Low vitamin B-12 concentrations in patients without anemia: The effect of folic acid fortification of grain

James L. Mills, Isabelle Von Kohorn, Mary R. Conley, Jack A. Zeller, Christopher Cox, Robert E. Williamson, D. Robert Dufour

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations


Background: In some patients with vitamin B-12 deficiency mistakenly treated with folic acid, anemia resolved but neurologic complications became worse (masking). Fortification of enriched cereal grains with folic acid has raised concerns that people who consume large quantities of cereal grains, particularly the elderly, may be at increased risk of masking. It is unclear, however, what proportion of people with low vitamin B-12 concentrations do not have anemia and whether the proportion is increasing. Objective: We investigated whether fortification has increased the proportion of patients with low vitamin B-12 but without anemia. Design: We reviewed the laboratory results of every patient for whom a vitamin B-12 concentration was measured at the Veterans Affairs Medical Center in Washington, DC, between 1992 and 2000. Those with a low vitamin B-12 concentration (<258 pmol/L) had their hematocrits and mean cell volumes checked. The proportion without anemia was examined by year before, during, and after folic acid fortification began. Results: There were 1573 subjects with a low vitamin B-12 concentration. The proportion without anemia did not increase significantly from the prefortification period (39.2%) to the period of optional fortification (45.5%) and the postfortification period (37.6%). These findings did not change when the analysis was limited to patients aged > 60 y or when a more conservative definition of low vitamin B-12 (< 150 pmol/L) was used. Conclusions: Despite evidence that folic acid exposure has increased dramatically since food fortification began, this population showed no evidence of an increase in low vitamin B-12 concentrations without anemia. If confirmed, these results would indicate that food fortification has not caused a major increase in masking of vitamin B-12 deficiency.

Original languageEnglish (US)
Pages (from-to)1474-1477
Number of pages4
JournalAmerican Journal of Clinical Nutrition
Issue number6
StatePublished - Jun 2003
Externally publishedYes


  • Cobalamin
  • Folate
  • Folic acid
  • Masking of pernicious anemia
  • Pernicious anemia
  • Vitamin B-12
  • Vitamin B-12 deficiency

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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