Paul,

I apologize if this has been adressed somewhere, and I missed it, but
is it possible the human's livers are metabolizing resveratrol into
something that lacks the activity seen in animals from trans
resveratrol i.e. does anyone know that resveratrol glucuronides do in
humans what trans resveratrol does in animals?

[I think the answer to your question is no. Resveratrol is not such a strange
chemical that the livers of most animals do not work on it the same way. The
absorption and metabolism of resveratrol by mice and rats is essentially the
same as by humans (PMID: 12523673). All studies show that no significant amount
of free resveratrol (same as trans-resveratrol) is found in the serum after
ingestion. Nevertheless multiple in vivo studies also show that it appears to be
highly beneficial in many ways. Most scientists seem now to realize that the in
vitro studies of pure resveratrol are not very meaningful wrt the in vivo
effects and that what should instead be studied in vitro are the effects of the
metabolites of resveratrol which are mainly the 3- and 4-glucuronides and the
3-sulfate. It is possible that these are acting as storage and transport forms
of resveratrol and that it is being converted back to the free form within
cells, or it may be that these metabolites themselves are producing its
beneficial effects. This may particularly be true for the sulfate form since
many chemicals are sulfated and unsulfated regularly within the body. However,
this has yet to be fully discovered.

[Humans have also an enzyme called beta-glucuronidase which could convert
resveratrol glucuronides back to resveratrol (PMID: 15349955). But whether this
happens in vivo and to what degree has yet to be determined AFAIK -°Olafur]

However, there is no question that resveratrol has multiple beneficial effects
in rats, mice, fish, etc and since its metabolism by these animals appears to be
little different than for humans, I see no reason for skepticism that is will
not have the same beneficial effects in humans. --Paul]


Mol Nutr Food Res. 2005 May;49(5):495-504.
Bioavailability of trans-resveratrol from red wine in humans.

* Vitaglione P,
* Sforza S,
* Galaverna G,
* Ghidini C,
* Caporaso N,
* Vescovi PP,
* Fogliano V,
* Marchelli R.

Dipartimento di Scienza degli Alimenti, Universita degli Studi di
Napoli Federico II, Portici NA, Italy.

Many in vitro studies demonstrated significant biological effects of
trans-resveratrol. Thus, understanding the rate of intestinal
absorption and metabolization in vivo of trans-resveratrol is the
prerequisite to evaluate its potential health impact. Bioavailability
studies mainly in animals or in humans using the pure compound at very
high doses were performed. In this work, trans-resveratrol
bioavailability from a moderate consumption of red wine in 25 healthy
humans has been studied by three different experiments. The wine
ingestion was associated to three different dietary approaches:
fasting, a standard meal, a meal with high and low amount of lipids.
Trans-resveratrol 3- and 4'-glucuronides were synthesized, purified,
and characterized as pure standards. Bioavailability data were
obtained by measuring the concentration of free, 3-glucuronide and
4'-glucuronide trans-resveratrol by high-performance liquid
chromatography (HPLC), both with ultraviolet (UV) and mass
spectrometry (MS) detection, in serum samples taken at different times
after red wine administration. Free trans-resveratrol was found, in
trace amounts, only in some serum samples collected 30 min after red
wine ingestion while after longer times resveratrol glucuronides
predominated. Trans-resveratrol bioavailability was shown to be
independent from the meal or its lipid content. The finding in human
serum of trans-resveratrol glucuronides, rather than the free form of
the compound, with a high interindividual variability, raises some
doubts about the health effects of dietary resveratrol consumption and
suggests that the benefits associated to red wine consumption could be
probably due to the whole antioxidant pool present in red wine.

Scott La Pidus