nutritional supplement for mood modulation
You should consult your Doctor if you are taking any medication.
L-theanine is a non-protein amino acid mainly found naturally in the green tea plant (Camellia sinensis). L-theanine is the predominant amino acid in green tea and makes up 50% of the total free amino acids in the plant. The amino acid constitutes between 1% and 2% of the dry weight of green tea leaves. L-theanine is considered the main component responsible for the taste of green tea, which in Japanese is called umami. L-theanine is marketed in Japan as a nutritional supplement for mood modulation.
L-theanine is a derivative of L-glutamic acid. It is a water-soluble solid substance with the molecular formula C 7 H 14 O 3 N and a molecular weight of 160.19 daltons. L-theanine is also known as gamma-ethylamino-L-glutamic acid, gamma-glutamylethylamide, r-glutamylethylamide, L-glutamic acid gamma-ethylamide and L-N-ethylglutamine. The chemical structure is:
L-theanineACTIONS AND pHARMAColOGY ACTIONS
L-theanine may have activity in modulating the metabolism of cancer chemotherapeutic agents and ameliorating their side effects. It may also have mood-modulating activity.MECHANISM OF ACTION
In animal tumor models, L-theanine has been found to increase the antitumor activity of some anthracyline agents (doxorubicin, idarubicin) and to ameliorate some of the side effects of these agents. It appears that L-theanine inhibits the efflux of these agents from tumor cells, increasing the inhibitory concentration of the drugs in the target cells. At the same time, L-theanine appears to decrease the oxidative stress caused by these agents on normal cells. Most of the side effects of these agents are due to oxidative stress. The mechanism by which L-theanine inhibits the efflux of such cancer chemotherapeutic agents as doxorubicin is unclear. L-theanine appears to have modest antioxidant activity, and this may explain, in part, L-theanine's ability to ameliorate some of the side effects of the chemotherapeutic agents. Further, L-theanine, by an unclear mechanism, appears to inhibit the influx of chemotherapeutic normal cells.
The mechanism of L-theanine's possible mood-modulating activity is also unclear. The amino acid might affect the metabolism and the release of some neurotransmitters in the brain, such as dopamine.pHARMACOKINETICS.
Little is known about the pharmacokinetics of L-theanine in humans. From animal studies, it appears that L-theanine is absorbed from the small intestine via a sodium-coupled active transport process and appears to cross the blood-brain barrier. Not much is known beyond that. However, research is ongoing.INDICATIONS AND USAGE
L-theanine has exhibited anticancer effects and an ability to favorably modulate the activity of some anticancer drugs in in vitro and animal experiments. It has also demonstrated hypotensive effects in animal work. It has inhibited LDL-cholesterol oxidation in preliminary in vitro tests. It was recently reported to enhance learning ability in animals and to induce relaxation in human subjects, possibly through its effects on serotonin, dopamine and other neurotransmitters. It has also been shown to inhibit caffeine stimulation in another preliminary animal study.RESEARCH SUMMARY
L-theanine has been shown to enhance the anticancer activity of doxorubicin and idarubicin in in vitro and animal studies. In an in vitro study, L-theanine increased doxorubicin's inhibition of Ehrlich ascites carcinoma more than two-fold and increased nearly three-fold the concentration of doxorubicin in the tumor compared with treatment with doxorubicin alone.
Subsequently, L-theanine, in combination with doxorubicin, was shown to significantly reduce tumor weight (to 62% of the control level) in M5076 ovarian sarcoma-bearing mice. The doxorubicin dose used in this combination was ineffective by itself in inhibiting tumor growth. L-theanine was reported to increase doxorubicin concentration in the tumor by two- to seven-fold while simultaneously decreasing doxorubicin concentrations in normal tissues.
A combination of L-theanine and doxorubicin significantly inhibited both primary ovarian sarcoma and hepatic metastasis of the tumor. L-theanine was credited in this study with enhancing the activity of doxorubicin.
In another study, L-theanine was used in conjunction with idarubicin, a recently synthesized anthracyline derivative being used clinically in some parts of the world to treat acute myelocytic leukemia. The use of idarubicin had been limited due to the frequency with which it produces severe leukopenia. Combined with idarubicin in the treatment of p388 leukemia-bearing mice, L-theanine significantly inhibited suppression of bone marrow cells and leukopenia, while simultaneously enhancing the antitumor activity of idarubicin.
Very recently, L-theanine, in combination with doxorubicin, was further shown to have the ability to significantly inhibit even doxorubicin-resistant leukemia in mice.
In an in vitro test, L-theanine showed some ability to inhibit LDL peroxidation. The polyphenol component of a green-tea extract was more potent in this regard than the L-theanine component. The caffeine component, on the other hand, was less effective than L-theanine.
L-theanine has also exhibited hypotensive effects in spontaneously hypertensive rats but not in Wistar kyoto rats. Recently, L-theanine, at certain doses, was shown to inhibit caffeine stimulation, measured by electroencephalography in rats.
Recently, L-theanine, previously shown to penetrate the blood-brain barrier through the leucine-preferring transport system, has been demonstrated to produce significant increases in serotonin and/or dopamine concentrations in the brain, principally in the striatum, hypothalamus and hippocampus.
These findings led to recent studies investigating the possibility that L-theanine might enhance learning ability, induce relaxation and relieve emotional stress. Memory and learning ability were said to be improved in young male Wistar rats given 180 mg of L-theanine daily for four months. performance was assessed using a test for learning ability and passive and active avoidance tests for memory.
The mental effects of L-theanine were tested in a small group of volunteers divided into two groups defined as "high-anxiety" and "low-anxiety" groups. The volunteers were females aged 18 to 22. Their level of anxiety was assessed by a manifest anxiety scale. Subjects received water, 50 mg of L-theanine or 200 mg of L-theanine solution once a week. Brain waves were measured 60 minutes after administration. The 200 mg dose (dissolved in 100 ml of water) resulted in significantly greater production of alpha waves than was observed in subjects receiving water. Greatest production was consistently seen about 40 minutes after L-theanine intake. The effect was dose-dependent. The researchers regarded the significantly increased production of alpha-brain wave activity as an index of increased relaxation. More rigorous followup is needed.CONTRAINDICATIONS, pRECAUTIONS, ADVERSE REACTIONS CONTRAINDICATIONS
L-theanine is contraindicated in those who are hypersensitive to any component of an L-theanine-containing product.pRECAUTIONS
pregnant women and nursing mothers should avoid L-theanine supplements. Use of L-theanine supplements concomitantly with cancer chemotherapeutic agents must be done under medical supervision.ADVERSE REACTIONS
There are no known adverse reactions.INTERACTIONS DRUGS
Doxorubicin and Idarubicin : L-theanine may enhance the antitumor effects of these drugs and may ameliorate some of their side effects.DOSAGE AND ADMINISTRATION
L-theanine supplements are available in Japan for promotion of relaxation and modulation of mood. Doses used are between 50 and 200 mg, as necessary.
L-theanine is available in some green tea preparations. The amino acid constitutes between 1% and 2% of the dry weight of green tea leaves.liTERATURE
Juneja LR, Chu D-C, Okubo T, et al. L-Theanine -- a unique amino acid of green tea and its relaxation effect in humans. Trends Food Sci Tech. 1999; 10:199-204.
Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamylethylamide on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res . 1998; 23:667-673.
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