Evidence from a randomized trial that exposure to supplemental folic acid at recommended levels during pregnancy does not lead to increasedunmetabolized folicacid concentrations in maternal or cord blood

Journal of Nutrition

Volumn 146, Issue 3, 2016, Pages 494-500

  Pentieva, Kristina ^a   Selhub, Jacob ^b   Paul, Ligi ^b   Molloy, Anne M ^c   McNulty, Breige ^e   Ward, Mary ^a   Marshall, Barry ^f   Dornan, James ^g   Reilly, Rosie ^a   Parle McDermott, Anne ^h   Bradbury, Ian ⁱ   Ozaki, Mari ^h   Scott, John M ^d   McNulty, Helene ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b TUFTS UNIVERSITY   (United States)

^c TRINITY COLLEGE DUBLIN   (Ireland)

^d TRINITY COLLEGE DUBLIN   (Ireland)

^e UNIVERSITY COLLEGE DUBLIN   (Ireland)

^f NORTHERN HEALTH AND SOCIAL CARE TRUST   (United Kingdom)

^g Royal Jubilee Maternity Service   (United Kingdom)

^h DUBLIN CITY UNIVERSITY   (Ireland)

ⁱ FRONTIER SCIENCE SCOTLAND LTD   (United Kingdom)

Author keywords

Folic acid fortified foods; Folic acid supplementation; Maternal and cord blood; Plasma; Pregnancy; Unmetabolized folic acid and total folate

Indexed keywords

5 METHYLTETRAHYDROFOLIC ACID; FOLIC ACID; PLACEBO; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); MTHFR PROTEIN, HUMAN;

ADULT; ARTICLE; BLOOD SAMPLING; COMPARATIVE STUDY; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DELIVERY; DRUG EFFECT; FEMALE; FIRST TRIMESTER PREGNANCY; FOLIC ACID BLOOD LEVEL; GESTATIONAL AGE; HUMAN; LIQUID CHROMATOGRAPHY; MATERNAL BLOOD; MATERNAL PLASMA; NEWBORN; NORMAL HUMAN; PRENATAL CARE; PRENATAL EXPOSURE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; SECOND TRIMESTER PREGNANCY; TANDEM MASS SPECTROMETRY; THIRD TRIMESTER PREGNANCY; UMBILICAL CORD BLOOD; VITAMIN SUPPLEMENTATION; ADOLESCENT; BLOOD; CHEMISTRY; DIETARY SUPPLEMENT; DOSE RESPONSE; FETUS BLOOD; FORTIFIED FOOD; GENETIC POLYMORPHISM; METABOLISM; PREGNANCY; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ADOLESCENT; ADULT; DIETARY SUPPLEMENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FETAL BLOOD; FOLIC ACID; FOOD, FORTIFIED; HUMANS; METHYLENETETRAHYDROFOLATE REDUCTASE (NADPH2); POLYMORPHISM, GENETIC; PREGNANCY; YOUNG ADULT;

EID: 84960456373     PISSN: 00223166     EISSN: 15416100     Source Type: Journal    
DOI: 10.3945/jn.115.223644     Document Type: Article

References (33)

1. Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory, 3rd JF, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, et al. Biomarkers of nutrition for development-folate review. J Nutr 2015;145:1636S-80S.
2. Kelly P, McPartlin J, Goggins M, Weir DG, Scott JM. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 1997;65:1790-5.
3. Dickinson CJ. Does folic acid harm people with vitamin B12 deficiency? QJM 1995;88:357-64.
4. Savage JD, Lindenbaum J. Folate-cobalamin interactions. In: Bailey LB, editor. Folate and health and disease. New York: Marcel Decker; 1995. p. 237-86.
5. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors. Am J Clin Nutr 2010;91:1733-44.
6. Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, et al. Folic acid for the prevention of colorectal adenomas: a randomised clinical trial. JAMA 2007;297:2351-9.
7. Bailey RL, Mills JL, Yetley EA, Gahche JJ, Pfeiffer CM, Dwyer JT, Dodd KW, Sempos CT, Betz JM, Picciano MF. Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged > or =60 y in the United States. Am J Clin Nutr 2010;92:383-9.
8. Boilson A, Staines A, Kelleher CC, Daly L, Shirley I, Shrivastava A, Bailey SW, Alverson PB, Ayling JE, McDermott AP, et al. Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program. Am J Clin Nutr 2012;96:613-21.
9. Pfeiffer CM, Sternberg MR, Fazili Z, Yetley EA, Lacher DA, Bailey RL, Johnson CL. Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. J Nutr 2015;145:520-31.
10. Kalmbach RD, Choumenkovitch SF, Troen AM, D'Agostino R, Jacques PF, Selhub J. Circulating folic acid in plasma: relation to folic acid fortification. Am J Clin Nutr 2008;88:763-8.
11. Sweeney MR, Staines A, Daly L, Traynor A, Daly S, Bailey SW, Alverson PB, Ayling JE, Scott JM. Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification? BMC Public Health 2009;9:295.
12. West AA, Yan J, Perry CA, Jiang X, Malysheva OV, Caudill MA. Folatestatus response to a controlled folate intake in nonpregnant, pregnant, and lactating women. Am J Clin Nutr 2012;96:789-800.
13. Obeid R, Kasoha M, Kirsch SH, MunzW, HerrmannW. Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood. Am J Clin Nutr 2010;92:1416-22.
14. Plumptre L, Masih SP, Ly A, Aufreiter S, Sohn KJ, Croxford R, Lausman AY, Berger H, O'Connor DL, Kim YI. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood. Am J Clin Nutr 2015;102:848-57.
15. Houghton LA, Sherwood KL, Pawlosky R, Ito S, O'Connor DL. [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation. Am J Clin Nutr 2006;83:842-50.
16. Sweeney MR, McPartlin J, Weir DG, Daly S, Pentieva K, Daly L, Scott JM. Evidence of unmetabolised folic acid in cord blood of newborn and serum of 4-day-old infants. Br J Nutr 2005;94:727-30.
17. McNulty B, McNulty H, Marshall B, Ward M, Molloy AM, Scott JM, Dornan J, Pentieva K. Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters. Am J Clin Nutr 2013;98:92-8.
18. Hannisdal R, Ueland PM, Svardal A. Liquid chromatography-tandem mass spectrometry analysis of folate and folate catabolites in human serum. Clin Chem 2009;55:1147-54.
19. Molloy AM, Scott JM. Microbiological assay for serum, plasma, and red cell folate using cryopreserved, microtiter plate method. Methods Enzymol 1997;281:43-53.
20. Kelleher BP, Broin SDO. Microbiological assay for vitamin B12 performed in 96-well microtitre plates. J Clin Pathol 1991;44:592-5.
21. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boeurs GJH, den Heijer M, Kluijtmans LAJ, Van den Heuvel LP, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-3.
22. Ozaki M, Molloy AM, Mills JL, Fan R, Wang Y, Gibney ER, Shane B, Brody LC, Parle-McDermott A. The dihydrofolate reductase 19 bp polymorphism is not associated with biomarkers of folate status in healthy young adults, irrespective of folic acid intake. J Nutr 2015;145:2207-11.
23. Hoey L, McNulty H, Askin N, Dunne A, Ward M, Pentieva K, Strain JJ, Molloy AM, Flynn CA, Scott JM. Impact of a voluntary food fortification policy on folate, related B-vitamin status and homocysteine in healthy adults. Am J Clin Nutr 2007;86:1405-13.
24. Landon MJ, Oxley A. Relation between maternal and infant blood folate activities. Arch Dis Child 1971;46:810-4.
25. Ek J. Plasma and red cell folate values in newborn infants and their mothers in relation to gestational age. J Pediatr 1980;97:288-92.
26. Molloy AM, Mills JL, McPartlin J, Kirke PN, Scott JM, Daly S. Maternal and fetal plasma homocysteine concentrations at birth: the influence of folate, vitamin B12, and the 5, 10-methylenetetrahydrofolate reductase 677C/T variant. Am J Obstet Gynecol 2002;186:499-503.
27. Henderson GI, Perez T, Schenker S, Mackins J, Antony AC. Maternalto-fetal transfer of 5-methyltetrahydrofolate by the perfused human placental cotyledon: evidence for a concentrative role by placental folate receptors in fetal folate delivery. J Lab Clin Med 1995;126:184-203.
28. Landon MJ, Eyre DH, Hytten FE. Transfer of folate to the fetus. Br J Obstet Gynaecol 1975;82:12-9.
29. Weitman SD, Weinberg AG, Coney LR, Zarawski VR, Jennings DS, Kamen BA. Cellular localization of the folate receptor: potential role in drug toxicity and folate homeostasis. Cancer Res 1992;52:6708-11.
30. Pentieva K, McNulty H, Reichert R, Ward M, Strain JJ, McKillop D, McPartlin JM, Connolly E, Molloy A, Krämer K, et al. The short-term bioavailabilities of [6S]-5-methyltetrahydrofolate and folic acid are equivalent in men. J Nutr 2004;134:580-5.
31. US FDA. Food labeling: health claims and labeling statements: folate and neural tube defects. Fed Regist 1993;58:53254-95.
32. Picciano MF, McGuire MK. Use of dietary supplements by pregnant and lactating women in North America. Am J Clin Nutr 2009;89:663S-7S.
33. Simpson JL, Bailey LB, Pietrzik K, Shane B, Holzgreve W. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess: part I-folate, vitamin B12, vitamin B6. J Matern Fetal Neonatal Med 2010;23:1323-43.