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Unmetabolized folic acid is associated with TNF-α, IL-1β and IL-12 concentrations in a population exposed to mandatory food fortification with folic acid: a cross-sectional population-based study in Sao Paulo, Brazil

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Abstract

Purpose

The study assessed associations between inflammatory markers, as cytokines, adhesion molecules and unmetabolized folic acid (UMFA) among a population exposed to mandatory fortification.

Methods

Data were collected from a cross-sectional population-based survey (n = 302) conducted in São Paulo City, Brazil. UMFA was assayed by a modified affinity-HPLC method with electrochemical detection to measure the different forms of the folate in plasma. We used a commercial test kit to analyze cytokines and adhesion molecules. Multiple logistic regressions were applied to investigate the association between inflammatory markers and UMFA. Multiple models were adjusted for sex, age, self-reported skin color, BMI and smoking status.

Results

The prevalence of detectable UMFA in this population was high (81.2%), with median concentration of 1.67 nmol/L. The odds ratios (95% CIs) for having higher immunological markers levels among individuals in the highest tertile of UMFA were 0.44 (0.24; 0.81) for TNF-α, 0.92 (0.49; 1.75) for CRP, 1.32 (0.70; 2.48) for ICAM, 0.99 (0.54; 1.81) for VCAM, 0.45 (0.25; 0.83) for IL-1β, 0.74 (0.40; 1.38) for IL-6, 1.34 (0.73; 2.44) for IL-8, 0.65 (0.36; 1.18) for IL-10 and 0.49 (0.27; 0.89) for IL-12.

Conclusion

UMFA concentrations were inversely associated with elevated proinflammatory markers (TNF-α, IL-1β and IL-12). These results signalize a link between folate metabolism and the inflammatory status of adults in an apparently folate-replete population.

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Acknowledgements

This work was supported by Municipal Health Secretariat of São Paulo; National Counsel of Technological-CNPq; and Scientific Development and São Paulo Research Foundation–FAPESP [Grant Number: #2010/19899–5, #2011/19788–1, #2012/05505–0 and #2015/12196–2].

We thank the participants of the study and researchers of the GEIAS (“Grupo de Estudos Epidemiológicos e Inovação em Alimentação e Saúde”), GAC (“Grupo de Pesquisa de Avaliação do Consumo Alimentar”) 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 of unmetabolized folic acid. We also thank Prof. Marcelo M. Rogero for analyzing the inflammatory markers.

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Authors and Affiliations

  1. Department of Nutrition, School of Public Health, University of Sao Paulo, São Paulo, 01246-904, Brazil

    Josiane Steluti, Andreia Machado Miranda, Eduardo De Carli, Cecília Zanin Palchetti, Regina Mara Fisberg & Dirce Maria Lobo Marchioni

  2. Public Policies and Collective Health Department, Health and Society Institute, Federal University of Sao Paulo, Santos, 11015-020, Brazil

    Josiane Steluti

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  1. Josiane Steluti
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Contributions

JS, RMF and DMLM conceived and designed the work. JS, AMM, EC, CZP were responsible for drafting the article and revising it critically for important intellectual content. All authors read and approved the final version of the manuscript.

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Correspondence to Josiane Steluti.

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Conflict of interest

J. Steluti, A. M. Miranda, E. De Carli, C. Z. Palchetti, R. M. Fisberg, D. M. L. Marchioni have no conflict of interest.

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Steluti, J., Miranda, A.M., De Carli, E. et al. Unmetabolized folic acid is associated with TNF-α, IL-1β and IL-12 concentrations in a population exposed to mandatory food fortification with folic acid: a cross-sectional population-based study in Sao Paulo, Brazil. Eur J Nutr 60, 1071–1079 (2021). https://doi.org/10.1007/s00394-020-02307-z

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