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It seems that procyanidins, not reveratrol, which is
associated with CR-like
SirT1 modulation, is responsible for the pluses of red wine.


Oenology: Red wine procyanidins and vascular health
R. Corder, W. Mullen, N. Q. Khan, S. C. Marks, E. G. Wood,
M. J. Carrier and
A. Crozier
Nature 444, 566 (30 November 2006)

Regular, moderate consumption of red wine is linked to a
reduced risk of
coronary heart disease and to lower overall mortality1, but
the relative
contribution of wine's alcohol and polyphenol components to
these effects is
unclear2. Here we identify procyanidins as the principal
vasoactive
polyphenols in red wine and show that they are present at
higher
concentrations in wines from areas of southwestern France
and Sardinia,
where traditional production methods ensure that these
compounds are
efficiently extracted during vinification. These regions
also happen to be
associated with increased longevity in the population.

High consumption of polyphenols inhibits atherosclerosis in
experimental
models3, 4. Red-wine polyphenols induce
endothelium-dependent dilatation of
blood vessels and suppress the synthesis of endothelin-1
(ET-1), a peptide
that has a vasoconstricting effect5, 6, 7, and this may
account for their
anti-atherosclerotic activity. However, there is a lack of
consensus on the
protective effects of red wine, which may be due to
variability in
vasoactive constituents in different wines.

Red-wine polyphenols are a complex mixture of flavonoids
(mainly
anthocyanins and flavan-3-ols) and non-flavonoids (such as
resveratrol and
gallic acid). Flavan-3-ols are the most abundant, with
oligomeric and
polymeric procyanidins (condensed tannins) often
representing 25-50% of the
total phenolic constituents8.

We used cultured endothelial cells to identify the most
potent vasoactive
polyphenols in red wine (for methods, see supplementary
information). These
were shown by high-performance liquid chromatography with
mass spectrometry2
to be straight-chain B-type oligomeric procyanidins (OPCs)
(tetra-epicatechin gallate, m/z = 1,305; procyanidin
trimer-gallate, m/z =
1,017; procyanidin tetramer, m/z = 1,153; and
pentamer-gallate, m/z = 1,593;
see supplementary information).

Total polyphenols and OPC content of each wine correlated
with the
suppression of ET-1 synthesis (Fig. 1a, b). However, the
linear regression
plot for total polyphenols intercepted the y-axis at about 5
mM, which is
consistent with most polyphenols (anthocyanins, catechins
and resveratrol)
lacking vasoactivity at the concentrations found in wine5, 7.

Figure 1: Relationship between procyanidin content and
vasoactive properties
of red wine.
a, b, Total polyphenol (a) and oligomeric procyanidin (OPC)
(b) content
correlate with the inhibition of synthesis of endothelin-1,
expressed as
ED50 (dilution inhibiting by 50%; see supplementary
information); R = 0.84
for both, n = 165. c, d, Comparison of inhibition of
endothelin-1 synthesis
(c) with OPC concentration (d) of wines from different
geographical regions.
Au, Australia; EU, France, Greece, Italy or Spain; SA, South
America; US,
United States; Sd, Sardinia; Nu, Nuoro province, Sardinia;
swF, southwest
France. CE, catechin equivalents (see supplementary
information). ***P <
0.001 compared with all the other wines; *P < 0.01 compared
with the United
States [Nu, polyphenolds], and P < 0.001 swF for polyphenols
and log OPC]
compared with the other wines; **P < 0.02 compared with the
United States
and South America [Nu, log OPC], and P < 0.001 compared with
the other wines
[Nu, log OPC].

To investigate how the OPC content of red wines from a
particular region
might relate to mortality in that region, we compared wines
produced in
areas of increased longevity (as an index of overall good
health) with a
broad selection of wines from different countries. People
living in Nuoro
province, Sardinia, have high longevity, particularly men9.
In France, there
are marked regional variations in mortality from coronary
heart disease. We
used the 1999 census data to identify unusual patterns of
ageing in France
(see supplementary information) and found that there are
relatively more men
aged 75 or over in the département of Gers in the
Midi-Pyrenees in southwest
France.

Wines from Nuoro and the Gers area have 2-4-fold more
biological activity
and OPC content than other wines (Fig. 1c, d). This
difference remains (P <
0.001) when OPC measurements are extended to a wider
selection of wines from
the Gers area (2.9 0.1 mM, n = 58), from France (1.8 0.1
mM, n = 61) and
from other parts of the world (1.5 0.04 mM, n = 227).

Grape seeds are the main source of OPCs but poor solubility,
combined with
oenological and viticultural factors, influence the amount
of OPCs in wine8.
The higher OPC concentration in wines from southwest France
is due to
traditional wine-making, which ensures that high amounts of
OPCs are
extracted, and to the flavonoid-rich grape Tannat, which
makes up a large
proportion of grapes used to produce local wines in the Gers
area but is
rarely grown elsewhere.

Absorption of OPCs and their identification in plasma has
been demonstrated
in vivo10, but little is known about their biological
availability and
metabolism. Further investigation of OPC-rich wines and
foods should provide
insight into how vascular function might be optimally
maintained.