Suntheanine: A pure and safe L-theanine dietary supplement for relaxation and stress relief

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NUTRACEUTICALS
INTRODUCTION
Ever since the discovery of tea in
China, it spread all over the world
and has been consumed as a
refreshing drink. At present, tea is
consumed as green, oolong, and
black tea, which are originated
from the same plant Camellia
sinensis. Green teas are subject to
minimal oxidation, whereas Oolong and
back teas are allowed to partially and
extensively oxidize respectively. The taste of
all types of teas can be attributed to the
presence of many amino acids, in particular
L-theanine (1) – an abundant free amino
acid. Lately the refreshing or the relaxation
property and many other neurological,
physiological and some of the
pharmacological functions of tea are
attributed to the L-theanine (2).
L-theanine was first discovered in green
tea leaves by Japanese scientists in 1949
(3) and later in other forms of tea (4,5). Its
only other known natural occurrence is in
the edible wild mushroom Xerocomus
badius (6). The chemical nature was
determined as L-glutamic acid-γ-ethylamide
(Figure 1). In 1964, the Japanese Ministry
of Health and Welfare approved L-theanine
as a food additive in all foods except infant
food (7,8). Since then, its popularity has
spread from Japan to Europe, with more
than 50 food products containing
L-theanine available in those two places. In
2000, L-theanine was introduced as a
dietary supplement in the United
States (9).
Like most amino acids, theanine is also
chiral and available in D- and L-enantiomers
(10). The pharmacological effects of one
enantiomer over another may vary
significantly. L-theanine alone, the form in
which it is found in tea, has been proved to
have all the refreshing and beneficial
functions. Suntheanine, a pure L-theanine
enantiomer, the brand name of Taiyo
Kagaku was produced by a patented
L-isomer-specific enzymatic method (11)
and proved to have all the benefits related
to L-theanine.
Among various theanine products in the
market, only Suntheanine meets all the
safety standards and health claims set forth
by the Dietary Supplement Health and
Education Act of 1994 for use as dietary
supplements. Taiyo has implemented strict
quality control systems in the manufacturing
of Suntheanine to ensure the GMP (good
manufacturing practice) regulations of the
US Food and Drug Administration. Above
all, only Suntheanine was thoroughly
studied for its purity and safety, and for its
relaxation effects in several conditions of
humans. Also, animal studies have
confirmed several neurological,
physiological and pharmacological functions
of Suntheanine.
PURITY
Since the introduction of theanine as a
dietary supplement, several commercial
synthesized products are flooding into
market. Theanine when extracted from tea
leaves is predominantly in the L-form, as
opposed to the enantiomeric racemic
combination of L- and D-theanine found in
many synthesized supplements labeled as
L-theanine. Moreover, various research
reports have assigned the refreshing
neurological and physiological functions to
L-theanine. While the functions of
Suntheanine: A pure
and safe L-theanine
dietary supplement
for relaxation and
stress relief
RAO T.P. *
OZEKI M.
JUNEJA L.R.
Taiyo Kagaku Co. Ltd.
1-3 Takaramachi, Yokkaichi
Mie 510-0844 Japan
*Corresponding author
Tel +81-90-4857-3422
tprao@taiyokagaku.co.jp
In the competitive dietary supplement
market for relaxation, many products are
introduced labeled as L-theanine, but the
purity and safety of these compounds are
seldom checked. Suntheanine produced by
a patented L-isomer enzymatic process is
the only pure in its L-enantiomer
composition. An API-MS analysis
confirmed the isomeric composition of
Suntheanine to be L-theanine (>99%).
The safety of Suntheanine has been
thoroughly examined following
international protocols. Various human
studies indicated that Suntheanine is
effective in relieving the stress and
inducing the sense of relaxation during
anxiety, fatigue, physical stress, and PMS.
Suntheanine is also effective promoting
relaxed sleep and refreshed awakening in
humans. Suntheanine is found effective in
improving hypertension, learning
performance, and concentration in
animals. Immune enhancer and anti-
obesity properties are also observed.
ABSTRACT
26 JANUARY/FEBRUARY 2007 NUTRACEUTICALS
Figure 1 – Structure of L-theanine
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D-theanine are unknown, it warrants a
caution to use such synthetic products. A
product with predominant L-theanine is
therefore necessary for the safety and for
all the benefits of theanine.
Suntheanine is prepared by the way it
is synthesized in the tea plant (12,13).
Suntheanine is being produced using a
soil-derived microorganism and the “starter”
ingredients ethylamine and glutamic acid
(two naturally occurring constituents of tea
and the breakdown products of theanine).
This method allowed standardized
production of ultra-pure L-theanine in
commercial scale. The enantiomeric purity
of Suntheanine has been proven to be that
of L-theanine.
Desai and Armstrong (14) established
a method using the Chirobiotic T
(teicoplanin) chiral stationary phase, native
and derivatized theanine enantiomers were
separated and detected via high-
performance liquid chromatography
(HPLC) coupled to atmospheric pressure
ionization mass spectrometry (API-MS).
They evaluated the enantiomeric
composition of six commercially available
L-theanine samples using the above
method and confirmed with photodiode
array detection. Among the six samples,
only Suntheanine has
demonstrated >99%
L-isomer purity (Figure 2).
The other five samples
tested contained a 50-50
(racemic) mix of D- and
L-theanine.
SAFETY
Following the international
protocols, the safety of
Suntheanine has been
evaluated in an acute
toxicity study, a subacute
toxicity study, a chronic
toxicity/carcinogenicity
study and a mutagenicity
study.
28 Day Subacute
Toxicity Study
Healthy male and female
rats (five each) were
administered daily with
2,000 mg of Suntheanine
per kg of body weight for
twenty eight days. The
effects of ingesting
Suntheanine were
evaluated by urine analysis,
hematology, ophthalmic
testing, biochemical tests, a
macro pathology study and
examinations for clinical
symptoms. There were no
observed treatment related
effects.
78 Week Evaluation of Toxicity and
Carcinogenicity of Administration of
L-theanine
Healthy male and female mice (150 each)
were randomly divided, into three groups
of 50 each. After keeping for 2 weeks on
basal feed, they were allowed to consume
freely 5.0%-Suntheanine test feed in first
test group, 2.5%-Suntheanine test feed in
the second test group, and to continue
basal feed in the control group.
Measurements of body weight and feed
consumption volume were performed
periodically on 4-week intervals. The
administration period was set for
78 weeks. Thereafter the surviving
rats were sacrificed and examined
for carcinogenic and pathological
indices in the internal organ and
tissue. The results indicated that
the long-term oral administration of
Suntheanine did not cause any
carcinogenesis or pathogenesis in
any of the organs tested.
Acute Toxicity/LD-50
Determination
LD50 value of Suntheanine was
determined to be more than
5,000 mg/kg. No rat died consuming the
above dose during a 7 day observation
period.
Ames Salmonella/Microsome Plate
Test for Mutagenicity
Suntheanine was found to be
non-mutagenic in the Ames tests
performed.
2 week Dietary Range Finding
Toxicity Study in Rats
Suntheanine was well tolerated up to a
dose of 6500 mg/kg/day in a two-week
study. Assessment of toxicity was based
on mortality, clinical observations, clinical
pathology, organ weights and macroscopic
observations. All animals survived and no
remarkable clinical observations were
observed.
RELAXATION EFFECTS IN
HUMANS
Most people in modern times who live
especially in urban areas are exposed too
much to stress and mental pressures.
Relaxation is the effective way to
overcome these stress and mental
pressures. Suntheanine is effective in
stimulating the sense of relaxation and
refreshness in various stress conditions of
human.
Relaxation from Anxiety
Human brain-wave studies confirm
L-theanine as Suntheanine produces a
state of alert relaxation by generating the
α-brain waves within 30 min from the
administration (1). In one study (15), 50
female volunteers (18-22 years old)
classified into five groups according to
anxiety levels, were given Suntheanine
solution (50-200 mg/100 ml) for
6weeks and the brain waves were
measured after intake. An
electroencephalograph was used to
record four sets of brain waves
(Figure 3): alpha (awake and relaxed),
beta (awake and excited), delta (deep
sound sleep), and theta (drowsy, dozing,
light sleep). The test results were
compared with water placebo. Results
Figure 2 – Enantiomeric composition of Suntheanine
Figure 3 – Classification of brain waves
Figure 4 – Effect of Suntheanine®on emission of
α-waves based on anxiety in women (2)
27
JANUARY/FEBRUARY 2007
NUTRACEUTICALS

showed no alpha waves observed with
the water solution. However, both groups
experienced significant increases in their
alpha waves 30 minutes after
administration of both Suntheanine
solutions, indicating they were in a
relaxed state of mind. The intensity of the
alpha brain wave emissions appeared to
increase in a dose-dependent manner, in
that the 200 mg L-theanine solution
produced more alpha waves than the
50 mg solution, especially in the high-
anxiety group (Figure 4). Moreover, the
levels of theta waves in both groups
remained unchanged during the
observation period for all the test
solutions, indicating that L-theanine did
not induce drowsiness.
A similar brain-wave study (16)
examined the relaxation
effects of Suntheanine
using 15 healthy men (18
to 30 years old). In this
study, the placebo and
Suntheanine (200 mg)
were in the form of tablets
instead of oral solutions.
Despite the different
delivery form, the outcome
confirmed the previous
study’s conclusion that
L-theanine promoted the
alpha power both in frontal
(Figure 5) and occipital
(Figure 6) regions, with the
greatest impact on those
with high anxiety.
Relaxation from
Fatigue
The relaxation and
refreshing effects of
Suntheanine were
evaluated in another
cross over study (17)
with 20 healthy
volunteers (30 to
55 years old), who
experienced constant
tiredness for more than
one month without any
known underlying disease
as the cause. Subjects
were given either a
placebo or test solution
containing 200 mg
Suntheanine for seven
consecutive days. They
were then crossed over
to the opposite treatment
for another week. An EEG
was used to measure
brain waves for one hour
after each administration,
and a fatigue-sensitivity-
scale questionnaire was
given before and after
each seven-day test
period. A significant
increase in alpha power
and decrease in fatigue scores were
observed after a week of taking the
Suntheanine solution (Figure 7). This
results proved the efficiency of
Suntheanine in promoting mental
relaxation and sense of refreshment in
fatigue.
Relaxation from Physical Stress
Relaxation from physical stress with
Suntheanine was examined with 14 non-
smoking healthy male sport-students in a
cross-over study (18). The down
regulation after physical stress in the brain
(measured by EEG-mapping) and in
peripheral hormonal systems (plasma
levels of catecholamines, cortisole,
prolactine, serotonin, measured by HPLC)
was examined. After exhaustive bicycle-
ergometer test the stress model subjects
recovered by lying in a segregated
shaded room. Three test drinks containing
0, 50 or 200 mg Suntheanine were given
in a randomized, double-blind order. EEG-
recordings (closed eyes) and peripheral
hormonal analysis were carried out
directly after exercise (M1) and 30 (M2),
45 (M3), 60 (M4), 120 (M5) min after
the drink.
Suntheanine seemed to accelerate
the normalization of EEG spectral power
in high frequency waves. Qualitative
different behavior trends were found in
frontal-, central-, occipital-regions with
increased alpha 1, theta (frontal) and
decreasing beta relative-power earlier in
recovery with the dose of 200 mg
Suntheanine. These findings were related
to relaxing effects. After ingestion of
Suntheanine, alpha2-, beta1-power at
occipital regions decreased faster (M2) to
placebo recovery levels (M3/M4)
(Figure 8). Also Suntheanine altered the
correlations between EEG spectral power
and some hormones (slow wave
power/some catecholamines except
norepinephrine/delta disappeared and
new correlations with prolactine
appeared). The results suggest that
Suntheanine acts as the switch in the
human brain for the peripheral stress
regulation during the recovery after
physical stress.
Relaxed Sleep and Refreshed
Awakening
Sleep disorders generally associated with
lack of good sleep and refreshed
awakening. The effect of Suntheanine on
sleep disorders was examined using
standardized OSA sleep inventory
questionnaire in 22 volunteers – 13
daytime workers of 25 to 36 years old
and 11 students of 20 to 33 years
old (19). Participants were free of
significant psychopathology, medical
disorders, and central nervous system
active medications as determined by
physical examination, medical history, and
laboratory tests. The study was a
randomized, double-
blind, placebo controlled,
crossover study.
Participants were given
200 mg L-theanine (four
50 mg Suntheanine
tablets) or four placebo
tablets one hour before
bedtime. The study
encompassed two
six-night treatment
periods, with an initial
three-night adaptation
period and a one-day
washout between
crossovers. The
participants were asked
to answer the
Figure 5 – Effect of Suntheanine®on α-power in the frontal
channel of anxiety men
Figure 6 – Effect of Suntheanine®on α-power in the occipital
channel of anxiety men
Figure 7 – Effect of Suntheanine®on α/β-power and fatigue in men
28 JANUARY/FEBRUARY 2007 NUTRACEUTICALS

questionnaire about their state of sleep
and mood upon wakening on each day.
No significant difference in feelings of
daytime sleepiness between the
L-theanine and placebo treatments was
observed, confirming that L-theanine does
not cause drowsiness. However,
compared with the placebo, the
L-theanine treatment did improve sleep
quality, dream quality and sleep onset,
with a noticeable reduction in nighttime
awakenings and nightmares (Figure 9).
Even though sleep time was the same for
both treatments, subjects taking
L-theanine reported a feeling of
prolonged sleep and a significant
decrease in fatigue upon rising. They
awoke feeling refreshed, good-spirited
and more self-confident (Figure 10).
Relaxation from PMS
Premenstrual Syndrome (PMS) in
women often reported to be high
1-2 days prior to menstruation. Typical
symptoms of PMS are generally
categorized as mental, physical and social
symptoms. In a volunteer study (20), the
effect of Suntheanine on PMS was
examined in twenty subjects. The subjects
were treated with tablets containing either
Suntheanine or placebo. Subjects took
two tablets twice a day equal to an
amount of 200 mg Suntheanine per day
for two weeks before the beginning of
their menstrual period. The test duration
consisted of three menstruation cycles.
The first cycle was regarded as the
control, where subjects were randomly
treated with Suntheanine or placebo. In
the second cycle, the subjects were
divided into either Suntheanine or
placebo group and treated accordingly. In
third cycle, the subjects in each group
were treated crossover. Three days prior
to the expected date of the beginning of
each menstruation cycle, the test subjects
were asked to answer Moos’s Menstrual
Distress Questionnaire (MDQ) (21). The
symptoms were ranked in 0 to 3 scales,
where the high score represents severe
symptoms. The survey results indicated
that the subjects administered with
Suntheanine scored low compared to
placebo in both mental and physical
symptoms (Figure 11). These results
suggest that Suntheanine is very effective
in relieving the symptoms of PMS.
Figure 8 – Effect of Suntheanine®on physical stress
Figure 9 – Effect of Suntheanine®on sleep quality.
Quality of Sleep: Sleep latency, sleep induction and its maintain.
Dream: Reduction of nightmares and frequency of dreams.
Figure 10 – Effect of Suntheanine®on mood at awakening
Figure 11 – Effect of Suntheanine®on PMS (MDQ scores)
29
JANUARY/FEBRUARY 2007
NUTRACEUTICALS

30 JANUARY/FEBRUARY 2007 NUTRACEUTICALS
CONCLUSION
Suntheanine, the brand name of Taiyo
Kagaku Co. ltd, Japan, is the pure and
safe L-theanine enantiomer. Suntheanine
has been studied for many years for its
relaxation functions in various human
stress conditions and proven to be
effective in promoting the sense of
relaxation during the anxiety, fatigue,
physical stress, and PMS. It promotes
relaxation without sedation to improve the
quality of sleep and refreshed awakening.
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