Consuming enough folate helps prevent neural tube defects

If you are pregnant or could become pregnant, the amount of folate in your blood is important to help prevent a neural tube defect (a serious birth defect of the brain or spine) in a developing baby.¹ You can increase the amount of folate in your blood to help prevent a neural tube defect by consuming folic acid in addition to food with folate from a varied diet. Folic acid can be found in some vitamins and in fortified foods labeled as “enriched.”

The amount of folate in your blood depends on how much folic acid you consume each day and the number of days that you consume folic acid.¹ To make sure you have enough folate in your blood to help prevent a neural tube defect

• Get the recommended 400 micrograms (mcg) of folic acid each day.
  • It can take several months to reach an amount of folate in your blood to help prevent neural tube defects.
  • You can get folic acid by taking a vitamin with folic acid in it, eating fortified foods, or a combination of the two.
  • You don’t need to consume more than 400 mcg of folic acid each day unless you have already had a baby or pregnancy affected by a neural tube defect.

How the MTHFR gene variant affects the amount of folate in your blood

In addition to the amount of folic acid consumed and the length of time it is consumed, your MTHFR genotype affects the amount of folate in your blood. The MTHFR protein affects how your body processes folate, which, in turn, affects the amount of folate in your blood.

When consuming the same amount of folic acid, people with the MTHFR 677 TT genotype have an average amount of folate in their blood that is only slightly lower (about 16% lower) than people with the MTHFR 677 CC genotype.² However, reseachers have shown that people with any of the MTHFR genotypes who consume 400 mcg of folic acid each day will increase (almost double) the amount of folate in their blood to an amount that is high enough to help prevent a neural tube defect in a developing baby.³ This means that your folic acid intake is more important than your MTHFR genotype for determining the amount of folate in your blood.

Research shows that the MTHFR C677T variant is related to a small increased chance of poor health outcomes^4-7 and birth defects.⁷ This shows the importance of consuming enough folate for optimal health and the possible role of folic acid in preventing other health disorders.^8-11 Research has also shown that neural tube defects are more common among people with the MTHFR 677 CT and TT genotypes, but these studies are generally conducted in countries without folic acid fortification.^12-15 This means that women in these studies are not getting folic acid in their diets from fortified foods. If you have the MTHFR 677 CT or TT genotype, consuming 400 mcg of folic acid each day almost doubles the amount of folate in your blood. This amount of folate in your blood is enough to help lower the chance of having a baby with a neural tube defect, no matter which MTHFR C677T genotype (CC, CT, or TT) you have.

References

1. Crider KS, Devine O, Hao L, et al. Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ. 2014;349:g4554.
2. Tsang BL, Devine OJ, Cordero AM, et al. Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies. Am J Clin Nutr. 2015;101(6):1286-1294.
3. Crider KS, Devine O, Qi YP, et al. Systematic review and Bayesian meta-analysis of the dose-response relationship between folic acid intake and changes in blood folate concentrations. Nutrients. 2019;11(1):E71.
4. Ge W, Jiao Y, Chang L. The association between MTHFR gene polymorphisms (C677T, A1298C) and oral squamous cell carcinoma: a systematic review and meta-analysis. PloS One. 2018;13(8):e0202959.
5. ElGendy K, Malcomson FC, Lara JG, Bradburn DM, Mathers JC. Effects of dietary interventions on DNA methylation in adult humans: systematic review and meta-analysis. BrJ Nutr. 2018;120(9):961-976.
6. Luo Z, Lu Z, Muhammad I, et al. Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis. Lipids Health Dis. 2018;17(1):191.
7. Zhang Y, He X, Xiong X, et al. The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes. Prenat Diagn. 2019;39(1):3-9.
8. Huo Y, Li J, Qin X, 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):1325-1335.
9. Stampfer M, Willett W. Folate supplements for stroke prevention: targeted trial trumps the rest. JAMA. 2015;313(13):1321-1322.
10. 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.
11. Gamble MV, Liu X, Slavkovich V, et al. Folic acid supplementation lowers blood arsenic. Am J Clin Nutr. 2007;86(4):1202-1209.
12. Yan L, Zhao L, Long Y, et al. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies. PloS One. 2012;7(10):e41689.
13. Crider KS, Zhu JH, Hao L, et al. MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation. Am J Clin Nutr. 2011;93(6):1365-1372.
14. Zhang T, Lou J, Zhong R, et al. Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature. PloS One. 2013;8(4):e59570.
15. Yadav U, Kumar P, Yadav SK, Mishra OP, Rai V. “Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis”. Metab Brain Dis. 2015;30(1):7-24.