Nutritional enhancement versus food fortification

The importance of enhancing the levels of a natural protective constituent in plant foods is well illustrated in the case of the folates. There is a good chance that folate status even in affluent countries is not optimal. [25,26] The most important sources of folates in the diet are liver, products derived from yeast, eggs, green vegetables, legumes and certain fruits. Plant foods (vegetables, fruits and potatoes) are by far the single largest contributor to the overall folate intake of adults. [27,28,29] Some40%of the total folate intakeis from fruit andvegetable consumption in these countries even when the average consumption is not very high.

Folates have the effect of reducing the levels of plasma homocysteine which is a sensitive biomarker of folate status. A variety of studies have suggested that increased plasma homocysteine levels are a risk factor for cardiovascular disease and stroke. [30] Human studies have shown that if individuals consume a supplement of 100µg/day of folic acid their plasma homocysteine is reduced to a level of about 7.0µM/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 7.0µM/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 200µg/day to 600µg/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 150µg/1 red cell folate) have a 0.7% risk of NTDs in their offspring, whereas supplementation with folic acid at doses of between 100–200µg/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 about100µg/day from the diet it would require at least 500µg of natural folate to be consumed (preferably 600µg/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 300µg. Intakes in excess of this cause un-metabolised folic acid to enterthe circulation. [34] The control of how muchnaturalfolate 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. Conversely folic acid does not pass through the methionine synthase pathway and can be conjugated directly, retained and metabolised.

The ability of folic acid to bypass an important regulatory step is that excess cellular levels cause 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.