Folate – a scoping review for Nordic Nutrition Recommendations 2023

  • Anne-Lise Bjørke Monsen Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
  • Per Magne Ueland Department of Clinical Science, University of Bergen, Bergen, Norway
DOI: https://doi.org/10.29219/fnr.v67.10258
Keywords: folate, folic acid, one-carbon metabolism, homocysteine, nutrition recommendations

Abstract

Folate is an essential micronutrient for normal development and metabolic function, and folate deficiency is associated with an increased risk of cancer, cardiovascular disease, mental dysfuntion and negative pregnancy outcomes. When estimating folate requirements, one must consider different bioavailability and functionality between synthetic folic acid and dietary folate, together with increased needs of folate in women of fertile age, pregnant and lactating women, preterm and small for gestational age weight infants and individuals who are homozygote for the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism. In order to achieve an adequate metabolic status based on the metabolic marker total homocysteine, and not merely the absence of clinical signs of folate deficiency, the recommended intake of folate differs according to age, pregnancy and lactation. According to the World Health Organization, a decision limit for folate deficiency in adults is serum folate level below 10 nmol/L, and in women of fertile age a red blood cell folate level below 906 nmol/L in order to prevent neural tube defects. Qualified systematic reviews along with identified relevant literature have been used for this scoping review prepared for the Nordic Nutrition Recommendations 2023.

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References


1.
Ohrvik VE, Witthoft CM. Human folate bioavailability. Nutrients 2011; 3(4): 475–90. https://doi.org/10.3390/nu3040475


2.
Bailey LB, Gregory JF, 3rd. Folate metabolism and requirements. J Nutr 1999; 129(4): 779–82. https://doi.org/10.1093/jn/129.4.779


3.
Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF, 3rd, Mills JL, et al. Biomarkers of nutrition for development-folate review. J Nutr 2015; 145(7): 1636S–80S. https://doi.org/10.3945/jn.114.206599


4.
Kim YI. Folate and cancer: a tale of Dr. Jekyll and Mr. Hyde? Am J Clin Nutr 2018; 107(2): 139–42. https://doi.org/10.1093/ajcn/nqx076


5.
Li Y, Huang T, Zheng Y, Muka T, Troup J, Hu FB. Folic Acid supplementation and the risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. J Am Heart Assoc 2016; 5(8): e003768. https://doi.org/10.1161/JAHA.116.003768


6.
Han YY, Blatter J, Brehm JM, Forno E, Litonjua AA, Celedon JC. Diet and asthma: vitamins and methyl donors. Lancet Respir Med 2013; 1(10): 813–22. https://doi.org/10.1016/S2213-2600(13)70126-7


7.
Parr CL, Magnus MC, Karlstad O, Haugen M, Refsum H, Ueland PM, et al. Maternal folate intake during pregnancy and childhood asthma in a population-based cohort. Am J Respir Crit Care Med 2017; 195(2): 221–8. https://doi.org/10.1164/rccm.201604-0788OC


8.
Doets EL, Ueland PM, Tell GS, Vollset SE, Nygard OK, Van’t Veer P, et al. Interactions between plasma concentrations of folate and markers of vitamin B(12) status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study. Br J Nutr 2014; 111(6): 1085–95. https://doi.org/10.1017/S000711451300336X


9.
Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008; 4: CD004514. https://doi.org/10.1002/14651858.CD004514.pub2


10.
Lassi ZS, Salam RA, Haider BA, Bhutta ZA. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev 2013; 3: CD006896. https://doi.org/10.1002/14651858.CD006896.pub2


11.
Scholl TO, Johnson WG. Folic acid: influence on the outcome of pregnancy. Am J Clin Nutr 2000; 71(5 Suppl): 1295S–303S. https://doi.org/10.1093/ajcn/71.5.1295s


12.
MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338(8760): 131–7. https://doi.org/10.1016/0140-6736(91)90133-A


13.
Kancherla V, Botto LD, Rowe LA, Shlobin NA, Caceres A, Arynchyna-Smith A, et al. Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid. Lancet Glob Health 2022; 10(7): e1053–7. https://doi.org/10.1016/S2214-109X(22)00213-3


14.
Monsen AL, Refsum H, Markestad T, Ueland PM. Cobalamin status and its biochemical markers methylmalonic acid and homocysteine in different age groups from 4 days to 19 years. Clin Chem 2003; 49(12): 2067–75. https://doi.org/10.1373/clinchem.2003.019869


15.
Cordero AM, Crider KS, Rogers LM, Cannon MJ, Berry RJ. Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep 2015; 64(15): 421–3. https://doi.org/10.1007/s00394-016-1328-4


16.
Ohrvik V, Lemming EW, Nalsen C, Becker W, Ridefelt P, Lindroos AK. Dietary intake and biomarker status of folate in Swedish adults. Eur J Nutr 2018; 57(2): 451–62. https://doi.org/10.1007/s00394-016-1328-4


17.
Bramswig S, Prinz-Langenohl R, Lamers Y, Tobolski O, Wintergerst E, Berthold HK, et al. Supplementation with a multivitamin containing 800 microg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women. Int J Vitam Nutr Res 2009; 79(2): 61–70. https://doi.org/10.1024/0300-9831.79.2.61


18.
De Bree A, Van Dusseldorp M, Brouwer IA, Van het Hof KH, Steegers-Theunissen RP. Folate intake in Europe: recommended, actual and desired intake. Eur J Clin Nutr 1997; 51(10): 643–60. https://doi.org/10.1038/sj.ejcn.1600467


19.
Blomhoff R, Andersen R, Arnesen EK, Christensen JJ, Eneroth H, Erkkola M, et al. Nordic Nutrition Recommendations 2023. Copenhagen: Nordic Council of Ministers; 2023.


20.
Christensen JJ, Arnesen EK, Andersen R, Eneroth H, Erkkola M, Hoyer A, et al. The Nordic Nutrition Recommendations 2022 – principles and methodologies. Food Nutr Res 2020; 64: 4402. https://doi.org/10.29219/fnr.v64.4402


21.
Donovan S, Dewey K, Novotny R, Stang J, Taveras E, Kleinman R, et al. Folic Acid from Fortified Foods and/or Supplements during Pregnancy and Lactation and Health Outcomes: A Systematic Review [Internet]. Alexandria (VA): USDA Nutrition Evidence Systematic Review; 2020 Jul. PMID: 35289987.


22.
Butterworth CE Jr., Baugh CM, Krumdieck C. A study of folate absorption and metabolism in man utilizing carbon-14 – labeled polyglutamates synthesized by the solid phase method. J Clin Invest 1969; 48(6): 1131–42. https://doi.org/10.1172/JCI106070


23.
Laanpere M, Altmae S, Stavreus-Evers A, Nilsson TK, Yngve A, Salumets A. Folate-mediated one-carbon metabolism and its effect on female fertility and pregnancy viability. Nutr Rev 2010; 68(2): 99–113. https://doi.org/10.1111/j.1753-4887.2009.00266.x


24.
Bhandari SD, Gregory JF, 3rd. Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats. J Nutr 1992; 122(9): 1847–54. https://doi.org/10.1093/jn/122.9.1847


25.
Gregory JF, 3rd. Bioavailability of folate. Eur J Clin Nutr 1997; 51(Suppl 1): S54–9.


26.
Brouwer IA, Van Dusseldorp M, West CE, Meyboom S, Thomas CM, Duran M, et al. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. J Nutr 1999; 129(6): 1135–9. https://doi.org/10.1093/jn/129.6.1135


27.
Hannon-Fletcher MP, Armstrong NC, Scott JM, Pentieva K, Bradbury I, Ward M, et al. Determining bioavailability of food folates in a controlled intervention study. Am J Clin Nutr 2004; 80(4): 911–8. https://doi.org/10.1093/ajcn/80.4.911


28.
Bjork M, Riedel B, Spigset O, Veiby G, Kolstad E, Daltveit AK, et al. Association of folic acid supplementation during pregnancy with the risk of autistic traits in children exposed to antiepileptic drugs in utero. JAMA Neurol 2018; 75(2): 160–8. https://doi.org/10.1001/jamaneurol.2017.3897


29.
Clark SL. Oral folic acid tolerance test in normal human subjects and patients with pernicious anemia. Proc Soc Exp Biol Med Soc Exp Biol Med 1958; 82: 25–7. https://doi.org/10.3181/00379727-82-20011


30.
Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington, DC: The National Academies Collection: Reports funded by National Institutes of Health; 1998.


31.
Jacques PF, Bostom AG, Williams RR, Ellison RC, Eckfeldt JH, Rosenberg IH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996; 93: 7–9. https://doi.org/10.1161/01.CIR.93.1.7


32.
Huang X, Qin X, Yang W, Liu L, Jiang C, Zhang X, et al. MTHFR gene and serum folate interaction on serum homocysteine lowering: prospect for precision folic acid treatment. Arteriosc Thromb Vascu Biol 2018; 38(3): 679–85. https://doi.org/10.1161/ATVBAHA.117.310211


33.
Hibbard BM. The role of folic acid in pregnancy with particular reference to anaemia, abruption and abortion. J Obstet Gynaecol Br Commonw 1964; 71: 529–42. https://doi.org/10.1111/j.1471-0528.1964.tb04317.x


34.
McPartlin J, Halligan A, Scott JM, Darling M, Weir DG. Accelerated folate breakdown in pregnancy. Lancet 1993; 341(8838): 148–9. https://doi.org/10.1016/0140-6736(93)90007-4


35.
Rosenblatt DS, Whitehead VM. Cobalamin and folate deficiency: acquired and hereditary disorders in children. Semin Hematol 1999; 36(1): 19–34.


36.
Allen LH. B vitamins in breast milk: relative importance of maternal status and intake, and effects on infant status and function. Adv Nutr 2012; 3(3): 362–9. https://doi.org/10.3945/an.111.001172


37.
Cooperman JM, Dweck HS, Newman LJ, Garbarino C, Lopez R. The folate in human milk. Am J Clin Nutr 1982; 36(4): 576–80. https://doi.org/10.1093/ajcn/36.4.576


38.
Mackey AD, Picciano MF. Maternal folate status during extended lactation and the effect of supplemental folic acid. Am J Clin Nutr 1999; 69(2): 285–92. https://doi.org/10.1093/ajcn/69.2.285


39.
Houghton LA, Yang J, O’Connor DL. Unmetabolized folic acid and total folate concentrations in breast milk are unaffected by low-dose folate supplements. Am J Clin Nutr 2009; 89(1): 216–20. https://doi.org/10.3945/ajcn.2008.26564


40.
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(3): 499–503. https://doi.org/10.1067/mob.2002.121105


41.
Baker H, Thind IS, Frank O, DeAngelis B, Caterini H, Louria DB. Vitamin levels in low-birth-weight newborn infants and their mothers. Am J Obstet Gynecol 1977; 129(5): 521–4. https://doi.org/10.1016/0002-9378(77)90090-4


42.
Pathak A, Godwin HA. Vitamin B 12 and folic acid values in premature infants. Pediatrics 1972; 50(4): 584–9. https://doi.org/10.1542/peds.50.4.584


43.
Samuel PD, Burland WL, Simpson K. Response to oral administration of pteroylmonoglutamic acid or pteroylpolyglutamate in newborn infants of low birth weight. Br J Nutr 1973; 30(2): 165–9. https://doi.org/10.1079/BJN19730021


44.
Bjorke-Monsen AL, Ueland PM. Cobalamin status in children. J Inherit Metab Dis 2011; 34(1): 111–9. https://doi.org/10.1007/s10545-010-9119-1


45.
Montgomery JA, Clayton SJ, Thomas HJ, Shannon WM, Arnett G, Bodner AJ, et al. Carbocyclic analogue of 3-deazaadenosine. A novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target. J Med Chem 1982; 25: 626–9. https://doi.org/10.1021/jm00348a004


46.
Salmenpera L, Perheentupa J, Siimes MA. Folate nutrition is optimal in exclusively breast-fed infants but inadequate in some of their mothers and in formula-fed infants. J Pediatr Gastroenterol Nutr 1986; 5(2): 283–9. https://doi.org/10.1097/00005176-198605020-00021


47.
Han YH, Yon M, Han HS, Kim KY, Tamura T, Hyun TH. Folate contents in human milk and casein-based and soya-based formulas, and folate status in Korean infants. Br J Nutr 2009; 101(12): 1769–74. https://doi.org/10.1017/S0007114508158974


48.
Howard MR, Turnbull AJ, Morley P, Hollier P, Webb R, Clarke A. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol 2002; 55(10): 754–7. https://doi.org/10.1136/jcp.55.10.754


49.
Mitchell ES, Snell ES, Williams RJ. Folate. In: Combs GF, ed. The vitamins fundamental aspects in nutrition and health. North Dakota: Academic Press; 1998, pp. 377–401.


50.
Hunt SE, Netting MJ, Sullivan TR, Best KP, Houghton LA, Makrides M, et al. Red Blood cell folate likely overestimated in Australian National Survey: implications for neural tube defect risk. Nutrients 2020; 12(5): 1283. https://doi.org/10.3390/nu12051283


51.
Clifford AJ, Noceti EM, Block-Joy A, Block T, Block G. Erythrocyte folate and its response to folic acid supplementation is assay dependent in women. J Nutr 2005; 135(1): 137–43. https://doi.org/10.1093/jn/135.1.137


52.
Gunter EW, Bowman BA, Caudill SP, Twite DB, Adams MJ, Sampson EJ. Results of an international round robin for serum and whole-blood folate. Clin Chem 1996; 42(10): 1689–94. https://doi.org/10.1093/clinchem/42.10.1689


53.
Wright AJ, Finglas PM, Southon S. Erythrocyte folate analysis: a cause for concern? Clin Chem 1998; 44(9): 1886–91. https://doi.org/10.1093/clinchem/44.9.1886


54.
Wickramasinghe SN. Nutritional anaemias. Clin Lab Haematol 1988; 10: 117–34. https://doi.org/10.1111/j.1365-2257.1988.tb01164.x


55.
Bull CF, Mayrhofer G, Zeegers D, Mun GL, Hande MP, Fenech MF. Folate deficiency is associated with the formation of complex nuclear anomalies in the cytokinesis-block micronucleus cytome assay. Environ Mol Mutagen 2012; 53(4): 311–23. https://doi.org/10.1002/em.21688


56.
Bjorke-Monsen AL. Hva betyr en høy plasma-homocysteinverdi? [What does a high plasma homocysteine level signify?]. Tidsskr Nor Laegeforen. 2021 Mar 22;141(5). https://doi.org/10.4045/tidsskr.21.0023.


57.
Ozarda Y, Sikaris K, Streichert T, Macri J, Intervals ICoR, Decision L. Distinguishing reference intervals and clinical decision limits – A review by the IFCC Committee on Reference Intervals and Decision Limits. Crit Rev Clin Lab Sci 2018; 55(6): 420–31. https://doi.org/10.1080/10408363.2018.1482256


58.
Steluti J, Selhub J, Paul L, Reginaldo C, Fisberg RM, Marchioni DML. An overview of folate status in a population-based study from Sao Paulo, Brazil and the potential impact of 10 years of national folic acid fortification policy. Eur J Clin Nutr 2017; 71(10): 1173–8. https://doi.org/10.1038/ejcn.2017.60


59.
WHO. [cited 24 June 2022]. Available from: https://www.who.int/elena/titles/guidance_summaries/daily_iron_pregnancy/en/


60.
Bjorke-Monsen AL, Renstrom R. What is optimal folate status? Tidsskr Nor Laegeforen. 2020 May 4;140(7). https://doi.org/10.4045/tidsskr.19.0588. PMID: 32378856.


61.
Bjørke-Monsen AL, Roth C, Magnus P, Midttun Ø, Nilsen RM, Reichborn-Kjennerud T, et al. Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements. Mol Nutr Food Res 2013; 57(4): 645–52. https://doi.org/10.1002/mnfr.201200114


62.
Caudill MA. Folate bioavailability: implications for establishing dietary recommendations and optimizing status. Am J Clin Nutr 2010; 91(5): 1455S–60S. https://doi.org/10.3945/ajcn.2010.28674E


63.
Lemming EW, Pitsi T. The Nordic Nutrition Recommendations 2022 – food consumption and nutrient intake in the adult population of the Nordic and Baltic countries. Food Nutr Res 2022; 66: 8572. https://doi.org/10.29219/fnr.v66.8572


64.
Medici V, Halsted CH. Folate, alcohol, and liver disease. Mol Nutri Food Res 2013; 57(4): 596–606. https://doi.org/10.1002/mnfr.201200077


65.
Moazzen S, Dolatkhah R, Tabrizi JS, Shaarbafi J, Alizadeh BZ, de Bock GH, et al. Folic acid intake and folate status and colorectal cancer risk: a systematic review and meta-analysis. Clin Nutr 2018; 37(6 Pt A): 1926–34. https://doi.org/10.1016/j.clnu.2017.10.010


66.
Zhang D, Wen X, Wu W, Guo Y, Cui W. Elevated homocysteine level and folate deficiency associated with increased overall risk of carcinogenesis: meta-analysis of 83 case-control studies involving 35,758 individuals. PLoS One 2015; 10(5): e0123423. https://doi.org/10.1371/journal.pone.0123423


67.
Pieroth R, Paver S, Day S, Lammersfeld C. Folate and its impact on cancer risk. Curr Nutr Rep 2018; 7(3): 70–84. https://doi.org/10.1007/s13668-018-0237-y


68.
Bird CL, Swendseid ME, Witte JS, Shikany JM, Hunt IF, Frankl HD, et al. Red cell and plasma folate, folate consumption, and the risk of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 1995; 4(7): 709–14.


69.
Gao QY, Chen HM, Chen YX, Wang YC, Wang ZH, Tang JT, et al. Folic acid prevents the initial occurrence of sporadic colorectal adenoma in Chinese older than 50 years of age: a randomized clinical trial. Cancer Prev Res (Phila) 2013; 6(7): 744–52. https://doi.org/10.1158/1940-6207.CAPR-13-0013


70.
Gibson TM, Weinstein SJ, Pfeiffer RM, Hollenbeck AR, Subar AF, Schatzkin A, et al. Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States. Am J Clin Nutr 2011; 94(4): 1053–62. https://doi.org/10.3945/ajcn.110.002659


71.
Konings EJ, Goldbohm RA, Brants HA, Saris WH, Van den Brandt PA. Intake of dietary folate vitamers and risk of colorectal carcinoma: results from The Netherlands Cohort Study. Cancer 2002; 95(7): 1421–33. https://doi.org/10.1002/cncr.10866


72.
Fu H, He J, Li C, Deng Z, Chang H. Folate intake and risk of colorectal cancer: a systematic review and up-to-date meta-analysis of prospective studies. Eur J Cancer Prev 2022; 32(2): 103–12. https://doi.org/10.1097/CEJ.0000000000000744


73.
Smith AD, Refsum H. Homocysteine – from disease biomarker to disease prevention. J Intern Med 2021; 290(4): 826–54. https://doi.org/10.1111/joim.13279


74.
Park JH, Saposnik G, Ovbiagele B, Markovic D, Towfighi A. Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: a meta-analysis. Int J Stroke 2016; 11(2): 206–11. https://doi.org/10.1177/1747493015616512


75.
Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA 2015; 313(13): 1325–35. https://doi.org/10.1001/jama.2015.2274


76.
Nilsson TK, Yngve A, Bottiger AK, Hurtig-Wennlof A, Sjostrom M. High folate intake is related to better academic achievement in Swedish adolescents. Pediatrics 2011; 128(2): e358–65. https://doi.org/10.1542/peds.2010-1481


77.
Nurk E, Refsum H, Tell GS, Engedal K, Vollset SE, Ueland PM, et al. Plasma total homocysteine and memory in the elderly: the Hordaland Homocysteine Study. Ann Neurol 2005; 58(6): 847–57. https://doi.org/10.1002/ana.20645


78.
Wang Z, Zhu W, Xing Y, Jia J, Tang Y. B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis. Nutr Rev 2022; 80(4): 931–49. https://doi.org/10.1093/nutrit/nuab057


79.
Ramos MI, Allen LH, Mungas DM, Jagust WJ, Haan MN, Green R, et al. Low folate status is associated with impaired cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005; 82(6): 1346–52. https://doi.org/10.1093/ajcn/82.6.1346


80.
Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011; 378(9793): 804–14. https://doi.org/10.1016/S0140-6736(11)60813-1


81.
Magnusson M, Sorensen TI, Olafsdottir S, Lehtinen-Jacks S, Holmen TL, Heitmann BL, et al. Social inequalities in obesity persist in the Nordic Region despite its relative affluence and equity. Curr Obes Rep 2014; 3: 1–15. https://doi.org/10.1007/s13679-013-0087-2


82.
Kreusler P, Vogel M, Willenberg A, Baber R, Dietz Y, Korner A, et al. Folate and cobalamin serum levels in healthy children and adolescents and their association with age, sex, BMI and socioeconomic status. Nutrients 2021; 13(2): 546. https://doi.org/10.3390/nu13020546


83.
Mojtabai R. Body mass index and serum folate in childbearing age women. Eur J Epidemiol 2004; 19(11): 1029–36. https://doi.org/10.1007/s10654-004-2253-z


84.
Bjørke-Monsen AL, Ulvik A, Nilsen RM, Midttun Ø, Roth C, Magnus P, et al. Impact of pre-pregnancy BMI on B vitamin and inflammatory status in early pregnancy: an observational cohort study. Nutrients 2016; 8(12): 776. https://doi.org/10.3390/nu8120776


85.
Kimmons JE, Blanck HM, Tohill BC, Zhang J, Khan LK. Associations between body mass index and the prevalence of low micronutrient levels among US adults. MedGenMed Medscape Gen Med 2006; 8(4): 59.


86.
De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2015; 12: CD007950. https://doi.org/10.1002/14651858.CD007950.pub3


87.
Viswanathan M, Treiman KA, Kish-Doto J, Middleton JC, Coker-Schwimmer EJ, Nicholson WK. Folic acid supplementation for the prevention of neural tube defects: an updated evidence report and systematic review for the US preventive services task force. JAMA 2017; 317(2): 190–203. https://doi.org/10.1001/jama.2016.19193


88.
Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstetr Gynecol 2011; 4(2): 52–9.


89.
Castro K, Klein Lda S, Baronio D, Gottfried C, Riesgo R, Perry IS. Folic acid and autism: what do we know? Nutr Neurosci 2016; 19(7): 310–7. https://doi.org/10.1179/1476830514Y.0000000142


90.
Gao Y, Sheng C, Xie RH, Sun W, Asztalos E, Moddemann D, et al. New perspective on impact of folic acid supplementation during pregnancy on neurodevelopment/autism in the offspring children – A systematic review. PLoS One 2016; 11(11): e0165626. https://doi.org/10.1371/journal.pone.0165626


91.
Caffrey A, McNulty H, Rollins M, Prasad G, Gaur P, Talcott JB, et al. Effects of maternal folic acid supplementation during the second and third trimesters of pregnancy on neurocognitive development in the child: an 11-year follow-up from a randomised controlled trial. BMC Med 2021; 19(1): 73. https://doi.org/10.1186/s12916-021-01914-9


92.
Julvez J, Fortuny J, Mendez M, Torrent M, Ribas-Fito N, Sunyer J. Maternal use of folic acid supplements during pregnancy and four-year-old neurodevelopment in a population-based birth cohort. Paediatr Perinat Epidemiol 2009; 23(3): 199–206. https://doi.org/10.1111/j.1365-3016.2009.01032.x


93.
Roza SJ, Van Batenburg-Eddes T, Steegers EA, Jaddoe VW, Mackenbach JP, Hofman A, et al. Maternal folic acid supplement use in early pregnancy and child behavioural problems: the Generation R Study. Br J Nutr 2010; 103(3): 445–52. https://doi.org/10.1017/S0007114509991954


94.
Valera-Gran D, Garcia de la Hera M, Navarrete-Munoz EM, Fernandez-Somoano A, Tardon A, Julvez J, et al. Folic acid supplements during pregnancy and child psychomotor development after the first year of life. JAMA Pediatr 2014; 168(11): e142611. https://doi.org/10.1001/jamapediatrics.2014.2611


95.
Brown SB, Reeves KW, Bertone-Johnson ER. Maternal folate exposure in pregnancy and childhood asthma and allergy: a systematic review. Nutr Rev 2014; 72(1): 55–64. https://doi.org/10.1111/nure.12080


96.
Hua X, Zhang J, Guo Y, Shen M, Gaudet L, Janoudi G, et al. Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: a systematic review and meta-analysis. Hypertens Pregnan 2016; 35(4): 447–60. https://doi.org/10.1080/10641955.2016.1183673


97.
Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao S, Fisher DJ, et al. Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia 2008; 51(1): 29–38. https://doi.org/10.1007/s00125-007-0793-y


98.
Scientific Committee on Food (SCF) and the EFSA Panel on Dietetic Products NaAN. Overview on Tolerable Upper Intake Levels as derived by the Scientific Committee on Food (SCF) and the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) Summary of Tolerable Upper Intake Levels – version 4. 2018. https://www.efsa.europa.eu/sites/default/files/assets/UL_Summary_tables.pdf


99.
Maruvada P, Stover PJ, Mason JB, Bailey RL, Davis CD, Field MS, et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. Am J Clin Nutr 2020; 112(5): 1390–403. https://doi.org/10.1093/ajcn/nqaa259


100.
Selhub J, Miller JW, Troen AM, Mason JB, Jacques PF. Perspective: the high-folate-low-vitamin B-12 interaction is a novel cause of vitamin B-12 depletion with a specific etiology-a hypothesis. Adv Nutr 2022; 13(1): 16–33. https://doi.org/10.1093/advances/nmab106


101.
Butterworth CE Jr, Tamura T. Folic acid safety and toxicity: a brief review. Am J Clin Nutr 1989; 50(2): 353–8. https://doi.org/10.1093/ajcn/50.2.353


102.
Pfeiffer CM, Sternberg MR, Fazili Z, Yetley EA, Lacher DA, Bailey RL, et al. Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults. J Nutr 2015; 145(3): 520–31. https://doi.org/10.3945/jn.114.201210


103.
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(6): 1733–44. https://doi.org/10.3945/ajcn.2009.28671


104.
Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr 2006; 136(1): 189–94. https://doi.org/10.1093/jn/136.1.189


105.
EFSA Panel on Dietetic Products NaAN. SCIENTIFIC OPINION Scientific Opinion on Dietary Reference Values for folate. EFSA J. 2014; 12(11): 3893. https://doi.org/10.2903/j.efsa.2014.3893


106.
Koehler KM, Baumgartner RN, Garry PJ, Allen RH, Stabler SP, Rimm EB. Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use. Am J Clin Nutr 2001; 73(3): 628–37. https://doi.org/10.1093/ajcn/73.3.628


107.
Chen MY, Rose CE, Qi YP, Williams JL, Yeung LF, Berry RJ, et al. Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation. Am J Clin Nutr 2019; 109(5): 1452–61. https://doi.org/10.1093/ajcn/nqz027


108.
Fenech M. The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat Res 2001; 475(1–2): 57–67. https://doi.org/10.1016/S0027-5107(01)00079-3


109.
Hursthouse NA, Gray AR, Miller JC, Rose MC, Houghton LA. Folate status of reproductive age women and neural tube defect risk: the effect of long-term folic acid supplementation at doses of 140 microg and 400 microg per day. Nutrients 2011; 3(1): 49–62. https://doi.org/10.3390/nu3010049


110.
Caudill MA, Cruz AC, Gregory JF, 3rd, Hutson AD, Bailey LB. Folate status response to controlled folate intake in pregnant women. J Nutr 1997; 127(12): 2363–70. https://doi.org/10.1093/jn/127.12.2363


111.
Haugen M, Brantsaeter AL, Alexander J, Meltzer HM. Dietary supplements contribute substantially to the total nutrient intake in pregnant Norwegian women. Ann Nutr Metab 2008; 52(4): 272–80. https://doi.org/10.1159/000146274


112.
Bjorke-Monsen AL, Roth C, Magnus P, Midttun O, Nilsen RM, Reichborn-Kjennerud T, et al. Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements. Mol Nutr Food Res 2013; 57(4): 645–52. https://doi.org/10.1002/mnfr.201200114


113.
Green R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, et al. Vitamin B12 deficiency. Nat Rev Dis Prim 2017; 3: 17040. https://doi.org/10.1038/nrdp.2017.40


114.
Pawlak R. To vegan or not to vegan when pregnant, lactating or feeding young children. Eur J Clin Nutr 2017; 71(11): 1259–62. https://doi.org/10.1038/ejcn.2017.111


115.
Smith AM, Picciano MF, Deering RH. Folate intake and blood concentrations of term infants. Am J Clin Nutr 1985; 41(3): 590–8. https://doi.org/10.1093/ajcn/41.3.590


116.
Asfour R, Wahbeh N, Waslien CI, Guindi S, Darby WJ. Folacin requirement of children. III. Normal infants. Am J Clin Nutr 1977; 30(7): 1098–105. https://doi.org/10.1093/ajcn/30.7.1098


117.
Tamura T, Yoshimura Y, Arakawa T. Human milk folate and folate status in lactating mothers and their infants. Am J Clin Nutr 1980; 33(2): 193–7. https://doi.org/10.1093/ajcn/33.2.193


118.
Sichert-Hellert W, Kersting M. Fortifying food with folic acid improves folate intake in German infants, children, and adolescents. J Nutr 2004; 134(10): 2685–90. https://doi.org/10.1093/jn/134.10.2685


119.
Oncel MY, Calisici E, Ozdemir R, Yurttutan S, Erdeve O, Karahan S, et al. Is folic acid supplementation really necessary in preterm infants </= 32 weeks of gestation? J Pediatr Gastroenterol Nutr 2014; 58(2): 188–92. https://doi.org/10.1097/MPG.0000000000000181
Published
2023-12-26
How to Cite
Bjørke Monsen A.-L., & Ueland P. M. (2023). Folate – a scoping review for Nordic Nutrition Recommendations 2023. Food & Nutrition Research, 67. https://doi.org/10.29219/fnr.v67.10258
Issue
Vol 67 (2023)
Section
Nordic Nutrition Recommendations
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