Theanine , also known as L-theanine, L-gamma-glutamylethylamide, or ''N''⁵-ethyl-L-glutamine, is a

non-proteinogenic amino acid In biochemistry, non-coded or non-proteinogenic amino acids are distinct from the 22 proteinogenic amino acids (21 in eukaryotesplus formylmethionine in eukaryotes with prokaryote organelles like mitochondria), which are naturally encoded in the ...

similar to the

proteinogenic amino acids Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation (biology), translation from RNA. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically e ...

L-glutamate and L-glutamine. It is produced by certain plants such as the

tea Tea is an aromatic beverage prepared by pouring hot or boiling water over cured or fresh leaves of '' Camellia sinensis'', an evergreen shrub native to East Asia which probably originated in the borderlands of south-western China and nor ...

plant (''

Camellia sinensis ''Camellia sinensis'' is a species of evergreen shrub or small tree in the flowering plant family Theaceae. Its leaves, leaf buds, and stems can be used to produce tea. Common names include tea plant, tea shrub, and tea tree (unrelated to ''Me ...

''), and by some

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

. Theanine was discovered in 1949 as a constituent of

green tea Green tea is a type of tea made from the leaves and buds of the '' Camellia sinensis'' that have not undergone the withering and oxidation process that creates oolong teas and black teas. Green tea originated in China in the late 1st millenn ...

and was isolated in 1950 from ''

gyokuro is a type of green tea from Japan. It differs from the standard ''sencha'' (a classic green tea grown in the sun) in being grown under the shade rather than the full sun. The name "gyokuro" translates as "jewel dew" (or "jade dew"). According to ...

'' tea leaves. It constitutes about 1–2% of the dry weight of green tea leaves. The name ''theanine'' usually refers to the

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

''L-theanine'', which is the form found in

tea leaves ''Camellia sinensis'' is a species of evergreen shrub or small tree in the flowering plant family Theaceae. Its leaves, leaf buds, and stems can be used to produce tea. Common names include tea plant, tea shrub, and tea tree (unrelated to '' M ...

from which it is

extract An extract (essence) is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures or absolutes or dried and powdered. The aromatic principles of ma ...

ed as a powder. The right-handed enantiomer, ''D-theanine'', is less-studied. Theanine is sold as a

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

. It is packaged in

gelatin capsule In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms—techniques used to enclose medicines—in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as supposit ...

s, tablets, and as a

powder A powder is a dry solid composed of many very fine particles that may flow freely when shaken or tilted. Powders are a special sub-class of granular materials, although the terms ''powder'' and ''granular'' are sometimes used to distinguish se ...

, and may be an ingredient in branded supplements with

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

. It is also used as an

ingredient In a general sense, an ingredient is a substance which forms part of a mixture. In cooking, recipes specify which ingredients are used to prepare a dish, and the term may also refer to a specific food item in relation to its use in different re ...

in food and beverages. In 1964 Japan approved its unlimited use in all foods (including chocolates, soft drinks, and herb teas) except infant food, while since 2007 it is considered to be

safe A safe (also called a strongbox or coffer) is a secure lockable enclosure used for securing valuable objects against theft or fire. A safe is usually a hollow cuboid or cylinder, with one face being removable or hinged to form a door. The body ...

at doses up to 250

milligram The kilogram (also spelled kilogramme) is the base unit of mass in the International System of Units (SI), equal to one thousand grams. It has the unit symbol kg. The word "kilogram" is formed from the combination of the metric prefix kilo- (m ...

s (mg) per serving by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

. In 2011 the

European Food Safety Authority The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002 ...

found there was insufficient evidence for a

causal relationship Causality is an influence by which one event, process, state, or object (''a'' ''cause'') contributes to the production of another event, process, state, or object (an ''effect'') where the cause is at least partly responsible for the effect, ...

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''⁵-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-'')

, derived from the related proteinogenic L-amino acid

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

. Theanine is an analog of this amino acid, and its primary

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

, L-

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

(also a proteinogenic amino acid). Theanine is a derivative of glutamine that is ethylated on the

nitrogen (as the name ''N''⁵-ethyl-L-glutamine describes), or alternatively, to the amide formed from

ethylamine Ethylamine, also known as ethanamine, is an organic compound with the chemical formula, formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It condenses just below room temperature to a liquid miscibility, miscible with virtual ...

and L-glutamic acid at its γ- (5-) side chain

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

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 Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme- catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve ...

L- enantiomeric form, mishandled isolates and racemic chemical preparations of theanines necessarily contain both theanine and its D-enantiomer (and from

racemic In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...

syntheses, in equal proportion), and studies have suggested that the D-isomer may actually ''predominate'' in some commercial supplement preparations. Amino acid

racemization In chemistry, racemization is a conversion, by heat or by chemical reaction, of an optically active compound into a racemic (optically inactive) form. This creates a 1:1 molar ratio of enantiomers and is referred to as a racemic mixture (i.e. cont ...

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 (''

)'' in 1949, and in 1950 a laboratory in Kyoto successfully isolated it from

leaf, which has high theanine content. Theanine is substantially present in black, green, and white

s from ''Camellia sinensis'' in quantities of about 1% of the dry weight. Deliberately shading tea plants from direct sunlight, as is done for

matcha is a finely ground powder of green tea specially processed from shade-grown tea leaves. Shade growing gives matcha its characteristic bright green color and strong umami flavor. Matcha is typically consumed suspended in hot water. Matcha ori ...

and

green tea, increases L-theanine content. The L-

is the form found in freshly prepared teas and some human dietary supplements.

Digestion and metabolism

As a

structural analog A structural analog, also known as a chemical analog or simply an analog, is a chemical compound, compound having a chemical structure, structure similar to that of another compound, but differing from it in respect to a certain component. It can ...

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

and

, the theanine in teas or supplements is absorbed in the

small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

after oral ingestion; its

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

to L-glutamate and

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

, and binds to

glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

, though with much lower affinity in comparison. Specifically, it binds to

ionotropic glutamate receptor Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in ...

s in the

micromolar Molar concentration (also called molarity, amount concentration or substance concentration) is the number of moles of solute per liter of solution. Specifically, It is a measure of the concentration of a chemical species, in particular, of a s ...

range, including the

AMPA α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate Glutamic acid (symbol Glu or E; kn ...

and

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a dr ...

s and, to a lesser extent, the

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

. It acts as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.partial co-agonist of the

s. In vitro, theanine also binds to

group I Group 1 may refer to: * Alkali metal, a chemical element classification for Alkali metal * Group 1 (motorsport), a regulation set of the FIA for series-production touring cars used in motorsport. * Group One Thoroughbred horse races, the leading e ...

mGluRs. In addition, it inhibits glutamine transporters and

glutamate transporter Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate – the principal excitatory neurotransmitter – across a membrane. The family of glutamate transporters is composed of two primary subclasses: the ex ...

s, and thus blocks the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmi ...

of glutamine and glutamate. Theanine may elicit

umami Umami ( from ), or savoriness, is one of the five basic tastes. It is characteristic of broths and cooked meats. People taste umami through taste receptors that typically respond to glutamates and nucleotides, which are widely present in me ...

taste, a consequence potentially associated with binding to and activation of the T1R1 +

T1R3 Taste receptor type 1 member 3 is a protein that in humans is encoded by the ''TAS1R3'' gene. The ''TAS1R3'' gene encodes the human homolog of mouse Sac taste receptor, a major determinant of differences between sweet-sensitive and -insensitive m ...

heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

or umami (savory) taste receptor.

Regulatory status

The regulatory status of theanine varies by country. It is sold as a dietary supplement across the United States and European Union. 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 Gras may refer to: People * Basile Gras (1836–1901), French firearm designer * Enrico Gras (1919–1981), Italian filmmaker * Felix Gras (1844–1901), Provençal poet and novelist * Laurent Gras (disambiguation) * N. S. B. Gras (1884–1956), ...

and allows its use as an ingredient in foods and beverages up to a maximum of 250 mg per serving. In 2003, the German Federal Institute for Risk Assessment (''Bundesinstitut für Risikobewertung'', BfR), an agency of their

Federal Ministry of Food and Agriculture The Federal Ministry of Agriculture, Food and Regional Identity (; abbreviated BMLEH) is a cabinet-level ministry of the Federal Republic of Germany. Its primary headquarters are located in Bonn with a secondary office in Berlin. From 1949 to ...

, objected to the addition of isolated theanine to beverages. 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 were 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, it was the opinion of the BfR that

pharmacological Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

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 Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

and

hypnotics A hypnotic (from Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness). Th ...

. 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 A prime number (or a prime) is a natural number greater than 1 that is not a product of two smaller natural numbers. A natural number greater than 1 that is not prime is called a composite number. For example, 5 is prime because the only ways ...

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

s 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 Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

to treat stress and anxiety. Evidence from a systematic review of randomised controlled trials suggests that L-theanine supplementation may be more effective than placebo in alleviating psychopathological symptoms associated with

anxiety disorder Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

, and

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. Theanine supplements have been marketed with a variety of claims that they improve cognitive performance, reduce stress, improve sleep quality, and alleviate

menstrual cramps The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of egg ...

. Evaluating these claims in 2011, the

assessed they were not supported by evidence in studies provided at that time.