Folic acid as ultimate in disease prevention:Beware of vitamin B12 deficiency

BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7442.769 (Published 25 March 2004) Cite this as: BMJ 2004;328:769
  1. Stephen Malnick, director (stevash{at}tredline.co.il),
  2. Sorel Goland, senior cardiologist (stevash{at}tredline.co.il)
  1. Kaplan Medical Centre, Rehovot 76100, Israel
  2. department of internal medicine C, heart institute, Kaplan Medical Centre, Rehovot 76100, Israel

    EDITOR—In response to the review by Lucock on folic acid supplementation,1 we have a word of caution about possible concomitant vitamin B12 deficiency, which may also cause raised concentrations of homocysteine.

    Vitamin B12 deficiency can be subtle, manifesting only as an increase in concentrations of homocysteine and methylmalonic acid in blood and urine, with concentrations of vitamin B12 at the lower limit of normal.2 Vitamin B12 concentration varies in different populations. The US NHANES III survey found a mean serum B12 value of 518 pg/ml, and 3% of the population had a concentration of less than 200 pg/ml.3 In Israel we reported a vitamin B12 deficiency of 30% in 130 serial patients undergoing coronary angiography.4 Health maintenance organisations in Israel responded to the widespread deficiency of vitamin B12 by lowering the normal values of their laboratories.

    Since folic acid supplementation may be harmful in the presence of undiagnosed vitamin B12 deficiency, we recommend that vitamin B12 concentrations be determined before administration of folic acid. Another approach may be to use multivitamin tablets. The use of a “folate” supplement consisting of 1 mg folic acid, 400 µg vitamin B12, and 10 mg pyridoxine both reduces the concentrations of homocysteine and decreases the rate of restenosis after angioplasty.5 The cost effectiveness of these approaches may differ from country to country, depending on the prevalence of vitamin B12 deficiency.


    • Competing interests None declared


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