Caffeine and coffee as therapeutics against Alzheimer's disease.

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Olafur Pall Olafsson

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Jun 12, 2010, 4:27:02 PM6/12/10
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J Alzheimers Dis. 2010;20 Suppl 1:S117-26.
Caffeine and coffee as therapeutics against Alzheimer's disease.
Arendash GW, Cao C.

The Florida Alzheimer's Disease Research Center, Tampa, FL, USA.
aren...@cas.usf.edu
Abstract
Epidemiologic studies have increasingly suggested that caffeine/coffee
could be an effective therapeutic against Alzheimer's disease (AD). We
have utilized a transgenic mouse model for AD in well-controlled
studies to determine if caffeine and/or coffee have beneficial actions
to protect against or reverse AD-like cognitive impairment and AD
pathology. AD mice given caffeine in their drinking water from young
adulthood into older age showed protection against memory impairment
and lower brain levels of the abnormal protein (amyloid-beta; Abeta)
thought to be central to AD pathogenesis. Moreover, "aged" cognitively-
impaired AD mice exhibited memory restoration and lower brain Abeta
levels following only 1-2 months of caffeine treatment. We believe
that the cognitive benefits of chronic caffeine administration in AD
mice are due to caffeine itself, and not metabolites of caffeine;
this, because our long-term administration of theophylline to AD mice
provided no cognitive benefits. In acute studies involving AD mice,
one oral caffeine treatment quickly reduced both brain and plasma
Abeta levels - similarly rapid alterations in plasma Abeta levels were
seen in humans following acute caffeine administration. "Caffeinated"
coffee provided to AD mice also quickly decreased plasma Abeta levels,
but not "decaffeinated" coffee, suggesting that caffeine is critical
to decreasing blood Abeta levels. Caffeine appears to provide its
disease-modifying effects through multiple mechanisms, including a
direct reduction of Abeta production through suppression of both beta-
and gamma-secretase levels. These results indicate a surprising
ability of moderate caffeine intake (the human equivalent of 500 mg
caffeine or 5 cups of coffee per day) to protect against or treat AD
in a mouse model for the disease and a therapeutic potential for
caffeine against AD in humans.

PMID: 20182037 [PubMed - in process]

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Arbor B

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Jun 12, 2010, 6:34:58 PM6/12/10
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On Jun 12, 10:27 am, Olafur Pall Olafsson <olafurp...@yahoo.com>
wrote:

> J Alzheimers Dis. 2010;20 Suppl 1:S117-26.
> Caffeine and coffee as therapeutics against Alzheimer's disease.
> Arendash GW, Cao C.
>"These results indicate a surprising
> ability of moderate caffeine intake (the human equivalent of 500 mg
> caffeine or 5 cups of coffee per day) to protect against or treat AD
> in a mouse model for the disease and a therapeutic potential for
> caffeine against AD in humans.
> PMID: 20182037 [PubMed - in process]
>
I don't know many people can tolerate 500 mg of caffeine/day (at
least as far as maintaining sleep quality);-(.
I
> "[W]e believe that the cognitive benefits of chronic caffeine administration in AD

mice are due to caffeine itself, and not metabolites of caffeine;"
> [A]n acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels - similarly rapid > alterations in plasma Abeta levels were seen in humans following acute caffeine administration."

Which means a continuous (throughout the day) consumption of
caffeine. Unfortunately, this is possible only in people who are fast
metabolizers of caffeine.

Arbor

Arbor B

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Jun 12, 2010, 6:39:44 PM6/12/10
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On Jun 12, 12:34 pm, Arbor B <soowhatdouth...@hotmail.com> wrote:

> > [A]n acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels - similarly rapid > alterations in plasma Abeta levels were seen in humans following acute caffeine administration."
>
> Which means a continuous (throughout the day) consumption of
> caffeine.  Unfortunately, this is possible only in people who are fast
> metabolizers of caffeine.
>
> Arbor

However, I wonder if amounts smaller than 500 mg/day for slow
metabolizers is sufficient.

Arbor

David

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Jun 12, 2010, 11:53:52 PM6/12/10
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On Jun 12, 3:39 pm, Arbor B <soowhatdouth...@hotmail.com> wrote:

> However, I wonder if amounts smaller than 500 mg/day for slow
> metabolizers is sufficient.
>
> Arbor


I'd think so, since total caffeine exposure over time should be the
important part, rather than what the liver is doing. In fact, as
caffeine (rather than its metabolites) appears to be the active
molecule, slow metabolizers may in theory receive an even greater
benefit.

And I'd think that even part-day caffeine exposure would be better
than none. I'm a slow caffeine metabolizer, so I ingest caffeine in
the a.m. and then just after lunch -- anything later than that
completely screws up my sleep.

Message has been deleted

Doug Freyburger

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Jun 13, 2010, 5:06:11 PM6/13/10
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Arbor B wrote:
> Olafur Pall Olafsson <olafurp...@yahoo.com> wrote:
>
>> J Alzheimers Dis. 2010;20 Suppl 1:S117-26.
>> Caffeine and coffee as therapeutics against Alzheimer's disease.
>> Arendash GW, Cao C.
>>"These results indicate a surprising
>> ability of moderate caffeine intake (the human equivalent of 500 mg
>> caffeine or 5 cups of coffee per day) to protect against or treat AD
>> in a mouse model for the disease and a therapeutic potential for
>> caffeine against AD in humans.
>> PMID: 20182037 [PubMed - in process]
>>
> I don't know many people can tolerate 500 mg of caffeine/day (at
> least as far as maintaining sleep quality);-(.

You haven't encountered ADD/ADHD folks who use caffeine to moderate
their traits then. If I have trouble falling asleep I can take another
cup of coffee and it helps quiet the chorus and reduce the spinning that
causes the distractability. Bingo, with a quieter inside I can dose off.

Olafur Pall Olafsson

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Jun 13, 2010, 5:47:34 PM6/13/10
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On Jun 13, 3:53 am, David <david.spro...@gmail.com> wrote:
> On Jun 12, 3:39 pm, Arbor B <soowhatdouth...@hotmail.com> wrote:
>
> > However, I wonder if amounts smaller than 500 mg/day for slow
> > metabolizers is sufficient.
>
> > Arbor
>
> I'd think so, since total caffeine exposure over time should be the
> important part, rather than what the liver is doing.  In fact, as
> caffeine (rather than its metabolites) appears to be the active
> molecule, slow metabolizers may in theory receive an even greater
> benefit.
>
> And I'd think that even part-day caffeine exposure would be better
> than none.  

I agree with David here. Reasonably a lower dose would be needed for
slow metabolizers.

> I'm a slow caffeine metabolizer, so I ingest caffeine in
> the a.m. and then just after lunch  -- anything later than that
> completely screws up my sleep.

That seems like a good approach in your case. BTW since I have never
drunken coffee (I dislike it's taste and smell) I am not sure if I am
a slow or a fast caffeine metabolizer or something in between. I have
drunken green tea a lot of times in the past but there isn't enough
caffeine in it for me to obviously notice it's effects.

David

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Jun 13, 2010, 8:17:41 PM6/13/10
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On Jun 13, 2:47 pm, Olafur Pall Olafsson <olafurp...@yahoo.com> wrote:

> That seems like a good approach in your case. BTW since I have never
> drunken coffee (I dislike it's taste and smell) I am not sure if I am
> a slow or a fast caffeine metabolizer or something in between. I have
> drunken green tea a lot of times in the past but there isn't enough
> caffeine in it for me to obviously notice it's effects.


There's always No-Doz! (i.e. over the counter caffeine pills -- 200
mg per scored tablet)

RArmant

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Jun 14, 2010, 1:56:48 PM6/14/10
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What is needed are controlled studies using caffeine for Alzheimer's.
Don't expect big pharma to pay for these studies.

Also, the ketogenic diet looks promising for Alzheimer's.


Arbor B

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Jun 14, 2010, 6:30:50 PM6/14/10
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On Jun 12, 5:53 pm, David <david.spro...@gmail.com> wrote:
> [A]nd I'd think that even part-day caffeine exposure would be better > than none. I'm a slow caffeine metabolizer, so I ingest caffeine in

> the a.m. and then just after lunch -- anything later than that
> completely screws up my sleep.

My husband is a very fast metabolizer of caffeine (his estimated
caffeine intake is ~500-700 mg/daily w/o any interference with sleep
length and architecture). Based on his life experience with
medications he is also happens to be a fast metabolizer of most med
that he has ever taken. So much so that when he is prescribed a
medication he always asks for a larger daily dose to make sure that he
gets the therapeutic effect. His 3 sisters have had the same
experience.
I, on the other hand, am a very slow metabolizer of caffeine as well
as of medications and so is my sister. Until a study would find
otherwise, I have to conclude, from these family observations, that
the effective dose of daily caffeine intake (vs. AD) in humans might
vary as well.
The introduction to [1] posted below is relevant to this discussion.
It mentions other variables that affects the clearance of caffeine and
medications.
You can figure your daily dose by taking, for a period of few weeks,
caffeine pills (like NoDoz, which has 200 mg/each) or even light
beverages that specify caffeine contents, while avoiding any caffeine
from unmeasured sources. Once you know your daily dose, it can be
divided over the hours that you can take it without interference with
sleep to maintain a contentious "caffeinated blood".

Arbor

1. Application of the PKCYP-test in cases of altered CYP1A2 for
multiple CYP systems in rat models of disease.
Matsunaga N, Hattori K, Iizasa H, Kizu J, Takanaka A, Nakashima E.
Biol Pharm Bull. 2001 Sep;24(9):1037-43.PMID: 11558565 Free Article

“In order to evaluate the drug metabolism capacity of individual
patients, selective substrate probes have been used in vivo to
identify the cytochrome P450 (CYP) isozymes involved in a variety of
drug metabolism processes.1) It has been suggested that the in vivo
intrinsic clearance by hepatic metabolism can be predicted from in
vitro metabolism data by the use of either liver microsomes or a
recombinant system of human CYP isozymes.2,3).
Previously, we developed a novel method for determining drug
metabolism capacity based on a pharmacokinetic estimation of the
quantity of CYP in vivo (PKCYP-test). By using a specific probe, the
drug metabolism capacity of each CYP isozyme can be estimated from the
PKCYP-test incorporating the apparent liver-to-blood free
concentration gradient in vivo (qg).4) In rats whose CYP1A2 level has
been induced by the administration of 3-methylcholanthrene (MC
treated rats), the amount of CYP1A2 could be predicted by the PKCYP-
test using acetanilide as the probe. Furthermore, caffeine clearance
could also be predicted by using the predicted amount of CYP1A2.
However, there were some differences between observed and predicted
values as far as the amount of CYP1A2 and caffeine clearance were
concerned.
Both acetanilide and caffeine have been reported to be metabolized
mainly by CYP1A2 in rats.5,6) However, there is a contradictory report
that another CYP isozyme is also involved in the metabolism of
caffeine.7) Since CYP1A2 participates mainly in the metabolism of both
acetanilide and caffeine in MC-treated rats, the error in predicting
the amount of CYP1A2 and caffeine clearance may be negligible. It is
anticipated that the role of other CYP isozymes in their metabolism
might have little effect on the prediction of the amount of CYP1A2 and
caffeine clearance in other models in which the CYP1A2 enzyme level is
reduced. Since there are many patients with reduced CYP levels, there
is a need to investigate the application of the PKCYP-test to the
reduced CYP model. Moreover, it is still unclear if the PKCYP-test can
be applied to drugs that are metabolized by multiple CYP isozymes.
It has been reported that the amount of CYP is reduced both in rats
fed a choline-deficient diet and in aged rats, and the amount of CYP
in these rat models is regulated differently by each CYP isozyme.(8—
11) In order to examine the application of the PKCYP-test to drugs
that are metabolized by multiple CYP isozymes and/or in models with
reduced CYP levels, we examined the application of the PKCYP-test to
the clearance of acetanilide and caffeine mediated by CYP1A2 using
rats fed a choline-deficient diet and aged rats. “

trigonometry1972@gmail.com |

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Jun 16, 2010, 9:42:10 AM6/16/10
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> You haven't encountered ADD/ADHD folks who use caffeine to moderate
> their traits then.  

Like the Brazilian school official of some years ago that started
to offer coffee to his school district's kids and claimed improvements
in study performance?

Doug Freyburger

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Jun 16, 2010, 2:27:36 PM6/16/10
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Ritalin is given to ADD/ADHD kids with good results. Ritalin is a
stimulant to the lower-focus-intensity majority but reduces
distraction to the ADD/ADHD. Caffeine is a stimulant as well so I
wondered if it would work as a weaker non-prescription version for me.
It does.

I'm not surprised that such a study has reported that result. It
wouldn't work like that for non-ADD/ADHD folks.

Ted

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Jun 17, 2010, 5:35:33 PM6/17/10
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I have no problem drinking 5 or 6 cups a day. I drink it in the
evening too. I just got use to it after a period of time.

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