Serum folate status among blood donors in south-central China

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[Formula: see text]nmol[Formula: see text]l[Formula: see text] (95% CI, 12.7–14.1). The prevalence of serum folate concentrations below 6.8[Formula: see text]nmol[Formula: see text]l[Formula: see text] was 5.2% (95% CI, 2.5–8.0). There were significant differences in serum folate concentrations with respect to sex ([Formula: see text]-values [Formula: see text] 0.05), age ([Formula: see text]-values [Formula: see text] 0.05), fruit and vegetable consumption ([Formula: see text]-values [Formula: see text] 0.05), and alcohol consumption habits ([Formula: see text]-values [Formula: see text] 0.05). The concentration of serum folate increased with age ([Formula: see text]-values [Formula: see text] 0.05) and fruit and vegetable consumption ([Formula: see text]-values [Formula: see text] 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.

Low vitamin B12 but not folate is associated with incident depressive symptoms in community-dwelling older adults: a 4 year longitudinal study

The objective was to examine the prospective relationship between folate and vitamin B12 (B12) status and incident depressive symptoms in a representative cohort of community-dwelling older people. This was a longitudinal study utilising the Irish Longitudinal Study on Aging (n =3,849 aged ≥50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). Participants with depression at wave 1 were excluded. A score ≥9 on the Center for Epidemiologic Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. Plasma B12 and folate concentrations were determined by microbiological assay. B12 status profiles (pmol/l) were defined as: <185, deficient-low; 185 - <258, low normal; >258 - 601, normal and >601 high. Folate status profiles (nmol/l) were defined as: ≤10.0, deficient-low; >10 - 23.0, low normal; >23.0 - 45.0, normal; >45.0, high. Logistic regression models reporting odds ratios were used to analyse the longitudinal association of B-vitamin categories with incident depression. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms vs. non depressed (folate: 21.4 vs. 25.1 nmol/L; P=0.0003); (B12: 315.7 vs. 335.9 pmol/L; P=0.0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression four years later (odds ratio 1.51, 95% CI 1.01-2.27, P=0.043). This finding remained robust after controlling for relevant covariates including physical activity, chronic disease burden, vitamin D status. cardiovascular disease and antidepressant use. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51% increased likelihood of developing depressive symptoms over 4 years. Given the high rates of B12 deficiency, these findings are important and highlight the need to further explore the low cost benefits of optimising vitamin B12 status for depression in older adults.

Prenatal folic acid supplementation and folate status in early pregnancy: ECLIPSES study

This research evaluates the prevalence of inadequate folate status in early pregnancy, the pattern of prenatal folic acid (FA) supplementation and associated factors in Spanish pregnant women from the ECLIPSES study, which included 791 participants prior gestational week 12. A cross-sectional evaluation of red blood cell (RBC) folate levels was performed at recruitment and used to calculate the prevalence of folate deficiency (RBC folate<340 nmol/L) and insufficiency (RBC folate<906 nmol/L). Sociodemographic and lifestyle data, as well as information on prenatal FA supplementation were recorded. Descriptive and multivariate statistical analyses were performed. The prevalence of folate deficiency and insufficiency were 9.6% and 86.5%, respectively. Most of women used prenatal FA supplements but only 6.3% did so as recommended. Supplementation with FA during the periconceptional period abolished folate deficiency and reduced folate insufficiency. Prenatal folic acid supplementation with ≥1000 µg/d in periconceptional time and pregnancy planning increased RBC folate levels. The main risk factor for folate insufficiency in early pregnancy were getting prenatal FA supplementation out of the periconceptional time (OR 3.32, 95%CI 1.02–15.36), while for folate deficiency they were young age (OR 2.02, 95%CI 1.05–3.99), and smoking (OR 2.39, 95%CI 1.30–4.37). In addition, social and ethnic differences according to folate status were also identified. As conclusion, periconceptional FA use is crucial for achieving optimal folate levels in early pregnancy. Pregnancy planning should focus on young women, smokers, those with low consumption of folate-rich foods, low socioeconomic status or from ethnic minorities.

Red cell folate status among a subset of Canadian children with Down Syndrome post-fortification

ABSTRACTBackgroundTrisomy 21 or Down Syndrome (DS) is associated with altered methylation pathways. Children with DS may therefore represent a population subgroup with vulnerability to increased exposures to folic acid, which is involved in one-carbon metabolism. Folic acid (FA) fortification of flour and maternal FA supplementation are intended to reduce neural tube defects related to folate deficiency. The interventions have been widely successful in Canada. Emerging evidence suggests that higher FA exposures may also have potential negative consequences, including implications for DNA methylation. This retrospective chart review provides insight on the RBC folate status of a subset of Canadian children and infants with DS, post-fortification.MethodChildren with DS in 2 Canadian provinces were assessed in the community. Access to RBC folate testing was variable, limiting sample size to 39 (n=27 for children ≤ 6 years; n=12 for children 6-18 years). All children with DS and an RBC folate result were included. Use of FA-containing supplements and formula was documented.ResultsAmong children 6-18 years, 100% had RBC folates > 1000 nmol/L, 50% were > 2000 nmol/L and 25% had levels above the reporting limit. Among the younger children (< 6 years), 52 % had RBC folates >2000 nmol and 2 children exceeded 3000 nmol/L. Among exclusively breast-fed infants (<12 months), 100% had RBC folates > 1000 nmol/L and 50% had levels > 2000 nmol/L, suggestive of in-utero or maternal exposures. RBC folate status among this subset of Canadian children with DS is higher than documented for the larger Canadian population, and higher than among US children with DS.ConclusionsYoung Canadian children with DS demonstrated high post-fortification RBC folate status. RBC folate status was higher than reported for the larger Canadian population, and higher than for US children with Down Syndrome. Consumption of folic acid-containing formula and/or supplements was relatively low among these Canadian children with DS, suggesting maternal FA supplements and/or FA-fortified foods may be important etiological factors. A larger, prospective study is needed to validate these results, and to explore potential health implications among this vulnerable population.

Relationship between disease severity and folate status of children with sickle cell anaemia in Enugu, South East Nigeria

Background: Repeated crises in children with sickle cell anaemia (SCA), which is a manifestation of disease severity, results in depletion of their minimal tissue folate stores, with higher likelihood of folate deficiency. The study aimed to determine the relationship between disease severity and the folate status of children with SCA attending University of Nigeria Teaching Hospital (UNTH), Enugu. Methods: This was a hospital based, cross-sectional study conducted between September 2018 and March 2019. One hundred participants were recruited, consisting of 50 children having sickle cell crisis and 50 age and gender matched hae- moglobin AA genotype controls. Relevant information was documented using a pretested questionnaire. Sickle cell severity score was determined using frequency of crisis, admissions and transfusions in the preceding one year, degree of liver and splenic enlargement, life-time cummulative frequency of specific complications of SCA, leucocyte count and haematocrit. Results: Folate deficiency was observed in eight percent of the subjects and none of the controls. The difference was not significant (Fisher’s exact = 4.167, p=0.117). The odds of being folate deficient was 8.5 times more likely during anaemic crisis than in vaso-occlusive crisis, though not significant (95% C.I 0.05 – 89.750, p = 0.075). The mean SCA severity score was 8.06 ± 3.64, signifying a moderate SCA severity in the study population. There was a no relationship between folate status and severity of SCA (Fisher’s exact = 0.054, p = 0.949) Conclusion: Folate status in children with SCA is not affected by their disease severity. Therefore, there may be no need for additional folate supplementation with increasing severity of sickle cell anaemia. Keywords: Sickle cell anaemia; disease severity; folate status; children; Enugu.

Ischemia-Reperfusion Injury Reduces Kidney Folate Transporter Expression and Plasma Folate Levels

Acute or chronic kidney disease can cause micronutrient deficiency. Patients with end-stage renal disease, kidney transplantation or on dialysis have reduced circulating levels of folate, an essential B vitamin. However, the molecular mechanism is not well understood. Reabsorption of folate in renal proximal tubules through folate transporters is an important process to prevent urinary loss of folate. The present study investigated the impact of acute kidney injury (AKI) on folate transporter expression and the underlying mechanism. AKI was induced in Sprague-Dawley rats that were subjected to kidney ischemia (45 min)-reperfusion (24 h). Both male and female rats displayed kidney injury and low plasma folate levels compared with sham-operated rats. The plasma folate levels were inversely correlated to plasma creatinine levels. There was a significant increase in neutrophil gelatinase-associated lipocalin (NGAL) and IL-6 mRNA expression in the kidneys of rats with ischemia-reperfusion, indicating kidney injury and increased inflammatory cytokine expression. Ischemia-reperfusion decreased mRNA and protein expression of folate transporters including folate receptor 1 (FOLR1) and reduced folate carrier (RFC); and inhibited transcription factor Sp1/DNA binding activity in the kidneys. Simulated ischemia-reperfusion through hypoxia-reoxygenation or Sp1 siRNA transfection in human proximal tubular cells inhibited folate transporter expression and reduced intracellular folate levels. These results suggest that ischemia-reperfusion injury downregulates renal folate transporter expression and decreases folate uptake by tubular cells, which may contribute to low folate status in AKI. In conclusion, ischemia-reperfusion injury can downregulate Sp1 mediated-folate transporter expression in tubular cells, which may reduce folate reabsorption and lead to low folate status.

Impact of Voluntary Folic Acid Fortification of Corn Masa Flour on RBC Folate Concentrations in the U.S. (NHANES 2011–2018)

Objectives Surveillance data have highlighted continued disparities in neural tube defects (NTDs) among infants of Hispanic women of reproductive age (HWRA) in the United States. Starting in 2017, the US Food and Drug Administration implemented voluntary folic acid fortification of corn masa flour to reduce the risk of NTDs. We assessed folate status, using red blood cell (RBC) folate concentrations, in HWRA (aged 12–49 y) before (2011–2016) and after (2017–2018) voluntary fortification of corn masa, stratified by acculturation factors (i.e., primary language spoken at home, length of time residing in the US). Methods Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 with available RBC folate concentrations for HWRA were analyzed. Additional analyses were conducted among HWRA whose only folic acid source was fortified foods (enriched cereal grain products (ECGP) only), including usual intake and NTD prevalence estimations based on previously published models. Results Overall, RBC folate concentrations (adjusted geometric means) among HWRA remained similar from 2011–2016 to 2017–2018, though RBC folate significantly increased in 2017–2018 among lesser acculturated HWRA consuming ECGP only. Concentrations for those who were born outside the US and resided in the US &lt; 15 y increased from 894 nmol/L (95% CI: 844–946) in 2011–2016 to 1018 nmol/L (95% CI: 982–1162; p &lt; 0.001) in 2017–2018. Primarily Spanish speaking HWRA who consumed ECGP only increased from 941 nmol/L (95% CI: 895–990) in 2011–2016 to 1034 nmol/L (95% CI: 966–1107; p = 0.03) in 2017–2018. We observed no significant changes in the proportion at risk of NTD (&lt;748 nmol/L) and no changes in Bayesian model-based estimated NTD rates. Conclusions This early analysis following voluntary corn masa fortification found an increase in RBC folate concentrations in lesser acculturated groups relying on fortified foods as their primary folic acid source, though HWRA overall had no significant increase in folate concentrations. These early data suggests that there is remaining risk among Hispanics for folate sensitive NTDs; continued monitoring of folate status with NHANES will help assess the long-term efficacy of voluntary fortification. Funding Sources No funding sources outside of salaries.

Folic Acid From Supplements or Fortified Foods Consumed During Pregnancy and/or Lactation and Health Outcomes in Mothers and Their Children: A NESR Systematic Review

Objectives To inform the Dietary Guidelines for Americans, 2020–2025, USDA and HHS identified the following important public health question for the 2020 Dietary Guidelines Advisory Committee to answer with support from USDA's Nutrition Evidence Systematic Review (NESR) team: What is the relationship between folic acid from supplements and/or fortified foods consumed before and during pregnancy and lactation and health outcomes? Methods The Committee developed protocols to describe how they would use NESR's systematic review methodology to examine the evidence. NESR conducted a literature search and dual-screened the results using pre-defined inclusion and exclusion criteria for articles published between 1980 and 2019. NESR extracted data and assessed risk of bias of included studies. The Committee synthesized the evidence, developed conclusion statements, and graded the strength of the evidence underlying the conclusion statements. Results This systematic review included 30 articles, most of which were well-designed RCTs. Observational studies had risk of bias concerns. The study populations did not fully represent the diversity of the U.S. population. Conclusions Strong evidence indicates that folic acid supplements consumed before and/or during pregnancy are positively associated with folate status. Moderate evidence indicates that folic acid supplements consumed during lactation are positively associated with folate status. Limited evidence suggests that folic acid supplements consumed during early pregnancy may have a beneficial effect on reducing the risk of hypertensive disorders during pregnancy among women at high-risk versus no supplementation. Moderate evidence indicates that higher versus lower levels of folic acid supplements consumed during pregnancy does not affect the risk of hypertensive disorders during pregnancy among women at low-risk. Moderate evidence indicates that folic acid supplements consumed during lactation does not influence folate levels in human milk. Insufficient or no evidence was available to examine folic acid and gestational diabetes or child developmental, or folic acid from fortified foods and any outcome. Funding Sources USDA, Food and Nutrition Service, Center for Nutrition Policy and Promotion.