Abstract: Neural tube defects (NTD) affect almost two in every 1000 pregnancies in Australia. Between 1980 and 1995, 14 human studies of varied design have collectively demonstrated very convincingly that increased intake of folate at the start of pregnany can reduce the incidence of NTDs by about 75%. The studies have been case-control and cohort epidemiological studies, and randomised and non-randomised controlled prevention trials. Meta-analysis diagrams in the paper illustrate the strength of the evidence. There is also suggestive evidence that folate can help to prevent some other foetal malformations, for example, cleft palate. There are three possible preventive approaches: nutrition education; folic acid supplements; and/or fortification of staple foods with folic acid. However, increased folate must be taken peri-conceptually to be effective and this presents practical difficulties. Some progress has been made with increasing awareness in Western Australia. Raising public and professional awareness, and raising it now, is a public health imperative. (Aust J Nutr Diet 1996;53(Suppl):S5-S8)

How folate functions inside the body.
Richard I. Christopherson.

Abstract: Folic acid is a vitamin, required to sustain the growth of cells. In the body it exists mainly in the reduced form, tetrahydrofolate. One-carbon units are attached at positions N5 or N10 on the folate molecule (or bridge between the two). Inside cells, folate is attached to a series of glutamate residues, i.e. it is 'poly-glutamated'. It can only enter or leave cells as N5 methyltetrahydrofolate, which carries only one glutamate residue. Polyglutamated folate with different one-carbon units (methyl, formyl, methylene, etc.) are one-carbon donors for important reactions; in the synthesis of purines and of thymidylate, precursors of DNA, and in the conversion of homocysteine to methionine (which also requires vitamin B12). In folate deficiency, plasma homocysteine increases and, because DNA cannot be synthesised, cells cannot divide. Some anticancer drugs, for example, methotrexate, act by inhibiting the enzyme dihydrofolate reductase that completes the reduction of folate to the active tetrahydro- form. Thus proliferation of rapidly dividing cells is blocked, and these are mostly cancer cells. (Aust J Nutr Diet 1996;53(Suppl):S8-S10).

Homocysteinaemia and cardiovascular risk: the relevance of folic acid supplementation.
David E.L.Wilcken.

Abstract: The inborn errors of metabolism producing marked homocysteine elevation are associated with precocious vascular disease and lowering of these levels reduces cardiovascular risk in these patients. About 20% of patients with premature vascular disease (coronary, ceberal or peripheral) have mild homocysteine elevation. Chronic renal failure is associated with increased risk of vascular disease and also with mild to moderate increases in circulating homocysteine. Folic acid supplementation normalises mild homocysteine elevation. It remains to be established whther or not this also reduces cardiovascular risk. (Aust J Nutr Diet 1996;53(Suppl):S11-S12)

Folate and cancer initiation. Will folate fortification help to prevent genetic events that could initiate cancer?
Michael Fenech.

Abstract: Folic acid plays an important role in the synthesis of nucleotides required for DNA synthesis and repair, as well as production of S-adenosyl methionine required for the maintenance methylation of CpG dinucleotides found in the regulatory regions of the genetic code. Under folate deficient conditions there is an increase in the rate of gene mutation and abnormal gene expression which enhances the risk for cancer development. In view of the fact that folate deficiency is one of the most common vitamin deficiencies in the Western world, and because folate deficit is correlated with a higher risk for cancer initiation, it is important to consider whether supplementation of staple foods with folic acid may benefit the prevention of cancer. It is not possible from current knowledge to provide a definite statement on this issue but the available evidence suggests that prevention of folate deficiency is likely to minimise the rate of chromosome damage, gene mutation and abnormal gene expression. (Aust J Nutr Diet 1996;53(Suppl):S13-S17).

Prospects for folic acid fortification and its monitoring.
A. Stewart Truswell.

Abstract: Evidence of the role of folic acid in preventing neural tube defects (NTDs) has been accumulating for as long as 40 years. Impressive prevention trials were first reported 20 years ago but treatment and control groups were not randomised. Since publication of the Medical Research Council recurrence prevention trial in 1991 and the Hungarian occurrence prevention trial in 1992, there is a scientific consensus that a moderately increased intake of folate will greatly reduce the incidence of NTDs and possibly other malformations. The Australian National Health and Medical Research Council has made pronouncements on what to do about folate and NTD in 1992, 1993 and again in 1994. In the 1994 statement, voluntary fortification of all cereal foods, fruit and vegetable juices and yeast extracts (with 50% RDI per standard serving) was recommended and this was permitted in the new Standard for Vitamins and Minerals (Standard A9) by the National Food Authority (NFA) in mid-1995. Some monitoring will be needed: such as, Australian statistics on terminations of pregnancy for NTDs and births with NTD; number of products fortified with folic acid and their market share; and blood folate values in different subgroups. We are currently measuring the change of serum folate in groups of healthy young women for different additions of pure folic acid in the nutritional range to produce a graph relating average serum folate to folic acid intake. Some specific relaxation of the NFA's ban on health claims may be needed before we shall see fortification of enough foods. (Aust J Nutr Diet 1996;53(Suppl):S17-S23).

Prospects for measuring folates in Australian foods.
Peter Scheelings.

Abstract: There has been an increasing number of studies on the role of folates in food and more recent debate on the value of fortification programs of cereal-based foods with folic acid in particular for reducing the incidence of neural tube defects. Strategically it is important to have access to accurate base-line levels of natural folate levels in foods prior to designing and implementing a food fortification program. The measurement of folate in foods is not a trivial task and, from the data reported in the literature, very method-dependent. A number of international collaborative studies are in progress to establish the reliability and comparability of analytical methods. This paper reports on the current status of the analytical methodology and the prospect for measuring folate levels in Australian foods. (Aust J Nutr Diet 1996;53(Suppl):S23-S28).

Vitamin B12 neuropathies: the role of folate supplementation.
John D. Pollard.

Abstract: Vitamin B12 deficiency is most commonly due to pernicious anaemia. Neurological symptoms are commonly the presenting features of vitamin B12 deficiency and may occur in the absence of anaemia. In patients with peripheral neuropathy and/or evidence of a spinal cord syndrome characterised by posterior and lateral column impairment, deficiency of vitamin B12 should be considered, whether or not anaemia is present. There has been concern that fortification of foods with folic acid may delay the diagnosis of vitamin B12 deficiency since it may correct the anaemia of cobalamin deficiency but not the neurological features. This concern is not founded on substantial evidence since the diagnosis should be made on the basis of the neurological features and serum B12 levels. If the serum B12 level is borderline, antibodies to intrinsic factor, measurement of the metabolites, methylmalonic acid and homocysteine should be sought;serum gastrin levels may be helpful and hypersegmented polymorphonuclear leukocytes and megaloblasts may be detected even in the absence of anaemia and leukocytosis. (Aust J Nutr Diet 1996;53(Suppl):S28-S30).

Effects of processing and preparation of foods on folate content.
Wendy Morgan.

Abstract: Although Australian foods have not been analysed for folate, it appears (using overseas food composition data) that vegetables, fruits and juices, breads, crackers and processed meats are major contributors of folate to the Australian diet. Some folate is usually lost when wheat is milled and when vegetables are cooked. Retention varies widely, depending on the preparation and processing techniques employed. When a food manufacturer considers nutrient fortification of any products, the questions to be considered are: do consumers want it; is it safe; is it feasible; will it affect taste or appearance; is the cost, including labelling and quality control, acceptable; and, how can the company communicate the health advantage of this extra input to consumers? If folic acid is added to cereal products, its retention during storage is high but losses during production (e.g. during extrusion) can be considerable. (Aust J Nutr Diet 1996;53(Suppl):S31-S35).