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Providing perspectives on recent research into vitamins and nutritionals


Assessing Folate Intake and Status for Pregnancy and Cardiovascular Health

By Michael McBurney

Folic acid status is especially important for women during pregnancy and to maintain healthy homocysteine levels (a risk factor for cardiovascular disease) throughout life. Changes in folate assessment methods have made it difficult to compare data (Pfeiffer et al, 2010) and to reliably quantify dietary folate recommendations for optimal health.

Duffy and colleagues conducted a dose-response meta-analysis in healthy adults to quantify the relationship between folic acid intake and folate biomarkers.  In 27 randomized controlled intervention trials (RCTs), serum/plasma folate concentrations increased with supplementation. Overall, for every doubling in folic acid intake, serum/plasma concentrations increased 56%. As they write,

“an individual with a folic acid intake of 200 µg/d would have a serum/plasma folate that is 56% higher than an individual with an intake of 100µg/d.”

Using a subset of 12 RCTs with red blood cell (RBC) measurements, they found increases in RBC folate content with a 32% increase for every doubling in folic acid intake.

Plasma total homocysteine concentrations decreased in all but 2 studies. Overall, individuals with a folic acid intake of 200 µg daily would have a plasma homocysteine concentration 65 lower than someone consuming 100 µg daily. The greatest impact on lowering homocysteine levels was observed with lower doses of folic acid. The reasons for this observation are not apparent but the authors suggest adherence or renal thresholds for reabsorption could be factors.

Finally, most of these RCTs were conducted in persons with fair to good RBC folate status. Of the 15 studies with baseline RBC folate levels, 11 had baseline RBC folate values > 630 nmol/L. Despite a sharp increase in folate status after mandatory fortification, RBC folate concentrations in the US have fallen 12% from 1999 to 2010 (Pfeiffer et al., 2012). In Belgium, a country without mandatory folate fortification, 35% of women have a RBC folate concentration < 906 nmol/L (threshold for protecting fetus against neural tube defects) and 14% are < 680 nmol/L (Vandevijvere et al, 2012).

This study advances our understanding because both intake and folate biomarkers are assessed. Duffy and colleagues also affirm that the gold standard to measure total folate in serum and RBC is the microbiological assay.

Main Citation

Duffy ME, Hoey L, Hughes CF, Strain JJ, Rankin A, Souverein OW, Dullemeijer C, Collings R, Hooper L, McNulty H. Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials. 2013 Am J Clin Nutr doi:10.3945/ajcn.113.062752

Other Citations

Pfeiffer CM, Hughes JP, Lacher DA, Bailey RL, Berry RJ, Zhang M, Yetley EA, Rader JI, Sempos CT, Johnson CL. Estimation of trends in serum and RBC folate in the US population from pre- to postfortification using assay-adjusted data from the NHANES 1088-2010. 2012 J Nutr doi:10.3945/jn.111.156919

Pfeiffer CM, Hughes JP, Durazo-Arvizu RA, Lacher DA, Sempos CT, Zhang M, Yetley EA, Johnson CL. Changes in measurement procedure from a radioassay to a microbiologic assay necessitate adjustment of serum and RBC folate concentrations in the US population from the NHANES 1988-2010. 2012 J Nutr doi:10.3945/jn.111.156901

Vandevijvere S, Amsalkhir S, Van Oyen H, Moreno-Reyes R. Determinants of folate status in pregnant women: results from a national cross-sectional survey in Belgium. 2012 Eur J Clin Nutr doi:10.1038/ejcn.2012.111