[extropy-chat] Resveratrol Bioavailability Analysis

[Ian Goddard]

Regarding Resveratrol :
http://www.sirtuins.com/life-extension.html

The question of the bioavailability of resveratrol may
not have come up on extropy-chat, but since it is an
important question for many life extensionists, I'm
posting my analysis below in hopes that it may advance
the life-extending efforts of members. ~Ian


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FACT: Almost zero free resveratrol is found in the
bloodstream after oral dosing due to the conjugation
of resveratrol with sulfur and glucuronic acid in the
liver. [1,2]

HYPOTHESIS: The evidenced effects of non-oral
resveratrol dosing (for example, in vitro or in vivo
by injection) are not available by oral resveratrol
dosing.

	Hypothesis Test:

	Non-oral Resveratrol Effects
	  * Blood thinning [3]
	  * Ischemia protection [4]
	  * Life extension [5]

	Oral Resveratrol Effects
	  * Blood thinning [6] 
	  * Ischemia protection [7]
	  * Life extension [8]

ERGO: The hypothesis is falsified since there exists
at least three evidenced effects of non-oral
resveratrol that appear to be available by oral
resveratrol. We are thus compelled to adopt the
contrary hypothesis: at least some (if not all)
evidenced effects of non-oral resveratrol are
available by oral resveratrol. There are means by
which resveratrol may deliver effect despite hepatic
conjugation, but mechanisms are beyond the scope of
this logical empirical-results analysis.

(This analysis is expressed in formal logic following
its empirical referents.)
_____________________________________________________

[1] http://www.hubmed.org/display.cgi?uids=15779070
[2] http://www.hubmed.org/display.cgi?uids=12554065

Non-oral Resveratrol Effects:

[3] British Journal of Pharmacology (1999):
"trans-Resveratrol inhibits human platelet aggregation
both in vitro and in vivo." 
http://www.nature.com/bjp/journal/v128/n1/full/0702749a.html

[4] Brain Research (2003): "Resveratrol was injected
i.p. (30 mg/kg body weight) [...] This study
demonstrated for the first time that resveratrol, a
polyphenolic antioxidant, can cross the blood-brain
barrier and exert protective effects against cerebral
ischemic injury."
http://www.hubmed.org/display.cgi?uids=12470882

[5] Nature (2003): "In yeast, resveratrol mimics
calorie restriction by stimulating Sir2, increasing
DNA stability and extending lifespan by 70%." NOTE:
This is an instance of non-oral dosing because yeast
are ahepatic.
http://www.nature.com/nature/journal/v425/n6954/abs/nature01960.html

Oral Resveratrol Effects:

[6] Clinica Chimica Acta (1996): "studies were
performed on 24 healthy males aged 26-45 years [...]
commercial juice lowered the IC50 for thrombin (P <
0.001) whereas the resveratrol-enriched juice caused a
dramatic increase (P < 0.001). [...] We conclude that
trans-resveratrol can be absorbed from grape juice in
biologically active quantities and in amounts that are
likely to cause reduction in the risk of
atherosclerosis."
http://www.hubmed.org/display.cgi?uids=8814965

[7] Life Sciences (2005): "Male Balb/C mice were
treated with resveratrol for 7 days (50 mg/kg,
gavage). [...] elevated levels of MMP-9 were
significantly attenuated in the resveratrol-treated
mice as compared to the vehicle MCAo mice. The study
suggests that resveratrol has protective effects
against acute ischemic stroke." NOTE: Feeding by
"gavage" is tube-to-stomach feeding, which does not
bypass the liver.
http://www.hubmed.org/display.cgi?uids=16321402

[8] Current Biology (2006): "120 mg/g [ resveratrol /
food ] caused an increase of median and maximum
lifespan of 33% and 27%, respectively (p < 0.001, log
rank test), and 600 mg/g food induced 56% and 59%
increase in median and maximum lifespan, respectively
(p < 0.001, log rank test). 600 mg/g food was
significantly more effective than 120 mg/g food in
prolonging lifespan (p = 0.01, log rank test)."
http://www.hubmed.org/display.cgi?uids=16461283

Progress of resveratrol life-extension research:
http://www.longevinex.com/images/resveratrol_experiments_full.jpg

_____________________________________________________

Translating the hypothesis into formal logic for
evaluation where

N = non-oral resveratrol dosing
O = oral resveratrol dosing

HYPOTHESIS: The evidenced effects of N are not
available by O.

HYPOTHESIS-TEST STATEMENT: 
If X is an effect of N, then X is not an effect of O.

Fleshing out that statement for clarity of
translation:

For any effect X and any studies x and y, if x uses N
and x finds X, then it is NOT the case that if y uses
O, y finds X.

Now translating it into second-order predicate logic:

(X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]

Now instantiating it step-by-step into the first
empirical case where

B = found blood-thinning
a = study [3]
b = study [6]

1. (X)(x)(y)[ (Nx & Xx) -> ~(Oy -> Xy) ]
2. (x)(y)[ (Nx & Bx) -> ~(Oy -> By) ]
3. (y)[ (Na & Ba) -> ~(Oy -> By) ]
4. (Na & Ba) -> ~(Ob -> Bb)

And then applying two replacement rules to step 4:

4. (Na & Ba) -> ~(Ob -> Bb)
5. (Na & Ba) -> ~(~Ob v Bb)  -  conditional exchange
6. (Na & Ba) -> (Ob & ~Bb)  -  de Morgan's

Now by the semantics of predicate logic we can see
that the hypothesis-test statement is false by
observing that its antecedent (Na & Ba) is true (study
[3] has the properties N and B), yet its consequent is
false because in fact b (study [6]) has the properties
O and B. However, according to the hypothesis-test
statement, b must have the property ~B. So it turns
out that ~Bb is false since Bb is true, and thus the
consequent (Ob & ~Bb) is false since one of its
conjuncts is false. Therefore, with a true antecedent
and false consequent, the whole statement (Ba & Na) ->
(Ob & ~Bb) is false, and thus the hypothesis is
falsified by this single case alone. Instantiating the
hypothesis-test statement into the other two cases
cited above follows same steps to the same result.

Because the hypothesis is falsified we must by logical
consequence adopt the contrary: at least some (if not
all) evidenced effects of non-oral resveratrol are
available by oral resveratrol.


http://www.IanGoddard.net

"Without philosophy thoughts are, as it were, cloudy
and indistinct; its task is to make them clear and to
give them sharp boundaries." Ludwig Wittgenstein 




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