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American Journal of Clinical Nutrition, Vol. 82, No. 1, 155-162, July 2005
© 2005 American Society for Clinical Nutrition


ORIGINAL RESEARCH COMMUNICATION

Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine1,2,3

Stephanie E Chiuve, Edward L Giovannucci, Susan E Hankinson, David J Hunter, Meir J Stampfer, Walter C Willett and Eric B Rimm

1 From the Departments of Nutrition (SEC, ELG, DJH, MJS, WCW, and EBR) and Epidemiology (ELG, DJH, SEH, MJS, WCW, and EBR), Harvard School of Public Health, Boston, MA, and the Division of Preventive Medicine (SEC) and the Channing Laboratory (ELG, DJH, SEH, MJS, WCW, and EBR), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA

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.

Design: 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.

Key Words: Folate intake • homocysteine • plasma folate • methylenetetrahydrofolate reductase • MTHFR • polymorphism • alcohol


Related articles in AJCN:

Alcohol, methylenetetrahydrofolate 677C->T genotype, and low folate intake: concurrent causes for hyperhomocysteinemia
Marilia Cravo
AJCN 2005 82: 3-4. [Full Text]  



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