There is some evidence that folate supplements in excess of 400 μg/day may impair zinc absorption. In addition, there are two potential problems that have to be considered when advocating either widespread use of folate supplements or enrichment of foods with folate for protection against neural tube defect and possibly cardiovascular disease and cancer.
● Folate supplements will mask the megaloblastic anemia of vitamin B12 deficiency, so that the pre-senting sign is irreversible nerve damage. This is especially a problem for older people, who may suffer impaired absorption of vitamin B12 as a result of atrophic gastritis. This problem might be over-come by adding vitamin B12 to foods as well as folate. Whereas gastric acid is essential for the release of vitamin B12 bound to dietary proteins, crystalline vitamin B12 used in food enrichment is free to bind to cobalophilin without the need for gastric acid.
●Antagonism between folic acid and the anticonvul-sants used in the treatment of epilepsy is part of their mechanism of action; about 2% of the population have (drug-controlled) epilepsy. Relatively large supplements of folic acid (in excess of 1000 μg/ day) may antagonize the beneficial effects of some anticonvulsants and may lead to an increase in the frequency of epileptic attacks. If enrichment of a food such as bread with folate is to provide 400 μg/ day to those who eat little bread, those who eat a relatively large amount may well have an intake in excess of 1000 μg/day. There is, however, no evi-dence of a significant problem in countries where enrichment of flour has been mandatory for some years.