Folate absorption in women with a history of neural tube defect-affected pregnancy

Background: The risk of neural tube defects (NTDs) is significantly reduced by supplemental folic acid. NTD risk may be associated with impaired absor ption of polyglutamyl folate, the primary form of naturally occurring food folate, and of folic acid in supplements or fortified food. Stable-isotope methods provide the specificity needed to test this hypothesis. Objective: We determined whether women who had an NTD-affected pregnancy ha d a reduced ability compared with control women to absorb polyglutamyl fola te relative to Folic acid. Design: Healthy, nonpregnant women with a history of an NTD-affected pregna ncy (cases, n = 11) and control women (n = 11)were administered an oral dos e containing a mixture of [H-2]pteroylpentaglutamate ([H-2(2)]PteGlu(5); 23 3 nmol) and [C-13]pteroylmonoglutamate ([C-13(5)]PteGlu(1): 567 nmol) after a 30-d saturation protocol (2 mg unlabeled folic acid/d). Relative extents of absorption were evaluated by urinary excretion of H-2(2)-and C-13(5)-la beled folates 48 h postdose. Results: During the first 24 h postdose, cases excreted less ((x) over bar +/- SD) [H-2(2)]PteGlu(5) (21 +/- 12% compared with 37 +/- 19%; P = 0.01) a nd [C-13(5)]PteGlu(1) (17 +/- 8% compared with 31 +/- 14%; P = 0.007) than did controls. No significant differences between cases and controls were de tected in the percentage of [H-2(2)]PteGlu(5) or [C-13(5)]PteGlu(1) excrete d during the second 24 h postdose or when the data were averaged over 48 h. However, excretion of the [H-2(2)]folates tended to be lower in cases than in controls over the 48-h period (33 +/- 13% compared with 45 +/- 26%; P = 0.21). A similar trend (P = 0.29) for lower excretion of [C-13(5)]folates in cases was also observed(31 +/- 16% compared with 39 +/- 17%). The ratio of urinary [H-2(2)]folates to [C-13(5)]folates did not differ significantly between cases and controls. Conclusion: These data suggest the need for a larger-scale study using stab le-isotope methods to further investigate this hypothesis.