Red Blood Cell Folate Research Articles

Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case-Control Study in Men of Subfertile Couples from the Netherlands.

IntroductionGastric acid-related symptoms are highly prevalent in the general population (21–40%), and more than 11% of individuals use medication for the treatment of these symptoms. The uptake of micronutrients is dependent on the gastrointestinal potential of hydrogen (pH).ObjectiveWe hypothesized that medication affecting gastrointestinal pH reduces the availability of B vitamins, thereby deranging one-carbon metabolism and detrimentally affecting spermatogenesis.MethodsThis explorative nested case–control study in men of subfertile couples investigated associations between medication used for gastric acid-related symptoms and semen parameters. We included 40 men using medication for gastric acid-related symptoms and 843 men not using medication. Semen analyses were performed between 70 days before and 21 days after the visit.ResultsThe use of medication was associated with a twofold higher risk of a low total motile sperm count [TMSC <1 × 106, odds ratio (OR) 2.090, p = 0.049] and negatively with sperm concentration (β −0.320, p = 0.028). Red blood cell folate was positively associated with TMSC (β 0.257, p = 0.026), sperm count (β 1.679, p = 0.013) and ejaculate volume (β 0.120, p = 0.023), and total homocysteine (tHcy) was negatively associated with sperm count (β −0.077, p = 0.021).ConclusionHere we delineate associations between the use of medication for gastric acid-related symptoms and poor semen quality in men of subfertile couples. The use of medication for gastric acid-related symptoms is associated with a twofold higher risk of a low TMSC and a decreased sperm concentration. Although these findings warrant further research on causality, the associations between folate, tHcy and semen quality emphasize the importance of preconception counselling in male subfertility.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-016-0488-8) contains supplementary material, which is available to authorized users.

Folate, homocysteine and selected vitamins and minerals status in infertile women

Objectives: Diet has been recognised as a crucial factor influencing fetal and maternal health. Adequate levels of substances such as homocysteine, folate and vitamin B12 have been associated with a higher rate of success in infertility treatments. Few data, however, are available on the average levels of micronutrients in the blood of reproductive-aged women, and specific values for adequate levels are not available. The aim of this cross-sectional study was to measure levels of folate, homocysteine and selected vitamins and minerals in women attending the infertility unit of an academic hospital for in vitro fertilisation (IVF).Methods: Fasting venous blood samples were taken in the morning during routine screening before IVF in order to measure: serum folate, red blood cell (RBC) folate, total plasma homocysteine, vitamin B12, vitamin A, vitamin E, serum iron and serum ferritin.Results: Among 269 women aged 37 ± 4 years, only 69% and 44% showed adequate levels of homocysteine and vitamin B12, respectively. Serum folate was appropriate in 78% of the study participants, but only a minority (12%) had a concentration of RBC folate regarded as optimal for the prevention of fetal neural tube defects. Serum levels of vitamin A, vitamin E, iron and ferritin were, however, appropriate in the vast majority of participants (>80%).Conclusion: Folate levels were largely inadequate among women attending an infertility clinic for IVF. Vitamin B12 levels were also found to be inadequate.

A thymidylate synthase polymorphism is associated with increased risk for bone toxicity among children treated for acute lymphoblastic leukemia.

Bone fractures and osteonecrosis frequently complicate therapy for childhood acute lymphoblastic leukemia (ALL). Bone toxicity has been associated with exposure to corticosteroids and methotrexate (MTX) and age greater than 10 years. We tested whether common genetic polymorphisms were associated with bone toxicity during treatment for ALL. A total of 615 of 794 children enrolled on Dana Farber Cancer Institute ALL Consortium protocol 05-001 (NCT00400946) met eligibility criteria for inclusion in this analysis. Nineteen candidate polymorphisms were selected a priori, targeting genes related to glucocorticoid metabolism, oxidative damage, and folate physiology. Polymorphisms were genotyped using either PCR-based allelic discrimination or PCR product length analysis. Twenty percent of subjects were homozygous for two 28 bp repeats (2R/2R, where 2R is two 28-nucleotide repeats within the 5' untranslated region [UTR] of the thymidylate synthase [TS] gene) within the 5' UTR of the gene for TS. This 2R/2R genotype was associated with increased risk of osteonecrosis among children younger than 10 years at diagnosis (multivariable hazard ratio [HR] 2.71; 95%confidence interval [CI] 1.23-5.95; P = 0.013), and with bone fracture among children ≥ 10 years (multivariable HR 2.10; 95%CI 1.11-3.96; P = 0.022). No significant association was observed between TS genotype and red blood cell (RBC) folate, RBC MTX, or relapse risk. A common genetic variant is associated with increased risk of osteonecrosis among children younger than 10 years at diagnosis and with bone fractures among older children. These findings suggest that children and adolescents with the 2R/2R TS genotype should be closely monitored for the development of bone toxicity during therapy for ALL, and support a clinical trial testing the efficacy of protective interventions specifically in this vulnerable population.

Applying inappropriate cutoffs leads to misinterpretation of folate status in the US population

Background: Folate cutoffs for risk of deficiency compared with possible deficiency were originally derived differently (experimental compared with epidemiologic data), and their interpretations are different. The matching of cutoffs derived from one assay with population-based data derived from another assay requires caution.Objective: We assessed the extent of folate-status misinterpretation with the use of inappropriate cutoffs.Design: In the cross-sectional NHANES, serum and red blood cell (RBC) folate were first measured with the use of a radioprotein-binding assay (RPBA) (1988–2006) and, afterwards, with the use of a microbiologic assay (2007–2010). We compared prevalence estimates for assay-matched cutoffs (e.g., with the use of an RPBA cutoff with RPBA data) and assay-mismatched cutoffs (e.g., with the use of microbiologic assay cutoff with RPBA data) for risk of deficiency on the basis of megaloblastic anemia as a hematologic indicator in persons ≥4 y of age (e.g., serum folate concentration <7 nmol/L and RBC folate concentration <305 nmol/L derived with the use of a microbiologic assay), possible deficiency on the basis of rising homocysteine as a metabolic indicator in persons ≥4 y of age (e.g., serum folate concentration <10 nmol/L and RBC folate concentration <340 nmol/L derived with the use of an RPBA), and insufficiency on the basis of elevated risk of neural tube defects in women 12–49 y old (e.g., RBC folate concentration <906 nmol/L derived with the use of a microbiologic assay).Results: Pre–folic acid fortification (1988–1994), risks of deficiency for assay-matched compared with assay-mismatched cutoffs were 5.6% compared with 16% (serum folate), respectively, and 7.4% compared with 28% (RBC folate), respectively; risks declined postfortification (1999–2006) to <1% compared with <1% (serum folate), respectively, and to <1% compared with 2.5% (RBC folate), respectively. Prefortification (1988–1994), risks of possible deficiency for assay-matched compared with assay-mismatched cutoffs were 35% compared with 56% (serum folate), respectively, and 37% compared with 84% (RBC folate), respectively; risks declined postfortification (1999–2006) to 1.9% compared with 7.0% (serum folate), respectively, and to 4.8% compared with 53% (RBC folate), respectively. Postfortification (2007–2010), risks of insufficiency were 3% (assay matched) compared with 39% (assay mismatched), respectively.Conclusions: The application of assay-mismatched cutoffs leads to a misinterpretation of folate status. This confusion likely applies to clinical assays because no comparability data are available, to our knowledge.

Red blood cell folate vs serum folate: Which one to measure?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Intakes of Folate and Vitamin B12 and Biomarkers of Status in the Very Old: The Newcastle 85+ Study.

Very old adults are at increased risk of folate and vitamin B12 deficiencies due to reduced food intake and gastrointestinal absorption. The main aim was to determine the association between folate and vitamin B12 intake from total diets and food groups, and status. Folate or vitamin B12 intakes (2 × 24 h multiple pass recalls) and red blood cell (RBC) folate or plasma vitamin B12 (chemiluminescence immunoassays) concentrations were available at baseline for 731 participants aged 85 from the Newcastle 85+ Study (North-East England). Generalized additive and binary logistic models estimated the associations between folate and vitamin B12 intakes from total diets and food groups, and RBC folate and plasma B12. Folate intake from total diets and cereal and cereal products was strongly associated with RBC folate (p < 0.001). Total vitamin B12 intake was weakly associated with plasma vitamin B12 (p = 0.054) but those with higher intakes from total diets or meat and meat products were less likely to have deficient status. Women homozygous for the FUT2 G allele had higher concentrations of plasma vitamin B12. Cereals and cereal products are a very important source of folate in the very old. Higher intakes of folate and vitamin B12 lower the risk of “inadequate” status.

Serum and red-blood-cell folate demonstrate differential associations with BMI in pregnant women.

To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women. A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual. The Ottawa Hospital and Kingston General Hospital, Ontario, Canada. Pregnant women recruited between 12 and 20 weeks of gestation. A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited. BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.

Risk of Neural Tube Defects Based on Red Blood Cell Folate among Women in the Dominican Republic

Evidence shows a strong causal association between low maternal folic acid (FA) in take and increased risk for neural tube defects (NTD). Folic acid intake of at least 400μg per day is recommended for women of reproductive age (WRA) capable of becoming pregnant to reduce the prevalence of NTDs. Red blood cell (RBC) folate ≤151 ng/mL (≤340 nmol/L) is commonly used to define FA deficiency and is a metabolic indicator based on the relationship between RBC folate and homo cysteine concentrations. In a new WHO guideline, RBC folate concentration ≤400 ng/mL (≤906 nmol/L) define FA insufficiency among WRA at the population level based on the functional indicator of risk of NTD‐affected pregnancies. We examined RBC folate results from a national survey conducted in the Dominican Republic in 2009 among 443 non‐pregnant women 15–49 yrs using these different cut‐offs. FA deficiency was 7.0% when using the metabolic indicator cut off and FA insufficiency was 75.8% when using the functional indicator cut‐off. The risk for NTD‐affected pregnancies in the Dominican Republic was high based on the prevalence of FA insufficiency in this population. Countries may find a much larger percentage of WRA have FA insufficiency and are at risk of NTD‐affected pregnancies than previously considered based on the metabolic indicator, making it important to examine RBC folate data using the new functional indicator cut‐off.

Abstract P064: Inverse Associations Between Inorganic Arsenic and Obesity: Findings From the National Health and Nutrition Examination Survey

Introduction: Arsenic is ubiquitous in the environment as an element of the earth’s crust. Human exposure predominantly occurs through ingestion of contaminated drinking water and arsenic-rich foods such as seafood and rice. Chronic exposure to inorganic arsenic has been associated with certain cancers, and more recently with cardiovascular disease and diabetes that are common among the obese. However, little is known about the specific relationship between inorganic arsenic exposure and obesity. Hypothesis: We assessed the hypothesis that inorganic arsenic exposure was correlated with obesity in the general population of the United States. Methods: We analyzed a representative sample of 4,105 adults from the U.S. population using data from the 2007-2010 National Health and Nutrition Examination Survey (NHANES). Arsenobetaine and arsenocholine concentrations, which are forms of organic arsenic, were subtracted from total urinary arsenic concentrations to estimate the amount of inorganic arsenic in urine as a biomarker of exposure. These values were standardized by urinary creatinine to control for hydration status. Obesity was assessed using measured body mass index (BMI) in kg/m 2 and waist circumference in cm. Crude and adjusted survey-weighted linear regression models were performed. Results: Creatinine-adjusted urinary inorganic arsenic concentrations were inversely associated with log-transformed BMI (p for trend = 0.0003) and log-transformed waist circumference (p for trend = 0.0001). The highest quintile of inorganic arsenic concentration (&gt;10.4 to 483.3 μg/L) was associated with a 5% (95% CI: 3 to 8%) lower BMI and a 4% (95% CI: 2 to 6%) smaller waist circumference compared to the lowest quintile (0 to 2.3 μg/L). Adjustments for age, gender, race, thyroid problems, diabetes, smoking status, seafood consumption, rice consumption, red blood cell folate, serum folate, socioeconomic status, and survey cycle did not appreciably alter these results. There was no evidence of effect modification between urinary inorganic arsenic concentrations and covariates on obesity. Conclusions: While inorganic arsenic exposure has generally been positively associated with obesity-related diseases, we observed a negative association between urinary inorganic arsenic concentrations and obesity in this representative cross-sectional analysis. It is unclear if this is a true association in which inorganic arsenic exposure is protective against obesity, or if this finding reflects differential arsenic absorption, metabolism, or storage by adiposity level.

Synthetic folic acid intakes and status in children living in Ireland exposed to voluntary fortification

In the context of mandatory and voluntary folic acid fortification, the exposure of children to folic acid has been a focus of concern, particularly regarding the possibility of whether any potentially adverse effects will emerge in the future. We explored concentrations of fasting unmetabolized folic acid (UFA) in the circulation of children living in Ireland who were exposed to the voluntary folic acid-fortification regimen in place in Ireland. Healthy children who were attending Our Lady's Children's Hospital, Crumlin, for routine minor surgery were recruited to provide a fasting 3-mL blood sample that was taken while a general anesthetic was administered. The samples were analyzed for plasma folate, red blood cell folate, and UFA concentrations. A short dietary questionnaire that captured recent and habitual intakes of folic acid, both as supplements and as fortified foods, was completed face to face with parents. We collected fasting samples (n = 68) and completed questionnaires that captured recent and habitual daily folic acid intakes of children grouped as follows: 0-5 y of age: 6 girls and 21 boys (27 children total); 6-10 y of age: 10 girls and 10 boys (20 children total); and 11-16 y of age: 10 girls and 11 boys (21 children total). UFA was detected in 10.3% of the samples tested (range: 0.5-1.3 nmol/L). Mean plasma folate and red blood cell folate concentrations were 35.1 nmol/L (range: 21-47 nmol/L) and 956 nmol/L (range: 305-2319 nmol/L), respectively. Mean daily intake of folic acid from fortified foods and supplements was 109 μg (range: 0-767 μg). We showed that there was UFA in the plasma of just >10% of the children sampled after an overnight fast. These findings should be considered by policy makers who are responsible for folic acid fortification. This trial was registered at www.isrctn.com as ISRCTN90038765.

A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming

Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL. Data for this analysis were collected as part of a prospective cohort study that recruited pregnant women upon admission into labor and delivery. Cord blood was collected for 96 maternal-fetal dyads, and DNA analysis was performed using quantitative polymerase chain reaction. The telomere to single copy gene ratio method was used to determine TL, and RBC folate levels were measured. Statistical analysis was conducted by incorporating a bootstrapping approach into generalized linear modeling–based analyses. Consistent significant positive correlations were observed between RBC folate and TL (telomere to single copy gene ratio) with 9880 of the 10000 (98.8%) iterations performed having a P value less than .05. Our study shows a positive association between umbilical cord RBC folate and fetal TL at birth. These findings may provide a pathway of understanding and preventing adult-onset disease and mortality through intrauterine reprogramming.

Association of Vitamin B12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults: A Longitudinal Population-Based Study.

Vitamin B12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. To investigate the association of circulating levels of vitamin B12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, β (SE) was 0.048 (0.013) for vitamin B12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (β [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140 mm Hg (β [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. This study suggests that both vitamin B12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B12 supplementation on slowing brain aging in older adults.

WHO Guideline: Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects

WHO Guideline: Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects

Significant nutritional variables in patients with eating disorders

Retrospective chart analysis of 113 patients presenting to a general practitioner with eating disorders was conducted, in an attempt to identify statistically and clinically significant nutritional variables. Blood tests are a useful diagnostic tool in eating disorders, and this research suggests that current testing should be broadened to include trace minerals such as zinc and manganese. Results were analysed for cholesterol, red blood cell folate, vitamin B12, magnesium, manganese, zinc, vitamin D, phosphate, ferritin, white cell count, red cell count and platelets. Patients were analysed as an entire group, but also separately as those suffering from Anorexia Nervosa (1), Bulimia Nervosa (2), EDNOS (3) and classic AN followed by BN (4). Analysis using T tests and chi squared showed that variables most likely to lie outside the population reference range were manganese, cholesterol, ferritin, vitamin B12, zinc and vitamin D.

Are Dieting and Dietary Inadequacy a Second Hit in the Association with Polycystic Ovary Syndrome Severity?

BackgroundThe composition of the diet is of increasing importance for the development and maturation of the ovarian follicles. In Polycystic Ovary Syndrome (PCOS) healthy dietary interventions improve the clinical spectrum. We hypothesized that dieting and diet inadequacy in the reproductive life course is associated with impaired programming of ovarian follicles and contributes to the severity of the PCOS phenotype.Methods and FindingsTo determine associations between the use of a self-initiated diet and diet inadequacy and the severity of the PCOS phenotype, we performed an explorative nested case control study embedded in a periconception cohort of 1,251 patients visiting the preconception outpatient clinic. 218 patients with PCOS and 799 subfertile controls were selected from the cohort and self-administered questionnaires, anthropometric measurements and blood samples were obtained. The Preconception Dietary Risk Score (PDR score), based on the Dutch dietary guidelines, was used to determine diet inadequacy in all women. The PDR score was negatively associated to cobalamin, serum and red blood cell folate and positively to tHcy. PCOS patients (19.9%), in particular the hyperandrogenic (HA) phenotype (22.5%) reported more often the use of a self-initiated diet than controls (13.1%; p = 0.023). The use of an inadequate diet was also significantly higher in PCOS than in controls (PDR score 3.7 vs 3.5; p = 0.017) and every point increase was associated with a more than 1.3 fold higher risk of the HA phenotype (adjusted OR 1.351, 95% CI 1.09–1.68). Diet inadequacy was independently associated with the anti-Müllerian Hormone (AMH) concentration (β 0.084; p = 0.044; 95% CI 0.002 to 0.165) and free androgen index (β 0.128; p = 0.013; 95% CI 0.028 to 0.229) in PCOS patients.ConclusionsThe use of a self-initiated diet and diet inadequacy is associated with PCOS, in particular with the severe HA phenotype. This novel finding substantiated by the association between diet inadequacy and AMH needs further investigation.

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023–0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038–0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032–0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005–0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005–0.018, p<0.01; RCD/CRL:β = 0.011mm/mm, 95%CI = 0.005–0.017, p<0.01). Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538–1813 nmol/L). These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child’s neurodevelopmental outcome are yet unknown and warrant further investigation.

The Dihydrofolate Reductase 19 bp Polymorphism Is Not Associated with Biomarkers of Folate Status in Healthy Young Adults, Irrespective of Folic Acid Intake1–3

Background: Dihydrofolate reductase (DHFR) is essential for the conversion of folic acid to active folate needed for one-carbon metabolism. Common genetic variation within DHFR is restricted to the noncoding regions, and previous studies have focused on a 19 bp deletion/insertion polymorphism (rs70991108) within intron 1. Reports of an association between this polymorphism and blood folate biomarker concentrations are conflicting.Objective: In this study, we evaluated whether the DHFR 19 bp deletion/insertion polymorphism affects circulating folate biomarkers in, to our knowledge, the largest cohort to address this question to date.Methods: Healthy young Irish individuals (n = 2507) between 19 and 36 y of age were recruited between February 2003 and February 2004. Folic acid intake from supplements and fortified foods was assessed with the use of a customized food intake questionnaire. Concentrations of serum folate and vitamin B-12, red blood cell (RBC) folate, and plasma total homocysteine (tHcy) were measured. Data were analyzed with the use of linear regression models.Results: Folic acid intake was positively associated with serum (P < 0.0001) and RBC (P = 0.0005) folate concentration and was inversely associated with plasma tHcy (P = 0.001) as expected. The DHFR 19 bp polymorphism was not significantly associated with either serum (P = 0.82) or RBC (P = 0.21) folate, or plasma tHcy (P = 0.20), even in those within the highest quintile of folic acid intake (>326 μg folic acid/d; P = 0.96). A nonsignificant trend toward lower RBC folate by genotype (P = 0.09) was observed in the lowest folic acid intake quintile (0–51 μg/d).Conclusion: In this cohort of healthy young individuals, the DHFR 19 bp deletion allele did not significantly affect circulating folate status, irrespective of folic acid intake. Our data rule out a strong functional effect from this polymorphism on blood folate concentrations.

High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood

Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.

High red blood cell folate is associated with an increased risk of death among adults with diabetes, a 15-year follow-up of a national cohort

Background and aimTo describe the mortality and fatality of diabetes and assess their relationship with the level of red blood cell (RBC) folate. Methods and resultWe analyzed the data of 526 adults with diabetes who participated in the National Health and Nutrition Examination Survey (1991–1994) as the baseline examination, and were followed up through December 31, 2006. Estimates of the hazard ratios (HRs) of selected death causes for individuals with different levels of RBC folate were obtained from Cox proportional hazards regression. A total of 295 deaths were recorded by the end of a 15-year follow-up with a mortality rate of 58.48 per 1000 person year (py). Diabetes was listed as a contributing cause for 136 deaths, accounting for 46.1% of the total deaths with a fatality rate 26.96 per 1000 py. Mortality rate for all-cause in the group with upper quartile of RBC folate was almost twice as high as that among the group with lower quartile, 82.75 vs. 44.10 per 1000 py. After adjusting for covariates, including serum concentration of vitamin B12, cotinine, homocysteine and the history of cardio-cerebral vascular diseases assessed at the baseline, the HRs for dying from any causes were 1.00 (reference), 1.82 (95% CI = 1.25–2.66) and 2.10 (1.37–3.20) among diabetic adults with lower, intermediate, and upper quartiles of RBC folate. ConclusionDiabetes was listed as a contributing cause for less than half of the deaths among adults with diabetes after 15+ years of follow-up; high RBC folate concentration was associated with an elevated risk of death among adults with diabetes.

Association of Nut Consumption with Cardiometabolic Risk Factors in the 2008/2009 New Zealand Adult Nutrition Survey.

Nut consumption has been associated with improvements in risk factors for chronic disease in populations within North America, Europe and Iran. This relationship has not been investigated in New Zealand (NZ). The associations between nut consumption and cardiometabolic risk factors among New Zealanders were examined. Data from the 24-h diet recalls of 4721 participants from the NZ Adult Nutrition Survey 2008/2009 (2008/2009 NZANS) were used to determine whole and total nut intake. Anthropometric data and blood pressure were collected, as well as blood samples analysed for total cholesterol (total-C) and HDL cholesterol (HDL-C), glycated haemoglobin (HbA1c), C-reactive protein (CRP) and folate. Participants were classified according to their five-year cardiovascular disease (CVD) risk. Both whole and total nut consumers had significantly lower weight, body mass index (BMI), waist circumference and central adiposity than non-nut consumers (all p ≤ 0.044). Whole blood, serum and red blood cell folate concentrations were significantly higher among whole nut consumers compared to non-whole nut consumers (all p ≤ 0.014), with only serum folate higher in total nut consumers compared to non-total nut consumers (p = 0.023). There were no significant differences for blood pressure, total-C, HDL-C and HbA1c; however, significant negative associations between total nut consumption and CVD risk category (p < 0.001) and CRP (p = 0.045) were apparent. Nut consumption was associated with more favourable body composition and a number of risk factors, which could collectively reduce chronic disease.