Too much testosterone kills brain cells

[bigjayo]

WASHINGTON (Reuters) -- Too much testosterone can kill brain cells, researchers say, in a finding that may help explain why steroid abuse can cause behavior changes such as aggressiveness and suicidal tendencies.

Tests on brain cells in lab dishes showed that while a little of the male hormone is good, too much of it causes cells to self-destruct in a process similar to that seen in brain illnesses such as Alzheimer's.

"Too little testosterone is bad, too much is bad but the right amount is perfect," said Barbara Ehrlich of Yale University in Connecticut, who led the study.

Testosterone is key to the development, differentiation and growth of cells and is produced by both men and women, although men produce about 20 times more of the hormone.

It can also be abused, and recent scandals have involved athletes who use the hormone, or steroids that turn into testosterone in the body, for an unfair advantage.

"Other people have shown that high levels of steroid can cause behavioral changes," Ehrlich said in a telephone interview.

"We can show that when you have high levels of steroids, you have high testosterone and that can destroy the nerve cells. We know that when you lose brain cells you lose function."

Ehrlich's team tried the same thing with the "female" hormone estrogen, just to be fair.

"We were surprised, but it actually looks like estrogen is neuroprotective. If anything, there is less cell death in the presence of estrogen," she said.

Writing in the Journal of Biological Chemistry, Ehrlich and colleagues said their findings meant people should think twice about supplementing with testosterone, even if it does build muscle mass and aid recovery after exercise.

"These effects of testosterone on neurons will have long-term effects on brain function," they wrote.

"Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad -- just take a deep breath and realize that it might not be his fault," Ehrlich said in a statement.

The cells die via a process called apoptosis, also known as cell suicide or programmed cell death.

"Apoptosis is an important thing for the brain -- the brain needs to weed out some of the cells. But when it happens too frequently, you lose too many cells and causes problems."

A similar process is seen in Alzheimer's disease, the most common cause of dementia in the United States, affecting an estimated 4.5 million Americans, and Huntington's disease, another fatal brain illness.

"Our results suggest that the responses to elevated testosterone can be compared with these pathophysiological conditions," the researchers wrote.

Copyright 2006 Reuters. All rights reserved.This material may not be published, broadcast, rewritten, or redistributed.



UH OH, thoughts?

[perfectbeast2001]

Duh Say What?

[bigjayo]

Read it, several university published a study today, steroids kill nerve function, and in turn kill brain cells.

[DHew]

Whoa...

[V_Vandetta]

Read it, several university published a study today, steroids kill nerve function, and in turn kill brain cells.

BRo not to bust the study down But what they fail to tell you is that at what at what dose did IF ANY THING REALLY HAPPEN .......... was in controled ? To many unanswered question? IMO it Bs and what brain tissue did they compare the study with? man It's just another AAS bashing to scare bro's I am not buying it also Please post the Reffernces

[V_Vandetta]

Testosterone 's Influence on the Brain
The male hormone, testosterone, does more than you think. Its claim to fame once was its effect on a man's reproductive system. Now, new research indicates that it also can influence the brain. It aids memory and protects the brain from the memory-impairing disorder, Alzheimer's disease, according to the studies. The findings may lead to new therapies, particularly for older men.

For a while it seemed that women had a leg up in the battle of the sexes.

Over the years, much research on estrogen indicated that, in addition to influencing a woman's reproductive functions, this "female" hormone also helps a variety of brain functions, including memory. Now, recent studies find evidence that evens the playing field. The "male" hormone, testosterone, known for its role in maintaining a man's reproductive system, shares estrogen's double duty. The research is leading to:

Possible new brain-aiding therapies, particularly for older men who, like older women, appear to experience a hormone decrease as they age.
A better understanding of how testosterone interacts with other players in the brain to carry out many tasks.
Testosterone and estrogen were thought to do no more than activate and oversee the male and female organ systems that produce offspring. Then in the 1970s, researchers found evidence that mature female rats had brain cells with receiving areas, known as receptors, which were specifically constructed to process estrogen. This suggested that a woman's estrogen could help the brain perform certain duties. Since that time, many studies indicate that the hormone can aid memory in women as well as protect their brains from developing ailments such as the memory impairing disorder, Alzheimer's disease (AD).

Taking this lead, researchers recently examined the male side and found that testosterone also provides men with some brain advantages.

For example, new studies show that supplements of testosterone can aid certain types of memory in men. Working memory, which allows you to manipulate information over brief periods of time in order to make a response, improves. Verbal memory, which helps you recall lists of words, and spatial memory, which helps you navigate a route, also benefit.

Other work suggests that testosterone, like estrogen, may help prevent the development of AD and its resulting memory decline. Scientists found that compared with healthy men, those with AD have lower levels of testosterone . Another group found that testosterone supplements improved verbal and spatial memory in a small group of men with AD. The researchers currently are testing more patients to confirm the results.

Testosterone may prevent AD by warding off the brain destruction that marks the ailment. Studies of rat brain cells found that the hormone limits the production of beta-amyloid peptides. These sticky protein fragments, thought to be a prime contributor to AD, build up into small, round deposits and clog the brains of people with the disease.

The hormone also may help ward off AD by directly preventing brain cell death. In studies, researchers manipulated human brain cells, sending them on a course to die. Adding doses of testosterone, however, limited the cell death (see images).

While together the results show a new positive side to testosterone, scientists say they need to conduct more research before they would encourage people to take testosterone supplements for brain aid. With its benefits, the powerful hormone also may create some negative effects. For example, some believe that it may spur the development of prostate cancer in certain recipients. Additional studies on large groups of people will help researchers evaluate whether the pluses of testosterone supplementation outweigh the minuses.

Scientists also plan to define the specific mechanisms that carry out the brain benefit. Currently, they are using brain-imaging techniques and molecular methods to track how testosterone induces its actions. Testosterone can convert to estrogen in the brain, so as part of this work, they also want to know whether the benefits are directly from testosterone or from mechanisms that occur after its conversion. Researchers are testing this by blocking an enzyme that converts testosterone to see if it can still create positive effects. Armed with specific information on how testosterone works, a drug might be developed that activates only the positive effects without unwanted side effects.








The series of images below provide evidence that the "male" hormone testosterone can protect brain cells from dying. The top row shows three samples of brain cells, tinted red. The researchers manipulated the cells, sending them on a course to die. Then they administered either no hormones, testosterone or estrogen. The bottom row highlights in yellow the brain cells that died. Notice that many cells died in the sample that received no hormone, but this cell death was limited in the testosterone and estrogen samples. The research indicates that, like estrogen, testosterone can help preserve brain cells.

[DHew]

citations? references? sources?

[Surrender]

If true this leaves me brain dead. So all my replies should be ignored as your talking to the dead

[IIIIIIIIIIII]

wait a sec.... top post says BAD... v's post says good!

what the hell am i to think???


all i want to know is 750MG a week of test gonna make me a RETARD!!??

[Maetenloch]

Here's the summary of the paper - http://www.jbc.org/cgi/content/abstract/281/35/25492

Of course this is just one study involving brain cells in a dish. It's not clear how much testosterone they were using or if these results are seen in living tissue. Given the number of men who have cycled with testosterone over the last several decade, if the effects were really noticable, you would think you'd see a higher level of cognitive disfunction. Most athletes who have used seem about as smart/dumb as they were before taking test.

[DSM4Life]

The more i read about all these "studies" the more i learn how much science DOESN'T know.

[JohnBall]

wait a sec.... top post says BAD... v's post says good!

what the hell am i to think???


all i want to know is 750MG a week of test gonna make me a RETARD!!??

HAHAHAHAHA, I'm thinking any dose under 1000mg/week for say 4 months isn't going to do crazy damage to your brain. Consider that many people shoot heroin, crack, meth and who knows what other designer drugs for years and come out of it to full recover. Now some of the doses I see people taking on this site make me wonder, but I'd say you are alright at 750mg/week for 4 months out of the year. I'd even say cigaretts probably kill more brain cells than a cycle of that. The problem with articles like that is that they don't back the findings up with the numbers. That makes that article nothing more than agenda driven propoganda. That article changes nothing for me.

[shortie]

Just don't open up you skull and pour in test, you'll be fine . That study is about as scientific as when they used to put the seashell bullshit in the glass with water and fat and show you how it absorbed the fat-it was complete bullshit as it in no way mimicks all of the other metabolic factors in living tissue. Junk science at best IMO~

[Ya Dig?]

what a piece of shit that article is

[stupidhippo]

Ill answer the same way as I did to the other simlar thread. I dont find that report credible at all.. but is it possible that long term steroid use would cause nerve cell death enough to cause real problems? well, we cant rule that out on present knowledge..

an interesting study would be to compare a large group of steroid users (+20 yrs of use) at their old age to controls and see if there indeed would be a correlation with alz's or other similar conditions..

also V's study aint applicable here (if i got it right, just glanced it quickly).. the other study specifically says HIGH DOSES of T... they also admitted that in physiological levels it does good... where there doses mentioned btw?

[bigjayo]

Read the full study, google it. They mention steroids , however they are just talking about high levels of natural test in a man's body can cause nerve cell suicide. They are using STEROIDS as a direct cause of nerve cell suicide, which means if you are to believe this, even 250mg(about 2x natural test) would put you at a SEVERE risk. As for all the bullshit about this not being creditable, maybe not 100% but for all you people living in the stone age saying "let me see 20 yr studies". Yes I'm sure someone is going to do 20 year studies on STEROIDS which are illegal, please, these drugs are still new and not much research has been done. There is a risk, if you don't want to believe it and keep being a ****ing meathead, go for it. The last time I checked Journal of Biological Chemistry was a creditable source AND Alzheimer's disease was a very serious disease.

My 2 cents

[auslifta]

ill sacrifice a few brain cells for more pounds when i decide to run a cycle

[stupidhippo]

Read the full study, google it. They mention steroids , however they are just talking about high levels of natural test in a man's body can cause nerve cell suicide. They are using STEROIDS as a direct cause of nerve cell suicide, which means if you are to believe this, even 250mg(about 2x natural test) would put you at a SEVERE risk. As for all the bullshit about this not being creditable, maybe not 100% but for all you people living in the stone age saying "let me see 20 yr studies". Yes I'm sure someone is going to do 20 year studies on STEROIDS which are illegal, please, these drugs are still new and not much research has been done. There is a risk, if you don't want to believe it and keep being a ****ing meathead, go for it. The last time I checked Journal of Biological Chemistry was a creditable source AND Alzheimer's disease was a very serious disease.

My 2 cents

haha and u think journal of biological chemistry cannot have articles that arent the final truth? Havent read the article yet but it seems like its very speculative, they are puerly hypothesizing after some possible relation.. U prolly know urself also that things arent that simple. I could name u a hundred similar cases where in vivo studies have proven to be sumin else. There are million other reasons that also cause nerve cell apoptosis (including alcohol) but still the risk to develop Alz's is still a whole another question. Yes the risk is bigger but how significantly. I am well aware there are no 20 year studies but to say from that study that there is an association with getting some neurological diseases from cycling is premature to say the least... If the correaltion wasw really strong I bet there would alerady be more evidence to point that out.. but lets say that AAS use for 10 years raises ur chances to develop Alz's by 10 %, well it is possible but that would be such a minor increase that I wouldnt quit just because of that.

[guest589745]

what are these conclusions based on? Any studies, cited? What is "too much" 500mg? 5000mg ?

[Bigmax]

I guess all us BIG guys have DRAIN BAMAGE!!!!

[MACHI]

In the study they showed that 1-10micromoles of testosterone can trigger cell death in vitro, while 100 nanomoles didnt.

If anyone has any clue to what real world dosages that would represent please tell us Who knows what kind of brain levels are achived by injecting 1g of test??

This is the first real question everyone should be asking... For all we know based on the pharmacokinetics and dynamics of I.M. injected testosterone esters the corresponding clinical doses could be as high as 20 grams per week to acheive the concentration of 10 micro moles of testosterone around each cell. If I just did my sratch calculations right 250mgs of testosterone propionate is about .00029moles or 290umol (micromoles). For longer esters there are even less moles per mg weight. 7mgs of pure testosterone (a reasonable amount of test a male produces each day) is about 24umol. The study summary says that "Here we show that supraphysiological levels of testosterone (micromolar range) initiate the apoptotic cascade." Even a person's daily normal production is in the micromolar range.

IMO the fault is not in the study itself but the the all or nothing assertion made in the article that too much testosterone kills brain cells. Once a person has a steady state concentration of testosterone in his blood, they need to find a way to calculate how much of that testosterone exists in the extracellular fluid or even the cerebrospinal fluid before they make practical claims that testosterone kills brain cells. The focus on this study was all or none but they didn't really ask the question - how much is too much - on a practical/clinical level. A hypo or hypertonic solution will kill brain cells. So will too much of many types of neurotransmitters.

[taiboxa]

DeRP!~ ><

[Habeed]

Unfortunatly, I did the math and it's pretty sobering. I'm now a bit worried. According to a study I saw, 600mg a week is enough to raise bioavailable testosterone to 100 nanomolar, and by extrapolation 6g per week would raise testosterone to the level at which neurons would start dying. 6g is not as much safety margin as I would like - because it's 6g EQUIVALENT ANDROGEN. In theory, 1g of tren per week might be enough to KO your brain.

That's the theory.

On the plus side, the neurons with the most androgen receptors are SPINAL NERVES. Loss of these cells gives IMMEDIATE, visible symptoms : partial paralysis and neuromuscle disorders! This has NEVER, EVER been reported by bodybuilders at ANY dosage levels - and if my theory is right, that means that noone has ever taken enough androgens to damage their brain by the mechanism described in the paper.

Ask Hose Cansceco if he lost motor nerves due to abusing steroids . I would say this is a "hell no" answer : professional athletes would know instantly if the steroids lowered their coordination.

[stupidhippo]

what was wrong with ur initial calculations? never did bother to check em...

[Habeed]

Hippo : nothing was wrong. I just needed more data. I found out, based on a study in the New England Journal of medicine, that 600mg of enanthate per week gives you a total testosterone serum value of about 3500 ng/dl. The "deadly" number according to this study is 28,800 ng/dl of bioavailable testosterone. If the number is to be believed, then at that point neurons will start dropping like flies (20% were dead in 24 hours in the study) : it should be fatal because neurons are involved in respiration. To reach that would take merely 6g per week, with possible neurological side effects before that point.

The weakest, most sensitive cells should be spinal nerves : they have the greatest number of anabolic receptors.

However, if spinal nerves are damaged, the effects should be immediatly apparent : loss of coordination. You couldn't, oh, hit a world record in home runs or anything.

[stupidhippo]

ok, + there are also other things involved here... Many ppl use sigificantly over that and have had no such symptoms.. I prolly dont need to point out to u that these are very complex and only so much is known presently.. thx for the info.

[Mike Dura]

That sounds like good information and a good deduction. I couldn't determine the validity of what you're saying because I'm not an expert or (even a novice) but to me, your reasoning process stands out relative to the major BS being fronted as knowledge by many of the imposters on these boards. I guess you are trained in a relative field?

Unfortunatly, I did the math and it's pretty sobering. I'm now a bit worried. According to a study I saw, 600mg a week is enough to raise bioavailable testosterone to 100 nanomolar, and by extrapolation 6g per week would raise testosterone to the level at which neurons would start dying. 6g is not as much safety margin as I would like - because it's 6g EQUIVALENT ANDROGEN. In theory, 1g of tren per week might be enough to KO your brain.

That's the theory.

On the plus side, the neurons with the most androgen receptors are SPINAL NERVES. Loss of these cells gives IMMEDIATE, visible symptoms : partial paralysis and neuromuscle disorders! This has NEVER, EVER been reported by bodybuilders at ANY dosage levels - and if my theory is right, that means that noone has ever taken enough androgens to damage their brain by the mechanism described in the paper.

Ask Hose Cansceco if he lost motor nerves due to abusing steroids. I would say this is a "hell no" answer : professional athletes would know instantly if the steroids lowered their coordination.

[Drkodiak1]

since i live 1 mile from Yale i will go knock on her door and ask her the real story

[taiboxa]

DeRP!~ ><

yeah, what he said!

[Habeed]

Unfortunatly, the study addresses these issues. The mechanism for signaling does NOT depend on the Androgen receptor, but on a different protein. (InsP3R type 1). So, high levels of testosterone could destroy brain tissue and cause the mood and behavoir issues reported.

Testosterone is lipid soluble, so yes, it passes the blood brain barrier readily.

There is still hope, however. While NOT mentioned in the study, a gradual increase in intercellular Calcium ion levels might activate various mechanisms to compensate. It's possible that in real subjects taking estered testosterone, the blood levels increase slowly enough that their neurons adapt.

The "hyper-excitability", depression, and behavoir changes could all be caused by what one would expect : testosterone increasing activity of some regions of the brain and leading to aggression. Depression would be caused by discontinuation of the drug or it might be related to the inducable sterility that long term use of testosterone causes.

[Stackertoo]

TIMMMMMMMMMMMMMMMMMMMMMAAAAAAAAAAAAAAYYYYYYYYYYYY! !!!!!!!!!!!!
This is ONE study.
And I wouldn't be able to type this, either, were it true.

[Farang]

I heared about this on Fox news (American Al-Jezeera).

I am a sports scientist, so I am interested in the findings. However I need to look at the research. Looks like BS though.

A few thoughts though:

"We were surprised, but it actually looks like estrogen is neuroprotective. If anything, there is less cell death in the presence of estrogen,"

-Of course most steroids make you produce more estrogen - does this counter balance the effect? (sarcastically) - maybe this is a reason to drop the tamoxifen during a cycle!


"Tests on brain cells in lab dishes"
:aaok****t

-This wasn't even a study on living humans. How can you make claims over experiments conducted in petri-dishes (bizzare!)


"Apoptosis is an important thing for the brain - the brain needs to weed out some of the cells. But when it happens too frequently, you lose too many cells and causes problems."

"These effects of testosterone on neurons will have long term effects on brain function,"

Brain cells are being recycled all the time. The study didn't show there was permanent damage. It was not a protracted study and did not follow subject brain states over a prolonged period (during which testosterone would be normalised). It did not show brain regenerating effects on cessation of steroid use (of which we know occurs with other drugs).

How the hell can they make these claims when they did not test for them- idiots!

The study did not even measure the effects of other circulating hormones/ brain interactions in LIVING humans, with feedback mechanisms.

"Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad -- just take a deep breath and realize that it might not be his fault," Ehrlich said in a statement.

What a wanker. It is so called scientist like this that make me sick. He is obviously not profesional making these kind of comments (and a skinny twat). These kind of wild claims (on anything form nutrition to cancer) are made all the time, with thinking being revised or completely reversed due to unsubstantiated so called science. These characters send out PR photos of themselves and contact news agencies in order to try to get exposure, improve personal self estime, to try and attract funding for their dubious endeavours, or just because they are ego-maniacs.

"A similar process is seen in Alzheimer's disease, the most common cause of dementia in the United States, affecting an estimated 4.5 million Americans, and Huntington's disease, another fatal brain illness."

This is complete nonsense! - Alzheimers occurs as a result of a build up of plaque in the brain, which inturn restricts blood flow; kills off brain cells and shrinks regions of the brain.

"Our results suggest that the responses to elevated testosterone can be compared with these pathophysiological conditions,"

Our results on the effect of testosterone in a petri dish

- what a buch of total tossers!

In addition. As someone who has written and papers and done some exercise physiology based lab tests, you will almost always get conflicting results when you look at multiple studies - sometimes giving completely the reverse opinion. Infact you can write papers to make say some kind off nutritional supplent, say, Gingseng look as if it greatly increases cardiovascular performance. You would just have to include the rogue studies that found this (huge numbers do not support such a claim) and exclude others.

There was no mention of a control being used, or the competence of testers, facilities or environmental factors.

This is just one study! - The scientific community will only accept something as a truth, if it has reproducable effects in hundreds of studies - even then some will argue.

I doubt the professionalism of this buch of muppets making stupid statements to the press. They obviously are out to get a bit of glory and 15 minutes of fame.

I suspect that they started out with the preconcieved idea that this effect would occur. This happens a lot, with testers WANTING an effect to occur. In my experience, you must have no pre-conceived ideas before conducting experiments/assesing data - otherwise it can have an effect on your findings



O.K. got the paper now;

Just a few thoughts:

"Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis".

This study was not conducted on living humans. Therefore- they know how much additional testosterone (whether micro or macromolar).


The abstract quoted:
Caspase-3-induced truncation of type 1 inositol trisphosphate receptor accelerates apoptotic cell death and induces inositol trisphosphate-independent calcium release during apoptosis.


However in a Belgian study Inositol 1,4,5-trisphosphate receptor-deficient (IP3RKO) B-lymphocytes were used to investigate the functional relevance of type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) and its cleavage by caspase-3 in apoptosis.

Interestingly:

Expression of caspase-3-non-cleavable mutant receptor, however, dramatically slowed down the rate of apoptosis and prevented both Ca2+ overload and secondary necrosis. (Assafa et al. 2004)

It seems that the brain has a feedback mechanism!

This could not be tested for in a petri dish!


whereas high concentrations (1-10 µM) induced a sustained Ca2+ increase.I

In agreement with Asafa's observations, "caspase inhibitors impeded apoptosis and the associated rise in [Ca2+]i. Both the staurosporine- and B-cell receptor-induced apoptosis and increase in [Ca2+] could be induced in nominally Ca2+-free and serum-free culture media, suggesting that the apoptosis-related rise in [Ca2+] was primarily because of the release from internal stores rather than of influx through the plasma membrane".

-Internal stores are FINITE, thus the continual release of CA2+ would only be short term (if at all).

In other words

(Assefa et al. 2004)


Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP3R)-mediated Ca2+ release

Yes, as we have previously established, this is a natural phenomena that occurs in the brain of a LIVING person. You have shown that your findings mean nothing in your own abstract.

These results support our hypothesis that elevated testosterone alters InsP3R type 1-mediated intracellular Ca2+ signaling and that the prolonged Ca2+ signals lead to apoptotic cell death.

No they don't - you just said that the effect was "abolished in the presence of inhibitors od capases/inositol 1,4,5-triphosphate (InsP3R)- mediated CA2+ release - this is a natural phenomenon in human brains - the feedback mechanism (via the previously mentioned caspase-3-non-cleavable mutant receptor!)

I have spent a small amount of time to easily disprove these claims. I can't be bothered to research more, but I'm sure I could uncover a whole host of information which could show this sensationalist crap up.

This study may be valid ,so as to show short term effects. However the noted feedback mechanism would negate effects in the longterm. There may be a downgrade of the feedback mechanism with prolonged use (those who abuse steroids and do not come off) - but that would have to be substantiated with relevant proof from relevant studies.

As an aside:

Actual values of concentrations of testosterone need to be measured in human beings over sustained periods, as it is not known how much testosterone can breach the plasma barrier.


A BRIEF DECRIPTION OF THE MECHANISM OF BRAIN CELLS:

A human brain has roughly 10 billion neurons. A neuron or nerve cell processes and transmits information from the nervous system. Neurons (most) comprise
soma, dendrites, axons and terminals buttons. Neurons are polarised with an electical charge. They contain neucleolus and chromosomes (made up of long strings of DNA). These messenger RNA, assisting protein synthesis.
Neurons are possitively charged (a mechanism of flowing pottasium ions), and thus retain a negatively charge ions in the cell. When pottasium ions are stimmulated, they cause an influx, thus effecting a possitive charge, or an action potential. After this event, the ions are exchanged at the nodes of Ranvier, with high sodiium concentrations pumping out potassium and sodium ions (sodium-potasium pump). The event occurs in 1/1000th of a second and restores the negative charge.
I could go into more setail about chemical mechanisms, but it would be getting away from the point. Although it is important to note that Neuro-dilators, neuro modulatos and Hormones are released by the brain.

Note hormones can stimulate bothe sides of the cell membrane and the cell neucleus. Thus they can alter behaviour - this does not mean that in excess (say in the case of increased testosterone) they KILL brain cells. They attatch to a binding site, like a lock and key mechanism. They "key" being known as a ligand. For this reason and others that I mentioned in relation to caspase-3-non-cleavable mutant receptors, I do not think cell death occurs at all.
Should there be a disturbance in neural communication, the vesicle of a neuron collapses in on itself and mixes with the cell membrane, leading to the cell later being retrieved and recylced.

THIS IS LIKELY TO OCCUR.

The vesicles (that are filled with neurotransmitters) are then readily availiable to be re-used.

Brain cells use a shuttle system in order to effect more or less receptors for a transmitting signal, aiding neural pathways, via synapse communication, to be formed and to MAINTAIN function (by assisting the creation of other pathways) following cell death (if any).

Regulatory signals in the brain manage the number of receptors. The recycling of these receptors PREVENT THE WEAKENING OF SYNAPSES THAT OCCUR IN NEURODEGENERATIVE STATES.

Unlike "drugs" Testosterone does not shut off recycling. As testosterone, as a hormone, is integral in neuronal communication; an increase should INCREASE cellular recycling! Testosterone does not cause any degradation and it does not decrease the activity of the receptors.

[stupidhippo]

for the third time.... very well put... gives some perspective.. thanks for the input!

[Seattle Junk]

Wow Farang, you disected that study. I'm just too stupid from the test to understand what you just wrote...

[Farang]

Thanks, just a shame I can't spellll

[Farang]

Me again!
-Just to say that if anyone is still worried, I can recommend a harmless drug that can improve your health and could perhaps be used to negate any SUPPOSED damage. It also improves mood, enhances LDL cholesterol oxidation and gives vascular protection. It acts as an antioxidant, of which it is particularly active in the brain. It is cardio-protetive and an antiatherogenic).

THE DRUG: DEPRENYL (also known as Seligiline or L-Deprenyl)


I shall highlight a couple of passages from Sabelli et al. 1996 –

“Such an action could contribute to reported extension of life span associated with long-term administration of the drug.”

“Prophylactic use of low doses of l-deprenyl may accord protection against vascular and neurodegenerative diseases associated with aging.”

-If you believe “The Idiot Formally Known as Ehlrich” (T.I.F.K.E.),it is certainly something those of us on gear could do with! – with the additional added benefits mentioned above!


Please exercise caution though, as you MUST NOT EAT FOODS HIGH IN TYRAMINE – see below.

“Tyramine is found in many foods, including aged cheeses, some wines, beans, yeast products, chicken liver and pickled herring, to name just a few”. –Need to do more research here.

At this point I would like to say that after looking into Ehlrich, it is clear to see where her motivation for these statements and erroneous study lies. I have found that most of her research centers around the efflux of calcium ions in the brain (as seen in degenerative brain disorders). She has even personally funded other scientists to do similar research. This rhetoric is just a sad attempt in trying to gain attention for her main pursuit - by doing terrible, poorly analyzed lab experiments and linking it to something completely non-analogous
- Not what you would expect from a professor at Yale!
Anyway, for those STILL concerned, the use Deprenyl might be prudent.

I have posted some of my research on the drug below. Read it and draw your own conclusions


Deprenyl is a drug that was discovered around 1964-65 by Dr. Joseph Knoll and colleagues. It was originally developed as a “psychic energizer,” designed to integrate some amphetamine-like brain effects with antidepressant effects. Also known as L-deprenyl, (-)-deprenyl, and selegiline, deprenyl has been intensively researched over the past 36 years - many hundreds of research papers on deprenyl have been published. Knoll has stated that deprenyl “...is an exceptionally lucky modification of PEA [phenylethylamine], an endogenous ... member of the family to which also the transmitters noradrenaline and dopamine belong.” Deprenyl has shown a unique and exciting pharmacologic/clinical profile. It is the only potent, selective MAO-B inhibitor in medical use.Deprenyl is a “catecholamine activity enhancer.” Deprenyl has been shown to protect nerve cells against a wide (and growing) number of neurotoxins. Deprenyl has also been shown to be a “neuroprotection/ neurorescue agent” when nerve cells are exposed to damaging or stressful conditions.
Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative of phenylethylamine (PEA), is a drug with a unique pharmacological spectrum. Whereas PEA and its long-lasting variants, the amphetamines, are mixed-acting stimulants of the sympathetic system in the brain, they primarily enhance the impulse propagation generated release of catecholamines (catecholamine activity enhancer, CAE, effect) and displace catecholamines in higher concentration (catecholamine releasing effect). (-)Deprenyl is the first CAE substance in clinical use devoid of catecholamine releasing activity. (-)Deprenyl is a highly potent and selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain. The activity of this enzyme significantly increases with age. (-)Deprenyl, the first selective inhibitor of MAO-B described in the literature, has become a universally used research tool for selectively blocking B-type MAO and is still the only selective MAO-B inhibitor in world wide clinical use. In contrast to MAO inhibitors which strongly potentiate the catecholamine releasing effect of tyramine, (-)deprenyl inhibits it and is free of the 'cheese effect', which makes it a safe drug. Because its lack of the catecholamine releasing activity deprenyl is devoid of amphetamine like dependence capacity.
DEPRENYL: MAO-B INHIBITOR EXTRAORDINAIRE
By 1971 Knoll had shown that deprenyl was a unique kind of MAO inhibitor - a selective MAO-B inhibitor, without the “cheese effect.” To fully appreciate what this means, some technical background is necessary.
Some of the most important neurotransmitters in the brain are the monoamine transmitters: serotonin, dopamine and noradrenalin. After being secreted into the synaptic gap, where one neuron connects to another, many to the transmitter molecules are reabsorbed by the secreting neuron and then disposed of by enzymes called “monoamine oxidases” (MAO). This prevents excessive levels of transmitters from accumulating in the synaptic gap and “over-amping” the brain. However, with aging MAO activity significantly increases in the human brain, often to the point of severely depressing necessary levels of monoamine transmitters. In the 1950s the first antidepressant drugs to be developed were MAO inhibitors.
By 1968, further research had shown that there were two types of MAO-A and B. It is primarily intestinal MAO-A that digests incoming tyramine. Most of the MAO inhibitors that have been used clinically inhibit both MAO-A and MAO-B, however deprenyl has the unique ability to prevent tyramine from getting into noradrenalin-using nerve calls, and it’s only when tyramine enters noradrenalin nerve cells that control arterial blood pressure that it triggers the “cheese effect.” Deprenyl thus has a dual “safety lock” in preventing the “cheese effect,” making it far safer than other MAO inhibitors. At doses over 20-30 mg/day, however, deprenyl does start to significantly inhibit MAO-A

“CHEESE EFFECT”: When most MAO inhibitors are used in people consuming a diet rich in a substance called “tyramine,” a dangerous, even fatal, high blood pressure crisis can be triggered. Tyramine is found in many foods, including aged cheeses, some wines, beans, yeast products, chicken liver and pickled herring, to name just a few.

MAO-B breaks down dopamine and the “traceamine” phenylethylamine (PEA). At doses of 10 mg + per day deprenyl will inhibit MAO-B about 90%. MAO-B inhibition can significantly increase synaptic dopamine levels.

Deprenyl (and its “cousin”, PEA) are “catecholamine activity enhancers”.
Catecholamines refers to the inter-related neurotransmitters dopamine, noradrenalin, and adrenalin. Catecholamines are the transmitters for key activating brain circuits - the mesolimbic-cortical circuit and the locus coeruleus. The neurons of the mesolimbic-cortical circuit and locus coeruleus project from the brain stem, through the mid-brain, to the cerebral cortex. They help to maintain focus, concentration, alertness and effortful attention. Dopamine is also the transmitter for a brainstem circuit - the nigrostriatal tract - which connects the substantia nigra and the striatum, a nerve tract that helps control bodily movement and which partially dies off and malfunctions in Parkinson’s disease.
When an electrical impulse travels down the length of a neuron - from the receiving dendrite, through the cell body, and down the transmitting axon - it triggers the release of packets of neurotransmitters into the synaptic gap. These transmitters hook onto receptors of the next neuron, triggering an electrical impulse which then travels down that neuron, causing yet another transmitter release. What Knoll and colleagues discovered through their highly technical experiments is that deprenyl and PEA act to more efficiently couple the release of neurotransmitters to the electrical impulse that triggers their release.
In other words, deprenyl (and PEA) cause a larger release of transmitters in response to a given electrical impulse. It’s like “turning up the volume” on catecholamine nerve cell activity. And this may be clinically very useful in various contexts - such as Parkinson’s disease and Alzheimer’s disease, where the nigrostriatal tract and mesolimbic-cortical circuits under-function, as well as in depression, where they may be under-activity of both dopamine and noradrenalin neurons.
Knoll’s research also indicates that after sexual maturity the activity of the catecholamine nervous system gradually declines, and that the rate of decline determines the rate at which a person or animal ages.
Knoll therefore believes that deprenyl's catecholamine activity enhancers effect explains its anti-aging benefit. Knoll also believes that deprenyl's catecholamine activity enhancer activity is independent of its MAO-B inhibition effect, because in rats he has shown catecholamine activity enhancer effect at doses considerably lower than that needed to achieve MAO-B inhibition.
Knoll’s work indicates that PEA is also a catecholamine activity enhancer substance. (16) PEA is a trace amine made in the brain that modulates (enhances) the activity of dopamine/noradrenalin neurons. (16,21) Autopsy studies have shown that while deprenyl increases dopamine levels in Parkinson patient brains by only 40-70%, deprenyl increases PEA levels 1300 - 3500%! PEA is the preferred substrate for MAO-B, the MAO that deprenyl inhibits. Paterson and colleagues have shown that PEA has an extremely rapid turnover due to its rapid and continuous breakdown by MAO-B. (21) Thus deprenyl's catecholamine activity enhancer activity has a dual mode of action. At low, non-MAO-B inhibiting doses, deprenyl has a direct catecholamine activity enhancer activity.
At higher, MAO-B inhibiting doses, deprenyl creates an additional catecholamine activity enhancer effect, due to the huge increases in brain PEA levels that deprenyl causes, PEA also being a catecholamine activity enhancer substance. Many authors have pointed out the probable dopamine neuron activity enhancing effect of PEA in Parkinson patients taking deprenyl.
Knoll’s discovery of PEA’s catecholamine activity enhancer effect now explains this PEA dopamine-enhancing effect


Maintenance on (-)deprenyl selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum and protects the nigrostriatal dopaminergic neurons from selective neurotoxins (6-hydroxydopamine, MPTP, DSP- Maintenance of an animal on deprenyl prevents the characteristic age-related morphological changes in the neuromelanin granules of the neurocytes in the substantia nigra. Many other protective effects of (-)deprenyl, denoted as 'neuroprotective', 'trophiclike neurorescue', 'apoptosis reducing', etc, have been described. All the protective actions of (-)deprenyl are thought to be primarily related to the CAE effect of the drug. All in all, (-)deprenyl increases the activity of the nigrostriatal dopaminergic system and slows its age-related decline. Maintenance of male rats on (-)deprenyl delays the age-related loss of their capacity to ejaculate, slows the age-related decline of their learning capacity and prolongs their life. Parkinsonian patients on levodopa plus (-)deprenyl (10 mg daily) live significantly longer than those on levodopa alone. Parkinsonian patients maintained, after diagnosis, on (-)deprenyl, need levodopa significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improves the performance of patients with Alzheimer's disease. It is concluded that patients developing Parkinson's or Alzheimer's disease need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication. Because of the peculiar pharmacological spectrum and safety of the drug it may be advisable to combat the age-related decline of the nigrostriatal dopaminergic neurons in man by taking 10-15 mg (-)deprenyl weekly during the postdevelopmental phase of life. Prophylactic (-)deprenyl medication may improve the quality of life in the latter decades, delaying the time of natural death and decreasing the susceptibility to age-related neurological diseases.



Effect of low-dose treatment with selegiline on dopamine transporter (DAT) expression and amphetamine-induced dopamine release in vivo
Itschak Lamensdorf1, Shai Porat2, Rabi Simantov2 and John P.M. Finberg*,1
1 Rappaport Faculty of Medicine, Technion, POB 9649, Haifa, Israel
2 Department of Molecular Genetics, Weizmann Institute of Science, Israel
*Correspondence to: John P.M. Finberg, Rappaport Faculty of Medicine, Technion, POB 9649, Haifa, Israel
1. Chronic treatment with low doses of the selective monoamine oxidase (MAO) type B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes elevation in extracellular level of 3,4-dihydroxyphenylethylamine (dopamine) in the rat striatum in vivo (Lamensdorf et al., 1996). The present study was carried out to determine whether this effect of selegiline could be the result of an inhibition of the high-affinity dopamine neuronal transport process.
2. Changes in activity of the dopamine transporter (DAT) in vivo following selegiline treatment were evaluated indirectly by microdialysis technique in the rat, from the change in striatal dopamine extracellular concentration following systemic amphetamine administration (4 mg kg-1, i.p.). Striatal levels of the DAT molecule were determined by immunoblotting. Uptake of [3H]-dopamine was determined in synaptosomes from selegiline-treated animals.
3. Amphetamine-induced increase in striatal extracellular dopamine level was attenuated by one day and by chronic (21 days) treatment with selegiline (0.25 mg kg-1, s.c.).
4. Striatal levels of DAT were elevated after 1 and 21 days treatment with selegiline, but were not affected by clorgyline, rasagiline, nomifensine or amphetamine.
5. The increase in DAT expression, and attenuation of amphetamine-induced dopamine release, were not accompanied by a change in [3H]-dopamine uptake in synaptosomes of selegiline-treated animals.
6. The results suggest that a reversible inhibition of dopamine uptake occurs following chronic low dose selegiline treatment in vivo which may be mediated by an increase in endogenous MAO-B substrates such as 2-phenylethylamine, rather than by the inhibitor molecule or its metabolites. Increased DAT expression appears to be a special property of the selegiline molecule, since it occurs after one low dose of selegiline, and is not seen with other inhibitors of MAO-A or MAO-B. The new DAT molecules formed following selegiline treatment appear not to be functionally active.
Sustained antidepressant effect of PEA replacement
by
Sabelli H, Fink P, Fawcett J, Tom C
Rush University and the
Center for Creative Development,
Chicago, Illinois, USA.
J Neuropsychiatry Clin Neurosci 1996 Spring; 8(2):168-71

ABSTRACT
Phenylethylamine (PEA), an endogenous neuroamine, increases attention and activity in animals and has been shown to relieve depression in 60% of depressed patients. It has been proposed that PEA deficit may be the cause of a common form of depressive illness. Fourteen patients with major depressive episodes that responded to PEA treatment (10-60 mg orally per day, with 10 mg/day selegiline to prevent rapid PEA destruction) were reexamined 20 to 50 weeks later. The antidepressant response had been maintained in 12 patients. Effective dosage did not change with time. There were no apparent side effects. PEA produces sustained relief of depression in a significant number of patients, including some unresponsive to the standard treatments. PEA improves mood as rapidly as amphetamine but does not produce tolerance.







L-deprenyl (Selegiline) used in the treatment of Parkinson's and Alzheimer's disease also enhances longevity. Oxidized low density lipoprotein promotes atherosclerosis and is toxic to both vascular and neural tissue. The reported association between vascular dysfunction and neurodegenerative diseases prompted us to investigate the effect of l-deprenyl, a MAO-B inhibitor, on low density lipoprotein (LDL) oxidation. LDL was isolated from freshly collected blood and the kinetics of copper induced oxidation of LDL was monitored continuously by spectrophotometry. Oral administration (10 mg) or in vitro (2.8 to 84 microM) addition of l-deprenyl inhibited oxidation of LDL isolated from healthy men and post-menopausal women. This is the first report demonstrating that the antioxidant action of l-deprenyl may be antiatherogenic and cardioprotective. Such an action could contribute to reported extension of life span associated with long-term administration of the drug. In conjunction with inhibition of LDL oxidation, l-deprenyl is unique in that it demonstrates protective effects on both vascular and neuronal tissue. Prophylactic use of low doses of l-deprenyl may accord protection against vascular and neurodegenerative diseases associated with aging.

P.S. I WILL SOON BE POSTING (WHEN I HAVE THE TIME) INFO ON A CHEAP SUPPLEMENT THAT EVERYONE ON STEROIDS SHOULD BE TAKING - GREEN TEA! - DO NOT UNDERESTIMATE HOW EFFECTIVE THIS MIRACLE DRINK IS IN COMBATING THE NEGATIVE EFFECTS OF DRUG USE! I WILL LEAVE YOU WITH ONE QUESTION - WHY HAS IT BEEN SHOWN THAT LUNG CANCER IS HALF AS PREVALENT IN CHINESE SMOKERS, DESPITE THEM SMOKING TWICE AS MANY AS WESTERN SMOKERS? - YES, LARGE GREEN TEA CONSUMPTION!
-DRINK UP!

[stupidhippo]

[QUOTE=Farang]Me again!
-Just to say that if anyone is still worried, I can recommend a harmless drug that can improve your health and could perhaps be used to negate any SUPPOSED damage. It also improves mood, enhances LDL cholesterol oxidation and gives vascular protection. It acts as an antioxidant, of which it is particularly active in the brain. It is cardio-protetive and an antiatherogenic).

first of all has this drug went through clinical trilas on humans? after glancing through it I wouldnt be comfortable in recommeding it to everyone.

enhances LDL oxidation? that would cause atherosclerosis, not prevent it. Maybe a typo by u? other than that an interesting article but I wouldnt go as far as recommending it to everyone. Other MAO inhibitors are also used as antidepressants but they for sure have side effects.. I mean this drug could have use in medicine in the future (if its not used allready) but like most drugs . they have side-effects!

also green tea (while indeed it has been shown to have several beneficial effects) it also has been shown to have some negative effects too... as far as should everyone drink it? dont knoe, u gotta outweigh the risks and benefits and make up ur own mind... also traditional tea has been recently shown to have many of the same health benefits (not all but...) I mean if u make things look totally onesided u can say y alcohol is good for u

[Farang]

Cheers for the feedbac Johan. I'm a bit starved of doing
scientific research over here in Thailand!

Sorry, typo (LDL) -opposite effect (DECREASES LDL oxidation)

There have been many long term trials on humans, with no negative effects - have to search that out for you (at the internet cafe - need to get back to family).
It has been studied for over 50 years with many research papers, and is currently used by large numbers of people with neurodegenerative diseases, with no recorded ill effects.
Something I neglected to comment on is the action of PEA (a compound commonly found in chocolate) - this is the stuff that gives you the high feeling, through dopamine expression. In part it metabolises into amphetamine and methanphetamine, and enhances catcholamine activity, thus is a potent fat burner.

I've actually sent a very polite email to Ehrlich about her study. I've asked her what she thinks of deprenyl for steroid users - interesting to hear her response (not counting my chickens though)

I will write something more detailed in respect to green tea, but will give you a few bits of info - yes the tannins in black tea have been proven to be benefitial antioxidants, but there ARE marked differences in studies comparing black and green tea, studies have shown this.

:

Antioxidant activity on free-radicals following exercise - rats given green tea or water.

A biomarker for free radical activity that was introduced into the rats and showed a 290% increase in free radicals (water group) and 0% in green tea group! (FREE RADICALS MEASURED IN THE LIVER).

Green tea has been repeatedly been shown in trials to reduce risk of practically every cancer - from prostrate to colon reduce the chance of heart disease.

Long term studies show a 7% drop in B.P. , with improved cholesterol balance, enhanced mood and improvements in memory.

Green tea is rich in L-theanine - which improves mental focus and produces alpha waves in the brain. This is the same pattern that is seen in athletes prior to an important race (boosts performance). This also explains the calming effect of green tea, despite caffeine content.



The antioxidants in green tea are highly bioavailiable - as such they are highly absorbed in all the organs of the body. The kidneys and liver have been particularly well studied, with the antioxidants in green tea shown by meta-analysis to be vastly superior to that of vit C and Vit E.

Studies have also shown a number of positive effects in conjunction with drug users.

Scientists unanimously reccomend at least 6 cups a day, with 10 cups+ being preferable for optimal catcholamine content (of which is a potent fat burner)


I am unaware of any negative research regarding green tea, although if you find some I'd be interested to have a look thanks.


I'M A DUMB ASS! - I JUST REMEMBERED THAT WROTE/RESEARCHED SOME INFO FOR A PARALYMPIC ATHLETE. IT WAS ABOUT SUPPLEMENTS (INCLUDING GREEN TEA)- I'LL PASTE IT IN. Am planning on writing something a bit more comprehensive and substantiated though.

- SEE BELOW:


J Agric Food Chem 1999 Oct;47(10):3967-73
Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans.

Nakagawa K, Ninomiya M, Okubo T, Aoi N, Juneja LR, Kim M, Yamanaka K, Miyazawa T.

Laboratory of Biodynamic Chemistry, Tohoku University Graduate School of Life Science and Agriculture, Sendai 981-8555, Japan.

The effect of green tea catechin supplementation on antioxidant capacity of human plasma was investigated. Eighteen healthy male volunteers who orally ingested green tea extract (254 mg of total catechins/subject) showed 267 pmol of epigallocatechin-3-gallate (EGCg) per milliliter of plasma at 60 min after administration. The plasma phosphatidylcholine hydroperoxide (PCOOH) levels attenuated from 73.7 pmol/mL in the control to 44.6 pmol/mL in catechin-treated subjects, being correlated inversely with the increase in plasma EGCg level. The results suggested that drinking green tea contributes to prevent cardiovascular disease by increasing plasma antioxidant capacity in humans.

Biofactors 2000;13(1-4):55-9
Absorption, metabolism and antioxidative effects of tea catechin in humans.

Miyazawa T.

Biodynamics Chemistry, Lab., Tohoku University Graduate School of Life Science & Agriculture, Sendai, Japan. [email protected]

Green tea is consumed as a popular beverage in Japan and throughout the world. During the past decade, epidemiological studies have shown that tea catechin intake is associated with lower risk of cardiovascular disease. In vitro biochemical studies have reported that catechins, particularly epigallocatechin-3-gallate (EGCg), help to prevent oxidation of plasma low-density lipoprotein (LDL). LDL oxidation has been recognized to be an important step in the formation of atherosclerotic plaques and subsequent cardiovascular disease. Metabolic studies have shown that EGCg supplement is incorporated into human plasma at a maximum concentration of 4400 pmol/mL. Such concentrations would be enough to exert antioxidative activity in the blood stream. The potent antioxidant property of tea catechin may be beneficial in preventing the oxidation of LDL. It is of interest to examine the effect of green tea catechin supplementation on antioxidant capacity of plasma in humans by measuring plasma phosphatidylcholine hydroperoxide (PCOOH) as a marker of oxidized lipoproteins.

Am J Clin Nutr 1999 Dec;70(6):1040-5
Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans.

Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J.

Department of Physiology, Faculty of Medicine, University of Geneva. a**[email protected]

BACKGROUND: Current interest in the role of functional foods in weight control has focused on plant ingredients capable of interfering with the sympathoadrenal system. OBJECTIVE: We investigated whether a green tea extract, by virtue of its high content of caffeine and catechin polyphenols, could increase 24-h energy expenditure (EE) and fat oxidation in humans. DESIGN: Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary excretion of nitrogen and catecholamines were measured in a respiratory chamber in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among 3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch, and dinner. RESULTS: Relative to placebo, treatment with the green tea extract resulted in a significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen. Twenty-four-hour urinary norepinephrine excretion was higher during treatment with the green tea extract than with the placebo (40%, P < 0.05). Treatment with caffeine in amounts equivalent to those found in the green tea extract had no effect on EE and RQ nor on urinary nitrogen or catecholamines. CONCLUSIONS: Green tea has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se. The green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both.

Int J Obes Relat Metab Disord 2000 Feb;24(2):252-8

Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity.

Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J.

Institute of Physiology, University of Fribourg, Fribourg, Switzerland. a**[email protected]

The thermogenic effect of tea is generally attributed to its caffeine content. We report here that a green tea extract stimulates brown adipose tissue thermogenesis to an extent which is much greater than can be attributed to its caffeine content per se, and that its thermogenic properties could reside primarily in an interaction between its high content in catechin-polyphenols and caffeine with sympathetically released noradrenaline (NA). Since catechin-polyphenols are known to be capable of inhibiting catechol-O-methyl-transferase (the enzyme that degrades NA), and caffeine to inhibit trancellular phosphodiesterases (enzymes that break down NA-induced cAMP), it is proposed that the green tea extract, via its catechin-polyphenols and caffeine, is effective in stimulating thermogenesis by relieving inhibition at different control points along the NA-cAMP axis. Such a synergistic interaction between catechin-polyphenols and caffeine to augment and prolong sympathetic stimulation of thermogenesis could be of value in assisting the management of obesity. International Journal of Obesity (2000) 24, 252-258

J Hypertens 1999 Apr;17(4):457-63
Effects on blood pressure of drinking green and black tea.

Hodgson JM, Puddey IB, Burke V, Beilin LJ, Jordan N.

University of Western Australia Department of Medicine and the Western Australian Heart Research Institute, Royal Perth Hospital, Australia. [email protected]

BACKGROUND: The flavonoid components of tea have been associated in epidemiological studies with a decreased risk of cardiovascular disease. Flavonoids have been shown to have antioxidant and vasodilator effects in vitro; we therefore postulated that drinking green or black tea attenuates the well-characterized acute pressor response to caffeine and lowers blood pressure during regular consumption. OBJECTIVE: To determine whether green and black tea can attenuate the transient pressor effect of caffeine, or lower blood pressure during regular consumption. METHODS: In the first study, the acute effects of four hot drinks - green tea and black tea (at a dose equivalent to four standard cups), water matched to the teas for caffeine content ('caffeine') and water - were assessed in 20 normotensive men using a Latin-Square designed study. Clinic blood pressure was measured before and 30 and 60 min after each drink had been ingested. In the second study, the effects on blood pressure of regular green and black tea ingestion were examined in 13 subjects with high-normal systolic blood pressure and mild systolic hypertension (systolic blood pressure in the range 130-150 mmHg) using a three-period crossover study. Five cups per day of green tea, black tea and caffeine (in hot water and matched to the teas) were consumed for 7 days each, in random order. Twenty-four hour ambulatory blood pressure was measured at the end of each seven-day intervention. Results are presented as means and 95% confidence intervals (CI). RESULTS: An acute pressor response to caffeine was observed. Relative to caffeine, there were further acute increases in systolic and diastolic blood pressure at 30 min among those drinking green tea [5.5 mmHg (95%CI -1.4 to 12.4) and 3.1 mmHg (95%CI -0.1 to 6.3), respectively] and black tea [10.7 mmHg (95%CI 4.0 to 17.4) and 5.1 mmHg (95%CI 1.8 to 8.4), respectively]. The changes in blood pressure at 60 min were not significant The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [increases of 1.7 mmHg (95%CI -1.6 to 5.0) and 0.9 mmHg (95%CI -1.3 to 3.1), respectively] or black tea [increase of 0.7 mmHg (95%CI -2.6 to 4.0) and decrease of 0.7 mmHg (95%CI -2.9 to 1.5), respectively] was not significant relative to caffeine. CONCLUSIONS: Contrary to our initial hypothesis, tea ingestion caused larger acute increases in blood pressure than caffeine alone. However, any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption.

Green Tea Extract

This powerful supplement has been widely used for immuno-enhancing effects. The major components of interest in green tea extract are the polyphenols (including EGCG--epigallocatechin gallate which seems to provide the strongest antioxidant effects). Most of its research is actually focused on its cancer-protective effects. Some research suggests that this potent extract has greater anti-oxidant protection than Vitamin C and E . A study published in the American Journal of Clinical Nutrition in Dec. 1999 showed that green tea extract actually increased 24 hour energy expenditure and fat oxidation in humans. Many people "in the know" would say that this is due to its caffeine content since caffeine has been shown to have some of these properties in previous research. However, the authors of this study concluded "green tea extract has thermogenic properties and promotes fat oxidation beyond that explained by its caffeine content per se." They continued to say "Green tea extract may play a role in the control of body composition via sympathetic activation of thermogenesis, fat oxidation, or both." I believe it is most likely linked to its EGCG content. Another study showed the synergy of green tea extracts catechin-polyphenol and caffeine content discussing how it stimulates brown adipose tissue thermogenesis. The study mentions that green tea extract and the synergistic relationship of its contents may be a valuable tool in assisting in the management of obesity. This is all very good news for all those fat loss candidates out there!.
In my opinion, you should try to drink as much green tea as possible. It is truly amazing stuff. 5-6 cups/ day is recommended as a minimum for health benefits, but more IS better. Look at the Chinese, they smoke twice as much as the west – but have half the incidence of lung cancer! This has been contributed primarily to their high consumption of green tea – literally drink it like fish!
Many studies have shown the antioxidant properties of green tea, especially in response to acute exercise –results are remarkable. In one study I remember, the effects on young rats were studied, following a 6.5 week exercise protocol. In comparison to the water fed rats, post exercise levels of malonaldehyde (a marker of oxidative stress) was zero in green tea fed rats – but 290% in the water only subjects! Green tea lowers blood pressure (both diastolic and systolic shown to decrease by 7% when rats were fed 2mg of tea (Yakozawa et al. 2004).
It decreases cholesterol as showed by Norwegian research. It decreases the chance of cardiovascular disease, with studies in the 80’s showing a marked increase in HDL cholesterol (good) and a decrease in LDL cholesterol (bad). Green tea ADP platelet aggression and inhibits LDL oxidation.
Cancer- large numbers of studies show big reductions in risk of cancer following green tea consumption (mainly through the polyphenolic EGCG content. It has been shown effective against many types of cancer – gastric, oral, pharyngeal, gastric, breast and digestive, lung, liver, kidney, skin, esophaegus, pancreas and prostrate; to name only a few! It seems as tough that the antioxidant, polyphenol, catchins and theaflavins inhibit cell transformation inhibit cell transformation, cell growth and the activity of tumour-proting enzymes in animals (Sinclair et al 2000). It seems that EGCG gets directly transported to all the organs in the body, and is extremely bioavailiable. This therefore provides excretion enhanced antioxidant protection from analogous drugs or exercise-induced stress. (Alesio et al. 2002). There is also supporting evidence fom animal research to show that tea also enhances the immune system.

[Farang]

Here are some additional abstracts ascertaining to caffeine; just for the hell of it:

Caffeine, coffee and ephedrine: impact on exercise performance and metabolism.

Graham TE.

Department of Human Biology and Nutritional Sciences, University of Guelph Guelph, ON.

This paper addresses areas where there is controversy regarding caffeine as an ergogenic aid and also identifies topics that have not been adequately addressed. It is clear that caffeine, in moderate amounts, can be used orally as an ergogenic aid in aerobic activity lasting for more than 1 min. It increases endurance and speed, but not maximal VO2 and related parameters. While there are fewer well-controlled studies for resistance exercise, the literature would suggest similar improvements: increased endurance at submaximal tension and power generated in repeated contractions and no change in maximal ability to produce force. It is likely that theophylline (a related methylxanthine) has similar actions and it has been suggested that the combination of caffeine and sympathomimetics may be a more potent erogenic aid. The voids in our understanding of caffeine include the dose (what amount is optimal, what vehicle is used to deliver the drug as well as method, pattern, and mode of administration), the potential side effects (particularly in competitive settings), health implications (insulin resistance and if combined with ephedrine, cardiovascular risks) and mechanisms of action. It appears unlikely that increased fat oxidation and glycogen sparing is the prime ergogenic mechanism.

J Appl Physiol 1998 Sep;85(3):883-9

http://jap.physiology.org/cgi/content/full/85/3/883

Metabolic and exercise endurance effects of coffee and caffeine ingestion.

Graham TE, Hibbert E, Sathasivam P.

Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. [email protected]

Caffeine (Caf) ingestion increases plasma epinephrine (Epi) and exercise endurance; these results are frequently transferred to coffee (Cof) consumption. We examined the impact of ingestion of the same dose of Caf in Cof or in water. Nine healthy, fit, young adults performed five trials after ingesting (double blind) either a capsule (Caf or placebo) with water or Cof (decaffeinated Cof, decaffeinated with Caf added, or regular Cof). In all three Caf trials, the Caf dose was 4.45 mg/kg body wt and the volume of liquid was 7.15 ml/kg. After 1 h of rest, the subject ran at 85% of maximal O2 consumption until voluntary exhaustion (approximately 32 min in the placebo and decaffeinated Cof tests). In the three Caf trials, the plasma Caf and paraxanthine concentrations were very similar. After 1 h of rest, the plasma Epi was increased (P < 0.05) by Caf ingestion, but the increase was greater (P < 0.05) with Caf capsules than with Cof. During the exercise there were no differences in Epi among the three Caf trials, and the Epi values were all greater (P < 0.05) than in the other tests. Endurance was only increased (P < 0. 05) in the Caf capsule trial; there were no differences among the other four tests. One cannot extrapolate the effects of Caf to Cof; there must be a component(s) of Cof that moderates the actions of Caf.

Med Sci Sports Exerc 2000 Nov;32(11):1958-63
Enhancement of 2000-m rowing performance after caffeine ingestion.

Bruce CR, Anderson ME, Fraser SF, Stepto NK, Klein R, Hopkins WG, Hawley JA.

Department of Human Biology and Movement Science, RMIT University, Bundoora, Victoria Australia.

PURPOSE: To investigate the effect of caffeine ingestion on short-term endurance performance in competitive rowers. METHODS: In this randomized double-blind crossover study, eight competitive oarsmen (peak oxygen uptake [VO2peak] 4.7+/-0.4 L x min(-1), mean +/- SD) performed three familiarization trials of a 2000-m rowing test on an air-braked ergometer, followed by three experimental trials at 3- to 7-d intervals, each 1 h after ingesting caffeine (6 or 9 mg x kg(-1) body mass) or placebo. Trials were preceded by a standardized warm-up (6 min at 225+/-39 W; 75+/-7.7% VO2peak). RESULTS: Urinary caffeine concentration was similar before ingestion (approximately 1 mg x L(-1)) but rose to 6.2+/-3.6 and 14.5+/-7.0 mg x L(-1) for the low and high caffeine doses, respectively. Plasma free fatty acid concentration before exercise was higher after caffeine ingestion (0.29+/-0.17 and 0.39+/-0.20 mM for 6 and 9 mg x kg(-1), respectively) than after placebo (0.13+/-0.05 mM). Respiratory exchange ratio during the warm-up was also substantially lower with caffeine (0.94+/-0.09 and 0.93+/-0.06 for the low and high dose) than with placebo (0.98+/-0.12). Subjects could not distinguish between treatments before or after the exercise test. Both doses of caffeine had a similar ergogenic effect relative to placebo: performance time decreased by a mean of 1.2% (95% likely range 0.4-1.9%); the corresponding increase in mean power was 2.7% (0.4-5.0%). Performance time showed some evidence of individual differences in the effect of caffeine (SD 0.9%; 95% likely range 1.5 to -0.9%). CONCLUSIONS: Ingestion of 6 or 9 mg x kg(-1) of caffeine produces a worthwhile enhancement of short-term endurance performance in a controlled laboratory setting.


Diabetes 2002 Mar;51(3):583-90

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise.

Thong FS, Derave W, Kiens B, Graham TE, Urso B, Wojtaszewski JF, Hansen BF, Richter EA.

Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Canada. [email protected]

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.

Sports Med 2001;31(11):785-807

Caffeine and exercise: metabolism, endurance and performance.

Graham TE.

Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada. [email protected]

Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. It can be a powerful ergogenic aid at levels that are considerably lower than the acceptable limit of the International Olympic Committee and could be beneficial in training and in competition. Caffeine does not improve maximal oxygen capacity directly, but could permit the athlete to train at a greater power output and/or to train longer. It has also been shown to increase speed and/or power output in simulated race conditions. These effects have been found in activities that last as little as 60 seconds or as long as 2 hours. There is less information about the effects of caffeine on strength; however, recent work suggests no effect on maximal ability, but enhanced endurance or resistance to fatigue. There is no evidence that caffeine ingestion before exercise leads to dehydration, ion imbalance, or any other adverse effects. The ingestion of caffeine as coffee appears to be ineffective compared to doping with pure caffeine. Related compounds such as theophylline are also potent ergogenic aids. Caffeine may act synergistically with other drugs including ephedrine and anti-inflammatory agents. It appears that male and female athletes have similar caffeine pharmacokinetics, i.e., for a given dose of caffeine, the time course and absolute plasma concentrations of caffeine and its metabolites are the same. In addition, exercise or dehydration does not affect caffeine pharmacokinetics. The limited information available suggests that caffeine non-users and users respond similarly and that withdrawal from caffeine may not be important. The mechanism(s) by which caffeine elicits its ergogenic effects are unknown, but the popular theory that it enhances fat oxidation and spares muscle glycogen has very little support and is an incomplete explanation at best. Caffeine may work, in part, by creating a more favourable intracellular ionic environment in active muscle. This could facilitate force production by each motor unit.

J Appl Physiol 1995 Mar;78(3):867-74 Related Articles, Links


Metabolic, catecholamine, and exercise performance responses to various doses of caffeine.

Graham TE, Spriet LL.

School of Human Biology, University of Guelph, Ontario, Canada.

This study examined the exercise responses of well-trained endurance athletes to various doses of caffeine to evaluate the impact of the drug on exercise metabolism and endurance capacity. Subjects (n = 8) withdrew from all dietary sources of caffeine for 48 h before each of four tests. One hour before exercise they ingested capsules of placebo or caffeine (3, 6, or 9 mg/kg), rested quietly, and then ran at 85% of maximal O2 consumption to voluntary exhaustion. Blood samples for methylxanthine, catecholamine, glucose, lactate, free fatty acid, and glycerol analyses were taken every 15 min. Plasma caffeine concentration increased with each dose (P < 0.05). Its major metabolite, paraxanthine, did not increase between the 6 and 9 mg/kg doses, suggesting that hepatic caffeine metabolism was saturated. Endurance was enhanced with both 3 and 6 mg/kg of caffeine (increases of 22 +/- 9 and 22 +/- 7%, respectively; both P < 0.05) over the placebo time of 49.4 +/- 4.2 min, whereas there was no significant effect with 9 mg/kg of caffeine. In contrast, plasma epinephrine was not increased with 3 mg/kg of caffeine but was greater with the higher doses (P < 0.05). Similarly only the highest dose of caffeine resulted in increases in glycerol and free fatty acids (P < 0.05). Thus the highest dose had the greatest effect on epinephrine and blood-borne metabolites yet had the least effect on performance. The lowest dose had little or no effect on epinephrine and metabolites but did have an ergogenic effect. These results are not compatible with the traditional theory that caffeine mediates its ergogenic effect via enhanced catecholamines.


Int J Obes Relat Metab Disord 1994 May;18(5):345-50 Related Articles, Links


Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment in obese women.

Yoshida T, Sakane N, Umekawa T, Kondo M.

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.

To clarify whether there were any differences in basal metabolic rate (BMR) and thermogenic response to caffeine in individual obese women, and if so, whether such differences affected weight loss, the basal and resting metabolic rates at 30 min after a caffeine loading test (4 mg/kg ideal body weight, per os) were measured in 136 obese women and ten lean age-matched controls. The obese subjects were then asked to follow a combined low calorie diet and exercise regimen. There were no differences in the BMR and thermogenic responses to caffeine between the obese and lean groups. However, the BMR and the thermogenic responses to caffeine varied widely in obese subjects. After two months of treatment, body weight and percentage body fat in obese women were significantly (P < 0.001) reduced. There were significant correlations between the BMR and body weight loss (r = 0.3621, P < 0.001), between BMR/lean body mass and body weight loss (r = 0.3196, P < 0.001) and between the thermogenic response to caffeine and body weight loss (r = 0.6943, P < 0.001). When the criterion of a BMR less than 3.10 kJ/min (less than two standard deviations below the mean of the age-matched lean control) was used to define an obese group with reduced BMR, there were 30 obese subjects in this group, and their body weight was significantly decreased by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Int J Sports Med 1999 Aug;20(6):354-61

Caffeine improves cognitive performance after strenuous physical exercise.

Hogervorst E, Riedel WJ, Kovacs E, Brouns F, Jolles J.

Department of Psychiatry and Neuropsychology, Brain & Behaviour Institute, European Graduate School for Neurosciences, The Netherlands.

The effects of three carbohydrate electrolyte solutions (CES) containing different amounts of caffeine on cognitive function and the combined effects of these drinks and exercise on cognitive functions were investigated in a double-blind, cross-over study. On five separate occasions, fifteen endurance trained male athletes (23.3 years) received water placebo, CES placebo (68.8 g/l), and three CES drinks containing low, medium and high dosages of caffeine (150, 225 and 320 mg/l). Each occasion, 8 ml/kg of the drink was consumed before -- and 6 ml/kg of the drink was consumed during an all-out 1 hour time trial on a bicycle ergometer. Cognitive (attentional, psychomotor, and memory) tests were carried out immediately before and immediately after exercise. Before exercise, long term memory was improved by CES plus low dose caffeine compared to both placebos. Immediately after exercise, all cognitive functions were improved by CES plus low- and medium-dose caffeine compared to placebo. These results comprise the first practical demonstration of the cognition improving effects of low amounts of caffeine in CES after strenuous physical exercise.

Can J Physiol Pharmacol 1990 Jul;68(7):889-92

Effects of caffeine ingestion on body fluid balance and thermoregulation during exercise.

Falk B, Burstein R, Rosenblum J, Shapiro Y, Zylber-Katz E, Bashan N.

Faculty of Health Sciences, McMaster University, Hamilton, Ont., Canada.

This study investigated the effects of caffeine supplementation on thermoregulation and body fluid balance during prolonged exercise in a thermoneutral environment (25 degrees C, 50% RH). Seven trained male subjects exercised on a treadmill at an intensity of 70-75% of maximal oxygen consumption to self-determined exhaustion. Subjects exercised once after caffeine and once after placebo ingestion, given in a double-blind crossover design. Five milligrams per kilogram body weight of caffeine followed by 2.5 mg.kg-1 of caffeine were given 2 and 0.5 h before exercise, respectively. Rectal temperature was recorded and venous blood samples were withdrawn every 15 min. Water loss and sweat rate were calculated from the difference between pre- and post-exercise body weight, corrected for liquid intake. Following caffeine ingestion, when compared with placebo, no significant difference in final temperature or in percent change in plasma volume were found. No significant differences were observed in total water loss (1376 +/- 154 vs. 1141 +/- 158 mL, respectively), sweat rate (12.4 +/- 1.1 vs. 10.9 +/- 0.7 g.m-2.min-1, respectively), rise in rectal temperature (2.1 +/- 0.3 vs. 1.5 +/- 0.4 degrees C, respectively), nor in the calculated rate of heat storage during exercise (134.4 +/- 17.7 vs. 93.5 +/- 22.5 W, respectively). Thus, in spite of the expected rise in oxygen uptake, caffeine ingestion under the conditions of this study does not seem to disturb body fluid balance or affect thermoregulation during exercise performance.