Theanine is an amino acid analog of the proteinogenic amino acids L-glutamic acid and L-glutamine
and is found primarily in particular plant and fungal species. It is also known as N5-ethyl-L-glutamine,
and by a variety of other synonyms. It was discovered as a constituent of a green tea
in 1949; in 1950 it was isolated from gyokuro leaves, which have high theanine content.
It is substantially present in black, green, and white teas prepared from Camellia sinensis,
and has also been isolated from Amazonian guayusa, and from the basidiomycete mushroom
Boletus badius. Appearance of the name "theanine" without a prefix can be understood to imply
the L-enantiomer; this is the form found in fresh teas and in some, but not all human
dietary supplements; the opposite D-enantiomer has far less studied pharmacologic properties,
but is present in racemic chemical preparations, and substantially in some studied theanine
supplements. As an analog of glutamate and glutamine, the
theanine in common preparations is absorbed in the small intestine after oral ingestion;
its hydrolysis is to L-glutamate and ethylamine and occurs both in the intestine and liver.
It can also cross the blood–brain barrier intact, and register pharmacological effects
directly. Theanine has been approved for use in all
foods, including herb teas, soft drinks, desserts, etc. with some restrictions applying to infant
foods. It provides a unique brothy or savory flavor to green tea infusions. It is generally
recognized as safe as an ingredient by the Food and Drug Administration, and is sold
as a dietary supplement in the US. However, the German Federal Institute for Risk Assessment,
an agency of their Federal Ministry of Food and Agriculture, has objected to the addition
of isolated theanine to beverages.
Structure and properties All except the common name of theanine reflect
its actual chemical structure; for instance, it is also known as N5-ethyl-L-glutamine,
and by a variety of other synonyms. The name theanine, without prefix, is generally understood
to imply the L- enantiomer, derived from the related proteinogenic L-amino acid glutamic
acid. Hence, theanine is an analog of this amino acid. Simply put, it is equivalent to
the amino acid L-glutamine when ethylated on the amide nitrogen, alternatively, to the
ethyl amide formed from ethylamine and L-glutamic acid at its γ- side chain carboxylic acid
group. Relative to theanine, the opposite enantiomer is largely absent from the literature,
except inexplicitly. 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 studies
have suggested that the D-isomer may actually predominate in some commercial supplement
preparations. Discovery and distribution
Theanine is found primarily in plant and fungal species; it was discovered as a constituent
of green tea prepared from Camellia sinensis in 1949; in 1950, a laboratory in Kyoto successfully
isolated it from gyokuro leaf, which has high theanine content. In actuality, theanine is
substantially present in black, green, and white teas in varying quantities, when prepared
from this plant. It has also been isolated from Amazonian guayusa, and from the basidiomycete
mushroom Boletus badius. The L-enantiomer is the form found in freshly prepared teas,
and some but not all human dietary supplements. Digestion and metabolism
As an analog of glutamate and glutamine, the theanine in preparations is absorbed in the
small intestine after oral ingestion; its hydrolysis to L-glutamate and ethylamine occur
both in the intestine and liver. It can also cross the blood–brain barrier intact, and
register pharmacological effects directly. Pharmacological effects
Able to cross the blood–brain barrier, theanine has reported psychoactive properties. Theanine
has been studied for its potential ability to reduce mental and physical stress, improve
cognition, and boost mood and cognitive performance in a synergistic manner with caffeine.
Theanine is reported to promote alpha wave production in the brain. Early studies of
theanine involved much larger doses than those found in an everyday cup of tea. Researchers
wonder whether drinking tea might have the same effects found in those studies. However,
one recent study funded by Unilever found that smaller doses typical of those found
in a cup of tea did induce changes in alpha waves as shown by EEG. It is structurally
similar to the excitatory neurotransmitter glutamate, however has only weak affinity
for the glutamate receptors on postsynaptic cells. While it only has a low affinity for
the ionotropic glutamate receptors - AMPA, kainate, and NMDA receptors - it does however
increase brain dopamine levels. Its effect on serotonin is still a matter of debate in
the scientific community, with studies showing increases and decreases in brain serotonin
levels using similar experimental protocols. It has also been found that injecting spontaneously
hypertensive mice with theanine significantly lowered levels of 5-hydroxyindoles in the
brain. Researchers also speculate it may inhibit glutamate excitotoxicity thereby increasing
glutamate. Studies on test rats have shown even repeated,
extremely high doses of theanine cause little to no harmful psychological or physical effects.
Theanine showed neuroprotective effects in one rat study.
A placebo-controlled trial has shown adding theanine to ongoing antipsychotic medication
is helpful in reducing some symptoms of schizophrenia. Several beverage manufacturers are selling
drinks containing theanine and are marketing them as drinks to help people focus and concentrate,
while other manufacturers claim relaxing and tranquillizing properties.
Supplement use In 2003, the German Federal Institute for
Risk Assessment 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.
In 2006, a study found no consistent, statistically significant treatment-related adverse effects
on behavior, morbidity, mortality, body weight, food consumption and efficiency, clinical
chemistry, hematology, or urinalysis in rats fed high doses of theanine for 13 weeks. Large
studies in humans have not been undertaken, however several smaller-scale studies have
shown increased alpha wave generation and lowered anxiety, along with benefits to sleep
quality in patients with ADHD. The combination of theanine and caffeine has
been shown to promote faster simple reaction time, faster numeric working memory reaction
time and improved sentence verification accuracy. Theanine may help the body's immune response
to infection by boosting the disease-fighting capacity of gamma delta T cells. The study,
published in 2003, included a four-week trial with 11 coffee drinkers and 10 tea drinkers,
who consumed 600 milliliters of coffee or black tea daily. Blood sample analysis found
the production of antibacterial proteins was up to five times higher in the tea drinkers,
an indicator of a stronger immune response. L-Theanine may contain mast cell-stabilizing
properties in an animal model. Theanine has been reported to raise levels
of brain serotonin, dopamine, and GABA, with possible improvement in to specific memory
and learning tasks. See also
gamma-Glutamylmethylamide Green tea
Notes and References
Further reading Y. Orihara & T. Furuya "Production of theanine
and other γ-glutamyl derivatives by Camellia sinensis cultured cells," Plant Cell Reports
9(2):65–68, DOI 10.1007/BF00231550, PMID 24226431.
E.K. Keenan, M.D.A. Finnie, P.S. Jones, P.J. Rogers, C.M. Priestley How much theanine in
a cup of tea? Effects of tea type and method of preparation, Food Chemistry 125(2):588–594,
DOI 10.1016/j.foodchem.2010.08.071.