The nutritional enhancement of plant foods 203 of about 7.0HM/. Increasing the intake of folic acid beyond that level has no further effect. However, the bulk of the population have homocysteine levels in of 7.0uM/1. Folic acid is not the natural form of folate that is found in plants where natural folate consists of ten different polyglutamate complexes. Folic acid is, however the form of folate that is used in the fortification of food as it is more stable. It the bioavailability of folic acid. 31, natura is also found to be more bioavailable. Natural folates show only 50%o or less of current average of 200ug/day to 600ug/day3 This increased intake is also likely to have an important impact on the reduction of Neural Tube Defects(NTDs) Women with a low folate status(about 150ug/ red cell folate) have a 0.7%o risk of NTDs in their offspring, whereas supplementation with folic acid at doses of between 100 and 200 g/day resulted in red blood cell folate levels that have been associated with an optimal reduction in NTD incidence. Since average intakes of natural folates are about 100ug/day from the diet it would require at least 0Omg of natural folate to be consumed (preferably 600 mg/day) to ensure that he incidence of NTD in the population was kept to a minimum The fact that supplemental folic acid can achieve these same effects whilst being more stable and bioavailable would imply that there was little purpose in supplementing natural levels of folate. This ignores the intrinsic difference between the cellular metabolism of synthetic pro-vitamin folic acid compared to the natural folates The mucosa converts all of the natural forms of folate into 5-methylenetetrahydrofolate monoglutamate. This reaction also occurs when folic acid is consumed but the difference is that for folic acid the process can be saturated at around 300ug. Intakes in excess of this cause un-metabolised folic acid to enter the circulation 4 The control of how much natural folate is taken up and retained by cells is regulated by the enzyme methionine synthase which acts on 5-methyltetrahydrofolate to conjugate it into a polyglutamate which is then retained in the cell. Folic acid does not pass through the methion ine synthase pathway and can be conjugated directly, retained and metabolised. If folic acid is present in excess of the mucosal capacity to metabolise it can bring about dNA biosynthesis in vitamin B12-deficient cells in cases of pernicious anaemia via the DNA cycle. This causes a haematological response with the risk that the anaemic state is masked and the associated neuropathy is not avoided. Natural folates on the other hand will be poorly metabolised by vitamin BI2-deficient cells enabling the anaemia to be detected at an earlier stage. Another oncern that has been raised against increasing population levels of folate is that the increased capacity to cause DNA biosynthesis could promote tumour growth This would be expected to be more of a problem with folic acid than natural folates because of folic acid's less controlled uptake into cellsof about 7.0mM/l. Increasing the intake of folic acid beyond that level has no further effect. However, the bulk of the population have homocysteine levels in excess of 7.0mM/l. Folic acid is not the natural form of folate that is found in plants where natural folate consists of ten different polyglutamate complexes. Folic acid is, however, the form of folate that is used in the fortification of food as it is more stable. It is also found to be more bioavailable. Natural folates show only 50% or less of the bioavailability of folic acid.31, 32 There is good evidence that to achieve the ideal level of plasma homocysteine dietary levels of folate (as opposed to folic acid) would have to increase from the current average of 200mg/day to 600mg/day.33 This increased intake is also likely to have an important impact on the reduction of Neural Tube Defects (NTDs). Women with a low folate status (about 150mg/l red cell folate) have a 0.7% risk of NTDs in their offspring, whereas supplementation with folic acid at doses of between 100 and 200 g/day resulted in red blood cell folate levels that have been associated with an optimal reduction in NTD incidence. Since average intakes of natural folates are about 100mg/day from the diet it would require at least 500 mg of natural folate to be consumed (preferably 600 mg/day) to ensure that the incidence of NTD in the population was kept to a minimum. The fact that supplemental folic acid can achieve these same effects whilst being more stable and bioavailable would imply that there was little purpose in supplementing natural levels of folate. This ignores the intrinsic difference between the cellular metabolism of synthetic pro-vitamin folic acid compared to the natural folates. The mucosa converts all of the natural forms of folate into 5-methylenetetrahydrofolate monoglutamate. This reaction also occurs when folic acid is consumed but the difference is that for folic acid the process can be saturated at around 300mg. Intakes in excess of this cause un-metabolised folic acid to enter the circulation.34 The control of how much natural folate is taken up and retained by cells is regulated by the enzyme methionine synthase which acts on 5-methyltetrahydrofolate to conjugate it into a polyglutamate which is then retained in the cell. Folic acid does not pass through the methion￾ine synthase pathway and can be conjugated directly, retained and metabolised. If folic acid is present in excess of the mucosal capacity to metabolise it can bring about DNA biosynthesis in vitamin B12-deficient cells in cases of pernicious anaemia via the DNA cycle. This causes a haematological response with the risk that the anaemic state is masked and the associated neuropathy is not avoided. Natural folates on the other hand will be poorly metabolised by vitamin B12-deficient cells enabling the anaemia to be detected at an earlier stage. Another concern that has been raised against increasing population levels of folate is that the increased capacity to cause DNA biosynthesis could promote tumour growth. This would be expected to be more of a problem with folic acid than natural folates because of folic acid’s less controlled uptake into cells. The nutritional enhancement of plant foods 203