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

Eur J Nutr. 2019 Dec;58(8):3069-3077. doi: 10.1007/s00394-018-1852-5. Epub 2018 Nov 2.


Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Circulating folic acid; Folic acid; Fortified foods; Mandatory fortification.

MeSH terms

  • Adolescent
  • Adult
  • Brazil
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Diet / methods*
  • Female
  • Folic Acid / blood*
  • Genetic Variation*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Vitamin B Complex / blood*
  • Young Adult


  • Vitamin B Complex
  • Folic Acid