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Increased Red Cell Folate Concentrations in Women of Reproductive Age after Canadian Folic Acid Food Fortification

2002; Lippincott Williams & Wilkins; Volume: 13; Issue: 2 Linguagem: Inglês

10.1097/00001648-200203000-00026

1531-5487

Joel G. Ray, Marian J. Vermeulen, S. Boss, David E.C. Cole,

Pregnancy and preeclampsia studies

To the Editor: Low concentrations of folate are associated with an increased risk of neural tube defects, while preconception supplementation with folic acid attenuates that risk. 1 The government of Canada mandated that all flour and some corn and rice products be fortified with folic acid, a policy that was fully implemented by January 1998 [G. Carson, Grain Based Products, Robin Hood Multifoods, Inc., Canada, personal communication, 2001]. We studied the effect of this fortification program among women of reproductive age, age 18–42 years. Comparing data from before and after fortification, we considered all red blood cell (RBC) folate and serum vitamin B12 (Se B12) samples analyzed by MDS Laboratories (Toronto, Ontario, Canada), which provides diagnostic services to approximately one-third of community-based patients in the province of Ontario. These tests, paid for under Ontario’s publicly funded universal Ontario Health Insurance Plan, were ordered on clinical grounds, but the reasons were not available. Vitamin concentrations were determined by competitive protein binding (Bio-Rad Laboratories, Mississauga, Ontario, Canada), with a maximum reporting limit of 1,450 nmol/L for RBC folate and 1,600 pmol/L for Se B12. Identifiers were removed to protect patient confidentiality, and the Ethics Review Boards of Sunnybrook and Women’s College Health Sciences Centre and MDS Laboratories approved this study. A total of 8,408 consecutive, nonredundant samples were analyzed for the intervals of January 1, 1996 to December 31, 1997 (prefortification) and 30,061 samples for January 1, 1998 to December 31, 2000 (postfortification). The mean participant age was 31.8 years for both periods. The geometric mean RBC folate concentration rose from 527 nmol/L prefortification to 741 nmol/L after January 1, 1998 (mean difference 214 nmol/L) (Table 1 and Figure 1). The respective mean concentrations for Se B12 were 276 and 270 pmol/L (mean difference −6 pmol/L) (Table 1 and Figure 1). Similar trends were seen for the fifth-percentile concentrations of RBC folate and Se B12 (Table 1). Table 1: Red Blood Cell (RBC) -Folate and Serum Vitamin B12 (Se B12) Concentrations before and after Folic AcidFIGURE 1: Mean and 95% confidence interval concentrations of red blood cell (RBC) folate (upper curve) and serum vitamin B12 (Se B12; lower curve) after folic acid fortification (vertical line).We did not obtain information on the clinical indications for folate and cobalamin (vitamin B12) testing, which is a potential source of study bias. Furthermore, we did not account for use of folic acid supplements, which, in addition to lead-time compliance with folate fortification by the milling industry, could also explain the rise in RBC folate concentrations before January 1998. Because Se B12 levels have remained nearly constant over time, however, multivitamin supplement use could not account for more than a small portion of the rise in RBC folate. As in the U.S. general population, 2,3 Canada’s national folic acid fortification program has probably enhanced the folate status of women of reproductive age. Experimental data have demonstrated that withdrawal of dietary folic acid for as little as 12 weeks can significantly reduce RBC folate concentrations in women, 4 suggesting that an increase in RBC folate concentrations would be evident soon after the addition of folic acid to flour. We must highlight the fact that Se B12 concentrations have remained relatively constant since folic acid food fortification was introduced. Although cobalamin deficiency too has been implicated in the formation of neural tube defects, 5 its detection before and during pregnancy is a point of controversy. 6–8 Thus, with the rising popularity of ovo-lacto vegetarianism, 9 unrecognized vitamin B12 insufficiency may become an issue among women of reproductive age. 6 There is an urgent need to consider both the addition of synthetic vitamin B12 to current fortification programs 10 and the long-term health consequences of fortifying flour with folic acid but not cobalamin. 11 Joel G. Ray Marian J. Vermeulen Sheila C. Boss David E. C. Cole