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Background Achieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit. Objective Here, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy. Methods Using data from the Maternal–Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n  = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors. Results Almost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 μg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 μg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI. Conclusions In the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses. [ABSTRACT FROM AUTHOR]

Folate deficiency has been confirmed to be related to various diseases. Unfortunately, there are few reports on the folate status of Chinese adults. This study aims to evaluate the serum folate status of blood donors in south-central China. In this study, 248 blood donors were included. The information on subjects was collected by a brief questionnaire concerning alcohol consumption habits, smoking habits, fruit and vegetable consumption and physical activity. The serum folate concentration was measured by electrochemiluminescence immunoassay. The geometric mean serum folate concentration was 13.4 nmol l − 1 (95% CI, 12.7–14.1). The prevalence of serum folate concentrations below 6.8 nmol l − 1 was 5.2% (95% CI, 2.5–8.0). There were significant differences in serum folate concentrations with respect to sex (p-values < 0.05), age (p-values < 0.05), fruit and vegetable consumption (p-values < 0.05), and alcohol consumption habits (p-values < 0.05). The concentration of serum folate increased with age (p-values < 0.05) and fruit and vegetable consumption (p-values < 0.05). Individuals with an age of 30 years or younger were nearly 3.5 times as likely as those aged over 30 years to have an insufficient level of serum folate (OR = 3.48; 95% CI: 1.01–11.99). An age of 30 years or younger was a risk factor for folate deficiency. Most blood donors had sufficient serum folate concentrations in south-central China. National surveys of folate status should be implemented in China. [ABSTRACT FROM AUTHOR]

Background Periconceptional folic acid (FA) supplementation is recommended to prevent the occurrence of neural tube defects. Currently, most over-the-counter FA supplements in Canada and the United States contain 1 mg FA and some women are prescribed 5 mg FA/d. High-dose FA is hypothesized to impair 1-carbon metabolism. We aimed to determine folate and 1-carbon metabolism biomarkers in pregnant women exposed to 1 mg or 5 mg FA. Objectives This was an ancillary study within the Folic Acid Clinical Trial (FACT), a randomized, double-blinded, placebo-controlled, phase III trial designed to assess the efficacy of high-dose FA to prevent preeclampsia. Methods For FACT, women were randomized at 8–16 gestational weeks to receive daily 4.0 mg FA (high dose) or placebo (low dose) plus their usual supplementation (≤1.1 mg). Women were recruited from 3 Canadian FACT centers and provided nonfasting blood samples at 24–26 gestational weeks for measurement of RBC and serum total folate, serum unmetabolized FA (UMFA), tetrahydrofolate (THF), 5-methylTHF, 5-formylTHF, 5,10-methenylTHF, and MeFox (pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF, a 5-methylTHF oxidation product); total vitamins B-12 and B-6; and plasma total homocysteine. Group differences were determined using χ2, Fisher exact, and Wilcoxon rank-sum tests. Results Nineteen (38%) women received high-dose FA and 31 (62%) received low-dose FA. The median RBC folate concentration was 2701 (IQR: 2243–3032) nmol/L and did not differ between groups. The high-dose group had higher serum total folate (median: 148.4 nmol/L, IQR: 110.4–181.2; P  = 0.007), UMFA (median: 4.6 nmol/L, IQR: 2.5–33.8; P  = 0.008), and 5-methylTHF (median: 126.6 nmol/L, IQR: 98.8–158.6; P  = 0.03) compared with the low-dose group (median: 122.8 nmol/L, IQR: 99.5–136.0; median: 1.9 nmol/L, IQR: 0.9–4.1; median: 108.6 nmol/L, IQR: 96.4–123.2, respectively). Other biomarkers of 1-carbon metabolism did not differ. Conclusions High-dose FA supplementation in early pregnancy increases maternal serum folate but not RBC folate concentrations, suggesting tissue saturation. Higher UMFA concentrations in women receiving high-dose FA supplements suggest that these doses are supraphysiologic but with no evidence of altered 1-carbon metabolism. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the effect of folic acid supplements on infant and child allergic diseases through systematic review and meta-analysis.Design: PubMed, The Cochrane Library and references of related articles published before January 1, 2020 were searched.Setting: Meta-analysis was used to explore the influence of folic acid on skin allergies (eczema, and atopic dermatitis) and respiratory allergies (asthma, wheezing, and allergic rhinitis).Participants: Data were collected from 15 studies with 244,018 individual participants from five different countries for meta-analysis.Results: Folic acid was confirmed as a risk factor for allergic diseases in infant and child. The risk of allergic diseases dramatically increased when maternal folic acid intake

Background: 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. Methods: Red blood cell folate levels were measured at 28‐32 weeks' 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 (>) 1360 nmol/L. Binomial regression was used to examine associations between trimester three RBC folate and allergic outcomes, adjusting for potential confounders. Results: Red blood cell folate levels were measured in 88% (894/1064) of pregnant women. The mean concentration was 1695.6 nmol/L (standard deviation 415.4) with 82% (731/894) >1360 nmol/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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status. [ABSTRACT FROM AUTHOR]

Objective: To assess the nutritional status of folate and vitamin B12 with anaemia in young children. Design: A cross-sectional study was conducted at the primary health-care centres of four Brazilian cities. Folate and vitamin B12 were assessed by fluoroimmunoassay. Multilevel Poisson regression models were used to explore the association of folate and vitamin B12 status in relation to anaemia in young children. Setting: Brazil. Participants: Children (n 460) aged 11 to 15 months. Results: The median (interquartile range) of serum folate was 39·7 (28·8–55·3) nmol/l and only four children presented with folate deficiency (<10 nmol/l). Surprisingly, 30·9 % of children presented with serum folate concentrations above the upper limit of detectable values by the commercial kit used for analysis. The frequency of vitamin B12 deficiency (<148 pmol/l) was 15 % and it was inversely associated with the highest tertile of serum folate concentrations (P <0·001). Having high serum folate concentration (≥50·1 nmol/l) and vitamin B12≥148 pmol/l was associated with lower frequency of anaemia in these children (prevalence ratio=0·53; 95% CI 0·30, 0·92). Conclusions: High frequency of elevated serum concentration of folate was found among young Brazilian children and 15 % of them had vitamin B12 deficiency. The combination of high serum folate and normal vitamin B12 status was associated with a lower frequency of anaemia in these children. Improvements in the current strategies to promote healthy food-based complementary feeding along with prevention and control of micronutrient deficiencies are recommended to improve children's health. [ABSTRACT FROM AUTHOR]

Objective: While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB.Design: Observational study.Setting: Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.ParticipantsMother-infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24-72 h after delivery.Results: Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3-5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB.Conclusions: If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era. [ABSTRACT FROM AUTHOR]

Objective: To assess the nutritional status of folate and vitamin B12 with anaemia in young children.Design: A cross-sectional study was conducted at the primary health-care centres of four Brazilian cities. Folate and vitamin B12 were assessed by fluoroimmunoassay. Multilevel Poisson regression models were used to explore the association of folate and vitamin B12 status in relation to anaemia in young children.Setting: Brazil.ParticipantsChildren (n 460) aged 11 to 15 months.Results: The median (interquartile range) of serum folate was 39·7 (28·8-55·3) nmol/l and only four children presented with folate deficiency (<10 nmol/l). Surprisingly, 30·9 % of children presented with serum folate concentrations above the upper limit of detectable values by the commercial kit used for analysis. The frequency of vitamin B12 deficiency (<148 pmol/l) was 15 % and it was inversely associated with the highest tertile of serum folate concentrations (P<0·001). Having high serum folate concentration (≥50·1 nmol/l) and vitamin B12≥148 pmol/l was associated with lower frequency of anaemia in these children (prevalence ratio=0·53; 95% CI 0·30, 0·92).Conclusions: High frequency of elevated serum concentration of folate was found among young Brazilian children and 15 % of them had vitamin B12 deficiency. The combination of high serum folate and normal vitamin B12 status was associated with a lower frequency of anaemia in these children. Improvements in the current strategies to promote healthy food-based complementary feeding along with prevention and control of micronutrient deficiencies are recommended to improve children's health. [ABSTRACT FROM AUTHOR]

Summary Background & aims To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. Methods PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. Results Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta-analysis of randomized controlled trials, RR: 1.07 (95% CI: 0.86–1.43). The effect on risk was not significant in cohort studies either; RR = 0.96 (95% CI: 0.76–1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59–0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62–0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85–1.30). Conclusion The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlight the importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed. [ABSTRACT FROM AUTHOR]

Purpose: National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status.Methods: Folate intake was estimated using a web-based 4-d food record in adults aged 18-80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status.Results: Median folate intake was 246 µg/day (Q1 = 196, Q3 = 304, n = 1797) and for women of reproductive age 227 µg/day (Q1 = 181, Q3 = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q1 = 201, Q3 = 323) and for women of reproductive age 239 µg/day (Q1 = 185, Q3 = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations <6.8 nmol/L) of the participants, respectively. None of the women of reproductive age had erythrocyte folate concentrations associated with the lowest risk of neural tube defects. Dietary patterns associated with higher folate status were rich in vegetables, pulses and roots as well as cheese and alcoholic beverages, and low in meat.Conclusions: Prevalence of low erythrocyte folate concentrations was low in this population, and estimated dietary intakes are well above average requirement. However, to obtain a folate status optimal for prevention of neural tube defects major dietary changes are required and folic acid supplements recommended prior to conception. [ABSTRACT FROM AUTHOR]

Several studies have described a positive association between elevated BMI and birth defects risk. Data on plasma concentration of folate in pregnant women with obesity have shown values far below those recommended, regardless of diet, while folate levels should increase before pregnancy to reduce neural tube defects. We report a descriptive review of the most recent studies (from 2005 to 2015) to evaluate folate status through a population of women of childbearing age affected by obesity. The literature contains few studies, which present conflicting results regarding folate status in non-pregnant women of childbearing age affected by obesity and it appears that there is a modification in folate metabolism, with a reduction in plasma folate levels and an increase in erythrocyte folate uptake. In conclusion, the folate status in women of childbearing age should be assessed by both plasma and erythrocyte levels to start a personalised and more adequate supplementation before conception. Further studies need to be conducted in a larger population, which take into account variables that can affect folate metabolism, such as dietary intake, lifestyle and genetic factors, oral contraceptives or other drug use, previous weight-loss programmes, or a history of bariatric surgery. [ABSTRACT FROM AUTHOR]

Abstract Objective : To describe serum folate status and the socio‐demographic correlates of serum folate status in a national sample of women aged 26–36 years in Australia, 2004–2006. Methods: Stored serum samples from 1,046 women, collected as part of the Childhood Determinants of Adult Health study, were analysed for serum folate. Results: Median (IQR) serum folate was 27.1 nmol/L (18.8–35.0 nmol/L) with only 7.0% of samples below 11 nmol/L. Serum folate was positively associated with supplement use, educational level, occupational status and urban dwelling. Conclusions: In this population‐based sample, most women had folate levels in the normal range with few having low serum folate. Those of lower socioeconomic position or with poorer health behaviours had lower folate levels, though most were still within the normal range. Implications: In the absence of comprehensive national survey data on the folate status of women of child‐bearing age, these data provide a valuable baseline for evaluating the impact of mandatory folic acid fortification in Australia, which commenced in 2009. It is likely that mandatory fortification of the food supply with folic acid will reduce the disparities in folate status between socioeconomic groups and in people with poorer health behaviours.

Objetivo: Estudiar la situación de folatos de escolares españoles y su asociación con la presencia del hábito tabáquico en los padres. Métodos: Se estudiaron 511 escolares entre 9 y 12 años de Madrid (España). La información sobre el hábito tabáquico de los padres fue autodeclarada. La ingesta de energía y de nutrientes (especialmente folatos) se calculó utilizando el método de registro de alimentos durante tres días (de domingo a martes) y en dos de ellos (lunes y martes) se procedió a controlar los alimentos consumidos en el comedor escolar, utilizando el método de pesada precisa individual (pesando alimentos servidos y restos dejados en el plato). La ingesta de folatos se comparó con la ingesta recomendada (IR). Se analizaron las concentraciones séricas de folatos, vitamina B12 y homocisteína. Para el análisis estadístico se utilizaron los test de t-student, Mann Whitney, correlación de Pearson y Spearman, ANCOVA, MANCOVA y regresión lineal múltiple. Se consideraron valores significativos de P < 0,05. Resultados: El consumo de verduras, hortalizas y de frutas, la ingesta de folatos y su contribución a las ingestas recomendadas (I/IR%) y las concentraciones séricas de folatos fueron mayores en los hijos de madres no fumadoras que en los hijos de madres fumadoras. El 13,3% de los escolares presentaron cifras de folatos séricos inferiores a las indicadoras de deficiencia moderada (6 ng/mL) y un 0,26% mostraron deficiencia severa (3 ng/mL). Teniendo en cuenta variables interferentes se observó una correlación negativa y significativa entre las concentraciones séricas de folatos de los escolares y el hábito tabáquico de la madre (r = -0,257, p = 0,01). Conclusión: La presencia del hábito tabáquico en la madre condiciona la ingesta dietética y las concentraciones séricas de folatos en sus descendientes.Aim: To study the folate status in a group of Spanish schoolchildren and its association with parental smoking habits. Methods: A group of 511 schoolchildren between 9 and 12 years old from Madrid (Spain) were studied. Parental smoking habits were self-reported by a questionnaire. Energy and nutrients intake (especially folates) were calculated with a "3-day diet record" and during two days (Monday and Tuesday) the food consumption was controlled in the school canteen using the "precise weighing method" (recording the weights of food served and leftovers on the plate). Folate intake of the sample was compared with the recommended intakes (RI) for this vitamin. Folate, vitamin B12 and homocysteine were determined. Student's t-test, Mann Whitney Test, Pearson and Spearman correlation, ANCOVA, MANCOVA and multiple linear regression were applied for statistical analysis. Significance was set at P < 0.05. Results: Vegetable and fruit consumption, folate intake and its coverage to recommended folate intake (I/RI%) and serum folate levels were higher in children of nonsmoking mothers than in children of smoking mothers. Serum folate level in 13.3% of the children studied was below 6 ng/mL (moderate deficit), and in 0.26% was below 3 ng/mL (severe deficit). Taking into account others confounding factors a negative and significant correlation was observed between serum folate levels of children and smoking habits in mothers (r = -0.257, p = 0.01). Conclusion: The maternal smoking habits might determine folate intake and serum folate levels on their offspring.

Background: Recent studies revealed that obesity is associated with decreased serum but at the same time increased red blood cell (RBC) folate concentrations compared with lean subjects, thus casting doubt upon the agreement between serum and RBC folate measurements for assessing folate status. This work aimed to determine whether these two metrics lead to the same classification of folate status in obese patients. Methods: RBC and serum folate concentrations were measured with a chemiluminescent immunoassay in 263 adults with body mass index ≥30 kg/m and without previous bariatric surgery. Among them, 68.1 % were eligible for bariatric surgery. Each serum and RBC folate result was classified as deficient or not according to thresholds recommended by the kit manufacturer (model A) or by the World Health Organization (model B). The agreement between serum and RBC folate results was evaluated using the proportion of overall agreement and the prevalence-adjusted bias-adjusted kappa (PABAK) statistics. Results: The overall percentage agreements between serum and RBC measurements were 91.6 % (95 % CI 87.6-94.7 %) and 92.4 % (95 % CI 88.5-95.3 %) with PABAK coefficients of 0.87 (95 % CI 0.82-0.93) and 0.88 (95 % CI 0.83-0.94) in the models A and B, respectively, corresponding to almost perfect agreement. The same was true in the subgroup of patients eligible for bariatric surgery. Gender, age, and BMI did not influence the quality of agreement between the two parameters. Conclusions: The present study showed that folate measurements in serum and in RBC display similar performances to assess folate status in obese patients. [ABSTRACT FROM AUTHOR]

The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children's Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1.48; 95% CI 1.32, 1.66), lower educational level (AOR 1.27; 95% CI 1.17, 1.39) and lower annual income (AOR 1.11; 95% CI 1.01, 1.22). Plasma cotinine concentrations of 1.19-65.21 nmol/l increased the risk of low folate status (AOR 1.20; 95% CI 1.10, 1.31) and concentrations >65.21 nmol/l further increased the risk (AOR 1.91; 95% CI 1.70, 2.14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0.19; 95% CI 0.17, 0.22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women. [ABSTRACT FROM AUTHOR]

This study was based on 63 subjects (mean age 50 ± 9) including 41 patients with clinical and objective investigational evidence of vascular disease (age 30-66 years) and 22 control subjects (age 26-54 years). Dietary intake of folate was estimated from a food questionnaire of folate (Q.folate). There was no statistically significant difference between controls and patients for dietary folate. Also the plasma folate level did did noly slightly differ between the controls and patients (6.68 ± 2.52 ng/mL versus 5.62 +4.16 ng/mL, not significant). Patients had higher average homocysteine concentrations than control subjects (12.93 ± 8.79 vs 9.07 ± 3.08 μmol/l, p

Fortification of select grain products with folic acid and periconceptional supplementation recommendations in Canada and the USA have improved folate status, and have been associated with a reduced risk of neural tube defects. In the present study, we aimed to conduct a comparison of erythrocyte folate concentrations from the 2007–9 Canadian Health Measures Survey (CHMS) and the 2007–8 US National Health and Nutrition Examination Survey (NHANES). Erythrocyte folate concentration was assessed in participants aged 6–79 years (CHMS, n 5248; NHANES, n 7070). To account for different folate assays employed – Immulite 2000 immunoassay (CHMS) and microbiological assay (NHANES) – a conversion equation was generated (n 152 adults) to adjust the CHMS data. t Tests were used to examine country differences. Median Canadian erythrocyte folate concentrations (method-adjusted) were lower than those of Americans (988 and 1100 nmol/l, respectively), but unadjusted median Canadian erythrocyte folate concentrations were higher (1250 nmol/l). The upper 95 % CI boundary of the method-adjusted Canadian erythrocyte folate distribution overlapped that of the American erythrocyte folate concentrations, while the lower 95 % CI boundary of the method-adjusted Canadian erythrocyte folate data was below the American distribution. In summary, the fact that erythrocyte folate concentrations were either higher or lower in Canadians compared with Americans, depending on whether an adjustment was made to account for assay differences, suggests that caution must be exercised in evaluating erythrocyte folate data from different countries because analytical methods are not readily comparable. Furthermore, we cannot unequivocally conclude that there are true differences in erythrocyte folate concentrations between the Canadian and American populations in the post-fortification era. [ABSTRACT FROM PUBLISHER]

Objective: Folate status has been associated with neural tube defects and cerebrovascular disease. The aim of this study was to evaluate possible differences in folate status in two European Union countries and to assess their possible association with dietary patterns and/or other lifestyles. Methods: In the framework of the European Union-funded IMMIDIET Project, 1068 individuals (534 male-female pairs), ages 26 to 64 y, were enrolled in Italy and the United Kingdom. One-year-recall food frequency questionnaire was used to evaluate dietary intake. Reduced rank regression analysis was used to derive a dietary pattern better describing high dietary folate intake. Results: Of the total participants, 11.3% of the Italians and 45.1% of the British exceeded the optimal dietary folate intake of 400 µg/d (Recommended Dietary Allowance). Of the women, 66.7% and 22.1% of Italian and British women, respectively, all at childbearing age, had folate serum levels <6.62 ng/mL (P = 0.01). The percentage of total variance of dietary folate intake explained by food group consumption was 14.2% and 16.3% in Italy and the United Kingdom, respectively. Reduced rank regression analysis indicated a healthy pattern that was positively associated with folate serum levels in both countries (for all β-coefficients >0; P < 0.001): 100 mg/d increase in dietary folate intake was associated with 13.8% and 10.5% increase in folate serum levels in the Italian and British population, respectively (for 100 mg/d increase eβ-coef = 1.138 and 1.105; P < 0.001). Smoking habit was negatively but physical activity positively associated with folate serum levels (P < 0.05). Conclusions: An inadequate dietary folate intake and subsequent serum levels were observed in the Italian participants. High consumption of food sources of folate was positively associated with folate serum levels, explaining a good proportion of its variability. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess the folate status of US women in a study of a folate-fortified oral contraceptive (OC) using the Short Folate Food Frequency Questionnaire and plasma and red blood cell (RBC) folate samples.DesignSub-analysis from a multi-centre, randomised, double-blind, controlled contraceptive trial with assessments at baseline and 6 months. We calculated dietary folate equivalents (DFE) consumed and the proportion of participants meeting folate adequacy benchmarks.SettingEight centres in the USA.SubjectsHealthy women aged 18–40 years requesting contraception with no contraindications for OC use.ResultsOverall, 385 participants were randomised to either a novel folate-fortified OC or a marketed OC. The 262 (68 %) participants compliant with the protocol were included in the analysis set. Baseline daily DFE consumption was 529·8 (sd 342·1) μg and similar in both groups. At follow-up, the fortified OC group had higher intake than the conventional OC group (1225·9 (sd 346·2) μg compared with 500·6 (sd 361·2) μg). Mean plasma folate level increased from 44·5 (sd 17·2) to 55·8 (sd 21·1) nmol/l. Mean RBC folate level increased from 996·7 (sd 369·8) to 1311·9 (sd 436·0) nmol/l. The proportion meeting selected folate adequacy benchmarks increased in the fortified OC group (P < 0·001).ConclusionsLack of adequate folate intake in reproductive-aged women from dietary sources or supplements alone suggests the need for novel approaches. Use of folate-fortified OC ensures adequate folate levels and meeting of folate benchmarks. [ABSTRACT FROM AUTHOR]

In most countries, the dietary folate intake associated with adequate status of red cell folate and/or serum folate provides the basis for formulating reference values. One of the major challenges in setting dietary reference values for folate, however, is the need to account for the differences in bioavailability between the natural forms of the vitamin and the synthetic form, folic acid, albeit to date, few countries in Europe take bioavailability into consideration. A series of systematic reviews that included only those studies which used the most robust measures of both folate intake and folate status were carried out by the EURRECA Network of Excellence to examine the relationships between folate intake, status, and a number of health outcomes relevant to specific stages of the lifecycle. This review summarizes the available evidence and the issues to consider in the setting of dietary reference values for folate. [ABSTRACT FROM PUBLISHER]

Highlights: [•] Urinary folate catabolites are useful as non-invasive markers of folate status. [•] Low concentrations and interfering compounds complicate quantification. [•] Derivatization to butyl esters improves ionization efficiency and separation. [•] UPLC–APCI-MS/MS method provides high accuracy, sensitivity and specificity. [•] The assay is extensively validated and optimized for cost-effective high-throughput. [Copyright &y& Elsevier]

Folate deficiency has been linked to diverse clinical manifestations and despite the importance of accurate assessment of folate status, the best test for routine use is uncertain. Both serum and red cell folate assays are widely available in clinical laboratories; however, red cell folate is the more time-consuming and costly test. This review sought to evaluate whether the red cell assay demonstrated superior performance characteristics to justify these disadvantages. Red cell folate, but not serum folate, measurements demonstrated analytical variation due to sample pre-treatment parameters, oxygen saturation of haemoglobin and haematocrit. Neither marker was clearly superior in characterising deficiency but serum folate more frequently showed the higher correlation with homocysteine, a sensitive marker of deficiency. Similarly, both serum and red cell folate were shown to increase in response to folic acid supplementation. However, serum folate generally gave the greater response and was able to distinguish different supplementation doses. The C677T polymorphism of methylenetetrahydrofolate reductase alters the distribution of folate forms in red cells and may thereby cause further analytical variability in routine red cell folate assays. Overall, serum folate is cheaper and faster to perform than red cell folate, is influenced by fewer analytical variables and provides an assessment of folate status that may be superior to red cell folate. [ABSTRACT FROM AUTHOR]

Abstract: Promoting folate intake from natural food sources is a healthy worldwide strategy for attaining safe levels of folate in overall nutritional status and avoiding potential harm from chronic excessive intakes of folic acid from fortified food products or supplements in certain population groups. Over recent years the consumption of ready-to-eat foods, such as packed vegetables or precooked meals, has become a significant part of the diet. Accordingly, the folate composition of these food categories must be investigated. There is a broad lack of folate data in food composition tables and databases, especially for ready-to-eat products. This context warrants the need for providing new data on total folate and individual forms of folate in ready-to-eat commercial products, either to complete food composition tables or databases and/or to achieve regulatory objectives, or to assess population dietary intakes. Currently, intake recommendations for folate in some European countries range from 400 to 500μg/day for folate for women of childbearing age, 600μg/day for the second half of pregnancy and 500μg/day for women who are breastfeeding. For other population groups, the recommended daily intakes (RDI) for folate are established depending on the age and sex of the individuals (children around 150–200μg/day, and adults and elderly, 300–400μg/day), but vary considerably among European countries. Moreover, contradictory data exist concerning both recommended and real dietary intake of folate throughout Europe. Despite a wide variety of analytical methods available for food folate measurement (microbiological assay or high performance liquid chromatography (HPLC), with a previous enzyme extraction based on the use of amylase, protease and/or folate conjugase; HPLC coupled with mass spectrometry; alternative protein-binding and immunoassay methods), many procedural complexities continue to result in poor agreement among methods and laboratories. Given the uncertainty involved in accurately measuring folate, the available certified reference materials should be used by laboratories to check the accuracy of folate data. The challenge to improve quantity and quality of folate data in food composition databases exists in most developed countries, and particularly in Europe, in the absence of mandatory food fortification policies for folate. [Copyright &y& Elsevier]

BACKGROUND Obesity is associated with an increased risk of having a pregnancy affected by a neural tube defect (NTD). It is not clear whether the amount of folic acid required by obese women to protect against NTDs is the same as that for nonobese women. METHODS We analyzed data from the National Health and Nutrition Examination Survey, representative of the noninstitutionalized civilian U.S. population, to assess whether body mass index (BMI; normal weight, overweight, and obese categories) modified the association between supplemental folic acid intake and folate status. We estimated the geometric mean concentration among nonpregnant women of childbearing age (15-44 years) during the postfortification period of: serum folate (2003-2008); red blood cell (RBC) folate (2007-2008); and plasma total homocysteine (tHcy; 2003-2006), adjusted for age, race and ethnicity, and total dietary folate expressed as dietary folate equivalents for strata of supplement use and BMI. RESULTS BMI was inversely associated with serum folate among women who did not use supplements containing folic acid; no differences between women in different BMI categories were observed among supplement users. Regardless of supplement use, obese women had the highest RBC folate concentrations. There were no differences in tHcy by BMI, regardless of supplement use. CONCLUSIONS These results do not support a straightforward modification of the relationship between supplemental folic acid intake and folate status by BMI. In this population, BMI may affect the body distribution of folate, as reflected by lower serum and higher RBC folate levels in obese women who do not use supplements. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

To investigate ten year trends in folate status in Taiwanese aged ≥19 yrs by three Nutrition and Health Survey in Taiwan (NAHSIT) in 1993-1996, 1999-2000 and 2005-2008. Women had higher blood folate levels than men in all three surveys. The prevalence of folate deficiency (5.2% <3 ng/mL) and insufficiency (34.1%≤<6 ng/mL) in men was highest in 2005-2008. Adults aged 19-30 yrs had the lowest blood levels and the highest prevalence of deficiency (8. I% in men; 3.5% in women) and insufficiency (48.6% in men; 25% in women) as compared to other age groups in 2005-2008. Folate insufficiency rate in those aged 31-44 yrs was twice as high in men and three times as high in women in 2005-2008 compared to 1993-1996. In the elderly, folate insufficiency rate (28%) in 2005-2008 was not higher than that of 1993-1996, although it was higher than that found in 1999-2000 (18.4%). Men aged ≥ 80 yrs had the poorest folate status in 2005-2008, and men were twice as likely to have inadequate status as women. Plasma homocysteine (Hcy) levels were higher in older men than older women in both surveys. The elderly had significantly higher plasma tHcy in 20015-2008 compared to the 1999-2000 survey. Dark green vegetables and fruit intake frequency in young adults (19-30 yrs) was the lowest among all age groups. This study suggests that folate status in Taiwan has not improved during the past fifteen years, and has worsened in the young population. [ABSTRACT FROM AUTHOR]