High-dose folic acid supplementation in rats: effects on gestation and themethionine cycle

There is new evidence that a good folate status may play a critical role in the prevention of neural-tube defects and in lowering elevated homocystein e concentrations. This adequate folate status may be achieved through folic acid dietary supplementation. Folate is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term high-d ose folic acid supplementation are unknown, especially those related to the methionine cycle, where folate participates as a substrate. With the aim o f evaluating such possible effects, four groups of Wistar rats were classif ied on the basis of physiological status (virgin v. pregnant) and the exper imental diet administered (folic-acid-supplemented, 40 mg/kg diet v. contro l, 2 mg folic acid/kg diet). Animals were fed on the diets for 3 weeks. Res ults showed that gestation outcome was adequate in both groups regardless o f the dietary supplementation. However, there were reductions (P < 0.001) i n body weight and vertex-coccyx length in fetuses from supplemented dams v. control animals. Folic acid administration also induced a higher (P < 0.01 ) S-adenosylmethionine : S-adenosylhomocysteine value due to increased S-ad enosylmethionine synthesis (P < 0.01). However, hepatic DNA methylation and serum methionine concentrations remained unchanged. Serum homocysteine lev els were reduced in supplemented dams (P < 0.05). Finally, pregnancy caused lower serum folate, vitamin B-6 and vitamin B-12 levels (P < 0.05). Folic acid administration prevented the effect of pregnancy and raised folate lev els in dams, but did not change levels of vitamins B-12 and B-6. These new findings are discussed on the basis of potential benefits and risks of diet ary folic acid supplementation.