0040 Different dietary agents result in distinct alter-
ations in the expression in phase I and II enzymes.
For example, butylated hydroxy toluene (BHT),
ethoxyquin, indol-3-carbinol, and phenethyl isothio-
cyanate induced both the phase I and the phase II
isozymes and are therefore referred to as bifunctional
agents. Caffeic acid, garlic oil, and propyl gallate
induced phase II enzymes, but not phase I. 4-Methyl
catechol, a-tocopheral, and red wine decreased phase
I and induced GST. The type of red wine used in this
study was not defined. The ratio of the phase I/phase
II is more important in understanding protection or
toxicity as opposed to the levels of one or the other. If
the relative increase in phase II enzymes is greater
than the phase I enzymes, then the assumption is
that it is overall protective. If phase I enzymes in-
crease relatively greater than phase II, then the poten-
tial for damage, by free radicals or production of
toxic compounds, is greater. Alcohol consumption is
known to induce phase I CYP2E1, resulting in pro-
duction of acetaldehyde. Acetaldehyde, whether
generated by this mechanism or by alcohol dehydro-
genase, is potentially damaging due to its participa-
tion in free radical generation.
0041 In one of the few articles that used the wine itself,
Chan et al. showed that red wine solids, but not white
wine solids, inhibited CYP3A4. In the study by Perci-
val and Sims, liver microsomal cytochrome CYP2E1
and GST were altered by wine consumption, and
Muscadine wine resulted in different patterns relative
to the Cabernet Sauvignon. The Muscadine wine
reduced CYP2E1 about 80%, whereas the Cabernet
had no effect. Although the GST activity was also
reduced in the mice that drank Muscadine, the ratio
between the two enzymes was increased threefold,
suggesting a beneficial effect of the Muscadine wine.
GST activity was no different in the ethanol group
or the Cabernet group compared with the water-
consuming group, suggesting that there are unique
components in the Muscadine wine that resulted in
the observed changes. Moreover, the mice that drank
the Cabernet Sauvignon did not have an extensive
change in the microsomal detoxification enzymes,
signifying a unique response of the mice to the
Muscadine wine.
0042 Ellagic acid has been shown to increase phase II
enzymes GST and quinone reductase in mice. It has
also been shown to inhibit metabolic activation of
carcinogens. For example, ellagic acid inhibits the
conversion of polycylic aromatic hydrocarbons,
nitroso compounds, and aflatoxin B1 into com-
pounds that cause genetic damage. Ellagic acid was
also shown to inhibit CYP1A1. The anticarcinogenic
effectiveness of ellagic acid was due to several
different structural aspects of the molecule.
Summary
0043Red wine consumption results in an increase in anti-
oxidant levels in the blood. Data on benefits of the
individual compounds are emerging, but the study
of red wine itself is limited. Health benefits can be
demonstrated in epidemiological and animal studies
regarding heart disease, but information is less solid
regarding cancer, and nonexistent for other disease.
The data cannot be ascribed solely to the phytochem-
ical content of the wine since moderate alcohol intake
is known to have benefits, both physiologically and
psychologically.
0044The mechanisms by which the phenolic/poly-
phenolic compounds confer benefits are via their
antioxidant activity, intracellular signal modification,
alterations in gene expression, and alterations in
microsomal detoxification enzyme activity. Other
functional modifications that occur due to pheno-
lics/polyphenolics, such as antimutagenic, anticarci-
nogenic, or antiinflammatory activity are derived
from one of these major mechanisms.
0045The contribution of red wine to health can only be
understood in the context of the whole diet. In popu-
lations that consume limited amounts of fruits and
vegetables, as in Denmark, the consumption of wine
is likely a significant contributing factor of phenolics
and other phytochemicals and therefore more likely
to provide benefits. In other populations, such as
those that consume a Mediterranean-style diet, red
wine is less likely to contribute to the overall health
and disease risk reduction due to the consumption of
olive oil, fruits, and vegetables. Recommendations to
consume red wine for its beneficial effects may be
imprudent, due to the health problems associated
with overuse. However, if a person drinks alcohol
sensibly, red wine has an advantage due to its contents
of beneficial compounds.
See also: Antioxidants: Role of Antioxidant Nutrients in
Defense Systems; Bioavailability of Nutrients; Cancer:
Epidemiology; Coronary Heart Disease: Etiology and
Risk Factor; Immunology of Food; Phenolic
Compounds; Tannins and Polyphenols
Further Reading
Auw J, Blanco V, O’Keefe S and Sims CA (1996) Effect of
processing on the phenolics and color of Cabernet
Sauvignon, Chambourcin, and Noble wines and juices.
American Journal of Enology and Viticulture 47:
279–286.
Bravo L (1998) Polyphenols: chemistry, dietary sources,
metabolism, and nutritional significance. Nutrition
Reviews 56: 317–333.
6216 WINES/Dietary Importance