Scientific Support

June 6th 2005

Department of Psychiatry : Sir Ganga Ram Hospital Lahore, Pakistan concludes scientific study with HBC Protocols Thea-Zen. 

Study concludes Thea-Zen produced excellent results in the treatment of Mild Depression, Anxiety, Stress and lack of concentration. (click here to view results)



Research studies are quite clear on the facts that people who produce more alpha brain waves also experience less anxiety as well as increased creativity when faced with problem solving. For example, elite athletes tend to produce a burst of alpha waves on the left side of their brain during their best performances. In addition to being considered a "relaxing" substance, theanine has also been shown to improve learning performance in mice, as well as concentration in human subjects.
 
One of the most unique aspects of theanine activity is its ability to increase the brain's output of alpha waves. Alpha waves are one the four basic brain brain-wave patterns (delta, theta, alpha, and beta) that can be monitored using an electroencephalogram (EEG). Each wave pattern is associated with a particular oscillating electrical voltage in the brain, and the different brain brain-wave patterns are associated with different mental states and states of consciousness (Theta = Drowsiness; Alpha = Relaxed/Alertness; Beta = Stress/Anxiety). A handful of studies (in rats) have shown theanine to be an effective anti-hypertension agent. In these studies, it is interesting to note that theanine was able to bring elevated blood pressure back toward normal levels, but it had no effect in reducing normal blood pressure levels.
 
There are also more than a dozen reports in the scientific literature which show a clear benefit of theanine in fighting various forms of experimental cancer. Theanine has been shown to enhance the anti-tumor activity of some cancer drugs such as pirarubicin, doxorubicin and adriamycin. It appears that theanine slows the ability of the tumor cells to eject the cancer drugs - so combination therapy with the chemotherapy agent plus theanine seems to maintain high levels of the drug in the tumor cells and both slow their growth and accelerate their death.
 
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.
 
Japan is credited with most of the clinical studies and information L-theanine. There are no dietary limits on L-theanine intake by the Japan Food Additive Association. In 1964, the Japanese Ministry of Health and Welfare approved L-theanine for unlimited use in all foods, with the exception of infant foods. The intended use of L-theanine is that of a mental and physical relaxant that does not induce drowsiness. Although there is no set schedule for taking L-theanine, it may generally be taken at the first signs of stress. Based on the results of the clinical studies, L-theanine is most effective in the range of 50-200 mg, with the effect being felt within 30 minutes and lasting for 8-10 hours. Individuals with high stress levels may increase their dosage of L-theanine to at least 100 mg, with no more than 600 mg being taken in a six hour period. FDA recommends a maximum dose of 1200 mg daily, although the reason for this limit is not clear, due to its demonstrated safety.
 
There are no known adverse reactions to L-theanine and no drug interactions have been reported. L-theanine is not affected by food and may be taken anytime, as needed. Absorbed from the small intestine via a sodium-coupled active transport process, L-theanine crosses the blood-brain barrier. L-theanine competes for absorption in the intestinal tract and the brain with the amino acids found in the methionine group (leucine, isoleucine, and valine), however the concentrations of amino acids are unchanged by simultaneous ingestion of L-theanine. L-theanine is extremely safe.  Although it is probably safe for pregnant women and nursing mothers, we discourage its use by them pending conclusive research.
 
Conclusion Research into L-theanine derived from the contradictory observation that green tea, with its high caffeine content, produces a very calming effect. The seemingly multi-dimensional reasons for this relaxation effect will continue to be studied. Current areas of ongoing research include using L-theanine as an alternative to Ritalin in children and adults, as a treatment for PMS, in controlling certain conditions of high blood pressure, in sharpening mental acuity and concentration, and as an anti-cancer agent alone and in synergy with other cancer-fighting agents. L-theanine may find another area of application for its use as a supplement in reducing the negative side effects of caffeine brought on by the over-consumption of coffee, soft drinks, or other caffeine-containing substances. 7.) References 1. Kakuda T, Nozawa A, Unno T, et al. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechno Biochem 2000; 64:287-293. 2. Mason R. 200 mg of Zen; L-theanine boosts alpha waves, promotes alert relaxation. Alternative & Complementary Therapies 2001,April; 7:91-95 3. 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. 4. Yokozawa T, Dong E. Influence of green tea and its three major components upon low-density lipoprotein oxidation. Exp Toxicol Pathol 1997; 49(5):329-335. After more than 15 years research, we can supply 100% natural Green Tea L-Theanine std. 10%, 20%, 50%, 80%, 90%, 98%, 99% (Tested by HPLC method) now!
 
Refrences: 1. Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93. 2. Kakuda T, Yanase H, Utsunomiya K, Nozawa A, Unno T, Kataoka K. Protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed neuronal death in gerbils. Neurosci Lett. 2000 Aug 11;289(3):189-92. 3. Sadzuka Y, Sugiyama T, Hirota S. Modulation of cancer chemotherapy by green tea. Clin Cancer Res. 1998 Jan;4(1):153-6. 4. Sadzuka Y, Sugiyama T, Miyagishima A, Nozawa Y, Hirota S. The effects of theanine, as a novel biochemical modulator, on the antitumor activity of adriamycin. Cancer Lett. 1996 Aug 2;105(2):203-9. 5. Sadzuka Y, Sugiyama T, Sonobe T. Efficacies of tea components on doxorubicin induced antitumor activity and reversal of multidrug resistance. Toxicol Lett. 2000 Apr 3;114(1-3):155-62. 6. Sadzuka Y, Sugiyama T, Sonobe T. Improvement of idarubicin induced antitumor activity and bone marrow suppression by theanine, a component of tea. Cancer Lett. 2000 Oct 1;158(2):119-24. 7. Sadzuka Y, Sugiyama T, Suzuki T, Sonobe T. Enhancement of the activity of doxorubicin by inhibition of glutamate transporter. Toxicol Lett. 2001 Sep 15;123(2-3):159-67. 8. Sadzuka Y, Yamashita Y, Sugiyama T, Sonobe T. Effect of dihydrokainate on the antitumor activity of doxorubicin. Cancer Lett. 2002 May 28;179(2):157-63. 9. Sugiyama T, Sadzuka Y, Tanaka K, Sonobe T. Inhibition of glutamate transporter by theanine enhances the therapeutic efficacy of doxorubicin. Toxicol Lett. 2001 Apr 30;121(2):89-96. 10. Sugiyama T, Sadzuka Y. Combination of theanine with doxorubicin inhibits hepatic metastasis of M5076 ovarian sarcoma. Clin Cancer Res. 1999 Feb;5(2):413-6. 11. Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett. 1998 Nov 13;133(1):19-26. 12. Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 1995 Apr;59(4):615-8. 13. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylmethylamide in spontaneously hypertensive rats. Life Sci. 1998;62(12):1065-8. 14. Yokogoshi H, Terashima T. Effect of theanine, r-glutamylethylamide, on brain monoamines, striatal dopamine release and some kinds of behavior in rats. Nutrition. 2000 Sep;16(9):776-7. 15. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., Takeuchi, N. "Reduction Effect of Theanine on Blood Pressure and Brain 5-Hydroxyindoles in Spontaneously Hypertensive Rats." Biosciences, Biotechnology, and Biochemistry, April 1995, 59(4): 615-18. 16. Yokogoshi, H., Terashima, T. "Effect of Theanine, R-Glutamylethylamide, on Brain Monoamines, Striatal Dopamine Release and Some Kinds of Behavior in Rats." Nutrition, Sept. 2000, 16(9): 776-77. 17. Zhang G, Miura Y, Yagasaki K. Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats. Biosci Biotechnol Biochem. 2002 Apr;66(4):711-6