Lower Serum Folate Concentrations Research Articles

Association of serum folate concentrations with the mortality of cancer: a prospective cohort study.

The association between serum folate concentrations and the mortality of cancer remains unclear. We aim to investigate the association of serum folate concentrations with all-cause and cause-specific mortality among American adults with cancer. This cohort study included 4535 patients with cancer from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. During a median follow-up of 37,792 person-years, there were 1998 all-cause deaths and 616 cancer deaths. Non-linear and L-shaped associations were observed between serum folate concentrations and the risk of all-cause and cancer mortality among patients with cancer. Notably, the mortality rates reached a plateau at 23.7ng/mL for all-cause mortality and 23.57ng/mL for cancer mortality. When folate levels fell below these thresholds, the risk of all-cause and cancer mortality decreased by approximately 2.1% (HR 0.979; 95% CI 0.969-0.989) and 3.6% (HR 0.964; 95% CI 0.948-0.981), respectively, with each unit increase in the folate concentration up to the thresholds. Our study reveals that low serum folate concentrations are linked to an elevated risk of cancer mortality among individuals with cancer within a certain range and supplementation of folate in cancer patients to achieve specific serum folate level threshold (23.7ng/mL) might reduce the risk of cancer mortality.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Potential mechanism for hyperhomocysteinemia in Greyhound dogs.

Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear. Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress. Healthy pet Greyhounds (n = 31) and non-sighthound control dogs (n = 15). Analysis of serum HCy, cobalamin, folate, and methionine, and plasma cysteine, glutathione, and total 8-isoprostane concentrations. Homocysteine concentrations were higher in Greyhounds (median, 25.0 μmol/L) compared to controls (13.9 μmol/L; P < .0001). Cobalamin concentrations were lower in Greyhounds (median, 416 ng/L) compared to controls (644 ng/L; P = .004) and were inversely correlated with HCy (r = -0.40, P = .004). Serum concentrations of folate, which is regenerated when HCy is converted to methionine, also were inversely correlated with HCy (r = -0.47, P = .002). Serum methionine concentrations were more than 4-fold lower in Greyhounds (median, 3.2 μmol/L) compared to controls (median, 15.0 μmol/L), but this difference was not significant (P = .3). Plasma cysteine, glutathione, and 8-isoprostane concentrations did not differ significantly between groups. Our findings suggest a primary defect in conversion of HCy to methionine in Greyhounds, with related impaired folate generation. Ineffective cycling by methionine synthase could lead to secondary cobalamin depletion. Notably, low serum folate and cobalamin concentrations can be observed in Greyhounds without signs of intestinal disease.

Associations of Serum Folate and Homocysteine Concentrations with All-Cause, Cardiovascular Disease, and Cancer Mortality in Men and Women in Korea: the Cardiovascular Disease Association Study

BackgroundEvidence on the association of serum folate and homocysteine concentrations with risk of mortality in the general population is unclear. ObjectivesThis study aimed to examine the associations of serum folate and homocysteine concentrations with all-cause, CVD, and cancer mortality risk in Korean men and women aged ≥40 y. MethodsIn this population-based prospective cohort study, serum folate and homocysteine concentrations were measured in a subset of participants enrolled between 2005 and 2012. A total of 21,260 participants were linked to mortality data from the survey date to 31 December 2019. Cox proportional hazards models and restricted cubic splines were used to identify the associations of serum folate and homocysteine concentrations with mortality. ResultsDuring a median follow-up of 12.3 y, 2501, 549, and 842 deaths were attributed to all-cause, CVD, and cancer, respectively. The prevalence of folate deficiency and hyperhomocysteinemia were higher in men than in women. In men, a nonlinear inverse association was observed between serum folate concentrations and all-cause mortality. Men in the third quartile of serum folate concentrations exhibited a lower risk of all-cause mortality (HR: 0.85; 95% CI: 0.73, 0.99) than those in the lowest quartile. Serum homocysteine concentration was positively associated with all-cause and CVD mortality. Men and women in the highest compared with those in the lowest serum homocysteine quartile showed a higher risk of CVD mortality (HR: 1.60; 95% CI: 1.07, 2.39; and HR: 1.79; 95% CI: 1.11, 2.89, respectively). Hyperhomocysteinemia combined with folate deficiency was associated with increased all-cause, CVD, and cancer-related mortality rates. ConclusionsHigher serum homocysteine and lower serum folate concentrations were associated with an increased risk of all-cause, CVD, and cancer-related mortality in Korean adults. The finding of a nonlinear inverse relationship between serum folate concentration and mortality in men warrants further investigation.

Low serum folate concentrations in dogs with non-associative immune-mediated haemolytic anaemia.

Folate deficiency in people can occur in conditions causing increased demand, including haemolytic anaemia. This has not been investigated in dogs with non-associative immune-mediated haemolytic anaemia (IMHA). Cohort study of 15 dogs with non-associative IMHA. Haematocrit (HCT) and serum folate concentrations were measured at presentation and each subsequent venipuncture performed for monitoring. The relationship between serum folate concentrations and HCT was investigated using linear and logistic mixed-effects regression models and in paired samples using a one-tailed paired t-test. Low serum folate concentrations occurred in five of 15 dogs. In 126 samples, a significant positive relationship was found between HCT and corresponding serum folate concentrations. A significant relationship was found between dichotomised folate concentrations (below the reference interval or within/above the reference interval) and HCT and between serum folate concentrations and dichotomised HCT (less than or equal/above 0.30 L/L). For paired samples (available in eight dogs), the mean serum folate concentration of samples with the lowest HCT was significantly lower than that of samples in which the HCT first exceeded 0.30 L/L. Low serum folate concentrations were observed in some dogs with non-associative IMHA. Further studies are needed to determine the cause and investigate whether folate supplementation would be beneficial.

Serum folate and vitamin B12 levels in cutaneous melanoma.

Vitamin B12 and folate are the major micronutrients that play significant roles in DNA synthesis. Epidemiological studies and clinical evidences displayed alterations in serum concentrations folate and of vitamin B12 in various human malignancies, yet their roles in patients with melanoma have yet to be understood. To assess circulating vitamin B12 and folate concentrations of patients with melanoma and compare them with other malignant tumors and healthy subjects. A total of 98 skin melanoma cases from university clinic were enrolled into the study. Serum vitamin B12 and folate concentrations were analyzed by electrochemiluminescence binding assay. Circulating levels of vitamin B12 in patients with melanoma were similar compared with other malignancies and healthy controls (P>.05). However, melanoma cases had significantly lower serum folate concentrations than healthy control group (P=.04). Melanoma patients with metastatic disease (P=.001) and with short history of disease (P=.05), and those who had active diseases in course of the study (P=.04) had low serum folate concentrations. Serum levels of folate were found significantly lower in melanoma cases, and this association was stronger for patients with metastatic melanoma; however, no such association was found between melanoma and serum vitamin B12 levels.

Simultaneous supplementation with iron and folic acid can affect Slc11a2 and Slc46a1 transcription and metabolite concentrations in rats.

The present study aimed at analysing how dietary folic acid (FA) and Fe deficiency, followed by supplementation with these nutrients, affects the expression of folate and Fe transporters in the duodenum, as well as FA and Fe status. After a deficiency period, Wistar rats were randomised to a group fed with a diet deficient in FA and supplemented with Fe (DFE), a diet deficient in Fe and supplemented with FA, a diet supplemented with Fe and FA (FEFOL), a diet deficient in Fe and FA (D) or a control diet (C). Tissue collection was performed after 2, 10 or 21 d of these diets. Group D had higher Slc11a2 mRNA levels than the DFE group at every time point and there were differences in mRNA levels of Slc46a1 between the DFE and the FEFOL groups at the third time point, but we observed no differences in protein levels between the groups. The DFE and D groups not only had lower serum folate concentrations at every time point but also had the highest homocysteine concentrations. Total Fe binding capacity concentrations were the lowest in the DFE group at the first time point and in the DFE and the FEFOL groups at the final time point. Simultaneous supplementation with FA and Fe resulted in significantly higher Hb concentrations than did supplementation with these nutrients alone. Our findings indicate that dietary FA and Fe deficiency, and subsequent supplementation with these nutrients, affects transcription but not the protein levels of FA and Fe transporters in the duodenum.

Obesity is associated with folate metabolism.

Objective: The aim of the present study is to perform a systemic review of the previous studies executed on the association between obesity and folate. Method: In the present research, the selected keywords were scanned on the PubMed, Web of Science, Cochrane and Lilac databases between May and June, 2017 through Gazi University's network. In total, 4236 clinical, randomized controlled, cross-sectional and prospective studies were determined and 17 of these that specifically fit the aims of the present research were reviewed. This study involved an electronic literature search of databases on folic acid and obesity published in the English language between 2000 and 2016. Results: Of the 17 studies, 5 were based on folic acid supplementation and 12 were related with participants' folate status. As a general consequence of both intake and serum/status measurements of folic acid supplementation: It was found that obesity-associated metabolic changes might affect individual folate use and obese individuals had lower serum folate levels, although there was no change in folate intake. Conclusion: Overweight and obese individuals have lower serum folate concentrations when compared with individuals with normal weight. It is explained by increased use of folic acid, urinary excretion, dilution of blood volume, different levels in different tissues and changes in the endocrine functions of folate. Individuals with higher Body Mass Indexes have less supplement use, unhealthier diets and donot consume sufficient vegetables and fruits, all of which can affect decrease in folate levels. Furthermore, adiposity may affect folate absorption by intestinal epithelium.

Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP &gt; 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of...

Serum Cobalamin and Folate Concentrations in Common Marmosets (Callithrix jacchus) with Chronic Lymphocytic Enteritis.

Serum cobalamin and folate concentrations can serve as surrogate markers of gastrointestinal disease in dogs and cats, where they can have diagnostic, therapeutic, and prognostic implications. Chronic disease of the gastrointestinal tract, particularly chronic lymphocytic enteritis (CLE), occurs frequently in captive common marmosets. The aims of this study were to validate a commercially available assay for measuring serum cobalamin and folate concentrations in common marmosets, to establish reference intervals for these analytes in healthy marmosets, and to measure serum concentrations in common marmosets with CLE. The commercial assay was linear, accurate, precise, and reproducible for the measurement of serum cobalamin and folate concentrations in common marmosets. In healthy marmosets, the serum cobalamin concentration ranged from 322 to 2642 pg/mL (n = 35) and serum folate concentration from 54.8 to 786.4 ng/mL (n = 37). Low serum folate concentrations were moderately sensitive (greater than 70%) for CLE, and low serum cobalamin concentrations were moderately (greater than 70%) specific for CLE. Both serum cobalamin and folate concentrations were relatively unchanged in marmosets during 120 to 220 d. Serum cobalamin and folate concentrations were stable for approximately 7 y when samples were stored at -80 °C. Additional studies are warranted to further study the clinical implications of low serum cobalamin and folate concentrations in common marmosets.

One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.

Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case–control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre‐diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non‐aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98–1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02–1.75; p‐heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62–10.81, p‐interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81–1.95; p‐heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.

Comparison of body condition score and other minimally invasive biomarkers between dogs with gastric carcinoma and dogs with chronic gastritis.

OBJECTIVE To identify minimally invasive biomarkers to help differentiate dogs with gastric carcinoma from those with chronic gastritis. DESIGN Prospective study. ANIMALS 15 dogs with gastric carcinoma, 29 dogs with chronic gastritis, and 7 healthy dogs. PROCEDURES Dogs with clinical signs of upper gastrointestinal tract disease for > 14 days that underwent gastroscopy or necropsy for collection of gastric biopsy specimens for histologic evaluation were prospectively enrolled. Gastric carcinoma and chronic gastritis were diagnosed on the basis of histologic findings. Additionally, gastric biopsy specimens were collected endoscopically from 7 healthy (control) dogs while they were anesthetized for a routine neutering procedure. Prior to being anesthetized for gastroscopy or euthanized, all dogs underwent a physical examination, and a blood sample was collected for quantification of select serum biomarker concentrations. Histologic findings, body condition score (BCS), and serum biomarker concentrations were compared among the 3 groups. RESULTS Dogs with gastric carcinoma were significantly older and had a significantly lower BCS, lower serum folate concentration, and greater serum C-reactive protein (CRP) concentration, compared with dogs with chronic gastritis and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age > 8 years, BCS < 4, serum CRP concentration > 25 mg/L, and an abnormally low serum folate concentration might be useful noninvasive biomarkers for identification of dogs with gastric carcinoma. For underweight older dogs with signs of upper gastrointestinal tract disease and high serum CRP and low serum folate concentrations, gastric biopsy specimens should be obtained and evaluated so that a prompt definitive diagnosis can be made and appropriate treatment initiated.

Serum cobalamin and folate as prognostic factors in canine exocrine pancreatic insufficiency: An observational cohort study of 299 dogs

Exocrine pancreatic insufficiency (EPI) in dogs is a gastrointestinal condition leading to a severe impairment of nutrient absorption. The disease is frequently associated with vitamin disturbances especially regarding cobalamin and folate. Dogs with EPI need daily expensive supportive treatment. The aim of the present study was to identify prognostic factors for EPI in dogs, through a long-term survival study of 299 dogs, taking into account epidemiological, clinical, biological and therapeutic data, with particular emphasis on serum cobalamin and folate concentration.The prevalence of low serum cobalamin (cobalamin<350ng/L) and high serum folate (folate>12μg/L) concentrations were 67% (200/299) and 55% (164/299), respectively. Dogs with hypocobalaminemia at diagnosis were significantly older than those with serum cobalamin concentration within the reference interval (P<0.001). Hypocobalaminemia at diagnosis (P=0.04), male sex (P=0.01), decreased appetite at diagnosis (P=0.008) and not receiving enzyme replacement therapy (P=0.003) were significant and independent risk factors for decreased survival in EPI. In contrast, hyperfolatemia was associated with improved prognosis (P=0.02). These results confirm the importance of measuring serum cobalamin and folate concentrations at the time EPI is diagnosed, as hypocobalaminemia is negatively associated with prognosis, particularly in the absence of a high serum folate concentration.

Serum folate concentrations, asthma, atopy, and asthma control in Peruvian children.

The relationship between folate status and asthma-related outcomes has not been carefully examined in low- and middle-income countries where folate deficiency is common. Ancillary analysis of an unmatched case-control study in which we analyzed serum folate concentrations in 412 children with asthma and 342 controls living in peri-urban communities in Lima, Peru. We examined baseline associations between folate and asthma, atopy, total serum IgE, pulmonary function, and fractional exhaled nitric oxide. We then followed children with asthma longitudinally for 6-9 months and assessed associations between folate and odds of uncontrolled asthma (defined as Asthma Control Test score≤19) and of ≥1 emergency visits during follow-up. A 10ng/mL decrease in serum folate was associated with 45% higher adjusted odds of asthma (OR=1.45, 95% CI 1.05-2.02). The folate-asthma relationship differed by atopic status: a 10ng/mL decrease in serum folate was associated with a 2.4-fold higher odds of asthma among children without atopy (2.38, 1.20-4.72) and 23% higher odds of asthma in children with atopy (1.23, 0.85-1.80). Among children with asthma, a 10ng/mL decrease in serum folate was associated with 62% higher odds of uncontrolled asthma (1.62, 1.02-2.56) and 73% higher odds of ≥1 emergency visits during follow-up (1.73, 1.05-2.85). Serum folate concentrations were inversely associated with asthma, but this effect was stronger in children without atopy. Among children with asthma, lower serum folate concentrations were associated with higher risk of uncontrolled asthma.

Association between blood folate concentrations and depression in reproductive aged U.S. women, NHANES (2011–2012)

BackgroundBlood folate concentrations have been linked to an increased risk of depression in adults. Depression is particularly pronounced among women; however, the association between folate concentration and depression is not well-examined among women of reproductive age. The purpose of our study was to assess the association between low serum and red blood cell folate concentration and the risk of moderate to severe depression among non-pregnant women of reproductive age in the United States (U.S.). MethodsWe used data from nationally representative, population-based U.S. National Health and Nutrition Examination Survey (NHANES) (2011–2012) examining non-pregnant women of reproductive age (20–44 years). We compared serum and red blood cell (RBC) folate concentrations between women with and without self-reported depression based on Patient Health Questionnaire-9 (PHQ-9) scores, and examined the association between folate concentrations and depression using linear and logistic regression analysis. ResultsA total of 16.7% of eligible women in our study reported to have moderate to severe depression. The median serum folate concentrations for women with and without depression were 17.8ng/ml and 17.2ng/ml, respectively (P = <0.01). There was no statistical difference in median RBC folate concentrations between women with and without depression (P = 0.2). Serum folate concentration was weakly associated with an increased risk of moderate to severe depression among non-pregnant women of reproductive age, after adjusting for important demographic and life-style factors (aOR: 1.11; 95% CI: 1.01, 1.22). There was no interaction with race and ethnicity. LimitationsCross-sectional design. ConclusionsFolate concentrations in the blood may partly explain the increased risk of moderate to severe depression among non-pregnant women of reproductive age in the U.S. Robust prospective studies are needed to confirm our findings.

Serum folate concentration and the incidence of lung cancer.

BackgroundLung cancer is a leading cause of cancer-related mortality globally. Folate helps to maintain DNA integrity and to regulate gene expression. Serum folate levels may affect the risk of several cancers, including lung cancer. In this study we evaluated the association between serum folate concentration and variations in genes involved in folate metabolism with lung cancer incidence in Poland.MethodsThe study included 366 lung cancer patients and 366 control subjects. We measured serum folate concentration and genotyped six variants in MTHFR, MTR and MTRR genes. The odds ratios of being diagnosed with lung cancer were calculated using conditional univariable and multivariable logistic regression with respect to folate level and genotypes.ResultsThe mean serum folate level was lower in lung cancer cases than in control group (20.07 nmol/l vs. 22.52 nmol/l, p = 0.002). The odds ratio for lung cancer declined with increasing serum content of the folate. The folate concentration of >25.71 nmol/l (IVth quartile) in comparison to <15.92 nmol/l (Ist quartile) was associated with an odds ratio of 0.61 (95%CI 0.40–0.95, p = 0.03). The analysis of variations in MTHFR, MTR and MTRR genes did not reveal any significant difference between lung cancer cases and controls in univariable and multivariable analyses.ConclusionIn this case-control study, lower serum folate concentrations were associated with a higher risk of lung cancer diagnosis. Although previous findings have been somewhat mixed, our results add to the evidence that circulating folate levels may be an indicator of lung cancer risk.

Association of serum vitamin B12 and folate with mortality in incident hemodialysis patients

Vitamin B12 (B12) and folate are essential vitamins that play important roles in physiological processes. In the general population, many studies have evaluated the association of these vitamins with clinical outcomes, yet this association in hemodialysis (HD) patients remains unclear. We examined the association of serum folate and B12 with mortality in a 5-year cohort of 9517 (folate) and 12 968 (B12) HD patients using Cox models with hierarchical adjustment for sociodemographics, comorbidities, and laboratory variables associated with the malnutrition and inflammation complex syndrome. The associations of baseline B12 and folate (separately) with all-cause mortality were evaluated across five categories of B12 [<400 (reference), 400-<550, 550-<650, 650-<750 and ≥750 pg/mL] and folate [<6.2, 6.2-<8.4, 8.4-<11 (reference), 11-<14.3 and ≥14.3 ng/mL]. The study cohort with B12 measurements had a mean ± standard deviation age of 63 ± 15 years, among whom 43% were female, 33% were African-American, and 57% were diabetic. Higher B12 concentrations ≥550 pg/mL were associated with a higher risk of mortality after adjusting for sociodemographic and laboratory variables. However, only lower serum folate concentrations <6.2 ng/mL were associated with a higher risk of all-cause mortality when adjusted for sociodemographic variables [adjusted hazard ratio (95% confidence-interval): 1.18 (1.03-1.35)]. Higher B12 concentrations are associated with higher all-cause mortality in HD patients independent of sociodemographics and laboratory variables, whereas lower folate concentrations were associated with higher all-cause mortality after accounting for sociodemographic variables. Further studies are warranted to determine the optimal B12 and folate level targets in this population.

B vitamins related to homocysteine metabolism in adults celiac disease patients: a cross-sectional study.

BackgroundThe only treatment for celiac disease is the gluten-free diet. Few studies have assessed the nutritional adequacy of this diet, especially of B vitamins related to homocysteine metabolism. The aim of this study was to assess the nutritional status and serum concentrations of B vitamins involved in homocysteine metabolism, and to determine whether the dietary intake of these vitamins are meeting Dietary Reference Intakes in celiac patients.MethodsA cross-sectional study enrolled a total of 20 celiac patients (36.3 ± 13.7 years old; 65 % women), following strict gluten-free diet (GFD) and 39 healthy controls matched by sex and age. The dietary intake was assessed by 3-day food records, and serum concentrations of homocysteine and vitamins B6, B12, and folate were determined after overnight fasting. Comparisons between the two groups were performed by Student’s t test or Mann–Whitney U-test, for continuous variables. Pearson’s chi-square test or Fisher’s exact test was used for categorical variables. An alpha level of 5 % were considered significant.ResultsCeliac patients had lower serum folate concentrations (7.7 ± 3.5 ng/mL, P < 0.05) than controls. All celiac patients had folate intake below the Estimated Average Requirement (EAR) (130.8 ± 53.6 μg/d). However, only a small proportion of celiac patients had hyperhomocysteinemia.ConclusionsCeliac patients treated with GFD presented inadequacy of dietary folate intake and low-serum concentrations of folate, suggesting that more attention should be given to the quality of the nutrients offered by the GFD, as it constitutes a lifelong treatment.

Vitamin paradox in obesity: Deficiency or excess?

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.