009,41, 1149–1160. [CrossRef] [PubMed]
43.
Sheehan, D.V.; Lecrubier, Y.; Sheehan, K.H.; Amorim, P.; Janavs, J.; Weiller, E.; Hergueta, T.; Baker, R.;
Dunbar, G.C. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation
of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry
1998
,59 (Suppl.
20), 22–33.
44.
Otsubo, T.; Tanaka, K.; Koda, R.; Shinoda, J.; Sano, N.; Tanaka, S.; Aoyama, H.; Mimura, M.; Kamijima, K.
Reliability and validity of Japanese version of the Mini-International Neuropsychiatric Interview. Psychiatry
Clin. Neurosci. 2005,59, 517–526. [CrossRef] [PubMed]
45.
American Psychiatric Association. Diagnostic and Statistical Manual Mental Disorders 5th Edition Text Revision;
American Psychiatric Publication: Arlington, VA, USA, 2013.
46.
World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for
medical research involving human subjects. JAMA 2013,310, 2191–2194. [CrossRef]
47.
Hopewell, S.; Clarke, M.; Moher, D.; Wager, E.; Middleton, P.; Altman, D.G.; Schulz, K.F.; Group, C. CONSORT
for reporting randomised trials in journal and conference abstracts. Lancet 2008,371, 281–283. [CrossRef]
48.
Ota, M.; Wakabayashi, C.; Matsuo, J.; Kinoshita, Y.; Hori, H.; Hattori, K.; Sasayama, D.; Teraishi, T.; Obu, S.;
Ozawa, H.; et al. Eect of l-theanine on sensorimotor gating in healthy human subjects. Psychiatry Clin.
Neurosci. 2014,68, 337–343. [CrossRef]
49.
De Mejia, E.G.; Ramirez-Mares, M.V.; Puangpraphant, S. Bioactive components of tea: Cancer, inflammation
and behavior. Brain Behav. Immun. 2009,23, 721–731. [CrossRef]
50.
Van der Pijl, P.C.; Chen, L.; Mulder, T.P.J. Human disposition of l-theanine in tea or aqueous solution. J.
Funct. Foods 2010,2, 239–244. [CrossRef]
51.
Zung, W.W.; Richards, C.B.; Short, M.J. Self-rating depression scale in an outpatient clinic: Further validation
of the SDS. Arch. Gen. Psychiatry 1965,13, 508–515. [CrossRef]
52.
Sakamoto, S.; Kijima, N.; Tomoda, A.; Kambara, M. Factor structures of the Zung Self-Rating Depression
Scale (SDS) for undergraduates. J. Clin. Psychol. 1998,54, 477–487. [CrossRef]
53. Spielberg, C.D. STAI Manual; Consulting Psychologists Press: Palo Alto, CA, USA, 1970.
54.
Suzuki, T.; Tsukamoto, K.; Abe, K. Characteristics factor structures of the Japanese version of the State-Trait
Anxiety Inventory: Coexistence of positive-negative and state-trait factor structures. J. Personal. Assess.
2000
,
74, 447–458. [CrossRef] [PubMed]
Nutrients 2019,11, 2362 13 of 13
55.
Buysse, D.J.; Reynolds, C.F., 3rd; Monk, T.H.; Berman, S.R.; Kupfer, D.J. The Pittsburgh Sleep Quality Index:
A new instrument for psychiatric practice and research. Psychiatry Res. 1989,28, 193–213. [CrossRef]
56.
Doi, Y.; Minowa, M.; Uchiyama, M.; Okawa, M.; Kim, K.; Shibui, K.; Kamei, Y. Psychometric assessment
of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in
psychiatric disordered and control subjects. Psychiatry Res. 2000,97, 165–172. [CrossRef]
57.
Bowie, C.R.; Harvey, P.D. Administration and interpretation of the Trail Making Test. Nat. Protoc.
2006
,1,
2277–2281. [CrossRef] [PubMed]
58. Stroop, J.R. Studies of interference in serial verbal reactions. J. Exp. Psychol. 1935,18, 643–662. [CrossRef]
59.
Kaneda, Y.; Sumiyoshi, T.; Keefe, R.; Ishimoto, Y.; Numata, S.; Ohmori, T. Brief assessment of cognition in
schizophrenia: Validation of the Japanese version. Psychiatry Clin. Neurosci. 2007,61, 602–609. [CrossRef]
60.
Keefe, R.S.; Goldberg, T.E.; Harvey, P.D.; Gold, J.M.; Poe, M.P.; Coughenour, L. The Brief Assessment of
Cognition in Schizophrenia: Reliability, sensitivity, and comparison with a standard neurocognitive battery.
Schizophr. Res. 2004,68, 283–297. [CrossRef]
61.
Gardener, M.C.; Gillman, M.P. Analyzing variability in nectar amino acids: Composition is less variable than
concentration. J. Chem. Ecol. 2001,27, 2545–2558. [CrossRef]
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2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... As mentioned previously, L-theanine is one of the main constituents of green tea and is also available in over-thecounter supplements. L-theanine is a non-essential amino acid and acts as a partial agonist at the N-methyl-D-aspartate receptor and as a modulator of glycinergic, glutaminergic, serotonergic, and dopaminergic systems [74]. Large, well-powered human studies are lacking, but existing literature points to L-theanine's role in improving anxiety, depression, insomnia, attention, verbal fluency, and executive function [74][75][76]. ...
... L-theanine is a non-essential amino acid and acts as a partial agonist at the N-methyl-D-aspartate receptor and as a modulator of glycinergic, glutaminergic, serotonergic, and dopaminergic systems [74]. Large, well-powered human studies are lacking, but existing literature points to L-theanine's role in improving anxiety, depression, insomnia, attention, verbal fluency, and executive function [74][75][76]. There are no known hepatoprotective benefits among adults taking L-theanine, and there are also no cases of L-theanine-induced liver toxicity. ...
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Purpose of Review Traditional, complementary, and integrative medicine (TCIM) modalities are widely employed. However, TCIM, specifically herbal and non-herbal dietary supplements, can pose challenges in the context of organ transplantation. In this review, we discuss common supplements used for psychiatric purposes and highlight important considerations for candidates and recipients of liver transplants. Recent Findings Ashwagandha, kava kava, green tea extract, skullcap, turmeric, and valerian have known idiosyncratic hepatotoxic potential and may complicate the liver transplantation course. Multiple supplements reportedly carry a lower risk of hepatotoxicity, though evidence for widespread use in those at risk for or with hepatic impairment is limited. Summary Psychiatrists caring for candidates and recipients of liver transplants must recognize that patients may find supplements helpful in alleviating psychiatric symptoms, despite an overall limited evidence base. Evaluating benefit versus risk ratios and reviewing drug-drug interactions is essential to promote transplant candidacy and mitigate the possibility of native or graft liver dysfunction.
... This beneficial effect is attributed to theanine, a constituent of matcha. A crossover study by Hidese et al. on healthy participants with an average age of 48 years revealed that theanine intake (200 mg/day) for 4 weeks significantly reduced the total PSQI score [44]. As the change in the total score in the matcha group compared with that in the placebo group showed a decreasing trend (P = 0.073), theanine was suggested to improve sleep quality. ...
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Objective Lifestyle habits after middle age significantly impact the maintenance of cognitive function in older adults. Nutritional intake is closely related to lifestyle habits; therefore, nutrition is a pivotal factor in the prevention of dementia in the preclinical stages. Matcha green tea powder (matcha), which contains epigallocatechin gallate, theanine, and caffeine, has beneficial effects on cognitive function and mood. We conducted a randomized, double-blind, placebo-controlled clinical study over 12 months to examine the effect of matcha on cognitive function and sleep quality. Methods Ninety-nine participants, including 64 with subjective cognitive decline and 35 with mild cognitive impairment were randomized, with 49 receiving 2 g of matcha and 50 receiving a placebo daily. Participants were stratified based on two factors: age at baseline and APOE genotype. Changes in cognitive function and sleep quality were analyzed using a mixed-effects model. Results Matcha consumption led to significant improvements in social acuity score (difference; -1.39, 95% confidence interval; -2.78, 0.002) (P = 0.028) as evaluated by the perception of facial emotions in cognitive function. The primary outcomes, that is, Montreal Cognitive Assessment and Alzheimer’s Disease Cooperative Study Activity of Daily Living scores, showed no significant changes with matcha intervention. Meanwhile, Pittsburgh Sleep Quality Index scores indicated a trend toward improvement with a difference of 0.86 (95% confidence interval; -0.002, 1.71) (P = 0.088) between the groups in changes from baseline to 12 months. Conclusions The present study suggests regular consumption of matcha could improve emotional perception and sleep quality in older adults with mild cognitive decline. Given the widespread availability and cultural acceptance of matcha green tea, incorporating it into the daily routine may offer a simple yet effective strategy for cognitive enhancement and dementia prevention.
... Conversely, research on functional ingredients in foods has reported that several food ingredients (GABA, theanine, rosmarinic acid, and so on) contribute to mental health improvement, reduced mental stress, diminished negative mood, and improved motivation. They might also be useful for improving daily mood status [5][6][7][8]. ...
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... l-theanine supplementation has been shown to reduce the physiological impact of stressors among human participants (hidese et al., 2019;Yamada et al., 2005;Yokogoshi et al., 1998;Yoto et al., 2012). supplementation with l-theanine (~200mg/day) has been shown to reduce heart rate and concentrations of salivary secretory immunoglobulin a (siga) in response to acute stress (Kimura et al., 2007). ...
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... SAS consists of 20 items and uses the Likert 4-point scale to assess the frequency of symptoms, Cronbach's α= 0.80 (10). SDS was proposed to assess the patient depression levels in 1965 by W.K.Zung (11). Depression index less than 0.50 is no depression, 0.50 to 0.59 is mild depression, 0.60 to 0.69 is moderate to severe depression, and 0.70 or more is severe depression. ...
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Relevance. Chronic insomnia is one of the most common forms of nighttime sleep disorders. It leads to a decrease in human performance, the development of social maladjustment, and even changes in the personal sphere. Chronic insomnia can become a trigger for decompensation of somatic, neurological and mental diseases, which determines the need to find ways to overcome it. Objective. To determine the efficacy and safety of the dietary supplement Alpha-Melatonin Relax in the treatment of chronic insomnia in patients with chronic cerebral ischemia. Materials and methods. The study involved 30 patients (18 women and 12 men) with chronic cerebral ischemia of stage I and II, the average age of which was 46.12 ± 4.98 years. The course of treatment consisted of 30 days of taking Alpha-Melatonin Relax, 1–2 tablets 30–60 minutes before bedtime. Clinical and neurological symptoms were assessed and tested using the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Daytime Sleepiness Scale, and the Hospital Anxiety and Depression Scale (HADS) in dynamics. Results and their discussion. The study results showed that 30-day administration of Alpha-Melatonin Relax provided a significant p≤0.05 improvement in the subjective assessment of the quality of night sleep, a decrease in the time to fall asleep, an increase in sleep duration, a decrease in the severity of emotional disorders and daytime dysfunction. Clinical and neurological follow-up of patients during the treatment course revealed a significant reduction in the severity of chronic insomnia, asthenia, and anxiety-depressive symptoms, which allows us to recommend the use of the dietary supplement Alpha-Melatonin Relax in clinical practice. Conclusions. Based on the data of a clinical-neurological and psychodiagnostic study, the statistically significant effectiveness of the dietary supplement AlphaMelatonin Relax in correcting the symptoms of chronic insomnia in patients with the initial stages of chronic brain ischemia has been proven.
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L-Theanine (or L-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient and environmentally-friendly chemical synthesis of L-Theanine and L-γ-N-propyl-Gln and their corresponding D isomers. L-Theanine, and its derivatives obtained so far, exhibited partial co-agonistic action at N-methyl-D-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons. This activity was retained on NMDA receptors expressed in Xenopus oocytes. In addition, both GluN2A and GluN2B containing NMDA receptors were equally modulated by L-Theanine. The stereochemical change from L-Theanine to D-Theanine along to the substitution of the ethyl for a propyl moiety in the γ-N position of L- and D-Theanine significantly enhanced the biological efficacy, as measured on cultured hippocampal neurons. L-Theanine structure thus represents an interesting backbone to develop novel NMDA receptor modulators.
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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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L-theanine (L-Th), a non-protein amino acid present in tea, is a valuable nutraceutical product with unique health benefits and used as an additive in food industry. L-Th enhances the umami taste but its use is limited due to its inadequate production. Different extraction approaches from tea shoots, chemical synthesis to microbial transformation have been tried to meet its demand. In vitro, in vivo as well as clinical studies have shown its positive effect in regulating CNS disorders. L-Th has become choice ingredient in CNS active products due to its anti-stress and neuroprotective role in dementias particularly in retrogression of Alzheimer's. L-Th biochemically modulates various anti-neoplastic agents by increasing their bioavailability in tumour cells. The review, is an effort to condense the recent research on L-Th highlighting its biological resource, plausible role in tea plant, production approaches, its physiological role on human health and future prospects.
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Background: Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain. Purpose: To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans. Methods: We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement. Outcome: We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9). Conclusions: The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact.
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Objective: l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Methods: Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). Results: HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. Conclusion: Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.
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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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Tea has been a very popular beverage around the world for centuries. The reason that it is delicious, enabling hydration, showing warming and relaxing effect can be mentioned why it is consumed so much in addition to its prominent health effects. Although the catechins and caffeine are the primary bioactive components that are related with the health effects of the tea, the health effects of theanine amino acid, which is a non-proteinic amino acid special to tea, has become prominent in recent years. It has been known that the theanine amino acid in tea has positive effects especially on relaxing, cognitive performance, emotional status, sleep quality, cancer, cardiovascular diseases, obesity and common cold. The results of acute and chronic toxicity tests conducted on the safety of theanine express that L-theanine is reliable in general even if it is consumed too much with diet. However, it is not revealed a clear evidence based result yet regarding theanine metabolism, health effects and its safety. Within this frame, chemical structure of theanine, its bio-synthesis, dietary sources, metabolism, health effects, and safety are discussed in present study.