24 replies to this topic

[Blue]

"Following acute ingestion of green tea by six human subjects, HPLC-MS2 analysis revealed that flavan-3-ol methyl, glucuronide and sulfate metabolites appeared in the bloodstream but did not pass through the blood-cerebrospinal fluid barrier. These observations emphasize the discrepancies between in vitro and in vivo evidence on the neuroprotective role of these compounds. If, as has been proposed, green tea exerts neuroprotective effects, this finding indicates that the active components are not flavan-3-ols or their metabolites. Alternatively, a systemic action may be hypothesised whereby dietary flavan-3-ols up-regulate antioxidant defences and/or reduce inflammation, the benefit of which may be effective throughout the body."
http://www.ncbi.nlm....pubmed/16910171

Which should make about a zillion or so brain cell studies looking at EGCG and brain disease irrelevant for humans. EGCG passes the blood-brain barrier in rats but according to this not in humans. So another zillion animal studies looking at EGCG and brain disease may very will be irrelevant for humans. Strange that this study from 2006 has not received more attention.

Edited by Blue, 24 August 2009 - 10:12 PM.

[niner]

I started taking Green Tea Extract last year for various health benefits, and had a noticeable psych effect; I found that my motivation was significantly higher. There was no obvious CNS stimulation, but I was sure accomplishing a lot more. I'm not sure what all the study you linked looked at. I don't know about the methyl metabolite, that would depend on what was methylated, but I would have been very surprised if the glucuronide or sulfate metabolites passed the BBB. Like they say, maybe it's something other than the flavan-3-ols, or maybe this is telling us that in vitro evidence isn't worth much. The latter is true regardless. Green Tea has enough other valuable properties that it's still on my shelf, even if it doesn't do anything for my brain.

[navyblue]

The L-Theanine in green tea is said to increase both dopamine and gaba levels. I'm guessing the motivation would be coming from the increase in dopamine. Niner, do you get the same effects from L-Tyrosine as well?

[niner]

The L-Theanine in green tea is said to increase both dopamine and gaba levels. I'm guessing the motivation would be coming from the increase in dopamine. Niner, do you get the same effects from L-Tyrosine as well?

dunno; never tried it.

[okok]

I take decaff green-tea, and i attribute the effects on mood to mao-inhibition.

[youandme]

Still seems to me that GreenTea is worth a try after reading that.
Though I prefer White Tea's flavour.

Hmm Got me wondering what Neuro Protective Supps/Foods DO cross the BBB

Edited by youandme, 25 August 2009 - 10:30 AM.

[Athanasios]

Whole green tea on cognitive function, for those who are wondering:

Am J Clin Nutr. 2006 Feb;83(2):355-61. Links
Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, Awata S, Nagatomi R, Arai H, Tsuji I.
Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. kuriyama-thk@umin.ac.jp
BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.
PMID: 16469995 [PubMed - indexed for MEDLINE]

Powerful, but like blue said, likely not the EGCG in action.

[JLL]

Doesn't prove causation, though. But, there's this study as well:

Green Tea Protects from the Psychological Effects of Stress in Rats

Psychological stress negatively affected the behavior and memory of rats. This adverse effect was associated with higher levels of cortisol, reactive oxygen species, IL-2, and IL-6, and lower levels of norepinephrine, dopamine, and total antioxidative capacity.

These changes were partially inhibited by diets containing 0.5% and 1% green tea polyphenols, except for IL-6, which was further increased by GTPs. A diet containing only 0.1% GTPs did not show significant results.

Maybe inflammation and cognitive impairment are related in the elderly?

Edited by JLL, 25 August 2009 - 07:35 PM.

[Blue]

Regarding human epidemiologic studies there are many problems the most important being that drinking lots of green tea is not unlikely related to many other healthy behaviors. It would not be surprising if those drinking a lot of green tea also smoke less, eat more fruits and vegetables in general, exercise more etc. This would almost certainly be the case in western nations. It may be different in Japan but who knows.

[niner]

Regarding human epidemiologic studies there are many problems the most important being that drinking lots of green tea is not unlikely related to many other healthy behaviors. It would not be surprising if those drinking a lot of green tea also smoke less, eat more fruits and vegetables in general, exercise more etc. This would almost certainly be the case in western nations. It may be different in Japan but who knows.

Epidemiology is all about controlling for such confounders. I'm sure the obvious ones were covered. The only question is was there one they missed?

The effect of green or other teas on congnitive function could probably be attributed to differences in vascular health. That's pretty highly correlated with cognitive function. So even if EGCG doesn't cross the BBB, it could still contribute to cognitive function through enhanced vascular health.

[Blue]

"Background: Laboratory research suggests that tea has potential neurocognitive protective effects, but this is not established in humans. Objective: We aimed to examine the relation between tea intake and cognitive impairment and decline.

Design: Among community-living Chinese adults aged 55 y in the Singapore Longitudinal Ageing Studies cohort, we measured tea consumption at baseline and administered the Mini-Mental State Examination (MMSE) at baseline and 1–2 y later. Cognitive impairment was defined as an MMSE score 23 and cognitive decline as a drop in MMSE score of 1 point. We performed cross-sectional analysis of baseline data from 2501 participants and longitudinal analysis of data from 1438 cognitively intact participants. Odds ratios (ORs) of association were calculated in logistic regression models that adjusted for potential confounders.

Results: Total tea intake was significantly associated with a lower prevalence of cognitive impairment, independent of other risk factors. Compared with the ORs for rare or no tea intake, the ORs for low, medium, and high levels of tea intake were 0.56 (95% CI: 0.40, 0.78), 0.45 (95% CI: 0.27, 0.72), and 0.37 (95% CI: 0.14, 0.98), respectively (P for trend < 0.001). For cognitive decline, the corresponding ORs were 0.74 (95% CI: 0.54, 1.00), 0.78 (95% CI: 0.55, 1.11), and 0.57 (95% CI: 0.32, 1.03), respectively (P for trend = 0.042). These effects were most evident for black (fermented) and oolong (semi-fermented) teas, the predominant types consumed by this population. In contrast, no association between coffee intake and cognitive status was found.

Conclusion: Regular tea consumption was associated with lower risks of cognitive impairment and decline."
http://www.ajcn.org/...stract/88/1/224

Interesting that black tea was better.

[okok]

Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration.

Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S.
Eve Topf, Technion-Faculty of Medicine, Haifa, Israel.
In the present study we demonstrate neuroprotective property of green tea extract and (-)-epigallocatechin-3-gallate in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin caused dopamine neuron loss in substantia nigra concomitant with a depletion in striatal dopamine and tyrosine hydroxylase protein levels. Pretreatment of mice with either green tea extract (0.5 and 1 mg/kg) or (-)-epigallocatechin-3-gallate (2 and 10 mg/kg) prevented these effects. In addition, the neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase (165%) activities, both effects being prevented by (-)-epigallocatechin-3-gallate. (-)-Epigallocatechin-3-gallate itself also increased the activities of both enzymes in the brain. The neuroprotective effects are not likely to be caused by inhibition of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine conversion to its active metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase-B, as both green tea and (-)-epigallocatechin-3-gallate are very poor inhibitors of this enzyme in vitro (770 microg/mL and 660 microM, respectively). Brain penetrating property of polyphenols, as well as their antioxidant and iron-chelating properties may make such compounds an important class of drugs to be developed for treatment of neurodegenerative diseases where oxidative stress has been implicated.

also,

Indian J Exp Biol. 2006 Nov;44(11):913-7. Links
Green tea [Camellia sinensis (L.) O. Kuntze] extract reverses the despair behaviour in reserpinised and diabetic mice.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.

Green tea (C. sinensis) extract (GTE) dose dependently produced reversal of despair in normal, reserpinised and diabetic mice, thereby demonstrating an antidepressant effect. Although the exact mechanism is yet to be explored, the possible inhibition of catechol-o-methyl transferase and monoamine oxidase enzymes may be responsible for antidepressant activity of GTE.

PMID: 17205714 [PubMed - in process]

(bbb impaired in diabetes).

Edited by okok, 25 August 2009 - 11:35 PM.

[Blue]

Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration.

Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S.
Eve Topf, Technion-Faculty of Medicine, Haifa, Israel.
In the present study we demonstrate neuroprotective property of green tea extract and (-)-epigallocatechin-3-gallate in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease. N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin caused dopamine neuron loss in substantia nigra concomitant with a depletion in striatal dopamine and tyrosine hydroxylase protein levels. Pretreatment of mice with either green tea extract (0.5 and 1 mg/kg) or (-)-epigallocatechin-3-gallate (2 and 10 mg/kg) prevented these effects. In addition, the neurotoxin caused an elevation in striatal antioxidant enzymes superoxide dismutase (240%) and catalase (165%) activities, both effects being prevented by (-)-epigallocatechin-3-gallate. (-)-Epigallocatechin-3-gallate itself also increased the activities of both enzymes in the brain. The neuroprotective effects are not likely to be caused by inhibition of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine conversion to its active metabolite 1-methyl-4-phenylpyridinium by monoamine oxidase-B, as both green tea and (-)-epigallocatechin-3-gallate are very poor inhibitors of this enzyme in vitro (770 microg/mL and 660 microM, respectively). Brain penetrating property of polyphenols, as well as their antioxidant and iron-chelating properties may make such compounds an important class of drugs to be developed for treatment of neurodegenerative diseases where oxidative stress has been implicated.

Hmm, the catalase and superoxide dismutase increase in the brain cells is unlikely to come from EGCG acting on blood vessels but more likely from EGCG inside the BBB. Which is a sign that animal models regarding green tea and brain diseases are unreliable.

[okok]

So maybe at least metal chelation may be of benefit (in stress pathologies).

[niner]

Hmm, the catalase and superoxide dismutase increase in the brain cells is unlikely to come from EGCG acting on blood vessels but more likely from EGCG inside the BBB. Which is a sign that animal models regarding green tea and brain diseases are unreliable.

So EGCG penetrates the BBB in mice, but apparently not humans. The paper in the first post of this thread only looked at flavanols. It would be great to get some more data since it was so small, but it's kind of an ugly experiment; not something very easy to get past the human studies review board, I'd think. There's still a lot of epidemiology that finds tea to be neuroprotective, but maybe it doesn't work via the mechanisms suggested by in vitro work. In vitro is crap... Some times it's the only crap we have, but don't expect it to translate to humans.

[JLL]

Regarding human epidemiologic studies there are many problems the most important being that drinking lots of green tea is not unlikely related to many other healthy behaviors. It would not be surprising if those drinking a lot of green tea also smoke less, eat more fruits and vegetables in general, exercise more etc. This would almost certainly be the case in western nations. It may be different in Japan but who knows.

In the Western world that's probably true, but I think it's a lot different in Asia. From what I saw in China, it's the older generation (35+ years) that drinks green tea like it's going out of style. And these were not people that looked like they were leading an otherwise healthy lifestyle, quite the opposite. So I think epidemiologic studies on green tea in Asia are actually pretty reliable.

[Pike]

I would imagine that the neuroprotective action of EGCG on dopaminergic neurons would probably be absolutely dependant on the fact that it does NOT cross the blood brain barrier.

EGCG is a COMT inhibitor and an irreversible peripheral armomatic l-amino acid decarboxylase inhibitor. both essentially have the same effect in that they inhibit the peripheral metabolism of l-dopa and l-tryptophan into dopamine and serotonin (respectively) until it hits the brain. if EGCG were able to cross the blood brain barrier then i imagine it would probably leave you pretty depressed.

essentially, it has the same effect as drugs like Carbidop and Entacapone, but at the same time. This effect, plus L-Theanine's dopaminergic effects would probably act in a synergistic manner, much in the same way that the drug Sinemet works.

here:
http://www.cababstra...cNo=20053092663
http://cat.inist.fr/...cpsidt=14737203
http://grande.nal.us...p;therow=137300
http://www.biology-o...discussion.html


so yeah... it would probably be necessary for EGCG to not be able to cross the BBB in order for it to have any sort of theraputic effect on mental health.

Edited by Pike, 27 August 2009 - 09:59 AM.

[Blue]

Neuroprotection does not necessary mean a good effect on mood. It is very possible for a substance to be antidepressive and cause neuronal damage at the same time and vice versa.

[VespeneGas]

Regarding human epidemiologic studies there are many problems the most important being that drinking lots of green tea is not unlikely related to many other healthy behaviors. It would not be surprising if those drinking a lot of green tea also smoke less, eat more fruits and vegetables in general, exercise more etc. This would almost certainly be the case in western nations. It may be different in Japan but who knows.

In the Western world that's probably true, but I think it's a lot different in Asia. From what I saw in China, it's the older generation (35+ years) that drinks green tea like it's going out of style. And these were not people that looked like they were leading an otherwise healthy lifestyle, quite the opposite. So I think epidemiologic studies on green tea in Asia are actually pretty reliable.

+1, I've read the same thing about Japan.

Neuroprotection does not necessary mean a good effect on mood. It is very possible for a substance to be antidepressive and cause neuronal damage at the same time and vice versa.

Edit: Also +1

Edited by VespeneGas, 27 August 2009 - 02:28 PM.

[Blue]

Regarding human epidemiologic studies there are many problems the most important being that drinking lots of green tea is not unlikely related to many other healthy behaviors. It would not be surprising if those drinking a lot of green tea also smoke less, eat more fruits and vegetables in general, exercise more etc. This would almost certainly be the case in western nations. It may be different in Japan but who knows.

In the Western world that's probably true, but I think it's a lot different in Asia. From what I saw in China, it's the older generation (35+ years) that drinks green tea like it's going out of style. And these were not people that looked like they were leading an otherwise healthy lifestyle, quite the opposite. So I think epidemiologic studies on green tea in Asia are actually pretty reliable.

Taking the example of Okinawa the older generations has or had an extremely good diet while the younger generations has "westernized" and they are now getting very fat. So hard to tell.

Epidemiology is all about controlling for such confounders. I'm sure the obvious ones were covered. The only question is was there one they missed?

Agree.

Edited by Blue, 02 September 2009 - 10:55 AM.

[Blue]

The L-Theanine in green tea is said to increase both dopamine and gaba levels. I'm guessing the motivation would be coming from the increase in dopamine.

Theanine is interesting. As an amino acid analog it should have a good chance of crossing the BBB. I wonder how many of the effect of tea are due to theanine? Do extracts extract it?

Edited by Blue, 02 September 2009 - 11:03 AM.

[yoyo]

uh, so why is a study say some metabolite doesn't cross the BBB being taken as indicating that nothing does?

[Blue]

uh, so why is a study say some metabolite doesn't cross the BBB being taken as indicating that nothing does?

Who said nothing from tea cross?

[amere]

Can't reducing full body inflammation explain much of the benefit with or without BBB crossing? Surely it leaves more resources to be devoted to cerebral defense mechanisms.

[renwosing]

Might as well try N-acetyl cysteine amide.