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LETTERS TO THE EDITOR |
Barts & London Queen Mary School of Medicine & Dentistry
Wolfson Institute of Preventive Medicine
Charterhouse Square
London, EC1M 6BQ
United Kingdom
E-mail: n.j.wald{at}qmul.ac.uk
Royal Free Hospital
London
United Kingdom
Dear Sir:
In May 2002, the Food Standards Agency in the United Kingdom decided against endorsing the recommendation of the Committee on Medical Aspects of Food and Nutrition Policy that universal folic acid fortification of flour be introduced to prevent neural tube defects, but the agency also indicated a willingness to reconsider the decision in the light of further evidence. In coming to its decision, the Food Standards Agency was influenced by a recently completed study claiming that vitamin B-12 deficiency among the elderly is more common than had been previously suspected. The investigators linked this claim to the theoretical concern that folic acid fortification might delay the diagnosis of vitamin B-12 neuropathy or even precipitate its onset.
The report of that study, recently published in the Journal (1), does not distinguish serum vitamin B-12 concentrations that are sufficiently low to cause clinical disease (eg, symptomatic anemia or neuropathy) from those that may be low relative to the average but are not low enough to cause clinical disease. Somewhat arbitrary cutoffs were used, so that, for example, a serum vitamin B-12 concentration <150 pmol/L was regarded as "low," and a person with that concentration was considered to be "at high risk of vitamin B-12 deficiency." Serum methylmalonic acid is also used as a test for vitamin B-12 deficiency. As the authors acknowledged, and as their data showed, elevated serum methylmalonic acid may be associated with decreased renal function as well as with vitamin B-12 deficiency.
Clarke et al (1) did not quantify or define high risk. Few clinicians in the United Kingdom report having seen a case of irreversible vitamin B-12 neuropathy in the past decade, which indicates that, even in the vitamin B-12-"deficient" group, the likelihood of vitamin B-12 neuropathy (which results only from very severe vitamin B-12 deficiency) is negligible. Anemia was defined in men as a hemoglobin concentration <130 g/L, and, on this basis, the prevalence of anemia in men with "normal" vitamin B-12 concentrations was as high as 25%. No evidence was given that, in any of the subjects tested, vitamin B-12 deficiency was responsible for the anemia, and the prevalence of symptoms attributable to vitamin B-12 deficiency was not considered.
Unfortunately, the report does not provide information that would be helpful in determining the prevalence of illness in a population that is due to vitamin B-12 deficiency. If there were a problem, the solution would not be population screening for vitamin B-12 deficiency among the elderly, because that would be expensive and unwieldy, would create anxiety, and is unlikely to be specific. The use of the cutoffs reported by Clarke et al would result in 10% of people aged 65-74 y and 20% of those aged >75 y being under regular medical supervision and taking vitamin B-12 supplements in sufficiently high doses to treat neuropathy, in an attempt to prevent a problem (irreversible vitamin B-12 neuropathy) that may not exist. There may, however, be a case for fortifying flour with vitamin B-12 as well as with folate if it could be shown that this step would improve the nutritional status and health (eg, would reduce cardiovascular disease) of the elderly.
The report by Clarke et al provides no new evidence to suggest any concern about the folic acid fortification of flour (as introduced in North America in 1998) to prevent neural tube defects. New evidence shows that this fortification has not led to the "masking" of vitamin B-12 deficiency by correcting the anemia due to the lack of vitamin B-12 (2). It provides no information as to whether relatively low serum vitamin B-12 concentrations in the community represent a medical problem, and the proposal to introduce nationwide screening for vitamin B-12 (and folate) deficiency is unwarranted.
REFERENCES
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