Bioavailability for humans of deuterium-labeled monoglutamyl and polyglutamyl folates is affected by selected foods

Dietary folate exists mainly as polyglutamyl forms that require deconjugation by Zn-dependent pteroylpolyglutamate hydrolase prior to intestinal absorption. Because deconjugation by pteroylpolyglutamate hydrolase is an essential step in the absorption of dietary polyglutamyl folates, factors influencing the deconjugation process may affect folate bioavailability. This study was conducted to evaluate in vivo the bioavailability of [H-2(4)]folic acid (d(4)-PteGlu(1)) and [H-2(2)]-pteroylhexaglutamate (d(2)-PteGlu(6)) administered in solution in water or citrate buffer or added to selected foods using a single-dose, dual-label protocol. In each of six trials, healthy men (n = 7) were given a single oral dose of d(2)-PteGlu(6) and d(4)-PteGlu(1) (677 nmol of each form) blended into orange juice, tomatoes, lime beans, 52 mmol/L citrate (pH 4.1), or water as the control. Urine was collected for 48 h and the isotopic labeling of urinary folates used as criteria of the relative bioavailability of administered PteGlu(1) and PteGlu(6). Urinary excretion of d(4)-folates and d(2)-folates derived from the respective oral doses did not differ from the control in any treatment within the statistical power of this protocol. High relative bioavailability of the polyglutamyl folate was reflected by ratios of urinary d(2)/d(4) folates of similar to 1.0 for control, tomato, lima bean and citrate buffer trials, whereas the ratio of urinary d(2)/d(4) folates when subjects consumed orange juice was similar to 33% less than the control ratio (P < 0.05). These findings suggest that the bioavailability of polyglutamyl folates in orange Juice would be partially incomplete. However, this would be compensated by the high total folate concentration of orange juice. The relation of these findings to endogenous dietary folates requires further investigation.