Maternal vitamin B12 deficiency in rats alters DNA methylation in metabolically important genes in their offspring.

PMID: 

Mol Cell Biochem. 2020 May ;468(1-2):83-96. Epub 2020 Mar 18. PMID: 32189172

Abstract Title: 

Maternal vitamin Bdeficiency in rats alters DNA methylation in metabolically important genes in their offspring.

Abstract: 

Vitamin Bdeficiency is a critical problem worldwide and peri-conceptional deficiency of this vitamin is associated with the risk of complex cardio-metabolic diseases. Nutritional perturbations during these stages of development may lead to changes in the fetal epigenome. Using Wistar rat model system, we have earlier shown that low maternal Blevels are associated with low birth weight, adiposity, insulin resistance, and increased triglyceride levels in the offspring, which might predispose them to the risk of cardio-metabolic diseases in adulthood. In this study, we have investigated the effects of maternal Bdeficiency on genome-wide DNA methylation profile of the offspring and the effect of rehabilitation of mothers with Bat conception. We have performed methylated DNA immunoprecipitation sequencing of liver from pups in four groups of Wistar rats: Control (C), B-restricted (BR), B-rehabilitated at conception (BRC), and B-rehabilitated at parturition (BRP). We have analyzed differentially methylated signatures between the three groups as compared to controls. We have identified a total of 214 hypermethylated and 142 hypomethylated regions in the 10 kb upstream region of transcription start site in pups of B-deficient mothers, which are enriched in genes involved in fatty acid metabolism and mitochondrial transport/metabolism. Brehabilitation at conception and parturition is responsible for reversal of methylation status of many of these regions to control levels suggesting a causal association with metabolic phenotypes. Thus, maternal Brestriction alters DNA methylation of genes involved in important metabolic processes and influences the offspring phenotype, which is reversed by Brehabilitation of mothers at conception.

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The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy.

PMID: 

Sultan Qaboos Univ Med J. 2020 Feb ;20(1):e90-e94. Epub 2020 Mar 9. PMID: 32190375

Abstract Title: 

Vitamin B12 Deficiency in Diabetic Patients on Metformin Therapy: A cross-sectional study from Oman.

Abstract: 

Objectives: This study aimed to determine the prevalence of vitamin B12 deficiency amongst diabetic patients on metformin therapy.Methods: This cross-sectional study was conducted at general clinics at the University Health Center and diabetes outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January and December 2017. All Omani adults who were diagnosed with type 2 diabetes mellitus and took metformin were invited to participate in the study. The variables included in this study were age, gender, duration of diabetes, dose and duration of metformin therapy, haemoglobin and glycosylated haemoglobin level.Results: A total of 248 subjects were included (response rate = 95.4%) of which 26 (10.5%) were vitamin B12 deficient and 53 (21.4%) were borderline deficient. The mean daily dose of metformin was highest among vitamin B12 deficient group (1,981± 222 mg;= 0.004).Conclusion: The prevalence of vitamin B12 deficiency is considerable among diabetic patients on metformin therapy. Further research is needed to confirm the need for routine screening and monitoring.

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Higher vitamin B12 level at Parkinson’s disease diagnosis is associated with lower risk of future dementia.

PMID: 

Parkinsonism Relat Disord. 2020 Mar 16 ;73:19-22. Epub 2020 Mar 16. PMID: 32203914

Abstract Title: 

Higher vitamin B12 level at Parkinson's disease diagnosis is associated with lower risk of future dementia.

Abstract: 

INTRODUCTION: To determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.METHODS: We utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.RESULTS: PD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p 

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Low vitamin B12 levels: An underestimated cause Of minimal cognitive impairment and dementia.

PMID: 

Cureus. 2020 Feb 13 ;12(2):e6976. Epub 2020 Feb 13. PMID: 32206454

Abstract Title: 

Low Vitamin B12 Levels: An Underestimated Cause Of Minimal Cognitive Impairment And Dementia.

Abstract: 

Background Vitamin B12 deficiency is linked to impaired cognition and memory along with a sensation of tingling and numbness, an outcome of poor myelination. Elevated methylmalonic acid and serum homocysteine levels are markers of Vitamin B12 deficiency. Elevated homocysteine levels are also often associated with Alzheimer's disease and stroke. We conducted this study to determine the effect of vitamin B12 replacement therapy on vitamin B12-deficient patients with noted cognitive impairment. Methods We conducted a cross-sectional, multicenter study of patients with minimal cognitive impairment (MCI) to assess for Vitamin B12 and homocysteine levels. All patients found to be deficient in vitamin B12 underwent replacement therapy and were assessed again after three months via the Mini-Mental State Examination (MMSE) and a review of symptoms. Results A total of 202 patients were included in the study. Of those, 171 (84%) patients reported marked symptomatic improvement after vitamin B12 replacement while MMSE scores improved in 158 (78%) patients. Of the remaining 44 patients who reported no symptomatic improvement, MMSE scores improved in 26 while 18 patients showed no MMSE score improvements. Conclusions Vitamin B12 deficiency is linked to cognition, and replacement therapy may be an option to improve patient cognition outcomes. Further studies are needed to confirm and refine the observed associations over a larger scale and to determine whether these findings will translate to a reduction in cognitive decline.

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Vitamin B12 regulates glial migration and synapse formation through isoform-specific control of PTP-3/LAR PRTP expression.

PMID: 

Cell Rep. 2020 Mar 24 ;30(12):3981-3988.e3. PMID: 32209461

Abstract Title: 

Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression.

Abstract: 

Vitamin B12 is known to play critical roles during the development and aging of the brain, and vitamin B12 deficiency has been linked to neurodevelopmental and degenerative disorders. However, the underlying molecular mechanisms of how vitamin B12 affects the development and maintenance of the nervous system are still unclear. Here, we report that vitamin B12 can regulate glial migration and synapse formation through control of isoform-specific expression of PTP-3/LAR PRTP (leukocyte-common antigen-related receptor-type tyrosine-protein phosphatase). We found the uptake of diet-supplied vitamin B12 in the intestine to be critical for the expression of a long isoform of PTP-3 (PTP-3A) in neuronal and glial cells. The expression of PTP-3A cell autonomously regulates glial migration and synapse formation through interaction with an extracellular matrix protein NID-1/nidogen 1. Together, our findings demonstrate that isoform-specific regulation of PTP-3/ LAR PRTP expression is a key molecular mechanism that mediates vitamin-B12-dependent neuronal and glial development.

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Vitamin B12 is neuroprotective in experimental pneumococcal meningitis.

PMID: 

J Neuroinflammation. 2020 Apr 1 ;17(1):96. Epub 2020 Apr 1. PMID: 32238192

Abstract Title: 

Vitamin Bis neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation.

Abstract: 

BACKGROUND: Bacterial meningitis (BM) causes apoptotic damage to the hippocampus and homocysteine (Hcy) accumulation to neurotoxic levels in the cerebrospinal fluid of children. The Hcy pathway controls bioavailability of methyl, and its homeostasis can be modulated by vitamin B, a cofactor of the methionine synthase enzyme. Herein, the neuroprotective potential and the underlying mode of action of vitamin Badjuvant therapy were assessed in an infant rat model of BM.METHODS: Eleven-day old rats were intracysternally infected with Streptococcus pneumoniae serotype 3, or saline, treated with Bor placebo, and, 24 h after infection, their hippocampi were analyzed for apoptosis in the dentate gyrus, sulfur amino acids content, global DNA methylation, transcription, and proximal promoter methylation of candidate genes. Differences between groups were compared using 2-way ANOVA followed by Bonferroni post hoctest. Correlations were tested with Spearman's test.RESULTS: Battenuated BM-induced hippocampal apoptosis in a Hcy-dependent manner (r = 0.80, P 

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The results of this study indicated that intervention with vitamin B12 in pregnancy reduces possibilities of the onset of anemia.

PMID: 

J Med Food. 2020 Apr 17. Epub 2020 Apr 17. PMID: 32302504

Abstract Title: 

Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial.

Abstract: 

Vitamin B12 plays an important role in cell division and is of vital importance during pregnancy. Iron and B12 deficiency increase the risk of neonatal morbidity and the outcome of the overall pregnancy. The aim of our study was to analyze whether the use of vitamin B12, with standard supplements of folic acid and iron among nonanemic pregnant women, will result in improvements of hemogram parameters in terms of hematological and biochemical markers. Study participants were 200 healthy pregnant women, randomized into an intervention group and a control group, recruited from gynecological primary care practices in Split, Croatia. In addition to standard supplementation (350 mg/day ferrous iron, 5 mg folic acid), participants in the intervention group were given 5 g of vitamin B12 each morning for 100 days. Both biochemical and hematological measurings were conducted in two intervals: 8th-10th week of gestation and then again in the 34th-36th week of gestation. Participants in the control group were given only standard-of-care iron and folic acid supplementation. Significantly lower values of haptoglobin postintervention, compared with baseline, were found only in the intervention group; for erythrocytes, significantly lower values postintervention were found only in the control group. For parameter hematocrit, we found decreased values postintervention, compared with baseline, in both intervention and control group; however, this decrease was within the reference range for the control group, whereas it was above the reference range for the intervention group. The results of this study indicated that intervention with vitamin B12 in pregnancy reduces possibilities of the onset of anemia, but within reference range.

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The results of the study show that vitamin B12 deficiency or insufficiency and elevated homocysteine may contribute to the etiopathogenesis of depression.

PMID: 

Child Adolesc Ment Health. 2020 Apr 18. Epub 2020 Apr 18. PMID: 32304285

Abstract Title: 

The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents.

Abstract: 

BACKGROUND: Depression is a heterogeneous disorder and is thought to develop as a result of complex interactions between genetic and environmental factors. One-carbon metabolism that includes vitamin B12, folic acid, and homocysteine has been investigated in psychiatric disorders like depression. In recent years, vitamin D has also been considered to contribute to psychiatric disorders. In this study, serum levels of folate, vitamin B12, and homocysteine related to one-carbon metabolism and vitamin D were investigated in children and adolescents with depression and to assess possible roles in depression pathogenesis.METHODS: The study included 89 children and adolescents with depression (69 female, 20 male; mean age ± SD = 15.08 ± 1.46) and 43 control subjects (31 female, 12 male; mean age ± SD = 14.41 ± 2.32) without any DSM-5 diagnosis. Each subject completed a sociodemographic form, Childhood Depression Inventory, State-Trait Anxiety Inventory 1-2 and measured serum folate, vitamin B12, homocysteine, and 25-OH vitamin D levels.RESULTS: There was no significant difference between the groups in terms of folate levels (p = .052). In the patient group, the vitamin B12 and vitamin D levels were clearly low (p values for both levels were

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Anti-obesity effects of a mixed extract containing Platycodon grandiflorum, Apium graveolens and green tea.

PMID: 

Exp Ther Med. 2020 Apr ;19(4):2783-2791. Epub 2020 Feb 5. PMID: 32256761

Abstract Title: 

Anti-obesity effects of a mixed extract containingand green tea in high-fat-diet-induced obese mice.

Abstract: 

The anti-obesity effect of a combination of extracts made of(PGE),(AGE) and green tea (GTE) extracts was investigated in a high-fat diet-induced obese C57BL/6N mouse model. Body weight, epididymal adipose tissue weight, liver weight, adipocytes size and serum lipid profile, insulin, leptin and glucose levels were investigated. Additionally, hepatic steatosis, injury and oxidative burden were evaluated in the present study. The current study demonstrated that the PGE, AGE, and GTE (PAG) mixture were most effective in preventing obesity and its associated complications compared with the single extracts used alone. This was evidenced by the PAG's prevention of weight gain, reduction of adipocyte size, beneficial effects in serum lipid profile, levels of insulin, leptin and glucose, and the prevention of liver injury by reducing fat accumulation in the liver, decreased GOT and GPT enzymes and the upregulation of liver antioxidant enzymes. These results suggested that PAG may provide insights into functional food ingredients for use in the prevention of obesity.

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