Below is the clinical studies based on L-Theanine.

L-Theanine, SunTheanine Studies

Korean J Nutrition 36(9): 918-923 2003

Effects of Theanine on the Release of Brain Alpha Wave in Adult Males

Song, Chan Hee; Jung, Ju Hae, Oh, Je Sung; Kim, Kyug Soo

Department of Family Medicine, Obesity Clinic, St. Mary 's Hospital, The Catholic University of Korea, Seoul, 150-713 Korea

Abstract:

L-theanine is an amino acid in green tea and has been known to decrease serotonin and increase norepinephrine in rat brains, and also reported to produce mental relaxation, lower blood pressure and improve learning ability in human beings. But, few studies on these effects for human beings have been conducted so far. This study was conducted to evaluate the effect of L-theanine on the release of brain alpha waves known to be related with mental relaxation and concentration. Twenty healthy male volunteers aged 18 to 30 years without any physical and psychological diseases were recruited through written advertisement. Alpha power values of EEG as a surrogate marker of mental relaxation and concentration were measured in frontal and occipital regions for 400 minutes after administration of four placebo or test tablets and 20 minute resting period. The same procedure crossed over at 7-day interval. We analyzed average alpha power values in frontal and occipital regions at 10 minute intervals. Repeated ANOVA revealed that there were significant differences of occipital alpha power values between placebo and test groups with high anxiety (p < 0.05). The mean values at 20, 30, 40, 50 and 60 minute intervals were 0.23. 0.24. 0.28, 0.25 and 0.34 in placebo, respectively and 0.23, 0.29 0.40, 0.34, and 0.45 in test, respectively. But there were no significant differences of frontal and occipital alpha power values between placebo and test groups with low anxiety (p > 0.05). The results of this study suggest that L-theanine containing tablets promote the release of alpha waves related to mental relaxation and concentration in young adult males.

Biol Pharm Bull 2002 Dec;25(12):1513-8

Neuroprotective effects of the green tea components theanine and catechins.

Kakuda T.

Central Research Institute, Itoen, Ltd., Shuzuoka, Japan

Abstract:

The neuroprotective effects of theanine and catechins contained in green tea are discussed. Although the death of cultured rat cortical neurons was induced by the application of glutamic acid, this neuronal death was suppressed with exposure to theanine. The death of hippocampal CA1 pyramidal neurons caused by transient forebrain ischemia in the gerbil was inhibited with the ventricular preadministration of theanine. The neuronal death of the hippocampal CA3 region by kainate was also prevented by the administration of theanine. Theanine has a higher binding capacity for the AMPA/kainate receptors than for NMDA receptors, although the binding capacity in all cases is markedly less than that of glutamic acid. The results of the present study suggest that the mechanism of the neuroprotective effect of theanine is related not only to the glutamate receptor but also to other mechanisms such as the glutamate transporter, although further studies are needed. One of the onset mechanisms for arteriosclerosis, a major factor in ischemic cerebrovascular disease, is probably the oxidative alteration of low-density lipoprotein (LDL) by active oxygen species. The oxidative alterations of LDL were shown to be prevented by tea catechins. Scavenging of *O(2)(-) was also exhibited by tea catechins. The neuroprotective effects of theanine and catechins contained in green tea are a focus of considerable attention, and further studies are warranted.

Journal:  Amino Acids (Vienna) 2001 Vol. 21, No. 1, PP 62

Correlations between central nervous parameters and hormonal regulations during recovery from physical stress are influenced by L-theanine.

Weiss, M.; Schnittker, R.; Barthel, T.; Falke, W.; Geiss, K. E.; Juneja, L.R.

Proceedings from the 7th International Congress on Amino Acids and Proteins, August 06-10, 2001 Institute of Sports Medicine, University of Paderborn, Paderborn, Germany

Abstract:

In animal studies L-theanine was shown to influence neuro-transmitter systems. Thus it may be helpful in managing stress regulation. So we observed 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). N=14 healthy students consumed drinks containing either 0, 50 or 200mg L-theanine in randomized double-blind trials in the min 6-14 after a near maximal bicycle step test. Measurements were done directly after exercise (Ml) and 30 (M2), 45 (M3), 60 (M4), 120 (M5) min after the drink.

Results:  L-theanine seemed to accelerate the normalization of EEG spectral power in high frequency waves. The physiological return of increased hormone levels to basal levels / the circadian rhythm up to M2 (catecholamines) or M5 (cortisole, serotonin, prolactine) was not influenced by the drinks. But in the L-theanine trials correlations between EEG spectral power and some hormones were altered (slow wave power/some catecholamines except norepinephrine/delta disappeared and new correlations with prolactine appeared). Thus we conclude that L-theanine acts at the switch from the brain to the peripheral stress regulation and thereby supports physiological relaxing after severe exercise.

Journal:  Amino Acids (Vienna) 2001 Vol. 21, No. 1, PP 60

Does L-theanine have an influence on relaxation after severe physical exercise? Evaluation using electrosympathicography.

Weiss, M.; Reinsberger, C.; Liesen, H.; Juneja, L. R.; Herwegen, H.; Geiss, K. R.

Proceedings from the 7th International Congress on Amino Acids and Proteins, August 06-10, 2001 Institute of Sports Medicine, University of Paderborn, Paderborn, Germany

Abstract:

50 percent of amino acids in green tea leaves are represented by L-theanine (5-N-ethylglutamine). Previous rat experiments demonstrated effects of L-theanine to act on metabolism of neurotransmitters. It was therefore suggested that this causes the relaxing effects of green tea. To examine its influence as a component of a drink on the sympathetic nervous system after maximal physical exercise skin resistance measurements through electrosympathicography (ESG) were used. After individual maximal exercise on a bicycle-ergometer, test drinks with different amounts of L-theanine (0, 50 and 200 mg) were administered to 14 healthy volunteers in a randomized cross-over double-blind distribution on a weekly base. ESG was monitored before and immediately after exercise as well as 15, 30, 45, 60, 75 and 135 minutes after end of exercise. All test conditions were standardized strictly, A characteristic ESG course with subsequent qualities could be shown 1. Decreasing skin resistances after exercise could be established in each volunteer. 2. ESG-activation levels before exercise could not be reached again even after a period of regeneration of 2 3/4 hours. 3. Maximal electrodermal activity did not appear immediately after exercise, but after 13 minutes. However, L-theanine could not significantly influence peripheral sympathetic electrodermal activity during the regeneration after maximal physical exercise.

Journal:  Amino Acids (Vienna) 2001 Vol. 21, No. 1, PP 59

EEG-changes in humans during regeneration after heavy physical strain with the influence of L-Theanine; an amino acid in green tea.

Weiss, M.; Schnittker, R.; Liesen, H.; Juneja, L. R.; Geiss, K.-R.; Barthel, T.

Proceedings from the 7th International Congress on Amino Acids and Proteins, August 06-10, 2001, Institute of Sports Medicine, University of Paderborn, Paderborn, Germany

Hypothesis:  "L-theanine has relaxing effects of central nervous system of human beings", was verified by electroencephalographical methods.

Methods: 14 male healthy sport-students, free of drugs or stimulants, participated weekly in a cross-over study. After exhaustive bicycle-ergometer test as an individual, reliable, stress model, the subjects recovered by lying in a segregated shaded room. Three test drinks with different L-theanine content (dl=placebo, d2=50 mg, d3=200 mg) were given in a randomized, double-blind order. All test conditions were standardized strictly. EEG-recordings (closed eyes) were carried out (M 1 = 3min after stress/before test drink, M2 = 30 min., M3 = 45 min., M4 = 60 min., MS = 120 min. after test drink) with the CATEEM system. Absolute and relative EEG-spectral-power were examined.

Results:  Significant reductions in all frequencies (exception theta-power) were found in early recovery, being not significant influenced by test drinks. 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 d3. These findings were related to relaxing effects. After ingestion of L-theanine, alpha2-, beta l-power at occipital regions decreased faster (M2) to placebo recovery levels (M3/M4). Thus it may be concluded that L-theanine has no pharmaceutical effect on the down regulation system but supports the physiological mechanisms during recovery after physical stress in human brain.

Trends in Food Science & Technology 10 (1999) 199-204

L-theanine: a unique amino acid of green tea and its relaxation effect in humans

Lekh Raj Juneja*,†, Djong-Chi Chu*, Tsutomu Okubo*,Yukiko Nagato* and Hidehiko Yokogoshi‡

*Nutritional Foods Division, Taiyo Kagaku Co., Ltd, 1-3

Takaramachi, Yokkaichi, Mie 510-0844, Japan

‡Laboratory of Nutritional Biochemistry, School of Food and Nutritional Sciences, The University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract:

Since ancient times, it has been said that drinking green tea induces relaxation. The substance that is responsible for a sense of relaxation is theanine. Theanine is a unique amino acid found almost solely in tea plants and the main component responsible for the exotic taste of ‘green’ tea. It was found that L-theanine administered intraperitoneally to rats reached the brain within 30 minutes without any metabolic change. Theanine also acts as a neurotransmitter in the brain and decreased blood pressure significantly in hypertensive rats. In general, animals always generate very weak electric pulses on the surface of the brain, called brain waves. Brain waves are classified into four types, namely a, b, d, and q-waves, based on mental conditions. Generation of a-waves is considered to be an index of relaxation. In human volunteers, a-waves were generated on the occipital and parietal regions of the brain surface within 40 minutes after the oral administration of theanine (50-200 mg), signifying relaxation without causing drowsiness. With the successful industrial production of L-theanine, we are now able to supply Suntheanine™ (trade name for L-theanine) which offers a tremendous opportunity for designing foods and medical foods targeting relaxation and the reduction of stress. Taiyo Kagaku Co., Ltd, Japan won the 1998 “Food Ingredient Research Award” for development of Suntheanine™ at Food Ingredients in Europe (Frankfurt). The judges felt it was a particularly well-documented and fascinating piece of research. © 1999 Published by Elsevier Science Ltd. All Rights reserved

Society for Neuroscience, Volume 24, 1998 p 978

Theanine, a major flavorous amino acid in green tea leaves, inhibits glutamate-induced neurotoxicity on cultured rat cerebral cortical neurons

A Nozawa, K. Umezawa, K. Kobayashi, M. Kawahara, K. Muramoto, T. Kakuda and Y. Kuroda. Dept of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183, Japan, ITOEN Central Research Institute, Shizuoka 421-05 Japan.

Abstract:

Theanine, L-glutamine g-ethylamide, is an amino acid which has a similar structure with glutamic acid and is contained in tea leaves as a flavorous constituent of green tea. It has been reported that theanine passed through the blood-brain barrier and inhibited the convulsions induced by caffeine (Kimura et al.: Chem. Pharm. Bull., 19:  1257-1261 1971). Theanine also inhibited the caffeine-induced excitation (Nozawa et al.; Soc. Neuriocience Abstract., 21:  835, 1995). Here we investigated the effect of theanine on glutamate-induced neurotoxicity on cultured rat cerebral cortical neurons. Rat cerebral corticies were dissected from 18-days embryos, and dissociated cells were cultured. Cultured neurons extended neuritis and made synaptic contacts. Pharmacological evidence suggested that excitatory synaptic transmission in our culture was mainly mediated by glutamate. The cell viability observed by WST-1 method, the modification of MTT assay, was decreased after the application of 25-800mM glutamate for 48hr at 14DIV in a dose dependent manner. Co-existence of theanine inhibited glutamate-induced neurotoxicity with dose dependency. More than 400mM theanine completely protected the cell death induced by the application of 50mM glutamate. Furthermore, The TUNEL staining revealed that cultured neurons affected by glutamate showed apoptotic cell death after 48hr. The apoptotic cell death was also remarkably inhibited by theanine. These results suggest that theanine prevents glutamate-induced neurotoxicity and may become a candidate for preventive or curative medicine for ischemia.

Society for Neuroscience, Volume 21, 1995 p 835

Theanine, a glutamate analog, stimulates NMDA-receptors but suppresses excitatory effect of caffeine in cortical neurons

A. Nozawa*12, K. Umezawa1, K. Kobayasi1, K. Muramoto1, M. Kawahara1, A. Mizutani1, T. Kakuda2, and Y. Kuroda1. 1Dept. of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo 183, Japan, 2ITOEN Central Research Institute, Shizuoka 421-05 Japan.

Abstract:

Green tea leaves contain 1-2% (W/W) theanine (L-glutammate g-ethylamide) which makes up 60% of the total amino acid content. Since theanine can pass through the blood-brain barrier, we have carried out an initial study on its effects on brain function, using cultured cortical neurons. When intracellular Ca2+ was monitored by fura-2 fluorometry (Kuroda et al.; Neurosci. Lett., 135:  255, 1992), the addition of theanine produced a Ca2+  increase in the neurons. This effect was inhibited in the presence of D-APV, suggesting that theanine stimulates NMDA-receptors. Since it has been reported that theanine prevents caffeine-induced convulsions and behavioral activation in mice, we studied whether theanine could inhibit the effect of caffeine on cultured neurons. Cultured neuronal networks with high synaptic convergence fire spontaneously in synchronous oscillations which can be monitored by Ca2+ fluorometry(Robinson et al., J. Neurophysiol., 70:  1606, 1993).  Caffeine increased the frequency of the Ca2+ oscillation, but theanine was able to inhibit the effect of caffeine. These results suggest that theanine is an interesting glutamate analog which has a dual concentration, but sedative at high concentration, suppressing excitation produced by caffeine, which is also a neuro-active constituent of tea leaves.

Brain Research, 151 (1978) 215 219 © Elsevier/North-Holland Biomedical Press

Theanine as a glutamate antagonist at a crayfish neuromuscular junction

H. Shinozaki and Michiko Ishida

The Tokyo Metropolitan Institute of Medical Science 2-18-22, Honkomagome, Bunkyo-ku, Tokyo 113 (Japan)

Yakugaku Zasshi. 1975 Jul; 95(7):  892-5.

Influence of Alkylamides of Glutamic Acid and Related Compounds on the Central Nervous System. III. Effect of Theanine on Spontaneous Activity of Mice

Ryohei KIMURA. Masako KURITA and Toshiro MURATA Shizuoka College of Pharmacy (Received October 18. 1974)

Previously we reported that theanine (L-GluNHEt) and L-glutamine (L-GluNH2) oppose compulsion of mice induced especially by caffeine (Caf), among other central stimulants. Based on this, it is considered that these compounds have inhibiting effects against central stimulation by Caf, and continued examinations of the inhibiting effects of L-GluNHEt and L-GluNH2 against spontaneous activity of mice have been performed. It has been confirmed with the current study that the inhibiting effects are valid against only the increase of' momentum by Cat'. and this report is provided as so.

OBSERVATION

We have previously reported that r-N alkylamides of glutamic acid, such as L-GluNHEt and L-GluNH2, have an antagonistic action against spasm death caused by large-quantity Caf consumption. And, when it was examined whether or not L-GluNHEt or L-GluNH2 shows inhibition against caffeine-increased spontaneous activity of mice, while only weak inhibition effect against spontaneous activity was observed with Caf not being administered, a significant inhibition effect was indicated against caffeine-increased spontaneous activity. Furthermore. regarding the activity level increase induced by other central stimulants. especially pipradrol for which the site of action is cerebrocortex, no inhibition was observed at all.

Based on the results of the time-lapse measurement, it is presumable that inhibition against caffeine-increased spontaneous activity of mice stand,, on the same function for both, L-GluNHEt and L-GluNH2. On the other hand. r-aminobutyric acid also showed inhibition, albeit a weak one. As has already been reported, when it is considered that combined L-GluNHEt and L-GluNH2 move through the blood brain barrier relatively quickly and that in-brain r-aminobutyric acid concentration increase was observed by i.p. administration of L- GluNHEt, r-aminobutyric acid indicated a weak effect as it did not move through the blood brain barrier easily and there is a possibility that the effect of L-GluNHEt emerges through the increase of the in-brain r-aminobutyric acid concentration.

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