Mandatory Fortification Of Flour Research Articles

Modeling Demonstrates That Folic Acid Fortification of Whole-Wheat Flour Could Reduce the Prevalence of Folate Inadequacy in Canadian Whole-Wheat Consumers ,

Background: Mandatory folic acid fortification of white-wheat flour and selected other grain products has reduced the prevalence of neural tube defects in Canada; however, the fortification of whole-wheat flour is not permitted.Objective: The objective of this study was to model the impact of adding folic acid to whole-wheat flour on the folate intake distribution of Canadians.Methods: Twenty-four-hour dietary recall and supplement intake data (n = 35,107) collected in the 2004 Canadian Community Health Survey 2.2 were used to calculate the prevalence of folate inadequacy (POFI) and the proportion of folic acid intakes above the Tolerable Upper Intake Level (UL). In model 1, folic acid was added to whole-wheat flour–containing foods in amounts comparable to those that are mandatory for white-wheat flour–containing foods. In model 2, a 50% overage of folic acid fortification was considered. Models 3 and 4 included assessment of folate intake distributions in adult whole-wheat consumers with or without a fortification overage. SIDE (Software for Intake Distribution Estimation; Department of Statistics and Center for Agricultural and Rural Development, Iowa State University) was used to estimate usual folate intakes.Results: Mean folate intakes increased by ∼5% in all sex and age groups when whole-wheat foods were fortified (models 1 and 2; P < 0.0001). Folic acid fortification of whole-wheat flour–containing foods did not change the POFI or percentage of intakes above the UL in the general population, whether in supplement users or nonusers. Among whole-wheat consumers, the POFI was reduced by 10 percentage points after fortification of whole-wheat flour–containing foods (95% CIs did not overlap). The percentage of whole-wheat consumers with intakes above the UL did not change.Conclusion: Although folic acid fortification of whole-wheat flour–containing foods is unlikely to change the POFI or proportion of folic acid intakes above the UL in the general Canadian population, this fortification strategy may reduce the POFI in adult whole-wheat consumers.

Anemia e nível de hemoglobina em gestantes de Cuiabá, Mato Grosso, Brasil, antes e após a fortificação compulsória de farinhas com ferro e ácido fólico, 2003-2006

OBJETIVO: avaliar a prevalencia de anemia e niveis de hemoglobina de gestantes, antes e apos a fortificacao compulsoria de farinhas com ferro, e os fatores associados. METODOS: foram comparadas duas amostras transversais independentes de gestantes de Cuiaba-MT, Brasil (2003 a 2006), alocadas em dois grupos - nao fortificado (n=414) e fortificado (n=539); realizou-se analise de regressao logistica e linear, com nivel de significância de 5%. RESULTADOS: nao houve diferenca entre os grupos nao fortificado e fortificado, na prevalencia de anemia (22,2% e 27,8%, respectivamente; p=0,051) e no nivel de hemoglobina (ambos com media de 11,7g/dL; p=0,058); maior prevalencia de anemia e menor media de hemoglobina associaram-se com maior numero de gestacoes anteriores, maior idade gestacional e baixo peso no inicio da gestacao. CONCLUSOES: nao se encontrou efeito significativo da fortificacao compulsoria de farinhas, embora a avaliacao da gestacao indique alta prevalencia de anemia e variaveis importantes a serem consideradas.

Primary prevention of neural tube defects in Brazil: insights into anencephaly.

Anencephaly is a lethal malformation characterized by the absence of the skull and both cerebral hemispheres caused by deficiency of closure of the neural tube at rostral level between 23 and 25 days of gestation (Bronberg et al. 2011). The occurrence of anencephaly and other neural tube defects (NTDs) such as meningocele and spina bifida are between 50 and 70 % preventable by periconceptional folic acid (FA) administration to reduce their prevalence across populations (Blencowe et al. 2010). The percentage decrease is dependent upon the background prevalence. The percentage of NTDs that are preventable by periconceptional folic acid intake is dependent on the prevalence of folate-sensitive NTDs in the population (Robbins et al. 2006; Bronberg et al. 2011). To prevent anemia due to iron deficiency and the occurrence of NTD, the Brazilian Ministry of Health approved the resolution RDC No. 344 on December 13, 2002, whereby the flour fortification of wheat and maize was regulated. This resolution determined that as of June 2004, wheat and corn flours be supplemented with at least 4.2 mg iron and 150 mcg of FA/100 g flour (ANVISA 2002). As in many South American countries, there are only two exceptions to penalized abortion in Brazil: in case of rape or to save the woman’s life. The Brazilian Criminal Code does not include fetal malformations as a cause of penalized abortion. This limitation was partially overcome in 2004, when the Brazilian Supreme Court of Justice authorized abortion in cases of anencephalic fetuses (Diniz 2007). Termination of pregnancy (TOP) with an anencephalic baby was made legal in 2012, without need of a special judicial authorization (Carvalho 2011). Until 2012, TOP had been legal in Brazil in cases of anencephaly only after special authorization from a judge. A survey performed with Brazilian obstetricians showed that 37 % of women with a pregnancy of anencephalic fetus had successfully obtained authorization for legal abortion (Diniz et al. 2009). About ten South American countries, in most of which abortion for congenital malformations is not authorized by law, primary prevention of anencephaly and other NTDs is managed through mandatory fortification of flour with FA (PAHO 2003). In some of these countries, fortification has proven to be an effective strategy for the primary prevention of anencephaly and NTDs. In particular, Argentina (Bronberg et al. 2011) and Chile (Cortes et al. 2012) have reduced the number of deaths by anencephaly by about 50 % in the post-fortification period compared to the pre-fortification stage. There are dissimilar records in Brazil in terms of fortification results according to NTDs, the type of data used (infant deaths or born alive), and level of spatial and temporal coverage these results are based on (Orioli et al. 2011; Pacheco et al. 2009; Fujimori et al. 2013; Schuler-Faccini et al. 2014). For its lethality, since 99 % of those born with anencephaly die within the first month of life and because the phenotype is well identified, even by non-specialists, anencephaly is a malformation whose epidemiological behavior can be analyzed with some confidence and provide an accurate and precise picture of the effect of flour fortification with FA and other preventive measures. Given the socioeconomic, geographical, ecological, and cultural diversity of Brazil, it is estimated that spatial and temporal variations of infant deaths from this NTD may be present. In this paper, the temporal variation and spatial distribution at different levels of the state organization in Brazil, infant and fetal deaths by anencephaly were analyzed in relation to the different phases that occurred in the process of fortification with FA.

Analysis of the Family Life Surveys in Indonesia: The Contribution of Wheat Flour Fortification to Reducing Anemia

Mandatory fortification of wheat flour with electrolytic iron, zinc, thiamine, riboflavin, and folic acid became effective in Indonesia in 2002. There have been no longitudinal evaluations of the effectiveness of wheat flour fortification on reducing anemia. This study estimated the contribution of wheat flour fortification to the change in anemia prevalence from the period before to after the introduction of mandatory fortification. The Indonesia Family Life Survey is a longitudinal study that followed over 30,000 Indonesians from 1993 to 2008. Data from 5,828 non‐pregnant women of child‐bearing age with hemoglobin measurements in 1997, 2000, and 2007 were analyzed. Anemia prevalence was calculated, adjusting for smoking status and altitude. Logistic regression was used to predict the effect of confounders on anemia status. Anemia prevalence significantly decreased (p&lt;0.0001) from the pre‐fortification period during 1997‐2000 (34.0%) to the post‐fortification period in 2007 (25.2%). The main variable of interest, whether a household purchased flour‐containing foods, was not significantly associated with anemia status. Wheat flour fortification does not appear to have significantly contributed to the reduction in anemia prevalence among women of child‐bearing age in Indonesia. It is recommended that the fortification iron source be changed from electrolytic iron to a more bioavailable form and that fortification iron, zinc and folic acid levels be increased. Funding: FFI, MI, Emory, SEAMEO‐RECFON.

Low folate levels are associated with reduced risk of colorectal cancer in a population with low folate status.

A diet rich in folate is associated with a reduced colorectal cancer risk, whereas the role of circulating levels is less clear. The aim of this study was to relate prediagnostic plasma folate, vitamin B12, and homocysteine concentrations to the risk of colorectal cancer. This was a prospective case-control study of 331 cases and 662 matched controls nested within the population-based Northern Sweden Health and Disease Study. Median follow-up time from recruitment to diagnosis was 10.8 years. Plasma folate concentrations were positively related to colorectal cancer risk; multivariate odds ratios were 1.62 [95% confidence intervals (CI), 1.08-2.42] and 1.42 (95% CI, 0.94-2.21) for the middle and highest versus lowest tertile, respectively. In subjects with follow-up <10.8 years, a statistically significant doubled risk was observed for the middle and highest versus lowest tertile, whereas findings for longer follow-up times were null. A positive risk relationship was also observed for tumor stage III-IV but not I-II. Plasma vitamin B12 concentrations were inversely associated with rectal cancer risk. Homocysteine was not significantly related to colorectal cancer risk. In this population-based, nested case-control study, low plasma folate concentrations were associated with a reduced colorectal cancer risk. This protective role was mainly observed in subjects with higher tumor stage or shorter follow-up time between recruitment and diagnosis. Low circulating folate status may protect against colorectal cancer or suppress progression of preneoplastic or neoplastic lesions. These findings may have relevance for the ongoing debate about mandatory folic acid fortification of flour.

An evaluation of the effectiveness of the flour iron fortification programme in Brazil.

The present communication reports a strategy to calculate the intake of Fe based on data available for folic acid and evaluate the programme of flour fortification in Brazil. Cross-sectional study conducted in Brazil during 2008 and 2009. A 2d dietary record of individuals was used. The usual intake of folic acid by sex and age group was estimated using the National Cancer Institute method. The quantity of folic acid and Fe established by mandatory food fortification in Brazil was used, and based on that quantity we calculated the amount of flour consumed and the intake of Fe from fortification and Fe from food. Then, the absorption of each nutrient was calculated. Brazilian households (n 16,764). Individuals (men and women, n 34,003, aged 10 to 60+ years) from a Brazilian nationwide survey. Mean intake and absorption of Fe from fortification (electrolytic Fe) was low in men and women. The impact from the consumption of fortified products is small in relation to Fe intake in Brazil. The strategy proposed to estimate Fe intake from the fortification programme indicates that the amount of flour intake observed in Brazil does not justify the current ranges of mandatory flour fortification and the form of Fe that is mainly used (electrolytic Fe).

Folic Acid Fortification and Women’s Folate Levels in Selected Communities in Brazil - A First Look

Several countries have implemented mandatory folic acid fortification of wheat flour and selected grain products to increase the folate intake of reproductive-aged women. Brazil implemented a folic acid fortification program in 2004. No previous studies have examined folate differences among Brazilian women following the mandate. We evaluate differences in serum and red blood cell (RBC) folate concentrations between two samples of women of childbearing age from selective communities in Brazil, one tested before (N = 116) and the other after the mandate (N = 240). We compared the baseline folate levels of women enrolled in a prevention study shortly before the fortification mandate was implemented, to baseline levels of women from the same communities enrolled in the same study shortly after fortification began. The participants were women enrolled in a folate supplementation clinical trial, at a hospital specializing in treating craniofacial anomalies in the city of Bauru from January 29, 2004 to April 27, 2005. We only compared baseline folate levels before the women received oral cleft prevention program (OCPP) folic acid supplements. Women enrolled after the fortification mandate had higher means of serum folate (20.3 versus 11.2 nmol/L; p < 0.001) and RBC folate (368.3 versus 177.6 nmol/L; p < 0.001) than women enrolled before the mandate. Differences in folate levels between the two groups remained after adjusting for several co-variables. The results suggest that serum and RBC folate levels among women of childbearing age increased after implementing the folic acid fortification mandate in Brazil.

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Reduction of anaemia.

Reduction of anaemia.

Lessons Learned from National Food Fortification Projects: Experiences from Morocco, Uzbekistan, and Vietnam

Fortification of staple foods has been repeatedly recommended as an effective approach to reduce micronutrient deficiencies. With the increased number of fortification projects globally, there is a need to share practical lessons learned relating to their implementation and responses to project-related and external challenges. To document the achievements, challenges, lessons learned, and management responses associated with national fortification projects in Morocco, Uzbekistan, and Vietnam. Independent end-of-project evaluations conducted for each project served as the primary data source and contain the history of and project activities undertaken for, each fortification project. Other sources, including national policy documents, project reports from the Global Alliance for Improved Nutrition (GAIN) and other stakeholders, industry assessments, and peer-reviewed articles, were used to document the current responses to challenges and future project plans. All projects had key achievements related to the development of fortification standards and the procurement of equipment for participating industry partners. Mandatory fortification of wheat flour was a key success in Morocco and Uzbekistan. Ensuring the quality of fortified foods was a common challenge experienced across the projects, as were shifts in consumption patterns and market structures. Adjustments were made to the projects' design to address the challenges faced. National fortification projects are dynamic and must be continually modified in response to specific performance issues and broader shifts in market structure and consumption patterns.

Baseline investigations of folate status in Aboriginal and non‐Aboriginal West Australians prior to the introduction of mandatory fortification

In September 2009, Australia implemented mandatory folic acid fortification of wheat flour for bread-making to reduce the incidence of neural tube defects. Our study aimed to establish baseline folate status data in Aboriginal and non-Aboriginal Western Australians. Patients who presented at a health service or collection centre for blood tests were invited to participate. One hundred and ninety-one Aboriginals and 159 non-Aboriginals were recruited between April 2008 and September 2009. Participants completed a five-minute questionnaire and had blood taken for red blood cell (RBC) folate and serum vitamin B12. Data were analysed using SPSS (version 17.0.2, SPSS Inc., Chicago, IL, USA). Ten per cent (95% confidence intervals (CI): 5, 19) of the Aboriginal women participants and 26% (95% CI: 16, 40) of men had RBC folate concentrations below 250 ng/mL, the cut-off associated with folate deficiency. None of the non-Aboriginal women (95% CI: 0, 4) and 4% of the non-Aboriginal men (95% CI: 2, 12) had RBC folate concentrations below 250 ng/mL. All participants were vitamin B12 replete. None of the 96 Aboriginal and 8% of non-Aboriginal women aged 16-44 reported consumption of supplements with a daily intake of >400 μg folic acid during the previous week. This study established a baseline of RBC folate, folate consumption and supplement use in Aboriginal and non-Aboriginal groups. We identified 10% of Aboriginal women and none of non-Aboriginal women participants with low folate concentrations. The higher prevalence of folate deficiency in Aboriginal participants suggests they are more likely to benefit from a universal program of folate fortification.

Vitamins for the First 1000 Days: Preparing for Life

Vitamins are essential nutrients for many body functions and particularly important during growth. Adequate supply in pregnancy and in early infancy is therefore crucial, but there is still a lack of knowledge about the needed amounts of vitamins of children older than six months and also during pregnancy. Recommendations for intake levels are generally derived by extrapolation from data for infants based in turn on the contents in breast milk and those for adults. A vitamin of particular importance in pregnancy is folic acid due to its role in the development of the brain and nerve system and the prevention of fetal neural tube defects (NTD). Mandatory fortification of flour and certain other grain products in many countries has been associated with a reduction in NTD incidence. However, other deficiencies or suboptimal status of B vitamins, especially B6 and B12 have been repeatedly reported in pregnant women also in high-income countries. Vitamin A is one of the three most critical micronutrients globally and pregnant women and young children are especially vulnerable to deficiencies. Night blindness, anemia, and immunodeficiency are major consequences of inadequate supply in these populations. Much attention has recently been accorded vitamin D that is also critical in pregnant women and young children for instance because of its involvement in bone mineralization but also its more recently discovered immune-modulating function that is thought to prevent development of autoimmune diseases like diabetes mellitus type I. A healthy balanced diet provides the best basis for optimal pregnancy outcome, lactation performance, and complementary feeding. However, supplements or fortified foods may be needed to cover the high requirements especially of critical vitamins such as vitamin D and folic acid and to correct unfavorable dietary patterns in women or to adapt foods to the needs of young children.

Lack of folate improvement in high risk indigenous Australian adults over an average of 6.5 years: a cohort study.

Socioeconomically vulnerable groups in developed countries suffer excess chronic disease due in large part to an energy dense but nutrient poor diet. Low folate can be a marker of poor dietary quality and is also affected by smoking and chronic alcohol intake, all of which cluster in groups with a low socioeconomic position. A 4.5 to 9 year follow-up study of 567 indigenous adults from remote communities in far north Queensland, Australia, from 1998 to 2007 was conducted. Analysis of the effects of demographic factors, smoking, risky alcohol drinking, fruit and vegetable intake and waist circumference on changes in red cell folate (RCF) status was conducted. Prevalence of low red cell folate doubled in the cohort from a high baseline over this seven year period: 36.9% deficient in 2007, 15.9% at baseline (p<0.001). Smoking was associated with lower folate levels. People with a normal RCF were less likely to be smokers, and were more likely to have a greater number of serves of vegetables (RR 1.06, 95% CI 1.02-1.10) than those who were deficient at follow-up. The introduction of voluntary folate fortification since 1995 does not appear to have impacted on the already poor folate status of this cohort of adults. The increased prevalence of low folate has occurred despite improvements in the food supply, indicating the need for nutrition promotion, and subsidies for healthy food in remote communities. The impact of mandatory folate fortification of flour since 2009 should be assessed in this high risk population.

Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program

In 2006 the Food Safety Authority of Ireland recommended mandatory folic acid fortification of flour for the prevention of neural tube defects in addition to the existing extensive voluntary folic acid fortification culture in place there. This recommendation is now suspended until further scientific evidence surrounding safety becomes available. The safety issues include concerns about the masking of vitamin B-12 deficiency and potential cancer acceleration, both of which may be of concern for the elderly population. The aim of this study was to measure the basal (fasted) concentrations of unmetabolized folic acid in the plasma of an elderly population group exposed to this liberal voluntary fortification of foodstuffs in Ireland. We invited participants aged 60-86 y from the Lifeways Cross-Generation Cohort Study to participate in this project. After providing informed consent, the participants were invited to provide fasting blood samples and to complete a standard food-frequency questionnaire and a questionnaire on recent and habitual intakes of folic acid. Samples were assayed for total plasma folate, red blood cell folate, homocysteine, and unmetabolized folic acid. A total of 137 subjects with a mean age of 67.4 y were studied. Unmetabolized folic acid was detected in 94.1% of the cohort with a mean concentration of 0.39 nmol/L (range: 0.07-1.59 nmol/L), accounting for 1.3% of total plasma folate. These results indicate unmetabolized folic acid in plasma in most of this elderly Irish cohort, even after an overnight fast. These results should be considered carefully by those legislating in this area.

Appeal to the European Food Safety Authority

About 4500 neural tube defects (NTD) occur every year in the European Union. Children with NTD will suffer from a lifelong disability often with inability to walk, hydrocephalus, learning problems, urinary infections and genital dysfunction. Up to two-thirds of these tragic cases can be prevented by folic acid supplementation. USA and Canada implemented mandatory folic acid fortification of wheat flour and corn in 1998. A number of other countries followed the North American rules including Australia, most states in South America and many countries in the Middle East and Africa. In China and India, it is voluntary. EU is an exception, although the UK is considering fortification. I feel particularly ashamed of my own country Sweden, where food is not even voluntarily fortified with folic acid. Thus, many children could be saved from being severely disabled, and several more foetuses would not be aborted owing to the detection of NTD by ultrasound. The cleft palate could also, to some extent, be prevented. In this issue of the Acta Paediatrica, Margaretha Jägerstad, professor emerita of food sciences, reviews the argument in favour of and against folic acid fortification. She reports that the daily folate intake among women is lower than the recommended levels. By fortification, most women will reach the recommended intake of folate (about 400 μg/day). With these levels there is no increased risk for cancer, which has been the strongest argument against fortification in the EU countries. Actually, it decreases the cancer risk, as the risk for cancer seems to be related in U-shaped fashion to folate concentrations. Only if a man eats more than five loaves of bread made of fortified flour every day, he may reach levels of folic acid that have been demonstrated to increase the risk of cancer in rats. The European Food Safety Authority (EFSA) is still hesitant to recommend fortification with folic acid and requires more investigations. However, neither EFSA nor the global World Cancer review present data on increased cancer risk at physiological folate intake. Therefore, EU should act to implement folic acid fortification as NTD prophylaxis as soon as possible. I am convinced that the EU Commission would act promptly if a preventable error was detected in the Airbus plane or European cars, which would cause thousands of deaths and/or severe handicaps every year.

Prospective study of methylenetetrahydrofolate reductase (MTHFR) variant C677T and risk of all-cause and cardiovascular disease mortality among 6000 US adults

The association between blood homocysteine concentration and the risk of cardiovascular disease (CVD) remains controversial, but few studies have examined the association between MTHFR C677T (a proxy for high homocysteine concentration) and death from CVD. The objective was to examine associations of MTHFR C677T, a proxy for high homocysteine concentrations, with CVD mortality and with all-cause mortality in a national representative prospective cohort of the US adult population before the introduction of mandatory folic acid fortification of flour. We used Mendelian randomization to examine the association of MTHFR C677T with cause-specific mortality in 5925 participants by accessing the NHANES III (1991-1994) Linked Mortality File (through 2006). A comparison of homozygotes at baseline showed that individuals with a TT genotype had a 2.2-μmol/L higher homocysteine and a 1.4-ng/mL lower folate concentration, respectively, than did those with a CC genotype. The TT genotype frequency varied from 1.2% (95% CI: 0.7, 2.0) in non-Hispanic blacks and 11.6% (95% CI: 9.6, 14.0) in non-Hispanic whites to 19.4% (95% CI: 16.7, 22.3) in Mexican Americans. After adjustment for ethnic group and other CVD risk factors, the MTHFR C677T TT genotype was associated with significantly lower CVD mortality (HR: 0.69; 95% CI: 0.50, 0. 95) but had no significant effect on all-cause mortality (HR: 0.79; 95% CI: 0.59, 1.05). After stratification by period of follow-up, the inverse association of MTHFR with CVD mortality was significant only in the period after introduction of mandatory folic acid fortification. The inverse association of MTHFR with CVD mortality was unexpected and highlights the need for caution in interpretation of Mendelian randomization studies, which, like other observational studies, can be influenced by chance, bias, or confounding.

Estimates of Total Dietary Folic Acid Intake in the Australian Population Following Mandatory Folic Acid Fortification of Bread

Mandatory folic acid fortification of wheat flour for making bread was implemented in Australia in September 2009, to improve the dietary folate status of women of child-bearing age, and help reduce the incidence of neural tube defects in the population. This paper presents estimates of folic acid intake in the target population and other subgroups of the Australian population following implementation of the mandatory folic acid fortification standard. In June/July 2010 one hundred samples from seven bread categories were purchased from around the country and individually analysed for the amount of folic acid they contained. A modification to the triple enzyme microbiological method was used to measure folic acid in the individual bread samples. The folic acid analytical values together with national food consumption data were used to generate estimates of the population's folic acid intake from fortified foods. Food Standards Australia New Zealand's (FSANZ) custom-built dietary modelling program (DIAMOND) was used for the estimates. The mean amount of folic acid found in white bread was 200 μg/100 g which demonstrated that folic-acid-fortified wheat flour was used to bake the bread. The intake estimates indicated an increase in mean folic acid intake of 159 μg per day for the target group. Other sub-groups of the population also showed increases in estimated mean daily intake of folic acid.

Small-scale milling and the feasibility of mandatory fortification of sorghum and maize flour in Botswana

In Botswana, as in many developing countries, food fortification is a potential strategy for addressing the malnutrition of low income groups. This article examines the potential costs of mandatory fortification of sorghum and maize flour for firms in Botswana. The results indicate that unit average fortification costs in pula per metric ton of flour range from 183 to 271, 118 to 170 and 103 to 149 (US$1 = P6.4 in 2007), respectively, for a typical small, medium and large firm. It is argued that the imposition of mandatory fortification may be feasible for large and perhaps some medium firms. However, small and (some) medium firms, are likely to collapse and exit the industry as a result of such action. A potentially realistic and sustainable option for small firms would be to consolidate so as to increase their scale of operation and avoid absolute collapse. However, public funding may be required to support such consolidation.

P1-340 Folate status and folic acid intake 6 years following mandatory fortification of flour in Brazil: a population-based study in SÃo paulo

IntroductionTo prevent neural tube defects (NTD) folic acid fortification of wheat and corn flour has been mandatory in Brazil since 2004. The purpose of this study was to examine the...

Efficacy of Flour Fortification with Folic Acid in Women of Childbearing Age in Iran

Background: Flour fortification with folic acid is one of the main strategies for improving folate status in women of childbearing age. No interventional trial on the efficacy of folic acid fortification has been conducted so far in Iran. Objectives: To study the effects of flour fortification with folic acid on any reduction in neural tube defects (NTDs) and folate status of women of childbearing age. Methods: In a longitudinal hospital-based study, 13,361 postpartum women were studied after admission for childbirth before and after fortification. In addition, two cross-sectional surveys were conducted before (2006) and after flour fortification (2008). The cluster sampling method was used and 580 women, 15–49 years old, were studied as a representative sample of Golestan province in the north of Iran. Fasting blood samples were collected to measure serum vitamin B₁₂, folate and plasma homocysteine. Sociodemographic data, health characteristics and dietary intake were determined. Results: The mean daily intakes of folate from natural food before and after flour fortification were 198.3 and 200.8 µg/day, respectively. The total folate intake increased significantly from 198.3 to 413.7 µg/day after fortification (p < 0.001). Folate intake increased by an average of 226 µg/day from fortified bread. The mean serum folate level increased from 13.6 to 18.1 nmol/l; folate deficiency decreased from 14.3 to 2.3% (p < 0.001). The incidence rate of NTDs declined by 31% (p < 0.01) in the post-fortification period (2.19 per 1,000 births; December 2007 to December 2008) compared to the pre-fortification period (3.16 per 1,000 births; September 2006 to July 2007). Conclusions: Implementation of mandatory flour fortification with folic acid can lead to a significant increase in serum folate and a significant decrease in NTDs.