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Review
. 2018 Jan 31;39:2.
doi: 10.1186/s40985-018-0079-6. eCollection 2018.

Public Health Failure in the Prevention of Neural Tube Defects: Time to Abandon the Tolerable Upper Intake Level of Folate

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Free PMC article
Review

Public Health Failure in the Prevention of Neural Tube Defects: Time to Abandon the Tolerable Upper Intake Level of Folate

Nicholas J Wald et al. Public Health Rev. .
Free PMC article

Abstract

The neural tube defects anencephaly and spina bifida are two of the most common serious congenital malformations. Most cases can be prevented by consuming sufficient folic acid immediately before pregnancy and in early pregnancy. Fortification of flour with folic acid to prevent these defects has been implemented in 81 countries without public objection or indication of harm. An obstacle to the wider adoption of fortification arises from the creation of a "tolerable upper intake level" for folate (which includes natural food folate as well as synthetic folic acid), and which has been set at 1 mg/day, thereby proscribing higher folate intakes. Increasing the intake of folic acid in a population will necessarily increase the number of people with a folate intake greater than 1 mg per day, and this concern is obstructing folic acid fortification. This paper shows that the scientific basis for setting any upper limit, let alone one at 1 mg/day, is flawed. An upper intake level is therefore unnecessary and should be removed, thus allaying unjustified concerns about folic acid fortification. As a result, the full global opportunity to prevent two serious fatal or disabling disorders can and should be realized.

Keywords: Anencephaly; Folate; Folic acid; Neural tube defects; Spina bifida; Tolerable upper intake level.

Conflict of interest statement

N/AConsent given.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Results of MRC randomised trial of folic acid in the prevention of neural tube defects [1]
Fig. 2
Fig. 2
Percentage of pregnant women who took folic acid supplements before pregnancy according to maternal age (1999–2012). Percentages adjusted for year screened, maternal weight, ethnicity, previous NTD pregnancy, previous Down’s syndrome pregnancy, IVF, diabetes, smoking, Down’s syndrome screening test, and region of England. [4]
Fig. 3
Fig. 3
Percentage of pregnant women who took folic acid supplements before pregnancy according to ethnicity among women who provided this information (1999–2012). Percentages adjusted for year screened, maternal age, maternal weight, previous NTD pregnancy, previous Down’s syndrome pregnancy, IVF, diabetes, smoking, Down’s syndrome screening test, and region of England [4]
Fig. 4
Fig. 4
Neuropathy in patients with B12 deficient anaemia erroneously given folic acid according to dose [15]
Fig. 5
Fig. 5
Distributions of folate intake with and without mandatory folic acid (FA) fortification (mean intake from mandatory fortification 0.2 mg/day) with (b) and without (a) adjustment for folic acid bioavailability. The percentage of people with a folate intake > 1 mg/day is shown in the boxes with and without mandatory fortification. Distributions include background intake from natural food folate and voluntary folic acid fortification. [Data on the usual intake of natural food folate and voluntary folic acid fortification in the UK from the National Diet and Nutrition Survey (NDNS 2008/9–2013/14) [20]. Almost identical distributions are obtained using the usual intake of folate in the USA from the Continuing Survey of Food Intakes by Individuals [21]. Intake from mandatory folic acid fortification assumed to be independent of natural food folate and folic acid from voluntary fortification but with the same population variance]
Fig. 6
Fig. 6
Distributions of folic acid (FA) intake with voluntary and mandatory fortification with and without 0.4 mg/day FA supplement (data on the usual intake of natural food folate and voluntary folic acid fortification in the UK from the National Diet and Nutrition Survey (NDNS 2008/9–2013/14). [20]. Almost identical distributions are obtained using the usual intake of folate in the USA from the Continuing Survey of Food Intakes by Individuals (CSFII) [21]. Intake from mandatory folic acid fortification assumed to be independent of natural food folate and folic acid from voluntary fortification but with the same population variance. Folic acid supplement assumed to be taken every day)

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References

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