Folic Acid supplementation: long term safety is not an excuse for inaction

I share Lucock´s (1) concerns related to the fact that "the form of folate in supplements and in fortified foods is pteroylmonoglutamate (PGA), a form that does not occur in nature". The author is rightly critical of increasing tendency among clinicians to give supraphysiological doses of PGA. 

In this regard, Ie would like to note that in Slovakia the single PGA is available only in 10 mg capsules. This dose is more than 20 times that needed to give maximal concentrations of the normal form of vitamin in plasma. Moreover, physicians are regularly prescribing up to 30mg/day of PGA according to the Prescription Drug Information. 

The major concern, as Lucock point out, is that "we do not know the long-term biological effects of exposure to unmodified synthetic folate". In fact, there is evidence that neurological complications in patients with vitamin B12 deficiency (2) are not the only possible risk of folate supplementation. For example, animal and some clinical studies have suggested that folate supplementation in higher doses may increase cancer risk and accelerate tumor progression (3). 

Because the long-term effects of PGA are not known, the best way of folate supplementation is through natural food. Those who are healthy and live healthy life (including eating natural food rich in folate) do not need to take folate in its synthetic supplement form. 

In certain situations, however, as is the case for some aged individuals and alcoholics, supplements containing recommended amounts of PGA may be warranted. (4,5) Nevertheless, the countries that adopted a policy of folate fortification of foods should provide monitoring of the benefits and possible harms of such fortification. 


1. Lucock M. Is folic acid the ultimate functional food component for disease prevention? BMJ 2004;328:211-4. 

2. Reynolds EH. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry 2002;72:567-71. 

3. Kim YI. Role of folate in colon cancer development and progression. J Nutr. 2003;133:3731S-3739S. 

4. Bailey LB. Folate, methyl-related nutrients, alcohol, and the MTHFR 677C-->T polymorphism affect cancer risk: intake recommendations. J Nutr 2003;133:3748S-3753S. 

5. Wharton B, Booth I. Fortification of flour with folic acid. BMJ 2001;323:1198-9.