Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine.
BACKGROUND
Folate intake increases plasma folate and reduces total homocysteine (tHcy) concentrations, which may lower coronary artery disease (CAD) and cancer risks. Folate metabolism may be altered by alcohol intake and 2 common polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, 677C-->T and 1298A-->C.


OBJECTIVE
We examined whether the associations between folate intake and plasma folate and tHcy concentrations were modified by alcohol intake or variations in the MTHFR gene.


METHODS
We conducted a cross-sectional analysis among 988 women by using multivariate linear regression models to estimate mean plasma tHcy and folate concentrations. Folate intake was the sum of food and supplemental sources.


RESULTS
We observed an inverse association between folate intake and tHcy, which was modified by alcohol intake (P for interaction = 0.04) and MTHFR677 genotype (P for interaction = 0.05) but not by MTHFR1298 genotype (P for interaction = 0.97). In the lowest quintile of folate intake, moderate drinkers (>/=15 g alcohol/d) had significantly higher tHcy concentrations (15.2 +/- 2.9 nmol/mL) than did light drinkers (11.3 +/- 0.7 nmol/mL) and nondrinkers (11.0 +/- 0.8 nmol/mL). However, the reduction in tHcy between the highest and lowest quintiles of folate intake was significantly greater in moderate drinkers (-6.6 nmol/mL) than in light drinkers (-2.3 nmol/mL) and nondrinkers (-2.1 nmol/mL). The elevated tHcy in women with low folate intake who also consumed moderate amounts of alcohol was even higher (22.4 +/- 4.8 nmol/mL) in the presence of the variant MTHFR677 allele. The positive association between folate intake and plasma folate was somewhat modified by alcohol intake (P for interaction = 0.08) but not by either MTHFR genotype.


CONCLUSIONS
Moderate alcohol intake and low MTHFR activity have adverse effects on tHcy, but those effects may be overcome by sufficient folate intake.
Department of Nutrition and the Channing Laboratory, Harvard Medical School, Boston, MA, USA. schiuve@hsph.harvard.edu
Stephanie E
SE
Chiuve
Edward L
EL
Giovannucci
Susan E
SE
Hankinson
David J
DJ
Hunter
Meir J
MJ
Stampfer
Walter C
WC
Willett
Eric B
EB
Rimm
D000328:Adult; D004032:Diet; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D006710:Homocysteine; D000431:Ethanol; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)