Cobalamin Levels Research Articles

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Association between redox imbalance, pterin metabolism markers, and early extrapyramidal side effects of antipsychotics in schizophrenia: pilot study

Antipsychotics (AP) administration in schizophrenia patients is associated with several side effects (SE), in particular, with extrapyramidal (EP). Data suggests that oxidative damage to dopaminergic neurons in the EP system may be related to tardive dyskinesia and Parkinson's disease (PD) development, although data on the role of oxidative stress in the development of early EPSE of AP is lacking. Another poorly studied hypothesis of the EP-symptoms pathogenesis considers disorders of folate (pterin) metabolism.Objective: to evaluate the relationship between redox imbalance and pterin metabolism with the severity of early EPSE caused by AP used in the schizophrenia treatment.Patients and methods. The study included 50 patients with the first episode of schizophrenia. EP symptoms were evaluated using the UKU Side-Effect Rating Scale (“UKU-SERS-Clin” version). The levels of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), aldehyde-2,4-dinitrophenylhydrazone, ketone-2,4-dinitrophenylhydrazone were assessed in blood plasma; levels of BH4, folate, cobalamin (vitamin B12), and homocysteine – in blood serum; superoxide dismutase (SOD) and catalase activity – in erythrocytes.Results and discussion. EPSE severity was inversely proportional inversely proportional to the GSH level and directly proportional to the SOD activity. EPSE severity was also associated with AP selectivity, but not with their dosages. However, AP selectivity was not associated with studied biochemical parameters. MDA level in patients prescribed with amantadine was lower than in other participants.Conclusion. Early AP-induced EPSE were associated with redox imbalance, which indicates the necessity for further research aiming at prevention of secondary neurodegenerative diseases in patients with schizophrenia receiving AP.

Newly Identified Deficiencies in the Multiple Sclerosis Central Nervous System and Their Impact on the Remyelination Failure.

The pathogenesis of multiple sclerosis (MS) remains enigmatic and controversial. Myelin sheaths in the central nervous system (CNS) insulate axons and allow saltatory nerve conduction. MS brings about the destruction of myelin sheaths and the myelin-producing oligodendrocytes (ODCs). The conundrum of remyelination failure is, therefore, crucial in MS. In this review, the roles of epidermal growth factor (EGF), normal prions, and cobalamin in CNS myelinogenesis are briefly summarized. Thereafter, some findings of other authors and ourselves on MS and MS-like models are recapitulated, because they have shown that: (a) EGF is significantly decreased in the CNS of living or deceased MS patients; (b) its repeated administration to mice in various MS-models prevents demyelination and inflammatory reaction; (c) as was the case for EGF, normal prion levels are decreased in the MS CNS, with a strong correspondence between liquid and tissue levels; and (d) MS cobalamin levels are increased in the cerebrospinal fluid, but decreased in the spinal cord. In fact, no remyelination can occur in MS if these molecules (essential for any form of CNS myelination) are lacking. Lastly, other non-immunological MS abnormalities are reviewed. Together, these results have led to a critical reassessment of MS pathogenesis, partly because EGF has little or no role in immunology.

Hair loss from scalp among women: Does serum levels of iron, cobalamin and folic acid matter?

Hair fall from the scalp is a common complaint by females attending a dermatologist’s out-patient clinic. The most common cause is telogen effluvium and the most common pattern is chronic diffuse non-scarring hair fall from the scalp. The aim of our study was to analyze deficiency status and correlate hemoglobin, ferritin, cobalamin, folic acid in females of reproductive age group. This is a descriptive study was conducted in the DVL department of a tertiary care medical college hospital between 2018-2019. Clinical and demographic data were collected and hemoglobin, ferritin, cobalamin, folic acid levels were investigated. A total of 85 patients were studied. Mean Hemoglobin was found at 11.92 g/dl and Anemia was recorded at 59.32%. Ferritin levels were lower than normal in 90% of the cases. Folate levels were in the normal range in the majority of our cases. Cobalamin was deficient in 50% of our patients. Ferritin and cobalamin levels were better indicators than hemoglobin levels alone in assessing chronic nonscarring hair loss from the scalp in females of reproductive age group.

Vitamin B12 Eksikliği Olan Çocuklarda Klinik ve Laboratuvar Bulguların ve Tanısal Zorlukların Değerlendirilmesi

Aim: In this study, we evaluated the clinical and laboratory data of healthy children with vitamin B12 deficiency. The benefits of methylmalonic acid (MMA) and homocysteine levels and the difficulties encountered in diagnosing vitamin B12 deficiency were pointed out. 
 Materials and Methods: A total of 70 healthy children whose serum cobalamin levels were below 126.5 pg/ml were included in the study. The age, gender, serum vitamin B12, urine MMA, plasma homocysteine, white blood cell, hemoglobin, thrombocyte, main corpuscular volume (MCV), main platelet volume (MPV), folic acid, and ferritin levels were obtained retrospectively from the hospital’s medical records. The correlation analysis test compared vitamin B12 with MMA and homocysteine.
 Results: The mean age was 8.21±6.15 years, and vitamin B12 deficiency was found in 6.29% of healthy children. Cobalamin levels ranged from 50-126 pg/ml, with a mean of 102.57±18.97 pg/ml. Urine MMA and serum homocysteine levels were 0.59±0.67 ng/ml and 13.50±0.67 g/dl, respectively. The correlation coefficient value (r) was found to be -0.342 and -0.437, moderately negative for MMA and homocysteine, respectively. MMA levels were normal in 36 patients, and homocysteine levels were normal in 48 patients. 
 Conclusions: Vitamin B12 deficiency is a common micronutrient deficiency in children. The diagnosis of vitamin B12 deficiency can be complex in healthy children who do not display typical laboratory findings, particularly elevated MMA and homocysteine.

Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial.

Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. ISRCTN Registry ISRCTN42569496.

High cobalamin levels as a five-year risk predictor for developing hematological cancer.

A high cobalamin level has been related to non-malignant diseases (mainly liver diseases, alcoholism, and renal diseases) and cancer (hematological malignancies and solid cancers such as liver and stomach cancer). However, a previous high level of cobalamin and the implications in the possible development of cancer is still unclear. The main aim of this study was to describe if a previous high cobalamin level is a determinant in the future development of cancer in five years of follow-up. The secondary objective was to determine any differences between cancer groups. A retrospective study was performed. Two databases were employed. The first one included all patients who had a determination of cobalamin in a routine blood test during the year 2010 (a total of 44,166 patients). The second one showed every patient who was admitted to the reference hospital, Hospital Clinico Universitario de Valladolid, during the following five years. Finally, a number of 6710 patients was included. Both databases belong to the medical records of the Hospital Data Surveillance System and are completely validated. Multivariate logistic regression analyses were employed to evaluate the association between cobalamin levels and the appearance of cancer (total and in each subgroup). All analyses were performed using IBM SPSS 24 software (IBM Corp., Armonk, NY, USA). The sample studied showed a clear association between the risk of hematological cancer and a previous high Cbl level. This relationship was higher among patients with the highest levels (over 779 pmol/L), showing almost two times more risk for development of hematological malignance within 5 years in the multivariate analysis (OR: 1.975, 95% CI: 1.056-3.697, P=0.033). Hematological malignancies were mostly diagnosed within the first three years (86.6%), showing a similar percentage in those three years. There was no association between this previous level and the development of any other type of cancer. Our study shows that a high cobalamin plasma level (hypervitaminosis) is associated with the development of hematologic cancer within five years after the measurement. The clinical implication of these findings, together with the clinical suspicion, reinforces the necessity of carrying out specific screening hematological tests in patients with not justified elevated plasma cobalamin levels. New prospective and multicenter studies are necessary to validate these results.

Genetic Bases of VitaminB12 Deficiency: Impact of MTHFR, TCN-II and GIF Polymorphisms on Vitamin B12 Level

Vitamin B12 deficiency is associated with serious health problems such as neurological disorders. In Jordan, few studies have evaluated the level of vitamin B21 in the Jordanian population with different prevalence. Genetic predisposition, lifestyle, environment, socioeconomic status, and geographic have been linked to vitamin B12 deficiency. Polymorphisms in the GIF, MTHFR, and Transcobalamins, have been proposed to be associated with the level of vitamin B12. The aim of the current study was to evaluate the impact of certain polymorphisms in MTHFR, TCN-II and GIF genes on the level of vitamin B12 in the Jordanian population. Polymorphic sites of the MTHFR (c.677 C&gt;T, rs1801133 and c.1286A&gt;C, rs1801131), TCN2-776C&gt;G (Arg259Pro) (rs1801198) and GIF-68 A&gt;G (Q5R) genes were analyzed by RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (n = 100). The control group included 100 matching individuals with a normal level of vitamin B12 (&gt;200 ng/mL). Our results showed a significant association between the homologous variant of the TCN2 gene (G776G) and MTHFR c.677C&gt;T genes and vitamin B12 deficiency. On the other hand, The MTHFR c.1286A&gt;C variant and GIF variants did not show significant association with vitamin B12 deficiency. This study expounds the association of TCN2 and MTHFR polymorphisms with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2, GIF, and MTHFR gene polymorphisms on vitamin B12 deficiency and associated disorders.

Определение кобальта в образцах плазмы крови методом масс-спектрометрии с индуктивно-связанной плазмой после перорального приема содержащих кобальт биологически активных добавок к пище

Salts of inorganic cobalt (Со) prevent the degradation of the alpha subunit of the hypoxia-inducible factor (HIF), imitating the state of hypoxia in the body and increasing the production of the endogenous hormone erythropoietin (EPO), and are used as doping substances that increase blood oxygen capacity and endurance, which give competitive advantages in sports. Currently, a large number of dietary supplements, including Co-containing ones, are offered on free sale. Their uncontrolled intake can affect not only the professional career of athletes, but also their health, due to the fact that this trace element and its salts are the strongest inorganic poisons and carcinogens. Despite this, their availability on the pharmaceutical market, a noticeable effect of erythropoiesis stimulation and a convenient oral form of administration lead to the need for their detection in modern doping control. The purpose of this research was to develop an approach to differentiate cobalt from vitamin B12, present in the body in its natural state, from the intake of cobalt salts by quantifying and comparing blood levels of vitamin B12 and total cobalt. Methods. The study involved 9 healthy volunteers (women and men) aged 25 to 45 years, leading an active lifestyle. Three of them took 2500 μg/day of cobalamin for 20 days (comparison group), three - dietary supplement containing cobalt asparaginate (100 μg/day in terms of pure cobalt), and the rest - dietary supplements with cobalt sulfate heptahydrate (100 μg/day in terms of pure cobalt) (administration groups) at the same time after meals. Blood samples were taken at baseline and on days 5, 9, 14 and 20. The concentrations of total cobalt in blood plasma samples of volunteers were measured by inductively coupled plasma mass-spectrometry (ICP-MS), the levels of cobalamin were determined on a Cobas 6000 immunochemical analyzer using the Elecsys Vitamin B12 II Assay ELISA kits. Results. It was found that oral intake of of cobalamin at a therapeutic dose significantly exceeding the recommended daily intake (3 μg), there was a regular slight increase in the blood concentration of total cobalt (1.1 times). At the same time intake of dietary supplements containing cobalt in the form of sulfate or asparaginate (about 100 μg per day in terms of pure cobalt) was accompanied by 4-6.7 fold increase in the concentration of total cobalt while unchanged vitamin B12 plasma concentration was observed. The detection of such changes can reliably indicate the use of prohibited salts and, of course, will be in demand for anti-doping control. Conclusion. Long-term monitoring of vitamin B12 and total cobalt levels, similar to hematological module of the Athlete Biological Passport program, will unambiguously detect possible abuse of cobalt salts and can be an additional evidence of the presence of these doping substances to other analytical methods, such as a combination of liquid chromatography and ICP-MS (LC-ICP-MS).

Does high serum cobalamin level in adults require further investigation or follow-up?

Does high serum cobalamin level in adults require further investigation or follow-up?

Homocysteine in Schizophrenia: Independent Pathogenetic Factor with Prooxidant Activity or Integral Marker of Other Biochemical Disturbances?

A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine (Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia—disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (p = 0.0041), and this may be due to the lower folate level in patients (p = 0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (ρ = −0.38, p = 0.0063) and with the level of B12 (ρ = −0.36, p = 0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (p = 0.00046) and lower catalase (CAT) activity (p = 0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 μmol/l, n = 42) compared with other patients (n = 8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p = 0.019), lack of spontaneity and flow in conversation (N6, p = 0.022), stereotyped thinking (N7, p = 0.013), and motor retardation (G7, p = 0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.

Decreased cortical Nrf2 gene expression in autism and its relationship to thiol and cobalamin status

Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes expression of a large number of antioxidant genes and multiple studies have described oxidative stress and impaired methylation in autism spectrum disorder (ASD), including decreased brain levels of methylcobalamin(III) (MeCbl). Here we report decreased expression of the Nrf2 gene (NFE2L2) in frontal cortex of ASD subjects, as well as differences in other genes involved in redox homeostasis. In pooled control and ASD correlation analyses, hydroxocobalamin(III) (OHCbl) was inversely correlated with NFE2L2 expression, while MeCbl and total cobalamin abundance were positively correlated with NFE2L2 expression. Levels of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and cystathionine were positively correlated with NFE2L2 expression, while homocysteine (HCY) was negatively correlated. The relationship between Nrf2 activity and cobalamin was further supported by a bioinformatics-based comparison of cobalamin levels in different tissues with expression of a panel of 40 Nrf2-regulated genes, which yielded a strong correlation. Lastly, Nrf2-regulated gene expression was also correlated with expression of intracellular cobalamin trafficking and processing genes, such as MMADHC and MTRR. These findings highlight a previously unrecognized relationship between the antioxidant-promoting role of Nrf2 and cobalamin status, which is dysfunctional in ASD.

Serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope.

Recent studies confirm the role of B vitamins deficiency and hyperhomocysteinaemia in the development of dysautonomia that has been considered to be the main factor in vasovagal syncope development. The aim of the study was to investigate serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope and to analyse the correlation between them and main clinical parameters of syncope. We studied 40 children, ages 8-17 years with a history of vasovagal syncope and 24 healthy volunteers. The serum pyridoxine, folate, cobalamin, and homocysteine levels were measured by a quantitative sandwich enzyme immunoassay technique using a commercial kit (Monobind, USA). Twenty-four-hour Holter monitoring and 24-hour ambulatory blood pressure monitoring were conducted for all participated patients. Serum pyridoxine (9.42±4.87, 16.11±5.53µg/L) and cobalamin (307.48±95.50, 447.28±108.85ng/L) levels were reasonably low (p < 0.05) in patients with vasovagal syncope. Although there was no significant change in folate levels between syncope and healthy children (4.00±1.34, 4.71±1.73µg/L; p = 0.20), we detected low folate-level association with longer duration of syncope (r=-0.42) and post syncope (r=-0.43) symptoms (p < 0.05). Finally, there was increased serum homocysteine level (13.55±5.03, 7.81±1.71µmol/L; p < 0.05) in patients with vasovagal syncope. It was positively correlated with the average PQ interval (r = 0.35, p < 0.05) and average QTc interval (r = 0.49, p < 0.05). The results suggested that pyridoxine, folate, cobalamin, and homocysteine may be involved in the pathogenesis of vasovagal syncope. This might provide a new approach for effective treatment of paediatric vasovagal syncope, requiring further study.

Decreased Cortical Nrf2 Gene Expression in Autism Spectrum Disorder and its Relationship to Thiol and Cobalamin status

Background The etiology of Autism spectrum disorder (ASD) is suspected to involve redox imbalances. In accordance with this, we previously published that sulfur metabolites in the methionine cycle and transsulfuration pathway were dysregulated in ASD frontal cortex. This was accompanied by disturbed vitamin B12 or cobalamin status. Cobalamin abundance and levels of the bioactive species methylcobalamin (MeCbl) were decreased, while levels of oxidized inert hydroxocobalamin (OHCbl) were increased in those tissues. Cellular cobalamin status is dependent on antioxidant availability. Reports have described decreased expression or activity of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in blood cells in ASD. Nrf2 is a transcription factor that promotes transcription of genes involved in maintaining antioxidant and detoxification status. We followed up on our postmortem study by performing real-time quantitative polymerase chain reaction (RT-qPCR) to investigate expression redox-linked genes. Genes included Nrf2 (NFE2L2), cystathionine beta synthase (CBS), cystathionine gamma-lyase (CTH), solute carrier family 1 member 1 (SLC1A1), glutathione synthetase (GSS), and glutathione reductase (GSR). We then searched for correlations among gene expression, thiols, and cobalamins to understand what factors may contribute to deranged sulfur and cobalamin metabolism in the brain in ASD. Methods RNA was isolated from control and ASD frontal cortex tissue using RNAqueous-4PCR kit manufactured by Ambion. Complementary DNA (cDNA) was synthesized with a Roche First Strand cDNA Synthesis kit. RT-qPCR was performed with a Roche LightCycler 480 model. Gene expression was normalized to glyceraldehyde 3-phosphate dehydrogenase. Bioinformatics searches were conducted with data downloaded from the consensus RNA dataset compiled by The Human Protein Atlas. Data were analyzed with Microsoft Excel and GraphPad Prism. Results NFE2L2, CBS, CTH, SLC1A1, and GSS RNA were decreased in ASD frontal cortex. Correlation analyses of pooled control and ASD data revealed strong associations between NFE2L2, cobalamin abundance, methionine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). An association was also found with the transsulfuration metabolite cystathionine. Homocysteine (HCY) and OHCbl were inversely correlated with NFE2L2 expression. We decided to use a bioinformatics approach to further probe a general connection between Nrf2 and cobalamin status, utilizing cobalamin levels in various tissues published by Hsu et al. in 1966. Data obtained from The Human Protein Atlas revealed impressive associations between the expression of Nrf2-regulated genes, NFE2L2 expression, and tissue cobalamin abundance as described by Hsu et al. Conclusion Our RT-qPCR data support a role for decreased Nrf2 activity as an important feature of ASD. We further find that NFE2L2 expression is related to the metabolic patterns we characterized in ASD frontal cortex. Results of our bioinformatics inquiry suggest a potential causal role for Nrf2 that requires further investigation.

Vitamin Cobalamin deficiency in macrocytic anemia reporting at a Tertiary Care Hospital.

Objective: Determine the frequency of vitamin cobalamin deficiency in macrocytic anemia cases reporting at tertiary care hospital. Study Design: Cross Sectional study. Setting: Faculty of Medicine and Allied Medical Sciences, Isra University, Hyderabad, Sindh Pakistan. Period: January 2017 to October 2018. Material &amp; Methods: 450 cases of both genders, diagnosed as macrocytic- megaloblastic anemia were studied for the vitamin Cobalamin levels. Cases were collected through non- probability convenient sampling by inclusion and exclusion criteria. Consenting volunteers were asked for blood sampling. 5 mL blood was taken from ante – cubital fossa. Samples were centrifuged and sera were collected for the estimation of vitamin cobalamin by ELISA – assay kit. Continuous and categorical variables were entered in SPSS (version 21.0) and analyzed by Student t-test and Chi-square test respectively at 95% CI (P ≤ 0.05). Results: Male and female comprised 225 (43.3%) and 294 (56.6%) of 519 subjects. Male to female ratio was noted 1.30:1. MCV, MCH and MCHC show statistically significant difference between male and female (P&lt;0.05). MCV in male was 96.8±9.92 fl vs. 105.5±12.04 fl in female (P=0.0001). Normal cobalamin was noted in 15.2% (n= 79) and any type of cobalamin deficiency was noted in 84.7% (n= 440) (P=0.0001). Conclusion: The present study reports frequency of 84.7% Cobalamin deficiency in macrocytic anemia reporting at Indus Medical College Hospital. Further studies are recommended by the treating physicians.

Causal Effects of Homocysteine, Folate, and Cobalamin on Kidney Function: A Mendelian Randomization Study.

Blood homocysteine level and related vitamin levels are associated with various health outcomes. We aimed to assess causal effects of blood homocysteine, folate, and cobalamin on kidney function in the general population by performing Mendelian randomization (MR) analysis. Genetic instruments for blood homocysteine, folate, and cobalamin levels were introduced from a previous genome-wide association (GWAS) meta-analysis of European individuals. Summary-level MR analysis was performed for the estimated glomerular filtration rate (eGFR) from the CKDGen consortium GWAS that included 567,460 European ancestry individuals. For replication, allele-score-based MR was performed with an independent U.K. Biobank cohort of 337,138 individuals of white British ancestry. In summary-level MR for the CKDGen data, high genetically predicted homocysteine levels were significantly associated with low eGFR (per 1 standard deviation, beta for eGFR change −0.95 (−1.21, −0.69) %), supported by pleiotropy-robust MR sensitivity analysis. Genetically predicted high folate levels were significantly associated with high eGFR change (0.86 (0.30, 1.42) %); however, causal estimates from cobalamin were nonsignificant (−0.11 (−0.33, 0.11) %). In the U.K. Biobank data, the results were consistently identified. Therefore, a high blood homocysteine level causally decreases eGFR. Future trials with appropriate homocysteine-lowering interventions may be helpful for the primary prevention of kidney function impairment.

A pilot study comparing the pharmacokinetics of injectable cyanocobalamin and hydroxocobalamin associated with a trace mineral injection in cattle.

Injectable vitamin B12 (cobalamin) is traditionally used to prevent or treat vitamin B12 deficiencies in ruminants. Sheep and human studies have demonstrated the superiority of a single dose of hydroxocobalamin (OHB12) over cyanocobalamin (CNB12) in maintaining high levels of cobalamin in plasma and liver. However, limited data are available for cattle. The purpose of this study was to compare the pharmacokinetics of two forms of cobalamin—OHB12 and CNB12—as a single subcutaneous injection of 28 µg/kg BW at the same time of a trace mineral injection in six non‐cobalt/B12‐deficient Holstein‐Friesian steers. Plasma and liver samples were obtained to determine cobalamin concentration after treatment. Cyanocobalamin had lower retention in plasma and liver than OHB12 (p < .05). Cobalamin levels peaked in plasma by 8 h after treatment in both groups. However, OHB12 reached a higher peak compared to CNB12. Levels of cobalamin in plasma dropped closer to baseline levels 24 h after CNB12 treatment while OHB12 maintained higher concentrations. Hydroxocobalamin increased significantly hepatic concentration of cobalamin 28 days after treatment, while CNB12 did not increase liver levels relative to pre‐treatment (p < .05). These results confirm that a single subcutaneous OHB12 injection increases the level of cobalamin in the blood in the first 24 hours, and this increase is maintained in the liver for at least 28 days.

Pyoderma gangrenosum and cobalamin deficiency in systemic lupus erythematosus: a rare but non fortuitous association

BackgroundPyoderma gangrenosum (PG) is an uncommon, idiopathic, ulcerative neutrophilic dermatosis. In many cases, PG is associated with a wide variety of different disorders but SLE in association with PG is relatively uncommon. In this article we present the case of a middle aged patient with PG as the initial clinical presentation of SLE. We also provide a brief review of cobalamin deficiency which occurred in our patient and evidence-based management options.Case presentationA 35 years old man presented with a 5 month history of debilitating painful lower limb and scrotal ulcers. This was associated with polyarthralgia and morning stiffness involving both hands. He also complained of swallowing difficulties. He had unintentional weight loss of 10 kg and fatigue. Physical examination revealed alopecia, multiple cervical lymphadenopathies, bilateral parotid gland enlargement and atrophic glossitis. There was Raynaud’s phenomenon noted over both hands and generalised hyper-pigmented fragile skin. Laboratory results disclosed anaemia, leukopenia, hyponatraemia and hypocortisolism. Detailed anaemic workup revealed low serum ferritin and cobalamin level. The autoimmune screen showed positive ANA, anti SmD1, anti SS-A/Ro 52, anti SSA/Ro 60, anti U1-snRNP with low complement levels. Upper gastrointestinal endoscopy with biopsies confirmed atrophic gastritis and duodenitis. Intrinsic factor antibodies and anti-tissue transglutaminase IgA were all negative. Punch biopsies of the leg ulcer showed neutrophilic dermatosis consistent with pyoderma gangrenosum. Based on the clinical findings and positive immunologic studies, he was diagnosed as systemic lupus erythematosus. His general condition improved substantially with commencement of corticosteroids, immunosuppressants and vitamin supplements.ConclusionsWe report a case of PG as the first manifestation of SLE which was treated successfully with immunosuppressants and vitamin supplements. Our report highlighted the need to consider connective tissue diseases such as SLE in a patient presenting with PG in order for appropriate treatment to be instituted thereby achieving a good outcome.

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman’s correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Biochemical Markers of Folate Metabolism Disorders in Schizophrenia in the Russian Population

Abstract—A range of foreign studies have shown that, in schizophrenia, hyperhomocysteinemia occurs more frequently than in the general population. Hyperhomocysteinemia may be an integrated marker of folate metabolism disorders (as a result of vitamin deficiency and/or genetic predisposition) or involved in the pathogenesis of the disease through several possible molecular mechanisms. In Russia, similar studies have not been conducted. In addition, there are conflicting results of studies on genetic factors involved in folate and homocysteine metabolism in schizophrenia. The aim of this study was to evaluate an association of serum homocysteine, folate, and cobalamin levels with schizophrenia in the Central part of Russia (Nizhny Novgorod region). For this purpose, 50 patients with schizophrenia and 36 healthy volunteers were randomly selected. The levels of homocysteine, folates and cobalamin (B12) were measured in blood serum. The concentration of homocysteine was measured using the Сobas analyzer (Roche Diagnostics) with an enzymatic assay. The content of folate and vitamin B12 was determined by chemiluminescent microparticle immunoassay (Architect, Abbott lab. S.A). It was found that the level of homocysteine was significantly higher in the patients than in the control group (p = 0.0041), and folate levels were significantly lower (p = 0.0072). The level of homocysteine in the patients had a weak negative statistically significant correlation with both folate level (ρ = –0.38; p = 0.0063) and with B12 level (ρ = –0.36; p = 0.0082). Homocysteine level was significantly higher in men than in women in the entire studied population (Z = –2.1068, p = 0.0351), as well as in subgroups of patients (Z = –2.11; p = 0.035) and healthy controls (z = 3.4; p = 0.00067). The data suggest the need for further investigation of hyperhomocysteinemia and other biochemical markers of folate metabolism disorders in schizophrenia in the Russian population and the development of ways to correct them to optimize the treatment of this mental disorder.