Folate Intake Research Articles

Folic Acid and Selected Risk Factors for Fetal Heart Defects-Preliminary Study Results.

The available data on the relationship between diet/folic acid and congenital heart disease (CHD) are not consistent. This study aimed to investigate the relationship between the intake and supplementation of folic acid and other selected factors in mothers and the risk of congenital heart defects in fetuses. A case-control study was conducted. The study group included pregnant women with fetuses from singleton pregnancies with prenatally diagnosed heart defects in the fetus (n = 79) and pregnant women whose course of pregnancy was normal with no heart defects or other developmental anomalies diagnosed in the fetus (n = 121). The patients were diagnosed at a reference center in Poland. The women completed a lifestyle questionnaire and FFQ and precisely described their use of dietary supplements. A univariate logistic regression model was used to evaluate the association between folic acid and selected risk factors and CHD. The association was significant and included such risk factors such as nutritional status, medications taken, smoking, and alcohol consumption. Additionally, the time of starting folic acid supplementation turned out to be statistically significant. The reference period of supplementation was the period before pregnancy. Lack of supplementation increases the risk of heart defects in children by more than four times compared to supplementation before pregnancy (OR = 4.19; p = 0.0117), whereas supplementation beyond the eighth week of gestation increases the risk almost threefold (OR = 2.90; p = 0.0474). The presence of congenital defects in the family is also an important factor. A history of congenital heart defects or other defects, lack of periconceptional folic acid supplementation, and lack of dietary supplementation before pregnancy were associated with congenital heart defects in the fetus. Place of residence, parents' education, lifestyle habits such as smoking and alcohol consumption, nutritional status before pregnancy, and mother's diseases did not show a significant relationship with congenital heart defects in the children. There is an urgent need to develop preventive strategies and conduct extensive public education.

Association between folate intake and radiographic progression, pain function scores in subjects with radiographic knee osteoarthritis: Data from the osteoarthritis initiative.

Folate has an important role in the functioning of the musculoskeletal system, including modulation of inflammation, immunity, cartilage regeneration, prevention of osteoporosis, and maintenance of muscle strength, but evidence on the association between folate intake and knee pain, functional scores, and radiographic progression in patients with knee osteoarthritis (OA) is still limited. Our population-based cohort was extracted from the osteoarthritis initiative (OAI), focusing on individuals with prevalent radiographic knee OA (with a Kellgren-Lawrence score ≥2). Folate consumption was determined using the food frequency questionnaire. Data regarding the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and radiographic readings were collected over 48 months. We analyzed the compiled data using generalized additive mixed models. Our cohort consisted of 1472 OA patients (626 men and 846 women, mean [SD] age 62.35 [8.92]). At the 48-month follow-up, we observed a significant correlation between higher folate intake and a slower progression of knee pain and functional scores, as evidenced by a statistically significant decrease in the WOMAC total score, WOMAC pain subscale score, and WOMAC function/disability subscale score (p < .05). The fully adjusted models estimated a reduction of -0.028 points per 50 μg/1000 kcal of daily folate intake on the WOMAC pain subscale, -0.117 points on the WOMAC function subscale, and -0.160 points on the total WOMAC scale. Furthermore, our nonparametric fit analysis suggested that a higher intake of folate might decelerate the radiographic progression of OA. Stratified analyses indicated that an increase in folate consumption might particularly benefit men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake. Higher folate intake is correlated with improved knee function and reduced pain in patients with knee OA and might deter the radiographic progression of OA. The benefits appear to be more pronounced in men, older adults, overweight and obese individuals, and those with a higher dietary fiber intake.

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Folate and cobalamin status, indicators, modulators, interactions, and reference ranges from early pregnancy until birth: the Reus–Tarragona birth cohort study

BackgroundFolate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care. ObjectivesTo investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification. MethodsIn a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24–27, 34 GW, labor and in the cord. Single nucleotide polymorphisms affecting folate and cobalamin status were determined. FA, cobalamin, micronutrient supplement use, and dietary folate and cobalamin intake (food frequency questionnaire) were recorded. Folate and cobalamin status predictors were assessed by multiple linear regression analysis. ResultsOnly 36.1% of the participants took FA preconceptionally and 47.4% and 7.3% had suboptimal RBCF (<906 nmol/L) and plasma cobalamin status (≤221 pmol/L), respectively, at ≤12 GW. RBCF determinants included planned pregnancy, FA supplementation, plasma cobalamin, and methylenetetrahydrofolate (MTHFR) 677C>T genotype. Cobalamin supplementation was positively associated with plasma cobalamin and early holoTC. Smoking and BMI were inversely associated with plasma cobalamin and early holoTC, but none were associated with MMA. Only participants with the MTHFR 677TT genotype, exceeding FA supplement recommendations, improved their folate status (interaction term: B (95% CI):0.15 (0.01, 0.29), P = 0.032). Smoking was inversely associated with plasma cobalamin status in participants with the methionine synthase reductase (MTRR) 524CC genotype only (interaction term:0.07 (0.01, 0.04), P = 0.014). Mothers with low early pregnancy cobalamin status and also those with bigger newborns, had lower cobalamin status at labor. ConclusionsSuboptimal early pregnancy folate or cobalamin status affected 47.4% and 7.3% of the participants, respectively. The MTHFR 677TT genotype predicted folate status throughout pregnancy. Smoking and BMI were negatively associated with cobalamin status throughout pregnancy.Clinical Trial Registry number and website where it was obtained: NCT01778205. www.clinicaltrials.gov

Factors related to the occurrence of fetal birth defects and the construction of a Nomogram model.

To explore the influencing factors of fetal birth defects (BD) and construct a nomogram model. A total of 341 newborns admitted to Meizhou people's hospital from September 2021 to September 2023 were randomly grouped into a modeling group (239 cases) and a validation group (102 cases). The modeling group fetuses were separated into BD and non-BD groups. Multivariate logistic regression analyzed risk factors for BD; R software constructed a nomogram model; Receiver operating characteristic (ROC) curve evaluated the model's discrimination for BD. The top 5 types of BD were congenital heart disease, polydactyly/syndactyly, cleft lip/palate, ear malformation, and foot malformation, with incidence rates of 23.81%, 20.63%, 12.70%, 11.11%, and 7.94%, respectively. BD incidence was 26.36% (63/239). Significant differences between BD and non-BD groups were found in maternal age, gestational age, history of adverse pregnancy/childbirth, gestational hypertension, adverse emotions during pregnancy, and folic acid intake duration (P<0.05). Logistic regression showed maternal age (OR: 4.125), gestational age (OR: 3.066), adverse pregnancy history (OR: 10.628), gestational hypertension (OR: 5.658), adverse emotions (OR: 5.467), and folic acid intake duration (OR: 4.586) were risk factors for BD (P<0.05). The modeling group's ROC AUC was 0.938, calibration curve slope close to 1, H-L test =8.342, P=0.692; external validation AUC was 0.961, calibration slope close to 1, H-L test =7.634, P=0.635. Identified risk factors include maternal age, gestational age, adverse pregnancy history, gestational hypertension, adverse emotions, and folic acid intake duration. The nomogram model shows good discrimination and consistency for evaluating neonatal BD risk.

Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population

PurposeThis study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population.Methods519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable.ResultsThe median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273.ConclusionIn pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.

Vitamin D, Folate, Vitamin B12, and Iron Status in Pregnant/Postpartum Old Order Anabaptist Women in Southwestern Ontario.

Purpose: To assess vitamin D, folate, vitamin B12, and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women.Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B12, and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007).Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes <EAR; 80% had folic acid supplement intakes >upper limit. One woman had low serum vitamin B12 (<148 pmol/L); serum vitamin B12 was high (>652 pmol/L) for 24%. None had vitamin B12 intakes <EAR; intakes were high compared to the recommended dietary intake. One woman had low hemoglobin; 13% had ferritin <15 μg/L. Thirteen percent had total iron intake <EAR.Conclusions: Overall, dietary intake and serum micronutrient status of OOA pregnant and postpartum women in our study were similar to those reported in previous studies of Canadian women. While some women had low intakes of vitamin D and iron, most had high intakes of folate and vitamin B12. These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.

Assessment of Milk and Beverage Intake Trends During Preschool Age and Modeling the Nutritional Impact of Replacing Nondairy Caloric Beverages with Milk

BackgroundMilk provides essential crucial public health nutrients, including 3–4 nutrients of public health concern, yet dairy consumption has declined over time, leading most Americans to fall short of meeting Dietary Guidelines recommendations. ObjectivesTo investigate milk and beverage consumption trends in preschool-age children, along with nutrient intakes from beverages, and to analyze the potential impact of replacing nondairy beverages with milk through isocaloric substitution. MethodsData from the National Health and Nutrition Examination Survey 2001–2018 for children aged 1–5 y (n = 4696) were used, and milk and other beverages intakes were estimated from the first 24-h in-person dietary recall. Nutrient intakes were determined using the United States Department of Agriculture’s food and nutrient database for dietary studies. Changes in nutrient intakes of children aged 2–5 y were modeled assuming isocaloric substitution with milk of all nondairy beverages consumed during lunch and dinner combined. Sample-weighted analyses were performed using SAS 9.4, and significance was set at P < 0.01. ResultsWith the increasing age of children, the intake of milk decreased, whereas the intake of energy, caloric beverages excluding milk, and sugar-sweetened beverages increased. Daily intakes of energy, protein, fat, saturated fatty acids (SFA), calcium, magnesium, potassium, sodium, vitamin A, folate, vitamin B-12, and vitamin D from caloric beverages including milk decreased with age, whereas the daily intake of fiber and added sugar increased with age. With the isocaloric replacement of nondairy caloric beverages with milk at lunch and dinner among children aged 2–5 y, intake of protein, fat, SFAs, calcium, magnesium, potassium, sodium, vitamin A, folate, vitamin B-12, and vitamin D increased, whereas for intake of carbohydrate, fiber, total sugar, and added sugar decreased. ConclusionsThe current findings indicate that increased efforts are needed to reverse the decrease in milk intake over time and as preschool children age and provide additional evidence to support specific dietary recommendations for milk.

Dietary intakes of vitamin B6, folate, vitamin B12 and erectile dysfunction: a national population-based study.

While deficiencies in vitamin B6, folate, and vitamin B12 are linked to various human diseases, including anemia, depression, peripheral neuropathy, and cardiovascular disease (CVD), literature regarding the association between vitamin B6, folate, and vitamin B12 and erectile dysfunction (ED) is scarce. We aimed to determine the dietary intake of vitamin B6, folate, and vitamin B12 and ED in the United States population. We extracted data from the 2001-2004 cycles of the National Health and Nutrition Examination Survey (NHANES). Dietary intakes of B vitamins were collected based on one 24-hour dietary recall. The association between dietary intake of vitamin B6, folate, vitamin B12 and ED was examined using multivariate logistic regression models. A total of 3,875 participants were included for analysis, with 1,201 reporting ED and 2,894 not experiencing ED. The multivariable odds ratios (ORs) for the highest vs. lowest quartiles of vitamin B6 was 0.77 [95% confidence interval (CI): 0.60-0.99; P for trend =0.03] for the prevalence of ED. Subgroup analyses demonstrated a significant inverse association between dietary intake of vitamin B6, folate, vitamin B12 and the prevalence of ED among men aged ≤60 years, individuals of Mexican American and non-Hispanic White ethnicity, and those without a history of CVD, diabetes, hypertension, and high cholesterol. The consumption of dietary vitamin B6, folate, and vitamin B12 was significantly linked to decreased risks of ED among younger healthier men, suggesting a potential protective role of these nutrients against ED in United States adults.

Knowledge and practice (KP) of Folic acid intake during conceptive period in Omdurman maternity hospital (OMH)

The objective of this study was to assess the knowledge and use of folic acid among pregnant women in Omdurman Maternity Hospital, Sudan. The study is a descriptive cross-sectional hospital-based study. One thousand pregnant women were interviewed, where a structured questionnaire was developed for the study. Results of the survey indicated that 91.2% of the women knew about folic acid, 16.2% knew that it prevents birth defects, 86.9% knew that it prevents anemia. The majority (88.6%) of women was taking the supplement, 51.3% were taking it regularly, but only 4.7% took it before getting pregnant. Knowledge and use were significantly influenced by age, education level, employment and family income. Preconception use of the supplement was lowest among illiterate and least educated women 7.02%. It was concluded that a high level of knowledge of folic acid was not reflected in regard to successful use of the folic acid supplement. Thus, it is justifiable for the prevention of all those affected by low levels of FA intake to introduce the policy of food fortification as is practiced in many developed countries.

Preconception Folic Acid and Multivitamin Supplementation for the Prevention of Neural Tube Defect: An Umbrella Review of Systematic Review and Meta-analysis.

Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of neural tube defect (NTD) in children, with no definitive conclusion. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and/or multivitamin supplementation for the prevention of NTD in offspring. Using the PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar reported that the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-analysis revealed that the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43 (95% CI: 0.29, 0.58) (I2 = 93.50%; p ≤0.001). In the subgroup analysis, the pooled effect was found to be 0.23 (0.09, 0.37) in folic acid group, while this estimate is 0.63 (0.53, 0.72) and 0.61 (0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 (0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20 (-0.01, 0.41) among SRMs, which aimed at reoccurrence (secondary) prevention, and 0.61 (0.46, 0.75) among those SRMs aimed to assess the effect folic acid or multivitamin for the prevention of both occurrence and reoccurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 (0.03, 0.87) in SRMs of observational studies, while this estimate is 0.43 (0.32, 0.54) among SRMs of randomized controlled trials. This umbrella review of systematic review and meta-analysis found that prenatal folic acid and/or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD compared with those who took multivitamin (37%). Reductions of 80% and 50% were observed for reoccurrence and occurrence prevention of NTD. Reductions of 57% and 55% of NTD have been found in SRM of RCTs and observational studies. This umbrella review revealed that both folic acid and multivitamin were associated with significantly lower levels of NTD in children. Considering the incorporation of those supplements in NTD prevention strategies during the preconception period is recommended. More large-scale prospective cohort and RCTs are needed to understand the protective effect of multivitamins and/or folic acid on NTD risk addressing the molecular mechanisms and to determine the optimal dose, duration, and timing of maternal multivitamin and folic acid intake for best child NTD risk reduction.

STRESS, PHYSICAL ACTIVITY, AND DIETARY INTAKE ARE ASSOCIATED WITH DYSMENORRHEA AMONG FEMALE STUDENTS

Background: The estimated prevalence of dysmenorrhea ranges from 45% to 93% of women of reproductive age. Approximately 10–15% of women complain about severe pain, resulting in a negative impact on their daily activities. Factors that cause dysmenorrhea are physical activity, nutritional status, dietary intake, stress, and body mass index. This study explores the prevalence of dysmenorrhea and investigates its correlation with physical activity, stress, and Dietary Intake among female students studying nutrition in Universitas Negeri Surabaya, Indonesia. Method: This research was cross sectional analytic descriptive study with minimum sample size of 114 female students. Primary data was collected using a set of questionnaires. Dysmenorrhea pain was assessed using the Numeric Rating Scale (NRS). Stress levels were measured by employing the Depression Anxiety Stress Scales 42 (DASS 42). Physical activity using The International Physical Activity Questionnaire (IPAQ). Dietary data including intakes of energy, iron, folate, and B12 was assessed using non-consecutive 3x24 hours food records, representing 2 weekdays and a weekend. The data were analyzed using chi-square for category data and one-way anova for continuous data. Result: Dietary intake especially vitamin B12 (p=0.02) were associated to the level of dysmenorrhea, whereas stress (p=0.36) and physical activity (p=0.82) was not associated of dysmenorrhea. Conclusion: This study emphasized the high prevalence of dysmenorrhea among female college students studying Nutrition, revealing important connections between stress, physical activity and dietary intake. Additionally, the research revealed a significant relationship between dietary intake (vitamin B12) and dysmenorrhea.

The Impact of the Dietary Intake of Vitamin B12, Folic Acid, and Vitamin D3 on Homocysteine Levels and the Health-Related Quality of Life of Levodopa-Treated Patients with Parkinson's Disease-A Pilot Study in Romania.

Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

The association between dietary, physical activity and the DNA methylation of PPARGC1A, HLA-DQA1 and ADCY3 in pregnant women with gestational diabetes mellitus: a nest case-control study

BackgroundGestational diabetes mellitus (GDM) is associated with DNA methylation and lifestyle. The effects of DNA methylation on GDM, and the interaction between DNA methylation and lifestyle factors are not well elucidated. The objective of this study was to explore the association between GDM, DNA methylation and lifestyle factors.MethodsA nest case-control design was performed. Sociodemographic data, dietary intake and daily physical activity information of pregnant women were collected. Bisulfate pyrosequencing was used to detect the DNA methylation level of PPARGC1A, HLA-DQA1, and ADCY3 genes. The differences of DNA methylation levels between the GDM group and the control group were compared. The correlation between clinical characteristics, dietary, physical activity and DNA methylation level was analyzed.ResultsA total of 253 pregnant women were enrolled, of which, 60 participants (GDM: 30; control: 30) were included in the final analysis. There were no significant differences in DNA methylation levels of six methylated sites between the two groups in this study (P > 0.05). Daily intake of potato and poultry were associated with DNA methylation level of the CpG 1 site of the ADCY3 gene in all participants and the control group (P < 0.05). Duration of folic acid intake before pregnancy was correlated with the methylation level of the CpG 1 site of the ADCY3 gene in all participants (r = 0.341, P = 0.04) and the control group (r = 0.431, P = 0.025). Daily oil intake was correlated with the methylation level of CpG 2 (r = 0.627, P = 0.016) and CpG 3 (r = 0.563, P = 0.036) of PPARGC1A in the GDM group.ConclusionThe association between the DNA methylation levels and GDM wasn’t validated. There were associations between dietary and DNA methylation in pregnant women. A large-sample-sized and longitudinal study is warranted to further investigate the impacts of lifestyle on DNA methylation.

Is There a Relationship Between the Dietary Inflammatory Index and Clinical Attachment Loss in Patients with Periodontitis?

Objective The pathogenesis of periodontal diseases is partially driven by oxidative stress. However, studies on the relationship between periodontitis and the inflammatory load of diet are still insufficient. Therefore, this study aimed to examine the relationship between the diet’s inflammatory load and periodontitis and clinical attachment loss (CAL). Methods This cross-sectional study included 119 participants diagnosed with periodontitis according to the 1999 classification. The dietary inflammatory index (DII) was calculated using three-day food consumption records and divided into quartiles (Q1, Q2, and Q3). Body mass index (BMI) was calculated as weight and height (kg/m2). Clinical attachment loss (CAL) score was determined, and the patients were grouped with those CAL scores as 7 < CAL and ≥7 CAL. Results Of the 119 patients with periodontitis, aged 46.24 ± 12.84 years, 45.3% were found to have an anti-inflammatory diet profile (n = 54). When the daily energy and nutrient intake of individuals were examined, it was found that the intake of omega-3 fatty acids (p = 0.004), black tea (p = 0.021), and green pepper (p = 0.029) was higher in those with CAL < 7 compared to those with CAL ≥ 7. There was no relationship between the patients’ DII and CAL values. Daily energy, protein, fiber, vitamin A, vitamin E, folic acid, Fe, Zn, and Mg intake in patients with an anti-inflammatory diet in Q1 were higher than in Q2 and Q3 (p < 0.001). Conclusion This study found no relationship between DII levels and CAL scores. However, it was observed that periodontitis patients following an anti-inflammatory diet had higher intakes of omega-3 fatty acids, vitamins A, E, and C, as well as zinc and magnesium which are nutrients known to be effective against inflammation. These patients also had CAL scores below 7. Therefore, reducing the inflammatory load of the diet may prevent the development of periodontitis, and further research in this regard would be beneficial.

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA. Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.

Association of food folate with asthma in US children and adolescents: a cross-sectional study

Background Asthma is a chronic inflammatory disease. Currently, contradictory findings exist regarding the association between food folate and asthma. Therefore, we hypothesize a positive correlation between food folate and asthma. Purpose To investigate the possible relationship between food folate intake and the development of asthma in children and adolescents in the United States. Methods Data from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018 were analyzed cross-sectionally by covariate adjustment using multivariate logistic regression, restricted triple spline curves, threshold effects, and stratified analyses. Results There were 8,821 participants, of whom 1,697 (19.2%) self-reported having received a diagnosis of asthma from a physician or other health professional. After accounting for potential confounders, the adjusted odds ratios (ORs) for asthma in the second (T2, 111–178 µg/day) and third (T3, >178 µg/day) groups were 1.15 (1–1.33) and 1.23 (1.04–1.46), respectively, compared with the group with the lowest food folate intake (T1, <111 µg/day). In addition, the association between food folate intake and asthma showed an inverse L-shaped curve (non-linear relationship, p = 0.003), and stratified analysis further validated the robustness of the results. The OR of asthma in subjects with food folate intake less than 263.9 µg/day was 1.002 (1.001–1.004). Conclusion In children and adolescents in the United States, there is a non-linear association (inverted "L" shape) between food folate intake and asthma, with an inflection point at 263.9 micrograms per day.

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.

A Comprehensive Investigation of Dietary Micronutrient Intakes and Risk of Alcoholic Liver Disease

BackgroundThe investigation of dietary micronutrient intakes and risk of alcoholic liver disease (ALD) based on observational studies was limited. ObjectivesOur study aimed to explore the associations of 30 dietary micronutrients intakes with risk of ALD, interactions between dietary micronutrients and genetic variation, and mediation effects of blood and urinary biomarkers on the associations between dietary micronutrients and risk of ALD. MethodsA case-control study was conducted within the UK Biobank cohort, with 231 incident ALD cases and 1386 controls. Dietary data were collected using a dietary questionnaire that relied on a 24-h dietary recall of the previous day. Logistic regression models were employed to assess the associations of dietary micronutrient intakes with risk of ALD. We conducted stratified analyses on the associations between dietary micronutrient intakes and risk of ALD by PNPLA3 rs738409 and tested the interactions between dietary micronutrients and genetic variation. In addition, we conducted mediation analyses to investigate the mediating effects of biomarkers on the associations between dietary micronutrients and risk of ALD. ResultsOur findings indicated significant inverse associations of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese with risk of ALD (all false discovery rate-Ptrend < 0.050). We also found a significant interaction between PNPLA3 rs738409 and magnesium (Pinteraction = 0.028). Creatinine (enzymatic) in urine, aspartate aminotransferase, and insulin-like growth factor 1 were the top 3 biomarkers with the highest number of significant mediation effects on the associations between the dietary micronutrients and risk of ALD. ConclusionsDietary intakes of thiamin, riboflavin, niacin equivalent, pantothenic acid, vitamin B-6, folate, vitamin E, calcium, magnesium, phosphorus, potassium, copper, iodine, and manganese were inversely associated with risk of ALD.

Spatial Transcriptomics and Single-Nucleus Multi-omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development.

Folate, an essential vitamin B9, is crucial for diverse biological processes including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Here, we employed mouse model and spatial transcriptomics and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.