Kristina Pentieva1, Jacob Selhub2, Ligi Paul2, Anne M Molloy3, Breige McNulty4, Mary Ward5, Barry Marshall6, James Dornan7, Rosie Reilly5, Anne Parle-McDermott8, Ian Bradbury9, Mari Ozaki8, John M Scott10, Helene McNulty5. 1. Northern Ireland Centre for Food & Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland; k.pentieva@ulster.ac.uk. 2. Vitamin Metabolism and Aging Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA; 3. School of Medicine and. 4. School of Agriculture & Food Science, University College Dublin, Dublin, Ireland; 5. Northern Ireland Centre for Food & Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland; 6. Causeway Hospital, The Northern Health and Social Care Trust, Coleraine, Northern Ireland; 7. Royal-Jubilee Maternity Service, Belfast, Northern Ireland; 8. School of Biotechnology, Dublin City University, Dublin, Ireland; and. 9. Frontier Science (Scotland), Kincraig, Scotland. 10. School of Biochemistry and Immunology, Trinity College, Dublin, Ireland;
Abstract
BACKGROUND: Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which has raised some health concerns. OBJECTIVE: The effect of supplemental FA at a dose of 400 μg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated. METHODS: A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18-35 y, who had taken 400 μg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 μg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC-tandem MS analysis. RESULTS: In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (≥0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean ± SD: 0.44 ± 0.80 compared with 0.13 ± 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 ± 20.1 compared with 34.5 ± 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 ± 20.3 compared with 34.5 ± 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups. CONCLUSIONS: Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 μg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods.
RCT Entities:
BACKGROUND: Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which has raised some health concerns. OBJECTIVE: The effect of supplemental FA at a dose of 400 μg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated. METHODS: A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18-35 y, who had taken 400 μg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 μg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC-tandem MS analysis. RESULTS: In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (≥0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean ± SD: 0.44 ± 0.80 compared with 0.13 ± 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 ± 20.1 compared with 34.5 ± 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 ± 20.3 compared with 34.5 ± 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups. CONCLUSIONS: Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 μg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods.
Authors: Padma Maruvada; Patrick J Stover; Joel B Mason; Regan L Bailey; Cindy D Davis; Martha S Field; Richard H Finnell; Cutberto Garza; Ralph Green; Jean-Louis Gueant; Paul F Jacques; David M Klurfeld; Yvonne Lamers; Amanda J MacFarlane; Joshua W Miller; Anne M Molloy; Deborah L O'Connor; Christine M Pfeiffer; Nancy A Potischman; Joseph V Rodricks; Irwin H Rosenberg; Sharon A Ross; Barry Shane; Jacob Selhub; Sally P Stabler; Jacquetta Trasler; Sedigheh Yamini; Giovanna Zappalà Journal: Am J Clin Nutr Date: 2020-11-11 Impact factor: 7.045
Authors: Ramkripa Raghavan; Jacob Selhub; Ligi Paul; Yuelong Ji; Guoying Wang; Xiumei Hong; Barry Zuckerman; M Daniele Fallin; Xiaobin Wang Journal: Am J Clin Nutr Date: 2020-11-11 Impact factor: 7.045
Authors: Malia S Q Murphy; Katherine A Muldoon; Hauna Sheyholislami; Nathalie Behan; Yvonne Lamers; Natalie Rybak; Ruth Rennicks White; Alysha L J Harvey; Laura M Gaudet; Graeme N Smith; Mark C Walker; Shi Wu Wen; Amanda J MacFarlane Journal: Am J Clin Nutr Date: 2021-05-08 Impact factor: 7.045
Authors: Karen B Kelly; John P Kennelly; Marta Ordonez; Randal Nelson; Kelly Leonard; Sally Stabler; Antonio Gomez-Muñoz; Catherine J Field; René L Jacobs Journal: Nutrients Date: 2016-09-23 Impact factor: 5.717