Folic acid, folate and homocysteine: human intervention studies.

Folate is the generic name for all derivatives of the B a controlled dietary intervention study that a diet high in vitamin with the biological activity of pteroylmonogdietary folate from vegetables and citrus fruit (560 mg/d) lutamic acid. Folic acid is the fully oxidised monoglutadecreased plasma total homocysteine concentrations and mate form of the vitamin, whereas the other naturally improved the folate status [8]. The bioefficacy of the occurring forms are referred to as folates. Folic acid dietary folate from vegetables and citrus fruit compared to supplementation around conception decreases the risk of folic acid was 60% in this study. The bioavailability was having offspring with a neural-tube defect [1,2]. Therefore, 78% when change in plasma folate was used as the Governments in several countries advise women planning determinant of bioavailability and 98% when change in red to become pregnant to consume additional folic acid or blood cell folate was used. However, women should still folate to prevent neural tube defects. Women who have not be advised to take additional folic acid to reduce the risk of previously given birth to a child with a neural-tube defect having a child with a neural-tube defect. Firstly, the aboveare advised to take 400 to 500 mg additional folic acid or mentioned problems with the intake of dietary folate still folate each day from at least 4 weeks before pregnancy exist. Secondly, lowering homocysteine may decrease the until at least the eighth week of pregnancy. Although lower risk of having a child with a neural-tube defect, but it is doses may be effective, no randomised trials have been not certain. carried out to test whether this is indeed the case. The Most studies that have investigated the effect of folic underlying mechanism of the preventive effect of folic acid acid supplementation on plasma total homocysteine conis unclear. centration have focused on persons with plasma total Some Governments specifically advise women to take homocysteine concentrations above the normal range. additional synthetic folic acid, because the effectiveness of Refsum et al. concluded from a review of the literature that natural food folate might be lower. Folate in food occurs in the relationship between plasma total homocysteine level many different forms. It is unclear whether high intakes of and cardiovascular disease is continuous without an apparfolate from food can also prevent neural-tube defects. ent threshold [9]. Therefore, the effect of intake of low Furthermore, it is difficult for women to reach a daily doses of folic acid and of dietary folate on total plasma intake of 400 mg of dietary folate. The average intake is homocysteine concentrations in subjects with plasma total only about 250 mg per day [3]. On the other hand, not all homocysteine concentrations in the normal range is of women in the target group do take folic acid tablets around interest. conception [4,5]. In a placebo-controlled study with 144 healthy women, Women who previously gave birth to a child with a we provided subjects with a normal homocysteine conneural-tube defect were shown to have elevated plasma centration, with either 500 mg of folic acid each day, 500 total homocysteine concentrations [6,7]. Thus, a decrease mg of folic acid every other day, or a placebo tablet daily in homocysteine concentrations may result in a lower risk for 4 weeks [10]. Both folic acid intervention strategies for having a child with a neural-tube defect. We showed in significantly improved plasma folate and red blood cell folate concentrations. Intervention with 500 mg of folic acid each day decreased plasma total homocysteine con*Present address: Wageningen Centre for Food Sciences, Wageningen, The Netherlands. centrations by 22% and intervention with 500 mg of folic