Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.
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 nmol/L and decreased mean plasma homocyst(e)ine concentrations 1.2 +/- 2.4 micromol/L. There was evidence of substantial interindividual variation in the homocyst(e)ine response from -18.5 to +7.1 micromol/L, including an increase in homocyst(e)ine in 20% of subjects (mean increase 1.5 +/- 1.4 micromol/L). Basal homocyst(e)ine, age, male gender, cigarette smoking, use of multivitamins, methylene tetrahydrofolate reductase, and cystathionine beta-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.
Malinow
M R
MR
Department of Pathobiology and Immunology, Oregon Regional Primate Research Center, Beaverton 97006, USA. malinowr@ohsu.edu
Duell
P B
PB
Williams
M A
MA
Kruger
W D
WD
Evans
A A
AA
Anderson
P H
PH
Block
P C
PC
Hess
D L
DL
Upson
B M
BM
Graf
E E
EE
Irvin-Jones
A
A
Wang
L
L
D000368:Aged; D000375:Aging; D003541:Cystathionine beta-Synthase / Q000235:genetics; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011110:Polymorphism, Genetic; D012727:Sex Characteristics; D012907:Smoking; D014815:Vitamins / Q000008:administration & dosage
D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003541:Cystathionine beta-Synthase