Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults.

Background: The bioavailability of dietary folate has been estimated to be approximately 50% of that of synthetic folic acid. Folate in the diet is linked to a polyglutamate chain that may restrict folate absorption.
Objective: Our goal was to quantify the bioavailability and bioefficacy of low doses of polyglutamyl folic acid relative to that of monoglutamyl folic acid.
Design: In total, 180 men and women aged 50-75 y ingested capsules containing 323 nmol heptaglutamyl folic acid/d or 262 nmol monoglutamyl folic acid/d or placebo in a randomized parallel trial. Serum and erythrocyte folate and plasma homocysteine concentrations were measured after an overnight fast at baseline and after 12 wk of intervention.
Results: Mean serum and erythrocyte folate concentrations increased less in the polyglutamyl folic acid group [6.1 (95% CI: 5.3, 7.0) and 155 (122, 188) nmol/L, respectively] than in the monoglutamyl folic acid group [11.8 (10.3, 13.3) and 282 (246, 318) nmol/L, respectively]. Differences remained statistically significant (P < 0.05) after correction for the difference in the amount of folic acid administered. The decrease in plasma homocysteine concentrations did not differ significantly between treatment groups [polyglutamyl: -12.1% (-14.8%, -9.3%); monoglutamyl: -14.1% (-16.3%, -11.9%)]. The relative bioavailability of polyglutamyl folic acid was 64% (52%, 75%) on the basis of serum folate and was 68% (51%, 84%) on the basis of erythrocyte folate concentrations. Bioefficacy, determined by changes in plasma homocysteine concentrations, was 106% (77%, 134%).
Conclusion: The polyglutamate chain of folates in the diet reduces their bioavailability.