Folic acid supplementation

Merck has developed a “new” folate supplement that is much improved over the folic acid now used for both supplements and food fortification. I say “new” because this supplement, though brought to us through the magic of chemistry, is methylfolate, the same chemical structure as the compound that is found in foods. Folate in this form has been available in the US for several years now, but due to its the expense, a different form of folate is used in supplements and for food fortification.
A recent British Medical Journal article describes the type of folic acid commonly used:

The form of folate in supplements and in fortified foods is pteroylmonoglutamate (PGA), a form that does not occur in nature. It is both cheap and stable unlike most native forms of the vitamin. The body metabolises PGA into methylfolate, the normal form of the vitamin transported in plasma. However, research shows that this absorption and biotransformation process is saturated at doses in the region of 400 µg PGA or less. Thus at doses at or just below 400 µg PGA all this synthetic form of folate is converted into biologically active methylfolate during absorption. At higher doses synthetic PGA is also transported into the blood in a manner that is directly proportional to dose. This raises the possibility of a lifetime’s exposure to unmetabolised PGA where mandatory fortification is undertaken. Although such exposure may present no health risk at all, we cannot know this for certain.

Since PGA is the form of folic acid most commonly used in supplement form, and since many physicians prescribe doses in the 5 mg range (5000 micrograms: more than ten times the amount needed to give maximal blood concentrations), this adds to the dosage one gets through food fortification, from primarily breads and cereals.
When Dr. Lucock, the researcher writing the BMJ article, analyzed patients who were taking large doses of PGA for vascular problems, he found that a number of them had exceedingly high values, which “were mirrored by the corresponding red cell folate values” indicating truly high values and not a measurement error. Upon more sophisticated analysis, Dr. Lucock found

that only around half of the serum folate measured by routine haematological assay was methylfolate. The assumption was that the remainder was unmodified PGA, as only this and other partially oxidised folates do not fluoresce and thus are not directly measurable by high pressure liquid chromatography.

Dr. Lucock then states:

Nobody yet knows what, if any, the long term biological effect of mandatory fortification of grain products would be at a national level. In a recent report on the situation in the United States, more people than expected were subjected to the established tolerable upper limit of exposure to PGA.

I looked at the article in the Journal of Nutrition that was the reference citation to the statement about more people in the US than expected had elevated folic acid levels. The paper points out that most of the people falling into this category were those who both ate fortified foods and took folic acid supplements.
Since bread and cereal products are those fortified in the US at this time, I would be willing to bet that most people on low-carbohydrate diets do not have excess levels of unaltered PGA.
A well designed low-carb diet will contain plenty of green leafy vegetables and colorful fruits, all of which have large quantities of folate. It’s only when the diet shifts from all these healthful foods to mainly refined carbohydrates, that folate fortification is needed. And what better foods to fortify than those that the great hordes of the unwashed masses are adopting as their dietary staples.