Folate and Vitamin B12 Status in Women of Reproductive Age in Rural Haryana, India: Estimating Population-Based Prevalence for Neural Tube Defects.

BACKGROUND: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs). METHODS: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design. RESULTS: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively. CONCLUSIONS: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared.

Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Association of Altered Ratio of Maternal Folic Acid and Vitamin B12 during Pregnancy with Newborn Birth Weight, Head Circumference, and Chest Circumference.

OBJECTIVE: This study evaluated the effect of an altered ratio of maternal RBC folate (MRF) to serum vitamin B12 (MB12) on pregnancy and newborn outcomes. METHODS: Blood samples were collected from pregnant women and the umbilical cord at the time of delivery. Estimations of RBC folate and serum vitamin B12 from maternal and cord blood samples and total homocysteine (HCY) were performed. Maternal and newborn anthropometric parameters like placental weight (PW), head circumference (HC), chest circumference (CC), and body weight (BW) were measured in offsprings after birth. We stratified the pregnant women into six groups (a) vitamin B12 normal and folic acid normal (BNFN)-control group, (b) vitamin B12 normal and folic acid elevated (BNFE), (c) vitamin B12 normal and folic acid deficient (BNFD), (d) vitamin B12 deficient and folic acid normal (BDFN), (e) vitamin B12 deficient and folic acid elevated (BDFE) and (f) vitamin B12 deficient and folic acid deficient (BDFD) based on their levels of RBC folate (MRF) and vitamin B12 (MB12). The expression of the one-carbon metabolism genes (methionine synthase (MS), glycine N-methyltransferase (GNMT), and cystathionine ß-synthase (CBS) was also studied in placental tissue by using real-time PCR. RESULTS: Cord blood RBC folate was significantly reduced in groups BDFE and BDFD as compared to the control group (BNFN). The cord blood vitamin B12 levels were also reduced in the BDFE group as compared to the BDFD. All the newborn parameters viz. PW, HC, CC, and BW, were reduced in the altered MRF/MB12 ratio (low & high vs. normal ratio). Total HCY was significantly elevated in the groups with (BDFE & BDFN) an imbalance of maternal RBC folate and serum vitamin B12 as compared to the control group. Downregulation of one-carbon metabolism genes like MS (p < 0.001), GNMT (p < 0.05), and CBS (p < 0.01) in placental tissue was observed in the high MRF/MB12 ratio group as compared to the normal ratio group. A strong positive correlation was also observed between MRF, MB12, and newborn parameters. CONCLUSIONS: The altered ratio of folate to vitamin B12 in the maternal blood is associated with adverse growth and development of the newborn.

Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India.

BACKGROUND: Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15µM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS: We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS: Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS: High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Association of maternal vitamin B12 and folate levels in early pregnancy with gestational diabetes: a prospective UK cohort study (PRiDE study).

AIMS/HYPOTHESIS: The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide in all ethnic groups. Low vitamin B12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence. Our aim is to assess the relationships of early pregnancy vitamin B12 and folate levels with the risk of GDM status at 26-28 weeks of gestation. METHODS: This was a prospective, multi-centre, multi-ethnic cohort study (n = 4746) in the UK. Participants who were eligible to be selectively screened as per the National Institute for Health and Care Excellence (NICE) criteria were included in the study. RESULTS: GDM prevalence was 12.5% by NICE and 14.7% by International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Folate deficiency (1.3%) was rare but B12 insufficiency (42.3% at <220 pmol/l) and folate excess (36.5%) were common in early pregnancy. Early pregnancy median B12 levels were lower, and folate levels higher, in women who were diagnosed with GDM at 26-28 weeks. B12 was negatively associated with fasting plasma glucose (1 SD: -0.06 mmol/l; 95% CI -0.04, -0.08; p < 0.0001) and 2 h plasma glucose levels (-0.07 mmol/l; 95% CI -0.02, -0.12; p = 0.004). Higher B12 was associated with 14.4% lower RR of IADPSG-GDM (0.856; 95% CI 0.786, 0.933; p = 0.0004) after adjusting for key confounders (age, parity, smoking status, ethnicity, family history, household income and folate status). Approximately half of this association was mediated through BMI. Folate was positively associated with 2 h plasma glucose levels (0.08 mmol/l; 95% CI 0.04, 0.13; p = 0.0005) but its relationship with fasting plasma glucose was U-shaped (quadratic ß: 0.011; p = 0.05). Higher folate was associated with 11% higher RR of IADPSG-GDM (adjusted RR 1.11; 95% CI 1.036, 1.182; p = 0.002) (age, parity, smoking status, ethnicity, family history, household income and B12 status). Although no interactions were observed for B12 and folate (as continuous variables) with glucose levels and GDM risk, a low B12-high folate combination was associated with higher blood glucose level and risk of IADPSG-GDM (adjusted RR 1.742; 95% CI 1.226, 2.437; p = 0.003). CONCLUSIONS/INTERPRETATION: B12 insufficiency and folate excess were common in early pregnancy. Low B12 and high folate levels in early pregnancy were associated with small but statistically significant changes in maternal blood glucose level and higher RR of GDM. Our findings warrant additional studies on the role of unmetabolised folic acid in glucose metabolism and investigating the effect of optimising early pregnancy or pre-conception B12 and folate levels on subsequent hyperglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT03008824.

Folate Levels in Patients Hospitalized with Coronavirus Disease 2019.

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.

The effects of folate and iron deficiency followed by supplementation on blood morphology and inflammation biomarkers in rats.

BACKGROUND: Little is known about the relation between iron and folic acid (FA) supplementation and inflammation. The aim of this study was to evaluate the effects of iron and folate deficiency and supplementation on blood morphology parameters, and to assess the role of iron and folate transporters in inflammation. METHODS: A four-week period of FA and iron deficiency in Wistar rats was followed by randomization into a group fed with a diet deficient in FA and supplemented with Fe (DFE), a group fed a diet deficient in Fe and supplemented with FA (DFOL), a group fed a diet supplemented with Fe and FA (FEFOL), a group fed a diet deficient in Fe and FA (D), and a group fed a control diet (C). The blood Crp concentration and blood count were determined. The expression of SLC11A2, SLC46A1, SLC19A1, and TFR2 proteins was assessed using the western blot method. RESULTS: After ten days on the experimental diets, the rats in the DFOL group had a 21% higher concentration of white blood cells (WBC) than the FEFOL group did (p < 0.05). We did not observe any differences between the groups in terms of C-reactive protein (Crp) concentration. We also did not find any other differences between the groups in other morphological parameters. Analysis of the correlation between blood count parameters and the expression of iron and folate transporters gave conflicting results. CONCLUSIONS: To conclude, iron and folate supplementation may affect WBC concentration in the blood.

Systematic analysis of gut microbiome reveals the role of bacterial folate and homocysteine metabolism in Parkinson's disease.

Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology.

Folate Intake Alters Mutation Frequency and Profiles in a Tissue- and Dose-Specific Manner in MutaMouse Male Mice.

BACKGROUND: While cancer is common, its incidence varies widely by tissue. These differences are attributable to variable risk factors, such as environmental exposure, genetic inheritance, and lifetime number of stem cell divisions in a tissue. Folate deficiency is generally associated with increased risk for colorectal cancer (CRC) and acute lymphocytic leukemia (ALL). Conversely, high folic acid (FA) intake has also been associated with higher CRC risk. OBJECTIVE: Our objective was to compare the effect of folate intake on mutant frequency (MF) and types of mutations in the colon and bone marrow of mice. METHODS: Five-week-old MutaMouse male mice were fed a deficient (0 mg FA/kg), control (2 mg FA/kg), or supplemented (8 mg FA/kg) diet for 20 wk. Tissue MF was assessed using the lacZ mutant assay and comparisons made by 2-factor ANOVA. LacZ mutant plaques were sequenced using next-generation sequencing, and diet-specific mutation profiles within each tissue were compared by Fisher's exact test. RESULTS: In the colon, the MF was 1.5-fold and 1.3-fold higher in mice fed the supplemented diet compared with mice fed the control (P = 0.001) and deficient (P = 0.008) diets, respectively. This contrasted with the bone marrow MF in the same mice where the MF was 1.7-fold and 1.6-fold higher in mice fed the deficient diet compared with mice fed the control (P = 0.02) and supplemented (P = 0.03) diets, respectively. Mutation profiles and signatures (mutation context) were tissue-specific. CONCLUSIONS: Our data indicate that dietary folate intake affects mutagenesis in a tissue- and dose-specific manner in mice. Mutation profiles were generally tissue- but not dose-specific, suggesting that altered cellular folate status appears to interact with endogenous mutagenic mechanisms in each tissue to create a permissive context in which specific mutation types accumulate. These data illuminate potential mechanisms underpinning differences in observed associations between folate intake/status and cancer.

Red blood cell folate and severe abdominal aortic calcification: Results from the NHANES 2013-2014.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) has been introduced as a good predictor of cardiovascular disease (CVD) events, but no previous study has investigated the relationship between folate levels and AAC. The present study aims to explore the relationship between red blood cell (RBC) folate, a better indicator reflecting long-term folate intake, and severe AAC in the United States (US) middle-aged and elderly population. METHODS AND RESULTS: Cross-sectional data were derived from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 of 2818 men and women aged 40 years or older. Multivariable logistic regression models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for severe AAC of each RBC folate quintile category. The restricted cubic spline model was used for the dose-response analysis. A U-shaped dose-response relation between RBC folate and the odds of severe AAC was found after adjustment for multiple potential confounding factors, p for nonlinear = 0.0032. With the third quintile category of RBC folate as the reference, multivariable-adjusted ORs and 95% CIs of the lowest, second, fourth, and the highest quintile categories were 2.34 (1.37-4.00), 1.24 (0.70-2.19), 1.58 (0.92-2.70), and 2.26 (1.35-3.76), respectively. CONCLUSIONS: Individuals with either low or high levels of RBC folate were at increased risks of severe AAC in a representative sample of US adults. While folate deficiency is widely recognized as harmful, these results highlight the need to investigate the potential adverse health outcomes of high folate level.

Serum Vitamins D, B9 and B12 in Greek Patients with Inflammatory Bowel Diseases.

Deficiencies in vitamin D, folate and cobalamin are common in Inflammatory Bowel Disease (IBD). The aim of the present study was to assess serum levels of these vitamins in IBD adults based on the respective serum cut off values for vitamin deficiencies, and to explore possible associations with IBD-related biomarkers and nutritional intake. A cross-sectional study was carried out and patients with Crohn's disease (CD) or ulcerative colitis (UC) from Attica-Greece were enrolled. Medical and dietary history, clinical examination and blood/stool biomarkers were evaluated. In total, 87 patients participated in the study. Serum levels of 25(OH)D, folate and cobalamin were deficient in 36.8%, 18.4% and 5.7% of patients, respectively. Linear regression analysis in the overall patients showed positive associations between (a) serum 25(OH)D with serum iron (beta = 0.083, p = 0.005) and (b) serum cobalamin with total bilirubin (beta = 0.357, p = 0.020) and direct bilirubin (beta = 0.727, p = 0.033), adjusting for age, sex, body mass index (BMI), disease activity and duration, smoking, nutritional intake and season of recruitment. In CD patients (N = 54), a negative linear association between serum folate and fecal lysozyme was evident (beta = -0.009, p = 0.020). No associations were found for UC patients (N = 33). The serum vitamin profile may be a complementary biomarker for the evaluation of disease activity next to serum and stool inflammatory biomarkers.

Alterations in Sulfur Amino Acids as Biomarkers of Disease.

Homocysteine (Hcy) is methylated by methionine synthase to form methionine with methyl-cobalamin as a cofactor. The reaction demethylates 5-methyltetrahydrofolate to tetrahydrofolate, which is required for DNA and RNA synthesis. Deficiency of either of the cobalamin (Cbl) and/or folate cofactors results in elevated Hcy and megaloblastic anemia. Elevated Hcy is a sensitive biomarker of Cbl and/or folate status and more specific than serum vitamin assays. Elevated Hcy normalizes when the correct vitamin is given. Elevated Hcy is associated with alcohol use disorder and drugs that target folate or Cbl metabolism, and is a risk factor for thrombotic vascular disease. Elevated methionine and cystathionine are associated with liver disease. Elevated Hcy, cystathionine, and cysteine, but not methionine, are common in patients with chronic renal failure. Higher cysteine predicts obesity and future weight gain. Serum S-adenosylhomocysteine (AdoHcy) is elevated in Cbl deficiency and chronic renal failure. Drugs that require methylation for catabolism may deplete liver S-adenosylmethionine and raise AdoHcy and Hcy. Deficiency of Cbl or folate or perturbations of their metabolism cause major changes in sulfur amino acids.

Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment.

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.

Milk fermented with Lactococcus lactis KLDS4.0325 alleviates folate status in deficient mice.

Folate is an essential B vitamin and its deficiency is common in many parts of the world. Natural folate produced by microorganisms may be an alternative to chemically synthesized folic acid (FA) as a dietary supplement. Previously, two lactic acid bacteria (LAB) strains, a high folate-producing Lactococcus lactis subsp. lactis KLDS4.0325 and a weak folate-producing Lactococcus lactis subsp. lactis KLDS4.0613, were identified. The aim of this study was to evaluate the effect of milk fermented with L. lactis KLDS4.0325 (folate-enriched fermented milk, FEFM) in alleviating folate deficiency status using murine folate deficiency models. In addition, the link between gut microbiota diversity and folate levels in mice was investigated. Results showed that FEFM increased FA and 5-methyltetrahydrofolate (5-MTHF) concentrations in the whole blood and liver, and decreased plasma homocysteine (Hcy) levels. 16S rDNA sequence analysis also revealed that the supplementation of FEFM (containing 0.6 µg mL-1 folate) and 0.6 µg d-1 FA (FEFM + LFA) significantly improved the poor status of the gut microbiota composition caused by folate deficiency, and the effect was better than that with 1.2 µg d-1 FA (HFA) supplementation. Our findings show that FEFM can be used as a folate-fortified food to alleviate folate deficiency effectively. In addition, it may be considered as a partial or total replacement for synthetic FA.

Joint effects of mitochondrial DNA4977 deletion and serum folate deficiency on coronary artery disease in type 2 diabetes mellitus.

BACKGROUND & AIMS: The 4977-bp mitochondrial deletion (mtDNA4977 deletion), as a hallmark of mitochondrial oxidative damage, may play an important role in coronary artery disease (CAD), but its interaction with folate deficiency among diabetic patients is largely unknown. We aimed to explore the joint association of leukocyte mtDNA4977 deletion and serum folate status with obstructive CAD in Chinese adults with type 2 diabetes. METHODS: We cross-sectionally analyzed the angiographic data of 2017 diabetic patients without B-vitamin supplementation. Of the 2017 participants, 756 who received percutaneous coronary intervention (PCI) completed prospective follow-up of one year. In vitro, we explored the mediation effects of mitochondrial reactive oxygen species (mtROS) in folic acid (FA)-deficient human aortic smooth muscle cells (HASMCs) under hyperglycemic conditions. RESULTS: Cross-sectionally, the multivariate odds ratios (ORs) for obstructive CAD were 1.41 (95% CI: 1.29-1.55) for greater mtDNA4977 deletion, and 1.15 (95% CI: 1.05-1.25) for lower folate levels. Particularly, the combination of high mtDNA4977 deletion (top tertile) and folate deficiency (serum folate < 6 ng/mL) was associated with more than 2-fold increased odds of having obstructive CAD and higher degrees of coronary stenosis. Prospectively, the hazard ratio for all-cause death at 1-year after PCI was up to 2.37 (95% CI: 1.21-4.63) for folate-deficient participants in the top tertile of mtDNA4977 deletion. In HASMCs, the adverse effects of FA deficiency were aggravated by induction of mtROS, and attenuated by scavenging of mtROS. CONCLUSIONS: The risk of obstructive CAD may be greatly increased by the interaction between greater mtDNA4977 deletion and folate deficiency among diabetic patients.

Prevalence, etiology and risk factors of anemia in patients with newly diagnosed cancer.

PURPOSE: To determine the prevalence of anemia, and to evaluate the etiology and risk factors of anemia in patients with newly diagnosed cancer. METHODS: In this cross-sectional study, 310 patients with newly diagnosed cancer who were referred to a university hospital in Turkey over a 6-month period and 218 age-matched healthy individuals as controls were evaluated in terms of anemia: complete blood count (CBC), ferritin, transferrin saturation (TS%), serum iron (SI), cobalamin (B12), and folate levels. Carcinoma of the breast (21.3%), lung (12.9%), and gastrointestinal tract (GIT) (35.8%) accounted for the majority of the patients, and 44.7% of the patients had metastatic disease. RESULTS: Anemia was observed in 49.7% of patients with cancer and in 11.9% of healthy controls (p < 0.001). SI and TS% were lower in patients with cancer than in the controls (p < 0.001); however, the median serum ferritin level, which is also an acute-phase reactant, was higher in the patient group than the healthy matched controls (42.2 ng/mL and 41 ng/mL, respectively, p < 0.001). Folate and B12 deficiencies were seen more frequently in the cancer group than in the controls [6.5% and 0.9% (p < 0.001); 39.3% and 18.9% (p < 0.05), respectively]. In the cancer group, anemia was seen more frequently in the metastatic subgroup than in the non-metastatic subgroup (59.7% and 55.3%, respectively, p < 0.05). The prevalence of anemia was similar in both groups of patients with and without primary GIT cancers, as well as in patients who did and did not undergo tumor surgery (p > 0.05). CONCLUSION: This study showed that, at the time a patient is diagnosed as having cancer, the patient already has a significant risk for anemia, nearly five times that of healthy people. Having metastatic disease, and having nutritional deficiencies as iron, B12, and folate were evaluated as possible risk factors for anemia in patients with newly diagnosed cancer, whereas cancer with GIT localization and previous history of tumor surgery were not.

Inpatient folate testing at an academic cancer center: single-year experience.

PURPOSE: The value of testing for folate deficiency has been scrutinized recently given low prevalence of deficiency with widespread dietary fortification. Numerous studies have shown folate testing to be low yield overall. However, the value of such testing in the inpatient cancer population has not been defined. METHODS: We queried all folate tests performed during 2017 at our center on admitted cancer patients. We used diagnosis codes and manual chart review to assess risk factors for folate deficiency. Descriptive statistics were used to summarize characteristics of patients undergoing folate testing, the frequency of vitamin B12 co-testing, and repeat folate testing. Fisher's exact test was used to compare the proportion of deficient vs. not deficient tests based on the presence of risk factors. A Cox proportional hazards model was fit to examine the association between folate deficiency and survival. RESULTS: In total, 937 patients had 1065 tests performed during 2017. Among all tests, 7.0% indicated folate deficiency. In patients who underwent two folate tests in a single hospitalization, 89% were deficient neither instance. Risk factors for folate deficiency were equally common in instances with deficient compared with replete testing (25.3 vs. 20.4%, P = 0.334). Folate deficiency was associated with higher risk for death (HR 1.49, 95% CI 1.10-2.03, P = 0.01). CONCLUSION: Folate deficiency was present in 7% of hospitalized cancer patients and associated with shorter overall survival. Repeat testing in the same patient over time was low yield. Traditional risk factors for folate deficiency do not appear to apply in this patient population.