L-theanine 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.
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