Fortification of bakery and corn masa-based foods in Mexico and dietary intake of folic acid and folate in Mexican national survey data.

BACKGROUND: In Mexico, wheat and corn flour fortification with folic acid (FA) was implemented in 2001 and mandated in 2008, but without direct enforcement. Current Mexican nutrient-content tables do not account for FA contained in bakery bread and corn masa-based foods, which are dietary staples in Mexico. OBJECTIVE: The objective of this study was to examine the impact of FA fortification of dietary staples on the proportion of the population consuming below the Estimated Average Requirement (EAR) for folate or above the Tolerable Upper Intake Level (UL) for FA. METHODS: We measured FA and folate content in dietary staples (bakery bread and tortillas) using microbial assays and MS, and we recalculated FA intake from 24-h recall dietary intake data collected in the 2012 Mexican National Health and Nutrition Survey (Encuesta Nacional de Salud y Nutrición) utilizing estimates from our food measurements, using nutrient concentrations from tortillas to approximate nutrient content of other corn masa-derived foods. The revised FA intake estimates were used to examine population-level intake of FA and dietary folate equivalent (DFE) accounting for geographic differences in FA content with statistical models. RESULTS: FA content in dietary staples was variable, whereas use of FA-fortified flour in corn masa tortillas increased with population size in place of residence. Accounting for dietary staples' FA fortification increased population estimates for FA and DFE intake, resulting in a lower proportion with intake below the EAR and a higher proportion with intake above the UL. Despite accounting for FA-fortified staple foods, 9-33% of women of childbearing age still have intake below the EAR, whereas up to 12% of younger children have intake above the UL. CONCLUSIONS: Unregulated FA fortification of dietary staples leads to unpredictable total folate intake without adequately impacting the intended target. Our findings suggest that monitoring, evaluation, and enforcement of mandatory fortification policies are needed. Without these, alternate strategies may be needed in order to reach women of childbearing age while avoiding overexposing children.

Validation of a food frequency questionnaire for retrospective estimation of diet during the first 2 years of life.

This study aims to validate a Food Frequency Questionnaire (FFQ), specifically designed to retrospectively estimate dietary intake and supplement consumption during the first 2 years of life in children from resource poor households in semi-rural Mexico. The FFQ querying about diet during the first 2 years of life was administered to mothers of children (N = 84), who participated in a prospective study 3-5 years earlier, in which complementary feeding practice questionnaires and 24-h recall (24hrR) were collected at several time points during the first 2 years of life to evaluate dietary and vitamin supplement intake. The resulting FFQ data were compared to intake data collected during the original study using Spearman correlations, deattenuated correlations and Wilcoxon signed-rank tests. Total energy intake, as estimated by the retrospective and original instruments, did not differ in the second year (Yr2); correlations between the measures were significant (r = 0.40, p < 0.001). The 24hrR and FFQ-Yr2 were significantly correlated for dietary intake of vitamins B6, B12 (p < 0.001) and folate (p < 0.01); however, after including vitamin supplement intake, the two dietary instruments were correlated only for vitamins A and B12 (p < 0.05). The FFQ provides a reasonable estimate of a child's dietary intake of energy and key micronutrients during the second year of life, and permits accurate ranking of intake 3-5 years after birth.

Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake.

BACKGROUND: The incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring. METHODS: The authors used a case-control study design to examine the association between retinoblastoma risk and maternal variations in the folate-metabolizing genes methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution at nucleotide 677 [MTHFR677C→T]; reference single nucleotide polymorphism rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron 1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with newly diagnosed unilateral retinoblastoma were enrolled in an institutional review board-approved study along with a control group of 97 mothers who had healthy children. Mothers were interviewed regarding perinatal characteristics, including use of prenatal vitamin supplements, and gave peripheral blood samples, which were used for polymerase chain reaction-based genotyping of rs1801133 and rs70991108. RESULTS: The risk of having a child with unilateral retinoblastoma was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95% confidence interval, 1.89-7.55; P = .0002), even after controlling for the child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32-5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of having a child with retinoblastoma. CONCLUSIONS: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Prenatal ingestion of synthetic folic acid supplements may be associated with increased risk for early childhood carcinogenesis in a genetically susceptible subset of the population.

Validation of a novel method for retrospectively estimating nutrient intake during pregnancy using a semi-quantitative food frequency questionnaire.

Case control studies evaluating the relationship between dietary intake of specific nutrients and risk of congenital, neonatal or early childhood disease require the ability to rank relative maternal dietary intake during pregnancy. Such studies are limited by the lack of validated instruments for assessing gestational dietary intake several years post-partum. This study aims to validate a semi-quantitative interview-administered food frequency questionnaire (FFQ) for retrospectively estimating nutrient intake at two critical time points during pregnancy. The FFQ was administered to women (N = 84), who 4-6 years earlier had participated in a prospective study to evaluate dietary intake during pregnancy. The FFQ queried participants about intake during the previous month (FFQ-month). This was then used as a reference point to estimate consumption by trimester (FFQ-pregnancy). The resulting data were compared to data collected during the original study from two 24-h recalls (24 h-original) using Spearman correlation and Wilcoxon sign-rank-test. Total energy intake as estimated by the retrospective and original instruments did not differ and was only weakly correlated in the trimesters (1st and 3rd) as a whole (r = 0.18-32), though more strongly correlated when restricted to the first half of the 1st trimester (r = 0.32) and later half of the 3rd trimester (r = 0.87). After energy adjustment, correlation between the 24hR-original and FFQ-pregnancy in the 3rd trimester were r = 0.25 (P < 0.05) for dietary intake of vitamin A, and r = 0.26 (P < 0.05) for folate, and r = 0.23-0.77 (P < 0.005) for folate, and vitamins A, B6 and B12 in the 1st and 3rd trimester after including vitamin supplement intake. The FFQ-pregnancy provides a consistent estimate of maternal intake of key micronutrients during pregnancy and permits accurate ranking of intake 4-6 years post-partum.

Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers.

BACKGROUND: Elevated benzo(a)pyrene [B(a)P]-DNA adducts have been associated with 3-fold increased risk of lung cancer in current smokers. We assessed the chemopreventive effects of antioxidant supplementation using B(a)P-DNA adducts in leukocytes as an intermediate cancer risk marker. METHODS: Subjects were randomized to a double-blinded placebo-controlled clinical trial of antioxidant vitamin supplementation [500 mg vitamin C and 400 IU vitamin E (dl-alpha-tocopherol) daily] or placebo. Smokers with > or =10 cigarettes per day and serum cotinine > or =25 ng/mL were eligible for the study. B(a)P-DNA adduct level was the outcome. The randomization was stratified by gender and cigarettes per day (< or =20 or >20). Smoking habits and blood samples were collected every 3 months during the 15-month treatment period. Samples were analyzed for B(a)P-DNA adducts (high-performance liquid chromatography), plasma cotinine, vitamin levels, and GSTM1 genotype. The intent-to-treat model adjusted for B(a)P-DNA and cotinine at randomization. RESULTS: Overall and among men, there was no effect of treatment on B(a)P-DNA adduct levels. Among treated women, B(a)P-DNA adducts decreased by 31% compared with women on placebo (P = 0.03). Among treated women with the GSTM1 genotype, there was a 43% decrease in adducts (P = 0.04). CONCLUSION: Our primary hypothesis that the mean level of smoking-related B(a)P-DNA adducts would be lower in all subjects in the vitamin treatment group compared with all placebo-treated subjects was not substantiated. However, oursecondary gender-specific analysis found a significant reduction in B(a)P-DNA adducts in women with vitamin treatment, suggesting that antioxidant supplementation maymitigate some of the procarcinogenic effects of exposuretoB(a)P. The effect in GSTM1-null women suggeststhat certain subgroups may derive more benefit fromsupplementation. Although the results of this trial showthe potential chemopreventive role of antioxidants, thebest way for smokers to reduce their cancer risk remains smoking cessation.