Folate Measurements Research Articles

Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNPin three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Pre-analytical stability of haematinics, lactate dehydrogenase and phosphate in whole blood at room temperature up to 24 h, and refrigerated serum stability of lactate dehydrogenase, folate and vitamin B12 up to 72 h using the CRESS checklist.

There is a lack of analyte stability data in whole blood (WB). The aim of this study was to determine the allowable delay in WB processing for lactate dehydrogenase (LDH), folate, vitamin B12, iron and phosphate measurement. The stability of LDH, folate and vitamin B12 was also assessed in stored serum at clinically relevant time points. Blood was taken from n=10 volunteers into Sarstedt serum gel tubes. We assessed stability in WB at room temperature up to 24 h, and stability in refrigerated serum up to 72 h. Mean percentage deviation at each time point was compared to criteria for minimum allowable bias. Results produced from one individual were removed due to discordant results, leaving n=9 specimens at each time point. Stability of folate and phosphate was variable in WB across 24 h, but was deemed to be clinically acceptable. LDH was unstable in WB, iron was stable for at least 12 h, and vitamin B12 and ferritin were acceptable for up to 24 h. Serum LDH, folate and vitamin B12 all demonstrated acceptable stability in refrigerated serum stored for up to 72 h. Blood should ideally be centrifuged within 7 h for phosphate, LDH and folate, and 12 h for iron. However, for phosphate, folate and iron, there is likely to be little clinical impact if serum separation is delayed up to 24 h. Further research is needed to assess LDH stability in WB at 0-12 h, but changes are minimal at 12 h. All other analytes assessed showed acceptable stability across the time-points tested.

Measurement of Methytetrahydrofolate Level among Sudanese Women with Hypertensive Disorders of Pregnancy, Khartoum State 2023

Background: Hypertensive disorders are a common complication of pregnancy that put women and their fetuses at disproportionate risk for further complications, as well as a life-long sequela. This study aimed to measure the Methytetrahydrofolate Level (folate) among Sudanese women with hypertensive disorders of pregnancy Material and method: This was a case-control hospital-based study conducted at the laboratory of the Omdurman maternity hospital – in Khartoum, Sudan during the period of January 2023 to March 2023. It included All patients attending Omdurman maternity hospital that diagnosed with hypertensive disorders of pregnancy, and apparently healthy women were included as a control group. ELIZA (mindary 8000) was used for folate level measurement. Results: The mean of folate levels in the cases was (12.9± 3.7), and in the control group was (33.9±2.5), when compared the folate mean between the case and control group there was a highly significant decrease with (p. v= 0.001). While the folate level had insignificant differences with the history of hypertension and types of hypertensive pregnancy (p. v > 0.05). Also has appositive correlation with the age (p. v<0.05). Conclusion: In the Sudanese women with hypertensive pregnancy the folate level was significantly decreased when compared between the case and control group, and had insignificant differences with the history of hypertension, and types of hypertensive pregnancy and had a positive correlation with the age.

Measurement of Methytetrahydrofolate Level among Sudanese Women with Hypertensive Disorders of Pregnancy, Khartoum state 2023

Hypertensive disorders are a common complication of pregnancy that put women and their fetuses at disproportionate risk for further complications, as well as a life-long sequela. This study aimed to measure the Methytetrahydrofolate Level (folate) among Sudanese women with hypertensive disorders of pregnancy. This were a case-control hospital-based study conducted at the laboratory of the Omdurman maternity hospital – in Khartoum, Sudan during the period of January 2023 to March 2023. It included All patients attending Omdurman maternity hospital that diagnosed with hypertensive disorders of pregnancy, and apparently healthy women were included as a control group. ELIZA (mindary 8000) was used for folate level measurement. The mean of folate levels in the cases was (12.9± 3.7), and in the control group was (33.9±2.5), when compared the folate mean between the case and control group there was a highly significant decrease with (p. v= 0.001). While the folate level had insignificant differences with the history of hypertension and types of hypertensive pregnancy (p. v > 0.05). Also has appositive correlation with the age (p. v<0.05). In the Sudanese women with hypertensive pregnancy the folate level was significantly decreased when compared between the case and control group, and had insignificant differences with the history of hypertension, and types of hypertensive pregnancy and had a positive correlation with the age.

The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Maternal folate has been shown to relate to the risk of gestational diabetes mellitus (GDM). However, the existing studies have yielded inconsistent conclusions. The purpose of this study was to systematically review the association between maternal folate status and the risk of GDM. Observational studies up to 31 October 2022 were included. Study characteristics, the means and standard deviations (SDs) of folate levels (serum/red blood cell (RBC)), the odds ratios (ORs) with 95% confidence intervals (CIs) and the time for folate measurement were extracted. Compared with the non-GDM group, serum and RBC folate levels in women with GDM were significantly higher. Our subgroup analysis demonstrated that serum folate levels in the GDM group were significantly higher than in the non-GDM group only in the second trimester. RBC folate levels in the GDM group were significantly higher than in the non-GDM group in the first and second trimesters. Taking serum/RBC folate levels as continuous variables, the adjusted odds ratios of GDM risk showed that increased serum folate concentration rather than RBC folate elevated the risk of GDM. In the descriptive analysis, five studies reported high serum folate levels increased GDM risk, whereas the other five showed no association between serum folate levels and GDM risk. Moreover, the rest three studies pointed out high RBC folate levels increased GDM risk. Altogether we found that the risk of GDM is associated with high serum/plasma and RBC folate levels. Future studies should determine the recommended folic acid cutoff balancing the risk for GDM and fetal malformations.

Association of folate concentrations with clinical signs and laboratory markers of chronic enteropathy in dogs.

Serum folate is considered a biomarker of chronic enteropathy (CE) in dogs, but few studies have examined associations with markers of CE. To evaluate serum folate concentrations in dogs with and without CE and associations with sample hemolysis and selected markers of CE. We hypothesized that hypofolatemia would be more common in dogs with CE and associated with hypocobalaminemia, higher CIBDAI, and hypoalbuminemia. Six hundred seventy-three dogs with available serum folate measurements performed at an academic veterinary hospital between January 2016 and December 2019. Medical records were retrospectively reviewed to categorize cases as CE or non-CE and record clinical details and laboratory markers. Relationships between serum folate, cobalamin, and CE variables were assessed using chi-square, Kruskal-Wallis, or Spearman's correlation tests. Of the 673 dogs, 99 CE were compared to 95 non-CE. In the overall cohort, serum folate concentration did not correlate with sample hemolysis (P= .75). In the CE subset, serum folate and cobalamin concentrations were positively associated (rho=0.34, FDR=0.02). However, serum folate concentrations (median [25th, 75th percentiles]) were higher (CE: 12.1 (8.9, 16.1), non-CE: 10.4 (7.2, 15.5); P= .04) and cobalamin concentrations were lower (CE: 343 (240, 597), non-CE: 550 (329, 749); P= .001) in the CE vs non-CE group. Serum folate was not associated with markers of CE, but serum cobalamin was associated with albumin (P= .04) and cholesterol (P= .03). Hypofolatemia is an inferior biomarker of CE compared to hypocobalaminemia.

Addition of exogenous γ-glutamyl hydrolase eliminates the need for lengthy incubation of whole blood lysate for quantitation of folate vitamers by high performance liquid chromatography-tandem mass spectrometry

BackgroundMeasurement of folate monoglutamates by HPLC-MS/MS in whole blood lysate (WBL) requires lengthy incubation prior to analysis, risking degradation of labile folate vitamers. ObjectiveWe explored whether addition of a commercially available recombinant exogenous γ-glutamyl hydrolase (exoGGH) enzyme reduced the required incubation time of WBL for measurement of folate as monoglutamates. MethodsFor conventional deglutamylation of polyglutamates, WBL was incubated 4 h at 37°C. Alternatively, we added exoGGH to WBL at varying concentrations (1–10 µg/mL) and incubation times (0–90 min). We also investigated modifications to the sample diluent (pH, ascorbic acid vs. sodium ascorbate, and ascorbate concentration). Finally, we tested the effect of the enzyme in different sample types: WBL from frozen whole blood vs. frozen WBL or vs. frozen washed red blood cells (RBC). Samples (n ≤ 15 per experiment) were analyzed by HPLC-MS/MS for 6 folate monoglutamates and 5-methyltetrahydrofolate diglutamate. ResultsOptimal deconjugation of folate polyglutamates was achieved using 1% ascorbic acid and 5 µg enzyme/mL WBL, requiring ≤ 30 min incubation time to achieve complete folate recovery as monoglutamates. This treatment resulted in similar folate concentrations as conventional deglutamylation (4 h at 37°C). The exoGGH enzyme was effective in samples stored frozen as whole blood and as WBL. However, extended thaw time of whole blood resulted in 5-methyltetrahydrofolate loss and unacceptable changes to non-methyl folate concentration. Total folate (with exoGGH) measured in washed RBC was ∼15% lower than RBC folate calculated from WBL concentrations (conventional deglutamylation). ConclusionsUse of exoGGH minimized incubation time and thus may avoid degradative losses of labile folate forms during sample preparation. The lower folate results in washed RBC may be due to inadequate packing of RBC among other unidentified factors. A larger study is required to confirm lack of differences in folate concentrations determined with and without the use of exoGGH.

The Continued Need for the Routine Assessment of Folate Status.

The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. Atotal of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

Efficacy and utility of a tool for both measurement of vitamin B6, B12, D, folate and iron status and assessment of diet quality in athletes.

NutriProfiel® is a tool to measure micronutrient status and to assess diet quality. It consists of measurement of micronutrient status in blood and a short food frequency questionnaire (FFQ) ('Eetscore-FFQ'). Based on the results, individuals receive a dietary advice. In this study, we evaluated the application of NutriProfiel in athletes ('NutriProfiel-Sport') by assessing the coverage of nutrient intake of the Eetscore-FFQ (part 1) and by evaluating athlete's dietary behaviour after using NutriProfiel-Sport and their satisfaction with this tool (part 2). For part 1, data of 419 athletes were used. We evaluated the coverage of nutrient intake of the Eetscore-FFQ using first and second MOMents (MOM1 and MOM2) sum scores of food items in the questionnaire. Forty-eight athletes were involved in part 2. They gave blood samples for micronutrient status measurement and were asked to complete the Eetscore-FFQ at baseline and after 3 months, as well as a questionnaire on their satisfaction with NutriProfiel-Sport. Results showed that for most nutrients, MOM1 and MOM2 scores were above 80 %, meaning that nutrient intake was sufficiently covered by the Eetscore-FFQ. No difference in diet quality was observed between baseline and after 3 months. Nevertheless, a majority of athletes reported the NutriProfiel-Sport results and advice as useful. On a scale from 0 to 10, NutriProfiel-Sport was graded with a mean (±sd) score of 7⋅6 (±0⋅8). In conclusion, NutriProfiel-Sport is a potential valuable and appreciated tool for athletes and the Eetscore-FFQ as part of this tool sufficiently covers nutrient intake in athletes.

Development of an improved standard reference material for folate vitamers in human serum.

The US National Institute of Standards and Technology (NIST) developed a Standard Reference Material® (SRM®) 3949 Folate Vitamers in Frozen Human Serum to replace SRM 1955 Homocysteine and Folate in Human Serum. The presence of increased endogenous levels of folic acid and 5-methyltetrahydrofolate (5mTHF) in SRM 3949, enhanced folate stability via addition of ascorbic acid, and inclusion of values for additional minor folates are improvements over SRM 1955 that should better serve the clinical folate measurement community. The new SRM contains folates at three levels. To produce SRM 3949, pilot sera were collected from 15 individual donors, 5 of whom were given a 400-µg folic acid supplement 1h prior to blood draw to increase serum levels of 5mTHF and folic acid for the high-level material. To stabilize the folates, 0.5% (mass concentration) ascorbic acid was added as soon as possible after preparation of serum. These pilot sera were screened for five folates plus the pyrazino-s-triazine derivative of 4-α-hydroxy-5-methyltetrahydrofolate (MeFox) at the US Centers for Disease Control and Prevention (CDC) by isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS). Based on these results, a blending protocol was specified to obtain the three desired folate concentrations for SRM 3949. ID-LC-MS/MS analysis at the CDC and NIST was utilized to assign values for folic acid and 5mTHF, as well as several minor folates.

Evaluation of feeding ruminal-protected folate and cobalt pectinate on growth performance, carcass characteristics and plasma vitamin B12 and folate status in finishing beef steers.

A large pen feedlot study was conducted to evaluate the response of yearling steers fed novel sources of rumen-protected folate (RPFA) and cobalt (cobalt pectinate; Co-PECT) on plasma levels of vitamin B12 and folate, growth performance, and carcass characteristics. A total of 2,100 steers (initial BW = 381 ± 45.2 kg.) were enrolled in the study at the time of randomization with 2,091 steers started on treatment diets following the transition to the finishing diet. A generalized randomized block design with sampling error (GRBD) with two treatments and 15 pen replications per treatment (5 blocks × 6 pens/block; 30 pens total with 70 steers/pen) were evaluated with pen serving as the experimental unit. A control (CON) treatment consisted of the standard finishing diet while the test diet consisted of the standard finishing diet providing 3.0 mg ∙ kg−1 DM of RPFA and 1.0 mg ∙ kg−1 DM total supplemental cobalt with approximately half coming from Co-PECT (TEST). Blood samples were collected from 60 randomly selected steers at study initiation and prior to shipping for plasma B12 and folate measurement. Data were analyzed with the model including fixed effects of treatment, block, and treatment within block interaction. Live growth performance was not affected by treatment; however, carcass-adjusted performance and hot carcass weight were numerically improved by TEST in 3 of the 5 blocks (treatment × within block interaction, P ≤ 0.03) of cattle. Plasma levels for both folic acid and vitamin B12 were extremely low at study initiation and increased over the course of the feeding period. Feeding TEST increased (P < 0.01) plasma B12 levels compared to CON by the completion of the trial; however, mean levels would still be considered marginal. Plasma folate was lower (P < 0.05) in TEST steers at the beginning of the study, with no difference between treatments by the time cattle were shipped. Results suggested that cattle coming into the feedlot may be of low or marginal status in both plasma folate and vitamin B12. While the status of folate and B12 improved in both CON and TEST with days on feed, providing RPFA and Co-PECT further helped improve vitamin B12 status; although, overall levels remained low, which may have affected the overall response to RPFA. Additional research is required to better understand the role of B vitamin supplementation for growing-finishing feedlots and develop methods for assessing the status and improving potential responses.

Robustness of the CDC Folate Microbiologic Assay Kit During Simulated Delayed Shipping

ObjectivesThe WHO has recommended the accurate and practical microbiologic assay (MBA) to assess population folate status. To help laboratories in low-resource countries conduct folate measurements, the CDC developed a folate MBA kit containing critical reagents: calibrator, microorganism, quality control (QC), and reagent stock solutions to prepare culture medium. Shipping frozen kits internationally is complex and sometimes delayed, potentially causing materials to thaw. We investigated whether refrigerated or ambient kit temperatures affect folate results.MethodsWe conditioned 5-methyltetrahydrofolate calibrator stock solution, L. rhamnosus microorganism inoculation, serum and whole blood lysate (WBL) QC samples, and reagent stock solutions (ascorbic acid, chloramphenicol, and manganese sulfate) at 6°C ≤ 3 d and 20°C ≤ 2 d protected from light; we then compared conditioned vs. optimally stored materials (-70°C) by analyzing serum and/or WBL samples (≥3 runs).ResultsThe conditioned calibrator showed a mean folate difference (range from 3 runs for 43 WBL samples) of −0.3% (−4.0 to 4.1%) at 6°C/3 d and 0.9% (−1.6% to 2.7%) at 20°C/2 d. Similarly, the conditioned microorganism showed a mean difference of 4.3% (0.7% to 8.3%) at 6°C/3 d and 0.6% (−3.5% to 4.9%) at 20°C/2 d. The conditioned reagents showed a mean difference (range from 3 runs for 5 serum and 5 WBL samples) of 0.3% (−7.4% to 9.0%) at 6°C/3 d and 3.6% (0.1% to 9.0%) at 20°C/2 d. The 2 conditioned serum QC samples (∼13 and ∼40 nmol/L) showed a mean difference (range from 6 runs) of −0.6% (−6.0% to 2.3%) at 6°C/1 d, but higher differences of −5.8%, −5.9%, and −20.7% at 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively. The conditioned low WBL QC sample (∼300 nmol/L) showed small mean differences (−1.5%, −2.4%, −1.7%, and −0.3% at 6°C/1 d, 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively), while the conditioned high WBL QC sample (∼600 nmol/L) showed higher mean differences (−3.1%, −12.4%, −6.9%, and −23.7%, respectively).ConclusionsAll kit components except for the QC materials demonstrated adequate stability (<5% change) at 6°C ≤ 3 d or at 20°C ≤ 2 d. The QC materials should not be exposed to 6°C for > 1 d to ensure stability. These findings provide important and practical information for kit shipment management.Funding SourcesNone.

Comparison of four different immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry assay for serum folate

Accurate measurement of serum folate is essential for the diagnosis and management of various disorders. This study aims to investigate the between-method differences of four immunoassays and a rapid isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method. Roche Cobas (USA), Abbott Alinity i2000 (USA), Beckman Coulter Access (USA), Mindray CL-6000i (China), and the ID-LC-MS/MS method were compared using 46 human serum samples. The results were analysed by Passing-Bablok regressions and Bland-Altman plots. A bias of 13.31% based on biological variation was used as the bias criterion. All the within-run and total coefficients of variation (CVs) met the specification. The folate concentrations determined by all the assays were significantly different (p=0.0028). All assays had correlation coefficients over 0.97 with each other. The 95% confidence intervals (CIs) for the slope seldom contained 1 and few 95% CIs for the intercept contained 0 in the regression equations. Compared to ID-LC-MS/MS, the biases of all assays ranged from-20.91 to13.56nmol/L, and the mean relative biases ranged from-9.85 to 40.33%. The predicted mean relative biases at the medical decision levels rarely met the criterion. Assays for serum folate had good correlations with each other but lacked good agreement. The accuracy and consistency of assays for serum folate should be measured and assessed routinely. Standardization work to improve the accuracy of serum folate assays, such as the extension of traceability to reference methods or materials, calibration standardization efforts, and assay-adjusted cut-offs should be promoted.

Robustness of the CDC Folate Microbiologic Assay Kit During Simulated Delayed Shipping

ObjectivesThe WHO has recommended the accurate and practical microbiologic assay (MBA) to assess population folate status. To help laboratories in low-resource countries conduct folate measurements, the CDC developed a folate MBA kit containing critical reagents: calibrator, microorganism, quality control (QC), and reagent stock solutions to prepare culture medium. Shipping frozen kits internationally is complex and sometimes delayed, potentially causing materials to thaw. We investigated whether refrigerated or ambient kit temperatures affect folate results.MethodsWe conditioned 5-methyltetrahydrofolate calibrator stock solution, L. rhamnosus microorganism inoculation, serum and whole blood lysate (WBL) QC samples, and reagent stock solutions (ascorbic acid, chloramphenicol, and manganese sulfate) at 6°C ≤ 3 d and 20°C ≤ 2 d protected from light; we then compared conditioned vs. optimally stored materials (-70°C) by analyzing serum and/or WBL samples (≥3 runs).ResultsThe conditioned calibrator showed a mean folate difference (range from 3 runs for 43 WBL samples) of −0.3% (−4.0 to 4.1%) at 6°C/3 d and 0.9% (−1.6% to 2.7%) at 20°C/2 d. Similarly, the conditioned microorganism showed a mean difference of 4.3% (0.7% to 8.3%) at 6°C/3 d and 0.6% (−3.5% to 4.9%) at 20°C/2 d. The conditioned reagents showed a mean difference (range from 3 runs for 5 serum and 5 WBL samples) of 0.3% (−7.4% to 9.0%) at 6°C/3 d and 3.6% (0.1% to 9.0%) at 20°C/2 d. The 2 conditioned serum QC samples (∼13 and ∼40 nmol/L) showed a mean difference (range from 6 runs) of −0.6% (−6.0% to 2.3%) at 6°C/1 d, but higher differences of −5.8%, −5.9%, and −20.7% at 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively. The conditioned low WBL QC sample (∼300 nmol/L) showed small mean differences (−1.5%, −2.4%, −1.7%, and −0.3% at 6°C/1 d, 6°C/3 d, 20°C/1 d, and 20°C/2 d, respectively), while the conditioned high WBL QC sample (∼600 nmol/L) showed higher mean differences (−3.1%, −12.4%, −6.9%, and −23.7%, respectively).ConclusionsAll kit components except for the QC materials demonstrated adequate stability (<5% change) at 6°C ≤ 3 d or at 20°C ≤ 2 d. The QC materials should not be exposed to 6°C for > 1 d to ensure stability. These findings provide important and practical information for kit shipment management.Funding SourcesNone.

Folate Status as a Nutritional Indicator among People with Substance Use Disorder; A Prospective Cohort Study in Norway.

Substance use disorder (SUD) is associated with poor nutrition. Vitamin B9, or folate, is an important micronutrient for health. The aim of this prospective longitudinal cohort study was to assess serum folate levels among people with SUD and to investigate the impact of factors related to substance use severity on folate status. Participants were recruited from outpatient clinics for opioid agonist therapy (OAT) and municipal health-care clinics for SUD in Western Norway. They were assessed annually, including blood sampling for determination of micronutrient status. Overall, 663 participants with a total of 2236 serum folate measurements were included. A linear mixed model was applied, and measures are presented as β-coefficients with 95% confidence interval (CI). Forty-eight percent (CI: 44–51) of the population had low serum folate levels (s-folate < 10 nmol/L), and 23% (CI: 20–26) were deficient (s-folate < 6.8 nmol/L) at baseline. Sixty percent (CI: 53–65) sustained their poor folate status in at least one subsequent assessment. Except for weekly use of cannabis (mean difference in serum folate [nmol/L]: −1.8, CI: −3.3, −0.25) and alcohol (1.9, CI: 0.15, 3.6), weekly use of no other substance class was associated with baseline differences in serum folate when compared to less frequent or no use. Injecting substances was associated with a reduction in serum folate over time (−1.2, CI: −2.3, −0.14), as was higher dosages of OAT medication (−1.1, CI: −2.2, −0.024). Our findings emphasize the need of addressing nutrition among people with severe SUD.

Reduced Kidney Function Is Associated with Increasing Red Blood Cell Folate Concentration and Changes in Folate Form Distributions (NHANES 2011-2018).

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108–390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.

Periconceptional maternal folate status and the impact on embryonic head and brain structures: the Rotterdam Periconceptional Cohort

Research questionDoes periconceptional maternal folate status influence the size of human embryonic head and brain structures? DesignThe study population was selected from the Rotterdam Periconceptional Cohort conducted at the Erasmus MC. Three-dimensional (3D) ultrasound scans were performed at 9 and 11 weeks of gestational age. Using 3D ultrasound datasets, head volume, head circumference, diencephalon (DTD), mesencephalon (MTD) and left/right telencephalon (TTL/TTR) measurements were performed offline using a virtual reality technique and specialized 3D software. Maternal venous blood samples were taken at study entry to determine red blood cell (RBC) folate. Linear regression models were applied to investigate associations between RBC folate status and embryonic head and brain structures adjusted for gestational age, alcohol use, smoking, maternal age and mode of conception. ResultsRBC folate measurements were available for 144 of the 166 singleton pregnancies eligible for analysis. RBC folate quartiles were defined: 466–1078 nmol/l (Q1), 1079–1342 nmol/l (Q2), 1343–1594 nmol/l (Q3), 1595–2919 nmol/l (Q4), with Q3 being used as reference. At 11 weeks of gestational age, head volume was largest in Q1 (β = 0.866; P = 0.004) and Q4 (β = 0.764; P = 0.007). In addition, head circumference at 11 weeks of gestational age was significantly larger in Q4 (β = 2.745; P = 0.03). There were no statistical significantly associations between the RBC folate quartiles and the sizes of the DTD, MTD, TTL and TTR. ConclusionsU-shaped associations were shown between the periconceptional maternal RBC folate status and embryonic head volume and head circumference. The clinical implication of these findings needs further investigation.

Homocysteine as a Predictor Tool in Multiple Sclerosis.

Multiple sclerosis (MS) is a progressive and irreversible disease which affects the central nervous system (CNS) with still unknown etiology. Our study aimes to establish the homocysteine pattern that can predict the MS diseases progression and to identify a potential disease progression marker that can be easy to perform and non-invasive, in order to predict the diseases outcome. In order to achieve this goal, we included 10 adult RRMS subjects, 10 adult SPMS subjects and 10 age-matched healthy subjects. The homocysteine plasma level was measured using automated latex enhanced immunoassay and the cobalamin and folate measurements were performed using automated chemiluminescence immunoassay (CLIA). HCR was calculated by dividing the homocysteine plasma level by cobalamin plasma level. We found that the homocysteine level in plasma of both RRMS patients and SPMS group are significantly increased compared with the control group. There is a significantly higher concentration of homocysteine in SPMS group compared with the RRMS group. In addition, the HCR is significantly increased in SPMS compared with the RRMS group and is a very good index of disease severity.

Habitüel Abortusta Vitamin B12 ve Folatın Rolü

Objective: Although several pathophysiological mechanisms are defined in the etiology of habitual abortion, still causes half of the cases haven’t been clarified yet. It has been reported that folate and vitamin B12 are effective in early pregnancy complications. In our study, we aimed to reveal the relationship between habitual abortion with folate and vitamin B12 levels.Materials and Methods: We included our study 124 pregnant having habitual abortion history and 242 pregnants without this, a total of 366 patients. Maternal and gestational age, height, weight, body mass index (BMI), gravidity, parity, abortion, and living children count and vitamin B12 and folate levels of these pregnants were evaluated retrospectively.Results: The ages, gravidity, and abortion counts of the study group were significantly higher than the control group (p&amp;lt;0.05). While the weight, height measurements, vitamin B12, and folate measurements showed no significant difference (p&amp;gt;0.05) between groups, the BMI measurements, living children count, and of the study group were significantly lower than the control group (p&amp;lt;0.05). Conclusion: According to our results, we didn’t find any relationship between habitual abortion with folate and vitamin B12 levels. Further larger sample-sized and prospective studies are required to contribute to the literature about this issue.

The Cerebrospinal Fluid Concentration of Methyltetrahydrofolate and Serum Folate in Children with Developmental Delay, Regression, and/or Refractory Epilepsy.

Folate is an important vitamin with a significant role in cell metabolism processes, and its deficiency is associated with several diseases. In addition, cerebral folate deficiency is associated with neurodevelopmental disorders. Studying the association of serum and cerebral folate deficiency with childhood neurodevelopmental disorders such as refractory epilepsy, developmental delay, and regression can be an important step towards the improvement of symptoms of such disorders. In this cross-sectional study, from February to October 2018, 60 children aged 6 months to 5 years; known cases of idiopathic refractory epilepsy; were selected randomly. After recording demographic, and clinical characteristics, cerebrospinal fluid (CSF) and blood samples were taken from the patients and sent to a laboratory for measurement of 5-methyltetrahydrofolate (5MTHF), folate, and homocysteine levels. Sixty patients completed the study, including 33 boys (55%) and 27 girls (45%). Mean ± SD of the studied population was 26.93 ± 19.97 months. Eighteen children (30%) had refractory epilepsy, 11 (18.3%) had developmental delay, 12 (20%) had refractory epilepsy and developmental delay, and 19 (31.7%) had refractory epilepsy and developmental regression. The results of brain magnetic resonance imaging (MRI) were normal in 47 (78.3%) children and atrophic in 13 (21.7%) children. Mean ± SD of serum level of homocysteine was 9.14 ± 8.58 μmol/L, that of folate was 11.60 ± 6.89 nmol/L, and that of 5MTHF was 69.23 ± 54.16 nmol/L. Measurement of serum folate, homocysteine, and CSF level of 5MTHF are of great importance in patients with developmental disabilities.