High Dietary Folate Supplementation Affects Gestational Development and Dietary Protein Utilization in Rats

Abstract

There is new evidence that good folate status may play a critical role in the prevention of neural tube defects and in the maintenance of adequate homocysteine levels, an amino acid recently identified as a risk factor for cardiovascular disease. This has led to different folate recommendations, all of them much higher than the present dietary recommendations. Folic acid is a water-soluble vitamin with a low potential toxicity. However, the possible consequences of long-term, high folate intakes are unknown. Therefore, the present study was undertaken to determine the effects of long-term, high dietary folate supplementation on gestational and nutritional markers in pregnant and virgin rats. Four groups of Wistar rats were classified on the basis of physiological status (virgin or pregnant) and the experimental diets administered (folic acid supplemented, 40 mg/kg diet; or control diet, 2 mg folic acid/kg diet). Rats were fed their respective diets for 3 wk. Two critical periods were used for metabolic balance studies (experimental d 1-5 and 17-21), which involved the determination of fat and protein digestibilities as well as metabolic protein utilization (MPU) and net protein utilization (NPU). Gestational development (number of live fetuses) was adequate in both diet groups regardless of folate supplementation. However, body weight and vertex-coccyx length in fetuses from supplemented dams were less than (P < 0.0001) in fetuses of control dams. Fat and nitrogen digestibilities were not affected by supplementation, but MPU and NPU coefficients were significantly lower (P < 0.05) in the folic acid-supplemented groups, irrespective of physiological status, compared to control rats. These new findings of macro-micronutrient interactions caused by high folate supplementation are discussed on the basis that the vitamin may act as a xenobiotic more than as a nutrient.

An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study

“…In rodents, a 20-fold enriched folate diet was associated with a smaller embryo and decreased newborn length and weight, but also with an increase in embryonic development at 10.5 days post coitum. 21,22 However, in these studies, synthetic FA and plasma folate were studied compared with long-term RBC folate in our study.…”

Micronutrient prenatal supplementation prevents the development of hypertension and vascular endothelial damage induced by intrauterine malnutrition

“…Control and restricted groups also received the same amount of vehicle by oral gavage, and no effects of this procedure were observed in these animals. The micronutrient concentrations were selected based on previous studies (Dashman et al 1973;Achón et al 1999;González-Correa et al 2006).…”

Concentrations of unmetabolized folic acid and primary folate forms in pregnant women at delivery and in umbilical cord blood

“…To our knowledge, no firm data are available to support the notion that folic acid in blood can cause harm. In a rat model, long-term supplementation with folic acid resulted in lower birth weights (13). However, these results cannot be extrapolated to humans because species differences in folic acid metabolism have recently been shown (14).…”