Higher Folate Levels Research Articles

Associations of serum folate and vitamin C levels with metabolic dysfunction-associated fatty liver disease in US adults: A nationwide cross-sectional study.

Clinical research results on the relationship between folate and non-alcoholic fatty liver disease are contradictory. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed concept. Evidence about the relationship between serum folate and MAFLD, especially considering the status of serum vitamin C, is scarce. This study was aimed to investigate the association of serum folate levels with the prevalence of MAFLD, and further to analyze the potential impact of serum vitamin C status on their association. Totally 2,797 participants from National Health and Nutrition Examination Survey (NHANES) 2017-2018 were included. Vibration-controlled transient elastography was used to detect liver steatosis and fibrosis. Participants were divided in groups based on the tertiles of serum folate or vitamin C, and the serum folate or vitamin C level in T1 was low. Logistic regression analysis in the complex sample module was performed to illustrate the association of serum folate levels with the prevalence of MAFLD. Stratification analysis by serum vitamin C status was performed as well. Compared with the serum folate levels of T1 group, participants in the T3 group had 47.9% lower risk of MAFLD [OR = 0.521 (95% CI: 0.401-0.677)]. However, when participants were stratified by serum vitamin C levels, there was no association between the serum folate levels and MAFLD in the T1 or T2 group. Among participants in the T3 group of vitamin C status, participants in the T3 group of serum folate had a 63.6% lower risk of MAFLD compared with the T1 group [OR = 0.364 (95% CI: 0.147-0.903)]. High serum folate level is associated with lower prevalence of MAFLD, especially in participants with sufficient vitamin C.

The establishment of LC-MS/MS assays-specific reference intervals for serum folates and its application in evaluating FA-supplemented folate deficiency patients: Appeals for a suitable and individualized supplementation

BackgroundLittle known about folates status in folate deficiency patients. This study aims to establish liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay-specific reference intervals (RIs) for serum 5-Methyltetrahydrofolate (5MeTHF), folic acid (FA), 5-Formyltetrahydrofolate (5FoTHF), and total folate (TFOL), and investigate the folates status in FA-supplemented folate deficient patients. MethodsSera from 120 reference subjects were selected and measured. An LC-MS/MS method for serum 5MeTHF, FA, and 5FoTHF was employed. RIs were derived based on the CLSI C28-A3. Serum folate levels of 38 FA-supplemented folate deficiency patients were analyzed. ResultsRIs (median) for 5MeTHF, FA, 5FoTHF, and TFOL were 3.83–62.33 nmol/L (12.27 nmol/L), 0.30–0.92 nmol/L (0.49 nmol/L), <0.73 nmol/L (0.00 nmol/L), and 4.17–63.47 nmol/L (12.66 nmol/L), respectively. Approximately 53 % (20/38), 74 % (28/38), and 63 % (24/38) of patients presented high levels of 5MeTHF, FA, and TFOL, respectively, which far exceeded the upper reference limit (URL) of the corresponding RIs. A half (18/38) of patients showed simultaneously higher 5MeTHF and FA levels which were beyond the URLs of RIs. Near one-third (11/38) of patients exhibited extremely high FA levels which exceeded the 100-fold URL of RIs. The highest levels can be 539 nmol/L for FA, 364 nmol/L for 5MeTHF, and 686 nmol/L for TFOL. ConclusionsLC-MS/MS assay-specific RIs were established for folates vitamers without age or gender partitioning. Abnormally high levels of unmetabolized FA and 5MeTHF were observed in quite a few FA-supplemented patients. Considering the adverse risks caused by folates excess, we appeal for a justifiable and individualized FA supplementation. We also recommend establishing LC-MS/MS assay-specific RIs for routine monitoring of folates status.

Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

BackgroundHyperhomocysteinemia is considered an independent risk factor for cognitive impairment.ObjectiveTo study the correlation between homocysteine levels and cognitive impairment in patients with PD.MethodsWe conducted a case–control study that included 246 patients with PD, of whom 32 were cognitively impaired. The levels of homocysteine, folate, and vitamin B12 were measured in peripheral blood. Multivariate logistic regression analysis was applied to determine differences in homocysteine levels between PD patients with and without cognitive impairment. A meta-analysis was performed to clarify the role of Hcy levels in PD with cognitive decline. Five polymorphisms in genes involved in Hcy metabolism, including MTHFR rs1801133 and rs1801131, COMT rs4680, MTRR rs1801394, and TCN2 rs1801198, were genotyped.ResultsOur case–control study showed that homocysteine levels were associated with cognitive impairment in PD after adjusting for possible confounding factors such as levodopa equivalent daily dose. The results of our meta-analysis further supported the positive association between homocysteine levels and cognition in PD. We found that the MTHFR rs1801133 TT genotype led to higher homocysteine levels in PD patients, whereas the MTHFR rs1801131 CC genotype resulted in higher folate levels. However, the polymorphisms studied were not associated with cognitive impairment in PD.ConclusionsIncreased homocysteine levels were a risk factor for cognitive decline in PD. However, no association was found between polymorphisms in genes involved in homocysteine metabolism and cognitive impairment in PD. Large-scale studies of ethnically diverse populations are required to definitively assess the relationship between MTHFR and cognitive impairment in PD.

High Folate, Perturbed One-Carbon Metabolism and Gestational Diabetes Mellitus.

Folate is a dietary micronutrient essential to one-carbon metabolism. The World Health Organisation recommends folic acid (FA) supplementation pre-conception and in early pregnancy to reduce the risk of fetal neural tube defects (NTDs). Subsequently, many countries (~92) have mandatory FA fortification policies, as well as recommendations for periconceptional FA supplementation. Mandatory fortification initiatives have been largely successful in reducing the incidence of NTDs. However, humans have limited capacity to incorporate FA into the one-carbon metabolic pathway, resulting in the increasingly ubiquitous presence of circulating unmetabolised folic acid (uFA). Excess FA intake has emerged as a risk factor in gestational diabetes mellitus (GDM). Several other one-carbon metabolism components (vitamin B12, homocysteine and choline-derived betaine) are also closely entwined with GDM risk, suggesting a role for one-carbon metabolism in GDM pathogenesis. There is growing evidence from in vitro and animal studies suggesting a role for excess FA in dysregulation of one-carbon metabolism. Specifically, high levels of FA reduce methylenetetrahydrofolate reductase (MTHFR) activity, dysregulate the balance of thymidylate synthase (TS) and methionine synthase (MTR) activity, and elevate homocysteine. High homocysteine is associated with increased oxidative stress and trophoblast apoptosis and reduced human chorionic gonadotrophin (hCG) secretion and pancreatic β-cell function. While the relationship between high FA, perturbed one-carbon metabolism and GDM pathogenesis is not yet fully understood, here we summarise the current state of knowledge. Given rising rates of GDM, now estimated to be 14% globally, and widespread FA food fortification, further research is urgently needed to elucidate the mechanisms which underpin GDM pathogenesis.

Design of Cereal Products Naturally Enriched in Folate from Barley Pearling By-Products.

Folate is a fundamental vitamin for human health in prevention of many diseases; however, unfortunately its deficiency is widespread, so a greater availability of folate rich foods is desirable. The aim of this study was to design new cereal products naturally enriched in folate using barley flour from pearling as ingredient. Folate content of unfortified and fortified commercial grain-based products was considered to identify the best ingredients for new formulation and for folate content comparisons. Nineteen Italian barley cultivars were evaluated for their folate content and Natura was chosen for its highest folate levels = 69.3 μg/100 g f.w. Application of pearling gave a by-product flour with a high folate level: 221.7 ± 7.0 μg/100 g; this flour was employed to design pasta and biscuits naturally enriched in folate: 87.1 μg/100 g and 70.1 ± 3.7 μg/100 g f.w., respectively. Folate content of new products is higher than commercial samples: 39.2 μg/100 g in refined pasta, 60.4 μg/100 g in wholemeal pasta, 62.1 μg/100 g in fortified biscuits and 10.4 μg/100 g in unfortified ones. Enriched pasta had higher folate retention (68.5%) after cooking compared to the fortified one (27.8%). This research shows promising results concerning the pearling technique to design new cereal products naturally enriched in folates.

Effect of Folic Acid Supplements on Progesterone Profile and Blood Metabolites of Heat-Stressed Holstein Cows during the Early Stage of Pregnancy.

Simple SummaryThe fertility of a dairy cow can be described as the female’s ability to conceive and maintain pregnancy when insemination is performed at the proper time relative to ovulation. In this context, poor estrous detection and embryonic or fetal losses are common causes for reduced reproductive performance in dairy cows. Furthermore, heat stress severely deteriorates conception and pregnancy rates in dairy farms. The aim of this study was to see how oral folic acid (FA) supplements affect progesterone levels, blood metabolites, endocrine patterns, and blood biochemical concentrations in heat-stressed pregnant cows. Oral FA supplementation (10 μg kg−1) in the first month of gestation improved the progesterone profile, as well as blood folates, pregnancy associated glycoprotein (PAG), growth hormone (GH), and Insulin-like growth factor-1 (IGF-1) concentrations in heat-stressed Holstein cows.The aim was to elucidate the impact of oral folic acid (FA) supplements on progesterone profile, blood metabolites and biochemical indices of heat-stressed Holstein cows during the early stage of pregnancy. The study lasted from the day of artificial insemination through the end of the fourth week of pregnancy. The first group (CON, n = 17) received 0 μg of FA/kg BW as a control. The second and third groups received oral FA doses of 5 (FA5, n = 19) and 10 (FA10, n = 20) μg kg−1 BW, respectively. At the 2nd and 3rd weeks of pregnancy, the FA10 group had greater progesterone levels than the CON group (p < 0.05). The FA10 group had a greater progesterone level than the FA5 and CON groups at the fourth week of pregnancy (p < 0.01). The FA10 group had higher folate levels than CON group during the first three weeks of pregnancy (p < 0.01). Both FA-supplemented groups had significantly greater serum folates than the CON group by the end of the fourth week of pregnancy (p < 0.01). At the 2nd and 4th weeks of pregnancy, the FA10 group had greater levels of serum glucose and globulin than the CON group (p = 0.028 and 0.049, respectively). Both FA-supplemented groups had greater serum growth hormone (GH) levels at the 4th week of pregnancy (p = 0.020). Additionally, the FA10 group showed significantly higher levels of IGF-1 at the 2nd and 4th week of gestation (p = 0.040 and 0.001, respectively). FA supplementation decreased the levels of non-esterified fatty acid (NEFA) at the 2nd and 4th week of gestation (p = 0.020 and 0.035, respectively). Additionally, the FA10 group showed significantly higher pregnancy-associated glycoprotein (PAG) levels at the 2nd and 4th week of gestation (p = 0.005 and 0.001, respectively). In conclusion, oral FA supplementation (10 mcg kg−1) in the first month of gestation improved the progesterone profile, as well as blood folates, PAG, GH, and IGF-1 concentrations in heat-stressed Holstein cows. These findings could be useful in developing practical strategies to keep dairy cows’ regular reproductive patterns under heat stress conditions.

Aberrant mitochondrial DNA methylation and declined pulmonary function in a population with polycyclic aromatic hydrocarbon composition in particulate matter

Air pollution exposure has been found to be associated with epigenetic modification of the mitochondrial genome, which could subsequently induce adverse health outcomes. However, very limited studies exist regarding the association between fine particulate matter (PM2.5) exposure and pulmonary function at the molecular level of mitochondrial epigenetic changes. This study aimed to investigate the association of platelet mitochondrial DNA (mtDNA) methylation with occupational PM2.5 exposure and pulmonary function. First, 768 participants were occupationally exposed to polycyclic aromatic hydrocarbon (PAH)-enriched PM2.5 in a coke-oven plant in East China. The levels of PM2.5, PAH components bound to PM2.5, and urinary PAH metabolites in the workplace environment were measured as an internal dose, respectively. mtDNA methylation was measured by bisulfite pyrosequencing of two genes of ATP synthase (MT-ATP6 and MT-ATP8). Mediation analysis was conducted to evaluate the role of mtDNA methylation in pulmonary alteration induced by PAH. A decreasing trend of platelet mtDNA methylation was observed with increase in PM2.5 exposure across all participants. As an important PAH metabolite in urine, 1-hydroxypyrene (1-OHP) was significantly negatively associated with FEV1/FVC (Forced Expiratory Volume in 1s/Forced Vital Capacity) ratio. The participants with high serum folate levels (≥10 nmol/L) showed positive association between MT-ATP6 methylation and FEV1/FVC ratio. Mediation analysis suggested that MT-ATP6 methylation mediated the significant association of urinary 1-OHP with FEV1/FVC. Our findings suggested the methylation of platelet mitochondrial gene MT-ATP6 and FEV1/FVC to be negatively associated with PM exposure. Platelet mtDNA methylation acted as an intermediary between PAH exposure and lung function decline. The mitochondrial epigenetic regulation in platelets, in response to PM exposure, might be involved in subsequent progress of abnormal pulmonary function.

Serum folate levels and hypertension

We aimed to examine the association between serum folate levels and hypertension in Korean adults. Our study population was 6343 Korean adults whose blood pressure and folate levels were measured in the Korea National Health and Nutrition Examination Survey 2016–2018. We aggregated the study populations into quintiles according to serum folate levels (1.5–4.3, 4.4–5.7, 5.8–7.5, 7.6–10.3, and 10.4–35.9 ng/mL). Multivariable logistic and linear regression models were used to analyze the relationships between serum folate levels, blood pressure, and hypertension. The weighted average of serum folate levels was 7.4 ng/mL, and the weighted prevalence of hypertension was 30.4% in the study populations. After adjusting for all potential confounders, compared to those in the lowest quintile of serum folate levels, systolic and diastolic blood pressure of the people in the other quintiles were not significantly different. The linear relationship between serum folate levels and blood pressure was not statistically significant. The odds for hypertension were not significantly different across the quintiles of serum folate levels. This study showed high serum folate levels was not significantly associated with lowering hypertension in Korean adults.

W230 Association between low serum Vitamin B12 and high folate level in pregnant women with gestational diabetes mellitus

W230 Association between low serum Vitamin B12 and high folate level in pregnant women with gestational diabetes mellitus

Folate Status and Mortality in US Adults With Diabetes: A Nationally Representative Cohort Study.

BackgroundPublic health concerns have gradually shifted from inadequate intakes to potential adverse effects associated with excessive folate intakes following the full implementation of mandatory folate fortification. This study aimed to examine the associations of red blood cell (RBC) folate with all-cause and cardiovascular disease (CVD) mortality among patients with diabetes.MethodsData of 15,514 adults aged 20 years or older, who participated in the National Health and Nutrition Examination Survey (1988–1994), were analyzed as the baseline examination. The participants were linked to mortality data from the survey date until December 31, 2015. The associations of RBC folate with all-cause and CVD mortality were examined using multivariable Cox regression models.ResultsDuring 297,708 person–years of follow-up (median of 19.2 years), 6,106 total deaths occurred, including 1,867 deaths from CVD, 1452 deaths from ischemic heart disease, and 415 deaths from stroke disease. The participants with the highest quartile of RBC folate had higher odds of diabetes (fully-adjusted odds ratio: 1.94 [95% CI: 1.53–2.48]). In Cox regression analyses, compared with the participants with the lowest quartile of RBC folate for diabetes, those from quartile 3 and quartile 4 had HRs (95% CIs) of 1.12 (0.87, 1.43) and 1.30 (1.04, 1.63) in all-cause mortality, respectively; in CVD mortality, the HRs were 1.73 (1.08, 2.76) and 1.47 (0.98, 2.22); in ischemic heart disease mortality, they were 2.01 (1.19, 3.39) and 1.62 (1.05, 2.50), respectively. However, high levels of RBC folate were negatively associated with all-cause mortality, CVD mortality and ischemic heart disease mortality in non-diabetes.ConclusionFrom the nationally representative data, increasing levels in RBC folate were independently associated with an increased risk of all-cause and CVD mortality among those diagnosed with diabetes, but high levels of RBC folate had a mild protective effect in non-diabetes. The underlying mechanism regarding folate and adverse outcomes in diabetes warrants further clarification.

Efficacy of biosynthesizing folate, riboflavin and typical probiotic traits reveal the potential use of \(\textit{Lactobacillus plantarum}\) LCN13 as a feed additive for swine farming

Lactic acid bacteria have been advocated as probiotics to replace antibiotic growth promoters, improve growth performance, and reduce cost production in swine farming. The aim of this study is to identify and evaluate the probiotic traits of strain LCN13 isolated from traditionally fermented feed for swine. Thirty-five bacterial isolates with different morphological characteristics were isolated, among which 9 isolates showed the ability to produce lactic acid and antibacterial activity against pathogenic bacteria. Among them, isolate LCN13 exhibited a strong capacity to produce lactic acid (18.5 ± 0.31 g/L), inhibited gastrointestinal pathogens such as Salmonella typhimurium ATCC 14028 (18.3 ± 1.52 mm), Escherichia coli ATCC 11105 (24.7 ± 2.14 mm), and Staphylococcus epidermidis ATCC 35984 (31.6 ± 2.93 mm), and produced 182 ng/mL folate and 233 ng/mL riboflavin as measured by LC-MS/MS after 24 hours of incubation. Based on morphological, biochemical, and 16S rRNA gene analysis, the isolate LCN13 was identified as Lactobacillus plantarum. Phenotypic analysis revealed that L. plantarum LCN13 showed remarkable resistance to 1.2% ox-bile salt, 2.0 mM H2O2, and pH 3.0. In addition, the ability to produce high levels of folate (253.6 ± 10.7 ng/mL) and riboflavin (312.0 ± 12.2 ng/mL) after 48 hours was exploited for the first time in the L. plantarum. Taken together, L. plantarum LCN13 might serve as a potential probiotic candidate for animal farming.

Excessive Folic Acid Mimics Folate Deficiency in Human Lymphocytes.

Food fortification with synthetic folic acid (FA), along with supplementation, results in a marked increase in the population total of serum folates and unmetabolized folic acid (UMFA). Despite the success in reducing neural tube defects at birth in the intended target population (women of childbearing age), the potential deleterious effects of chronically high levels of UMFA in susceptible segments of the population require further investigation. In this study, we examine the effects of FA concentrations, ranging from depletion to supraphysiological levels, on markers of proliferation, DNA methylation, and DNA damage and repair in a human lymphoblastoid cell line (LCL). We note that both low and high levels of FA similarly impact global DNA methylation, cytome biomarkers measured through the CBMN assay, DNA damage induced by oxidative stress, and DNA base excision repair gene expression.

High serum folate level is positively associated with pulmonary function in elderly Korean men, but not in women

A limited number of studies have been conducted on the relationship between serum vitamin levels and pulmonary function, particularly in the elderly population. This study attempted to confirm the association between serum vitamin levels (folate, vitamin A, and vitamin E) and pulmonary function in the elderly population of Korea. A total of 1166 subjects (528 men and 637 women) participated in the Korean National Health and Nutrition Examination Survey from 2016 to 2018. Serum levels of folate, vitamin A, and vitamin E were measured in the subjects. The subjects’ pulmonary function measurement items were as follows: forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory volume in one second/forced vital capacity (FEV1/FVC), forced expiratory flow at 25% and 75% of the pulmonary volume (FEF25–75%), forced expiratory volume in 6 s (FEV6), and peak expiratory velocity (PEV). We performed regression analysis considering FEV1, PEV, FVC, FEF25–75%, and FEV1/FVC and FEV6 as dependent variables. Serum vitamin A levels were not associated with pulmonary function. In elderly men, serum vitamin E levels were negatively correlated with FVC [B = − 0.012, 95% confidence interval (CI) − 0.022 to − 0.003, p = 0.012] and FEV1 (B = − 0.010, 95% CI − 0.115 to − 0.007, p = 0.028). We confirmed a positive correlation of the serum folate level with FEV1 (B = 0.017, 95% CI 0.004–0.030, p = 0.009), FEV1/FVC (B = 0.003, 95% CI 0.001–0.005, p = 0.007), and FEF25–75% (B = 0.031, 95% CI 0.010–0.053, p = 0.005) in elderly men. This study confirmed that high serum folate levels were positively associated with pulmonary function in elderly men in Korea. Further studies are needed to understand the longitudinal effect of folate and its biological mechanism in pulmonary function.

Levels of Folate and Vitamin B12, and Genetic Polymorphisms Involved in One-Carbon Metabolism May Increase the Risk of Cervical Cytological Abnormalities

To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42–8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46–18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

Effect of dietary folic acid and energy density on immune response, gut morphology, and oxidative status in blood and breast muscle of broiler chickens

Folic acid (FA) plays essential roles in many metabolic functions and has been reported to have antioxidant effects. Therefore, dietary supplementation with high levels of FA may improve gut health and prevent potential oxidative stress caused by feeding a high energy density diet to broiler chickens. Broiler chickens were assigned into eight treatments, consisting of either a normal energy (NE) or high energy (HE) density diet, and four FA levels (2.2, 5, 10, and 15 ppm). Data were analyzed by SAS 16 GLM procedure. Birds-fed HE diets had increased (P &lt; 0.05) plasma concentrations of calcium and albumin but reduced (P &lt; 0.005) weights of ceca and bursa compared with those fed NE diets. Dietary supplementation with 10 ppm FA significantly increased (P &lt; 0.05) birds’ heart weight and bile acid concentration. Folic acid and energy density interactions were significant for jejunal villus height (VH; P = 0.0226), villus width (VW; P &lt; 0.0001), and crypt depth (CD; P = 0.0332). Among the NE group, birds fed 5–15 ppm FA had reduced (P &lt; .0001) VW, while in the HE groups, 15 ppm FA supplementation resulted in an increased jejunal VH (P = 0.0317) compared with other treatments. In conclusion, dietary supplementation with increased levels of FA in HE diets could be beneficial for the intestinal health of broiler chickens.

Folic Acid Is Related to Muscle Strength and Vitamin A Is Related to Health-Related Quality of Life: Results of the Korea National Health and Nutrition Examination Survey (KNHANES VII 2016-2018).

This study investigated how folic acid affects muscle strength and the effects of vitamin A on quality of life in adults. Baseline data from the Korea National Health and Nutrition Examination Survey (KNHANES VII 2016–2018) was used to find 6112 adults (ages 19–80) meeting study criteria. The participants were divided into three groups: young adults (ages 19–39), middle-aged (ages 40–64), and elderly (≥65 years). Muscle strength was measured using a digital grip strength dynamometer. The EuroQol five-dimension questionnaire measured quality of life. Associations were assessed using multivariate regression and logistic regression. Vitamins and handgrip strength were divided into low and high groups based on the mean. Although vitamin A and folate levels were related to handgrip strength in all subjects, regression demonstrated a significant association between folate and handgrip strength in the elderly. The odds ratios (OR) of higher handgrip strength were statistically significant for elderly participants with high levels of folate compared to those with low levels (OR: 1.55). Vitamin A was associated with quality of life, especially in the self-care dimension for the elderly. Further longitudinal research is needed to examine the relationship between vitamins and muscle strength, as well as vitamins and quality of life.

Prevalence of hyperhomocysteinemia (HHcy) and its major determinants among hypertensive patients over 35 years of age.

Hyperhomocysteinemia (HHcy) and hypertension are associated with cardiovascular events. However, effects of Hcy-lowing interventions on cardiovascular outcome were conflicting. Serum folate level was proposed to be a possible determinant of efficacy of extra folate supplementation on cardiovascular outcome. The aims of the present study were to describe representative information on the levels of serum homocysteine and folate in hypertensive patients, and to explore the major determinants of HHcy. 11,007 participants with hypertension were analyzed in this cross-sectional study. Blood pressure and serum levels of biochemical indicators were measured. Multivariate logistic regression model was used to assess the associated factors of HHcy. Geometric mean of serum total homocysteine was 14.1 (95% CI: 13.9, 14.4) μmol/L and prevalence of HHcy was 36.1 (95% CI: 34.0, 38.1) % in hypertensive patients. HHcy was strongly associated with factors including male sex, older age, elevated serum creatinine (SCr), lower serum folate and vitamin B12, and uncontrolled blood pressure in hypertensive patients. Elevated SCr attributed to HHcy with the etiologic fraction of 0.29. The change of the odds ratio of HHcy associated with folate was significantly higher in patients with elevated SCr compared with that of patients with normal SCr. The results suggested the protection of female sex and higher levels of folate and vitamin B12 from HHcy and attribution of older age and elevated SCr to HHcy. Restoring renal function deserved attention for hypertensive patients to benefit from Hcy-lowing measures.

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

Aims/hypothesisThe 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.MethodsThis 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.ResultsGDM 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 β: 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/interpretationB12 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.Graphical abstract

RECURRENT APHTHOUS STOMATITIS ASSOCIATED WITH MYELODYSPLASTIC SYNDROME: A CASE REPORT

<h3>Objective</h3> The aim of this report is to present the process of diagnosis and management of a patient with myelodysplastic syndrome afflicted with recurrent aphthous stomatitis (RAS). <h3>Background</h3> RAS is one of the most common lesions of the oral mucosa seen in adolescents. Although the exact etiology of RAS is still unknown, different hematinic deficiencies have been proposed. <h3>Case Report</h3> A 71-year-old male patient with multicomorbidities suffered from frequent oral ulcerations for many years. Hematologic investigation showed normal iron serum concentration and higher folate levels. In addition, his serum zinc concentration was low. Although his vitamin B12 level was normal, his homocysteine level was slightly high. Furthermore, his red blood cell count, hemoglobin, and hematocrit were low, and mean corpuscular volume, mean corpuscular hemoglobin, and red blood cell distribution width were high, which were related to megaloblastic anemia. Treatment with prednisolone, zinc gluconate, hydroxocobalamin, and nystatin led to rapid improvement. Nevertheless, fluctuations in the state of his RAS occurred within 6 months. Hence, we consulted the Division of Hematology and Oncology for further evaluation. The hematology and oncology doctor arranged blood tests and bone marrow biopsy and prescribed ferrous gluconate-B. The bone marrow biopsy showed myelodysplastic syndrome, refractory cytopenia with multilineage dysplasia, and iron store deficiency. After iron supplementation, his recovery rate improved. <h3>Clinical Implication</h3> When patients have RAS, consider checking iron, vitamin B12, and folate levels and treating patients if levels are low. Such treatment could reduce some varieties of RAS. However, in patients with hematological diseases, further tests, such as bone marrow biopsy, may be needed.

Serum Folate and All-Cause Mortality is of Non-Linear Relationship Among Population with Chronic Kidney Disease: A Retrospective Cohort Study.

AimA transition toward high serum folate concentrations has been noticed following the mandatory folate fortification. To explore this further, we studied the relationship between folate and health outcomes in population with chronic kidney disease (CKD).MethodsWe retrospectively explored the relationships between serum folate and risk of all-cause death in this population. We analyzed data of 2142 subjects with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2006. Vital status was followed through December 31, 2006.ResultsCox regression was used to estimate hazard ratios (HRs) of mortality for individuals with serum folate in rest quintiles compared with individuals with the fourth quintile. After an average follow-up of 57.4 months with 157 deaths recorded, a reversed J-shaped association was revealed after conducting multivariable adjustment. The mortality rate in population with lower and higher folate levels were 8.29% and 12.67%, respectively, and the corresponding adjusted HRs were 2.41 (95% confidence interval, CI=1.32–4.40) and 2.10 (1.20–3.70). Kaplan–Meier curve showed survival benefits for the fourth quintile of serum folate as compared to the first and fifth quintile.ConclusionSerum folate concentrations may influence all-cause mortality in a non-linear pattern in the CKD population. It is reasonable to recommend periodic surveillance in the CKD population to maintain the serum folate concentration in an appropriate level.