Folate Assays Research Articles

Pediatric reference intervals for serum folate and cobalamin based on a European population without exposure to folic acid fortification

The aim of the present study was to define pediatric reference intervals for serum cobalamin and folate utilizing data generated from a population not exposed to food fortified with folic acid. Folate and cobalamin results analyzed by electrochemiluminescence immunoassay (Roche Cobas) were obtained from 2375 children (2 months to 17.99 years of age). The serum samples were collected between 2011 and 2015 as part of the LIFE (Leipzig Research Centre for Civilization Diseases) Child cohort study in Germany, where folic acid fortification of food is not mandated. These results were used to generate age- and gender-specific reference intervals presented as non-parametric 2.5 and 97.5 percentiles. Because of a subsequent restandardisation of the Roche folate assay in 2016, folate values were recalculated accordingly for adaptation to results obtained using the present calibration. In both genders, folate concentrations decreased continuously with age, whereas cobalamin concentrations peaked at five years of age and then declined. Teenage females had higher concentrations of cobalamin in the age group 12–17.99 years.

Verification of the analytical performance of the serum Folate assay on the Abbott Alinity ci®

In the evolving landscape of clinical diagnostics, the significance of folate takes center stage as precision and innovation shape advancements in analytical methodologies. Folate, a pivotal element in cellular metabolism, governs physiological processes and serves as an indicator for various medical conditions. This study employs the Chemiluminescent Microparticle Immunoassay (CMIA), known for its accuracy, to assess the reproducibility and repeatability of serum folate levels. Folate's role in cellular metabolism influences diverse physiological functions, making its precise quantification crucial for identifying and monitoring conditions such as folate deficiency. The CMIA method emerges as a robust approach, leveraging immunological specificity for high precision and reliability. Utilizing the Abbott Alinity ci® Analyzer, a technologically advanced clinical chemistry instrument, this study incorporates a systematic analytical method verification procedure. This involves quantification through a standardized protocol and a comparative analysis against criteria set by esteemed societies (RICOS and FSCB), ensuring comprehensive insights into analysis techniques. The reproducibility test, evaluating the impact of various factors on assay results, reveals low Coefficient of Variation (CV) values (CV1: 10.25%, CV2: 8.58%, CV3: 9.13%) across different levels. The results align with quality control limits, emphasizing the method's reliability. Repeatability assessment demonstrates exceptionally low CV values (CV1: 4.84%, CV2: 3.41%, CV3: 1.89%), highlighting the method's stability and precision under controlled conditions.

Validation, performance, and reliability of two automated tests for vitamin B12 and folate assay.

Deficiency of Vitamin B12 and folate may determine hematological, neurological, and metabolic alterations; therefore, an accurate quantification of their serum levels is required, especially in the presence of symptoms that might suggest a deficiency. CHORUS VIT B12 and CHORUS FOLATE are two automated immunoassays, developed to quantify vitamin B12 and folate, respectively, in human serum. This single-center, non-pharmacological, diagnostic study described the validation and characterization of CHORUS VIT B12 and CHORUS FOLATE, with a specific focus on performance, precision, and reliability. For each assay, 500 serum samples were analyzed. A comparison between CHORUS assays and commercially available kit was also performed. For CHORUS VIT B12 the lower limit of quantification (LLoQ) was 165.0 pg/mL and the upper LoQ (ULoQ) was 1846.8 pg/mL. The assay was linear within the calibration range (150-2000 pg/mL) and the accuracy was described with the International Standard Vitamin B12, Serum Folate, HOLO TC (NIBSC code: 03/178), with a mean recovery on two lots of 111%. For CHORUS FOLATE (calibration range of 2.0-20.0 ng/mL), LLoQ was 2.0 ng/mL and ULoQ 19.6 ng/mL. The linearity was demonstrated from 2.4 to 20.0 ng/mL; the accuracy was described with the International Standard mentioned above, achieving a mean recovery on three lots of 92%. The lowest and highest values of both CHORUS and COBAS kits were similar and the median values did not significantly vary. CHORUS VIT B12 and CHORUS FOLATE performed well, accurately, and reliably in quantifying vitamin B12 and folate in human serum.

Association of Methionine Synthase rs1805087 Polymorphism With Arsenic-Related Skin Pigmentary Changes: A Population-Based Case-Control Study

Objective: Chronic arsenic exposure causes skin lesions including skin cancers, pigmentary changes, and keratosis. Genetic polymorphism in arsenic metabolism may increase susceptibility to the development of arsenic-related skin lesions. This study was performed to determine whether arsenic metabolism-related gene variants are associated with arsenic-related pigmentary changes. Methods: This case–control study involved 189 patients with arsenic-related pigmentary changes and 103 controls. Thirty-eight polymorphisms in 10 genes determined by mass spectrometry assay served as candidate drivers of arsenic-induced pigmentary changes. Urine and plasma arsenic levels were determined by inductively coupled plasma mass spectrometry. Hair arsenic concentrations were measured by nondispersive atomic fluorescence spectrometry. Arsenic metabolites in urine were determined using high-performance liquid chromatography with inductively coupled plasma mass spectrometry. Serum folate was measured using a folate radio assay kit. Analysis of variance, nonparametric test, or the chi-square test was selected according to the data distribution. Spearman correlation analysis was used to determine the correlation between two parameters. Logistic regression was used to estimate the effect of single-nucleotide polymorphisms. Results: The arsenic concentrations in urine, plasma, and hair and the urine arsenic species were not significantly different between patients and controls. Logistic regression revealed that among the polymorphisms, the methionine synthase (MTR) rs1805087 polymorphism showed a protective effect against arsenic-related pigmentary changes. In the codominant model, the adjusted odds ratio for age, sex, and ethnicity was 0.41 (95% confidence interval [CI], 0.21–0.80; P = 0.008) for the AG genotype and 0.11 (95% CI, 0.02–0.60; P = 0.012) for the GG genotype. Conclusion: MTR polymorphism showed a protective effect against arsenic-related pigmentary changes in the logistic regression model. The effect of MTR rs1805087 might be independent of arsenic metabolism and one-carbon metabolism. More studies are needed to clarify the biological function of MTR rs1805087 and its relationship with the etiology of arsenic-related pigmentary changes.

To Study Hematological Features in Various Etiologies of Macrocytic Anemias

Background: Mean corpuscular volume (MCV) increases by more than 100 fl. in macrocytosis, a condition in which erythrocytes are larger than normal. The purpose of this study was to evaluate the haematological characteristics in various aetiologies and to determine the underlying reasons of macrocytosis, which was found in regular hemograms. In addition to doing full blood counts, renal function tests, liver function tests, vitamin B12 assays, folate assays, and peripheral smear evaluations and few case were bone marrow examination. Material and Methods: In this prospective observational study conducted over a period of one-year, medical records of 250 subjects were evaluated. Data was compiled of Megaloblastic, Non-megaloblastic Macrocytosis levels, along with clinical diagnosis and other biochemical parameters. Based on clinical evaluation and hematological and biochemeical evidence, patients were diagnosed as positive cases of Megaloblastic(166), Non-Megaloblastic (133).Among this two variable group Mean ±SD were also calculated .

ANEMIA IN HYPERTENSIVE PATIENTS WITH CHRONIC RENAL FAILURE, WHAT ARE THE CHARACTERISTICS?

Objective: During chronic renal failure, the progressive impairment of kidney functions results in a set of manifestations, initially biological, then clinical. Anemia and high blood pressure are common complications during chronic kidney disease. The aim of this study is to determinate the main characteristics of anemia in hypertensive patients with chronic kidney disease Design and method: This descriptive work is a retrospective cross-sectional study aimed at evaluating the iron status of 70 hypertensive chronic renal failure patients. The average age in this study was 65 years with a male predominance (51%). In our study, 70 patients with chronic renal failure of all stages participated, hypertensive and anemic. The count of the blood elements and the hemoglobin assay were done by optical measurement using the ADVIA® 2120i automaton. The assay of vit B12, folate and ferritin in the blood by enzymatic chemiluminescence. Results: In our study, the mean hemoglobin was 10.18 g/dl, In our series of hemodialysis patients, mean serum ferritin was 276±207.14 ng/ml. In our population, blood pressure averages are of the order of: 130.29 ± 22.33 mm Hg for PAS, and 69.86 ±10.16 mm Hg for DBP. Regarding patients with chronic renal failure not on dialysis 43.5% of patients had serum ferritin low. 50% had normal ferritinemia, and 6.45% of patients had elevated serum ferritin. Ford's study found 2.92% of patients with low serum ferritin, 25.05% had a normal level, and 72.02% had hyperferritinemia. At 26% of patients in our population, the blood pressure figures were > 140/90 mmHg, while 74% of patients reached the target . Conclusions: Chronic renal failure exposes to numerous hematological and cardiovascular type complications, which can themselves induce health problems, in addition Correction of anemia is not always beneficial for patients suffering from CKD in due to increased blood pressure. Perform periodic biological and hormonal analyzes. Recommend lifestyle and dietary measures in all hypertensive patients, chronic renal failure. Carry out awareness campaigns with the general public for a better understanding of chronic kidney disease

The prevalence and risk factors associated with Iron, vitamin B12 and folate deficiencies in pregnant women: A cross-sectional study in Mbeya, Tanzania.

Maternal nutrition is an important forecaster of infant's and mother's health status in most developing countries. This study aimed at assessing the prevalence and associated risk factors of iron, vitamin B12, and folate deficiencies among pregnant women in Mbeya Tanzania. A cross-sectional study using a cluster randomized sampling was conducted among 420 pregnant women. A structured questionnaire was used to collect socio-demographic and dietary assessment. Body iron store was assessed using serum ferritin measured by immunoturbidimetric assays using a Roche Cobas 400+ biochemistry analyzer. Serum folate was measured by folate microbiological assay, while serum vitamin B12 was measured by immunochemiluminescence assay using a Roche Cobas e411 immunoassay analyzer. Multivariate analysis was performed using Poisson regression. The prevalence of iron, folate, and vitamin B12 deficiencies among pregnant women in Mbeya was 37.8%, 24.0%, and 9.7% respectively. Higher odds of iron deficiency were seen in pregnant women aged 20-24 years older [Adjusted OR = 1.20 (95%CI 1.03, 1.35)], not employed [Adjusted OR = 3.0(95%CI 1.03-1.77)] and, not received iron/folic acid supplementation [Adjusted OR = 1.11 (95%CI 1.003-1.23)]. Pregnant women with highest and middle socio-economic statuses had lower odds of vitamin B12 deficiency [Adjusted OR = 0.83 (95%CI 0.76-0.92)] and [Adjusted OR = 0.89 (95%CI 0.81-0.98)] respectively. Pregnant women who were not employed, not received iron and folic acid supplement during pregnancy and, not consumed edible vegetable cooking oil had significant higher odds of serum folate deficiency [Adjusted OR = 3.0 (95%CI 1.58-5.68)], [Adjusted OR = 1.53 (95%CI 1.21-1.93)] and, [Adjusted OR = 2.77 (1.03-7.44)] respectively. This study confirms that iron, folate and vitamin B12 deficiencies are still a major challenge among pregnant women in Tanzania. We recommend for public health interventions for the provision of vitamin B12 along with iron and folic acid supplementations, especially in pregnant women belong to low socio-economic status and limited knowledge of healthy diet.

Prevalence of megaloblastic anaemia and its causative factors in a tertiary care centre at Western India

Background: Anaemia affected population includes male, females as well as children and is a common problem that has been seen in western India. Megaloblastic Anaemia is common in India but regarding its prevalence and causative factors data is insufficient. The most common cause of megaloblastic anaemia includes deficiency of folic acid and Vitamin B12. Due to vegetarian lifestyle of the people the deficiency of Vitamin B12 is more common rather than the other macronutrient. In today's time, only iron and folic acid is provided by Anaemia control or prophylaxis program. This issue needs focus and hence this study has been chosen. Objective: To focus on the incidences of Megaloblastic Anaemia in Western India and analyse the possible causative factors. Materials and Methods: Patients with a haemoglobin <10 g/dl and peripheral smear findings consistent with megaloblastic anaemia present in the hospital over a period of 2 months will be included in the study. Patient's diet, drug intake, present symptoms and other history will be taken into account. Recording of complete blood counts, peripheral film examination, reticulocyte count and cobalamin and folate assays will be done. Patients suffering from chronic disease like renal disease, cancer, tuberculosis, liver disease etc., Will be excluded from the study. All data will be collected and statistically evaluated. Results: In the current study, 500 patients who were admitted to the gynaecology, paediatric, and medical wards were all assessed. These patients were all eligible to participate. They were divided into three groups based on the mean corpuscular volume (MCV) value, serum assay, and peripheral smear results: Macrocytic, normocytic, and microcytic anaemia. A megaloblastic blood film or low serum indicators along with the normal MCV value were categorised as having macrocytic anaemia. A total of 100 patients had macrocytic anaemia identified. The distribution of sexes was: 70 (male), 30 (female). There were discovered to be 55% of patients with cobalamin deficit and 8% of patients with folate deficiency. Every patient were vegetarians, coming from a poor socioeconomic status. Conclusion: The diagnosis of Megaloblastic anaemia was done through complete blood counts, red cells and assays of two vitamins. Majority of patients having megaloblastic anaemia was due to deficiency of cobalamin. Poor diet in cobalamin or folate were the contributing factors in Megaloblastic anaemia. Prevention can be done through awareness camps and education programmes and also through proper diet. Vitamin B12 should be included in the diet of patients along with iron and folic acid.

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.

Clinical and hematological evaluation of geriatric anemia.

ABSTRACTBackground:Anemia in the elderly is a cause of concern. It is not merely physiological due to aging and requires appropriate evaluation. Anemia has a significant negative impact on cardiac function, cognition, sleep, frequent hospitalization, mobility, morbidity, and mortality. Anemia in the elderly is attributable to many causes: nutrient deficiencies, chronic inflammatory diseases, thyroid disorders, diabetes mellitus, gastrointestinal (GI) tumors and bleeding, chemotherapy-induced anemia, and drug-induced hemolysis.Objectives:We aimed to evaluate the clinical and hematological profile of anemia in 100 patients aged above 60 years.Methods and Material:We performed a cross-sectional type of study in a tertiary care center including male and female patients aged 60 years and above and whose hemoglobin was less than 13 g/dl and less than 12 g/dl, respectively. Clinical history, complete blood picture, and peripheral smear were obtained in all patients. Serum iron profile was done in patients with micro-normocytic anemia. Vitamin B12 and folate assays were done in patients with normo-macrocytic anemia and those with pancytopenia. Bone marrow studies and endoscopies were done in cases wherever deemed appropriate.Results:The majority of the patients had either severe or moderate anemia. 49% of the patients had normocytic anemia. The commonest cause for anemia was nutritional deficiencies (45%) followed by anemia of chronic inflammation (40%) and unexplained anemia (8%).Conclusions:It is essential that anemia deserves its due attention in clinical practice in older patients and is not normal always.

Probiotic Potential of a Folate-Producing Strain Latilactobacillus sakei LZ217 and Its Modulation Effects on Human Gut Microbiota.

Folate is a B-vitamin required for DNA synthesis, methylation, and cellular division, whose deficiencies are associated with various disorders and diseases. Currently, most folic acid used for fortification is synthesized chemically, causing undesirable side effects. However, using folate-producing probiotics is a viable option, which fortify folate in situ and regulate intestinal microbiota. In this study, the folate production potential of newly isolated strains from raw milk was analyzed by microbiological assay. Latilactobacillus sakei LZ217 showed the highest folate production in Folic Acid Assay Broth, 239.70 ± 0.03 ng/μL. The folate produced by LZ217 was identified as 5-methyltetrahydrofolate. LZ217 was tolerant to environmental stresses (temperature, pH, NaCl, and ethanol), and was resistant to gastrointestinal juices. Additionally, the in vitro effects of LZ217 on human gut microbiota were investigated by fecal slurry cultures. 16S rDNA gene sequencing indicated that fermented samples containing LZ217 significantly increased the abundance of phylum Firmicutes and genus Lactobacillus, Faecalibacterium, Ruminococcus 2, Butyricicoccus compared to not containing. Short-chain fatty acids (SCFAs) analysis revealed that LZ217 also increased the production of butyric acid by fermentation. Together, L. sakei LZ217 could be considered as a probiotic candidate to fortify folate and regulate intestinal microecology.

Interpretation of Folate Results in Hemolytic Plasma Samples: A Practical Approach.

Folate analysis in plasma is affected by hemolysis, which can lead to biased results. However, the degree of hemolysis that is considered acceptable is unclear. We explored the relationship between folate concentration and degree of hemolysis. Heparin plasma samples (N=77, hemolysis index ≤10 μmol/L) were spiked with increasing amounts of corresponding patient-specific hemolysate. Subsequently, the folate concentration and hemolysis index were measured using two Roche Cobas platforms, and their incremental relationship was investigated. The folate concentration ranged from 2.9 to 30.9 nmol/L with a median (interquartile range) of 11.4 (8.6-19.1) nmol/L. The linear relationship between the increments in folate concentration and hemolysis index was approximated by the function y=1.86x+1.56 (R2=0.996), where x represents the laboratory-specific critical difference in folate concentration, which can be calculated from the analytical variation of the employed folate assay(s), and y represents the hemolysis threshold. The hemolysis threshold did not significantly differ between the tertiles of plasma folate concentration (P=0.10). In conclusion, we have provided an evidence-based approach that can be used to reliably interpret folate concentrations in hemolytic samples, independent of the patient’s folate status.

A study on periconceptional folic acid supplement intake and serum folic acid levels in pregnant mothers

BackgroundSurvey-based studies have examined the timing of receiving periconceptional folic acid supplementation. To assess the impact of the periconceptional folic acid supplementation, a postulate that multigravida mothers are more likely to have received the supplementation and the level of serum folic acid in them assayed during the first trimester is likely to be higher than primigravida mothers was put forth. Serum folic acid levels were measured in primigravida and multigravida mothers during the first trimester. MethodsOne hundred twenty primigravida and multigravida mothers registered at antenatal clinic of a tertiary care referral centre were included. Serum folic acid assay from samples collected during the first trimester was carried out by chemiluminescence immuneassay. The mothers were followed up during subsequent OPD visits, during admission for delivery and through mobile phones for assessing the delivery outcomes. World Health Organization cutoff values for serum folic acid were used to analyse the results. ResultsNone of the mothers received folic acid supplement before conception. Mean interval from last menstrual period to receiving the first dose of folic acid supplementation was 71.2 days in primigravida and 67.6 days in multigravida mothers. Overall, 21/120 (17.5%) of primigravida mothers and 34/120 (28.3%) of multigravida mothers had serum folic acid values less than 6 ng/ml (deficiency and possible deficiency). ConclusionNone of the mothers received folic acid supplements before conception. Significant proportion of mothers, particularly the multigravida having less than normal levels serum folic acid indicates correctable lacunae amenable for preventive intervention.

Preoperative patient blood management during the SARS-CoV-2 pandemic.

Preoperative patient blood management during the SARS-CoV-2 pandemic.

Prevalence of Folate Deficiency in Korean Women of Reproductive Age Using a Serum Folate Assay Traceable to the WHO International Standard

We aimed to investigate serum folate level in Korean women of reproductive age and to evaluate the prevalence of folate deficiency by age using different cutoffs. We retrospectively reviewed data obtained with a serum folate assay traceable to World Health Organization international standard reference material 03/178. Between September 2017 and June 2019, data from a total of 8,380 Korean women aged 15 - 49 years were obtained. Mean (standard deviation) serum folate concentration for all women was 9.1 (6.7) ng/mL. Prevalence of folate deficiency using the cutoff of < 3 ng/mL was 6.2% and that for < 4 ng/mL was 14.9%. The prevalence of folate deficiency was higher in women of younger age (15 to < 25 years, even > 30% using the cutoff of 4 ng/mL) compared to other age groups. This study suggests that women aged 15 to < 25 years are at high risk of folate deficiency.

Reference Interval for Korean Serum Folate Assay Traceable to the WHO International Standard.

Little is known about the reference interval of serum folate concentration if using recently re-standardized assays traceable to the World Health Organization (WHO) international standard reference 03/178 in a Korean population. This study aimed to investigate serum folate levels in Korean subjects without macrocytic anemia or increased homocysteine, for the assessment of folate deficiency. We retrospectively reviewed data from Korean adults whose hemoglobin, mean corpuscular volume, and serum total homocysteine values were within reference limits. The median (interquartile range) serum folate level was 7.8 (5.4 - 12.6) ng/mL in men and 10.2 (6.9 - 15.6) ng/mL in women. The reference interval for serum folate (2.5th and 97.5th percentiles) ranged from 2.9 to 38.0 ng/ mL. From among 723 Korean adults, the lower limit of reference intervals of serum folate for folate deficiency, defined as the 2.5th percentile, was 2.9 ng/mL. The prevalence of folate deficiency was higher in men (6.5%) than in women (1.2%, p < 0.05) when a cutoff value of 3.0 ng/mL was applied. Using the cutoff value of 4 ng/mL for folate deficiency, which is in accordance with the instructions from the manufacturer of the new assay and the WHO 2012 guideline for homocysteine as a metabolic indicator before assay standardization, about 5% of subjects were reclassified as folate deficient. Our study suggests that any change of reference limits using a re-standardized assay needs to be verified in clinical laboratories.

Study of dimorphic anemia in adults with reference to basic etiology

Objective: To investigate the basic cause of dimorphic anemia in adult patients using hematological parameters, bone marrow iron stores, serum vitamin B12 and folate assays. Materials and Methods: Hematological parameters and bone marrow, serum vitamin B12 and folate assays of 62 patients with dimorphic anemia were studied to evaluate the basic etiology in dimorphic anemia. Results: The mean MCV was 95.01±13.14fl and MCV was normal in 56.45% cases. BM examination showed megaloblastic maturation in 32.36%, megaloblastic with micronormoblastic maturation in 64.52% cases. BM iron stores were deficient in 32.26% cases. 43.55% cases had only folic acid deficiency, 19.35% cases had only B12 deficiency and 27.42% cases had both B12 and folate deficiency. Combined iron and vitamin deficiencies in 25.8% cases. The mean MCV, MCH, MCHC and RDW were significantly high in combined deficiencies. Conclusion: The common basic cause for dimorphic anemia was folate deficiency. MCV is unreliable as a screening parameter for anemia with vitaminB12 or folate deficiencies. Concomitant deficiencies of B12 or folate with iron deficiency are not infrequent; one type of anemia may mask the other. Serum assays will be appropriate to establish the cause in cases with concomitant deficiencies, as it may result in discordant results with various other tests like hematological parameters. Keywords: Anemia, Dimorphic, Folate, Megaloblastic, Myelodysplasia, Vitamin B12.

Test utilization for the diagnosis of vitamin B12 and folate deficiency in local clinics in Korea.

BackgroundCurrent guidelines pertaining to diagnosing macrocytic anemia in association with vitamin B12 and folate deficiency recommend that vitamin B12, folate, homocysteine, and methylmalonic acid assays should be assessed concurrently due to their close relationship in metabolism. We aimed to investigate the completion of these assays in local clinics and hospitals without in‐house clinical laboratories in Korea.MethodsWe retrospectively reviewed data from the laboratory information system between September 25, 2017, and June 30, 2019, to investigate usage rates of vitamin B12, folate, homocysteine, and methylmalonic acid assays in patients with macrocytic anemia.ResultsDuring the study period, 14 894 Korean adults among 109 524 (13.6%) total hemoglobin‐tested subjects underwent concurrent erythrocyte mean corpuscular volume (MCV) tests. Among these 14,894 adults, 265 (1.2%) from 94 local clinics or hospitals without in‐house clinical laboratories in Korea had macrocytic anemia. Furthermore, among these 265 adults, only one woman underwent serum vitamin B12 and folate assay and one man underwent serum homocysteine testing during the study period. No patients among the 265 individuals with macrocytic anemia received erythrocyte folate or methylmalonic acid testing (with either serum, plasma, random urine, or 24‐hour collected urine).ConclusionsThe results of this study provide basic information regarding utilization rates of assays in association with vitamin B12 and folate deficiency. Making more data available is expected to improve rates of testing in patients with macrocytic anemia in local clinics and hospitals without in‐house clinical laboratories in Korea.

The influence of obesity on folate status, DNA methylation and cancer-related gene expression in normal breast tissues from premenopausal women

ABSTRACT Epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation inform the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We modified the Lactobacillus Casei microbiological folate assay and measured folate levels in our breast tissue samples. The DNA methylation of LINE-1, a biomarker of genome-wide methylation, and the expression of a panel of breast cancer-related genes was measured by pyrosequencing and real-time PCR. We found that a high BMI is associated with an increase of folate levels in mammary tissue, with an increase of 2.65 ng/g of folate per every 5-unit increase of BMI (p < 0.05). LINE-1 DNA methylation was significantly associated with BMI (p < 0.05), and marginally associated with folate concentration (p = 0.087). A high expression of SFRP1 was observed in subjects with high BMI or high folate status (p < 0.05). This study demonstrated that, in premenopausal women, obesity is associated with increased mammary folate status, genome-wide DNA methylation and SFRP1 gene expression. Our findings indicated that the improved folate and epigenetic status represents a novel mechanism responsible for the reverse association between obesity and pre-BC.

Physicochemical Compatibility Investigation of Mesalazine and Folic Acid Using Chromatographic and Thermoanalytical Techniques.

Inflammatory bowel disease is a common name for Crohn’s disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.