Heather C. Hamner

Folic acid source, usual intake, and folate and vitamin B-12 status in US adults: National Health and Nutrition Examination Survey (NHANES) 2003–2006

BACKGROUND US adults have access to multiple sources of folic acid. The contribution of these sources to usual intakes above the tolerable upper intake level (UL) (1000 microg/d) and to folate and vitamin B-12 status is unknown. OBJECTIVE The objective was to estimate usual folic acid intake above the UL and adjusted serum and red blood cell folate, vitamin B-12, methylmalonic acid, and homocysteine concentrations among US adults by 3 major folic acid intake sources-enriched cereal-grain products (ECGP), ready-to-eat cereals (RTE), and supplements (SUP)-categorized into 4 mutually exclusive consumption groups. DESIGN We used data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 (n = 8258). RESULTS Overall, 2.7% (95% CI: 1.9%, 3.5%) of adults consumed more than the UL of folic acid. The proportions of those who consumed folic acid from ECGP only, ECGP+RTE, ECGP+SUP, and ECGP+RTE+SUP were 42%, 18%, 25%, and 15%, respectively. Of 60% of adults who did not consume supplements containing folic acid (ECGP only and ECGP+RTE), 0% had intakes that exceeded the UL. Of 34% and 6% of adults who consumed supplements with an average of < or = 400 and >400 microg folic acid/d, <1% and 47.8% (95% CI: 39.6%, 56.0%), respectively, had intakes that exceeded the UL. Consumption of RTE and/or supplements with folic acid was associated with higher folate and vitamin B-12 and lower homocysteine concentrations, and consumption of supplements with vitamin B-12 was associated with lower methylmalonic acid concentrations (P < 0.001). CONCLUSION At current fortification levels, US adults who do not consume supplements or who consume an average of < or =400 microg folic acid/d from supplements are unlikely to exceed the UL in intake for folic acid.

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies

BACKGROUND The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects.

U.S. women of childbearing age who are at possible increased risk of a neural tube defect‐affected pregnancy due to suboptimal red blood cell folate concentrations, National Health and Nutrition Examination Survey 2007 to 2012

BACKGROUND Red blood cell (RBC) folate concentrations are a potential biomarker of folate-sensitive neural tube defect (NTD) risk in the population. The purpose of this analysis was to describe women in the U.S. population with RBC folate concentrations below those associated with optimal NTD prevention. METHODS We used data from the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES) to assess the RBC folate status of U.S. women of childbearing age relative to risk categories for NTD risk based on RBC folate concentrations. We defined suboptimal RBC folate concentrations as those associated with a prevalence of ≥9 NTDs per 10,000 live births. RESULTS Among nonpregnant women age 12 to 49 years, 22.8% (95% Confidence Interval: 21.1, 24.6) had suboptimal RBC folate concentrations. Women had greater odds of having a suboptimal RBC folate concentration if they did not use dietary supplements containing folic acid; had mandatorily fortified enriched cereal grain products as their only source of folic acid; were non-Hispanic black or Hispanic; or were current smokers. CONCLUSION Based on RBC folate concentrations, we would predict that the majority of U.S. women of reproductive age are not at increased risk for folate sensitive NTDs in the presence of mandatory folic acid fortification. Prevention policies and programs can be aimed at population subgroups identified as having higher predicted risk for folate-sensitive NTDs based on RBC folate concentrations.

Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States

BACKGROUND Obesity is associated with an increased risk of having a pregnancy affected by a neural tube defect (NTD). It is not clear whether the amount of folic acid required by obese women to protect against NTDs is the same as that for nonobese women. METHODS We analyzed data from the National Health and Nutrition Examination Survey, representative of the noninstitutionalized civilian U.S. population, to assess whether body mass index (BMI; normal weight, overweight, and obese categories) modified the association between supplemental folic acid intake and folate status. We estimated the geometric mean concentration among nonpregnant women of childbearing age (15-44 years) during the postfortification period of: serum folate (2003-2008); red blood cell (RBC) folate (2007-2008); and plasma total homocysteine (tHcy; 2003-2006), adjusted for age, race and ethnicity, and total dietary folate expressed as dietary folate equivalents for strata of supplement use and BMI. RESULTS BMI was inversely associated with serum folate among women who did not use supplements containing folic acid; no differences between women in different BMI categories were observed among supplement users. Regardless of supplement use, obese women had the highest RBC folate concentrations. There were no differences in tHcy by BMI, regardless of supplement use. CONCLUSIONS These results do not support a straightforward modification of the relationship between supplemental folic acid intake and folate status by BMI. In this population, BMI may affect the body distribution of folate, as reflected by lower serum and higher RBC folate levels in obese women who do not use supplements.

Fortification of corn masa flour with folic acid in the United States: an overview of the evidence.

Corn masa flour, used to make products such as corn tortillas, is a staple food for Hispanic populations residing in the United States, particularly among Mexican Americans and Central Americans. Research has indicated that Hispanic women in the United States continue to be at a higher risk of having a neural tube defect–affected pregnancy than women of other races/ethnicities, even after the introduction of folic acid fortification of cereal grain products labeled as “enriched.” Corn masa flour has, therefore, been suggested as a potential food vehicle for folic acid in the United States. This paper explores the potential impact that folic acid fortification of corn masa flour could have on the Hispanic population in the United States.

The Prevalence of Low Serum Vitamin B-12 Status in the Absence of Anemia or Macrocytosis Did Not Increase among Older U.S. Adults after Mandatory Folic Acid Fortification

Whether folic acid fortification and supplementation at the population level have led to a higher prevalence of vitamin B-12 deficiency in the absence of anemia remains to be examined among a nationally representative sample of older U.S. adults. We assessed the prevalence of low vitamin B-12 status in the absence of anemia or macrocytosis before and after fortification among adults aged >50 y using cross-sectional data from the NHANES 1991-1994 (prefortification) and 2001-2006 (postfortification). We compared the prefortification and postfortification prevalence of multiple outcomes, including serum vitamin B-12 deficiency (<148 pmol/L) and marginal deficiency (148-258 pmol/L) with and without anemia (hemoglobin <130 g/L for men, <120 g/L for women) and with and without macrocytosis (mean cell volume >100 fL) using multinomial logistic regression, adjusting for age, sex, ethnicity, body mass index, C-reactive protein, and vitamin B-12 supplement use. Prefortification and postfortification serum vitamin B-12 deficiency without anemia [4.0 vs. 3.9%; adjusted prevalence ratio (aPR) (95% CI): 0.98 (0.67, 1.44)] or without macrocytosis [4.2 vs. 4.1%; aPR (95% CI): 0.96 (0.65, 1.43)] remained unchanged. Marginal deficiency without anemia [25.1 vs. 20.7%; aPR (95% CI): 0.82 (0.72, 0.95)] or without macrocytosis [25.9 vs. 21.3%; aPR (95% CI): 0.82 (0.72, 0.94)] were both significantly lower after fortification. After fortification, higher folic acid intake was associated with a lower prevalence of low serum B-12 status in the absence of anemia or macrocytosis. Results suggest that the prevalence of low serum B-12 status in the absence of anemia or macrocytosis among older U.S. adults did not increase after fortification. Thus, at the population level, we found no evidence to support concerns that folic acid adversely affected the clinical presentation of vitamin B-12 deficiency among older adults.

Acculturation Factors Are Associated with Folate Intakes among Mexican American Women

Folic acid can prevent neural tube defects (NTD). Hispanic women have a higher prevalence of NTD than non-Hispanic white (NHW) women and consume less folic acid. Among Hispanics, acculturation has been associated with lower intakes of natural folate. It is unknown if this same relationship is seen for fortified foods. This article describes the associations of acculturation factors with usual folate intakes from foods and supplements and compares the proportion that meets recommended intakes of folic acid of US Mexican American (MA) women with those of NHW women. For US NHW and MA women aged 15-44 y (n = 3167), usual folate intakes (i.e., natural food folate, folic acid from food, total folic acid [fortified foods plus supplements], and total folate) were estimated using measurement error models from NHANES 2001-2008. Compared with NHW women, MA women did not differ in their intake of natural food folate or folic acid from food. Similarly, compared with NHW women (332 ± 17.3 μg/d), the mean total usual folic acid intakes were lower among MA women who reported speaking Spanish (224 ± 24.9 μg/d) but not for MA women who reported speaking English (283 ± 36.2 μg/d). MA women were more likely than NHW women to consume a total folic acid intake <400 μg/d. MA women with lower acculturation factors were the most likely to have an intake <400 μg/d compared to NHW women. Public health efforts should focus on increasing total folic acid intake among MA women, emphasizing those with lower acculturation factors (e.g., MA women who report speaking Spanish).

Modelling fortification of corn masa flour with folic acid and the potential impact on Mexican-American women with lower acculturation.

OBJECTIVE Hispanics with lower acculturation may be at higher risk for neural tube defects compared with those with higher acculturation due to lower total folic acid intake or other undetermined factors. Modelling has indicated that fortification of corn masa flour with folic acid could selectively target Mexican Americans more than other race/ethnicities. We assessed whether fortification of corn masa flour with folic acid could selectively increase folic acid intake among Mexican-American women with lower acculturation, as indicated by specific factors (language preference, country of origin, time living in the USA). DESIGN We used dietary intake and dietary supplement data from the National Health and Nutrition Examination Survey 2001-2008, to estimate the amount of additional total folic acid that could be consumed if products considered to contain corn masa flour were fortified at 140 μg of folic acid per 100 g of corn masa flour. SETTING USA. SUBJECTS Non-pregnant women aged 15-44 years (n 5369). RESULTS Mexican-American women who reported speaking Spanish had a relative percentage change in usual daily total folic acid intake of 30·5 (95 % CI 27·8, 33·4) %, compared with 8·3 (95 % CI 7·3, 9·4) % for Mexican-American women who reported speaking English. We observed similar results for other acculturation factors. An increase of 6·0 percentage points in the number of Mexican-American women who would achieve the recommended intake of ≥400 μg folic acid/d occurred with fortification of corn masa flour; compared with increases of 1·1 percentage points for non-Hispanic whites and 1·3 percentage points for non-Hispanic blacks. An even greater percentage point increase was observed among Mexican-American women who reported speaking Spanish (8·2). CONCLUSIONS Fortification of corn masa flour could selectively increase total folic acid intake among Mexican-American women, especially targeting Mexican-American women with lower acculturation, and result in a decrease in the number of pregnancies affected by neural tube defects.

Developing Effective Campaign Messages to Prevent Neural Tube Defects: A Qualitative Assessment of Women's Reactions to Advertising Concepts

The incidence of neural tube defects (NTDs), serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year, can be reduced by 50–70% with daily periconceptional consumption of the B vitamin folic acid. Two studies were designed to assess college womens reactions to and perceptions of potential campaign advertising concepts derived from preproduction formative research to increase folic acid consumption through the use of a daily multivitamin. Study one assessed draft advertising concepts in eight focus groups (N = 71) composed of college-enrolled women in four cities geographically dispersed across the United States. Based on study one results, the concepts were revised and reassessed in study two with a different sample (eight focus groups; N = 73) of college women in the same four cities. Results indicated that participants generally responded favorably to concepts in each of the two studies, and provided insight into individual concepts to increase their overall appeal and effectiveness. The specific findings and implications of these results are discussed.

Understanding Optimal Nutrition Among Women of Childbearing Age in the United States and Puerto Rico: Employing Formative Research to Lay the Foundation for National Birth Defects Prevention Campaigns

Neural tube defects (NTDs) are serious birth defects of the brain and spine that affect approximately 3,000 pregnancies in the United States each year and affected 404 pregnancies in Puerto Rico from 1996 to 2002. Consuming the B vitamin folic acid can reduce the incidence of NTDs 50%–70%, and recent efforts to reduce NTD rates have focused on increasing the number of childbearing-aged women who take a vitamin containing folic acid every day. As the first stage of formative research in campaign planning, two exploratory, qualitative studies were conducted in order to (a) understand the complexity of vitamin use among women in the United States and Puerto Rico and (b) serve as a foundation on which to develop national communication and education interventions. Also, this information shed light on theories that might be used to guide campaign development. Results indicated that campaign messages designed to increase folic acid use through multivitamin supplementation in the United States must address womens barriers to vitamin use (e.g., cost, time), increase womens perceived need for multivitamins (e.g., identify immediate, tangible results from taking a daily multivitamin), and address the relationship between daily food choices and the need for supplementation. Future campaign messages in Puerto Rico must focus on many of these same issues, in addition to increasing womens knowledge about when folic acid should be taken in relation to pregnancy and addressing womens perceptions that vitamins cause weight gain (an undesirable outcome for most participants). The practical and theoretical implications of these results are discussed in terms of their contribution to the development of a creative new approach to increase multivitamin consumption among women of childbearing age in the United States and Puerto Rico.