Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations

M. René Malinow, P. Barton Duell, Michelle A. Williams, Warren D. Kruger, Alison A. Evans, Peter H. Anderson, Peter C. Block, David L. Hess, Barbara M. Upson, Eric E. Graf, Andrea Irvin-Jones, Liqun Wang

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13 Scopus citations


Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation. The effects of folic acid supplementation (1 or 2 mg per day) for 3 wk on plasma homocyst(e)ine concentrations were assessed in 304 men and women. Overall, folic acid supplementation increased mean plasma folate 31.5 ± 98.0 μmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2 ± 2.4 μmol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from -18.5 to +7.1 μmol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5 ± 1.4 μmol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine β-synthase polymorphisms accounted for 47.6% of the interindividual variability in the change in homocyst(e)ine after folic acid supplementation, but about 50% of variability in response to folic acid was not explained by the variables we studied.

Original languageEnglish (US)
Pages (from-to)S27-S32
Issue numberSUPPL.
StatePublished - 2001

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Cell Biology


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