The Basis of Differential Responses to Folic Acid Supplementation

TY - JOUR

T1 - The Basis of Differential Responses to Folic Acid Supplementation

AU - Cotlarciuc, Ioana

AU - Andrew, Toby

AU - Dew, Tracy

AU - Clement, Gail

AU - Gill, Raj

AU - Surdulescu, Gabriela

AU - Sherwood, Roy

AU - Ahmadi, Kourosh R.

PY - 2011

Y1 - 2011

N2 - Background/Aims: Elevated levels of total homocysteine (tHcy) are associated with an increased risk of many common diseases. Supplementation with folic acid has been shown to significantly reduce tHcy levels. We used the classical twin model to partition the variability in changes in plasma tHcy levels through folic acid supplementation into genetic, environmental, and confounding epidemiological factors. Methods: We carried out an intervention study of folic acid using 101 healthy, female, identical and non-identical twins aged 50-80 years. Each twin was administered folic acid (0.8 mg/day) for 6 weeks. Total plasma folate, cobalamin and tHcy were measured at both baseline and after dosing. We calculated the heritability and tested for associations between the MTHFR C677T functional variant and response to folic acid supplementation. Results: Supplementation with folic acid led to a significant reduction in tHcy levels. The mean tHcy changed from 12.14 to 10.42 mu mol/l after supplementation (p <10(-5)). Moreover, the change in tHcy levels was highly heritable (64%), not associated with the C677T functional variant at MTHFR and not confounded by age, BMI or diet. Conclusions: Our results highlight the need to identify genetic factors associated with biomarkers of response to folate supplementation. Copyright (C) 2011 S. Karger AG, Basel

AB - Background/Aims: Elevated levels of total homocysteine (tHcy) are associated with an increased risk of many common diseases. Supplementation with folic acid has been shown to significantly reduce tHcy levels. We used the classical twin model to partition the variability in changes in plasma tHcy levels through folic acid supplementation into genetic, environmental, and confounding epidemiological factors. Methods: We carried out an intervention study of folic acid using 101 healthy, female, identical and non-identical twins aged 50-80 years. Each twin was administered folic acid (0.8 mg/day) for 6 weeks. Total plasma folate, cobalamin and tHcy were measured at both baseline and after dosing. We calculated the heritability and tested for associations between the MTHFR C677T functional variant and response to folic acid supplementation. Results: Supplementation with folic acid led to a significant reduction in tHcy levels. The mean tHcy changed from 12.14 to 10.42 mu mol/l after supplementation (p <10(-5)). Moreover, the change in tHcy levels was highly heritable (64%), not associated with the C677T functional variant at MTHFR and not confounded by age, BMI or diet. Conclusions: Our results highlight the need to identify genetic factors associated with biomarkers of response to folate supplementation. Copyright (C) 2011 S. Karger AG, Basel

KW - Folate

KW - Homocysteine

KW - Stroke

KW - Twin studies

KW - FOLATE STATUS RESPONSE

KW - PLASMA HOMOCYSTEINE

KW - METHYLENETETRAHYDROFOLATE REDUCTASE

KW - CARDIOVASCULAR-DISEASE

KW - SERUM HOMOCYSTEINE

KW - VASCULAR-DISEASE

KW - CONTROLLED-TRIAL

KW - YOUNG-WOMEN

KW - RISK

KW - STROKE

U2 - 10.1159/000327768

DO - 10.1159/000327768

M3 - Article

SN - 1661-6499

VL - 4

SP - 99

EP - 109

JO - Journal Of Nutrigenetics And Nutrigenomics

JF - Journal Of Nutrigenetics And Nutrigenomics

IS - 2

ER -