Theanine

(Redirected from L-theanine) Amino acid Not to be confused with threonine, a distinct amino acid, or theine, an archaic synonym of caffeine.

Pharmaceutical compound

Theanine
Clinical data

L-Theanine
Other names	γ-L-Glutamylethylamide
Dependence liability	None
Routes of administration	Oral
Drug class	dietary supplement
ATC code	none
Legal status
Legal status	US: OTC UN: Unscheduled
Pharmacokinetic data
Onset of action	about 1 hour
Elimination half-life	Capsule ~1.2 hours Green Tea ~0.8 hours
Identifiers
IUPAC name (2S)-2-Ammonio-5-(ethylamino)-5-oxopentanoate or N-Ethyl-L-glutamine
CAS Number	3081-61-6
PubChem CID	439378
DrugBank	DB12444
ChemSpider	388498
UNII	8021PR16QO
KEGG	C01047
ChEBI	CHEBI:17394
ChEMBL	ChEMBL3039113
CompTox Dashboard (EPA)	DTXSID80184817
ECHA InfoCard	100.019.436
Chemical and physical data
Formula	C₇H₁₄N₂O₃
Molar mass	174.200 g·mol
3D model (JSmol)	Interactive image Interactive image
Melting point	174.20 °C (345.56 °F)
Boiling point	215 °C (419 °F)
SMILES CCNC(=O)CC(N)C(=O)O CCNC(=O)CCC(N)C(O)=O
InChI InChI=1S/C7H14N2O3/c1-2-9-6(10)4-3-5(8)7(11)12/h5H,2-4,8H2,1H3,(H,9,10)(H,11,12) Key:DATAGRPVKZEWHA-UHFFFAOYSA-N

Theanine /ˈθiːəniːn/, commonly known as L-theanine and sometimes L-gamma-glutamylethylamide or N-ethyl-L-glutamine, is an amino acid analogue of the proteinogenic amino acids L-glutamate and L-glutamine. It is produced by certain plants such as Camellia sinensis (the tea plant), and by some fungi. It was discovered in 1949 as a constituent of green tea and isolated from gyokuro leaves in 1950, thus rendering it a natural product. It constitutes about 1–2% of the dry weight of green tea leaves.

The name theanine usually refers to the enantiomer L-theanine, which is the form found in tea leaves from which it is extracted as a powder. The right-handed enantiomer, D-theanine, is less-studied.

Theanine is sold as a dietary supplement and is considered to be safe at doses up to 250 milligrams (mg) by the US Food and Drug Administration. It is packaged in gelatin capsules, tablets, and as a powder, and may be an ingredient in branded supplements with caffeine.

The European Food Safety Authority found there was insufficient evidence for a causal relationship between theanine consumption and improved cognitive function, alleviation of psychological stress, maintenance of normal sleep, or reduction of menstrual discomfort.

Structure and properties

The chemical name N-ethyl-L-glutamine and other synonyms (see box) for theanine reflect its chemical structure. The name theanine, without prefix, is generally understood to imply the L- (S-) enantiomer, derived from the related proteinogenic L-amino acid glutamic acid. Theanine is an analog of this amino acid, and its primary amide, L-glutamine (also a proteinogenic amino acid). Theanine is a derivative of glutamine that is ethylated on the amide nitrogen (as the name N-ethyl-L-glutamine describes), or alternatively, to the amide formed from ethylamine and L-glutamic acid at its γ- (5-) side chain carboxylic acid group (as the name γ-L-glutamylethylamide describes).

Relative to theanine, the opposite (D-, R-) enantiomer is largely absent from the literature, except implicitly. While natural extracts that are not harshly treated are presumed to contain only the biosynthetic L- enantiomeric form, mishandled isolates and racemic chemical preparations of theanines necessarily contain both theanine and its D-enantiomer (and from racemic syntheses, in equal proportion), and studies have suggested that the D-isomer may actually predominate in some commercial supplement preparations. Amino acid racemization in aqueous media is a well-established chemical process promoted by elevated temperature and non-neutral pH values; prolonged heating of Camellia extracts—possible for oversteeped teas and in undisclosed commercial preparative processes—has been reported to result in increasing racemization of theanine to give increasing proportions of the nonnatural D-theanine, up to equal proportions of each enantiomer.

Discovery and distribution

Theanine is found primarily in plant and fungal species. It was discovered as a constituent of tea (Camellia sinensis) in 1949, and in 1950 a laboratory in Kyoto successfully isolated it from gyokuro leaf, which has high theanine content. Theanine is substantially present in black, green, and white teas from Camellia sinensis in quantities of about 1% of the dry weight. Deliberately shading tea plants from direct sunlight, as is done for matcha and gyokuro green tea, increases L-theanine content. The L-enantiomer is the form found in freshly prepared teas and some human dietary supplements.

Digestion and metabolism

As a structural analog of glutamate and glutamine, the theanine in teas or supplements is absorbed in the small intestine after oral ingestion; its hydrolysis to L-glutamate and ethylamine occur both in the intestine and liver, possibly functioning as a donor for glutamate synthesis.

Pharmacology

In vitro

Theanine is structurally similar to the excitatory neurotransmitter glutamate, and in accordance, binds to glutamate receptors in vitro, though with much lower affinity in comparison. Specifically, it binds to ionotropic glutamate receptors in the micromolar range, including the AMPA and kainate receptors and, to a lesser extent, the NMDA receptor. It acts as an antagonist of the former two sites, and a partial co-agonist of the NMDA receptors. In vitro, theanine also binds to group I mGluRs. In addition, it inhibits glutamine transporters and glutamate transporters, and thus blocks the reuptake of glutamine and glutamate.

Theanine may elicit umami taste, a consequence potentially associated with binding to and activation of the T1R1 + T1R3 heterodimer or umami (savory) taste receptor.

Regulatory status

The regulatory status of theanine varies by country. In Japan, L-theanine has been approved for use in all foods, with some restrictions in the case of infant foods. In the United States, the FDA considers it to be GRAS and allows its use as an ingredient in dietary supplements or foods up to a maximum of 250 mg per serving.

The German Federal Institute for Risk Assessment, an agency of their Federal Ministry of Food and Agriculture, objects to the addition of L-theanine to beverages. In 2003, the German Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung, BfR) objected to the addition of isolated theanine to beverages. The institute stated the amount of theanine consumed by regular drinkers of tea or coffee is virtually impossible to determine.

While it was estimated the quantity of green tea consumed by the average Japanese tea drinker per day contains about 20 mg of the substance, there are no studies measuring the amount of theanine being extracted by typical preparation methods, or the percentage lost by discarding the first infusion. Therefore, with the Japanese being exposed to possibly much less than 20 mg per day, and Europeans presumably even less, it was the opinion of the BfR that pharmacological reactions to drinks typically containing 50 mg of theanine per 500 milliliters could not be excluded—reactions such as impairment of psychomotor skills and amplification of the sedating effects of alcohol and hypnotics.

On 13 November 2023, the Inspection by the Administration of Food Safety, Veterinary Medicine and Plant Protection of the Republic of Slovenia banned the sale of Prime energy drinks in Slovenia as they contain L-theanine, which is not allowed in non-alcoholic beverages. Prime Hydration may be freely sold.

Research on supplement use

A 2020 review suggested that L-theanine supplementation of 200–400 milligrams per day may reduce stress and anxiety in people with acute stress, but there was insufficient evidence for the use of L-theanine as a medication to treat stress and anxiety.

Theanine supplements have been marketed with a variety of claims that they improve cognitive performance, reduce stress, improve sleep quality, and alleviate menstrual cramps. Evaluating these claims in 2011, the European Food Safety Authority assessed they were not supported by evidence.

References

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