title: The basis of differential responses to folic acid supplementation.
abstract: OBJECTIVE
  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 μmol/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.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College Hospital, London, UK.
authors.forename: Ioana
authors.initials: I
authors.lastname: Cotlarciuc
authors.forename: Toby
authors.initials: T
authors.lastname: Andrew
authors.forename: Tracy
authors.initials: T
authors.lastname: Dew
authors.forename: Gail
authors.initials: G
authors.lastname: Clement
authors.forename: Raj
authors.initials: R
authors.lastname: Gill
authors.forename: Gabriela
authors.initials: G
authors.lastname: Surdulescu
authors.forename: Roy
authors.initials: R
authors.lastname: Sherwood
authors.forename: Kourosh R
authors.initials: KR
authors.lastname: Ahmadi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D008957:Models, Genetic; D054647:Nutrigenomics; D020641:Polymorphism, Single Nucleotide; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12