Red Cell Folate Research Articles

Maternal Cotinine Levels and Red Blood Cell Folate Concentrations in the Periconceptual Period.

Studies have examined the association between tobacco use and folate levels in pregnancy, yet few have assessed this relation using objective and accurate measures of both smoking and folate. In this study, we evaluated the association between maternal cotinine levels and periconceptional red blood cell (RBC) folic acid reserves in a cohort of low-income pregnant mothers. Smoking information, based on salivary cotinine, a highly sensitive and specific tobacco smoke exposure biomarker, was used. Furthermore, folate was assessed using RBC folate, an indicator of long-term folate storage. Participants were early to mid-trimester pregnant women who received antenatal care between 2011 and 2015 at the Genesis Clinic of Tampa (Florida). A total of 496 women were enrolled in the study. Associations between smoking status/maternal salivary cotinine concentrations, sociodemographic factors, and folate concentrations were investigated using Tobit regression analyses. The mean folate level of the participants was 718.3 ± 183.2 ng/mL, and only 2 (0.4%) participants were deficient in folate. We observed no significant difference in folate levels by smoking status. In contrast, salivary cotinine levels were significantly associated with decreased RBC folate concentrations (β -11.43, standard error 5.45, P = 0.032). Prepregnancy maternal body mass index, gestational age, stress, and depression also were associated with folate levels. Low RBC folate is associated with perinatal factors, including high maternal cotinine levels, body mass index, stress, and depression. The effect of low folate levels among smokers cannot be overemphasized, considering that tobacco products not only reduce folate levels but also decrease the bioutilization of folate.

Moderately elevated first trimester fasting plasma total homocysteine is associated with increased probability of miscarriage. The Reus-Tarragona Birth Cohort Study

The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n = 544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded.Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C > T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined.The exposed group consisted of participants with first trimester tHcy ≥ P90 (7.1 μmol/L) (n = 57) and unexposed of those with tHcy < P90 (n = 487). Adherence to folic acid supplement recommendations, plasma folate, plasma vitamin B12, RBC folate and prevalence of optimal RBC folate status (≥ 906 μmol/L) were lower in the exposed compared to unexposed group. The prevalences of the MTHFR 677 TT genotype and miscarriage were higher in the exposed group. The relative risks (95% CI) of pregnancy ending in miscarriage were 2.5 (1.1, 5.7) and 2.1 (1.0, 4.5) for participants in the high tHcy and suboptimal RBC folate groups (compared to the reference groups) respectively. Adherence to folic acid supplement recommendations was positively associated, while the MTHFR 677 TT versus CC genotype and smoking versus non-smoking were negatively associated, with RBC folate status.

Relationship of obesity with B vitamin status: analysis of NDNS data from UK women of reproductive age

AbstractPre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an effect not explained by lower dietary folate intake, or non-use of folic acid supplements (as recommended globally to women before and in early pregnancy for NTD prevention). While the exact mechanism linking NTD and obesity is poorly understood, it is possible that a compromised status or metabolism of folate and/or of the closely related micronutrients (vitamin B12, B6 and riboflavin) may be involved. To date however, this hypothesis has not been adequately explored. This study therefore aimed to investigate the relationship of obesity with folate and related B vitamin biomarkers in a representative cohort of non-pregnant UK women of reproductive age. Data were accessed from the most recent UK National Diet and Nutrition Survey (NDNS; Years 7–8; 2015–16), a rolling cross-sectional survey designed to gather information from a representative sample of the UK population on nutrient intakes, food consumption and nutritional status. Data for women aged 16–45 years (non B vitamin supplement users; n 364), were extracted on: anthropometry (height, weight, body mass index [BMI] and waist circumference [WC]), dietary intakes of B vitamins and biomarkers for serum and red blood cell folate, vitamin B12 (total serum B12 and holotranscobalamin), vitamin B6 (plasma pyridoxal-5-phosphate [PLP]) and riboflavin (erythrocyte glutathione reductase activation coefficient EGRAac]). Prevalence of overweight and obesity (i.e. BMI: 25–30kg/m2 and &gt; 30kg/m2) was 28% and 22% respectively, whilst abdominal obesity (i.e. WC &gt; 88cm) was present in 31% of the women. Total serum B12 (r -0.215, P 0.012) and PLP (r -0.270, P 0.002) were negatively correlated with WC, with similar, albeit weaker, correlations found for BMI. Correspondingly, women with abdominal obesity compared to those without, had a lower status of total serum B12 (Median values of: 212 v 249 v pmol/L; P 0.049), B6 (31.5 v 40.5 nmol/L; P 0.002) and EGRac (1.43 v 1.36; P 0.031). No differences in B vitamin dietary intake were observed by categories of abdominal obesity. Abdominal obesity may be a risk factor for low status of both vitamins B12 and B6, independently of dietary intake. Further investigation to elucidate the potential underlying mechanism is warranted. These findings also highlight the importance of taking abdominal obesity into account, in addition to BMI, when examining possible adverse impacts of obesity on micronutrient status.

The role of fortified foods and nutritional supplements in the diets of older Irish adults

AbstractLow intakes and suboptimal status of vitamin D, riboflavin, vitamin B12, folate and calcium have been reported in older adults across Europe. Dietary strategies to improve micronutrient intakes and status could include food fortification (mandatory or voluntary) and/or the use of nutritional supplements. This study aims to examine the impact of fortified food consumption and nutritional supplement use on nutrient intakes and nutritional status of vitamin D, riboflavin, vitamin B12, dietary folate equivalents (DFE) and calcium in older Irish adults.Analyses were based on the National Adult Nutrition Survey (NANS) (2008–2010). A 4 day semi-weighed food record was used to collect food and beverage intake data (including nutritional supplement use) from a nationally representative sample of 1500 adults (226 older adults (≥ 65y)). Blood samples (n 1126 (n 145 ≥ 65y)) were collected, processed and analysed using standard operating procedures. Nutrient intakes were estimated using WISP© based on UK and Irish food composition data. Fortified foods were identified as those that had one or more micronutrients added in the ingredient list and a nutritional supplement was defined as a supplement containing vitamins and/or minerals (i.e. excludes herbal/non-nutritional supplements). A fortified food consumer or nutritional supplement user was defined as a participant who consumed a fortified food or took a nutritional supplement at any time over the 4-day recording period. Usual intakes of micronutrients were calculated via the NCI-method using SAS© Enterprise Guide and analyses of biomarker data were carried out using SPSS©.The consumption of fortified foods and/or use of nutritional supplements increased mean intakes of vitamin D (3.6 to 6.9μg/d), riboflavin (1.6 to 2.3mg/d), vitamin B12 (4.5 to 6.0μg/d), DFE (228 to 408μg/d) and calcium (784 to 947mg/d) in older Irish adults and reduced the prevalence of inadequate intakes of these micronutrients by up to 40%. Furthermore, consumers of fortified foods and/or nutritional supplements had improved biomarker status and reduced prevalence of low/deficient status for vitamin D (62 vs 16%), riboflavin (65 vs 11%), vitamin B12 (8 vs 0%) and folate (serum folate:18 vs 0%; red blood cell folate: 0% across all groups) when compared to non-consumers.This study has shown that fortified foods and/or nutritional supplements represent an opportunity to improve intakes and status of key micronutrients in older adults. The data presented in this study will serve to inform the development and implementation of updated dietary recommendations for older adults in Ireland.

Organochlorine pesticides exposure may disturb homocysteine metabolism in pregnant women

Maternal exposure to organochlorine pesticides (OCPs) has an adverse impact on maternal and fetal health, and excessive homocysteine is related to a variety of adverse pregnancy outcomes. Biomimetic studies suggest that OCPs interfere with folate-dependent pathways, but little evidence is available from studies with human subjects. This study explored whether exposure to OCPs interferes with the metabolism of homocysteine, which is folate dependent. A total of 313 pregnant women at 12–20 weeks gestation were recruited in Shanxi province, China, from 2014 to 2015. Plasma concentrations of 20 OCPs, including dichlorodiphenyltrichloroethane and metabolites (DDTs), hexachlorobenzene (HCB), and hexachlorocyclohexanes (HCHs), were analyzed by gas chromatography–mass spectrometry. Blood folate concentrations were analyzed by microbiological assay, and plasma homocysteine concentrations were determined by enzyme-linked immunosorbent assay. Information on demographics, lifestyle behaviors, and folic acid supplementation was collected by in-person interview. Of the women, 99% reported having taken folic acid supplements. Results of a logistic regression analysis showed that higher plasma levels of OCPs were associated with increased odds of higher plasma homocysteine after adjustment for potential confounding factors. Positive correlations were observed between plasma OCPs and plasma homocysteine concentrations: HCB (r = 0.176, p = 0.002), β-HCH (r = 0.172, p = 0.002), ρ,ρ′-DDE (r = 0.132, p = 0.020), ρ,ρ′-DDD (r = 0.161, p = 0.004), and ο,ρ′-DDT (r = 0.144, p = 0.011). Plasma concentrations of OCPs were negatively correlated with red blood cell (RBC) folate in the low-RBC-folate subgroup, but the correlations were not statistically significant. A positive correlation was observed between OCPs and homocysteine in the low-RBC-folate subgroup. These findings suggest that OCPs may disturb the folate-dependent homocysteine metabolism pathway.

Nutritional Risks in Adolescents After Bariatric Surgery

Little is known about prevalence and risk factors for nutritional deficiencies in adolescents after metabolic bariatric surgery. We performed a 5-year prospective cohort study of these. Adolescents who had Roux-en-Y gastric bypass (RYGB, n= 161) or vertical sleeve gastrectomy (VSG, n= 67) were enrolled at 5 tertiary-care centers from March 2007 through February 2012. The final analysis cohort included 226 participants (161 who had RYGB and 65 who had VSG). We measured serum levels of ferritin; red blood cell folate; vitamins A, D, B1, B12; and parathyroid hormone at baseline and annually for 5 years. General linear mixed models were used to examine changes over time and identify factors associated with nutritional deficiencies. The participants were 75% female and 72% white, with a mean age of 16.5 ± 1.6 years and mean body mass index of 52.7 ± 9.4 kg/m2 at surgery. Mean body mass index decreased 23% at 5 years, and did not differ significantly between procedures. After RYGB, but not VSG, serum concentrations of vitamin B12 significantly decreased whereas serum levels of transferrin andparathyroid hormone increased. Ferritin levels decreased significantly after both procedures. Hypo-ferritinemia was observed in 2.5% of patients before RYGB and 71% at 5 y after RYGB (P < .0001), and 11% of patients before VSG and 45% 5 y after VSG (P= .002). No significant changes in serum levels of folate or vitamins A, B1, or D were found between baseline and 5 y after either procedure. By 5 y, 59% of RYGB and 27% of VSG recipients had 2 or more nutritional deficiencies. Risk factors associated with specific deficiencies included surgery type, female sex, black race, supplementation intake, weight regain, and for females, pregnancy. In a prospective study of adolescents who underwent RYGB or VSG, we observed nutritional deficiencies by 5 y after the procedures-particularly in iron and B12 after RYGB. Ongoing nutrient monitoring and supplementation are recommended for all patients, but surgery type, supplementation intake, sex, and race might affect risk. (Clinical trial registration: Adolescent Bariatrics: Assessing Health Benefits and Risk [also known as Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS)], NCT00474318.).

Low folate status, and MTHFR 677C > T and MTR 2756A > G polymorphisms associated with colorectal cancer risk in Thais: a case-control study

Folate plays essential roles in DNA synthesis, repair, and methylation; thus, folate status may affect carcinogenesis. Genetics polymorphisms involved in folate metabolisms have been linked with colorectal cancer (CRC) development. Therefore, we hypothesized that low folate status and related genetic polymorphisms are associated with higher risk of CRC. This case-control study enrolled 105 new cases of CRC, 101 of colorectal adenoma (CRA), and 182 controls from hospitals in Bangkok, Thailand, to examine the association between folate status and methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine synthase (MTR) 2756A > G, and methionine synthase reductase (MTRR) 66A > G with the risk of CRC and CRA. Regarding CRC risk, the lowest quartile group of serum folate and folate intake had higher risk of CRC than the highest quartile group (odds ratio [OR] = 11.45, 95% confidence interval [CI] = 4.43-29.59) and (OR = 10.29, 95% CI = 4.17-25.41). The lowest quartile group of folate intake also had a higher risk of CRA (OR = 5.22, 95% CI = 2.19-6.09). Low red blood cell folate combined with MTHFR 677C > T polymorphism statistically increased CRC risk (OR = 10.00, 95% CI = 1.36-73.42). Low folate status combined with MTR 2756A > G significantly increased CRA risk (OR = 6.43, 95% CI = 1.38-29.94). Moreover, the risk of CRC was elevated with alcohol consumption and low exercise activity when combined with low folate status (P < .05). This study supported the hypothesis that, in Thais, low folate status is associated with a higher risk of CRC, particularly among those with polymorphisms of the MTHFR 677C > T and MTR 2756 A > G genes.

Folate levels in pregnancy and offspring food allergy and eczema

High folate status in pregnancy has been implicated in the increased prevalence of allergic disease, but there are no published data relating directly measured folate status in pregnancy to challenge-proven food allergy among offspring. The study aim was to examine the association between red blood cell (RBC) folate status in trimester three of pregnancy and allergic disease among offspring. Red blood cell folate levels were measured at 28-32weeks' gestation in a prospective birth cohort (n=1074). Food allergy outcomes were assessed in 1-year-old infants by skin prick testing and subsequent food challenge. Eczema was assessed by questionnaire and clinical review. High trimester three RBC folate was defined as greater than (>) 1360nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6nmol/L (standard deviation 415.4) with 82% (731/894) >1360nmol/L. There was no evidence of either linear or non-linear relationships between trimester three RBC folate and allergic outcomes, nor evidence of associations between high RBC folate and food allergy (adjusted risk ratio (aRR) 2.89, 95% CI 0.90-9.35), food sensitization (aRR 1.72, 95% CI 0.85-3.49), or eczema (aRR 0.97, 95% CI 0.67-1.38). The majority of pregnant women in this study had high RBC folate levels. There was no evidence of associations between trimester three RBC folate and food allergy, food sensitization, or eczema among the offspring, although larger studies are required.

Changes in intracellular folate metabolism during high-dose methotrexate and Leucovorin rescue therapy in children with acute lymphoblastic leukemia.

BackgroundMethotrexate (MTX) is an important anti-folate agent in pediatric acute lymphoblastic leukemia (ALL) treatment. Folinic acid rescue therapy (Leucovorin) is administered after MTX to reduce toxicity. Previous studies hypothesized that Leucovorin could ‘rescue’ both normal healthy cells and leukemic blasts from cell death. We assessed whether Leucovorin is able to restore red blood cell folate levels after MTX.MethodsWe prospectively determined erythrocyte folate levels (5-methyltetrahydrofolate (THF) and non-methyl THF) and serum folate levels in 67 children with ALL before start (T0) and after stop (T1) of HD-MTX and Leucovorin courses.ResultsErythrocyte folate levels increased between T0 and T1 (mean ± SD: 416.7 ± 145.5 nmol/L and 641.2 ± 196.3 nmol/L respectively, p<0.001). This was due to an increase in 5-methyl THF levels (mean increase: 217.7 ± 209.5 nmol/L, p<0.001), whereas non-methyl THF levels did not change (median increase: 0.6 nmol/L [-9.9–11.1], p = 0.676). Serum folate levels increased between T0 and T1 (median increase: 29.2 nmol/L [32.9–74.0], p<0.001). Results were not significantly affected by age, sex, ALL immunophenotype and MTHFR c.677C>T genotype.ConclusionIntracellular folate levels accumulate after HD-MTX and Leucovorin therapy in children with ALL, suggesting that Leucovorin restores the intracellular folate pool. Future studies are necessary to assess concomitant lower uptake of MTX.

Suitability and safety of L-5-methyltetrahydrofolate as a folate source in infant formula: A randomized-controlled trial.

L-5-methyltetrahydrofolate is the predominant folate form in human milk but is currently not approved as a folate source for infant and follow-on formula. We aimed to assess the suitability of L-5-methyltetrahydrofolate as a folate source for infants. Growth and tolerance in healthy term infants fed formulae containing equimolar doses of L-5-methyltetrahydrofolate (10.4 μg/ 100 ml, n = 120, intervention group) or folic acid (10.0 μg/ 100 ml, n = 120, control group) was assessed in a randomized, double-blind, parallel, controlled trial. A reference group of breastfed infants was followed. Both formulae were well accepted without differences in tolerance or occurrence of adverse events. The most common adverse events were common cold, poor weight gain or growth, rash, eczema, or dry skin and respiratory tract infection. Weight gain (the primary outcome) was equivalent in the two groups (95% CI -2.11; 1.68 g/d). In line with this, there was only a small difference in absolute body weight adjusted for birth weight and sex at visit 4 (95% CI -235; 135 g). Equivalence was also shown for gain in head circumference but not for recumbent length gain and increase in calorie intake. Given the nature of the test, this does not indicate an actual difference, and adjusted means at visit 4 were not significantly different for any of these parameters. Infants receiving formula containing L-5-methyltetrahydrofolate had lower mean plasma levels of unmetabolized folic acid (intervention: 0.73 nmol/L, control: 1.15 nmol/L, p<0.0001) and higher levels of red cell folate (intervention: 907.0 ±192.8 nmol/L, control: 839.4 ±142.4 nmol/L, p = 0.0095). We conclude that L-5-methyltetrahydrofolate is suitable for use in infant and follow-on formula, and there are no indications of untoward effects.Trial registration: This trial was registered at ClinicalTrials.gov (NCT02437721).

Les vitamines B9 et B12 : rôle métabolique, étiologies et conséquences des carences, méthodes d’exploration et recommandations nutritionnelles

Folates and cobalamins are cofactors both involved in DNA synthesis through one carbon metabolism. Any deficiency in one of these vitamins will impact tissues with a high mitotic index, particularly mucosa and hematopoiesis, leading to the classical glossitis and megaloblastic anemia. However, hematological impairment may be more discreet and difficult to recognize, restricted to macrocytosis or isolated thrombocytopenia. Of note, deficiency may lead to extra hematological features that depend on specific metabolic functions of each vitamin. Cobalamins are involved in myelin synthesis and deficiency may lead to sometimes irreversible neuropsychiatric complications. Folates deficiency in pregnant women has been associated with neural tube defects and peri-conception folic acid supplementation is now recommended. Routine biological diagnosis is based on serum folates and vitamin B12 immuno-assays that should be interpreted carefully and confronted with clinical data. In difficult cases, other tests with a higher sensitivity and/or specificity such as homocysteine, methylmalonic acid, holotranscobalamin and red blood cell folates level can be used.

Anemia and Iron, Vitamin B12, and Folate Deficiencies in Women of Reproductive Age in Ecuador: Results from the Ecuadorian National Health and Nutrition Survey (P10-027-19)

ObjectivesTo examine the burden of anemia and deficiencies of iron, vitamin B12, and folate in women of reproductive age (WRA) in Ecuador. MethodsData from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were analyzed to examine the burden of anemia and micronutrient deficiencies among 7658 women of reproductive age (12–49 y; n = 7383 non-pregnant, n = 275 pregnant). Venous blood samples were collected, and hemoglobin (Hb) was assessed viathe sodium lauryl sulfate method. Samples were centrifuged, processed, and stored < -50°C until analysis. Serum ferritin (SF), vitamin B12, serum folate, and red blood cell (RBC) folate were measured viachemiluminescence. Hemoglobin was adjusted for altitude; and anemia was defined as Hb <11.0 g/dL in pregnant women and <12.0 g/dL in non-pregnant women. Iron deficiency and insufficiency were defined as SF <15.0 μg/L and <20.0 μg/L, respectively. Vitamin B12 deficiency and insufficiency were defined as <148.0 pmol/L and <221.0 pmol/L; and folate deficiency was defined as serum folate <7.0 nmol/L and RBC folate <342.0 nmol/L. Survey logistic and linear regression were used to examine associations of micronutrients with hemoglobin concentrations and anemia. ResultsIn analyses among non-pregnant women, 11.3% were anemic, 14.4% were iron deficient, and 21.1% had iron insufficiency. A total of 4.3% of women had vitamin B12 deficiency, 23.9% had vitamin B12 insufficiency; and <1% of women were folate deficient. The prevalence of micronutrient deficiencies was higher in pregnant women, compared to non-pregnant women: 31.1% of pregnant women were iron deficient, 43.0% were iron insufficient, 21.3% were vitamin B12 deficient, and 55.4% were vitamin B12 insufficient. In non-pregnant WRA, higher SF (P < 0.0001), vitamin B12 (P < 0.01), and serum folate (P < 0.0001) concentrations were associated with higher Hb concentrations; and higher SF (OR: 0.96, 95% CI: 0.95, 0.97; P < 0.0001) and serum folate (OR: 0.98, 95% CI: 0.97, 0.98; P < 0.0001) concentrations were associated with lower odds of anemia. In pregnant women, SF (P < 0.01) and serum folate (P = 0.002) concentrations were associated with higher hemoglobin concentrations. ConclusionsFindings suggest that the burden of anemia, iron deficiency, and vitamin B12 insufficiency is high among women of reproductive age in Ecuador. Funding SourcesNot applicable.

Micronutrient Status of Recreational Runners with Vegetarian or Non-Vegetarian Dietary Patterns.

Vegetarian diets have gained popularity in sports. However, few data exist on the status of micronutrients and related biomarkers for vegetarian and vegan athletes. The aim of this cross-sectional study was to compare the micronutrient status of omnivorous (OMN, n = 27), lacto-ovo-vegetarian (LOV, n = 26), and vegan (VEG, n = 28) recreational runners. Biomarkers of vitamin B12, folate, vitamin D, and iron were assessed. Additionally, serum levels of calcium, magnesium, and zinc were examined. Lifestyle factors and supplement intake were recorded via questionnaires. About 80% of each group showed vitamin B12 adequacy with higher levels in supplement users. Mean red blood cell folate exceeded the reference range (>340 nmol/L) in all three groups (OMN: 2213 ± 444, LOV: 2236 ± 596, and VEG: 2354 ± 639 nmol/L; not significant, n.s.). Furthermore, vitamin D levels were comparable (OMN: 90.6 ± 32.1, LOV: 76.8 ± 33.7, and VEG: 86.2 ± 39.5 nmol/L; n.s.), and we found low prevalence (<20%) of vitamin D inadequacy in all three groups. Less than 30% of each group had depleted iron stores, however, iron deficiency anemia was not found in any subject. Our findings suggest that a well-planned, health-conscious lacto-ovo-vegetarian and vegan diet, including supplements, can meet the athlete’s requirements of vitamin B12, vitamin D and iron.

Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children's Health.

BackgroundLow red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan.MethodsIn total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression.ResultsBlood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4–21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74–1.32), 0.63 (95% CI, 0.30–1.33), and 4.10 (95% CI, 0.96–17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects.ConclusionsWe were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.

Folate/homocysteine metabolism and lung cancer risk among smokers.

BackgroundFolate and homocysteine are involved in DNA synthesis and methylation processes, which are deregulated during carcinogenesis.ObjectivesThe aim of this study was to assess the relationship between folate/homocysteine concentrations, the functional polymorphisms of folate/homocysteine genes and lung cancer risk among cigarette smokers.Study designThe study included 132 lung cancer patients and 396 controls from northern Poland, matched by sex, age and smoking status. The median cigarette pack-years of smoking among both cases and controls was 30.0. Serum, red blood cell (RBC) folates and serum homocysteine concentrations were measured. The genotypes in selected polymorphic sites of the MTHFR, CBS, SHMT1, MTHFD1, MTRR, MTR, TYMS DHFR, TCN2, and SLC19A1 genes were determined. All study participants underwent scanning with low-dose computed tomography.ResultsSerum folate concentrations above the median (> 17.5 nmol/l among the healthy controls) were associated with an increased lung cancer risk (odds ratio [OR], 1.54, 95% confidence intervals [CI], 1.04–2.29, P = 0.031). An analogous trend was observed when the population was analysed after subdivision according to RBC folate concentrations, that is, above a value of 506.5 nmol/l (OR, 1.53; 95% CI, 0.95–2.47; P = 0.084). Additionally, in a subset of women, an increased risk of lung cancer development was associated with the SLC19A1 c.80AA genotype (c.80AA versus GG OR, 3.14; 95% CI, 1.32–7.46; P = P = 0.010).ConclusionThese results suggest that, in the population consisting of heavy smokers, high folate levels add to the cancerogenic effect of smoking.

Urate and Homocysteine: Predicting Motor and Cognitive Changes in Newly Diagnosed Parkinson's Disease.

Background:Urate and homocysteine are potential biomarkers for disease progression in Parkinson’s disease (PD). Baseline serum urate concentration has been shown to predict motor but not cognitive decline. The relationship between serum homocysteine concentration and cognitive and motor impairment is unknown.Objectives:The aim of this study was to examine the association between baseline serum urate and homocysteine, and prospective measures of disease progression and cognition over 54 months in early PD.Methods:154 newly diagnosed PD participants and 99 age-matched controls completed a schedule of assessments at baseline, 18, 36 and 54 months. The Movement Disorders Society Unified Parkinson’s Disease Scale Part III (MDS-UPDRS III) was used to assess motor severity. The Montreal Cognitive Assessment (MoCA) was used to assess global cognition. Serum samples drawn at baseline were analysed for urate, homocysteine, red cell folate and vitamin B12 concentrations.Results:Baseline urate was 331.4±83.8 and 302.7±78.0μmol/L for control and PD participants, respectively (p = 0.015). Baseline homocysteine was 9.6±3.3 and 11.1±3.8μmol/L for controls and PD participants, respectively (p < 0.01). Linear mixed effects modelling showed that lower baseline urate (β= 0.02, p < 0.001) and higher homocysteine (β= 0.29, p < 0.05) predicted decline in motor function. Only higher homocysteine concentrations at baseline, however, predicted declining MoCA scores over 54 months (β= 0.11, p < 0.01).Conclusions:Lower serum urate concentration is associated with worsening motor function; while higher homocysteine concentration is associated with change in motor function and cognitive decline. Therefore, urate and homocysteine may be suitable biomarkers for predicting motor and cognitive decline in early PD.

Reducing red blood cell folate testing: a case study in utilisation management

Mandatory enrichment of wheat flour in Canada with folic acid since 1998 has caused folate deficiency to be rare. There were 3019 red blood cell (RBC) folate tests performed during...

The relationship between maternal plasma homocysteine in early pregnancy and birth weight

Background: There is limited evidence that plasma homocysteine (Hcy) is increased in women with adverse pregnancy outcomes, such as low birth weight (LBW). Objective: We examined the relationship between maternal Hcy at the first prenatal visit and birth weight. Study design: In a prospective observational study, women were recruited during their first prenatal visit after sonographic confirmation of gestational age. Along with the standard tests, blood was also taken for the measurement of maternal serum and red blood cell (RBC) folate, vitamin B12, and Hcy. In addition to collecting standard clinical and sociodemographic details, a detailed questionnaire on vitamin supplementation was completed under supervision. Birth outcomes were collected immediately after delivery. Results: Of 498 women recruited, 213 (42.8%) were nulliparous, 97 (19.4%) were obese, 64 (12.9%) selfreported as current smokers, and 489 (98.2%) were taking folic acid (FA) supplements at presentation. The mean (SD) birth weight was 3426.3 g (600.7), 14.0% of infants were small for gestational age, and 7.4% were large for gestational age. Mean (SD) plasma Hcy was 7.1 (2.1) µmol/l. On multiple linear regression, higher plasma Hcy was associated with selfreported smoking (p = .009), relative income poverty (p = .037) and Irish nativity (p = .009). There was no relationship between maternal plasma Hcy and birth weight centile, either overall or when analyzed separately for either smokers (r = 0.0001, p = .98) and nonsmokers (r = −0.007, p = .097). Plasma Hcy was correlated negatively with serum folate, RBC folate, and serum vitamin B12. There was no association between maternal Hcy and the duration of FA supplementation in weeks (r = −0.08, p = .083) or between maternal Hcy and gestational age at phlebotomy (r = −0.54, p = .35). Conclusions: In this well-characterized cohort of women in early pregnancy, there was no correlation between maternal plasma Hcy and birth weight. However, higher Hcy was associated with maternal smoking and social deprivation which may explain the association reported previously between an increased Hcy and LBW. Rationale This study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development. Rationale This study was conducted to investigate the relationship between maternal homocysteine in early pregnancy and infant birth weight. Increased plasma homocysteine in early pregnancy was not associated with a lower birth weight. However, there was a positive correlation between increasing plasma homocysteine and maternal smoking and social disadvantage which are risk factors for lower birth weight. This study highlights the importance of correcting for confounding variables, such as smoking and social disadvantage, when evaluating the relationship maternal nutritional biomarkers and intrauterine fetal development.

B-vitamins in Relation to Depression in Older Adults Over 60 Years of Age: The Trinity Ulster Department of Agriculture (TUDA) Cohort Study

ObjectivesMental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B12, vitamin B6, and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders. DesignThe Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study. Setting and ParticipantsCommunity-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012. MeasuresDepression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B12, plasma pyridoxal-5-phosphate (PLP; vitamin B6), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin). ResultsBiomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B6 (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B12, were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin–fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B6 (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety. Conclusions/ImplicationsBetter B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people.

Dried blood spot microbiological assay indicates high prevalence of folate deficiency in rural adult men and women in the Haitian Central Plateau

Although folate deficiency is linked to adverse health effects, limited data exist characterizing the problem in rural settings. This study determined the prevalence of folate deficiency and anemia in rural adults in the Haitian Central Plateau using combined laboratory methods. Dried blood spots (DBSs) and hemoglobin measurements were collected from adult men and women selected by cluster random sampling in Haiti's Central Plateau. DBSs were analyzed for folate using a microbiological assay. Hemoglobin levels were determined using both a HemoCue photometer and the sodium lauryl sulfate microplate method. Red cell folate (RCF) levels were determined by normalizing DBS folate to hemoglobin. Of the 197 subjects assessed for hemoglobin, 11.4% of males and 21.0% of females were anemic (male: hemoglobin<12 g/dL; female: hemoglobin<11 g/dL). Of the 173 subjects assessed for RCF, 27.9% of men and 14.9% of women were folate deficient (RCF<340 nmol/L). Among reproductive-age women, 83.6% had RCF levels associated with a risk of neural tube defects of >14 per 10 000 live births (RCF≤699 nmol/L). Adults in the Haitian Central Plateau suffer from high rates of anemia and folate deficiency, putting the population at elevated risk for disease. DBSs and microbiological assay make folate evaluation feasible, even in low-resource regions.