Explore the vast range of titles available.

ObjectiveNeural tube defects (NTDs) are a preventable folate deficiency disorder; increasing folic acid intake through food fortification increases serum and red blood cell folate and reduces the risk of an NTD pregnancy. There is controversy over the blood folate level needed to achieve the full preventive effect because of discrepant study conclusions.MethodsResults from two published studies were used to determine the relationship between serum folate and NTD risk which was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/mL to 44 ng/mL among women who took a 4 mg daily periconceptional folic acid supplement.ResultsBoth studies showed a proportional (logarithmic) relationship between serum folate and NTD risk without evidence of a folate threshold above which there is no further NTD risk reduction. The suggestion of a threshold is due to the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales, which conceals the proportional relationship between the two. Also, both studies accurately estimated the observed result from the randomised trial that achieved a median serum folate level of 44 ng/mL and an 83% preventive effect. This is much higher than has been achieved with current levels of folic acid fortification with serum folate between 10 and 16 ng/mL, resulting in an approximate 20% preventive effect.ConclusionTo achieve fully effective fortification, median population serum folate levels need to be about 44 ng/mL, which would globally prevent about 250 000 NTD cases every year.

Background: Within Cambodia, micronutrient deficiencies continue to be prevalent in vulnerable groups, such as women and children. Fortification of staple foods such as rice could be a promising strategy for Cambodia to improve micronutrient status. Objective: Our objective was to investigate the impact of multiple-micronutrient fortified rice (MMFR), distributed through a World Food Program school-meals program (WFP-SMP) on serum zinc concentrations and folate status in a double-blind, cluster-randomized, placebo-controlled trial. Methods: Sixteen schools were randomly assigned to receive one of three different types of extruded-fortified rice (UltraRice Original (URO), UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. A total of 1950 schoolchildren (6–16 years old) participated in the study. Serum zinc (all groups) and folate (only in NutriRice and placebo group) concentrations were assessed from morning non-fasting antecubital blood samples and were measured at three time points (baseline and after three and six months). Results: After six months of intervention, serum zinc concentrations were significantly increased in all fortified rice group compared to placebo and baseline (0.98, 0.85 and 1.40 µmol/L for URO, URN and NutriRice, respectively) (interaction effect: p < 0.001 for all). Children in the intervention groups had a risk of zinc deficiencies of around one third (0.35, 039, and 0.28 for URO, URN, and NutriRice, respectively) compared to the placebo (p < 0.001 for all). The children receiving NutriRice had higher serum folate concentrations at endline compared to children receiving normal rice (+2.25 ng/mL, p = 0.007). Conclusions: This study showed that the high prevalence of zinc and folate deficiency in Cambodia can be improved through the provision of MMFR. As rice is the staple diet for Cambodia, MMFR should be considered to be included in the school meal program and possibilities should be explored to introduce MMFR to the general population.

Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.

Abstract Background Olaparib is a polyadenosine 5’-disphosphoribose polymerase inhibitor approved to treat advanced ovarian cancers with germline mutations. The link between olaparib-induced anemia and folate deficiency was described in a retrospective case series in which 87.5% of patients developed concomitant folate deficiency and anemia. We sought to prospectively evaluate this association. Patients and Methods This is an open-label prospective trial of patients with solid tumors treated with olaparib to determine the frequency and timing of folate deficiency anemia. Patients who developed grade 1 anemia (Hgb < 12.0 g/dL) concomitantly with folate deficiency (serum folate < 7.0 ng/mL) were randomized to receive placebo or folic acid. Secondary endpoints included the impact of folic acid supplementation on serum folate and hemoglobin, transfusion needs, and need for olaparib treatment interruption, dose reduction, or drug discontinuation. Results Nine subjects were enrolled, with ovarian or breast cancer. Two patients were randomized to forgo folate supplementation, two were randomized to receive folate, and the rest were not randomized per protocol. Three withdrew due to disease progression. All patients demonstrated decreased folate levels after initiation of olaparib, eight occurring within 3 months. Seven patients developed a concomitant grade 1 anemia. Folate deficiency did not correlate with clinically significant anemia. Conclusions This trial demonstrated folate deficiency in nearly all patients starting olaparib within weeks but, deficiencies did not result in a clinically significant anemia. Folate levels normalized with supplementation and improved with olaparib discontinuation. This data warrant checking serum folate in patients receiving olaparib who develop anemia and replacing folate if deficiency is found.

Folic acid (FA), also termed folate, is an essential vitamin for health at all ages since it participates in the biosynthesis of nucleotides, amino acids, neurotransmitters, and certain vitamins. It is therefore crucial for rapidly growing tissues such as those of the fetus. It is becoming clear that FA deficiency and impaired folate pathways are implicated in many diseases of both early life and old age. FA can be transported into the cell by the folate receptor, the reduced folate transporter, and proton-coupled folate transporter. Folate transport proteins are present in certain eye tissues, which explains why FA plays an important role in eye development. The purpose of this literature review is to investigate the evidence relating FA deficiency to eye diseases.

IntroductionThe prevalence of neural tube defects (NTDs) is higher in Ethiopia than most other countries, and ~84% of Ethiopian women of reproductive age (WRA) have folate insufficiency, a major risk factor for NTDs. Salt fortification with folic acid is a potential strategy to improve women’s folate status, but data are needed on the acceptability, nutritional impact and safety of folic acid fortification of iodised salt.Methods and analysisThe study is designed as a community-based, household-randomised, dose–response trial. A total of 360 non-pregnant WRA 18–49 years of age will be randomly assigned to one of three intervention arms: (1) iodised salt fortified with 30 ppm folic acid to provide ~200 µg folic acid/day; (2) iodised salt fortified with 90 ppm folic acid to provide ~600 µg folic acid/day; or (3) iodised salt (comparator). The preweighed salts will be delivered to participants’ homes biweekly for 26 weeks; unused salt will be collected and weighed. Fasting, venous blood samples will be collected at baseline, end line and a randomly assigned intermediate time point for assessment of folate, iodine, vitamin B12 and other micronutrient status biomarkers. Women’s dietary intakes, including discretionary salt consumption, will be measured using weighed food records; 24-hour urine specimens will be analysed for sodium and iodine excretion. Primary outcomes are women’s consumption of study salts, change in biomarkers of folate and iodine status and prevalence of adverse events. Results will be analysed using analysis of covariance models to estimate group mean differences for continuous outcomes, controlling for baseline measurements, and log-binomial or modified Poisson regressions for categorical outcomes. Prespecified effect modifications will be explored.Ethics and disseminationThe study has been approved by the Ethiopian Public Health Institute’s Institutional Review Board, and the protocol has been registered with ClinicalTrials.gov (registration number NCT06223854). Study results will be published in open access scientific journals and disseminated nationally in Ethiopia.Trial registration number NCT06223854.

Background: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. Methods: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. Results: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn’s disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Conclusions: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

Sperm DNA injury is one of the common causes of male infertility. Folic acid deficiency would increase the methylation level of the important genes, including those involved in DNA double‐strand break (DSB) repair pathway. In the early stages, we analysed the correlation between seminal plasma folic acid concentration and semen parameters in 157 infertility patients and 91 sperm donor volunteers, and found that there was a significant negative correlation between seminal folic acid concentration and sperm DNA Fragmentation Index (DFI; r = −0.495, p < 0.01). Then through reduced representation bisulphite sequencing, global DNA methylation of sperm of patients in the low folic acid group and the high folic acid group was analysed, it was found that the methylation level in Rad54 promoter region increased in the folic acid deficiency group compared with the normal folic acid group. Meanwhile, the results of animal model and spermatocyte line (GC‐2) also found that folic acid deficiency can increase the methylation level in Rad54 promoter region, increased sperm DFI in mice, increased the expression of γ‐H2AX, that is, DNA injury marker protein, and increased sensitivity of GC‐2 to external damage and stimulation. The study indicates that the expression of Rad54 is downregulated by folic acid deficiency via DNA methylation. This may be one of the mechanisms of sperm DNA damage caused by folate deficiency.

Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment. In addition, CFD reduced the hepatic p-Akt/Akt ratio in response to acute insulin administration. Moreover, CFD increased serum triglyceride levels, upregulated hepatic Acc1 and Fasn mRNA expression, and downregulated hepatic Cd36 and ApoB mRNA expression. After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance. This study demonstrates that folate deficiency could induce obesity, glucose and lipid metabolism disorders and subsequent cognitive dysfunction.

Folate deficiency is associated with various health issues, including anemia, cardiovascular disease, and birth defects. Low folate intake and suboptimal folate status were found in several countries; however, this topic has not yet been investigated in Slovenia. Dietary folate intake and serum folate status were investigated through the nationally representative food consumption study SI.Menu/Nutrihealth. Folate intake was estimated using a sample of N = 1248 subjects aged 10–74 years, stratified in three age groups (adolescents, adults, elderly population), through two 24 h-dietary recalls and food propensity questionnaire. Data on serum folate and homocysteine was available for 280 participants. Very low folate intake (<300 µg/day) was observed in 59% of adolescents, 58% of adults and 68% of elderlies, and only about 12% achieved the WHO recommended level of 400 µg/day. Major dietary contributors were vegetables and fruit, and cereal products. Living environment, education, employment status and BMI were linked with low folate intake in adults; BMI, and sex in adolescents; and sex in elderlies. Considering low serum folate (<7 nmol/L) and high serum homocysteine (>15 nmol/L), folate deficiency was found in 7.6 and 10.5% in adults and elderlies, respectively. Additional public health strategies should be employed to promote the consumption of folate-rich foods. With current folate intakes, supplementation with folic acid is relevant especially in specific vulnerable populations, particularly in women planning and during pregnancy.