Folates are a group of vitamins that belong to the B vitamin group. Folic acid is a synthetic form of natural folates, but both folic acid and folates share the same vitamin activity. However, metabolism and absorption of folic acid and folates can differ somewhat, and this may have certain health implications. Folic acid is added to certain foods such as breakfast cereals and bread, and this is largely because of concerns about folate deficiencies in the general population. In particular, some evidence suggests that folate deficiencies during pregnancy may lead to birth defects. Of course, if a high quality diet is eaten, there may be no need to eat fortified foods as plant foods contain high amounts of folates, particularly green leafy vegetables. However, it is clear most choose not to eat a high quality diet and so the authorities in various countries have decided to add synthetic vitamins to certain foods to correct population wide deficiencies of folates. Whether this is a good or bad thing is open to argument.
The main problem with folic acid is that high intakes bypass normal folate metabolism and take alternative routes. This may have certain health implications. The normal circulating metabolite of folate absorption is 5-methyltetrahydrofolate, however large intakes of folic acid result in both 5-methyltetrahydrofolate and folic acid in the blood. This unmetabolised folic acid in the blood may produce health problems, as it can cause problems in the diagnosis of a cobalamin deficient anaemia, may pose a risk to a growing foetus and may pose other health problems, particularly if the folic acid can interfere with normal folate metabolism. For example, folates may be required for the normal control of cancer cells, and there is some concern that unmetabolised folic acid may interfere with this process increasing the risk of cancer. Therefore the ability of unmetabolised folic acid to be present in the blood in high amounts may have certain health implications, although the exact nature of these effect is not fully understood.
Green leafy vegetables contain high levels of natural folates. However synthetic folic acid is often added to food and is present in vitamin supplements. High intakes of folic acid may increase blood levels of unmetabolised folic acid, and this may have some negative health effects. Research in this area is ongoing and it is unclear as to what those health effects may be. Current recommendations are to obtain folate from natural sources in the diet, mainly from green leafy vegetables. If supplements of folic acid are used levels should be kept low enough not to exceed the 200 μg threshold per meal.
Studies have investigated the threshold required to cause the accumulation of folic acid in the blood. For example, in one study, researchers administered folic acid fortified ready to eat cereal and bread to subject for 5 days and measured the changes to their blood folic acid levels. The subjects also consumed their normal diet alongside the fortified cereals. At an intake of folic acid above 266 μg per meal, unmetabolised folic acid would appear in the blood of the subjects. When subjects were then administered folic acid in isotonic saline, milk or white bread, unmetabolised folic acid would appear in the blood at a threshold of 200 μg per meal. Based on these findings the researchers estimated that a typical Western diet consumed by someone living in the United States of America would be unlikely to provide enough folic acid to increase blood levels of unmetabolised folic acid. This is based on the assumption that the folic acid would be spread throughout the day in divided amounts. However, supplements may exceed this threshold.
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