l-Theanine reduces psychological and physiological stress responses
Introduction
In recent years, various healthful effects of the ingredients contained in green tea have been scientifically verified (Yamane et al., 1991, Cooper et al., 2005). l-Theanine, one of the major amino acids contained in green tea, has been a focus of attention due to its physical characteristics. As a biochemical characteristic of this substance, Yokogoshi et al., 1998a, Yokogoshi et al., 1998b reported that l-Theanine could pass through the blood–brain barrier, and that it increased by 1 h at the latest in serum, the liver, and the brain after administration, thereafter decreasing sharply in the serum and liver but only beginning to decrease in the brain 5 h after administration. Furthermore, another study reported that l-Theanine could influence the secretion and function of neurotransmitters in the central nervous system even at 30 min after oral administration (Terashima et al., 1999). l-Theanine binds to the glutamate receptor subtypes (AMPA, kainate, and NMDA receptors) and blocks the binding of l-glutamic acid to the glutamate receptors in cortical neurons (Kakuda et al., 2002). Despite the lower affinity of l-Theanine with glutamate receptor subtypes than with l-glutamic acid (about 80-fold lower with the AMPA and kainate receptors, and about 30,000-fold lower with the NMDA receptor), several reports demonstrating the neuroprotective effect of l-Theanine in cortical neurons via the antagonistic role (Kakuda et al., 2000, Nagasawa et al., 2004) suggest the functional role of l-Theanine in brain dynamics. These chemical and functional characteristics of l-Theanine in the brain suggest that it might down-regulate cerebral functions, at least to a moderate degree.
In fact, previous animal studies have reported that the administration of l-Theanine reduced blood pressure (Yokogoshi et al., 1995) and inhibited the excitatory effects of caffeine (Kakuda et al., 2000). Since emotional or physiological states in humans are modulated by the chemical behaviors of neurotransmitters, psychological and physiological states could also be influenced by l-Theanine. Although empirical findings concerning the effects of l-Theanine on human participants have been limited, Kobayashi et al. (1998) reported that the oral administration of 200 mg of l-Theanine resulted in an increase of the α-band component of electroencephalograms (EEG) in the occipital and parietal scalp regions when participants rested in a relaxing state. Furthermore, the observed result that the α-band component of EEG increased more remarkably at 30 min after oral administration was consistent with the result in the animal study showing that neurotransmitters in the brain were affected by l-Theanine 20 min after its administration (Yokogoshi et al., 1998a, Yokogoshi et al., 1998b), and might indicate that there was a time-lag between when l-Theanine was administered and when it took effect. Unfortunately, however, the researchers examined the influence of l-Theanine on EEG only during a resting situation. It is well known that the extracellular level of glutamate in the brain is increased by acute stressors (Lowy et al., 1993, Moghaddam, 1993), and it seems likely that such a glutamate increase would also result in facilitation of the activity of the sympathetic nervous system. Considering the competitive role of l-Theanine against excitation of the glutamatergic phenotype, we hypothesized that l-Theanine might be able to reduce stress-induced excitation of the peripheral sympathetic activity.
In laboratory acute stress studies, changes in several autonomic parameters, such as heart rate and blood pressure (BP), have been evaluated when participants were engaged in acute stress tasks such as the mental arithmetic, the public speaking, a stroop task, and a cold pressor task (Bachen et al., 1992, Herbert et al., 1994, Breznitz et al., 1998, Willemsen et al., 1998, Willemsen et al., 2000, Willemsen et al., 2002, Winzer et al., 1999, Atanackovic et al., 2002, Bosch et al., 2003). We previously developed a mental arithmetic task which elicits a continuous increase in the levels of HR, BP, and salivary secretory immunoglobulin A (s-IgA) (Isowa et al., 2004, Kimura et al., 2005). In addition, we attempted to estimate activity in the autonomic nervous system during the task by analyzing heart rate variability (HRV). HRV describes the variations between consecutive heartbeats, and has been widely used as a quantitative marker of the autonomic nervous system (Task Force of the European Society of Cardiology, The North American Society of Pacing and Electrophysiology, 1996). The frequency domain of HRV was divided into two major frequency bands, a high-frequency band (HF component: 0.15–0.5 Hz) and a low-frequency one (LF component: 0.05–0.15 Hz). The former is related to respiratory sinus arrhythmia and is exclusively attributable to parasympathetic influence reflecting vagal activity, while the latter mirrors the baroreceptor feedback loop that controls blood pressure and appears to reflect both sympathetic and parasympathetic activity. Furthermore, the relative contribution of LF and HF power (LF/HF) was thought to reflect the sympathovagal balance. Our observation of the significant decrease in the HF component and a remarkably increased LF/HF ratio during the task indicated that the sympathetic nervous system was prominently activated by this task. Moreover, the stress task successfully induced not only a physiological stress state, but also subjective stress feelings and state anxiety. Thus, this robust experimental paradigm allowed us to examine the possibility that l-Theanine could buffer autonomic activity and subjective stress feelings during an acute stress challenge in human participants.
In the present study, therefore, we measured the subjective stress intensity, HR, HRV, and the concentration of s-IgA as indices of acute stress responses, and examined the buffering effects of l-Theanine on such responses by asking participants to drink a cup of water containing l-Theanine before the acute stressor started. Additionally, to examine the buffering effects more precisely, we administered l-Theanine at two different time points, since previous studies pointed out the possibility that there was a time-lag effect after oral intake. If the time-lag effect existed, the observed stress responses would be buffered differentially between the time points. However, it is known that the effects of drug treatment are, in general, dependent on participants’ expectations. Because we had to take this expectation effect, called the placebo effect, into consideration, in addition to above two l-Theanine administration conditions, we set a placebo condition in which participants were required to drink a cup of water which did not contain l-Theanine. Furthermore, a control condition was added to the experimental protocol to confirm the effect of the acute psychological stressor and the oral administration of the solution itself. Together, all participants engaged in the four conditions in a double blind and counterbalanced order. In our hypotheses, as previous studies indicated, the acute stress task induces remarkable stress feeling and sympathetic nervous activation, which is reflected by the elevated HR, s-IgA level, relative decrement in HF component of HRV, and increment of LF/HF ratio. The oral administration of l-Theanine should reduce these variations via inhibiting sympathetic nervous activation based on the antagonistic role in glutamate receptors. That is, it is thought that an elevation in the HR, s-IgA, and LF/HF ratio should be reduced while the HF component reflecting vagal activity shows a lower decrement.
Section snippets
Participants
Twelve male undergraduate students (age range, 20–25 years; mean = 21.50, S.D. = 1.38) who were not suffering from any chronic or oral illnesses and not taking any medication known to influence immunity participated in the experiment. All participants received a detailed explanation of the study and gave their informed written consent to participate.
Treatment
200 mg of l-Theanine (Suntheanine, Taiyo Kagaku Inc., Japan) dissolved in 100 ml of water was used as a treatment. The safety of the oral administration
Psychological measures
Psychological data during the stress task and rest periods are presented in Fig. 2 and Table 2. Two-way ANOVAs revealed significant interactions between the condition and period in perception of stress (F (6, 83) = 3.91, p < 0.01) and state of anxiety (F (6, 80) = 4.29, p < 0.01). Post hoc comparisons using LSD tests clarified that the perception of stress in the task period showed a higher value under the placebo condition than under the other conditions. Furthermore, the change scores of the
Discussion
The main findings in this study were that the acute stress responses elicited by the mental arithmetic task were reduced by the oral administration of l-Theanine. Moreover, this effect of l-Theanine was consistently observed not only in the subjective perception of stress but also in physiological stress responses such as HR and s-IgA. Although there is a possibility that the buffering effect was induced by a placebo effect, as is frequently seen in clinical trials of medicine, we prevented the
References (31)
- et al.
Experimental induction and termination of acute psychological stress in human volunteers: effects on immunological, neuroendocrine, cardiovascular, and psychological parameters
Brain, Behavior, and Immunity
(1998) - et al.
Reactivity of immune, endocrine and cardiovascular parameters to active and passive acute stress
Biological Psychology
(2004) - et al.
Temporal variation of acute stress responses in sympathetic nervous and immune systems
Biological Psychology
(2005) - et al.
Possible involvement of group I mGluRs in neuroprotective effect of theanine
Biochemical and Biophysical Research Communications
(2004) - et al.
Secretory immunoglobulin A and cardiovascular activity during mental arithmetic: effects of task difficulty and task order
Biological Psychology
(2000) - et al.
Acute psychological stress simultaneously alters hormone levels, recruitment of lymphocyte subsets, and production of reactive oxygen species
Immunological Investigations
(2002) - et al.
Lymphocyte subset and cellular immune responses to a brief experimental stressor
Psychosomatic Medicine
(1992) - et al.
Differential effects of active versus passive coping on secretory immunity
Psychophysiology
(2001) - et al.
Innate secretory immunity in response to laboratory stressors that evoke distinct patterns of cardiac autonomic activity
Psychosomatic Medicine
(2003) - et al.
Immunoglobulin A secretion into saliva during dual sympathetic and parasympathetic nerve stimulation of rat submandibular glands
Experimental Physiology
(2000)
Medicinal benefits of green tea: Part II. Review of anticancer properties
Journal of Alternative and Complementary Medicine
Mutagenicity test of food additives with Salmonella typhimurium TA97 and TA102
Annual Report of Tokyo Metropolitan Institute of Public Health
Cardiovascular reactivity and the course of immune response to an acute psychological stressor
Psychosomatic Medicine
The E-adjustment procedure for repeated measures analysis of variance
Psychophysiology
Inhibition by theanine of binding of [3H]AMPA, [3H]Kainate, and [3H]MDL 105,519 to glutamate receptors
Bioscience, Biotechnology, and Biochemistry
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