L-theanine

Authored by Sumeet Sharma • 
July 10, 2016

theanine, glutamic acid, and GABA structures.

Origin

  • An amino acid found in Camellia sinensis, commonly known as Green Tea.
  • It's uncommon in the typical Western diet.
  • L-theanine is primarily harvested from tea plants, but can also be produced through fermentation techniques.

Also Known As

  • theanine

Metabolism and Excretion

  • L-theanine is processed into ethylamine and glutamic acid, and excess of L-theanine and these metabolic by-products are excreted in urine.
  • Plasma concentrations of the metabolites (ethylamine and glutamic acid) are not greatly increased in plasma after L-theanine ingestion.1
  • Plasma concentrations of L-theanine reach a peak 3 hours after consumption and return to baseline after 24 hours.

Neural Mechanism of Action

  • Orally ingested theanine crosses the blood-brain barrier, so it is active in the brain. The increased brain concentrations of the compound are mediated via neutral-charge amino acid transport.
  • L-theanine inhibits binding of glutamate to its cortical neuronal receptors: AMPA, kainate, and NMDA.2These excitatory receptors increase neuronal activity.
  • Since glutamate is known to increase during stress, the inhibition of glutamate receptor activity is thought to contribute to the anti-stress effects of L-theanine.3,4

Cognitive Effects (Healthy Human Cognition)

  • The general picture that emerges from L-theanine research is an anti-stress effect, with the strongest hypothesis being that anti-glutamate receptor activity is the primary driver of this effect. In particular, Kimura et al. 2002 demonstrated that stress (measured subjectively by the state-trait anxiety index and objectively by heart rate variability) is significantly reduced as a result of L-theanine administration during a stressful task (Figures 1 and 2).

L-theanine, HRV Figure 1. L-theanine reduces heart rate variability during an acutely stressful task.

L-theanine, STAI Figure 1. L-theanine reduces the state-trait anxiety index during an acutely stressful task.

  • There is also evidence to suggest that L-theanine administration before stress in academic settings can act to reduce stress levels as measured by questionnaires and the salivary marker alpha-amylase.5
  • L-theanine supplementation has also been shown to increase brain α-waves (8-10 Hz range) which are associated with reduced stress and anxiety. Increased α-waves are also associated with selective attention mechanisms and mental alertness. These altered wave functions are evidence that theanine has 'relaxing and attention promoting' properties. There's also literature that reports increased theta wave function which is associated with learning and memory.
  • High levels of stress are well known to result in cognitive and health deficits in both humans and animal models. In one study of mice, L-theanine reversed the lifespan reduction, cognitive deficits, and behavioral depression associated with chronic stress.6In another study in mice, L-theanine was shown to reverse stress-induced, depression-like phenotypes in mice.7These data point to strong effects of L-theanine on a variety of general and cognitive health correlates that are impacted by stress.
  • When taken in combination with caffeine, L-theanine has a host of cognitive enhancing effects:

Caffeine & L-theanine

Caffeine and L-theanine can act synergistically to improve alertness and attention. L-theanine can also potentially reverse some of the less favorable physiological effects of caffeine - including increased blood pressure, and reduced flow of oxygenated blood to the head. (Learn more)

Other Effects

  • L-theanine also reduces blood pressure, by stimulating nitric oxide production - a molecule that signals to blood vessels to relax.8In studies of the effects of the combination of caffeine and L-theanine, L-theanine reduced the increased blood pressure caused by caffeine intake and reduced the cerebral vasoconstriction caused by caffeine.9,10
  • It is possible that many of L-theanine's anti-stress cognitive effects are a consequence of its effects on blood pressure.

Side Effects & Drug-drug Interactions

  • L-theanine is "generally regarded as safe" (GRAS) by the FDA, at 250 mg per serving. There are no known negative effects at any tested dose of L-theanine.11

How to take

  • L-theanine should be taken in isolation specifically for anti-stress effects (>200 mg)
  • L-theanine should be taken in combination with caffeine for maximal cognitive benefit (200 mg L-theanine and 100 mg caffeine)
  • L-theanine can be taken in combination with magnesium, melatonin, and glycine to promote sleep.
  1. Scheid, L., Ellinger, S., Alteheld, B., Herholz, H., Ellinger, J., Henn, T., . . . Stehle, P. (2012). Kinetics of L-theanine uptake and metabolism in healthy participants are comparable after ingestion of L-theanine via capsules and green tea. The Journal of nutrition, 142(12), 2091-2096.

  2. Kakuda, T., Nozawa, A., Sugimoto, A., & Niino, H. (2002). Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem, 66(12), 2683-2686.

  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., & Takeuchi, N. (1995). Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem, 59(4), 615-618.

  4. Kakuda, T., Nozawa, A., Unno, T., Okamura, N., & Okai, O. (2000). Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem, 64(2), 287-293. doi:10.1271/bbb.64.287

  5. Unno, K., Tanida, N., Ishii, N., Yamamoto, H., Iguchi, K., Hoshino, M., . . . Yamada, H. (2013). Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary alpha-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav, 111, 128-135. doi:10.1016/j.pbb.2013.09.004

  6. Unno, K., Fujitani, K., Takamori, N., Takabayashi, F., Maeda, K., Miyazaki, H., . . . Hoshino, M. (2011). Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic Res, 45(8), 966-974. doi:10.3109/10715762.2011.566869

  7. Yin, C., Gou, L., Liu, Y., Yin, X., Zhang, L., Jia, G., & Zhuang, X. (2011). Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Phytother Res, 25(11), 1636-1639. doi:10.1002/ptr.3456

  8. Siamwala, J. H., Dias, P. M., Majumder, S., Joshi, M. K., Sinkar, V. P., Banerjee, G., & Chatterjee, S. (2013). L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation. J Nutr Biochem, 24(3), 595-605. doi:10.1016/j.jnutbio.2012.02.016

  9. Rogers, P. J., Smith, J. E., Heatherley, S. V., & Pleydell-Pearce, C. W. (2008). Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl), 195(4), 569-577. doi:10.1007/s00213-007-0938-1

  10. Dodd, F. L., Kennedy, D. O., Riby, L. M., & Haskell-Ramsay, C. F. (2015). A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology (Berl), 232(14), 2563-2576. doi:10.1007/s00213-015-3895-0

  11. Borzelleca JF, Peters D, Hall W A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats . Food Chem Toxicol. (2006)

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