European Journal of Nutrition

, Volume 58, Issue 8, pp 3069–3077 | Cite as

Presence of circulating folic acid in plasma and its relation with dietary intake, vitamin B complex concentrations and genetic variants

  • Josiane StelutiEmail author
  • Christina Reginaldo
  • Jacob Selhub
  • Ligi Paul
  • Regina Mara Fisberg
  • Dirce Maria Marchioni
Original Contribution



The aim of this study was to investigate circulating folic acid (FA) and predict circulating FA concentrations in the population related to dietary intake, vitamin concentrations, and interaction with the genetic variants involved in folate metabolism.


Data were from the ‘Health Survey of São Paulo’ a cross-sectional population-based survey, conducted in São Paulo City, Brazil. The participants (n = 750) provided fasting blood samples and food intake data. Folate, homocysteine, and B6 and B12 vitamins were assayed. DNA was isolated, and the genotypes for polymorphisms involved in folate metabolism were determined. A generalized linear model was performed to predict circulating FA concentration.


The circulating FA was detected in 80.0% of the population, with a median concentration of 1.6 nmol/L (IQR 0.5–2.9). The increase of circulating FA concentrations was directly associated with total folate concentration (β coeff. 1.03; 95% CI 1.02–1.04), age (β coeff. 1.01; 95% CI 1.01–1.02), current smoker (β coeff. 1.51; 95% CI 1.16–1.97), self-reported skin color (β coeff. 1.83; 95% CI 1.51–2.20), as well as interaction between folate concentration and 19-bp deletion polymorphism in DHFR (β coeff. 1.02; 95% CI 1.01–1.03), and inversely associated with vitamin B6 (β coeff. 0.99; 95% CI 0.98–0.99).


In the current study, the presence of detectable circulating folic acid is high, and its concentration is elevated compared with other populations. Age, smoking, lower concentration of vitamin B6 and genetic variant are associated with increased levels of circulating FA. Further researches are needed to acknowledge and guarantee the safety of exposure to folic acid, especially in countries which have mandatory fortification.


Folic acid Circulating folic acid Mandatory fortification Fortified foods 



We thank the participants of the study and researchers of the GEIAS (“Grupo de Estudos Epidemiológicos e Inovação em Alimentação e Saúde”) and GAC (“Grupo de Pesquisa de Avaliação do ConsumoAlimentar”) and the members (staff, technicians, students and scientists) of the Vitamin Metabolism Laboratory in the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University for helping during the biochemical analysis.


Financial Support from Municipal Health Secretariat of São Paulo; National Counsel of Technological-CNPq; and Scientific Development and São Paulo Research Foundation—FAPESP (Grant numbers: #2010/19899-5, #2011/19788-1, #2012/05505-0 and #2015/12196-2).

Compliance with ethical standards

Conflict of interest

J. Steluti, J. Selhub, L. Paul, C. Reginaldo, R. M. Fisberg, D. M. Marchioni have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Nutrition, School of Public HealthUniversity of São PauloSão PauloBrazil
  2. 2.Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts UniversityBostonUSA

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