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Risk factors for cardiovascular disease include a high body mass
index (BMI; being overweight or obese), a poor diet (including
an excessive dietary intake of animal fats and salt) and lack
of exercise, cigarette smoking, excessive alcohol consumption,
a high and unbalanced blood cholesterol concentration and a high
blood pressure, as well as genetic predisposition and certain
diseases and disorders, such as diabetes mellitus (Hunter et al.
1995, Norrish et al. 1995, Wieslisbach et al. 1997). Another recently recognized risk factor is a high concentration
of the amino acid, homocysteine, in plasma (Welsh et al. 1998).
A high level of risk factors for cardiovascular disease can mitigate
any cardioprotective effects of moderate alcohol and wine consumption.
In addition, above moderate consumption, the effects of the excessive
consumption of alcohol are additive to any other risk factors
for cardiovascular disease, increasing the risk by two to three-times
(Beilin and Puddey 1996, Puddey et al. 1998, Yusuf et al. 1998). Therefore, there are some moderate consumers of wine,
such as diabetics, whose risk of cardiovascular disease may be
increased rather than decreased.
In Australia, over 50% of men and women are overweight and 20%
are actually obese, having a BMI greater than 30 kg/m2. Blood
fat disturbance in combination with high blood pressure and type
2 diabetes often occur together in susceptible individuals, and
is referred to as the ‘metabolic syndrome’ (Reaven 1993). The
blood fat disturbance relates to being overweight or obese, especially
in individuals who store their fat in the abdominal area. An excess
of toxic free fatty acids in the blood stream may cause or contribute
to the insulin sensitivity and impaired insulin function observed
with this syndrome, which generally eventually develops into type
2 diabetes. Another potential beneficial health effect of alcohol
is the improvement of insulin sensitivity, possibly by reducing
the concentration of free fatty acids in blood (Avogaro et al.
2002). In turn, the improved insulin sensitivity lowers the concentration
of insulin, glucose and triglycerides in the blood, and increases
that of HDL. Additionally, LDL particles become less dense, less
adherent and less easily oxidized. Altogether, this reduces the
risk of developing type 2 diabetes, as well as improving control
of blood glucose and reducing the risk of cardiovascular disease
in type 2 diabetics, who have a greater risk of cardiovascular
disease compared with healthy individuals (Ajani et al. 2000a,
Solomon et al. 2000). Indeed, epidemiological studies suggest
that regular and moderate alcohol consumption significantly reduces
the risk of developing type 2 diabetes (Ajani et al. 2000b, Hu
et al. 2001). The American Diabetes Association now advises that
moderate alcohol consumption by type 2 diabetics should not be
routinely discouraged (Solomon et al. 2000).
The American Heart Association recommends that the concentration
of homocysteine in plasma should be maintained below 10 mmol/L.
Homocysteine is closely linked to the metabolism of the essential
amino acid, methionine. It has a direct toxic effect on the lining
of blood vessels that alters their function (Bellamy et al. 1998)
and leads to key early steps in the atherogenic process. Three
micronutrients are important cofactors in homocysteine metabolism.
Folate and vitamin B12 are cofactors for the methylation of homocysteine
to methionine, and vitamin B6 is involved in its breakdown. Deficiency
of any of these micronutrients leads to a higher concentration
of homocysteine and increased risk. It has recently been proposed
that the presence of folate and vitamin B6 in beer may lead to
a beverage-specific advantage through lowering of homocysteine
concentration (van der Gaag et al. 2000). While high or abusive
alcohol consumption is associated with an increased plasma concentration
of homocysteine (Cravo et al. 1996, Bleich et al. 2001), but the
effect of low to moderate consumption on the concentration of
homocysteine has been inconsistent (Ayaori et al. 2000, Cuevas
et al. 2000).
The severely obese (BMI >35 kg/m2) are at increased risk of type
2 diabetes, cardiovascular morbidity and mortality. In a study
of 486 severely obese subjects, their pattern of alcohol consumption
was monitored and their risk of cardiovascular disease determined.
Alcohol consumers showed a marked reduction in the prevalence
of type 2 diabetes compared with non-consumers. A U-shaped relationship
was observed between both the amount and frequency of alcohol
consumption and the plasma concentration of fasting triglyceride,
fasting glucose, glycosylated haemoglobin A1c and insulin measurements.
In this group, comprising predominantly women consumers of less
than 100 g/week had more favorable insulin measures, with insulin
sensitivity best in those consuming 20 to 100 g of alcohol/week,
that is, 2 to 10 standard drinks/week, which is considered to
be light alcohol consumption. Of the alcohol consumers, 165 nominated
wine and 111 spirits or beer as the alcoholic beverage most frequently
drunk. Wine consumers had a significantly lower fasting insulin
level and improved insulin sensitivity.
These patients went on to have a laparoscopic adjustable gastric
band placed to help them lose weight. Those patients consuming
more than 100 g/week of alcohol, especially wine, had significantly
better weight loss than those with nil or negligible consumption.
Those consuming 20 to 100 g/week had an intermediate outcome.
These results demonstrate that light to moderate alcohol consumption,
especially wine consumption, is associated with a lower prevalence
of type 2 diabetes, improved insulin sensitivity and more favorable
cardiovascular risk profile in the severely obese (Dixon et al.
2002).
The same 416 severely obese patients were also studied for any
relationship between both the amount and type of alcohol consumption
and concentration of fasting plasma homocysteine. A U-shaped relationship
was observed whereby light to moderate alcohol consumption was
associated with a lower and more favorable plasma concentration
of homocysteine. Those patients consuming up to 100 g/week of
alcohol had a significantly lower homocysteine concentration compared
with non-consumers. The lower concentration of homocysteine in
regular alcohol consumers was associated with a higher concentration
of folate. Red wine consumers had a significantly lower mean fasting
concentration of homocysteine compared with non-consumers, beer
and spirit consumers and white wine consumers. Red wine consumption
was an independent predictor for a lower plasma concentration
of homocysteine after controlling for sex, age, and weight, and
plasma concentration of folate and vitamin B12.
The mechanisms for the beneficial effect of red wine are unclear.
The concentration of micronutrients are unlikely to provide the
answer as it has been observed that the effect of red wine is
independent of the plasma concentration of folate and vitamin
B12, and red wine contains negligible quantities of vitamin B6
(van der Gaag et al 2000). An alteration in the relationship between
the concentration of homocysteine concentration, and that of folate
and vitamin B12 has been observed as people lose weight (Dixon
et al. 2001). A higher plasma concentration of folate and vitamin
B12 is needed to maintain the concentration of homocysteine as
weight is lost. It may be postulated that the phenolic compounds
alter the dose-response curve in the other direction with a lower
plasma concentration of homocysteine achieved with an equivalent
micronutrient concentration.
In conclusion, these studies of obese patients show that those
consuming wine regularly are far less likely to be diabetic, have
significantly better insulin sensitivity and a healthier blood
lipid profile, with a lower plasma concentration of triglyceride
and a higher plasma concentration of HDL. In addition, red wine
consumers have a significantly lower plasma concentration of homocysteine.
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