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Vitamins and plant ingredients

An overview of folate status in a population-based study from São Paulo, Brazil and the potential impact of 10 years of national folic acid fortification policy



Food fortification is an important strategy in public health policy for controlling micronutrient malnutrition and a major contributing factor in the eradication of micronutrients’ deficiencies. Approximately 50 countries worldwide have adopted food fortification with folic acid (FA). FA fortification of wheat and maize flours has been mandatory in Brazil since 2004. To assess the effect of 10 years of FA food fortification policy on folate status of residents of São Palo, Brazil using a population-based survey.


Data were from 750 individuals aged 12 years who participated in a cross-sectional population-based survey in São Paulo city, Brazil. Fasting blood samples were collected, and folate was assayed by affinity-high performance liquid chromatografy method with electrochemical detection. The participants provided information about food intake based on two 24 h dietary recall.


Only 1.76% of population had folate deficiency (<6.8 nmol/l). The mean folate concentration was 29.5 (95% confidence interval: 27.3–31.7) nmol/l for all sex–age groups. The mean folate intake for the population was 375.8 (s.e.m.=6.4) μg/day of dietary folate equivalents (DFEs). When comparing folate intake in DFE from food folate and FA from fortified foods, FA contributed 50% or more of the DFE in almost all sex–age groups. The major contributors of folate intake are processed foods made from wheat flour fortified with FA, especially among subjects younger than 20 years old.


The deficiency of folate is very low, and food fortification contributed to folate intake and had a notable influence on rankings of food contributors of folate.

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  1. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL . Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull 2008; 29 (2 Suppl), S101–S111.

    Article  Google Scholar 

  2. Hibbard ED, Smithells RW . Folic acid metabolism and human embryopathy. Lancet 1965; 285: 1254.

    Article  Google Scholar 

  3. CDC–Centers for Disease Control and Prevention. Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep 1992; 41: 1–7.

    Google Scholar 

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

    CAS  Article  Google Scholar 

  5. MRC Vitamin Study Research Group. Prevention of neural tube defects. Lancet 1991; 338: 131–137.

    Article  Google Scholar 

  6. WHO–World Health Organization/FAO–Food and Agricultural Organization. Guidelines on Food Fortification with Micronutrients. WHO: Geneva, Switzerland, 2006..

  7. Berry RJ, Bailey L, Mulinare J, Bower C Folic Acid Working Group. Fortification of flour with folic acid. Food Nutr Bull 2010; 31: S22–S35.

    Article  Google Scholar 

  8. FDA–Food and Drug Administration. United States Department of Health and Human Services–DHHS. Food standards: amendment of the standards of identify for enriched grain products to require addition of folic acid. Fed Regist 1996; 61: 8781–8807.

    Google Scholar 

  9. Health Canada. Regulations amending the Food and Drug Regulations (1066). Canada Gazette, Pat I. 1997, pp 3702-3705..

  10. Gobierno de Chile. Ministerio de Salud. Norma técnica para la fortificación de la harina de trigo con vitaminas y minerales, 1999..

  11. Brasil. Ministério da Saúde. Resolução no. 344, de 13 de dezembro de 2002. Aprova o regulamento técnico para a fortificação das farinhas de trigo e das farinhas de milho com ferro ácido fólico, constante no anexo desta resolução. Diário Oficial da República Federativado Brasil, 2002..

  12. Argentina. Ley no 25 630. Establécense normas para la prevención de las anemias y las malformaciones del tubo neural, 2002..

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

    CAS  Article  Google Scholar 

  14. Castillo-Lancellotti C, Tur JA, Uauy R . Impact of folic acid fortification of flour on neural tube defects: a systematic review. Public Health Nutr 2013; 16: 901–911.

    Article  Google Scholar 

  15. Pfeiffer CM, Johnson CL, Jain RB, Yetley EA, Picciano MF, Rader JI et al. Trends in blood folate and vitamin B-12 concentrations in the United States, 1988 2004. Am J Clin Nutr 2007; 86: 718–727.

    CAS  Article  Google Scholar 

  16. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL et al. Biomarkers of nutrition for development-folate review. J Nutr 2015; 145: 1636S–1680S.

    CAS  Article  Google Scholar 

  17. de Carvalho AM, César CL, Fisberg RM, Marchioni DM . Meat consumption in São Paulo-Brazil: trend in the last decade. PLoS One 2014; 9: e96667.

    Article  Google Scholar 

  18. Conway JM, Ingwersen LA, Vinyard BT, Moshfegh AJ . Effectiveness of the US Department of Agriculture 5-step multiple-pass method in assessing food intake in obese and nonobese women. Am J Clin Nutr 2003; 77: 1171–1178.

    CAS  Article  Google Scholar 

  19. Block G, Dresser CM, Hartman AM, Carroll MD . Nutrient sources in the American diet: quantitative data from the NHANES II survey.I. Vitamins and minerals. Am J Epidemiol 1985; 122: 13–26.

    CAS  Article  Google Scholar 

  20. Bagley PJ, Selhub J . Analysis of folate from distribution by affinity followed by reversed-phase chromatography with electrical detection. Clin Chem 2000; 46: 404–411.

    CAS  PubMed  Google Scholar 

  21. Haubrock J, Nöthlings U, Volatier JL, Dekkers A, Ocké M, Harttig U et al. Estimating usual food intake distributions by using the multiple source method in the EPIC-Potsdam Calibration Study. J Nutr 2011; 141: 914–920.

    CAS  Article  Google Scholar 

  22. Scorsatto M, Uehara SK, Luiz RR, de Oliveira GM, Rosa G . Fortification of flours with folic acid reduces homocysteine levels in Brazilian women. Nutr Res 2011; 31: 889–895.

    CAS  Article  Google Scholar 

  23. Britto JC, Cançado R, Guerra-Shinohara EM . Concentrations of blood folate in Brazilian studies prior to and after fortification of wheat and cornmeal (maize flour) with folic acid: a review. Rev Bras Hematol Hemoter 2014; 36: 275–286.

    Article  Google Scholar 

  24. Pfeiffer CM, Hughes JP, Lacher DA, Bailey RL, Berry RJ, Zhang M et al. Estimation of trends in serum and RBC folate in the U.S. population from pre- to postfortification using assay-adjusted data from the NHANES 1988-2010. J Nutr 2012; 142: 886–893.

    CAS  Article  Google Scholar 

  25. Shuaibi AM, House JD, Sevenhuysen GP . Folate status of young Canadian women after folic acid fortification of grain products. J Am Diet Assoc 2008; 108: 2090–2094.

    CAS  Article  Google Scholar 

  26. Ray JG, Vermeulen MJ, Langman LJ, Boss SC, Cole DE . Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification. Clin Biochem 2003; 36: 387–391.

    CAS  Article  Google Scholar 

  27. Hertrampf E, Cortés F, Erickson JD, Cayazzo M, Freire W, Bailey LB et al. Consumption of folic acid-fortified bread improves folate status in women of reproductive age in Chile. J Nutr 2003; 133: 3166–3169.

    CAS  Article  Google Scholar 

  28. Fulgoni VL 3rd, Keast DR, Bailey RL, Dwyer J . Foods, fortificants, and supplements: Where do Americans get their nutrients? J Nutr 2011; 141: 1847–1854.

    CAS  Article  Google Scholar 

  29. Marchioni DM, Verly Jr E, Steluti J, Cesar CL, Fisberg RM . Folic acid intake before and after mandatory fortification: a population-based study in São Paulo, Brazil. Cad Saude Publica 2013; 29: 2083–2092.

    Article  Google Scholar 

  30. Berner LA, Keast DR, Bailey RL, Dwyer JT . Fortified foods are major contributors to nutrient intakes in diets of US children and adolescents. J Acad Nutr Diet 2014; 114: 1009–1022.

    Article  Google Scholar 

  31. IOM - Institute of Medicine. Dietary Reference Intakes: for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline. National Academy Press: Washington, DC, USA, 1998..

  32. Dietrich M, Brown CJ, Block G . The effect of folate fortification of cereal-grain products on blood folate status, dietary folate intake, and dietary folate sources among adult non-supplement users in the United States. J Am Coll Nutr 2005; 24: 266–274.

    CAS  Article  Google Scholar 

  33. Pfeiffer CM, Rogers LM, Bailey LB, Gregory JF 3rd . Absorption of folate from fortified cereal-grain products and of supplemental folate consumed with or without food determined by using a dual-label stable-isotope protocol. Am J Clin Nutr 1997; 66: 1388–1397.

    CAS  Article  Google Scholar 

  34. Boen TR, Soeiro BT, Pereira-Filho ER, Lima-Pallone JA . Folic acid and iron evaluation in Brazilian enriched corn and wheat flours. J Braz Chem Soc 2008; 1: 53–59.

    Article  Google Scholar 

  35. Soeiro BT, Boen TR, Pereira-Filho ER, Lima-Pallone JA . Investigação da qualidade de farinhas enriquecidas utilizando Análise por Componentes Principais (PCA). Ciênc Tecnol Aliment 2010; 30: 618–624.

    Article  Google Scholar 

  36. Rock CL . Multivitamin-multimineral supplements: who uses them? Am J Clin Nutr 2007; 85: 277S–279S.

    CAS  Article  Google Scholar 

  37. Mudryj AN, de Groh M, Aukema HM, Yu N . Folate intakes from diet and supplements may place certain Canadians at risk for folic acid toxicity. Br J Nutr 2016; 116: 1236–1245.

    CAS  Article  Google Scholar 

  38. Brunacio KH, Verly-E Jr, Cesar CL, Fisberg RM, Marchioni DM . Use of dietary supplements among inhabitants of the city of São Paulo, Brazil. Cad Saude Publica 2013; 29: 1467–1472.

    Article  Google Scholar 

  39. López-Camelo JS, Castilla EE, Orioli IM INAGEMP (Instituto Nacional de Genética Médica Populacional); ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congénitas). Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries. Am J Med Genet A 2010; 152A: 2444–2458.

    Article  Google Scholar 

  40. Crider KS, Bailey LB, Berry RJ . Folic acid food fortification-its history, effect, concerns, and future directions. Nutrients 2011; 3: 370–384.

    Article  Google Scholar 

  41. Hamner HC, Mulinare J, Cogswell ME, Flores AL, Boyle CA, Prue CE et al. Predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001-2004. Am J Clin Nutr 2009; 89: 305–315.

    CAS  Article  Google Scholar 

  42. Pfeiffer CM, Caudill SP, Gunter EW, Osterloh J, Sampson EJ . Biochemical indicators of B vitamin status in the US population after folic acid fortification: results from the National Health and Nutrition Examination Survey 1999–2000. Am J Clin Nutr 2005; 82: 442–450.

    CAS  Article  Google Scholar 

  43. De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B et al. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med 2007; 357: 135–142.

    CAS  Article  Google Scholar 

  44. Quinlivan EP, Gregory JF 3rd . Effect of food fortification on folic acid intake in the United States. Am J Clin Nutr 2003; 77: 221–225.

    CAS  Article  Google Scholar 

  45. Sweeney MR, McPartlin J, Scott J . Folic acid fortification and public health: report on threshold doses above which unmetabolised folic acid appear in serum. BMC Public Health 2007; 7: 41.

    Article  Google Scholar 

  46. Kelly P, McPartlin J, Goggins M, Weir DG, Scott JM . Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 1997; 65: 1790–1795.

    CAS  Article  Google Scholar 

  47. Bailey RL, Mills JL, Yetley EA, Gahche JJ, Pfeiffer CM, Dwyer JT et al. Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged&gt; or =60 y in the United States. Am J Clin Nutr 2010; 92: 383–389.

    CAS  Article  Google Scholar 

  48. Wyckoff KF, Ganji V . Proportion of individuals with low serum vitamin B-12 concentrations without macrocytosis is higher in the post folic acid fortification period than in the pre folic acid fortification period. Am J Clin Nutr 2007; 86: 1187–1192.

    CAS  Article  Google Scholar 

  49. Mason JB . Folate consumption and cancer risk: a confirmation and some reassurance, but we're not out of the woods quite yet. Am J Clin Nutr 2011; 94: 965–966.

    CAS  Article  Google Scholar 

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We thank the individuals who participated in the study and researchers of the Dietary Assessment Group (GAC—Grupo de Pesquisa de Avaliação do Consumo Alimentar).

Author contributions

JS, RMF and DMLM designed the research and interpreted the data; JS, DMLM, JSe, LP and CR conducted the research; JS and DMLM analyzed and wrote the paper, and had primary responsibility for the final content. All authors read and approved the final manuscript.

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Correspondence to J Steluti.

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Steluti, J., Selhub, J., Paul, L. et al. An overview of folate status in a population-based study from São Paulo, Brazil and the potential impact of 10 years of national folic acid fortification policy. Eur J Clin Nutr 71, 1173–1178 (2017).

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