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The risks of folic acid to the nervous system in vitamin B12 deficiency: rediscovered in the era of folic acid fortification policies
  1. Edward H Reynolds
  1. Department of Clinical Neurosciences, King’s College London, UK
  1. Correspondence to Dr. Edward H Reynolds; reynolds{at}

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In the late 1940s and the 1950s, the risks of precipitating or aggravating the neurological manifestations of vitamin B12 deficiency by folic acid were well documented.1 2 In the last 20 years, these risks have been misinterpreted or doubted by advocates of folic acid fortification policies who have maintained that the only issue is the risk of ‘masking’ of the anaemia of vitamin B12 deficiency by folic acid. Mandatory folic acid fortification of cereal grains has been implemented in about 80 countries with reduced neural tube defect (NTD) rates of between 20% and 60%, overall about one-third. The UK and Europe have held back for a variety of cautious reasons, including the risk to elderly subjects increasingly vulnerable to vitamin B12 deficiency.2 3 In the era of fortification policies, the risks to the nervous system are gradually being rediscovered.


Advocates of fortification have overlooked that inappropriate excess folic acid in pernicious anaemia (PA) can eventually lead to relapse of the anaemia, usually after temporary and sometimes suboptimal remission, as well as neurological deterioration. At 5 and 10 years of follow-up, relapse of the anaemia is as common as neurological relapse. In the latter study,1 only 3 of 36 patients remained well and all three had very low vitamin B …

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  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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