The results of the present study revealed a J-shape association between ethanol consumption and homocysteine levels, of a large, random and population representative sample, free of cardiovascular disease. The lowest values of homocysteine were observed in daily ethanol intake of less than 12 gr, both in men and women and remained significant after adjustment for several potential confounders.
Our results are in line with that of some other studies. For example, De Bree et al.  observed lower homocysteine concentrations at higher levels of ethanol consumption, with non drinkers having a (geometric) mean homocysteine of 14.2 μmol/L, compared to 13.9 μmol/L in drinkers of ≤ 20 gr ethanol/ day, 12.5 μmol/L in drinkers of between 20 and 40 gr/day and 13.1 μmol/L in drinkers of ≥ 40 gr / day. In our study, the lowest homocysteine concentrations were observed with ethanol intakes <12 gr /day. This difference between our and the previous study may attribute to the type of alcoholic beverage consumed, since in the study of Bree et al. beer was the main alcoholic drink, while in our study it was wine. In another study the most positive association of ethanol (from beer consumption) on homocysteine levels was observed at ethanol intakes 4 to 14 gr/d . Another study in severely obese patients revealed a U-shaped association between homocysteine concentrations and the amount of ethanol consumption . In particular, the most beneficial effect was observed with consumption of < 100 gr ethanol/ week and especially in red wine consumers, compared to subjects who consumed white wine, beer or spirits. However, the lower homocysteine concentrations in those consuming less than 100 gr ethanol/ week were not significant after controlling for serum folate concentration. Finally a study in elderly subjects also found a J-shape relation, with nondrinkers and subjects consuming ≥ 60 drinks/ month, showing higher homocysteine concentrations, compared to those consuming ≤ 60 drinks/ month . However, the interpretation of the results from the previous study is difficult because the total amount of ethanol ingested was not calculated.
On the contrary, there are several studies that have shown a linear relationship between ethanol intake and homocysteine levels. For example, Folsom et al.  in a study of middle-aged men and women showed a positive association of ethanol on homocysteine. However, he studied very low intakes of ethanol, ranging from 27 to 47 gr/ week, and this may be the reason why a J -shaped association was not observed. According to our findings, a significant positive association was observed at much higher intakes (i.e. 84–168 gr/week). Another study in young women (aged 15–44)  showed that those consuming >7 drinks/ week were 90% more likely to have elevated homocysteine levels (> 10 μmol/l), compared to those who did not consume ethanol. In the same study, subjects consuming 1–7 drinks/week had the same homocysteine levels with those that didn't consume, supporting, partially, two relations between ethanol intake and homocysteine. However, the association between ethanol and homocysteine levels failed to achieve statistical significance. Finally, homocysteine was positively associated with ethanol intake in the Framingham Offspring cohort  at daily intakes of more than 15 g. In this study liquor and red wine consumption was significantly and positively associated with homocysteine. This association was not observed with beer and white wine consumption.
Our data were analyzed according to total ethanol intake and did not distinguish between different types of ethanol. Rimm et al. reviewed the literature with respect to beverage-specific effects on coronary heart disease and could not find any systematic effects. On the contrary, they showed that the U-shaped relation between ethanol intake and cardiovascular disease mortality persisted in populations with very different drinking patterns. Although there have been many publications on this topic since the aforementioned review, no systematic pattern or results have emerged until now. Perhaps most notably in this respect are the findings which suggest similar protective effects of ethanol not only in Bavaria (Germany) and the Czech Republic, where beer is mainly consumed, but also in Mediterranean countries, where wine is the most popular alcoholic beverage . Additionally, Greece is a Mediterranean country, where wine is the most commonly used alcoholic beverage. According to our findings as well as the recent results from the EPIC-Greece study  72% of women's total ethanol intake comes from wine, 26% from beer and 12% from spirits. For men wine contributes to 56% of total ethanol intake, beer 15% and aniseed drinks 20%. Therefore our data do not support the assumption of Mennen et al.  who suggested that the inverse association between ethanol and homocysteine is seen in populations which consume predominantly beer.
Chronic alcoholism has been found to be associated with hyper-homocysteinaemia, which could attribute to disturbed folate metabolism and to changes in circulating concentrations of vitamin B12 and pyridoxal phosphate, as well as to ethanol intake per se . Finally, the dual effect of ethanol consumption on homocysteine has also been confirmed from data of animal studies, which clearly show effects of excessive ethanol intake on the methionine cycle . Nevertheless, the finding that subjects who do not consume ethanol have higher homocysteine levels than light to moderate drinkers needs further investigation. Whether this fact can be attributed to ethanol per se or to other substances of alcoholic beverages (e.g. folate, B12, B6, betaine) remains unclear and more intervention and experimental studies are necessary.