Bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid in subjects with different genotypes of the glutamate carboxypeptidase II gene.
BACKGROUND
Before dietary folate is absorbed, polyglutamate folates are deconjugated to monoglutamates by folylpoly-gamma-glutamyl carboxypeptidase in the small intestine. The 1561T allele of the glutamate carboxypeptidase II gene (GCPII), which codes for folylpoly-gamma-glutamyl carboxypeptidase, may impair intestinal absorption of dietary folates.


OBJECTIVE
Our aim was to study the bioavailability of polyglutamyl folic acid relative to that of monoglutamyl folic acid across GCPII 1561 genotypes.


METHODS
In a randomized study, 180 healthy adults aged 50-75 y received 323 nmol monoglutamyl folic acid/d (n = 59), 262 nmol heptaglutamyl folic acid/d (n = 61), or placebo (n = 60) for 12 wk. Genotypes were assessed after the intervention. The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was calculated by using the changes in serum folate concentration in the treatment groups, after correction for changes in the placebo group and for the administered dose.


RESULTS
No subjects with the TT genotype were encountered. At baseline, serum and erythrocyte folate concentrations were higher (P < 0.05) in subjects with the CT genotype [16.3 nmol/L (geometric x; 95% CI: 13.7, 19.3 nmol/L) and 863 nmol/L (735, 1012 nmol/L), respectively; n = 19] than in subjects with the CC genotype [13.7 (13.1, 14.3) and 685 (652, 721) nmol/L, respectively; n = 161]. Baseline homocysteine concentrations were not significantly different between genotypes. The bioavailability of heptaglutamyl folic acid relative to that of monoglutamyl folic acid was not significantly different between subjects with the CC (64%; 52%, 76%) and CT genotypes (70%; 49%, 91%).


CONCLUSIONS
The 1561T allele of the GCPII gene does not impair the bioavailability of polyglutamyl folic acid. However, the allele is associated with higher folate status. This association may be explained by yet unidentified factors controlling the expression of the GCPII gene.
Melse-Boonstra
Alida
A
Wageningen Centre for Food Sciences and the Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands.
Lievers
Karin J A
KJ
Blom
Henk J
HJ
Verhoef
Petra
P
D000284:Administration, Oral; D000368:Aged; D000954:Antigens, Surface / Q000235:genetics*; D001682:Biological Availability; D019587:Dietary Supplements; D004311:Double-Blind Method; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005786:Gene Expression Regulation; D005838:Genotype; D043425:Glutamate Carboxypeptidase II / Q000235:genetics*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011624:Pteroylpolyglutamic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000954:Antigens, Surface; D011624:Pteroylpolyglutamic Acids; D006710:Homocysteine; D005492:Folic Acid; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II