Total Folate Intake Research Articles

Maternal Folic Acid and Dietary Folate Intake in Relation to Sex Ratio at Birth and Sex-Specific Birth Weight in China.

It is well-established that prenatal folic acid supplements can reduce neural tube defects. However, the associations between folic acid supplementation, dietary folate intake, and overall folate intake with sex-specific birth outcomes are not yet fully understood. This study aims to investigate the association of periconceptional folic acid supplement, dietary folate, and total folate intake with the sex ratio at birth and sex-specific birth weight. Data were sourced from a cross-sectional survey conducted between August and December 2013 in Northwest China, involving 7318 infants and their mothers, recruited using a stratified multistage random sampling method. Folic acid supplements (400 μg/d) were ascertained via a retrospective in-person interview. Dietary folate was evaluated using a validated food frequency questionnaire. Birth outcomes, including sex and weight at birth, were obtained from the Medical Certificate of Birth. Generalized linear models were employed to calculate relative risks (RRs) or differences with 95% confidence intervals (CIs). No association or dose-response relationship was observed between folic acid supplement, dietary folate, and total folate intake during periconception and the likelihood of male births. However, women who took folic acid supplements during pre- and post-conception were associated with an increased male birth weight by 52.8 (8.1 to 97.5) g. Additionally, the total folate intake during periconception was associated with birth weight for males (upper vs. lower tertile: β = 38.8, 95%CI: 5.0 to 72.5 g, p-trend = 0.024) and females (upper vs. lower tertile: β = 42.4, 95%CI: 6.7 to 78.1; p-trend = 0.022). Our findings indicate that periconceptional total folate intake does not correlate with sex ratio at birth but was positively linked to infant birth weights, regardless of gender. These findings offer novel insights into potential benefits of total folate intake, beyond the prevention of neural tube defects, for policymakers and public health.

Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing

BackgroundFolate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer. ObjectiveWe examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing. DesignParticipants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors. ResultsWe included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways. ConclusionsFolate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation.

Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study

Background & aimsPrenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. MethodsData come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. ResultsA reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P=0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P=0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P=0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. ConclusionsMaternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

High red blood cell folate is associated with an increased risk of diabetes death among a hypertensive cohort

The relationship between folate and diabetes remains inconclusive, possibly because of folate measured differentially between studies. Interference from mandatory folic acid fortification (FAF) has also been blamed. With both folate intake and circulating concentration measured, we assessed the relationship between folate and the risk of diabetes death in a hypertensive cohort established before FAF. We hypothesized that the association between folate and diabetes death is measurement dependent. We analyzed the data of 3133 hypertensive adults aged ≥19 years who participated in the Third National Health and Nutrition Examination Survey (1991–1994) and were followed up through December 31, 2010. Hazard ratios of diabetes death were estimated for participants with high (4th quarter) folate compared with those with moderate (2nd and 3rd quarters) or low (1st quarter) concentrations of folate. Dietary folate intake, total folate intake (including folate from supplements), serum, and red blood cell (RBC) folate were measured. After 42,025 person-years of follow-up, 165 diabetes deaths were recorded, and a dose-response positive association was observed between diabetes death and RBC folate. The adjusted hazard ratios of diabetes death were 1.00 (reference), 1.42 (95% CI. 1.20–1.68), and 2.21 (1.73–2.82), respectively, for hypertensive adults with low, moderate, and high RBC folate. No association was detected between diabetes death and serum folate concentration, folate intake, or either dietary intake or total intake. With minimized interference from FAF, neither dietary nor serum folate was associated with diabetes death, but elevated RBC folate was associated with a high risk of diabetes deaths among hypertensive patients.

Bean Consumption during Childhood Is Associated with Improved Nutritional Outcomes in the First Two Years of Life.

Bean consumption during childhood may play a role in promoting early-life health given their high nutritional quality. To examine the associations of children's bean consumption with the socio-demographic characteristics of the child and mother and the child's nutrient intake, we analyzed data from the WIC-ITFPS-2, which followed children and their mothers at 1, 3, 5, 7, 9, 11, 13, 15, 18, and 24 months (m) following birth. Caregivers (mostly mothers) responded to an interview-administered 24 h recall on their child's dietary intake at each time point. The intake of dried beans, chili, yellow beans, and lima beans was quantified. Correlate measures included socio-demographic characteristics. Outcome measures of interest focused on the intake of macronutrients (grams and % kcals) and micronutrients at 11 (infancy) and 24 m (toddler) only. To ensure statistical power, we only examined the associations of dried beans and chili with socio-demographics (Chi-square tests) and nutritional outcomes (ANOVA) at 11 and 24 m. The proportion of children who consumed dried beans or chili was very low in the first 6 m of age, started to increase at 7 m (1.2% and 0.4%) and 11 m (4.9% and 2.3%), and reached a high level at 18 m (10.5%) and 24 m (5.9%), respectively. Consumption of yellow or lima beans was rare (<0.1%). At 11 and 24 m, dried bean consumption was higher in children who were White (vs. Black). Dried bean and chili consumption was higher in children who were of Hispanic or Latino ethnicity (vs. non-Hispanic or non-Latino ethnicity). Children who consumed dried beans and chili at 11 or 24 m had a higher intake of total energy, protein, total fiber, potassium, folate, and magnesium compared with non-consumers. The bean consumption was low amongst children, differed by race and ethnicity, and was associated with improved macro- and micronutrient intake in children at 11 and 24 m.

Association between nutrient intake and female infertility: a study based on NHANES database

Background This study was designed to investigate the association between nutrients and female infertility. Methods A cross-sectional study on 18–45 years of age reproductive-age women was conducted using the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013–2014 and 2015–2016. Multivariate logistic regression analysis was performed to evaluate the association between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI). Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI). Results Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24–0.86, p = 0.018), vitamin A (OR: 0.44, 95% CI: 0.24–0.80, p = 0.009), vitamin C (OR: 0.48, 95% CI: 0.26–0.88, p = 0.020), magnesium (OR: 0.36, 95% CI: 0.17–0.76, p = 0.009), iron (OR: 0.43, 95% CI: 0.23–0.82, p = 0.012), lycopene (OR: 0.55, 95% CI: 0.33–0.91, p = 0.022), and total folate (OR: 0.38, 95% CI: 0.20–0.70, p = 0.003) were associated with a lower risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and lycopene were related to a lower risk of female infertility among women with a BMI being 18.5–24.9 kg/m2. Among women with BMI > 24.9 kg/m2, high intakes of magnesium, iron and total folate were associated with a decreased risk of female infertility. Conclusions The intake of several nutrients is associated with a decreased risk of female infertility. These findings provide insight into potentially modifiable lifestyle factors associated with female infertility.

Maternal Bean Consumption during Pregnancy: Distribution and Nutritional Outcomes

(1) Background: Due to their high nutritional value, we aimed to characterize the frequency and amount of maternal consumption of beans during pregnancy and their associations with diet quality and nutrient intake. (2) Methods: We conducted a secondary data analysis of US pregnant women (n = 1444) from the Infant Feeding Practices Study II, a longitudinal study that followed mother–infant pairs from late pregnancy to 1 year postpartum. Maternal bean intake (food types [dried beans, chili, and bean soup], frequency, serving size, and amount), diet quality (Healthy Eating Index [HEI]), and nutrient intake were estimated with a Food Frequency Questionnaire taken in the third trimester of pregnancy. Associations of bean consumption with diet quality and nutrient intake were examined with analysis of variance, Fisher’s least significant difference tests, correlation coefficients, and coefficients of determination. (3) Results: In general, maternal bean consumption was low during pregnancy: 0.31 cups/week of dried beans, 0.37 cups/week of chili, and 0.10 cups/week of bean soup. Maternal bean consumption varied by socio-demographics and geographic regions. In comparison with those who never consumed dried beans, mothers who ate dried beans ≥ 1 time per week had a higher mean HEI score (67.5 vs. 63.6), intake of total fiber (24.4 vs. 17.4 g/day), and protein (93.4 vs. 79.9 g/day), but a lower percentage of energy from added sugar (12.6 vs. 15.2%). Higher dried bean consumption had weak-to-moderate correlations with intake of total fiber (correlation coefficient, 0.320), insoluble fiber (0.316), soluble fiber (0.310), and folate (0.286). Similar but less extensive correlations were observed for chili and bean soup consumption. (4) Conclusions: In this US cohort of pregnant women, bean consumption was low. Increased intake of beans (≥1 time per week) may improve maternal diet quality during pregnancy.

Maternal intake of folate and folic acid during pregnancy and pubertal timing in girls and boys: A population-based cohort study.

Folate is essential for normal foetal development as it plays an important role for gene expression during different periods of foetal development. Thus, prenatal exposure to folate may have a programming effect on pubertal timing. To study the association between maternal intake of folate during pregnancy and pubertal timing in girls and boys. We studied 6585 girls and 6326 boys from a Danish population-based Puberty Cohort, 2000-2021. Information on maternal intake of folate from diet and folic acid from supplements was obtained from a food-frequency questionnaire in mid-pregnancy, and total folate was calculated as dietary folate equivalents. Information on age at menarche in girls, age at first ejaculation and voice break in boys, and Tanner stages, acne and axillary hair in both girls and boys was obtained every 6 months throughout puberty. We estimated mean monthly differences according to exposure groups for each pubertal milestone in addition to a combined estimate for the average age at attaining all pubertal milestones using multivariable interval-censored regression models. Total folate was analysed in quintiles, continuous and as restricted cubic splines. Maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls (combined estimate for overall pubertal timing per standard deviation (SD 325 μg/day) decrease in maternal intake of total folate: -0.14 months (95% confidence interval [CI] -0.51, 0.22)). Boys had slightly later overall pubertal timing per standard deviation (SD 325 μg/day) decrease in maternal intake of total folate (combined estimate: 0.40 months, 95% CI 0.01, 0.72). Spline plots supported these findings. Prenatal exposure to low maternal intake of total folate in mid-pregnancy was not associated with pubertal timing in girls but associated with slightly later pubertal timing in boys. This minor delay is likely not of clinical importance.

Associations between Folate and Alcohol Consumption with Colorectal Tumor Ki67 Expression in the Southern Community Cohort Study

Folate is hypothesized to accelerate cell proliferation in colorectal cancer (CRC) by supporting DNA synthesis, while alcohol is also linked to gastrointestinal epithelial proliferation, despite biological antagonism of folate. We report associations between folate and alcohol consumption with the proliferation marker Ki67 in CRC tumors from the Southern Community Cohort Study. Tumor samples were obtained from formalin-fixed paraffin-embedded tissue blocks. The percentage of cells expressing Ki67 was measured immunohistochemically. Exposures were assessed via questionnaire pre-diagnosis. Associations were assessed via linear regression. In 248 cases (40–78 years), neither dietary folate, folic acid supplements, nor total folate intake were associated with Ki67. Folic acid supplement use was associated with Ki67 in distal/rectal tumors (β [95% confidence interval]: 7.5 [1.2-13.8], p = .02) but not proximal tumors (-1.4 [-7.1-4.3], p=.62). A positive trend for total folate was observed for distal/rectal tumors (1.6 [0.0-3.3] per 200 μcg, p-trend=.05). Heavy drinking (women: ≥1 drink/day, men: ≥2 drinks/day) was associated with higher Ki67 (6.4 [1.0-11.9], vs. nondrinkers, p=.02), especially for distal/rectal tumors (10.4 [1.6-19.1], p=.02). Negative interaction between alcohol, total folate was observed for distal/rectal tumors (p-interaction=.06). Modest associations between folate, alcohol consumption and distal/rectal tumor Ki67 expression suggest accelerated proliferation, consistent with folate’s role in DNA synthesis.

Higher Than Recommended Folic Acid Intakes is Associated with High Folate Status Throughout Pregnancy in a Prospective French-Canadian Cohort

BackgroundFolate and vitamin B12 status during pregnancy are important for maternal and neonatal health. Maternal intake and prepregnancy body mass index (ppBMI) can influence biomarker status. ObjectivesThis study aimed to, throughout pregnancy; 1) assess folate and B12 status including serum total folate, plasma total vitamin B12, and homocysteine (tHcy); 2) examine how these biomarkers are associated with intakes of folate and B12 and with ppBMI; and 3) determine predictors of serum total folate and plasma total vitamin B12. MethodsIn each trimester (T1, T2, and T3), food and supplement intakes of 79 French-Canadian pregnant individuals were assessed by 3 dietary recalls (R24W) and a supplement use questionnaire. Fasting blood samples were collected. Serum total folate and plasma total vitamin B12 and tHcy were assessed by immunoassay (Siemens ADVIA Centaur XP). ResultsParticipants were 32.1 ± 3.7 y and had a mean ppBMI of 25.7 ± 5.8 kg/m2. Serum total folate concentrations were high (>45.3 nmol/L, T1: 75.4 ± 55.1, T2: 69.1 ± 44.8, T3: 72.1 ± 52.1, P = 0.48). Mean plasma total vitamin B12 concentrations were >220 pmol/L (T1: 428 ± 175, T2: 321 ± 116, T3: 336 ± 128, P < 0.0001). Mean tHcy concentrations were <11 μmol/L across trimesters. Most participants (79.6%–86.1%) had a total folic acid intake above the Tolerable Upper Intake Level (UL, >1000 μg/d). Supplement use accounted for 71.9%–76.1% and 35.3%–41.8% of total folic acid and vitamin B12 intakes, respectively. The ppBMI was not correlated with serum total folate (P > 0.1) but was weakly correlated with and predicted lower plasma total vitamin B12 in T3 (r = −0.23, P = 0.04; r2 = 0.08, standardized beta [sβ] = −0.24, P = 0.01). Higher folic acid intakes from supplements predicted higher serum total folate (T1: r2 = 0.05, sβ = 0.15, P = 0.04, T2: r2 = 0.28, sβ = 0.56, P = 0.01, T3: r2 = 0.19, sβ = 0.44, P < 0.0001). ConclusionsMost pregnant individuals had elevated serum total folate concentrations, reflecting total folic acid intakes above the UL driven by supplement use. Vitamin B12 concentrations were generally adequate and differed by ppBMI and pregnancy stage.

Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis.

Association between folate and non-alcoholic fatty liver disease among US adults: a nationwide cross-sectional analysis.

Association between dietary folate intake and cognitive impairment in older US adults: National Health and Nutrition Examination Survey

ObjectiveTo determine the association between dietary folate intake and low cognitive performance in older adults. MethodsIn this cross-sectional observational study, 2011-2014 data from the 2010 National Health and Nutrition Examination Survey, including 2,524 adults aged 60 years and older, included 24-hour dietary intakes. Total folic acid intake was calculated as the sum of folic acid supplements and dietary folic acid. Cognitive function was assessed using three tests. The association between folate intake and cognitive function was assessed using a multivariate conditional logistic regression model. Results2524 participants from two survey cycles (2011–2014) in the NHANES aged 60 years and over. In the multivariate logistic regression, the OR of developing folate was 0.96 (95% CI: 0.94∼0.98) in participants with Z test. Folate intake was negatively associated with cognitive function. Compared with Q1, Q4(≥ 616.3mg/day) in the AFT and DSST tests reduced the risk of cognitive impairment by 31% (OR = 0.69, 95% CI: 0.52-0.93) and 44% (OR = 0.56). 95% confidence interval: 0.44-0.7). In the comprehensive evaluation of IR and AFT scores, the association between dietary folate intake and low cognitive performance in US adults is linear. We also found a significant interaction between gender and cognitive ability (P value for the interaction was 0.021). ConclusionsDietary intake of folic acid may be inversely associated with cognitive impairment. The DSST study found an L-shaped association between dietary folate intake and cognitive decline in US adults, with an inflection point of approximately 510,383 mg/day.

MASA BAŞI ÇALIŞAN BİREYLERDE MAKRO-MİKRO BESİN ÖGESİ ALIMLARININ HEDONİK AÇLIK, KRONATİP VE DUYGU DÜZENLEME GÜÇLÜĞÜ ÜZERİNE ETKİSİ

Amaç: Bu çalışmanın amacı makro ve mikro besin ögesi alımlarının hedonik açlık, kronotip ve duygu düzenleme güçlüğü ile ilişkisinin belirlenmesidir.&#x0D; Yöntem: Çalışmanın örneklemini İstanbul’da beslenme ve diyet danışmanlık merkezinden danışmanlık hizmeti alan, masa başı çalışan, toplam 255 gönüllü birey oluşturdu. Katılımcılara yüz yüze görüşme yöntemiyle demografik özellikleri, beslenme alışkanlıkları, Besin Gücü Ölçeği (BGÖ), Sabahçıl-Akşamcıl Anketi (SAA) ve Duygu Düzenleme Güçlüğü Ölçeği (DDGÖ) uygulandı. Buna ek olarak bireylerin ağırlık ve boy ölçümleri ile beden kütle indeksi (BKİ) de değerlendirildi.&#x0D; Bulgular: Çalışmaya katılan bireylerin yaş ortalaması 36.1+8.75 yıl ve %70.2’si kadındı. BKİ ortalaması; 26.35±5.27 kg/m2’idi ve obezite oranı erkeklerde (%21.1) kadınlardan (%19.0) daha yüksekti. BKİ sınıflandırmasına göre toplam BGÖ puanı ve alt faktörleri olan Besin Bulunabilirliği, Besin Mevcudiyeti ve Besinin Tadına Bakılması puan ortalamalarının fazla kilolu olan bireylerde normal olan bireylere göre anlamlı olarak daha yüksek olduğu saptandı. BGÖ puanlarıyla tiamin, riboflavin, B6 vitamini, potasyum, magnezyum alım ortalamaları arasında anlamlı pozitif ilişki saptandı. DDGÖ puanlarının makro ve mikro besin alım ortalamaları incelendiğinde; çoklu doymamış yağ, E vitamini, riboflavin, folat ve potasyum alımı ile negatif ilişki bulundu. SAA puanları ile enerji, toplam yağ, çoklu doymamış yağ, kolesterol, tiamin, riboflavin, B6 vitamini, folat, C vitamini, potasyum, magnezyum ve demir alımlarında pozitif ilişki bulundu. Bunun yanı sıra BGÖ puanları ile SAA puanları ve DDGÖ puanları arasında da pozitif bir ilişki olduğu saptandı.&#x0D; Sonuç: Hedonik açlık, duygu düzenleme güçlüğü ve kronotip ile ilişkilidir. Bireylerin mikro besin ögesi alımı arttıkça hedonik açlık artmaktadır. Çoklu doymamış yağ asitleri ve mikro besin ögesi alımları azaldıkça duygu düzenleme güçlüğü artmaktadır. Sabahçıl tipteki kronotiplerin enerji, makro ve mikro besin ögeleri alımları daha fazladır.

Maternal intake of folate and folic acid during pregnancy and markers of male fecundity: A population-based cohort study.

Poor male fecundity is of concern, and a prenatal origin has been proposed. Folate, a methyl donor involved in DNA methylation, is essential for normal fetal development by regulating gene expression during different periods of fetal development. Thus, prenatal exposure to low maternal folate intake might have a programing function of the developing reproductive organs. To examine the association between maternal intake of folate from diet and folic acid from supplements during pregnancy and markers of fecundity in young men. We conducted a follow-up study using a Danish mother-son cohort of 787 young men born 1998-2000. Percentage differences in semen characteristics, testes volume, and reproductive hormone levels were analyzed according to total folate calculated as dietary folate equivalents from diet and supplements in midpregnancy, using multivariable negative binomial regression models. Total folate was analyzed in quintiles, continuous per standard deviation decrease (SD: 318μg/day) and as restricted cubic splines. Low maternal intake of total folate was associated with lower total sperm count (-5% (95% confidence intervals [CI]: -11%; 2%)), a lower proportion of non-progressive and immotile spermatozoa (-5% [95% CI: -8%; -3%]), and lower testes volume (-4% [95% CI: -6%; -2%]) per SD decrease in total folate intake. Spline plots supported these findings. The finding of a lower proportion of non-progressive and immotile spermatozoa, and hence a higher proportion of motile spermatozoa, in men of mothers with a lower intake of total folate in midpregnancy was surprising and may be a chance finding. Lower maternal intake of total folate in midpregnancy was associated with lower sperm count and lower testes volume, however, also with a lower proportion of non-progressive and immotile spermatozoa in adult men. Whether this actually affects the ability to obtain a pregnancy warrants further investigation.

Children Aged 5–6 Years in Vancouver, Canada Meet Dietary Recommendations for Folate and Vitamin B12 but not Choline

BackgroundCholine, folate, and vitamin B12 are required for growth and development, but there is limited information on the intakes and relationships to biomarkers of status in children. ObjectivesThe objective of this study was to determine the choline and B-vitamin intakes and relationship to biomarkers of status in children. MethodsA cross-sectional study was conducted in children (n = 285, aged 5–6 y) recruited from Metro Vancouver, Canada. Dietary information was collected by using 3 24-h recalls. Nutrient intakes were estimated by using the Canadian Nutrient File and United States Department of Agriculture database for choline. Supplement information was collected by using questionnaires. Plasma biomarkers were quantified by using mass spectrometry and commercial immunoassays, and relationships to dietary and supplement intake were determined by using linear models. ResultsDaily dietary intakes of choline, folate, and vitamin B12 were [mean (SD)] 249 (94.3) mg, 330 (120) DFE μg, and 3.60 (1.54) μg, respectively. Top food sources of choline and vitamin B12 were dairy, meats, and eggs (63%–84%) and for folate, were grains, fruits, and vegetables (67%). More than half of the children (60%) were consuming a supplement containing B-vitamins, but not choline. Only 40% of children met the choline adequate intake (AI) recommendation for North America (≥250 mg/d); 82% met the European AI (≥170 mg/d). Less than 3% of children had inadequate folate and vitamin B12 total intakes. Some children (5%) had total folic acid intakes above the North American tolerable upper intake level (UL; >400 μg/d); 10% had intakes above the European UL (>300 μg/d). Dietary choline intake was positively associated with plasma dimethylglycine, and total vitamin B12 intake was positively associated with plasma B12 (adjusted models; P < 0.001). ConclusionsThese findings suggest that many children are not meeting the dietary choline recommendations, and some children may have excessive folic acid intakes. The impact of imbalanced one-carbon nutrient intakes during this active period of growth and development requires further investigation.

Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls

Periconceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relation by food sources compared with folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known. We evaluated the relation between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study. Genome-wide DNA methylation status obtained from archived neonatal blood spots from pediatric ALL cases (n=189) and controls (n=205) in the California Childhood Leukemia Study (CCLS) from 1995-2008 was compared with periconceptional folate from total, food, and supplemental sources using multivariable linear regression. Further stratification was performed by income, education, ethnicity, and total folate intake. We evaluated variable DNA methylation response to periconceptional folate by ALL case status through an interaction term. Two significant differentially methylated probes (DMPs) were associated with food and supplemental periconceptional folate intake in all subjects (n=394). The top differentially methylated region at the promoter region of DUSP22(dual specificity phosphatase 22) demonstrated DNA hypermethylation in ALL cases but not in controls in response to total and food folate intake. We further identified 8 interaction term DMPs with variable DNA methylation response to folate intake by ALL case status. Further stratification of the cohort by education and ethnicity revealed a substantially higher number of DMPs associated with supplemental folic acid intake in Hispanic subjects with lower income and educational level. We identified modest associations between periconceptional folate intake and DNA methylation differing by source, including variation by ALL case status. Hispanic subjects of lower income and education appear uniquely responsive to periconceptional folate supplementation.

Interactions between folate intake and genetic predictors of gene expression levels associated with colorectal cancer risk

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein.

High Dietary Folic Acid Intake Is Associated with Genomic Instability in Peripheral Lymphocytes of Healthy Adults.

Mandatory fortification of food with synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18–40 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (p = 0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in vivo.

Folate intake and incident chronic kidney disease: a 30-year follow-up study from young adulthood to midlife

The relation of long-term dietary folate intake with incident chronic kidney disease (CKD) remains uncertain. We aimed to investigate the association between dietary folate intake and incident CKD in a 30-y follow-up study from young adulthood to midlife. A total of 4038 American adults aged 18-30 y and without reduced estimated glomerular filtration rate (eGFR) were enrolled in 1985-1986 and monitored until 2015-2016 in the CARDIA (Coronary Artery Risk Development in Young Adults) study. Diet was assessed by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The primary outcome was incident CKD, defined as an eGFR <60 mL · min-1 · 1.73 m-2 or a urinary albumin to creatinine ratio (ACR) ≥30 mg/g. The secondary outcomes included 1) incident decreased eGFR, defined as an eGFR <60 mL · min-1 · 1.73 m-2, and 2) incident albuminuria, defined as an ACR ≥30 mg/g. During the follow-up, 642 (15.9%) participants developed CKD. Overall, there was a significant L-shaped relation of dietary folate with incident CKD after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted HRs (95% CIs) in quintiles 2-5 for incident CKD were 0.69 (0.56, 0.85), 0.35 (0.27, 0.45), 0.34 (0.26, 0.45), and 0.39 (0.30, 0.51), respectively. Similar results were found for the secondary outcomes. Moreover, the L-shaped association was confirmed in a subset of the cohort (n = 1462) with serum folate measured at baseline, in 1992, and in 2000. Higher folate intake in young adulthood was longitudinally associated with a lower incidence of CKD later in life. Additional studies are warranted to establish the causal inference.

Maternal Dry Bean Consumption During Pregnancy: Distribution and Nutritional Outcomes

ObjectivesDry beans and other pulses have a high nutritional profile. We aimed to characterize the frequency and amount of maternal dry bean consumption during pregnancy and their associations with diet quality and nutrient intake.MethodsWe conducted a secondary data analysis of pregnant women (N = 1,403) from the Infant Feeding Practices Study II, a longitudinal study that followed mother-infant pairs from late pregnancy until 6 years postpartum. Maternal dry bean consumption (frequency and amount), diet quality (Healthy Eating Index [HEI]), and nutrient intake were estimated with a Food Frequency Questionnaire completed in the third trimester of pregnancy. Associations of dry bean consumption with dietary quality and nutrient intake were examined with Analysis of Variance, Tukey's HSD pairwise comparisons, and determination coefficients.ResultsMothers in the analytic sample were mainly White (83.5%), college educated (78.9%), and had middle household income (55.1% ≥ $40,000). Overall, maternal dry bean consumption was low (0.3 cups/week) during pregnancy, with 92% not meeting the current recommendation (1–3 cups/week). Maternal dry bean consumption significantly varied by race/ethnicity and geographic regions with mothers of Hispanics and Asian or living in South Central regions having relatively high consumption. Compared with never-consumers, mothers who consumed dry beans ≥ 1 time per week had a higher mean HEI score (67.5 vs 63.6), intake of total fiber (24.4 vs 17.4 g/d), and protein (93.4 vs 79.9 g/d), but a lower percentage of energy (12.6 vs 15.2%) from added sugar. Higher amount of dry bean consumption had a substantial contribution to the variation in intake of total fiber (determination coefficient, 10.3%), insoluble fiber (10.0%), soluble fiber (9.6%), and folate (8.2%).ConclusionsDry bean consumption was low during pregnancy. Consumption of dry beans ≥ 1 time per week might help to improve maternal diet quality.Funding SourcesUSDA (to XW and TR).