Abstract

Folate is a generic descriptor used to describe a family of complex compounds structurally resembling folic acid, the synthetic or supplemental form of the vitamin. This B vitamin functions in many co-enzyme forms in mammalian systems mediating a variety of one-carbon transfer reactions. Because of the pivotal role of these reactions in DNA, RNA and amino acid biosynthesis and cellular division, requirements for folate are especially high during stages of the life-cycle where there is enhanced anabolic activity, e.g., during reproduction. There is ample evidence to suggest that sub-optimal folate nutrition in humans may be involved in the etiology of a variety of disorders including neural tube defects (NTDs), low infant birthweight, cancer and cardiovascular disease. The weight of this evidence in the case of NTDs was sufficiently compelling to prompt Canadian health authorities in 1993 to advise that women planning a pregnancy consume a folic acidcontaining supplement of 400 ug/day. Results from randomized controlled trials supported by a series of case control and cohort studies suggested that if all women consumed this level of folic acid during the periconceptional period, up to 70% of NTDs could be prevented. As the neural tube is completely closed by the 28 day after conception, often before many women realize they are pregnant, this strategy only works if a woman is planning a pregnancy or happens to be a regular folic acid supplement user. In response to feasibility issues with this recommendation as a stand-alone strategy, Canadian Health authorities mandated the addition of folic acid to white flour and pasta products labelled “enriched” at a level of 150 ug /100 g effective November 1998. Neural tube defects are the most common major congenital malformations of the central nervous system. They are a result of a disturbance of the embryonic process of neurulation. There are several different types of NTDs, however spina bifida (e.g., meningomyelocele and meningocele) and anencephaly comprise 90% of all cases. Prior to enhanced folic acid fortification, it was estimated that 1 out of every 1,000 live births in Canada or 300 births annually were affected by an NTD. Folate intakes of Canadian women of reproductive age were low and were frequently less than half that recommended to support their own optimal folate status – never mind increased intake to reduce the risk of an NTD-affected pregnancy. Our own data, as well as others, suggest that young women and those of low income had intakes of dietary folate often only 25% of that recommended. Surveillance data from the United States suggest that enhanced folic acid fortification of the food supply (initiated January 1, 1998) has doubled blood folate concentrations, albeit few subjects in these studies are women of reproductive age. It is also noteworthy that while the folic acid fortification intervention was intended to raise daily intakes by about 100 ug, there is good evidence that food is being fortified at twice this level. It is usual practice for food manufacturers to over-fortify in order to meet their minimum label claim for the duration of a product’s shelf life, though it comes as somewhat a surprise that the overage may be two-fold. This issue of the Canadian Journal of Public Health includes three papers that provide some of the first comprehensive data to evaluate the overall strategy used to increase folate intakes of women of reproductive age in Canada. Morin et al. report that while 70% of pregnant FrenchCanadian women in their study (n = 1,240) were aware of the preventive role of folic acid, only 25% consumed the recommended dose (400 ug) during the periconceptional period. Belief in the importance of taking supplements at the beginning of pregnancy, knowledge of food sources of folate and the role of folic acid in preventing NTDs, family income and pregnancy planning intensity were significant determinants of early consumption of vitamin supplements. Not unlike other health behaviours (regular exercise, smoking cessation), these data suggest that additional work needs to be done to facilitate the translation of maternal knowledge about folic acid and birth defects into action. In this issue, Ray et al. report on the rate of folate and vitamin B12 insufficiency since initiation of the enhanced folic acid fortification program in Canada. This group of investigators retrospectively analyzed serum folate, red blood cell (RBC) folate and vitamin B12 samples (n=8,884) measured by a private laboratory responsible for ~ 30% of these measures in Ontario. Consistent with previous reports from the U.S., these authors demonstrate that plasma and RBC concentrations have increased dramatically since the initiation of the 1998 folic acid fortification strategy in Canada. Serum folates have increased from 18.5 nmol/L to 27.1 nmol/L and RBC folate concentrations increased from 680.3 nmol/ L to 851.6 nmol/L. These increases may, in fact, be an underestimate as the maximum reporting limit for serum and RBC folate concentrations in these laboratories is 45 nmol/L and 1450 nmol/L, respectively. In our laboratory, we find RBC folate concentrations well above 1450 nmol/L among some women consuming prenatal supplements (800-1000 ug/day folic acid). As with the American data published to date, the target population (women of reproductive age) is underrepresented in the Ray et al. study. Nonetheless, these data provide strong evidence that addition of folic acid to the food supply in Canada is raising blood folate concentrations. Senior Associate Scientist and Director of Clinical Dietetics, The Hospital for Sick Children; Associate Professor, Department of Nutritional Sciences, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8

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