Clin Invest Med 1996; 19 (3): 202-203
Reprint requests to: Dr. David S. Rosenblatt, Division of Medical Genetics, McGill University, Room H5-63, 687 Pine Ave., Montreal QC H3A 1A1; fax 514 843-1712
Copyright 1996, Canadian Medical Association
Canada, or at least the Health Protection Branch of Health Canada, has not even encouraged women to supplement their diet with folic acid, as recommended by others, including the Canadian College of Medical Geneticists, the Society of Obstetricians and Gynaecologists of Canada, the US Centers for Disease Control and Prevention and the British Department of Health. Instead, it is assumed that women will make the appropriate decisions about folic acid intake after communicating with their physicians - in spite of the fact that about 50% of women do not know they are pregnant until it is too late for folic acid to have its protective effect.
The hesitation in fortifying food is related to concerns about the ability of folic acid to mask the anemia of vitamin B12 (cobalamin) deficiency. Indeed, an article[2] and editorial[3] published in this journal in 1994 advocated food fortification under conditions in which its effects can be monitored. We understand that plans are under way for a pilot study in Newfoundland, which is encouraging.
Several recent reviews have re-examined the early data on the effect of folic acid on the neurological findings in vitamin B12 deficiency.[4,5] It is clear that folic acid can mask pernicious anemia while allowing the neurological disease to progress. It is less clear that folic acid either exacerbates or precipitates the neuropathy.[5]
It is also clear that many patients with vitamin B12 deficiency can have neuropathy without anemia and with serum cobalamin levels that may be only mildly depressed. Other methods, such as the measurement of serum methylmalonic acid and homocysteine levels, must be used to make the correct diagnosis.
There is also strong evidence that the total serum or plasma homocysteine (tHcy) level is an independent risk factor for coronary artery disease, cerebrovascular disease and peripheral vascular disease6 and that folic acid effectively lowers tHcy levels. (See "Molecular genetic aspects of hyperhomocysteinemia and its relation to folic acid," by Rozen, on pages 171 to 178 of this issue.) Thus, fortification of cereal grain may actually benefit elderly patients as well as reduce the frequency of neural tube defects in infants.
Folic acid fortification of basic foods would be unjust if the prevention of neural tube defects was paid for in the currency of increased suffering of the elderly from delayed diagnosis and treatment of vitamin B12 deficiency. However, that price need not be exacted. The one tragic event, neural tube defects, could occur significantly less often as a result of folic acid fortification, whereas the other tragic event, neurological deterioration resulting from improperly timed treatment of vitamin B12 deficiency, could be averted by physicians being on the alert. So folic acid fortification of foods needs to be accompanied and balanced by methods of clinical alert and monitoring to detect any postfortification rise in morbidity and mortality due to vitamin B12 deficiency. Suitably designed messages to inform the public via the media should also accompany any fortification program.
How do we balance what we know with certainty against undemonstrated potential risks and provide the most benefit with the least harm? Current efforts to educate women of child-bearing age have been less than successful. Moreover, given the proportion of pregnancies that are unplanned, education alone can never be expected to carry the whole burden of preventing neural tube defects. It is time to move rapidly toward fortification, along with re-education of physicians about the clinical spectrum of vitamin B12 deficiency.