Department of Psychiatry and Psychotherapy,
1 Department of Neurology, Georg-August-University of Göttingen,
2 Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nürnberg and
3 Department of Psychiatry and Psychotherapy, Medical School of Hannover, Germany
Received 4 December 2000; in revised form 4 January 2001; accepted 4 January 2001
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ABSTRACT |
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INTRODUCTION |
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SUBJECTS AND METHODS |
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Statistical analyses were made using the MannWhitney test for independent samples or the Wilcoxon test for matched samples (Statistical Analysis Software 6.12®). The results are presented as means ± SD. P < 0.05 was considered significant.
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RESULTS |
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DISCUSSION |
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There is evidence that chronic alcoholism linked with alcohol dependency is associated with hyperhomocysteinaemia (Bleich et al., 2000a,b
; Cravo and Camilo, 2000
). The reasons for the significant correlation between blood alcohol concentration on the one hand, and plasma homocysteine on the other, regardless of whether beer, wine or spirits had been consumed (Bleich et al., 2000d
), are most likely complex ones in alcohol-dependent patients: impairment of remethylation of homocysteine is brought about on account of a dysfunction of methionine synthase (MS), due to an alcohol-induced vitamin deficiency (folic acid and vitamin B12), as well as a direct inhibition of MS due to acetaldehyde (Kenyon et al., 1998
), the product of the oxidative degradation of alcohol. In the present study, consumers of red wine and spirits had significantly lower folate levels when compared with concentrations at baseline. Taking into account that plasma homocysteine concentrations are inversely correlated with the folate status, this might be consistent with the above-mentioned observation. In addition, it has been known for many years that ethanol has an effect on folate metabolism, which could not be explained by an alcohol-induced low intake of folate (Sullivan and Herbert, 1964
). The aetiology of folate deficiency in alcoholism can be ascribed to several causes, such as low dietary intake, poor absorption, decreased hepatic uptake and retention, and increased urinary excretion of folate (Halsted and Keen, 1990
). Furthermore, beer is a rich source of folate (about 90120 µg/40g alcohol) and vitamin B6 (about 0.30.5 mg/ 40 g alcohol), whereas red wine and spirits contain negligible amounts of these vitamins, which might explain that the consumers of beer had nearly consistent serum folate levels. Additionally, abstinent individuals were shown to have significantly higher levels of folate, which might be explained by the lack of an alcohol-induced folate depletion, as described above. Even though in all subjects routine laboratory analysis (i.e. liver enzymes) and nutritional assessment revealed no abnormalities, non-drinkers may have other hitherto unevaluated lifestyle habits, which possibly predispose them to lower homocysteine values.
Mildly elevated plasma homocysteine levels have been associated with an increased risk of coronary heart disease (Nygård et al., 1997; Folsom et al., 1998
; Refsum et al., 1998
). How can we explain the French paradox considering the inconsistent notions discussed above, especially the observation that homocysteine levels were raised after 6 weeks of consumption of red wine and spirits by 19% and 17%, respectively? The latter increase in homocysteine coincides with an increase of CHD risk of ~20% (Verhoef et al., 1998
). However, some other effects of alcohol may counteract the effect of homocysteine (Paassilta et al., 1998
; Bleich et al., 2000e
) and, in addition, other known risk factors for cardiovascular diseases (i.e. hypertension) must be taken into account. Furthermore, elevated plasma homocysteine levels may increase the risk for different types of vascular diseases (i.e. cerebral microangiopathy, brain infarction, peripheral vascular disease) whereby the exact mechanisms are largely unknown (Fassbender et al., 1999
).
A careful interpretation must be made of even the best studies on French paradox from the methodological point of view: it is not advisable to limit oneself to geographical studies naively comparing very different populations and attributing the differences in morbidity solely to the consumption of alcohol. For example, when analysing the French paradox, there are quite large differences between CHD death rates given by the official statistics and the MONICA data, from a project organized by the World Health Organization. For example, the northsouth gradient in CHD mortality observed in France was found to be much more pronounced for case fatality than for incidence (Lang et al., 1999), which could be called an under-certification bias, at least in part. Thus, it is feasible that official statistics underestimate CHD death rate in France and overestimate the French paradox. Additionally, it has not yet been sufficiently investigated if the French paradox might be due to the high dietary diversity in France, a low dietary diversity shown to be associated with an increased CHD mortality, rather than to be caused by a single food or beverage (i.e. red wine) (Kant et al., 1993
; Criqui and Ringel, 1994
).
Taking into account the present observation of elevated homocysteine levels in social drinkers, we would like to shed further light on this issue. We postulate that elevated levels of homocysteine in social drinkers with regular moderate alcohol intake are at risk of developing cardiovascular diseases, which contradicts the suggested cardioprotection of alcohol according to the French paradox. Furthermore, from a medical and ethical point of view, it must be considered alongside the significant negative effects of alcohol consumption; alcohol causes numerous health problems and immoderate intake can also lead to alcoholism, a disease with negative social and physiological effects that are likely to outweigh any benefits that accompany alcohol consumption. Nevertheless, further investigations and controlled studies are needed to clarify a possible risk assessment between social drinkers' alcohol consumption, homocysteine and the French paradox.
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FOOTNOTES |
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