Cobalamin Status Research Articles

Folate and cobalamin status, indicators, modulators, interactions, and reference ranges from early pregnancy until birth: the Reus–Tarragona birth cohort study

BackgroundFolate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care. ObjectivesTo investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification. MethodsIn a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24–27, 34 GW, labor and in the cord. Single nucleotide polymorphisms affecting folate and cobalamin status were determined. FA, cobalamin, micronutrient supplement use, and dietary folate and cobalamin intake (food frequency questionnaire) were recorded. Folate and cobalamin status predictors were assessed by multiple linear regression analysis. ResultsOnly 36.1% of the participants took FA preconceptionally and 47.4% and 7.3% had suboptimal RBCF (<906 nmol/L) and plasma cobalamin status (≤221 pmol/L), respectively, at ≤12 GW. RBCF determinants included planned pregnancy, FA supplementation, plasma cobalamin, and methylenetetrahydrofolate (MTHFR) 677C>T genotype. Cobalamin supplementation was positively associated with plasma cobalamin and early holoTC. Smoking and BMI were inversely associated with plasma cobalamin and early holoTC, but none were associated with MMA. Only participants with the MTHFR 677TT genotype, exceeding FA supplement recommendations, improved their folate status (interaction term: B (95% CI):0.15 (0.01, 0.29), P = 0.032). Smoking was inversely associated with plasma cobalamin status in participants with the methionine synthase reductase (MTRR) 524CC genotype only (interaction term:0.07 (0.01, 0.04), P = 0.014). Mothers with low early pregnancy cobalamin status and also those with bigger newborns, had lower cobalamin status at labor. ConclusionsSuboptimal early pregnancy folate or cobalamin status affected 47.4% and 7.3% of the participants, respectively. The MTHFR 677TT genotype predicted folate status throughout pregnancy. Smoking and BMI were negatively associated with cobalamin status throughout pregnancy.Clinical Trial Registry number and website where it was obtained: NCT01778205. www.clinicaltrials.gov

Implications of hypocobalaminemia as a negative prognostic marker in juvenile dogs with parvovirus enteritis.

Canine Parvovirus 2 (CPV-2) infection poses a significant global health risk to susceptible dogs. Hypocobalaminemia, defined as reduced serum cobalamin (CBL) concentrations, is a recognized complication in chronic enteropathies in adult dogs but remains poorly understood in the context of acute enteropathies, especially in young dogs. The aim of this study was to investigate the frequency and severity of hypocobalaminemia in young dogs with parvovirus enteritis and evaluation of CBL as a predictor of outcome. Thirty client-owned dogs diagnosed with parvovirus infection and thirty healthy controls were enrolled. Clinical, hematological, and biochemical tests, including CBL and serum methylmalonic acid (MMA) concentrations, were assessed. Results indicated a significantly higher prevalence of hypocobalaminemia in dogs with parvovirus enteritis compared to healthy controls, as well as a significant correlation with a disease severity score. Moreover, survivors demonstrated higher CBL concentrations than non-survivors, suggesting an eventual prognostic value of CBL status. However, parenteral CBL supplementation showed no significant effect on serum CBL or MMA concentrations, highlighting potential challenges in CBL uptake at the cellular level. Hypocobalaminemia in this population is caused by multiple factors such as reduced nutritional absorption, gastrointestinal losses, and increased metabolic demands. Further research is needed to develop tailored management strategies, evaluate the effectiveness of CBL supplementation, and understand the mechanisms behind hypocobalaminemia in parvovirus infection.

Indicators of Cobalamin Status During Pregnancy, Pregnancy Outcome and Long-Term Effects on Offspring Health.

Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources. However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting. Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted.

Defining Optimal Cobalamin Status for Neonates and Infants.

An optimal cobalamin status is necessary for normal neurodevelopment. To give a description of the epidemiology, pathophysiology and diagnostic challenges related to cobalamin insufficiency in neonates and infants in order to prevent its occurence. Inadequate cobalamin status is prevalent among neonates and young infants, due to a high prevalence of maternal cobalamin deficiency, exclusive breastfeeding for extended periods and late introduction of animal food. Cobalamin insufficiency is associated with delayed neurodevelopment and subtle clinical symptoms like feeding difficulties, regurgitations and constipation in young infants. Early diagnosis and treatment of impaired cobalamin status is important to prevent neurologic damage. Clinical suspicion of cobalamin insufficiency in infants should infer immediate biochemical testing and a plasma total homocysteine > 5.0 µmol/L indicate cobalamin insufficiency in need of intramuscular treatment with hydroxycobalamin, followed by introduction of animal food after 4 months of age.

Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda

BackgroundMicronutrient deficiencies and anemia are widespread among children with stunting. ObjectivesWe assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. MethodsThis was a secondary analysis of a randomized controlled trial. Children aged 12–59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. ResultsAmong 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). Conclusions: LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting.This trial was registered at ISRCTN as 13093195.

Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.

Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients.

Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study

Abstract Folate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0–12 months (n = 125) were recruited through public health clinics. We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, and MMA concentrations were 47 (35–66) nmol/L, 250 (178–368) pmol/L, 6.99 (5.69–9.27) µmol/L, and 0.35 (0.24–0.83) µmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (&lt; 148 pmol/L), and 23% had low vitamin B12 status (148–221 pmol/L). Elevated tHcy (&gt; 6.5 μmol/L) and MMA (&gt; 0.26 μmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (P &lt; 0.001), in addition to 47% and 39% lower cobalamin concentrations (P &lt; 0.001), respectively. However, the observed biomarker concentrations appeared to be independent of infant age. In conclusion, low vitamin B12 status was prevalent and appeared to be more common in the younger exclusively breastfed compared to older weaned infants. The implications of low vitamin B12 status in infancy are unknown and require further investigation.

Cobalamin Status In Patients With Type 2 Diabetes Mellitus At Primary Health Care Centers In Bahrain - A Cross-Sectional Study

Background and Objectives: Cobalamin, also known as vitamin B12, is essential for DNA synthesis and neurological functioning. Deficiency results in hematological and neurocognitive manifestations. One risk factor for vitamin B12 deficiency is the use of metformin, a common oral hypoglycemic agent. This study was conducted to determine cobalamin status in patients with type 2 diabetes mellitus at primary health care centers in Bahrain. Methods: This cross-sectional study was conducted in five randomly selected health centers in Bahrain. Vitamin B12 levels below 148 pmol/L were categorized as deficient, levels ranging from 148 to 221 pmol/L were considered borderline, and levels exceeding 221 pmol/L were classified as normal. Results: A total of 691 participants were included in the study, with a mean age of 58.7 years. The most common comorbid condition among our cohort was hypertension (63.1%), followed by dyslipidemia (53.1%). Analysis of the glycemic control showed that only 40% of the participants achieved control targets. Nearly 10% (9.4%, n=65) of the cohort had low levels of vitamin B12, and 31% had borderline values. A significant association was seen between low vitamin B12 levels and Bahraini nationality (P&lt;0.001), and patients who engaged in weekly exercise (P=0.007). Furthermore, the analysis revealed that the use of metformin (P=0.037) and alcohol (P=0.012) was significantly associated with low levels of vitamin B12. Conclusion: Although the overall prevalence of B12 deficiency among patients with type 2 diabetes in Bahrain was low, patients at high risk of B12 deficiency, including metformin users and alcohol consumers, should be periodically screened to prevent the associated neurological and hematological sequela. Keywords: Bahrain, Cobalamin, Diabetes Mellitus, Primary Health Care, Vitamin B12

Nutritional status of flexitarians compared to vegans and omnivores - a cross-sectional pilot study

BackgroundIn the Western world, there has been a notable rise in the popularity of plant-based, meat-reduced flexitarian diets. Nevertheless, there is insufficient data on the nutritional status of individuals following this dietary pattern. The aim of this study was to investigate the intake and endogenous status of various nutrients in a healthy German adult study population consisting of flexitarians (FXs), vegans (Vs) and omnivores (OMNs).MethodsIn this cross-sectional study, dietary intake of 94 non-smoking adults (32 FXs, 33 Vs, 29 OMNs) between 25 and 45 years of age was assessed using 3-day dietary records. In addition, blood samples were collected to determine different endogenous nutrient status markers.Results32%, 82% and 24% of the FXs, Vs, and OMNs respectively reported using dietary supplements. In the FXs, intake of total energy as well as macronutrients and most micronutrients were within the reference range. FXs had higher intakes of fiber, retinol-equ., ascorbic acid, folate-equ., tocopherol-equ., calcium, and magnesium compared to OMNs. However, cobalamin intake in FXs (2.12 µg/d) was below the reference (4 µg/d). Based on 4cB12, 13% of FXs showed a cobalamin undersupply [< -0.5 to -2.5] compared to 10% of OMNs, and 9% of Vs. The median 25(OH)D serum concentrations in FXs, Vs and OMNs were 46.6, 55.6, and 59.6 nmol/L. The prevalence of an insufficient/deficient vitamin-D status [< 49.9 nmol 25(OH)D/L] was highest in FXs (53%), followed by Vs (34%) and OMNs (27%). In FXs and Vs, the supplement takers had better cobalamin and vitamin-D status than non-supplement takers. Anemia and depleted iron stores were found only occasionally in all groups. In women, the prevalence of pre-latent iron deficiency and iron deficiency was highest in FXs (67%) compared to Vs (61%) and OMNs (54%).ConclusionOur findings indicated that all three diets delivered sufficient amounts of most macro- and micronutrients. However, deficiencies in cobalamin, vitamin-D, and iron status were common across all diets. Further studies are needed to investigate the nutrient supply status and health consequences of meat-reduced plant-based diets. The study was registered in the German Clinical Trial Register (number: DRKS 00019887, data: 08.01.2020).

Vitamin B12 – a scoping review for Nordic Nutrition Recommendations 2023

Vitamin B12 (cobalamin) is essential for normal metabolic function, and even moderate deficiency of this vitamin has negative health effects. Vitamin B12 is found in animal foods, and as vegetarian diets are increasingly popular in Western countries, one might expect a higher prevalence of vitamin B12 deficiency in the Nordic population. Setting recommendations for vitamin B12 intake has proven to be difficult, as uptake of vitamin B12 varies substantially, the clinical deficiency symptoms are often diffuse, and there is no clear agreement on the decision limits for vitamin B12 deficiency. Vitamin B12 deficiency is reported to be particularly common among pregnant women and infants, despite the fact that less than 1% of Norwegian pregnant women have a cobalamin intake below the Nordic Nutrition Recommendations 2012-recommended level of 2.0 µg/day. In addition, the assumption that breast milk contains sufficient vitamin B12 for optimal health and neurodevelopment during the first 6 months of life does not comply with the high prevalence of insufficient vitamin B12 status in this age group. Recommended intakes of vitamin B12 vary among age groups and must be based on markers of cobalamin status, indicating an optimal intracellular biochemical status, and not merely absence of clinical signs of vitamin B12 deficiency.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Vitamin B12 and/or folic acid supplementation on linear growth; a 6 years follow-up study of a randomised controlled trial in early childhood in North India.

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomized placebo-controlled trial in 1,000 young children. Starting at 6-30 months of age, we gave folic acid (∼2 RDAs), vitamin B12 (∼2 RDAs), both vitamins, or a placebo daily for six months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate, and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (SD) age at follow-up was 7.4 (0.7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup-effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/L (P interaction = 0.01). The effect of vitamin B12 supplementation in this group was 0.34 HAZ (95% CI: 0.11-0.58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (P interaction = 0.001). In this group, each doubling of the cobalamin concentration was associated with 0.26 (95% CI: 0.15 to 0.38) higher HAZ. Suboptimal B12 status in early childhood seemingly limits linear growth in North Indian Children.

Cobalamin status is negatively correlated with vascular endothelial-cadherin in vegetarian and vegan women with vitamin B12 deficiency

Optimal vitamin B12 status is important for vascular health. Vascular endothelial (VE) cadherin is an adherent junction protein involved in the maintenance of a functional endothelium. We hypothesized that vitamin B12 deficiency can negatively affect markers of vascular function, such as VE-cadherin. Within a human intervention study, we explored the possible association between cobalamin status (i.e., vitamin B12, holotranscobalamin, and homocysteine) and VE-cadherin (as marker of vascular health) in vegetarians/vegans (VEG) with B12 deficiency. The associations were evaluated at baseline and after 90-day supplementation with 2000 µg/wk of vitamin B12. On the whole, an inverse association between VE-cadherin and holotranscobalamin (P=.014) and a positive association between VE-cadherin and homocysteine (P=.041) was documented at baseline. VEG women showed higher levels of VE-cadherin compared with VEG men (P=.044), suggesting an increase in endothelial permeability. The intervention with vitamin B12 restored serum vitamin levels and improved the overall cobalamin status, whereas it did not affect VE-cadherin levels. The inverse association between holotranscobalamin and VE-cadherin was also maintained after intervention in women, corroborating the strong correlation between these 2 parameters. The results obtained seem to suggest a possible association between cobalamin status and VE-cadherin even if the intervention with B12 failed to positively affect VE-cadherin levels. Thus, further studies are needed to corroborate these findings and clarify the contribution of a vitamin B12 intervention on VE-cadherin levels in this target population. This trial was registered at ISRCTN registry (ISRCTN75099618).

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

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.

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.

Nutritional Interventions In The Treatment Of Acne Vulgaris: A Systematic Review Of Clinical Trials / Intervenções Nutricionais No Tratamento Da Acne Vulgaris: Uma Revisão Sistemática Dos Ensaios Clínicos

The aim of this study is to review the literature about dietary interventions on acne vulgaris in order to support the development of more effective treatments in clinical practice. A systematic review of the literature, from clinical trials over the last five years, available in Pub Med and SciELO . The selected articles were analyzed according to the Jadad scale, CONSORT and risk of bias using the Cochrane protocol. CONSORT indicated that most of the evidence score was attributed in the titles, abstracts and some of the methods. In particular, the methods of the studies evaluated, when lacking detail, received lower scores, among the evidence, expressed as a percentage. The results, after using the Jadad scale, indicated a similar profile to that obtained with the CONSORT protocol. However, this tool is limited with regard to randomization and blinding. Using the Cochrane method, the risk of bias was evaluated. Results corroborated the evaluations by CONSORT and Jadad scale. Supplementation with n-3 fatty acids, Camellia sinensis , Berberis vulgaris , chromium, selenium and probiotics were significant, but results were limited for the treatment of acne vulgaris. Consumption of foods with increased glycemic load and chocolate indicated a correlation with an increase in acneiform lesions. Changes in nutritional status of alfa-tocopherol, cobalamin and folic acid were associated with the use of isotretinoin. There is a need to increase the quantity and quality of scientific evidence on the nutritional treatment of acne vulgaris in order to more effectively and safely guide the nutritional actions of clinical practice today.

Folate and Cobalamin Serum Levels in Healthy Children and Adolescents and Their Association with Age, Sex, BMI and Socioeconomic Status.

This study proposes age- and sex-specific percentiles for serum cobalamin and folate, and analyzes the effects of sex, age, body mass index (BMI), and socioeconomic status (SES) on cobalamin and folate concentrations in healthy children and adolescents. In total, 4478 serum samples provided by healthy participants (2 months–18.0 years) in the LIFE (Leipzig Research Centre for Civilization Diseases) Child population-based cohort study between 2011 and 2015 were analyzed by electrochemiluminescence immunoassay (ECLIA). Continuous age-and sex-related percentiles (2.5th, 10th, 50th, 90th, 97.5th) were estimated, applying Cole’s LMS method. In both sexes, folate concentrations decreased continuously with age, whereas cobalamin concentration peaked between three and seven years of age and declined thereafter. Female sex was associated with higher concentrations of both vitamins in 13- to 18-year-olds and with higher folate levels in one- to five-year-olds. BMI was inversely correlated with concentrations of both vitamins, whilst SES positively affected folate but not cobalamin concentrations. To conclude, in the assessment of cobalamin and folate status, the age- and sex-dependent dynamic of the respective serum concentrations must be considered. While BMI is a determinant of both vitamin concentrations, SES is only associated with folate concentrations.

A comparison of homocysteine, troponin, cobalamin and folate status in acute myocardial infarction patients and healthy subjects: A case–control study

Introduction: Homocysteine (HCY), troponin, cardiac markers, folic acid and Vitamin B12 are known as the potential biomarkers for acute myocardial infarction (AMI) diagnosis. This study was designed to evaluate these markers as candidate biomarkers in the diagnosis, prognosis and prevention of AMI. Materials and Methods: This study was carried out on 40 AMI patients and 40 healthy subjects. After taking blood, HCY level was measured by an enzymatic, troponin and Vitamin B12, while the level of folic acid was determined by the radioimmunoassay method. In addition, the cardiac enzyme markers and lipid profile were measured by commercial kits and spectrophotometric method. Results: The results showed that patients' HCY levels were significantly more than the control group. Furthermore, the level of troponin was significantly different in the two groups (P = 0.0001), while serum levels of cardiac enzyme markers were significantly higher in patients (P 0.05). A positive correlation was identified between HCY with cholesterol (r = 0.32, P < 0.04) and low-density lipoprotein cholesterol (LDL-C) (r = 0.38, P < 0.02) in the patients. Conclusion: Elevated fasting HCY and troponin concentration are related to the lower circulation of folate and Vitamin B12 levels in the patients. The deficiency of these vitamins plays a role as an independent factor in HCY metabolism. As our findings revealed, despite a decrease in high-density lipoprotein cholesterol, the level of LDL-C increased in the patients. It can be inferred that merging enzymatic and non-enzymatic biomarkers might be more valuable in the diagnosis of AMI.

Cobalamin and folate status in women during early pregnancy in Bhaktapur, Nepal.

The demand for cobalamin (vitamin B12) and folate is increased during pregnancy, and deficiency during pregnancy may lead to complications and adverse outcomes. Yet, the status of these micronutrients is unknown in many populations. We assessed the concentration of cobalamin, folate and their functional biomarkers, total homocysteine (tHcy) and methylmalonic acid (MMA), in 561 pregnant women enrolled in a community-based randomised controlled trial in Bhaktapur, Nepal. Plasma concentrations of cobalamin, folate, tHcy and MMA were measured and a combined indicator of vitamin B12 status (3cB12) was calculated. We report mean or median concentrations and the prevalence of deficiency according to commonly used cut-offs, and assessed their association with indicators of socio-economic status, and maternal and dietary characteristics by linear regression. Among the women at gestational week less than 15, deficiencies of cobalamin and folate were seen in 24 and 1 %, respectively. Being a vegetarian was associated with lower plasma cobalamin, and a higher socio-economic status was associated with a better micronutrient status. We conclude that cobalamin deficiency defined by commonly used cut-offs was common in Nepalese women in early pregnancy. In contrast, folate deficiency was rare. As there is no consensus on cut-off points for vitamin B12 deficiency during pregnancy, future studies are needed to assess the potential functional consequences of these low values.