Alcohol consumption and plasma homocysteine: What's brewing?

Angelika De Bree, Wm Monique Verschuren, Henk J. Blom and Daan Kromhout

National Institute of Public Health and Environment (RIVM) Department of Chronic Diseases Epidemiology (pb 101) PO Box 1, NL-3720 BA Bilthoven, The Netherlands. E-mail: angelika.de.bree{at}rivm.nl

Sir—We would like to complement recent publications1,2 on a potential beneficial health effect of moderate alcohol consumption on the cardiovascular system with data on the relation between alcohol consumption and the plasma total homocysteine concentration (tHcy). A high tHcy is associated with an increased risk of cardiovascular diseases, therefore, it is important to know how lifestyle factors might influence tHcy.

Observational studies indicate that alcohol consumption might be related to tHcy in a J-shaped fashion:3 alcoholics have a very high tHcy4 and moderate alcohol consumers (<=4 glasses/ day) have a lower tHcy as compared to non-drinkers.3,5 In our study population, a random sample (n = 3025) of a population-based cohort of Dutch men and women (20–65 years),6 we cross-sectionally observed a lower tHcy at higher levels of alcohol consumption (assessed with a food frequency questionnaire). This trend was statistically significant in men (P < 0.001); non-drinkers (n = 132) had a (geometric) mean tHcy of 14.2 µmol/L, compared to 13.9 µmol/L in drinkers of <=2 glasses/day (n = 838), 12.5 µmol/L in drinkers of >2 to <4 glasses/day (n = 306) and 13.1 µmol/L in drinkers of >=4 glasses/day (n = 214). An overall statistically significant inverse trend (P < 0.05) remained after correction for age, smoking, physical activity, coffee and tea consumption, dietary folate intake and vitamin B supplements use.

An intriguing question is whether the inverse relation can be ascribed to ethanol intake or that the type of alcoholic beverages consumed is important, as the recent intervention trial of Van der Gaag et al.7 suggests. They showed, in a 3-week randomized cross-over trial, that despite the equally administered amount of ethanol (4 glasses/day = 40 g/day) beer does not affect tHcy, whereas wine and spirits induce an increase. Motivated by these results7 we studied whether different types of alcoholic beverage were differently related to tHcy in males (Table 1Go) we found that higher beer consumption was inversely associated to tHcy, whereas wine (red and white) and spirits showed no relation to tHcy. Thus, like Van der Gaag et al.,7 we showed that beer drinking does not have an adverse effect on tHcy. In fact, we observed a favourable effect, which may seem inconsistent. However, as the relation between alcohol consumption and tHcy might be J-shaped3 and our study contained few heavy drinkers (16% of the male drinkers drank >4 glasses/day) we were probably measuring an effect in the descending part of the J-curve. The intervention trial provided relatively high alcohol doses7 and might have measured an effect at or beyond the nadir of the curve.


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Table 1 Meana plasma homocysteine concentration (tHcy) in male alcohol drinkers by tertiles of beer, wine and spirits
 
The beneficial effect of beer drinking on tHcy could be due to its folate, riboflavin and vitamin B6 content, all important for the enzymatic homocysteine conversion. Nevertheless, the inverse relation with beer was independent of these nutrients (Table 1Go), which might indicate a dose effect of ethanol. This is further suggested by the absence of a significant association with alcohol consumption in female drinkers, who on average drink less than men, and the fact that the amount of ethanol consumed in the third tertile (T3) of beer consumption exceeds that of T3 in the wine and spirit drinkers by far. Intervention studies with moderate amounts of ethanol (<40 g/day), or observational studies in populations where beer is not the predominant alcoholic drink, may clarify whether our result is due to residual confounding by B vitamins in beer, or show that ethanol is responsible for the beneficial effect of moderate ethanol consumption on tHcy.

Acknowledgments

This work was financially supported by a grant of the Netherlands Heart Foundation (grant no. 96.147). HJ Blom is established investigator of the Netherlands Heart Foundation (grant no. D97.021).

References

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2 Nanchahal K, Ashton WD, Wood DA. Alcohol consumption, metabolic cardiovascular risk factors and hypertension in women. Int J Epidemiol 2000;29:57–64.[Abstract/Free Full Text]

3 Vollset SE, Hygard O, Kvale G, Ueland PM, Refsum H. The Hordaland Homocysteine Study: Lifestyle and total plasma homocysteine in Western Norway. In: Graham I, Refsum H, Rosenberg IH, Ueland PM, editors. Homocysteine Metabolism: From Basic Science to Clinical Medicine. Massachusetts: Kluwer Academic Publishers, 1997, pp.177–82.

4 Cravo ML, Gloria LM, Selhub J, Nadeau MR, Camilo ME, Resende MP et al. Hyperhomocysteinemia in chronic alcoholism: Correlation with folate, vitamin B-12, and vitamin B-6 status. AJCN 1996;63: 220–24.[Abstract]

5 Ubbink JB, Fehily AM, Pickering J, Elwood PC, Vermaak WJH. Homocysteine and ischaemic heart disease in the Caerphilly cohort. Atherosclerosis 1998;140:349–56.[ISI][Medline]

6 deBree A, Verschuren WMM, Blom HJ, De Graaf-Hess A, Trijbels FJM, Kromhout D. The homocysteine distribution: (mis)judging the burden. J Clin Epidemiol 2001 (in Press).

7 Gaag MS, Ubbink JB, Sillanaukee P, Nikkari S, Hendriks H. Effects of consumption of red wine, spirits, and beer on serum homocysteine. Lancet 2000;355:1522.[ISI][Medline]