Caffeine Tolerance II

Caffeine Tolerance II
Andre Willers
23 Jul 2011

Synopsis:
This is for humans with low (1/64 normal) of tolerance for caffeine .
Fluctuating overdose and withdrawal of neurotransmitter sites causes and triggers symptoms which are very similar to schizophrenic and psychotic breaks .

Discussion :
See Appendix A for the genetical cause .
Wikipedia has a very good discussion , and I am only going to summarise the gist of it here . See sites referenced below .

1.Poison :
Caffeine acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants . (See Plant-Herbivore Wars)
2. It works by blocking the adenosine receptor sites (remember AdenosineTriphosphate? Kinda fundamental .) . Survivors compensated by increasing the number of adenosine receptor sites .
3.The liver breaks down caffeine (about 100 mg=1 cup coffee) per 2 hours .
4. Low tolerance individuals breaks it down at 1/64 of this rate . It takes them 2x64 = 126 hours ( ~ 6 days) to break down one cup of coffee . Their body keeps a running total of caffeine with a period of six days . The body creates more receptor sites ,

5.An imbalance in the number of receptor sites cannot go away quickly . They can be inactivated by more caffeine molecules . This is addiction .
6. These imbalances cause all sorts of ripple effects on receptors and neurotransmitters .
You go nuts .

7. Caffeine has many advantages . A safe running dosage for low tolerance humans is
about 27 ml of espresso coffee per day . Bulk it as you like .(Latte)
That is about 200 ml of an cup of filter coffee per day .

8. Plague consequences :
Trade with East introduced caffeine into upper classes .(Circa Crusades) . Caffeine binded to CCR5 receptor sites . These sites then multiplied in compensation . On the downswing , unutilized CCR5 sites were colonized by Black Death organisms .
Anybody who had even tasted tea or coffee was dead . As well as anybody in touch with them . This is still applicable today .

9 . Ideal for plants . Humans are forced to cultivate coffee or tea .If they stop , unutilized stimulated CCR5 sites gives entry to baddies .Plagues result .

10 . A cup a day keeps the plague away .

11. Will humans do it ?
Not a chance . Humans (specifically self-styled Homo Sapiens Sapiens) will be extinct by 2060 . Well deserved .
But the wiggling is interesting ,

Andre
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http://en.wikipedia.org/wiki/Adenosine

Overdose : Too many receptors(caffeine withdrawal)
Side effects
"Many individuals experience facial flushing, a temporary rash on the chest, lightheadedness,diaphoresis, or nausea after administration of adenosine due to its vasodilatory effects.Metallic taste is a hallmark side effect of adenosine administration. These symptoms are transitory, usually lasting less than one minute. It is classically associated with a sense of "impending doom", more prosaically described as apprehension. This lasts a few seconds after administration of a bolus dose, during transient asystole induced by intravenous administration. In some cases adenosine can make patients' limbs feel numb for about 2–5 minutes after administration intravenously depending on the dosage (usually above 12 mg)."

http://en.wikipedia.org/wiki/Caffeine
http://en.wikipedia.org/wiki/Biological_halflife


Appendix A
Caffeine and Heart Attacks.
Andre Willers
14 Mar 2011

Synopsis:
Humans with 1 out of 2 defective copies of the gene P450 A12 (CYP1A2) on chromosome 15 are at least 64 times more likely to have a heart attack . (It governs enzymes in the liver that breaks down caffeine)

Discussion :
Source: J. Craig Venter , "A life decoded" , ISBN 978-0-141-01441-8 , p132 .
Somebody who should know .

A study of 4 000 persons over a year of coffee drinking showed risk of heart attack between 4+cups a day and 1 cup a day was in a ratio of 64:1 . These persons included the mixture of genes .

A separate test on only persons with both fully functional genes showed a less than 1% chance with 4+ cups of coffee per day .

I presume that if you have two bad copies of the gene , extreme caffeine intolerance will result , as it cannot be metabolized but only excreted .Basically , you die .

So , the system is very sensitive (by a factor of 64) to the mutation of one gene .

How do you tell if you have only one functioning gene ?
Absence of habituation .
If coffee always hits you the same way or more , then your liver is not breaking down the caffeine fast enough to compensate for intake . You have one defective gene ,

Is this good or bad ?
There is some historical evidence that caffeine or some metabolite competes with the CCR5 receptor site . This is the real baddy receptor site , where nasties like Black Death , smallpox , some flu's, etc enter the cell .
There was then strong positive selection for increasing caffeine tolerance , as it gave some protection against infectious diseases (apart from boiling the water)

Note the major usage of caffeine by doctors . This is usually ascribed to be kept alert , but it actually started as a fairly effective anti-infective agent .

It definitively kept them alert , mainly by keeping them alive .
As usual , humans got it the wrong way around .

The race between a heart attack and disease .
Having one defective gene means that caffeine stays around longer , but it causes heart problems if overindulged .

As usual with humans , the overindulgence won and selection heavily favoured two functional genes . The "more is better" school .

This results in all those huge coffees you get in Starbucks .
Also that doctors and other major caffeine imbibers will have more normal heart attacks , as some of them will still have one defective gene .

Historical notes :
Note the small old Chinese Tea-cups . (A cup of tea has about half the caffeine content of a cup of coffee .)
Or the original Turkish or Arabic cups .
All are small , because most people only had genes to slowly break down the caffeine .
Calculate optimals by using the 64 ratio .

If you have only one functioning gene.
Don't despair .
If you are partially caffeine intolerant , don't despair . Just drink less .
The effect , both stimulation and infection control is nearly the same .

Half a cup (a demi-tasse) a day of coffee will do the same .In the morning is best (Why do think they made all those millions of demi-tasse cups ?)
Or two demi-tasse's of tea a day . Or 4 chinese cups . You get the drift .

Children :
Treat them as having only one functioning gene.But this places those with two fully functioning genes at greater risk of disease . So , sort them out as soon as possible . A genetic test is preferable , otherwise just watch their behaviour after giving them a cup or two of coffee .

Why does caffeine compete with access to CCR5 receptor site ?
The old Plant-Herbivore Wars .
Plants dependant on cultivators (ie humans) benefit from reduced human susceptibility to disease . Those plants flourished , because humans survived to care for them . And so we are off to the races .

Plants are cultivating humans , and humans are cultivating plants .
A mutual bonsai .

Give a dinosaur a flower .

Andre

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