How does the tea <i>L</i>-theanine buffer stress and anxiety

Liwen Wang; Margaret Brennan; Shiming Li; Hui Zhao; Klaus W. Lange; Charles Brennan

doi:10.1016/j.fshw.2021.12.004

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Review Article | Open Access

How does the tea L-theanine buffer stress and anxiety

Liwen Wang^{^a}, Margaret Brennan^{^b}, Shiming Li^{^c}(), Hui Zhao^{^d}, Klaus W. Lange^{^e}, Charles Brennan^{^b^,^f}()

College of Food Science and Technology, Hebei Agricultural University, Baoding 071001, China

Department of Wine, Food and Molecular Biosciences, Lincoln University, Christchurch 7647, New Zealand

Hubei Key Laboratory of EFGIR, Huanggang Normal University, Huanggang 438000, China

Tianjin Key Laboratory of Food and Biotechnology, University of Commerce, Tianjin 300134, China

Department of Experimental Psychology, University of Regensburg, Regensburg 93040, Germany

School of Science, RMIT, Melbourne, VIC 3000, Australia

Peer review under responsibility of KeAi Communications Co., Ltd.

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Abstract

Tea (Camellia sinensis) is widely considered to promote feelings of calming and soothing. This effect is attributed to L-theanine (L-γ-glutamylethylamide) in tea, a non-protein amino acid mainly derived from tea leaves. As a naturally occurring structural analogue of glutamate, L-theanine competes for the receptors with glutamate and is able to pass the blood-brain barrier to exert its relaxation effect. This review focuses on the relaxation effect of L-theanine, including animal models and the latest human trials as well as the potential molecular mechanisms regarding neuron stem cells. The biological efficacy of dietary L-theanine in the food matrix has been further discussed in this review in relation to the physiological changes in the gastrointestinal tract and bindings of L-theanine with other food components.

Keywords

L-theanine Relaxation Stress Anxiety Food matrix

References

[1]

S. Cohen, D. Janicki-Deverts, G.E. Miller, Psychological stress and disease, JAMA 298(14) (2007) 1685-1687. https://doi.org/10.1001/jama.298.14.1685.

Mice model	Dosage/duration	Measurements/stress models	Outcomes	Reference
Male Wistar rats	0.2 μmol/2 μL perfusion/min; and L-trans-PDC 0.01 μmol/2 μL perfusion/min for 1 h	Brain microdialysis	L-theanine perfusion caused dopamine release up to 300% of the basal value; prevented aspartic acid release and increased glycine release.	Yamada et al. [16]
Male Sprague Dawley rats, chronic unpredictable mild stress	2 mg/kg for 21 days	CUMS chronic unpredictable mild stress randomly food privation (12 h), water privation (24 h), reversed light and dark (24 h), thermal stimulus (45 ℃, 5 min), shaking (180 r/min, lasting for 5 min), immersion in cold water (4 ℃, 1 min), tail pinch (1 min), electric shock in the foot (10 mA electricity was given, which lasted for 10 s per time for 30 times).	L-theanine increased the locomotor activity open-field test (P < 0.001); increased sucrose consumption level sucrose preference test (P < 0.001); decreased immobility time in forced swim test (P < 0.001).	Shen et al. [17]
Posttraumatic stress disorder (PTSD) male Std-ddY mice	5, 50, 500 mg/kg; 5 days; oral	Restraint stress in a metallic cage immersed in water at 25 ℃ up to the clavicle for 3 h.	L-theanine (50—500 mg/kg) significantly prevented the decline of BrdU incorporation, and for 5 days after stress; inhibited the prolonged immobility in mice with stress in forced swimming test 14 days later. Increased total spontaneous locomotion activity was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress.	Takarada et al. [34]
Wistar Kyoto rat	0.4 mg/kg/day intraperitoneal injection; 7 days	Anxiety vulnerability and refractory depression	Anxiety: longer time spent in arms in elevated plus maze test (P = 0.035).	Ogawa et al. [23]
Male ddY mice	L-theanine (> 5–100 μg/mL) in drinking water; 2 weeks	Psychosocial stress: confronting housing	Decreased immobility time in tail suspension test (P = 1.87 × 10^-5); no effect in marble-burying behaviour test.	Unno et al. [26]
Senescence-accelerated mice prone 10 (SAMP10) and ddY mice	6 mg/kg (20 μg/mL in normal tap water)	Psychosocial stress: confronting housing	L-theanine suppressed brain atrophy (volume of hippocampus and neocortex in brain).	Unno et al. [39]

Type/task	Participants/Age (years)	Dosage	Outcomes	Study design	Reference
Acute stress task; mental arithmetic task for 20 min.	12 male participants, age (21.50 ± 1.38) years	Oral 200 mg dissolved in. 100 mL water; acute 1 day	L-theanine reduced heart rate (P < 0.05) HRV (LF/HF) (P < 0.05) and salivary immunoglobulin A (P < 0.01); STAI (P < 0.01); and VAS (P < 0.01) compared with placebo.	Placebo-controlled, double-blind	Kimura et al. [31]
Healthy; light-to moderate caffeine consumers; visual probe task (10 min) or facial expression discrimination task (15 min).	48 healthy participants, age (20.5 ± 2.0) years	200 mg in drinks; 250 mg caffeine; 1 day	L-theanine lowered reaction time in visual probe task (P = 0.046); and agonisted the caffein increased systolic BP and diastolic BP (P = 0.017 and P = 0.008).	Between subjects; double-blind	Rogers et al. [6]
Visual attention task; audio response test.	18 healthy participants, age (19 ± 1) years	200 mg/100 mL water; 1 day	L-theanine decreased heart rate (P = 0.001 6), elevated visual attentional performance (P = 0.000 1), and improved reaction time response among high anxiety propensity subjects compared to a placebo (P = 0.001), no effect on STAI.	Double-blind; placebo-controlled	Higashiyama et al. [27]
Anticipatory anxiety model of electrical stimuli; 3-full day repeated test.	16 healthy participants; 12 males (age (24.8 ± 5.4) years) and 4 females (age (29.0 ± 1.4) years)	200 mg; acute; repeated 3 measurements	L-theanine reduced subjective anxiety on the tranquil-troubled subscale of the VAMS than placebo and alprazolam (P < 0.05); no significant anxiolytic effects in the anxiety state.	Double-blind; placebo-controlled	Lu et al. [28]
Auditory oddball target detection task (5 min); arithmetic mental task (10 min); physical stress task, cold pressor test.	14 healthy volunteers, 8 men, 6 women; age (22.8 ± 2.1) years	200 mg; caffeine (100 mg); with 250 mL warm water; 1 day	Decreased systolic blood pressure in AMT (after mental task) 4, 5, 6, periods; and diastolic blood pressure at AMT 4 (P = 0.006) and AMT 6 (P = 0.039); decreased Tension-Anxiety score (P = 0.004).	Cross-over, randomized, placebo-controlled	Yoto et al. [25]
Stress, assigned to practice in a hospital or a drug store.	14 man, 6 women (theanin: age (22.5 ± 0.2) years; placebo: age (22.5 ± 0.1) years)	In total 400 mg; 200 mg, twice a day, 17 days	L-theanine decreased salivary alpha-amylase activity (P = 0.032); subjective stress (P = 0.020); VAS (P = 0.020).	Placebo-controlled; group comparison design	Unno et al. [26]
Healthy; Trail-Making Test, Stroop Test, Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS).	30 individuals with no major psychiatric illness (9 men and 21 women); age (48.3 ± 11.9) years	200 mg/day; 4 weeks	L-theanine decreased SDCS, STAI, and Pittsburgh sleep quality index (PSQI) (P = 0.019, 0.006 and 0.013); Stress; Self-rating depression scale (SDS), anxiety: STAI; sleep: PSQI; L-theanine improved verbal fluency and executive function scores (P = 0.001, and 0.031).	Randomized; placebo-controlled, crossover and double-blind trial	Hidese et al. [8]
Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS).	Major depressive disorder; 20 patients with MDD (4 men (41.0 ± 14.1) and 16 women (42.9 ± 12.0))	250 mg/day for 8 weeks	L-theanine decreased HAMD-21-score (P = 0.007), STAI (P = 0.012), PSQI (P = 0.030).	Open-label study	Hidese et al. [30]
Trail-Making Task; Stroop task.	46 participants with a DSM-5 diagnosis of Generalized Anxiety Disorder (18–75 years)	450 and 900 mg; 225 mg 1 capsule twice/day; 8 weeks	No effect in anxiety Hamilton Anxiety Rating Scale score (P = 0.73), insomnia severity index (ISI: P = 0.35), sleep satisfactory (ISI item 4, P = 0.015).	Double-blind, randomised; placebo-controlled	Sarris et al. [4]
Multi-tasking framework (mathematical processing, Stroop, memory search and psychomotor tracking).	34 healthy participants: 15 men (26.53 ± 5.04); 19 women (27.03 ± 5.61)	200 mg L-theanine in 430 mL drinks (alpha glycerylphosphorylcholine 25 mg; phosphatidylserine, 1 mg) and micronized chamomile (10 mg); acute 1 day	Subjective stress was decreased after 1 h (P = 0.003); salivary cortisol was reduced 3 h after L-theanine treatment (P = 0.047).	Double-blind, randomised; placebo-controlled, crossover	White et al. [44]
Carbohydrate response caused by sorbet consumption.	11 healthy males, age (27.7 ± 10.8) years	200 mg L-theanine in Mango sorbet (100 g); 1 day	No significant effect on blood pressure (systolic and diastolic), heart rate variability (over 90 min), heart rate (P > 0.05).	Randomize, double-blind, placebo-controlled, crossover	Williams et al. [46]
No task stressor; high consumption of caco-content increase blood pressure.	122 participants (age 18—25 years)	128 mg L-theanine in 40 g chocolate (3.2 mg/g of chocolate); 1 g of chocolate for each kg of body weight; 1 day	L-theanine decreased diastolic (3.65 mm Hg) and systolic (5.15 mm Hg) blood pressure (4—8 mm Hg) (P < 0.0001 and P < 0.05).		Montopoli et al. [45]