Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods

Abstract

Objective To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid. Methods Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis. Results Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0–52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency (<7 nmol/L) in 10 (6.9%) participants. No one had vitamin B12 deficiency (<148 pmol/L). An elevated serum UMFA concentration was defined as > 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] D 1.02 [1.01–1.04)] and being a male (OR [95% CI] = 0.40 [0.19–0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively. Conclusion UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.

A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults

“…Detectable concentrations of serum UMFA were present in all of the participants at baseline (geometric mean: 0.59 nmol/L; 95% CI: 0.52, 0.68 nmol/L). In a previous cross-sectional study, carried out in 144 healthy Brazilian non–supplement users exposed to mandatory wheat and maize flour fortification with FA, it was observed that dietary FA was associated with UMFA concentrations (geometric mean: 0.55 nmol/L; 95% CI: 0.50, 0.61 nmol/L) (38). …”

Is natural (6S)-5-methyltetrahydrofolic acid as effective as synthetic folic acid in increasing serum and red blood cell folate concentrations during pregnancy? A proof-of-concept pilot study

“…17 National surveys have identified that since the initiation of food fortification, prevalence of folate deficiency (RBC folate <305 nmol/L) has decreased from 38% to 5% in the United States and is essentially non-existent in Canada (<1%). 16,17,20 High intakes of folic acid are concerning because it appears that DHFR activity is limited, [21][22][23] and the metabolic effects of unmetabolized folic acid (UMFA) are unknown. There is an acute appearance of plasma UMFA following oral intakes of folic acid >0.2 mg, suggesting that intestinal absorptive capacity becomes saturated at this dose.…”

Global Concerns with B Vitamin Statuses: Biofortification, Fortification, Hidden Hunger, Interactions, and Toxicity

“…Furthermore, unmetabolized free folic acid is found in serum samples from nearly all people who consume folic acid-containing foods (Pfeiffer et al, 2015). The amount of free serum folic acid increases with greater consumption of folic acid (Palchetti et al, 2017), but appears to be partially dependent on other nutrient statuses (Obeid et al, 2016;Palchetti et al, 2017). Variation exists in the dihydrofolate reductase enzyme and individuals with decreased enzyme activity are at higher risk of high blood concentrations of free folic acid (Bailey & Ayling, 2009).…”