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Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women

Abstract

Objective: Our aim was to determine if a once-a-week folic acid supplement increases women's red blood cell folate to concentrations (>905 nmol/l) that are associated with a low risk of bearing a child with a neural tube defect.

Design: Randomized control trial.

Setting: General community.

Subjects: In total, 114 nonpregnant women (18–40 y) volunteers, with red blood cell folate concentrations between 295 and 905 nmol/l at screening.

Interventions: Women were randomized to receive a once-a-week 2800 μg folic acid supplement, a daily 400 μg folic acid supplement or a daily placebo for 12 weeks.

Results: The mean (95% CI) red blood cell folate concentrations increased during the 12-week intervention from 608 (553–668) to 900 (828–978) in the weekly folic acid group (P<0.05) and from 615 (560–677) to 1053 (957–1158) nmol/l in the daily group (P<0.05) during the trial. At week 12, 49% of women ingesting the weekly folic acid supplement had red blood cell folate concentrations greater than 905 nmol/l compared to 74% of women ingesting the daily supplement.

Conclusions: A once-a-week 2800 μg folic acid supplement can increase women's red blood cell folate to concentrations associated with a reduced risk of bearing a child with a neural tube defect, but is less effective than a 400 μg daily supplement. Use of a weekly folic acid supplement over at least 12 weeks before conception by women of child-bearing age may prevent neural tube defects.

Funding: The Otago Medical Research Foundation (Laurenson Award). Healtheries (New Zealand) provided the supplements.

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References

  • Adank C, Green TJ, Skeaff CM & Briars B (2003): Weekly high dose folic acid supplementation is effective in lowering serum homocysteine concentration in women. Ann. Nutr. Metab. 47, 55–59.

    Article  CAS  Google Scholar 

  • Anonymous (1996): Food standard: amendment of the standards of identity for enriched grain products to require addition of folic acid. US Department of Health and Human Services, Food and Drug Administration. Fed. Regist. 61, 8781–8809.

    Google Scholar 

  • Anonymous (1999): Knowledge and use of folic acid by women of childbearing age—United States, 1995 and 1998. MMWR—Morbid. Mortal. Weekly Report 48, 325–327.

    Google Scholar 

  • Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, Hong SX & Correa A (1999): Prevention of neural-tube defects with folic acid in China. China–US Collaborative Project for Neural Tube Defect Prevention. N. Engl. J. Med. 341, 1485–1490.

    Article  CAS  Google Scholar 

  • Choumenkovitch SF, Selhub J, Wilson PW, Rader JI, Rosenberg IH & Jacques PF (2002): Folic acid intake from fortification in United States exceeds predictions. J. Nutr. 132, 2792–2798.

    Article  CAS  Google Scholar 

  • Cornel MC, Erickson JD & van der Veen WJ (1997): Comparison of national policies on periconceptional use of folic acid to prevent spina bifida and anencephaly (SBA). Teratology 55, 134–137.

    Article  CAS  Google Scholar 

  • Czeizel AE & Dudas I (1992): Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N. Engl. J. Med. 327, 1832–1835.

    Article  CAS  Google Scholar 

  • Daly LE, Kirke PN, Molloy A, Weir DG & Scott JM (1995): Folate levels and neural tube defects. Implications for preventions. JAMA 274, 1698–1702.

    Article  CAS  Google Scholar 

  • Daly S, Mills JL, Molloy AM, Conley M, Lee YJ, Kirke PN, Weir DG & Scott JM (1997): Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 350, 1666–1669.

    Article  CAS  Google Scholar 

  • Food and Nutrition Board (1998): Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, pantothenic acid, Biotin, and Choline. pp 273–283 Washington: Institute of Medicine.

  • Forrest JD (1994): Epidemiology of unintended pregnancy and contraceptive use. Am. J. Obstet. Gynecol. 170, 1485–1489.

    CAS  PubMed  Google Scholar 

  • Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD & Wong LY (2001): Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 285, 2981–2986.

    Article  CAS  Google Scholar 

  • Mills JL (2000): Fortification of foods with folic acid—how much is enough? N. Engl. J. Med. 342, 1442–1445.

    Article  CAS  Google Scholar 

  • MRC Vitamin Study Research Group (1991): Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 338, 131–137.

    Article  Google Scholar 

  • O'Broin S & Kelleher B (1992): Microbiological assay on microtitre plates of folate in serum and red cells. J. Clin. Pathol. 45, 344–347.

    Article  CAS  Google Scholar 

  • Ray JG, Meier C, Vermeulen MJ, Boss S, Wyatt PR & Cole DE (2002): Association of neural tube defects and folic acid food fortification in Canada. Lancet 360, 2047–2048.

    Article  Google Scholar 

  • Schader I & Corwin P (1999): How many pregnant women in Christchurch are using folic acid supplements in early pregnancy? N. Z. Med. J. 112, 463–465.

    CAS  PubMed  Google Scholar 

  • Schorah CJ, Devitt H, Lucock M & Dowell AC (1998): The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study. Eur. J. Clin. Nutr. 52, 407–411.

    Article  CAS  Google Scholar 

  • Skeaff M & Mann J (1998): Should folate be added to flour to prevent neural tube defects? N. Z. Med. J. 111, 417–418.

    CAS  PubMed  Google Scholar 

  • Smith C (2001): Dietary Supplement Use in the 1997. Otago: New Zealand National Nutrition Survey.

    Google Scholar 

  • Smithells RW, Nevin NC, Seller MJ, Sheppard S, Harris R, Read AP, Fielding DW, Walker S, Schorah CJ & Wild J (1983): Further experience of vitamin supplementation for prevention of neural tube defect recurrences. Lancet 1, 1027–1031.

    Article  CAS  Google Scholar 

  • Wright JD, Bialostosky K, Gunter EW, Carroll MD, Najjar MF, Bowman BA & Johnson CL (1988): Blood folate and vitamin B12: United States, 1988–94. National Centre for Health Statistics. Vital Health Stat. 11, 243.

    Google Scholar 

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Acknowledgements

We thank Sean O'Broin for advice on the microbiological assay; Margaret Waldron for blood collection; Steven Tzisavari, Ashley Duncan and Christian Thoma for their support with the laboratory analysis; Joanne Mackenzie for statistical advice.

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Guarantor: CM Skeaff.

Contributors: CMS and TG had the original idea and obtained funds for the project. All authors were responsible for planning the study. BN and CA recruited subjects and were responsible for sample collection and laboratory analysis. All authors contributed to statistical analysis and writing of the report.

Corresponding author

Correspondence to C M Skeaff.

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Norsworthy, B., Skeaff, C., Adank, C. et al. Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women. Eur J Clin Nutr 58, 548–554 (2004). https://doi.org/10.1038/sj.ejcn.1601843

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