Theanine Ameliorates Neuroinflammation And Protects Against Endotoxin-Induced Inflammation and Acute Liver Injury

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Theanine, a unique bioactive constituent from tea ( Camellia sinensis) leaves, is widely used as a functional ingredient and dietary supplement. To evaluate the anti-inflammatory and hepatoprotective effects of theanine and its molecular mechanism, the lipopolysaccharide (LPS)-induced inflammation mouse model was employed in this study. The survival rate of mice in the theanine-treated group increased significantly compared with that of LPS-only group mice. Furthermore, ICR male mice were randomly divided into three or four groups: control, LPS (LPS treatment only), LPS + theanine (20 mg/kg/day), and theanine (theanine treatment only). The results showed that compared with the LPS group, the liver damage and oxidative stress of the theanine-treated group decreased significantly, based on plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, hepatic total superoxide dismutase (T-SOD), and malondialdehyde (MDA) levels, and histological scores and apoptosis [terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase-3 activity] in the liver tissues. Furthermore, compared with no treatment, pretreatment with theanine significantly decreased the release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, inhibited the expression of several inflammatory factors (including IL-1β, TNF-α, and IL-6), and increased the IL-10/interferon (IFN)-γ ratio in the hepatic tissues. In the LPS-induced inflammation model, theanine inhibited the expression of proinflammatory mediators involved in the nuclear factor-kappa B (NF-κB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-κB in the hepatic tissues. Moreover, theanine suppressed the acute-phase response (elevated nitric oxide and C-reactive protein levels). Furthermore, theanine suppressed the LPS-induced inflammatory state by normalizing hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Taken together, the results suggest that theanine potentially ameliorates LPS-induced inflammation and acute liver injury; molecular mechanism of action may involve normalization of HPA axis hyperactivity and inactivation of the NF-κB signaling pathway.


A long term stressful event in life altering immune system is a major factor for the development of psychopathological conditions. By now it’s clear that stress induced neuroinflammatory cytokines are the key role in mediating neurochemical and neuroendocrine systems causing the behavioral disorders and cognitive impairment. Current anti depressants are unable to correct neurotransmitters levels directly or indirectly by inhibiting cytokines expression. Present study was conducted to elucidate the effect and mechanism of L-theanine on chronic restrainer stress (CRS) induced neuroinflammation, anxiety-like, depression, learning and memory impairment in C57BL/J male mice. Chronic restrain stress was induced by well ventilated 50ml conical tube for 6 hours/day 21 consecutive days. After stressor cessation behavioral and recognition tests were conducted, at the end of study mice were sacrificed, brain and blood was collected. Cytokines (TNF-α and IL-6), neurotransmitters were quantified in prefrontal cortex and estimated corticosterone levels in plasma. Histopathological examination of the hippocampus was performed. The results was implicated that L-theanine significantly (p<0.05) reversed the effect of CRS induced behavioral changes and memory impairment, reduced cytokines expression and restored neurotransmitter levels in prefrontal cortex. It also alleviated neuronal apoptosis and lowered the corticosterone levels in plasma of CRS mice. These results indicate that L-theanine exerted protective effect on chronic stress induced neuroinflammation, anxiety, depression and cognitive dysfunction. The mechanism of protective effect is by reducing cytokine expression in frontal cortex and preventing hippocampal apoptosis.
 

pauljacob

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There isn't any nutrient that will not heal you in one respect and kill you in another. Most of these studies are financed by interested parties. In this case, tea growers and sellers. In the above study it protects the liver. In the study below it damages the liver:
"EGCG of green tea extract is cytotoxic, and higher consumption of green tea can exert acute cytotoxicity in liver cells, a major metabolic organ in the body. Another study found that higher intake of green tea might cause oxidative DNA damage of hamster pancreas and liver."


Bottomline: Everything in moderation.
 
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Theanine, a unique bioactive constituent from tea ( Camellia sinensis) leaves, is widely used as a functional ingredient and dietary supplement. To evaluate the anti-inflammatory and hepatoprotective effects of theanine and its molecular mechanism, the lipopolysaccharide (LPS)-induced inflammation mouse model was employed in this study. The survival rate of mice in the theanine-treated group increased significantly compared with that of LPS-only group mice. Furthermore, ICR male mice were randomly divided into three or four groups: control, LPS (LPS treatment only), LPS + theanine (20 mg/kg/day), and theanine (theanine treatment only). The results showed that compared with the LPS group, the liver damage and oxidative stress of the theanine-treated group decreased significantly, based on plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, hepatic total superoxide dismutase (T-SOD), and malondialdehyde (MDA) levels, and histological scores and apoptosis [terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining and caspase-3 activity] in the liver tissues. Furthermore, compared with no treatment, pretreatment with theanine significantly decreased the release of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, inhibited the expression of several inflammatory factors (including IL-1β, TNF-α, and IL-6), and increased the IL-10/interferon (IFN)-γ ratio in the hepatic tissues. In the LPS-induced inflammation model, theanine inhibited the expression of proinflammatory mediators involved in the nuclear factor-kappa B (NF-κB) pathway, such as inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3), and attenuated the phosphorylation of NF-κB in the hepatic tissues. Moreover, theanine suppressed the acute-phase response (elevated nitric oxide and C-reactive protein levels). Furthermore, theanine suppressed the LPS-induced inflammatory state by normalizing hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Taken together, the results suggest that theanine potentially ameliorates LPS-induced inflammation and acute liver injury; molecular mechanism of action may involve normalization of HPA axis hyperactivity and inactivation of the NF-κB signaling pathway.


A long term stressful event in life altering immune system is a major factor for the development of psychopathological conditions. By now it’s clear that stress induced neuroinflammatory cytokines are the key role in mediating neurochemical and neuroendocrine systems causing the behavioral disorders and cognitive impairment. Current anti depressants are unable to correct neurotransmitters levels directly or indirectly by inhibiting cytokines expression. Present study was conducted to elucidate the effect and mechanism of L-theanine on chronic restrainer stress (CRS) induced neuroinflammation, anxiety-like, depression, learning and memory impairment in C57BL/J male mice. Chronic restrain stress was induced by well ventilated 50ml conical tube for 6 hours/day 21 consecutive days. After stressor cessation behavioral and recognition tests were conducted, at the end of study mice were sacrificed, brain and blood was collected. Cytokines (TNF-α and IL-6), neurotransmitters were quantified in prefrontal cortex and estimated corticosterone levels in plasma. Histopathological examination of the hippocampus was performed. The results was implicated that L-theanine significantly (p<0.05) reversed the effect of CRS induced behavioral changes and memory impairment, reduced cytokines expression and restored neurotransmitter levels in prefrontal cortex. It also alleviated neuronal apoptosis and lowered the corticosterone levels in plasma of CRS mice. These results indicate that L-theanine exerted protective effect on chronic stress induced neuroinflammation, anxiety, depression and cognitive dysfunction. The mechanism of protective effect is by reducing cytokine expression in frontal cortex and preventing hippocampal apoptosis.
Very nice. I get noticable mood and gut benefits the next day when taking theanine before bed, likely due to less inflammation.
There isn't any nutrient that will not heal you in one respect and kill you in another. Most of these studies are financed by interested parties. In this case, tea growers and sellers. In the above study it protects the liver. In the study below it damages the liver:
"EGCG of green tea extract is cytotoxic, and higher consumption of green tea can exert acute cytotoxicity in liver cells, a major metabolic organ in the body. Another study found that higher intake of green tea might cause oxidative DNA damage of hamster pancreas and liver."


Bottomline: Everything in moderation.
The study in the OP is about theanine though, not green tea. Polyphenols would be present in green tea, but not in the purified theanine, which seems to be very safe even in high doses, and it's those types of polyphenols that can cause toxicity. Too much green tea indeed seems to be harmful for the liver, and it also contains a significant amount of fluoride.
 

akgrrrl

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Very nice. I get noticable mood and gut benefits the next day when taking theanine before bed, likely due to less inflammation.

The study in the OP is about theanine though, not green tea. Polyphenols would be present in green tea, but not in the purified theanine, which seems to be very safe even in high doses, and it's those types of polyphenols that can cause toxicity. Too much green tea indeed seems to be harmful for the liver, and it also contains a significant amount of fluoride.
Yes, good post thankyou.
 

pauljacob

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Very nice. I get noticable mood and gut benefits the next day when taking theanine before bed, likely due to less inflammation.

The study in the OP is about theanine though, not green tea. Polyphenols would be present in green tea, but not in the purified theanine, which seems to be very safe even in high doses, and it's those types of polyphenols that can cause toxicity. Too much green tea indeed seems to be harmful for the liver, and it also contains a significant amount of fluoride.
Thank you Rafael Lao Wai for the correction. Appreciated :thumbsup:
 

Aleeri

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Worth noting, Ray Peat says green tea is very good in a recent One Radio episode. He also talks frequently about benefits of flavonoids during the past years podcast interviews. I think the liver toxicity is a no factor, it doesn't happen in dosages from regular daily consumption of tea, black tea seems easier to tolerate too.

I also haven't been able to see any estrogenic effects on my own lab results even at very high 6 cups of tea per day consumption. In fact my E2 was the best its ever been. Liver values was great as always.

There is a lot of studies on tea and COVID, it looks very promising and is frequently mentioned as a lead candidate, I recommend anyone interested to research it, I've been following that for over a year already. Italian researchers have started testing inhalers featuring EGCG.

Theanine is an amazing compound to me, I like it much more than caffeine.
 

Phosphor

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Worth noting, Ray Peat says green tea is very good in a recent One Radio episode. He also talks frequently about benefits of flavonoids during the past years podcast interviews. I think the liver toxicity is a no factor, it doesn't happen in dosages from regular daily consumption of tea, black tea seems easier to tolerate too.

I also haven't been able to see any estrogenic effects on my own lab results even at very high 6 cups of tea per day consumption. In fact my E2 was the best its ever been. Liver values was great as always.

There is a lot of studies on tea and COVID, it looks very promising and is frequently mentioned as a lead candidate, I recommend anyone interested to research it, I've been following that for over a year already. Italian researchers have started testing inhalers featuring EGCG.

Theanine is an amazing compound to me, I like it much more than caffeine.
Green tea (and black tea) contain fluoride.....drink enough and you will have the same thing happen, depending on your genetics, as happens to people with fluoroquinolone toxicity. So any detrimental effects from green tea can easily be the fluorine, which is highly toxic, and definitely nothing to do with the theonine.
 

Aleeri

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Green tea (and black tea) contain fluoride.....drink enough and you will have the same thing happen, depending on your genetics, as happens to people with fluoroquinolone toxicity. So any detrimental effects from green tea can easily be the fluorine, which is highly toxic, and definitely nothing to do with the theonine.
A case like this can easily be built for many supermarket goods or supplement almost, contamination, additives etc.

The worry for fluoride on this forum is often attributed to lowering thyroid function.

After a year of heavy tea consumption (mostly puerh which is supposed to be extra heavy in fluoride) my TSH is same as it was when consuming coffee. Overall none of my labs has changed for the worse since introducing tea, the labs were better in several areas which may or may not be attributed to tea. Whatever negative bias against tea here I really tried my best to find a trace of that in my own body and I simply cannot see any such effect.
 

Dave Clark

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A case like this can easily be built for many supermarket goods or supplement almost, contamination, additives etc.

The worry for fluoride on this forum is often attributed to lowering thyroid function.

After a year of heavy tea consumption (mostly puerh which is supposed to be extra heavy in fluoride) my TSH is same as it was when consuming coffee. Overall none of my labs has changed for the worse since introducing tea, the labs were better in several areas which may or may not be attributed to tea. Whatever negative bias against tea here I really tried my best to find a trace of that in my own body and I simply cannot see any such effect.
Yes. And I believe like many things, green tea and its components are hormetic in their effects. Moral of the story is the same, don't over do anything, even healthy foods and supplements. Green tea, when used responsibly has a great track record of being healthy and therapeutic.
 
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