Theanine Completely Abolishes The Cortisol Response To Stress In Humans

haidut

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As I mentioned in my recent post on glycine lowering cortisol, I have suspected for a long time that inhibitory amino acids that act as GABA agonists will lower cortisol levels. The reason for this suspicion is that GABA agonist pharma drugs are used for treating the high cortisol of people with Cushing syndrome/disease. I posted an animal study some time ago showing that a hefty dose of theanine (1g+) lowered cortisol in animals. Now, this human study replicated the results and the even better news is that the dose is quite "low" compared to the animal study. The human dose used in this study was only 200mg and the effects were quite long lived as the cortisol lowering did not kick in until 3 hours after the amino acid was administered.

Anti-Stress, Behavioural and Magnetoencephalography Effects of an l-Theanine-Based Nutrient Drink: A Randomised, Double-Blind, Placebo-Controlled, ... - PubMed - NCBI

"...Due to evidence of violations to the assumption of normality in cortisol change, which were not corrected by transformation, non-parametric analysis of treatment effects was conducted. Results of Wilcoxon signed ranks tests showed no significant differences in cortisol change between active treatment compared to placebo 1 h post-dose (z = 1.28, p > 0.05, median cortisol response: placebo = −0.19, active = −0.02), but a significantly lower cortisol response 3 h post-dose for the active treatment visit (z = −1.98, p = 0.047, median cortisol response: placebo = 0.44, active = −0.09). A series of analyses were run in order to exclude the possibility that completion of the MEG component of the study immediately preceding this assessment differentially impacted cortisol responses. Mann–Whitney U-tests indicated that cortisol levels did not differ between MEG and non-MEG participants at the 3-h pre-MTF assessment at either treatment visit (placebo: z = −0.92, p = 0.372; active: z = −1.32, p = 0.197), nor did the MTF-related change in cortisol differ between MEG and non-MEG participants at either treatment visit (placebo: z = −0.92, p = 0.372; active: z = −0.33, p = 0.771) Change in cortisol for each assessment point is plotted for both treatment visits in Figure 2."

Attached is also a screenshot from the study that shows that theanine basically lowered stress-induced cortisol levels back to placebo status BEFORE stress.
 

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marikay

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Any guess as to how long the cortisol lowering effect lasts once it kicks in?
 

madbored

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Theanine really helps mitigate the stress response for me unlike anything else, and without the side effects of cyproheptadine. Thank you for posting these studies haidut.
 

Peata

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Theanine really helps mitigate the stress response for me unlike anything else, and without the side effects of cyproheptadine. Thank you for posting these studies haidut.

I felt the same. I am currently back on Cyproheptadine after running out of theanine,but switching back over to theanine soon.
 

tyler

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Haidut! Do you think you would ever create a pure theanine supplement?
 

DaveFoster

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Great information. Definitely the best co-supplement to caffeine, along with cypro.
 

haidut

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Any guess as to how long the cortisol lowering effect lasts once it kicks in?

The study only looked at 1h and 3h post-dose since that is when they expected brain concentrations of theanine to be elevated. But they also say that some research suggests theanine concentrations in the brain really peak 5h after administration.
"...The two full testing days followed identical procedures, in which participants completed a cognitive stressor on three occasions (pre-treatment baseline, then one and three hours post-dose). Time of day was kept constant, with participants receiving a standardised light meal upon arrival at the laboratory (11:00), baseline stressor assessment beginning late morning (11:30) and the dose being given at midday (12:00). Measures of stress, fatigue and mood in addition to salivary cortisol were obtained immediately prior to and following each completion of the cognitive stressor. A subset (n = 17) of participants also participated in magnetoencephalography (MEG) recordings two hours post-dose in order to assess potential neurophysiological changes associated with treatment. l-theanine has been shown to reach peak concentrations in mammals between 30 and 120 min [4,5], with peak plasma concentrations in humans reported approximately 50 min post-dose [6]. Evidence from lower mammal research suggests that brain l-theanine levels may be increased after one hour, but peak as much as five hours post administration [42]. Thus, assessment one and three hours post-dose captures a period in which plasma and brain l-theanine concentrations are significantly elevated."

Given theanine's half life of 3 hours in blood, and the 5 hours peak in the brain, I would expect an effect that starts after 2h/3h and lasts for up to the 7th hour (4-5 hours of total effect). So, dosing theanine at 200mg every 6 hours seems optimal for this purpose. This is also the dose sufficient for lowering serotonin and raising dopamine. Keep in mind that anything that lowers serotonin will also lower cortisol, so a good portion of theanine's effects may be due to serotonin inhibition. That would make it one of the few multi-mechanism cortisol blockers since it would act both through the GABA pathway and the serotonin blocking pathway. Theanine is also a glutamate antagonist and that is yet another very cool property. Anti-glutamatergic, anti-cortisol, and anti-serotonin drugs have separately been shown to be very potent anti-depressants. Theanine, combing all of these effects, would make a really good anti-depressant IMO. Unsurprisingly, it is being studies as a possible cure for PTSD, which is a disorder that combines all of these dysfunctions.
Just my 2c.
 

haidut

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Haidut! Do you think you would ever create a pure theanine supplement?

I've thought about it but there are already vendors on the market offering theanine powder pretty cheaply. I may do a master anti-stress supplement that contains theanine and a few other ingredients in it. Right now I am trying to make more of less "orthogonal" supplements - i.e. ones not overlapping in ingredients. This means that a combination of a few of them would give you pretty much any desired effect without the need to release a specialized supplement for a very small niche. That being said, I am always open to releasing a product if there is sufficient interest in it. So, I am keeping my eyes/ears open.
 

Drareg

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I'm pretty sure Theanine lessens a double chin effect for me, Niacinamide seems to give me a double chin,creatine sometimes. was curious if this was a liver effect because k2 seems to lessen the double chin also.

I'm not overweight, more athletic shaped ,some friends in good shape wonder about double chin effect also.
I'm confident it's not a fat burning effect as no change in weight.
 

haidut

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I'm pretty sure Theanine lessens a double chin effect for me, Niacinamide seems to give me a double chin,creatine sometimes. was curious if this was a liver effect because k2 seems to lessen the double chin also.

I'm not overweight, more athletic shaped ,some friends in good shape wonder about double chin effect also.
I'm confident it's not a fat burning effect as no change in weight.

Creatine has studies showing it increases water retention.Maybe niacinamide does too even though I'd expect it to do the opposite actually. Interesting effect of theanine on skin, lowering cortisol is known to improve things like sagging skin and GERD.
 

Makrosky

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Yeah, if you are reliant on stress hormones, have something to boost your metabolism if you take theanine. Or it will knock you down.
 

Bodhi

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Could this be the reason why drinking green tea is estrogenic as it lowers cortisol, thus inhibit's conversion of T4 to T3...
 

Drareg

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Could be the case Bodhi.
Theanine Isolated from green tea does not increase estrogen from what I see, Peat recommends Theanine in one of his newer articles on serotonin,he must be satisfied with the research on it do far.
 

Agent207

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Very interesting Haidut. Im wondering if it would be a good idea to add it to a pre-workout shake, since its known too because its sedative effects.
 

haidut

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Very interesting Haidut. Im wondering if it would be a good idea to add it to a pre-workout shake, since its known too because its sedative effects.

If it takes a few hours for it to reach peaks in the brain then you are probably OK with ingesting it before working out unless you plan on running a marathon:):
 

haidut

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Could this be the reason why drinking green tea is estrogenic as it lowers cortisol, thus inhibit's conversion of T4 to T3...

Cortisol is one of the most potent stimulators of aromatase. The estrogenic effects of green tea are probably due to the flavanols and EGCG contents, not theanine. GABA agonists like theanine are highly unlikely to raise estrogen, and will probably lower it. GABA agonists also (usually) upregulate 5-AR, which is another point against estrogen.
 
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