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BMJ. 2007 July 28; 335(7612): 171.
PMCID: PMC1934491
Folic Acid Fortification

Clarify the neurological risks

Edward Reynolds, consultant neurologist

The head to head between Wald and Oakley and Hubner et al mainly focused on possible risks of cancer associated with folic acid fortification.1 2 However, there are also neurological risks from fortification.3

It is unwise of Wald and Oakley to dismiss as unscientific so many reports between 1945 and 1950 of the harmful effects of folic acid in the presence of vitamin B12 deficiency, and then to select only the observations that suit their own case.1 They are incorrect to state only that folic acid allowed the neurological consequences of vitamin B12 deficiency to progress. The earlier authors reported that both blood and nervous system could improve and relapse but to different degrees and at different rates.3 This is supported by the recent study of 1459 elderly subjects in the United States after fortification showing that in the presence of vitamin B12 deficiency high serum folate concentration was associated with anaemia, macrocytosis, and cognitive impairment, whereas with normal vitamin B12 status high serum folate concentration was associated with apparent protection from cognitive impairment.4

Wald and Oakley's extreme view that there is no credible evidence of any adverse health effects from folic acid supplementation or fortification is unsustainable. The protective effect of folic acid fortification on neural tube defects is real but modest (20-43% reduction), and even after fortification young women will still need additional supplementation. Folates and vitamin B12 are important for nervous system function, including methylation and epigenetic mechanisms,3 and it would be wise to clarify the benefits and risks at all ages, including elderly people, before exposing everyone to excessive folic acid long term.


Competing interests: ER has engaged in studies of folic acid and vitamin B12 in relation to the nervous system during the past 40 years.


1. Wald NJ, Oakley GP. Should folic acid fortification be mandatory? Yes. BMJ 2007;334:1252 (16 June.) [PMC free article] [PubMed]
2. Hubner RA, Hulston RD, Muir KR. Should folic acid fortification be mandatory? No. BMJ 2007;334:1253 (16 June.) [PMC free article] [PubMed]
3. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol 2006;5:949-60. [PubMed]
4. Morris MS, Jacques PF, Rosenberg IH, Selhub J. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr 2007;85:193-200. [PMC free article] [PubMed]

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