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J Nutr Sci. 2018 Nov 26;7:e32. doi: 10.1017/jns.2018.22. eCollection 2018.

Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods.

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Department of Chemistry and Biomedical Sciences, Faculty of Health and Life Sciences, Linnaeus University, 391 82 Kalmar, Sweden.
Food Industries Department, Faculty of Agriculture, Mansoura University, 35516, PO Box 46, Mansoura, Egypt.
Department of Molecular Sciences, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden.


Public health authorities recommend all fertile women to increase their folate intake to 400 µg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 µg/d synthetic folic acid from a supplement (n 18), 250 µg/d folate from intervention foods (n 19), or no additional folate (0 µg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently.


Dietary interventions; Folate; Folic acid; Metabolomics; OPLS-DA, orthogonal partial least-squares discriminant analysis; One-carbon metabolism; VIP, variable influence of projection

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