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Do the benefits of folic acid fortification outweigh the risk of masking vitamin B12 deficiency?

BMJ 2018; 360 doi: (Published 01 March 2018) Cite this as: BMJ 2018;360:k724
  1. James L Mills, senior investigator1,
  2. Anne M Molloy, associate professor, emeritus2,
  3. Edward H Reynolds, former consultant neurologist3
  1. 1Epidemiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
  2. 2School of Medicine, Trinity College Dublin, Ireland
  3. 3Maudsley and King’s College Hospitals, London, UK
  1. Correspondence to: J L Mills jamesmills{at}, E H Reynolds reynolds{at}

Adding folate to cereals can prevent neural tube defects and other health problems, say James Mills and Anne Molloy, but Edward Reynolds is concerned that prolonged excessive folate risks harm unless vitamin B12 is also supplemented

Yes—James L Mills, Anne M Molloy

Worldwide we are preventing only about 10% of the neural tube defects that can be avoided by folate.1 The EU and some of the world’s largest countries have not adopted mandatory fortification, the only population strategy definitively shown to reduce the incidence of these devastating birth defects.1 Some have argued that fortification will benefit only a small number of children at the expense of an unproved risk to a much larger number of elderly people. But arguments focusing on this unresolved issue overlook another compelling reason for mandatory fortification.

Folate deficiency

Folate deficiency is a far more common problem than neural tube defects and has been almost eliminated by mandatory folic acid fortification in the US. Before mandatory fortification, the prevalences of low serum (<10 nmol/L) and red cell folate (<340 nmol/L) were 24% and 3.5%, respectively, in a representative sample of the US population. After fortification these figures were both ≤1%.2 This translates into millions of cases of folate deficiency corrected or averted. Not only does this avoid the morbidity caused by folate deficiency anaemia, it reduces medical costs for healthcare visits, laboratory testing, and treatment.

Folate deficiency is common in many parts of the world. Chinese3 and Indian4 studies report a high population rate of anaemia. Even in the UK, one large population study reported that about 10% of people aged 65-74 and 20% of those >75 years old were at high risk of folate deficiency.5 Fortification is an excellent way to overcome this problem because folic acid is considerably more bioavailable and stable …

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