Absorption of Dietary and Supplemental Folate in Women with Prior Pregnancies with Neural Tube Defects and Controls

Abstract

Background: The Public Health Service of the United States recommends that all women capable of childbearing consume .4 mg (400 μg) folic acid per day to decrease the risk of having a pregnancy affected by a neural tube defect such as spina bifida or anencephaly. Three strategies are available to women to achieve this goal: use of dietary supplements; use of fortified foods; and/or increased intake of naturally occurring folate from foods. Identification of the most effective vehicle for delivery of folate to all women is critical in order to prevent these devastating congenital defects.

Objective: To investigate the difference in response to an oral load of folate both from naturally occurring food sources and synthetic supplements among women with prior pregnancies affected by neural tube defects and controls.

Methods: We compared the absorption of test doses of 400 μg pteroylglutamic acid (unconjugated or synthetic folic acid found in supplements) and 400 μg pteroylpolyglutamic acid (conjugated or food folate) in 10 women with a history of neural tube defect affected pregnancies and eight controls with normal birth outcomes. The folate test dose was given as either 32 fluid ounces of orange juice or a folic acid single supplement pill. All participants received each test dose at separate clinic visits. The response to each test dose was measured by constructing an area under the curve (AUC) from the serum folate levels at 1, 2 and 3 hours post dose and applying a t-test to compare within and between cases and controls. We also compared red cell folate, vitamin B₁₂, zinc and homocysteine between cases and controls.

Results: Within group comparisons showed that the area under the curve was significantly greater for the pteroylglutamic acid dose compared to the pteroylpolyglutamic acid dose for both cases and controls (p=0.02 and p=0.03, respectively). In a between group comparison, control women had a greater serum folate response to both forms of the vitamin compared to the case women, but the difference reached statistical significance only for the pteroylglutamic acid dose (p=0.02). Other measured nutrients differed between cases and controls, but did not reach statistical significance.

Conclusion: We conclude that for all women synthetic folic acid as supplements or fortified foods may be the best way to increase acute folate levels in the blood, and thus delivery to the developing embryo. Further, since case women had a diminished response to both forms of the vitamin, and some case women had almost no response, we speculate that women with prior affected pregnancies may need a larger dose of folate to elicit a plasma response equivalent to the general population.

• neural tube defects
• folic acid
• pregnancy
• anencephaly
• spina bifida
• vitamins

This research was supported by the University of Washington’s Royalty Research Fund Grant #608. The authors also wish to thank the General Clinical Research Center at the University of Washington Medical Center; the Clinical Nutrition Research Unit Core Laboratory (supported by NIH Grant #DK35816); the University of Washington Department of Hematology; David B. Shurtleff, MD, William Graf, MD, David Luthy, MD, Edith Cheng, MD, Bob Resta; the Spina Bifida Association of Puget Sound, Bill O’Brien and Don Martin.

Notes

M.L. Neuhouser, PhD, RD is currently a Post Doctoral Fellow at Fred Hutchinson Cancer Research Center.