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Folate (vitamin B9) plays a crucial role in fundamental cellular processes, including nucleic acid biosynthesis, methyl group biogenesis and amino acid metabolism. The detection and correction of folate deficiency prevents megaloblastic anaemia and reduces the risk of neural tube defects. Coexisting deficiencies of folate and vitamin B12 are associated with cognitive decline, depression and neuropathy. Folate deficiency and excess has also been implicated in some cancers. Excessive exposure to folic acid, a synthetic compound used in supplements and fortified foods, has also been linked to adverse health effects. Of at least three distinct laboratory markers of folate status, it is the total abundance of folate in serum/plasma that is used by the majority of laboratories. The analysis of folate in red cells is also commonly performed. Since the folate content of red cells is fixed during erythropoiesis, this marker is indicative of folate status over the preceding ~4 months. Poor stability, variation in polyglutamate chain length and unreliable extraction from red cells are factors that make the analysis of folate challenging. The clinical use of measuring specific folate species has also been explored. 5-Methyltetrahydrofolate, the main form of folate found in blood, is essential for the vitamin B12-dependent methionine synthase mediated remethylation of homocysteine to methionine. As such, homocysteine measurement reflects cellular folate and vitamin B12 use. When interpreting homocysteine results, age, sex and pregnancy, specific reference ranges should be applied. The evaluation of folate status using combined markers of abundance and cellular use has been adopted by some laboratories. In the presence of discordance between laboratory results and strong clinical features of deficiency, treatment should not be delayed. High folate status should be followed up with the assessment of vitamin B12 status, a review of previous results and reassessment of folic acid supplementation regime.

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.

Plant-based diets may increase the risk of vitamin B 12 deficiency due to limited intake of animal-source foods, while dietary folate increases when adhering to plant-based diets. In this cross-sectional study, we evaluated the B 12 and folate status of Norwegian vegans and vegetarians using dietary B 12 intake, B 12 and folic acid supplement use, and biomarkers (serum B 12 (B 12 ), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA) and serum folate). Vegans ( n 115) and vegetarians ( n 90) completed a 24-h dietary recall and a FFQ and provided a non-fasting blood sample. cB 12 , a combined indicator for evaluation of B 12 status, was calculated. B 12 status was adequate in both vegans and vegetarians according to the cB 12 indicator; however 4 % had elevated B 12 . Serum B 12 , tHcy, MMA concentrations and the cB 12 indicator (overall median: 357 pmol/l, 9·0 µmol/l, 0·18 µmol/l, 1·30 (cB 12 )) did not differ between vegans and vegetarians, unlike for folate (vegans: 25·8 nmol/l, vegetarians: 21·6 nmol/l, P = 0·027). Serum B 12 concentration < 221 pmol/l was found in 14 % of all participants. Vegetarians revealed the highest proportion of participants below the recommended daily intake of 2 µg/d including supplements (40 v . 18 %, P < 0·001). Predictors of higher serum B 12 concentrations were average daily supplement use and older age. Folate deficiency (< 10 nmol/l) was uncommon overall (< 2·5 %). The combined indicator cB 12 suggested that none of the participants was B 12 -depleted; however, low serum B 12 concentration was found in 14 % of the participants. Folate concentrations were adequate, indicating adequate folate intake in Norwegian vegans and vegetarians.

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.

This study aimed to evaluate the utility of serum folic acid testing in children and adolescents in a developed country without mandatory folic acid food fortification and to identify patients at risk for folic acid deficiency. In this cross-sectional study, records from primary care and hospitals were reviewed for patients aged 0–18 years who underwent serum folic acid testing. Data were retrieved from the Leumit-Health-Services database over a ten-year period (January 2008 to December 2018). Clinical and laboratory data were compared between patients with folic acid deficiency to those with normal levels. Among 20,411 pediatric patients tested, 884 (4.3%) had folic acid deficiency, of whom only 26.3% had anemia. Only two patients (0.2%) had megaloblastic anemia. Multivariate analysis showed that male gender (odds ratio(OR)1.6, 95% CI 1.22–2.12), older age (OR 1.32, 95% CI 1.26–1.39), higher BMI percentile (OR 1.01, 95% CI 1–1.01), antipsychotic treatment (OR 3.23, 95% CI 1.52–6.84), celiac (OR 2.97, 95% CI 1.66–5.34), and Attention-Deficit-and-Hyperactivity-Disease (ADHD) treated with psychostimulants (OR 2.21, 95% CI 1.56–3.12) were associated with folic acid deficiency (all p  <  0.01). Lower hemoglobin levels were independently associated with increased OR of folic acid deficiency (OR 0.77, 95% CI 0.66–0.90, p  =  0.001 ), but anemia as a diagnosis was not. Conclusion : Pediatric folic acid deficiency rates were low in this nationwide cohort and not linked to megaloblastic anemia, likely due to concomitant iron deficiency anemia. Although retrospective, this might suggest low utility for routine serum folic acid testing in healthy children in developed countries, except in cases of celiac disease or specific medication use such psychostimulants or antipsychotics. What is Known: • Folic acid deficiency is common among children in developing countries, causing megaloblastic anemia, growth delays, and cognitive impairments. In developed countries, the prevalence is considered low. What is New: • Of 20,411 pediatric patients tested for serum folate, in a developed country, only 4.3% had folate deficiency. • Risk factors for deficiency included celiac, antipsychotics, and psychostimulant treatment for ADHD. • Routine folate testing in developed countries may have limited utility; Targeted screening is recommended.

The objective of our study was to determine the prevalence of anaemia among 14-19 years school going girls, risk factors for it and profile of micronutrient status among rural girls from western state of India. Using a cross-sectional design, we obtained information on socio-demography, menstruation, dietary habits, knowledge and daily consumption of the government recommended iron and folic acid (IFA) tablets, and anthropometry. Blood was collected to assess Hb, red blood cell indices, serumFe, folate and vitamin B levels. Nagpur district, Maharashtra, India. A total of 221 girls aged 14-19 years studying in twenty-four government institutes included. 57 % girls were anaemic, 84 % had deficiency of one or more micronutrients and 60 % were malnourished based on body mass index (BMI). The prevalence of Fe, vitamin B and folate deficiency was 37·7 %, 69·8 % and 1·4 %, respectively. Among anaemic girls, Fe and vitamin B deficiency was observed in 45·5 % and 67·5 %, respectively, . among non-anaemic girls it was 27 % and 73 %, respectively. Fe deficiency was a predictor of anaemia and its severity. Girls residing in non-nuclear family were more likely to have anaemia. The consumption of daily non-vegetarian food and green leafy vegetables was 3 % and 3·6 %, respectively. Only 9 % consumed IFA tablets in the past 2 weeks. Anaemia is common in adolescent girls, particularly associated with Fe and vitamin B deficiency. There is need to reconsider the approach to prevention of anaemia in adolescent girls, particularly before they become pregnant.

To explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated BP in children and adolescents. Both a nested case control and a cohort study were designed to explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated blood pressure (BP). All the included participants were from primary school. A total of 326 subjects (116:210) in nested case control were from an established cohort. And 270 participants without hypertension at baseline and followed in 2019 in cohort. FA and VB12 levels were lower in the elevated BP group than in the control group, and homocysteine level was higher than that in the control group. In the elevated BP group, overweight/obese children had lower FA than overweight/obese children in the normal BP group. FA was positively correlated with high-density lipoprotein (HDL) and Apo lipoprotein A (APOA), but negatively correlated with triglyceride (TG). FA was significantly correlated with elevated BP in children and adolescents (β = –0.353, P = 0.032), after adjusting VB12, and homocysteine (HCY), and the interaction effect of FA*HCY was significant. Both systolic and diastolic BP levels were statistically lower in the FA high exposure group than in the FA low exposure group in the cohort study. This study found that FA and vitamin B12 deficiency in childhood was correlated with elevated BP levels, which may affect BP by regulating lipid levels, and confirmed the importance of maintaining high levels of FA and vitamin B12 in childhood either by diet or supplementation.

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.

Mandatory fortification of staple grains with folic acid and/or vitamin B12 (B12) is under debate in many countries including Ireland, which has a liberal, but voluntary, fortification policy. Older adults can be at risk of both deficiency and high folate status, although little is known on the actual prevalence and the major predictors. Population prevalence estimates from older adults (n 5290 ≥50 years) from the Irish Longitudinal Study on Ageing (TILDA) (Wave 1) are presented here. Measures included plasma total vitamin B12 and folate, whereas predictors included detailed demographic, socio-economic, geographic, seasonal and health/lifestyle data. The prevalence of deficient or low B12 status (<185 pmol/l) was 12 %, whereas the prevalence of deficient/low folate status was 15 %. High folate status (>45 nmol/l) was observed in 8·9 %, whereas high B12 status was observed in 3·1 % (>601 pmol/l). The largest positive predictor of B12 concentration was self-reported B12 injection and/or supplement use (coefficient 51·5 pmol/; 95 % CI 9·4, 93·6; P=0·016) followed by sex and geographic location. The largest negative predictor was metformin use (−33·6; 95 % CI −51·9, −15·4; P<0·0001). The largest positive predictor of folate concentration was folic acid supplement use (6·0; 95 % CI 3·0, 9·0 nmol/l; P<0·001) followed by being female and statin medications. The largest negative predictor was geographic location (−5·7; 95 % CI −6·7, −4·6; P<0·0001) followed by seasonality and smoking. B-vitamin status in older adults is affected by health and lifestyle, medication, sampling period and geographic location. We observed a high prevalence of low B12 and folate status, indicating that the current policy of voluntary fortification is ineffective for older adults.

We aimed to investigate the prevalence of decreased folate levels in patients hospitalized with Coronavirus Disease 2019 (COVID-19) and evaluate their outcome and the prognostic signifi-cance associated with its different levels. In this retrospective cohort study, data were obtained from the electronic medical records at the Sheba Medical Center. Folic acid levels were available in 333 out of 1020 consecutive patients diagnosed with COVID-19 infection hospitalized from January 2020 to November 2020. Thirty-eight (11.4%) of the 333 patients comprising the present study population had low folate levels. No significant difference was found in the incidence of acute kidney injury, hypoxemia, invasive ventilation, length of hospital stay, and mortality be-tween patients with decreased and normal-range folate levels. When sub-dividing the study population according to quartiles of folate levels, similar findings were observed. In conclusion, decreased serum folate levels are common among hospitalized patients with COVID-19, but there was no association between serum folate levels and clinical outcomes. Due to the important role of folate in cell metabolism and the potential pathologic impact when deficient, a follow-up of folate levels or possible supplementation should be encouraged in hospitalized COVID-19 patients. Fur-ther studies are required to assess the prevalence and consequences of folate deficiency in COVID-19 patients.