In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 micro g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was approximately 1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 micro g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected.

In recent years there has been growing interest in the vitamins folic acid and vitamin B12 because of the realization that the status of these vitamins in populations is less than adequate, and that such inadequacy may be linked to adverse public health outcomes. This concern has prompted the United States, Canada, and other countries to fortify grain products with folic acid, while additional countries are considering doing so in the near future. This presentation provides a new approach which relies on the combination of the concentrations in blood of vitamins and their respective functional indicators to establish cutoff points for assessing folate and vitamin B12 status in populations. The premise is based on the fact that the relationship between plasma vitamin concentrations and their respective functional indicators is inverse and biphasic, with a steep slope at low concentrations of the vitamin and a more moderate slope at higher plasma vitamin concentrations. We propose that the intersection of these two slopes be used as a guideline for assessing the status of these vitamins and the adequacy of fortification programs. The cutoff would be 10 nmol/L for serum folate and 340 nmol/L for red blood cell folate, based on lowest plasma homocysteine. For serum vitamin B12, the cutoff would be 150 pmol/L based on lowest methylmalonic acid and 300 pmol/L based on lowest homocysteine.

Background The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated concentrations after fortification and the possibility of adverse effects. Objective We assessed the effect of folic acid fortification on circulating concentrations of folic acid and 5-methyltetrahydrofolate in the Framingham Offspring Cohort. Design This is a cross-sectional study that used plasma samples from fasting subjects before and after fortification. Samples were measured for folate distribution with the use of an affinity-HPLC method with electrochemical detection. Results Among nonsupplement users, the median concentration of folic acid in plasma increased from 0.25 to 0.50 nmol/L (P < 0.001) after fortification, and among supplement users the median increased from 0.54 to 0.68 nmol/L (P = 0.001). Among nonsupplement users, the prevalence of high circulating folic acid (≥85th percentile) increased from 9.4% to 19.1% (P = 0.002) after fortification. Among supplement users, the prevalence of high circulating folic acid increased from 15.9% to 24.3% (P = 0.02). Folic acid intake and total plasma folate were positively and significantly related to high circulating folic acid after adjustment for potential confounding factors (P for trend < 0.001). Conclusions Folic acid fortification has resulted in increased exposure to circulating folic acid. The biochemical and physiologic consequences of this are unknown, but these findings highlight the need to understand the effects of chronic exposure to circulating folic acid.

Dihydrofolate reductase (DHFR) catalyzes the reduction of folic acid to tetrahydrofolate (THF). A 19-bp noncoding deletion allele maps to intron 1, beginning 60 bases from the splice donor site, and has been implicated in neural tube defects and cancer, presumably by influencing folate metabolism. The functional impact of this polymorphism has not yet been demonstrated. The objective of this research was to determine the effects of the DHFR mutation with respect to folate status and assess influence of folic acid intake on these relations. The relationship between DHFR genotype and plasma concentrations of circulating folic acid, total folate, total homocysteine, and concentrations of RBC folate was determined in 1215 subjects from the Framingham Offspring Study. There was a significant interaction between DHFR genotype and folic acid intake with respect to the prevalence of high circulating unmetabolized folic acid (defined as >85th percentile). Folic acid intake of >or=500 microg/d increased the prevalence of high circulating unmetabolized folic acid in subjects with the deletion (del/del genotype (47.0%) compared with the wild type (WT)/del (21.4%) and wild type (WT)/WT genotypes (24.4%) (P for interaction = 0.03). Interaction between the DHFR polymorphism and folic acid intake was also seen with respect to RBC folate (P for interaction = 0.01). When folic acid intake was <250 microg/d, the del/del genotype was associated with significantly lower RBC folate (732.3 nmol/L) compared with the WT/WT genotype (844.4 nmol/L). Our results suggest the del/del polymorphism in DHFR is a functional polymorphism, because it limits assimilation of folic acid into cellular folate stores at high and low folic acid intakes.

Background Despite the high rates of overweight and obesity among rural children, there have been limited interventions reported to improve the diet quality of rural, low-income children in the United States. Objective To evaluate student’s diet quality at baseline and after implementing the CHANGE (Creating Healthy, Active and Nurturing Growing-up Environments) study, a two-year (2007-2009) randomized, controlled, community- and school-based intervention to prevent unhealthy weight gain among rural school-aged children. Design School and community-based group randomized controlled design. Participants/setting Data were collected in eight rural communities in California, Kentucky, Mississippi, and South Carolina (one elementary school per community). Children in grades 1-6 participated in the study (n= 432; mean age = 8.65 years ± 1.6 years). Students’ diets were assessed at baseline (spring or early fall 2008) and post-intervention (spring 2009) using the Block Food Screener for ages 2–17 years. Statistical Analyses Mixed-model analysis of variance was used to examine the effect of the CHANGE study intervention on students’ diets. Results were adjusted for corresponding baseline dietary values, sex, age, grade, race/ethnicity, and state, with school included as a random effect nested within condition. Results At the end of one year, students enrolled in the CHANGE study intervention schools consumed significantly more vegetables (0.08cups/1000 kcal per day; p=0.03) and combined fruits and vegetables (0.22 cups/1000 kcal per day; P<0.05) compared to students in control schools. Students in the intervention schools also showed a reduction in the average daily dietary glycemic index (GI= −1.22; P<0.05) and a trend toward more fruit consumption (0.15cups/1000 kcal per day; P =0.07). There were no significant differences in students’ consumption of whole grains, legumes, dairy, potatoes/potato products, saturated fat, added sugars, or dietary fiber consumption. Conclusions The CHANGE study enhanced some aspects of rural students’ dietary intake. Implementing similar interventions in rural America may be promising to support vegetable consumption.

In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs. 354 individuals who were examined after implementation of fortification (exposed). We calculated the prevalence of deficient (<160 microg/L, 362.6 nmol/L) and acceptable (>200 microg/L, 453.2 nmol/L) RBC folate concentrations in both groups. Those exposed to folic acid fortification had a mean RBC folate of 450.0 microg/L (1019.7 nmol/L), a value 38% higher than the mean RBC folate of 325.3 microg/L (737.1 nmol/L) in those who were not exposed to fortification (P < 0.001). The prevalence of individuals with deficient RBC folate was 4.9% in the group not exposed to fortification compared with 1.9% in the group exposed to fortification (P < 0.02), and the prevalence of individuals with acceptable RBC folate was 87.0% in the group not exposed to fortification compared with 96.1% in the group exposed to fortification (P < 0.001). Similar results were seen in individuals who used supplements containing B-vitamins. The results of this study showed that in this cohort, the introduction of folic acid fortification significantly improved folate nutritional status measured as RBC folate.

The cystathionine beta-synthase knockout mouse provides a unique opportunity to study biochemical consequences of a defective cystathionine beta-synthase enzyme. The present study was undertaken to assess the effect of elevated plasma total homocysteine caused by cystathionine beta-synthase deficiency on one-carbon metabolism in 10 homozygous mutant mice and 10 age- and sex-matched wild-type mice. Plasma total homocysteine levels, S-adenosylmethionine and S-adenosylhomocysteine concentrations in liver, kidney and brain were measured by HPLC. Tissue DNA methylation status was measured by in vitro DNA methyl acceptance. Plasma total homocysteine concentration in food-deprived homozygous mutant mice (271.1 +/- 61.5 micro mol/L) was markedly higher than in wild-type mice (7.4 +/- 2.9 micro mol/L) (P < 0.001). In liver only, S-adenosylmethionine concentrations were higher in the homozygous mutant mice (35.6 +/- 5.9 nmol/g) than in wild type mice (19.1 +/- 6.1 nmol/g) (P < 0.001) and tended to be lower in kidney (P = 0.07). In contrast, S-adenosylhomocysteine concentrations were significantly higher in homozygous mutant mice compared with wild-type mice in all tissues studied. Genomic DNA methylation status in homozygous mutant compared with wild-type mice was lower in liver (P = 0.037) and tended to be lower in kidney (P = 0.077) but did not differ in brain (P = 0.46). The results of this study are consistent with the predicted role of cystathionine beta-synthase in the regulation of plasma total homocysteine levels and tissue S-adenosylhomocysteine levels. However, the fact that the absence of the enzyme had differential effects on S-adenosylmethionine concentrations and DNA methylation status in different tissues suggests that regulation of biological methylation is a complex tissue-specific phenomenon.

The transition from adolescence to adulthood is a unique period during which lifelong dietary habits are shaped. Dietary patterns (DPs) among young adults attending college have not been adequately described, and associations between DPs and indicators of disease risk are not well understood in this age group. Dietary data were collected from undergraduates participating in the Tufts Longitudinal Health Study (TLHS; 1998–2007) by Food Frequency Questionnaire (FFQ; n = 1323). DPs were derived using principal components analysis with varimax rotation. Scree plots; eigenvalues; factor loadings; and previous studies were used to determine and label the DPs retained. Cross-sectional relationships between DP scores and anthropometric measures (percent body fat (PBF) and (BMI) and lipid biomarkers (total; HDL and LDL cholesterol; and triglycerides) were assessed with multivariable regression models; adjusted for demographics; physical activity; smoking; intention to gain/lose weight; and total energy intake. Effect modification by sex was tested. Three DPs were identified: Prudent; Western; and Alcohol. Greater adherence to the Prudent DP was associated with favorable anthropometric outcomes. The Alcohol DP was associated with a favorable lipid profile. Associations between the Western DP and blood lipids differed by sex; with unfavorable impact observed only among males. Our findings add to the literature linking DPs in young adults with measurable adiposity and cardiometabolic outcomes; suggesting that improving nutrition among college students could reduce chronic disease risk.