L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance.
ABSTRACT Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and electrophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8-14 Hz) activity. We found an increase in hit rate and target discriminability (d') for the combined treatment relative to placebo, and an increase in d' but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral performance on the combined ingestion of these 2 major constituents of tea.
Article: Introduction to the proceedings of the Third International Scientific Symposium on Tea and Human Health: Role of Flavonoids in the Diet.Journal of Nutrition 11/2003; 133(10):3244S-3246S. · 3.92 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.Pharmacology Biochemistry and Behavior 06/2000; 66(1):19-28. · 2.53 Impact Factor
Article: A naturalistic investigation of the effects of day-long consumption of tea, coffee and water on alertness, sleep onset and sleep quality.[show abstract] [hide abstract]
ABSTRACT: The effects of caffeine, especially caffeinated coffee, on human performance have been extensively studied. However, few studies have been naturalistic representations of how tea/coffee is normally consumed in terms of dose and time of consumption. This study investigated the effects of day-long consumption of tea, coffee and water on cognitive and psychomotor performance, and sleep quality at night. Thirty healthy volunteers received equal volume drinks equivalent to either 1 or 2 cups of tea (containing 37.5 mg or 75 mg caffeine), or coffee (75 mg or 150 mg caffeine), or water, in a randomised five-way crossover design. Drinks were administered on four occasions during the day (0900, 1300, 1700 and 2300 hours). A psychometric battery consisting of critical flicker fusion (CFF), choice reaction time (CRT) and subjective sedation (LARS) tests, was administered pre-dose and at frequent time points post-dose. The Leeds Sleep Evaluation Questionnaire (LSEQ) was completed each morning and a wrist actigraph was worn for the duration of the study. Caffeinated beverages maintained CFF threshold over the whole day (P<0.05), independent of caffeine dose or beverage type. During the acute phase of beverage ingestion, caffeine significantly sustained performance compared to water after the first beverage for CFF and subjective sedation (P<0.05), and after the second beverage for the Recognition component of the CRT task (P<0.05). Additionally, there were significant differences between tea and coffee at 75 mg caffeine after the first drink. Compared to coffee, tea produced a significant increase in CFF threshold between 30 and 90 min post-consumption (P<0.01). However, following the second beverage caffeinated coffee at 75 mg significantly improved reaction time (P<0.05), compared to tea at the same dose, for the Recognition component of the CRT task. Caffeinated beverages had a dose dependent negative effect on sleep onset (P<0.001), sleep time (P<0.001) and sleep quality (P<0.001). These results indicate that ingestion of caffeinated beverages may maintain aspects of cognitive and psychomotor performance throughout the day and evening when caffeinated beverages are administered repeatedly. This study also demonstrates that day-long tea consumption produces similar alerting effects to coffee, despite lower caffeine levels, but is less likely to disrupt sleep. Other differences between tea and coffee were more subtle, and require further investigation.Psychopharmacologia 04/2000; 149(3):203-16. · 4.08 Impact Factor
The Journal of Nutrition
Proceedings of the Fourth International Scientific Symposium on Tea and Human Health
L-Theanine and Caffeine in Combination Affect
Human Cognition as Evidenced by Oscillatory
alpha-Band Activity and Attention
Simon P. Kelly, Manuel Gomez-Ramirez, Jennifer L. Montesi, and John J. Foxe*
Cognitive Neurophysiology Laboratory, Nathan S. Kline Institute for Psychiatric Research, Program in Cognitive Neuroscience
and Schizophrenia, Orangeburg, NY 10962 and Program in Cognitive Neuroscience, Department of Psychology, City College
of the City University of New York, New York, NY 10031
Recent neuropharmacological research has suggested that certain constituents of tea may have modulatory effects on
brain state. The bulk of this research has focused on either L-theanine or caffeine ingested alone (mostly the latter) and
has been limited to behavioral testing, subjective rating, or neurophysiological assessments during resting. Here, we
investigated the effects of both L-theanine and caffeine, ingested separately or together, on behavioral and elec-
trophysiological indices of tonic (background) and phasic (event-related) visuospatial attentional deployment. Subjects
underwent 4 d of testing, ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or these treatments
combined. The task involved cued shifts of attention to the left or right visual hemifield in anticipation of an imperative
stimulus requiring discrimination. In addition to behavioral measures, we examined overall, tonic attentional focus as well
as phasic, cue-dependent anticipatory attentional biasing, as indexed by scalp-recorded alpha-band (8–14 Hz) activity. We
found an increase in hit rate and target discriminability (d#) for the combined treatment relative to placebo, and an increase
in d# but not hit rate for caffeine alone, whereas no effects were detected for L-theanine alone. Electrophysiological results
did not show increased differential biasing in phasic alpha across hemifields but showed lower overall tonic alpha power in
the combined treatment, similar to previous findings at a larger dosage of L-theanine alone. This may signify a more
generalized tonic deployment of attentional resources to the visual modality and may underlie the facilitated behavioral
performance on the combined ingestion of these 2 major constituents of tea. J. Nutr. 138: 1572S–1577S, 2008.
In recent years, several potential health benefits of drinking tea
(Camelliasinensis)have cometolightthrough systematic study of
theeffects ofits constituentcompounds (1,2).Although anecdotal
evidence abounds, the psychological and neurophysiological
effects of tea have received relatively little experimental investi-
gation and thus remain unclear. Popular claims have centered on
generalized state changes such as the reduction of stress and
induction of relaxed wakefulness. Psychopharmacological studies
have indeed demonstrated mood effects that support these claims
and have further shown that tea affects elements of cognition
(3,4). Although caffeine (1,3,7-trimethylxanthine) is by far the
constituent most studied, with findings of increased alertness
and speeded reaction time (RT)4predominant (5,6), there
exists evidence that caffeine alone cannot fully account for the
positive effects of tea drinking. Tea has been shown to raise skin
1Published in a supplement to The Journal of Nutrition. Presented at the
conference ‘‘Fourth International Scientific Symposium on Tea and Human
Health,’’ held in Washington, DC at the U.S. Department of Agriculture on
September 18, 2007. The conference was organized by the Tea Council of the
U.S.A. and was cosponsored by the American Cancer Society, the American
College of Nutrition, the American Medical Women’s Association, the American
Society for Nutrition, and the Linus Pauling Institute. Its contents are solely the
responsibility of the authors and do not necessarily represent the official views
of the Tea Council of the U.S.A. or the cosponsoring organizations. Supplement
coordinators for the supplement publication were Lenore Arab, University
of California, Los Angeles, CA and Jeffrey Blumberg, Tufts University, Boston,
MA. Supplement coordinator disclosure: L. Arab and J. Blumberg received
honorarium and travel support from the Tea Council of the U.S.A. for
cochairing the Fourth International Scientific Symposium on Tea and Human
Health and for editorial services provided for this supplement publication;
they also serve as members of the Scientific Advisory Panel of the Tea Council
of the U.S.A.
2Author disclosures: S. P. Kelly, M. Gomez-Ramirez, and J. L. Montesi, no
conflicts of interest; J. J. Foxe received an honorarium and travel support from
the Tea Council of the U.S.A. for speaking at the Fourth International Scientific
Symposium on Tea and Human Health and for preparing this manuscript for
3Supported by a grant from the Lipton Institute of Tea in association with
Unilever Beverages Global Technology Centre in Colworth House, Sharnbrook,
* To whom correspondence should be addressed. E-mail: email@example.com.
4Abbreviations used: C, caffeine-alone condition; d#, discriminability index; EEG,
electroencephalographic; EOG, electro-oculographic; P, placebo condition; RT,
reaction time; T, theanine-alone condition; T1C, combined condition; TSE,
temporal spectral evolution.
0022-3166/08 $8.00 ª 2008 American Society for Nutrition.
at Mt Sinai Sch of Med (JN) Levy Lib on September 17, 2008
temperature to a higher level (7), to increase critical flicker fusion
threshold (4), and to reduce physiological stress responses and
increase relaxation ratings (8) when compared with coffee or
other control beverages matched for caffeine level.
L-Theanine (g-glutamylethylamide), a unique amino acid
present almost exclusively in the tea plant, has recently received
research interest in the neuroscience community with findings of
neuroprotective effects [see Kakuda (9)] and mood effects
indexed both bysubjective self-reports(10)andviapsychological
and physiological responses to stress (11). Using electroenceph-
alographic (EEG) recordings in humans, Kobayashi et al. (12)
and Juneja et al. (13) reported that activity within the alpha
frequency band (8–14 Hz) increased in reaction to L-theanine
ingestion when measured during a state of rest. This was of
interest to the attention community, as the alpha rhythm has long
been known to be sensitive to overall attentional states (i.e.,
intensity aspects such as arousal) (14) and, further, is involved in
the biasing of selective attention (15,16). In intersensory atten-
tion tasks, where the relevant modality is cued ;1 s before a
compound audiovisual target stimulus, parieto-occipital alpha
power in the intervening period is increased for attend-visual
trials relative to attend-auditory trials (15,17). In Gomez-
Ramirez et al. (18), this differential effect of cue information
on anticipatory alpha amplitude was found to be larger on in-
gestion of 250 mg of L-theanine relative to placebo. In addition,
tonic (background) alpha amplitude was relatively decreased for
L-theanine, in apparent contradiction to the findings of Juneja
et al. (13). In a follow-up study, we tested whether an analogous
alpha-mediated attention effect seenin visuospatial attention tasks
(16,19–22) is also affected by L-theanine ingestion (M. Gomez-
Ramirez, S. P. Kelly, J. L. Montesi, and J. J. Foxe, unpublished
results). L-Theanine, at a dosage of 250 mg, was not found to in-
crease the differential effect of attention. However, in a replication
of the previous intersensory attention study (18), overall tonic
alpha was greatly reduced on L-theanine.
An immediate question, given this replication, is whether this
tonic alpha reduction occurs at lower dosages of L-theanine,
closer to the amount ingested through a typical serving of tea. In
the present study, we administered a lower dosage of 100 mg to
address this. Also of critical interest is whether the ingestion of
caffeine, another major component of tea, exerts behavioral
and/or neurophysiological effects during such a demanding
visuospatial attention task, when ingested alone or when
ingested together with L-theanine. Here we present data from
a 4-d experiment using a balanced repeated-measures design,
with subjects receiving either placebo (P), L-theanine alone (T),
caffeine alone (C), or the combination of L-theanine plus caffeine
(T1C) on each day. We assessed effects of treatment with regard
to basic behavioral measures of RT and accuracy [including the
so-called discriminability index (d#), which is independent of
individual detection criteria], and in relation to both tonic and
phasic attentional processes as indexed by alpha power.
Participants. Sixteen (5 female) neurologically normal paid volunteers,
aged between 21 and 40 y (mean 27.5 y), participated in the study. All
subjects provided written informed consent, and the Institutional
Review Board of the Nathan S. Kline Institute for Psychiatric Research
approved the experimental procedures. All subjects reported normal or
corrected-to-normal vision. Four subjects were left-handed. The mean
habitual tea consumption across the subjects was 3.7 cups/wk, and for
coffee, 3.8 cups/wk (;250 mL/cup). Subjects arrived at the laboratory in
the morning between 0900 and 1200 h, having abstained from all
caffeinated beverages for the previous 24 h.
Treatment. The timing of treatment administration relative to testing
was based on published reports of amino acid concentration and plasma
concentration changes over time. L-Theanine concentration has been
found to increase significantly within 1 h after administration in rats, to
continue to increase gradually up to 5 h, and to decrease thereafter, with
complete disappearance evident after 24 h (23). Peak plasma caffeine
concentration is reached between 15 and 120 min postingestion in
humans, with a variable half-life typically between 2.5 and 4.5 h (5).
Accordingly, participants abstained from consuming caffeine for at least
24 h before testing and began experimental task runs 30 min after
ingestion of any given treatment. Subjects underwent 4 d of testing,
ingesting either placebo, 100 mg of L-theanine, 50 mg of caffeine, or
these treatments combined. Subjects were uninformed of the treatment,
which was served in 100 mL of water, with the placebo treatment
consisting only of water. Both theanine and caffeine are tasteless in water
Stimuli and task. Subjectswere seated150 cmfroma CRT monitorand
were instructed to maintain fixation on a central cross (white on midgray
background) at all times. Each trial began with a centrally presented
arrow cue (‘‘S1’’) of 100-ms duration, with equal probability pointing
leftward or rightward toward 1 of 2 bilateral locations centered at a
horizontal distance of 4.2? from the fixation cross and 1.2? above the
horizontal meridian. Each location was marked by 4 dots outlining a
2.4? 3 2.4? square. The cue consisted of a circle of 1? diameter with an
embedded arrow, designed to minimize any sensory effects related to
physical differences between the left and right cues. The colors of the
arrowand circle were red on green for half of the blocks of recording and
green on red for the other half, with the order counterbalanced across
subjects and days of testing. Red and green values were precalibrated for
each subject to be approximately isoluminant by flicker photometry.
Then, 933 ms after cue onset, a second imperative stimulus (‘‘S2’’) was
presented at the left or right marked location (valid or invalid with
respect to cue direction) with equal probability. The S2s (100 ms
duration) consistedof eithera white3 or1 (0.75? 30.75?) embeddedin
a circular array of 8 small circles such that the overall stimulus diameter
was 1.95?. The target stimulus was chosen randomly at the beginning of
each experimental run of ;4.5 min, and thereafter standard and target
stimuli were equally likely on each trial. Subjects were instructed to shift
their attention covertly to the location indicated by the cue, to respond
by pressing a mouse button with the index finger of the right hand when
a target S2 appeared on that side, and to ignore stimuli appearing on the
invalid side entirely. Trials were separated by a 1633-ms interval. A total
of 100 trials were presented per run. Subjects completed 20 runs on each
day of testing.
Data acquisition. Continuous EEG data, digitized at 512 Hz, were
acquired from 164 scalp electrodes and 4 electro-oculographic (EOG)
electrodes with a pass-band of 0.05–100 Hz. Off-line, the data were low-
pass filtered up to 45 Hz and rereferenced to the nasion. Noisy channels,
identified by taking the SD of amplitude over the entire run (from first to
last stimulus presented) and checking whether it is .50% greater than
that of at least 3 of the 6 closest surrounding channels,were interpolated.
Horizontal EOG data were recorded using 2 electrodes placed at the
outer canthi of the eyes, allowing measurement of eye movements during
testing. Based on a calibrated mapping of EOG amplitude to visual
angle, trials were rejected off-line if eye gaze deviated by .0.5? during
the cue-target interval.
Behavioral data analysis. We employed a d# as our principal per-
formance metric, taking into account the accuracy of responding on
nontargets as well as targets and controlling for individual differences
in detection criteria. The value of d# was derived from the hit rate
(proportion of all valid targets detected) and false alarm rate (proportion
of all valid nontargets incorrectly responded to), calculated only from
trials containing no eye movements or artifacts. Ceiling effects on hit rate
were corrected in the standard way by assuming 0.5 misses, andsimilarly,
a floor effect of zero false alarms was corrected to 0.5. RTwas measured
as the time (in milliseconds) from the point of S2 onset at which the
mouse button was correctly pressed in response to valid target trials.
L-Theanine, caffeine, and visuospatial attention1573S
at Mt Sinai Sch of Med (JN) Levy Lib on September 17, 2008
To control for the potential confound of practice effects on the
behavioral data, the order of treatments across the 4 d of testing was
fully counterbalanced across subjects. This is a standard procedure and
ensures unbiased comparison across conditions. However, in the case of
the present data, the variance in behavioral measures arising from the
day of testing (order effect) far superseded that arising from treatment.
Thus, a normalization of these measures was necessary to remove the
variance caused by practice, and this was carried out by transforming
each data point to a z-score with respect to the mean and SD of all scores
measured on that day (d 1, d 2, d 3, d 4). Because the distribution of
scores for each day contains an equal number of data points from each
treatment, it cannot resultin any bias for treatmentbut, rather, optimizes
statistical power to test for treatment effects.
Electrophysiological data analysis. EEG data were epoched from
2300 ms before to 1100 ms after cue onset and baseline-corrected
relative to the interval 2100 to 0 ms, with an artifact rejection threshold
of 6100 mV applied. Mean alpha amplitude was calculated using the
temporal spectral evolution (TSE) technique (15). TSE is carried out
simply by filtering each epoch with a passband of 8–14 Hz, rectifying,
then averaging across trials. The averaged TSE waveforms were then
smoothed by averaging data points within a sliding 100-ms window.
The first analysis concerned tonic (background) alpha amplitude,
which was found to decrease on L-theanine in our previous 2 studies
(18, M. Gomez-Ramirez, S. P. Kelly, J. L. Montesi, and J. J. Foxe,
unpublished results). Tonic alpha was measured as the integrated TSE
amplitude within the baseline period 2200 to 0 before the cue stimulus,
regardless of the direction of attentional deployment (i.e., to the left or
right hemifield). The dependent measure was computed as the baseline
alpha amplitude averaged across 6 electrodes, chosen on the basis of the
grand-average scalp distribution of alpha amplitude, collapsed across
the 4 d.
In a second analysis, we tested lateralized, anticipatory alpha ampli-
tude for effects of attention and possible interactions with treatment.
We normalized alpha amplitude relative to baseline by dividing the TSE
amplitude by the mean amplitude within the baseline interval (2200 to
0) and log-transforming, making the measure equivalent to a percentage
change from baseline. This narrows down the analysis to attention-
related differential activity, independent of tonic effects. The anticipa-
tory alpha dependent measure was computed as the integrated TSE
amplitude over the postcue interval500 to 900 ms, ending just before the
S2. Amplitude was averaged across 6 electrodes over each hemisphere,
determined based on grand-average difference topographies (cue-left
minus cue-right) collapsed across the 4 d.
Statistical methods. A 4-d balanced repeated-measures design was
employed, with subjects receiving 1 of the 4 treatments (including
placebo) on each day in counterbalanced order. SPSS for Windows
(version 12.0) was used for all statistical analyses. Tests were conducted
with an a level of 0.05 unless otherwise stated. In the analysis of
behavioral data, we tested specifically for improvements in performance
as a result of any of the 3 treatments. Thus, 1-tailed, paired t-tests (df ¼
15) were conducted between the placebo condition and each of the 3
treatments for hit rate, RT, and d# measures. Because 3 t-tests were
performed including the same placebo data, we applied a Bonferroni-
corrected a-level of 0.016 here.
To test for effects of tonic alpha amplitude, a 1-way ANOVA was
carried out with the factor of treatment having the levels P, T, C, and
T1C. Follow-up protected t tests were then conducted to unpack
significant differences existing between each of the T, C, and T1C
conditions and the P condition. Further post hoc paired comparisons
among the 4 treatment conditions were conducted as appropriate
through additional t-tests.
To test for effects on pretarget alpha amplitude a 4 3 2 32 ANOVA
was carried out with factors of treatment (P, T, C, T1C), attention
(cue-left, cue-right), and hemisphere (left, right). To unpack a potential
3-way interaction, we reduced the alpha cueing effect (typically seen as
a hemisphere 3 attention interaction) to a single measure by adding the
differential over the 2 hemispheres, i.e., subtracting cue-right from cue-
left on the left hemisphere, subtracting cue-left from cue-right on the
right hemisphere, and summing these 2 values. Thus reduced, testing of
treatment effects on the alpha cueing effect, as found in the analogous
intersensory study of Gomez-Ramirez et al. (18), could be done via
paired t-tests comparing each of the 3 treatments T, C, and T1C
Behavioral performance. Behavioral performance was signif-
icantly improved on the combined treatment (T1C) in terms of
hit rate (P , 0.016) and d# (P , 0.002). There was also a sig-
nificant improvement in d# on C compared with P (P , 0.016),
but not in hit rate. There were no significant effects of L-theanine,
and no effects of any of the 3 treatments on RT (Fig. 1).
Electrophysiology. There was a significant effect of treatment
on tonic alpha amplitude (P , 0.02). Follow-up t-tests revealed
that alpha was significantly lower for T1C than P (P , 0.02).
panel), mean d# (middle panel), and mean RT (lower panel) when
subjects ingested placebo (P), L-theanine (T), caffeine (C), or these
treatments combined (T1C). Values are means (n ¼ 16). Asterisks
indicate difference from P: *P , 0.05, **P , 0.01).
Mean hit rate (proportion of targets detected) (upper
at Mt Sinai Sch of Med (JN) Levy Lib on September 17, 2008
P did not differ from either T or C (see Fig. 2). Tonic alpha
differed between T1C and T (P , 0.005) but not between T1C
The typical alpha cueing effect was readily apparent in both
the nonnormalized alpha amplitude waveforms and normalized
pretarget measures (Fig. 3) for each treatment day. A strong
attention 3 hemisphere interaction (P , 0.0005) was found on
the pretarget anticipatory alpha measures as expected, reflecting
the typically observed alpha-mediated cueing effect. In addition,
there was a significant 3-way interaction among treatment, at-
tention, and hemisphere (P , 0.05). When we reduced the alpha
cueing effect to a single metric as described above, the effect
was smaller on C than P (P , 0.02) but did not differ for the
T or T1C conditions.
This study was aimed at extending our knowledge of the effects
of compounds contained in tea on the cognitive function of
attention. Testing relatively low-dosage treatments of L-theanine
alone (100 mg), caffeine alone (50 mg), and their combination,
we observed an interesting pattern of effects for both behavioral
and electrophysiological measures. Whereas no behavioral ef-
fects on hit rate were apparent for either treatment alone at the
low dosages tested here, when both L-theanine and caffeine were
ingested together, hit rate underwent an enhancement of ;3%.
In terms of d#, improvements were seen for both caffeine alone
and L-theanine plus caffeine, the latter having a larger effect size
(0.55 vs. 0.42 calculated as Cohen’s d). Given the absence of any
difference in hit rate for caffeine, the d# effect must result from
subjects making fewer false alarms on caffeine.
Tonic alpha amplitude was not found to decrease signifi-
cantly on the lower dosage of L-theanine. This indicates that the
effect is dose dependent because a drop was seen in both of our
previous studies using a 250-mg dosage (18, M. Gomez-Ramirez,
S. P. Kelly, J. L. Montesi, and J. J. Foxe, unpublished results).
There was, however, a significant decrease in tonic alpha for
the combined treatment. That this decrease marks a synergy be-
tween the 2 compounds is suggested by the numerical difference
in the alpha decrease caused by L-theanine with and without
caffeine (Fig. 2). That is, it seems unlikely that the greater
decrease on the combined treatment is simply a linear sum of the
decreases from each compound alone. Because only single
dosages of each compound were tested, however, a fair degree of
caution is appropriate in the interpretation of synergy at this
juncture. This study marks the third finding of decreased alpha
as a result of L-theanine ingestion (albeit a partial cause here) to
date, demonstrating the reliability of the effect. At this point, the
question of whether it translates to an improved functional brain
state requires serious consideration. Should the finding of a
decrease be received with positive connotations for health and/
or mental capabilities?
In the 80 y since the discovery of alpha waves (24), alpha has
been measured in almost any experimental situation and human
population, with significant effects abounding, but with a
complicated picture and quite disparate theoretical frameworks
arising (25–26). A consistent principle appears to be that
baseline tonic alpha measure was derived (upper panel). Cue-left and
cue-right trials are collapsed. Integrated amplitude over the baseline
period for each treatment, with significant difference from placebo
marked with an asterisk (lower panel). The electrodes from which
tonic alpha measures were derived are marked on the 168-channel
TSE waveforms at midline electrodes from which the
hemispheres, with cue-left (solid) and cue-right (dashed) super-
imposed, collapsed across treatment. The overall alpha-mediated
spatial cueing effect is highlighted. Electrode sites for cueing effect
measurement are marked on the montage. (Lower panel) Normalized
alpha measures forming the dependent variable in tests for effects of
treatment on the alpha cueing effect (P, placebo; T, L-theanine; C,
caffeine; T1C, combined).
(Upper panel) TSE waveforms over left and right
L-Theanine, caffeine, and visuospatial attention1575S
at Mt Sinai Sch of Med (JN) Levy Lib on September 17, 2008
stronger alpha infers positive functioning across individuals
(27,28), whereas phasic changes within individuals reflect
immediate stimulus processing and anticipatory enhancement
and/or suppression, with a greater retinotopically specific
decrease in alpha being predictive of better detection perfor-
mance (21). The tonic depression of alpha during task perfor-
mance over the day of testing, as observed here, is neither an
individual trait nor a phasic event-related response but a lasting,
tonic treatment effect, making it difficult to draw comparisons
with such previous studies. The finding of increased alpha on
ingestion of theanine has previously been taken to indicate
increased relaxation without increased drowsiness (13). But this
qualification appears tenuous in light of other observations of
treatment-related increased alpha, e.g., during marihuana-
induced euphoria (29). Can ‘‘good’’ and ‘‘bad’’ really be ascribed
to increases and decreases in alpha, in whatever direction?
Certainly, that this treatment-related decrease in tonic alpha
does not have negative implications is suggested, if not already
by the fact that tea has been keenly, routinely consumed for
centuries, by the concomitant facilitation in behavioral perfor-
mance found here in terms of both hit rate and d#.
Previous studies have reported a drop in absolute alpha
power during resting with eyes open on ingestion of caffeine at
higher dosages, e.g., 200 mg (30) and 400 mg (31). Although
alpha amplitude was numerically lower on 50 mg of caffeine
alone here, this did not reach significance (P ¼ 0.18). From this,
it is clear that alpha effects of both L-theanine and caffeine are
dose dependent, demonstrating that full characterization of
dose-response functions in future studies is called for.
Evidence of a synergistic relationship between L-theanine and
caffeine has been presented in recent behavioral studies. Parnell
et al. (32) reported improved speed and accuracy on an
attention-switching task at 60 min and reduced susceptibility
to distracting information during a memory task at both 60 and
90 min following ingestion of a combination of L-theanine and
caffeine in the same dosages as used here. Haskell et al. (33)
administered a large battery of cognitive tests before and after
consumption of a drink containing either placebo, 250 mg of
L-theanine, 150 mg of caffeine, or their combination. These
authors found improvements in simple and numeric working
memory RT, sentence verification accuracy, and alertness ratings
for the combined treatment but not for either treatment alone.
Using a similar crossover design but with a greater dosage of
caffeine (250 mg) than L-theanine (200 mg), Rogers et al. (34)
found that L-theanine tended to counteract the caffeine-induced
rise in blood pressure but did not interact with caffeine-induced
increases in either alertness or ‘‘jitteriness’’ on state anxiety
scales. Although the measures examined in these investigations
and our study are quite distinct in nature, an emerging pos-
sibility is that the presence of synergistic effects closely hinges
on dosages. That is, it may be that theanine was not effective in
augmenting the caffeine-induced effects in Rogers et al. (34)
because these were present at a saturated level. In the present
study, lower dosages were used, and a significant drop in tonic
alpha was observed for L-theanine and caffeine ingested together
but not for either L-theanine or caffeine when ingested alone.
However, the absence of a significant difference between the
ing strong claims of synergy at this point.
Similar to our previous visuospatial attention study (M.
Gomez-Ramirez, S. P. Kelly, J. L. Montesi, and J. J. Foxe,
unpublished results), we did not find any change in the alpha
differential cueing effect for the L-theanine-alone treatment.
However, it is interesting that the cueing effect was found to be
smaller on caffeine alone but not for the combined treatment.
This result was unexpected and thus will bear replication and
further investigation. For now, it appears that within visual
space, attentional biasing as indexed by alpha amplitude is not
affected by L-theanine. In contrast, the cued biasing of attention
between sensory modalities does appear to be affected (18). A
tentative interpretation of the current pattern of results is that
L-theanine works to enhance the tonic apportionment of
attentional resources to the visual modality and does so to a
significant degree when a large dosage is ingested by itself or in
combination with caffeine when a smaller dosage is ingested.
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