Serum Folate Concentrations Research Articles

Concentrations of vitamin B12 and folate in maternal serum and fetal fluids, metabolite interrelationships, and hepatic transcript abundance of key folate and methionine cycle genes: the impacts of maternal nutrition during the first 50 d of gestation.

Adequate maternal nutrition is key for proper fetal development and epigenetic programming. One-carbon metabolites (OCM), including vitamin B12, folate, choline, and methionine, play a role in epigenetic mechanisms associated with developmental programming. This study investigated the presence of B12 and folate in maternal serum, allantoic fluid (ALF), and amniotic fluid (AMF), as well as how those concentrations in all three fluids correlate to the concentrations of methionine-folate cycle intermediates in heifers receiving either a control (CON) or restricted (RES) diet for the first 50 d of gestation and fetal hepatic gene expression for methionine-folate cycle enzymes. Angus cross heifers (n = 43) were estrus synchronized, bred via artificial insemination with semen from a single sire, and randomly assigned to one of two nutrition treatments (CON = 20, RES = 23). Heifers were ovariohysterectomized on either day 16 (n = 14), 34 (n = 15), or 50 of gestation (n = 14), where samples of maternal serum (n = 42), ALF (n = 29), and AMF (n = 11) were collected and analyzed for concentrations of folate and B12. Concentrations of B12 and folate in ALF were greater (P < 0.05) in RES compared to CON. For ALF, folate concentrations were also greater (P < 0.01) on day 34 compared to day 50. There was a significant (P = 0.04) nutrition × fluid interaction for B12 concentrations where concentrations were greatest in restricted ALF, intermediate in control ALF, and lowest in CON and RES serum and AMF. Folate concentrations were greatest (P < 0.01) in ALF, intermediate in serum, and lowest in AMF. Additionally, positive correlations (P < 0.05) were found between ALF and AMF folate concentrations and AMF concentrations of methionine, serine, and glycine. Negative correlations (P < 0.05) between AMF folate and serum homocysteine were also observed. Both positive and negative correlations (P < 0.05) depending on the fluid evaluated were found between B12 and methionine, serine, and glycine concentrations. There was a downregulation (P = 0.05) of dihydrofolate reductase and upregulation (P = 0.03) of arginine methyltransferase 7 gene expression in RES fetal liver samples compared with CON fetal liver on day 50. Combined, these data show restricted maternal nutrition results in increased B12 and folate concentrations present in fetal fluids, and increased expression of genes for enzymes within one-carbon metabolism.

Elevated Maternal Serum Folate Concentrations are Associated with Risk of Developing Gestational Diabetes Mellitus

Elevated Maternal Serum Folate Concentrations are Associated with Risk of Developing Gestational Diabetes Mellitus

One-carbon metabolite supplementation to heifers for the first 14 d of the estrous cycle alters the plasma and hepatic one-carbon metabolite pool and methionine-folate cycle enzyme transcript abundance in a dose-dependent manner.

The objective of this study was to determine the dose of folate and vitamin B12 in beef heifers fed rumen protected methionine and choline required to maintain increased B12 levels and intermediates of the methionine-folate cycle in circulation. Angus heifers (n = 30; BW = 392.6 ± 12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: Total mixed ration (TMR) and saline injections at day 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen protected methionine (MET) fed at 0.08% of the diet DM, rumen protected choline (CHOL) fed at 60 g/d, and saline injections at day 0 and 7, 0.5X: TMR, MET, CHOL, 5 mg B12, and 80 mg folate at day 0 and 7, 1X: TMR, MET CHOL, 10 mg vitamin B12, and 160 mg folate at day 0 and 7, and 2X: TMR, MET, CHOL, 20 mg B12, and 320 mg folate at day 0 and 7. All heifers were estrus synchronized but not bred, and blood was collected on day 0, 2, 5, 7, 9, 12, and 14 of a synchronized estrous cycle. Heifers were slaughtered on day 14 of the estrous cycle for liver collection. Serum B12 concentrations were greater in the 0.5X, 1X, and 2X, compared with 0XNEG and 0XPOS on all days after treatment initiation (P < 0.0001). Serum folate concentrations were greater for the 2X treatment at day 5, 7, and 9 of the cycle compared with all other treatments (P ≤ 0.05). There were no differences (P ≥ 0.19) in hepatic methionine-cycle or choline analyte concentrations by treatment. Concentrations of hepatic folate cycle intermediates were always greater (P ≤ 0.04) in the 2X treatment compared with the 0XNEG and 0XPOS heifers. Serum methionine was greater (P = 0.04) in the 0.5X and 2X heifers compared with 0XNEG, and S-adenosylhomocysteine (SAH) tended (P = 0.06) to be greater in the 0.5X heifers and the S-adenosylmethionine (SAM):SAH ratio was decreased (P = 0.05) in the 0.5X treatment compared with the 0XNEG, 0XPOS, and 2X heifers. The hepatic transcript abundance of MAT2A and MAT2B were decreased (P ≤ 0.02) in the 0.5X heifers compared with the 0XNEG, 0XPOS, and 2X heifers. These data support that beef heifers fed rumen protected methionine and choline require 20 mg B12 and 320 mg folate once weekly to maintain increased concentrations of B12 and folate in serum. Furthermore, these data demonstrate that not all supplementation levels are equal in providing positive responses, and that some levels, such as the 0.5X, may result in a stoichiometric imbalance in the one-carbon metabolism pathway that results in a decreased SAM:SAH ratio.

Homocysteine, folate, and nonalcoholic fatty liver disease: a systematic review with meta-analysis and Mendelian randomization investigation

Circulating concentrations of homocysteine and folate are inconsistently associated with the risk of nonalcoholic fatty liver disease (NAFLD) in observational studies. We conducted a meta-analysis and Mendelian randomization (MR) analyses to examine these associations. We performed a meta-analysis of observational studies identified from 3 databases to evaluate the associations of serum homocysteine and folate concentrations with NAFLD from inception to 7 April 2022. We conducted MR analyses to strengthen the causal inference in these associations. Independent single-nucleotide polymorphisms without linkage disequilibrium (r2<0.01) that were strongly associated (P < 5×10-8) with serum homocysteine (n=13) and folate (n=2) concentrations were selected as instrumental variables from 2 meta-analyses of genome-wide association studies (GWASs) of 44,147 and 37,645 individuals of European ancestry, respectively. Data on NAFLD were obtained from a GWAS of 8434 NAFLD cases and 770,180 controls of European ancestry. We further included 4 liver enzymes as secondary outcomes from a GWAS of 361,194 individuals with European descent. Twenty-two observational studies comprising 30,368 participants were included in the meta-analysis. There was a positive association between serum homocysteine and NAFLD risk (n=20; OR: 1.96; 95% CI: 1.57, 2.45) and an inverse association between serum folate and NAFLD risk (n=12; OR: 0.75; 95% CI: 0.58, 0.99). In MR analysis, the ORs of NAFLD were 1.17 (95% CI: 1.01, 1.36) and 0.75 (95% CI: 0.55, 1.02) per 1-SD increment of genetically predicted circulating concentrations of homocysteine and folate, respectively. Each 1-SD increase of genetically predicted circulating homocysteine and folate conferred a change in ALT concentrations of 0.62 U/L (95% CI: 0.20, 1.04) and -0.84 U/L (95% CI: -0.14, -1.54). This study suggests a potential role of circulating homocysteine and possibly folate in NAFLD, which calls for future clinical exploration of the possibility of lowering homocysteine concentrations to prevent NAFLD. This systematic review was registered at PROSPERO as CRD42021296434.

The Effects of Serum Folic Acid and Vitamin B12 on the Risk of Gestational Diabetes Mellitus.

In order to gain more knowledge on the risk of gestational diabetes mellitus (GDM), and to provide evidence for clinical guidance on the optimum level of serum folic acid and vitamin B12, this study aimed to clarify the relationship between serum folic acid and vitamin B12 and the risk of GDM. This retrospective case-control study was conducted based on the clinical information system of the Maternal and Child Health Hospital of Hubei Province. Clinical data including maternal socio-demographical characteristics, serum folic acid, and vitamin B12 were collected. Logistic regression analyses and restricted cubic splines were performed to examine the impact of serum folic acid and vitamin B12 on the risk of GDM. Significantly elevated risks of GDM were observed in groups with high serum folic acid concentration (OR = 1.84, 95% CI: 1.07-3.16), and in low vitamin B12 concentration (OR = 2.14, 95% CI: 1.26-3.65). After stratified by age, the increased risk of GDM was still noticed in a low level of vitamin B12 among mothers aged <30 years (OR = 4.76, 95% CI: 1.45-15.61). In mothers with pre-pregnancy BMI <24, elevated risk of GDM was significantly associated with a high folic acid (OR = 2.09, 95% CI: 1.11-3.93) or a low vitamin B12 concentration (OR = 2.24, 95% CI: 1.22-4.14). Moreover, the risk of GDM was on the decline with the increased level of folic acid in the beginning, and it started to manifest an upward trend when the serum folic acid reached 19.02 ng/mL. This study demonstrated that serum folic acid excess or vitamin B12 deficiency could contribute to the increased risk of GDM, and revealed the potential side effect of serum folic acid overdose. As serum folic acid and vitamin B12 tests are widely applied in clinical practice, this finding could help clinicians to evaluate maternal risk from a new perspective.

Higher frequencies of anemia, hematinic deficiencies, and gastric parietal cell antibody positivity in vitamin B12-deficient Taiwanese male oral submucous fibrosis patients

Oral submucous fibrosis (OSF) is a progressive fibrotic oral mucosal disease associated with betel quid chewing. This study evaluated whether Taiwanese male OSF patients with vitamin B12 deficiency (the serum vitamin B12 level ≤ 450pg/mL, B12-deficient OSF patients) had high frequencies of blood hemoglobin (Hb) and serum iron and folic acid deficiencies, and serum gastric parietal cell antibody (GPCA) positivity. The blood Hb and serum iron, vitamin B12, folic acid, and GPCA concentrations in 66 Taiwanese male B12-deficient OSF patients were measured and compared with the corresponding data in 132 age-matched healthy male control subjects. We found that 6 (9.1%), 19 (28.8%), 35 (53.0%), and 9 (13.6%) of the 66 B12-deficient OSF patients had blood Hb (<13g/dL) and serum iron (≤70μg/dL), and folic acid (≤6ng/mL) deficiencies, and serum GPCA positivity, respectively. Furthermore, 66 OSF patients had significantly higher frequencies of blood Hb and serum iron and folic acid deficiencies, and serum GPCA positivity than 132 healthy control subjects (all P-values < 0.05). Of the 6 anemic B12-deficient OSF patients, one had macrocytic anemia, two normocytic anemia, and three thalassemia trait-induced anemia. Taiwanese male B12-deficient OSF patients have high frequencies of blood Hb, serum iron and folic acid deficiencies, and serum GPCA positivity. The anemia and hematinic deficiencies in B12-deficient OSF patients are likely due to OSF symptoms and signs-caused insufficient intake, poor chewing, and malabsorption of hematinic elements from ingested food stuffs rather than the GPCA positivity.

Association between serum folate concentrations and blood lead levels in adolescents: A cross-sectional study

As a heavy metal, lead is a common toxic agent. Its accumulation in the body is harmful to physical health, particularly in children and adolescents. Studies have reported that folate may play a protective role in lead exposure. An association between serum folate concentrations (SFC) and blood lead levels (BLL) has been documented in adults, but studies in adolescents are limited. This study investigated the relationship between SFC and BLL in American adolescents. This cross-sectional study collected relevant data on both SFC and BLL of 5,195 adolescents in the NHANES database from 2007 to 2018. Multivariable linear regressions and smooth curve fittings were adopted to evaluate the correlation between BLL and SFC. After adjusting potential confounders, we found negative relationships between BLL and SFC [β = -0.0041 (-0.0063, -0.0019)], and the associations were significant in non-Hispanic Whites, Mexican Americans, and other races but not significant in non-Hispanic blacks (P = 0.139). Furthermore, the negative trends were significant in adolescents aged 16-19 years and females aged 12-15 years but insignificant in males aged 12-15 years (P = 0.172). Therefore, these findings provide a basis for future research on the mechanism of folate in regulating blood lead levels.

Intake of Vitamin B12 and Folate and Biomarkers of Nutrient Status of Women within Two Years Postpartum.

Background: Little is known about variation in vitamin B12 and folate status among Chinese women 2 years postpartum. This study assessed intake of vitamin B12 and folate and biomarkers of nutrient status among Chinese women postpartum. Methods: Demographic information, multi-/single-nutrient supplementation, dietary data, serum vitamin B12 and serum folate were assessed in 982 women within 2 years postpartum, using ten investigation sites in Zhejiang Province from the National Nutritional Study 2016–2017, which is a nationally representative cross-sectional study, to form a representative provincial sample of Zhejiang Province. The dietary diversity score (DDS) was used for assessing the dietary pattern. Results: Vitamin B12 increased slightly at the early stage of postpartum and then dropped over time. Serum folate level elevated with postpartum time. The median serum vitamin B12 concentration was 494.59 (373.21–650.20) pg/mL, and folate was 7.58 (5.02–10.34) ng/mL. Correspondingly, vitamin B12 levels suggesting marginal deficiency (200–300 pg/mL) and deficiency (<200 pg/mL) resulted as 9.27% and 3.26%, respectively, and folate level suggesting deficiency (<3 ng/mL) was 9.16%. Multi-/single-nutrient supplementation during pregnancy was associated with log-transformed serum vitamin B12 and folate level after adjusting for potential confounders (vitamin B12: ß (SE) = 0.124 (0.028), p < 0.001; folate: 0.128 (0.035), <0.001). Additionally, postpartum nutrient supplementation was associated with log-transformed serum folate level, especially for lactating women (ß (SE) = 0.204 (0.062), p = 0.001). Increased DDS was significantly associated with elevated serum vitamin B12 and folate levels (vitamin B12: ß (SE) = 0.028 (0.011), p = 0.011; folate: 0.030 (0.014), 0.031). In addition, age and educational level were influencing factors for serum vitamin B12 and folate concentrations among postpartum women. Conclusion: Serum vitamin B12 level decreased and folate level increased with postpartum age among Chinese women. Nutrient supplementation during pregnancy was related to elevated serum vitamin B12 and folate concentrations. Postpartum nutrient supplementation was associated with the increased serum folate level of lactating women. Dietary diversity was related to increased serum vitamin B12 and folate levels, especially among postpartum women with younger age and lower educational level.

Associations of single and multiple perfluoroalkyl substances exposure with folate among adolescents in NHANES 2007–2010

BackgroundThe accumulation of perfluoroalkyl substances (PFAS) in human body has raised concerns about the potential health impacts on children and adolescents. However, no study has evaluated the associations of PFAS exposure with folate concentrations among adolescents. MethodsIn the present study, we mainly used three statistical approaches, namely multiple linear regression, Bayesian Kernel Machine Regression (BKMR), and quantile-based g-computation (Q-gcomp) models, to evaluate associations of individual PFAS and their mixtures with serum and red blood cell (RBC) folate concentrations in a sample of 721 adolescents from the NHANES 2007–2010. ResultsIn multiple linear regression models, for per unit increase in ln-transformed perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) concentrations, RBC folate concentrations decreased by 72.4 (95% confidence interval (CI): −112.7, −32.2), 58.3 (95% CI: −115.0, −1.6), 60.7 (95% CI: −107.5, −13.8), and 76.5 (95% CI: −119.0, −33.9) nmol/L, respectively. A similar significant inverse association was also observed between ln-transformed PFDA and serum folate. BKMR models further confirmed inverse associations of serum PFOS and PFDA with RBC folate, and serum PFDA with serum folate. However, the inverse associations of PFOA and PFNA with RBC folate shown in multiple linear regression model were not observed or less evident in BKMR analyses. We observed interactions of PFOA with PFOS, PFNA, and PFDA on RBC folate in BKMR models, with the negative slopes for PFOS, PFNA, and PFDA increased when PFOA concentration increased from the 10th percentile to the 90th percentile. Both BKMR and Q-gcomp models suggested that the mixtures of five PFAS showed inverse overall associations with RBC folate concentration. ConclusionsThe present study revealed that adolescent exposure to PFAS might affect serum and RBC folate concentrations.

Maternal serum concentrations of one-carbon metabolism factors modify the association between biomarkers of arsenic methylation efficiency and birth weight

BackgroundInorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes.MethodsData from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012) with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10).ResultsAmong urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise.ConclusionsTissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.

Circulating folate concentrations and the risk of mild cognitive impairment: A prospective study on the older Chinese population without folic acid fortification.

The longitudinal association between serum folate concentrations and the risk of cognitive impairment remains unclear in populations with low folate levels. We examined the association between serum folate concentrations and mild cognitive impairment (MCI) in older adults in China, where mandatory fortification of foods with folic acid has not been implemented. We further explored if homocysteine (Hcy) and leukocyte telomere length (LTL) mediate the association between serum folate and MCI. We performed a longitudinal analysis of 3974 participants aged ≥60 years from the Tianjin Elderly Nutrition and Cognition (TENC) cohort study. The associations between serum folate level and the risk of cognitive impairment overall and stratified by apolipoprotein E (APOE) ε4 genotypes were evaluated using multivariable Cox proportional hazards models. The mediating effects of Hcy and LTL on the folate-MCI association were explored via a path analysis approach. Within a 3-year follow-up, we documented 560 incident MCI cases. After multivariable adjustment, higher serum folate concentrations were associated with lower incidence of MCI, with hazard ratios (95% confidence interval) across quartiles of folate (from lowest to highest concentrations) of 1.00 (reference), 0.66 (0.52, 0.83), 0.57 (0.45, 0.73), 0.66 (0.52, 0.84), respectively (p for trend &lt;0.001). In mediation analyses, the status of serum folate deficiency and MCI were correlated via two intermediary pathways, Hcy and Hcy-telomere (p &lt; 0.05). Lower folate concentrations, independently of APOE genotype, were associated with increased risk of MCI among elderly Chinese people, a population with relatively low folate intake. Our data were compatible with the mediation hypothesis that the association between folate status and MCI was mediated by Hcy and LTL.

Association between Intake of Total Dairy and Individual Dairy Foods and Markers of Folate, Vitamin B6 and Vitamin B12 Status in the U.S. Population.

Vitamin B6, B12 and folate are required for energy metabolism and have been identified as nutrients of concern for certain population groups. This study examined the cross-sectional association between the consumption of dairy (total dairy, milk, yogurt and cheese) and biomarkers and adequacy for these nutrients in a nationally representative sample. Twenty-four-hour dietary recall data and concentrations of RBC folate (ng/mL), serum folate (ng/mL), and serum vitamins B6 (nmol/L) and B12 (pg/mL) were obtained from the National Health and Nutrition Examination Survey 2001–2018 (n = 72,831) and were analyzed by linear and logistic regression after adjusting for demographic variables. Significance was set at p < 0.01. Mean intakes of total dairy were 2.21, 2.17, 1.83 and 1.51 cups eq among consumers aged 2–8, 9–18, 19–50 and 51+ years, respectively. Higher intakes of total dairy as well as individual dairy foods (especially milk and yogurt) were positively associated with serum and RBC folate, serum vitamin B6 and serum B12, and generally, with 9–57% lower risk of inadequate or deficient levels of these vitamins. These findings suggest that encouraging dairy consumption may be an effective strategy for improving micronutrient status and provide continued evidence to support the current dietary recommendations for dairy and dairy products.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort

BackgroundThe protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. ObjectivesThis study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. MethodsThis was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018–2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. ResultsThe geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 μmol/L (7.48, 7.60 μmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 μmol/L (11.9, 12.2 μmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148–221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 μmol/L, 22.1% compared with 2.5%). ConclusionsMost pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Folate Deficiency Is Spatially Dependent and Associated with Local Farming Systems among Women in Ethiopia

ABSTRACTBackgroundFolate is essential for the synthesis and integrity of DNA, normal cell formation, and body growth. Folate deficiency among women of reproductive age (WRA) increases the risk of poor birth outcomes including neural tube defect (NTD)-affected pregnancies. Folate status is largely dependent on dietary intakes.ObjectivesWe aimed to explore the spatial distribution of biomarkers of folate status and their association with farming systems among nonpregnant WRA in Ethiopia.MethodsSerum and RBC folate concentration data were derived from the Ethiopia National Micronutrient Survey of 2015. The spatial dependencies of folate concentration of WRA were investigated and its relation with the dominant local farming system was explored.ResultsThe median serum folate and RBC folate concentrations were 12.3 nmol/L and 567.3 nmol/L, respectively. The national prevalence of folate deficiency using homocysteine concentration as a metabolic indicator based on serum and RBC folate concentration was 11.6% and 5.7%, respectively. The majority of women (77.9%) had low RBC folate concentrations consistent with increased risk of NTD-affected pregnancies. Folate nutrition was spatially dependent at distances of ≤ 300 km. A marked variability in folate concentration was observed between farming systems: greater RBC folate concentration (median: 1036 nmol/L) was found among women from the Lake Tana fish-based system, whereas the lowest RBC folate concentration (median: 386.7 nmol/L) was observed in the highland sorghum chat mixed system.ConclusionsThe majority (78%) of WRA in Ethiopia had low folate status potentially increasing the risk of NTD-affected pregnancies. These findings may help national and subnational nutrition intervention strategies to target the most affected areas in the country.

Association of dietary factors with plasma homocysteine and coronary heart disease outcome

ObjectiveThe aim of the present study was to investigate the association between serum levels of vitamins B12, B6, folic acid and hyperhomocysteinemia with the risk of coronary heart disease (CHD). Material and methodsA case control study was carried out involving 105 newly diagnosed coronary heart disease patient of both gender (age range 25–60years) and 105 age and sex matched normal healthy individuals at Punjab Institute of Cardiology, Lahore. Fasting blood samples were collected from both cases and controls. Sera were analyzed for folic acid, vitamin B6 and B12 using high performance liquid chromatography (HPLC). Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) and traditional risk factors were also assessed. ResultsMean plasma homocysteine level in cases (22.33±9.22μmol/L) was significantly higher (P=0.0001) than controls (12.5±3.73μmol/L). Mean serum folic acid concentration, serum vitamin B6 and vitamin B12 were significantly lower in cases than the mean levels in controls (P<0.05). When compared to controls the data revealed significantly greater deficiency of folic acid, vitamin B6 and B12 in coronary heart disease patients. Statistically significant inverse correlation was observed between folic acid, vitamin B6, B12 and plasma homocysteine concentration (r=−0.463, r=−0.431 and r=−0.294, respectively). ConclusionNutritional deficiency of folic acid, vitamin B12 and B6 were common in coronary heart disease patients with an inverse correlation of plasma homocysteine concentration with these vitamins. Substantial deficiency of these vitamins along with hyperhomocysteinemia could be further aggravating the risk of CHD in Pakistani population.

Investigation into the Properties of L-5-Methyltetrahydrofolate and Seal Oil as a Potential Atherosclerosis Intervention in Rats.

Atherosclerosis is a chronic inflammatory disease that leads to tissue ischemia. As the biologically active form of folic acid, L-5-methyltetrahydrofolate (L-5-MTHF) can improve endothelial function. And Seal oil plays a beneficial role in the progression of atherosclerosis. The study aims to evaluate beneficial effects of L-5-MTHF alone or in combination with Seal oil on atherosclerosis. Seventy-two male Wistar rats were randomly divided into 6 groups: control (normal diet), atherosclerosis (high-fat diet), folic acid (high-fat+3 mg/kg folic acid), low-dose L-5-MTHF (high-fat+3 mg/kg L-5-MTHF), low-dose L-5-MTHF+Seal oil (high-fat+3 mg/kg L-5-MTHF+0.5 g/kg Seal oil), high-dose L-5-MTHF (high-fat+10 mg/kg L-5-MTHF). After 13 wk, rats were sacrificed. Rats exhibiting atherosclerosis had dyslipidemia and serious aortic lesions. Supplementation with low-dose L-5-MTHF+Seal oil or use of high-dose L-5-MTHF increased serum folate concentrations, decreased homocysteine levels, improved the serum lipid profile, up-regulated expression of NO and NOS, enhancement of the antioxidant properties of GSH-Px activity and reduction in the concentration of MDA, levels of Olr1 and RelA mRNA decreased in aortic tissues, and expression of inflammatory factors, TNF-α, IL-6, IL-1β and endothelial cell injury factors ET-1 and sICAM-1, were also down-regulated. In addition, HD-L-5-MTHF increased the antioxidant activity of serum SOD. We conclude that L-5-MTHF has obvious anti-inflammatory and antioxidant effects on diseased blood vessels. The intervention of L-5-MTHF alone or in combination with Seal oil can improve atherosclerosis in rats and reduce the occurrence of aortic lesions. The anti-atherosclerotic mechanism may be related to down-regulation of Olr1 and RelA expression.

Association of Homocysteine Levels With Medial Temporal Lobe Atrophy Among Carriers and Non-carriers of APOE ε4 in MCI Subjects.

BackgroundDifferent clinical subtypes of mild cognitive impairment (MCI) involve heterogeneous underlying etiologies. This study investigated the association between demographics, neuropsychological performance, apolipoprotein E (APOE) genotype and magnetic resonance imaging (MRI) measures in patients with MCI (amnestic [aMCI] and non-amnestic [naMCI]).MethodsThis case–control study included 130 aMCI patients, 58 naMCI patients, and 1,106 healthy controls (HCs). APOE genotypes, medial temporal lobe atrophy (MTA), neurological evaluation results, and white matter hyperintensities (WMH) were investigated. Serum folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and plasma hyperhomocysteinemia (Hcy) was assessed by a high-performance liquid chromatography-fluorescence method.ResultsSerum folate levels were significantly lower, but plasma Hcy levels were higher, in patients with aMCI and naMCI than in healthy controls. There were significantly higher MTA scores in the aMCI group than the healthy control group. Multiple linear regression showed that serum Hcy and folate concentrations were positively associated with MTA (p < 0.05), while APOE4 showed a significant negative association with MTA in the aMCI group (p < 0.01). In addition, moderate/severe WMH showed a significant negative association with MTA in the naMCI and HC groups (p < 0.01).ConclusionThe combined presence of APOE4 and Hcy is associated with aMCI in elderly individuals, while moderate/severe WMH is related to naMCI, which suggests etiological differences across MCI subtypes.

Folate and vitamin B12 status: temporal evaluation after mandatory fortification in Brazil.

To perform temporal evaluation of folate and vitamin B12 status and their associated factors in a Brazilian population exposed to mandatory fortification. Data from the cross-sectional population-based studies 2008 and 2015 Health Surveys of São Paulo, including individuals ≥ 20 years, both sexes, N = 549 in 2008 and N = 610 in 2015. Folate and vitamin B12 biomarkers status, B-complex supplements and medications use, and dietary intake were assessed. Serum folate concentrations increased in the entire population, adults and older adults in 2015 compared to 2008, while serum vitamin B12 concentration increased only in older adults. B-complex supplement use raised in 2015, reflecting in serum vitamins status. Overall serum vitamin B12 deficiencies (<200 pg/mL) were 23.2% and 21.2%, while serum folate deficiencies (<4 ng/mL) were 4.1% and 1.5% in 2008 and 2015, respectively. The lowest quintile of serum folate (≤8.7 ng/mL) was positively associated with smoking and oral contraceptive use, while the highest quintile (≥17.8 ng/mL) was inversely associated with smoking and positively with B-complex supplement use. The odds of having vitamin B12 deficiency was inversely associated with B-complex supplement use, higher serum folate median, higher dietary vitamin B12 intake and positively associated with using oral contraceptive. Overall deficiency of folate has decreased in 2015, being almost non-existent. Low vitamin B12 status presented similar proportions in the overall population comparing both periods, except for older adults. Different predictive variables were identified to better understand vitamins status outcomes in the most recent period of the study.

Influence of narrowband ultraviolet B phototherapy on serum folate level in skin of color females: A cross-sectional study.

Background:Narrowband ultraviolet B (NB-UVB) (311–312 nm) is widely used for dermatological conditions with a favorable side-effect profile during pregnancy. Recently published data showed that NB-UVB might decrease serum folate level in Fitzpatrick skin phenotype I–III, especially at higher doses; this may predispose newborns to neural tube defects.Objective:To compare serum folate levels of skin of color females treated with NB-UVB and healthy females of childbearing age, as well as to note whether subsequent complications have been observed, if any.Methods:Multicenter, cross-sectional study of 30 females (N = 30): 15 female patients undergoing NB-UVB phototherapy as well as 15 age-, gender-, and skin phenotype-matched healthy volunteers who were enrolled into the study after excluding factors known to alter serum folate concentration. NB-UVB exposures were performed 2–3 times a week for at least 8–12 weeks (mean cumulative NB-UVB dose ± standard deviation [SD] was 55 ± 79 J/cm2).Results:Mean serum folate ± SD in NB-UVB exposed and healthy controls were 10.3 ± 4 and 8.3 ± 3 ng/mL, respectively. This was not a statistically significant difference between the 2 groups (P = .14).Limitations:Small sample size (N = 30) and a cross-sectional study type.Conclusion:Cumulative NB-UVB exposure is not associated with a statistically significant difference in serum folate level (P > .05) in skin of color females of childbearing age in comparison to age-, gender-, and skin phenotype-matched healthy females, even with the relatively higher cumulative doses (mean ± SD was 55 ± 79 J/cm2) that have been shown to reduce serum folate level in lighter skin phenotypes.

Serum folate deficiency and the risks of dementia and all-cause mortality: a national study of old age

BackgroundThe association between serum folate deficiency and the risk of dementia in old age is unclear, perhaps owing to small sample sizes, the competing risk of mortality or reverse causation.ObjectiveTo...