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Wine consumers may have a reduced cardiovascular risk through improved insulin sensitivity and a reduced plasma concentration of homocysteine
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.

References

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Avogaro, A., Watanabe, R.M., Gottardo, L., de Kreutzenberg, S., Tiengo, A., Pacini, G. Glucose tolerance during moderate alcohol intake: insights on insulin action from glucose/lactate dynamics. J Clin Endocrinol Metab, 87:1233-8; 2002.

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