Low Vitamin B12 Research Articles

Case report: Vitamin B12 deficiency-associated hemolytic anemia

Vitamin B12 deficiency is commonly known to cause hematological, neurological, and gastrointestinal disturbances including anemia, pancytopenia, sub-acute combined degeneration, and glossitis, among others. Hemolytic anemia is a rare but possible presentation of vitamin B12 deficiency. We present a case series of three elderly females with different past medical histories but with similar presentations of severe anemia. Initial investigation revealed pancytopenia and hemolytic anemia. Further evaluation indicated vitamin B12 deficiency and subsequently, pernicious anemia, as confirmed by low serum vitamin B12 levels and positive intrinsic cell antibody respectively. These findings directed the diagnosis toward vitamin B12 deficiency-induced hemolytic anemia, a rare clinical entity. All three patients responded to treatment with intramuscular vitamin B12 injections, showing significant improvement in their pancytopenia and hemolytic anemia. This case series highlight the importance of considering vitamin B12 deficiency as a potential cause of hemolytic anemia in patients presenting with pancytopenia and ineffective hematopoiesis. Further research is necessary to illuminate the therapeutic implications of this rare condition.

Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12

The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = − 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = − 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.

Correlation between serum vitamin B12, vitamin D, and suboptimal semen parameters in male infertility: A hospital-based cross-sectional study

ABSTRACT Background: Micronutrients such as vitamin B12 and D have recently gained attention for their potential roles in male reproductive health. Despite their significance, there’s a critical gap in understanding their association with male infertility, particularly concerning suboptimal semen parameters. This study aimed to address this knowledge gap by examining serum vitamin B12 and D levels in infertile males, providing insights that could inform targeted interventions for couples facing male infertility challenges. Methods: This cross-sectional study, conducted at Tertiary Health care centre in north India for 2 years, enrolled 73 infertile males aged 20–40 years from the fertility clinic (participants exhibited suboptimal semen parameters). Clinical and demographic data were collected through interviews and record reviews, while semen samples underwent meticulous processing for the analysis of various parameters. Blood samples were collected after overnight fasting for serum vitamin B12 (ELISA) and vitamin D (CLIA) assessment. Statistical analyses, performed using SPSS, included t-tests, Chi-square tests, and Pearson’s correlation analyses to explore associations between serum vitamin levels and semen parameters, with a significance level set at P &lt; 0.05. Results: The study comprised 73 infertile males with suboptimal semen parameters. Serum vitamin B12 levels (mean ± SD: 243.4 ± 69.3 pg/mL) and vitamin D levels (22.5 ± 13.2 ng/mL) were measured. Low vitamin B12 (&lt;200 pg/mL) was observed in 29 participants (39.7%), while low vitamin D (&lt;20 ng/mL) was noted in 51 participants (69.9%). Semen parameters revealed significant differences in sperm count, motility, and morphology between low and normal vitamin B12 groups. Similar patterns were observed with vitamin D levels, emphasizing potential associations between vitamin status and semen quality. Conclusion: Our findings suggest a potential link between low serum vitamin B12 and D levels and suboptimal semen parameters in infertile males. Addressing these nutritional deficiencies may hold promise for improving male fertility outcomes. Further research is warranted to elucidate the mechanisms involved and explore targeted interventions.

Association of Vitamin B12 and Polymorphism of TCN2 with Early-Onset Post-Stroke Depression.

Post-stroke depression (PSD) is a common neuropsychiatric complication after a stroke with complex mechanisms. However, few studies have identified the role of vitamin B12 and folate in the occurrence and pathophysiology of PSD. The aim of our study is to investigate the relationship among vitamin B12, folate, their transporter genes, and early-onset PSD. A total of 173 ischemic stroke patients were recruited in Xiangya Hospital of Central South University. We collected peripheral blood samples, clinical data, and demographics at admission. The 17-item Hamilton Depression Scale was used for screening for the existence of depression at 2weeks after stroke onset. Serum vitamin B12 and folate level were measured based on double-antibody sandwich enzyme-linked immune-sorbent assay. Four single nucleotide polymorphisms (SNP) of transcobalamin 2 (TCN2) and solute carrier family 19 member 1 were genotyped using SNPscanTM multiplex SNP typing Kit. Eighty-four patients were diagnosed with PSD at 2weeks after stroke onset, and the incidence rate was 48.6%. Serum vitamin B12 level in PSD group was significantly lower than those in the non-PSD group (p=0.018). Binary logistic regression revealed that TCN2 rs1801198 GG genotype and G allele were associated with an increased risk of PSD after adjustment for confounding factors (for GG genotype, OR = 4.253, 95% CI = 1.711~10.572, p = 0.002; for G allele, OR = 2.134, 95% CI = 1.362~3.343, p = 0.001). Moreover, individuals with the rs1801198 G allele in the PSD group exhibited lower vitamin B12 level than those with the rs1801198 G allele in the non-PSD group (p=0.045). TCN2 rs1801198 and vitamin B12 are associated with the risk of early-onset PSD, and they may be involved in the development of PSD. Our study presents a novel standpoint for the treatment of PSD and gains insights into the mechanistic underpinnings of PSD.

Metformin Use and Vitamin B12 Deficiency in People with Type 2 Diabetes. What Are the Risk Factors? A Mini-systematic Review.

Background and Aim: Metformin is recommended as the first-line agent for the management of type 2 diabetes following lifestyle and dietary changes. The long-term use of metformin has been associated with vitamin B12 deficiency. The aim of this review is to investigate the effect of metformin on vitamin B12 levels and identify any risk factors. Method: A literature search was conducted using MEDLINE, PubMed and ProQuest Central. Selected articles were peer-reviewed articles, written in English and published from 2015 and onwards. Excluded articles were case reports, reviews or meta-analyses, as well as those with no access to full text. Results: In total, 21 articles were included. There was a significant association between metformin use and vitamin B12 levels in 17 studies, while 4 studies found no such association. The risk factors examined were metformin dose, treatment duration, patient age and patient ethnicity. Conclusion: In summary, metformin use was associated with lower vitamin B12 concentrations, and higher doses and longer durations of treatment increase the risk of vitamin B12 deficiency. Routine vitamin B12 screening is recommended, prioritizing higher-risk patients. Further research is needed to identify when to initiate monitoring.

Vitamin B12 is correlated with insulin resistance and metabolism disorder markers in women with recurrent pregnancy loss

ObjectivesRecurrent pregnancy loss (RPL) seriously affects women's reproductive and mental health, and the incidence has increased in recent years. Insulin resistance (IR) acts as a significant contributing factor to RPL. Studies suggest that vitamin B12, folate intake, and homocysteine are correlated with IR, but the exact nature remains controversial and requires further investigation. In this study, we aimed to assess the levels and correlations between vitamin B12-folate-homocysteine and insulin resistance in RPL patients. Study design73 control subjects and 256 RPL patients (144 RPL patients without IR and 112 RPL patients with IR) were included in this observational retrospective cross-sectional study. The differences in vitamin B12, folate, and homocysteine levels between RPL patients with and without IR were analyzed using a Student's t-test. Pearson correlations were utilized to examine the correlation between vitamin B12-folate-homocysteine and glucose and lipid metabolism parameters. Multivariable linear regressions were used to assess the independent correlation of each factor with HOMA-IR. ResultsCompared to the control subjects, RPL patients exhibited lower vitamin B12 (p < 0.001) and folate (p < 0.001), and higher homocysteine (p = 0.001). RPL patients with IR described decreases in vitamin B12 (p = 0.003) and folate (p = 0.028), and increases in homocysteine (p = 0.033) as RPL patients without IR. Vitamin B12 in RPL patients was significantly negatively correlated with homocysteine (r = −0.348, p < 0.001), HOMA-IR (r = −0.214, p < 0.001), BMI (r = −0.160, p = 0.017), TG (r = −0.148, p = 0.039) and CHO (r = −0.149, p = 0.038) and positively correlated with folate (r = 0.217, p < 0.001). In multivariable linear regressions, after adjusting for age, strong correlations were observed between vitamin B12 (β = −0.197, p = 0.010), BMI (β = 0.466, p < 0.001), and HOMA-IR in RPL patients. ConclusionVitamin B12 is significantly correlated with IR in RPL patients. Circulating vitamin B12-folate-homocysteine metabolism could be a window of the pathological process of IR, obesity, and lipid metabolism disorders in RPL patients.

Maternal factors for neural tube defects in offspring: An umbrella review.

We conducted an umbrella review focusing on maternal risk factors during pregnancy associated with neural tube defects (NTDs). Our search was in databases PubMed, Scopus, and Web of Science. We specifically targeted meta-analyses examining maternal factors during pregnancy in relation to NTDs. The comparison involved assessing metrics such as odds ratio (OR) or related risk ratios reported in the included studies, as well as parameters like heterogeneity (I²), 95% prediction interval, small-study effects, excess significance biases, and sensitivity analysis. Three risk factors for fetal NTDs, namely hyperthermia with an OR of 1.92, obesity with an OR of 1.68, and passive smoking with an OR of 1.90, were classified as highly suggestive evidence (Class II). Influenza, with an OR of 3.33, was considered a risk factor with suggestive evidence (Class III). Multivitamin supplementation during pregnancy, with an OR of 0.76, and low maternal vitamin B12, with an OR of 2.41, were categorized as weak evidence (Class IV). We identified four risk factors including hyperthermia, influenza, obesity, and passive smoking as suggestive or highly suggestive evidence for NTDs. Low maternal vitamin B12 was identified as a risk factor for NTDs, supported by weak evidence.

Assessment of vitamin B12 and folate status and their determinants in children aged 6–59 months with severe acute malnutrition admitted to a tertiary-care centre in North India

ABSTRACT Background Vitamin B12 and folate are essential micronutrients, a deficiency of which causes anaemia, poor growth and an increased risk of infections, along with irreversible neurological damage to the developing brain in children. Methods A hospital-based prospective observational study was conducted in 100 children with severe acute malnutrition (SAM) aged 6–59 months admitted to a tertiary-care facility in northern India from July 2021 to June 2022. A structured proforma was used to record socio-demographic information, a detailed clinical history, results of general and systemic physical examination and a detailed anthropometric assessment. Serum folate and vitamin B12 were estimated by electrochemiluminescence. Results The mean age of the children was 24.18 months, and 64.0% were aged 6–12 months. The male-to-female ratio was 1.08:1. Anaemia was present in 87.0% of the children, and it was severe in 35% of them. There was serum vitamin B12 and folate deficiency in 61.0% and 19.0%, respectively. A deficiency of vitamin B12 was significantly associated with delayed developmental milestones in all domains, a mid-upper-arm circumference of <11.5 cm, severe anaemia, a low platelet count and folate deficiency, and a folate deficiency was significantly associated with older age, delayed developmental milestones in all domains, severe anaemia, a low platelet count and vitamin B12 deficiency. Conclusion Vitamin B12 deficiency is highly prevalent in children aged 6–59 months with SAM, but the prevalence of folate deficiency is much lower. Apart from iron and folic acid supplementation, government programmes should consider vitamin B12 supplementation for children aged 6–59 months.

A systematic review and meta-analysis of functional vitamin B12 status among adult vegans.

The dietary intake of vitamin B12 among unsupplemented vegans is notably lower compared to both vegetarians and omnivores. Prolonged low intakes of vitamin B12, such as seen in those adhering to a vegan diet, lead to physiological deficiency of vitamin B12 and an elevated risk of B12-related morbidity. However, while serum B12 serves as a conventional biomarker for assessing B12 status, its utility is limited given its sensitivity and specificity in ascribing physiological deficiency of B12 and the functional vitamin B12 status of those adhering to vegan diets is unclear. We conducted a systematic review and meta-analysis using data based on the full panel of biomarkers of vitamin B12 status to test whether adherence to a vegan diet is associated with an elevated risk of functional vitamin B12 deficiency compared to vegetarian or omnivorous diets. In addition, subgroup analysis was carried out to look at the effect of vitamin B12 supplement use on B12 status among vegans. Our search identified 4002 records, of which 19 studies met the inclusion criteria for the systematic review and 17 studies were taken forward for the meta-analysis. Meta-analysis results revealed significantly lower serum B12, pmol/ (-0.72 [-1.26, -0.18]; p = 0.01) and elevated total homocysteine, μmol/L (tHcy) (0.57 [0.26, 0.89]; p < 0.001) concentrations, alongside elevated methylmalonic acid, nmol/L (MMA) (0.28 [-0.01, 0.57]; p = 0.06) and lower holotranscobalamin, pmol/ (HoloTC) (-0.42 [-0.91, 0.07]; p = 0.09) levels among vegan adults compared to omnivores, indicating increased functional B12 deficiency in addition to low vitamin B12 status in vegan adults. There were no differences between vegans and vegetarians in HoloTC (0.04 [-0.28, 0.35]; p = 0.814) or MMA (-0.05 [-0.29, 0.20]; p = 0.708), but differences were found in serum B12 (-0.25 [-0.40, -0.10]; p = 0.001) and for tHcy (0.24 [0.09, 0.39]; p = 0.002) concentrations. Subgroup analyses indicated that the use of vitamin B12 supplements among vegans contributes to significant improvements in all biomarker concentrations compared to their unsupplemented counterparts. Our findings underscore the need for improved strategies to redress poor vitamin B12 status with appropriate B12 supplementation use among those adhering to vegetarian and vegan diets.

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (&amp;lt; 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (&amp;lt;1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

Association between dietary vitamin B6 intake and endometriosis risk: evidence from the national health and nutrition examination survey.

Endometriosis is a multifaceted disorder with genetic, immune, inflammatory, and multifactorial origins. Vitamin B6 serves as a pivotal coenzyme in various metabolic pathways involving lipids, hemes, nucleic acids, proteins, and carbohydrates. Dysregulation or deficiency of vitamin B6 can perturb human physiology. However, the relationship between dietary vitamin B6 and endometriosis remains elusive. This study aims to explore how dietary intake of vitamin B6 is associated with the risk of endometriosis. Using cross-sectional data from the National Health and Nutrition Examination Survey, we analyzed information from American women aged 20-54 years between 1999 and 2006. After adjusting for relevant covariates, multivariable logistic regression analysis was employed to evaluate correlations. A total of 4,453 women were included in the study. The multiple linear regression model revealed a positive association between dietary vitamin B6 intake and the risk of endometriosis, even after controlling for confounding variables. Compared to individuals with lower vitamin B6 consumption (Q1: <0.94 mg/day), the adjusted odds ratio (OR) values for dietary vitamin B6 intake and endometriosis in Q2 (0.95-1.39 mg/day), Q3 (1.40-1.99 mg/day), and Q4 (>1.90 mg/day) were 1.22 (95% CI: 0.88-1.69, p = 0.23), 1.22 (95% CI: 0.86-1.73, p = 0. 279), and 1.51 (95% CI, 1.01-2. 24, p = 0.04), respectively. Our findings suggest a positive correlation between endometriosis and dietary vitamin B6 intake. Further investigations are imperative to establish a causal relationship between dietary vitamin B6 intake and endometriosis.

Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report

BackgroundVitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption.Case presentationAn 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes.Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency.ConclusionWe report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.

Nutritional Status and Growth Outcomes in Pediatric Idiopathic Growth Hormone Deficiency: A Retrospective Study in Turkey

Objective: Growth and development in children are significantly influenced by nutritional status. Nutritional deficiencies such as low hemoglobin (Hb), ferritin, vitamin B12, and vitamin D have been linked to impaired growth. This study aims to evaluate the impact of these nutritional markers on growth outcomes in children with idiopathic growth hormone deficiency (IGHD) undergoing recombinant growth hormone therapy (rhGH). Material and Methods: A cross-sectional, retrospective study was conducted on 100 children with IGHD, aged under 16, diagnosed between 2000 and 2023. Data were collected from medical records, including height, body mass index (BMI), pubertal status, bone age, and nutritional markers [Hb, ferritin, vitamin B12, 25-hydroxy-vitamin D3 (25(OH)D3]. Growth parameters were assessed at the start and end of the first year of rhGH treatment. Results: The cohort had a median age of 11.3 years; 30% were female, and 50% were prepubertal. The median height standard deviation score (SDS) was -2.8, and median BMI SDS was -0.7. Prevalence of nutritional deficiencies included 23% with low Hb, 31% with low ferritin, 44% with low 25(OH)D3, and 15% with low vitamin B12. Despite these deficiencies, no significant differences were observed in height SDS or growth velocity when grouped by nutritional markers or supplementation status. Growth velocity showed a significant positive correlation with Hb levels and mid-parental height (MPH). Conclusion: Nutritional deficiencies were common among IGHD patients; there was no significant difference in terms of growth-related metrics in the first year of the rhGH therapy in comparisons between the groups with and without common nutritional deficiencies. This finding underscores the resilience of growth in the presence of these deficiencies. In contrast, growth velocity correlated positively with Hb levels and MPH, suggesting that these factors may play a significant role in influencing growth. Further research with larger samples and extended follow-up is needed to explore the long-term impact of nutritional supplementation on growth in IGHD.

Serum Vitamin B12 Levels as a Risk Factor and Prognostic Marker in Patients With Acute Ischemic Stroke at a Tertiary Care Center in Northern India: A Case-Control Study.

Objective Stroke is a leading cause of death and disability globally, with its incidence, prevalence, and mortality rising significantly over the past decades. Beyond traditional risk factors, vitamin B12 has garnered attention for its role in stroke prevention due to its influence on homocysteine metabolism. Deficiencies in vitamin B12 are linked to hyperhomocysteinemia, which increases the risk of ischemic stroke. This study aims to compare vitamin B12 and homocysteine levels in stroke patients versus control subjects. Methodology This observational case-control study was conducted at King George's Medical University (KGMU), Lucknow, involving 75 acute ischemic stroke patients and 75 age- and sex-matched controls. Serum vitamin B12 and homocysteine levels were measured, and stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. The modified Rankin scale (MRS) evaluated functional outcomes at discharge. Statistical analysis was performed to identify associations between vitamin B12 levels, stroke severity, and patient outcomes. Results Stroke patients had significantly lower vitamin B12 levels (194.24 ± 91.11 pmol/L) and higher homocysteine levels (16.33 ± 3.29 µmol/L) compared to controls (271.13 ± 91.19 pmol/L and 9.76 ± 4.55 µmol/L, respectively). Vitamin B12 levels were lower, and homocysteine levels were higher in patients who died during the study. Additionally, vitamin B12 levels were negatively correlated with MRS scores at discharge and 28 days post-discharge, and positively correlated with NIHSS scores, indicating worse outcomes in patients with lower vitamin B12 levels. Conclusions This study demonstrates a significant association between vitamin B12 deficiency and the occurrence and severity of ischemic stroke. Lower vitamin B12 levels correlated with higher stroke severity and poorer functional outcomes, highlighting the potential role of vitamin B12 in stroke management. Further research is needed to explore the therapeutic implications of vitamin B12 supplementation in reducing stroke risk and improving patient outcomes.

Taurine/chenodeoxycholic acid ratio as a potential serum biomarker for low vitamin B12 levels in humans.

Deficiency of vitamin B12 (B12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B12 deficiency lack specificity and sensitivity. Delays in detecting B12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B12 levels v control individuals, we set out to identify biomarker(s) of B12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B12 levels. Mechanistic studies using a mouse model of B12 deficiency showed that B12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B12 deficiency.

Vitamin B12 Deficiency in Thrombotic Thrombocytopenic Purpura-Like Cases.

Thrombotic microangiopathies (TMA) are characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and organ damage which occur in the setting of endothelial damage and platelet activation. Vitamin B12 (cobalamin) deficiency could lead to a picture that resembles TMA, termed metabolic mediated TMA (MM-TMA). A 60-year-old female was brought to the hospital after she was found unresponsive. On presentation, she was pale, lethargic, tachycardic, and febrile. Laboratory investigations revealed normocytic anemia, thrombocytopenia, and elevated bilirubin. Blood smear revealed schistocytes and tear drop cells. Given the presence of hemolytic anemia, thrombocytopenia, acute renal failure, and altered mental status, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made with a PLASMIC score of 7 indicating high risk. She received plasma exchange, caplacizumab, and intravenous methylprednisolone. Given the patient's low level of vitamin B12, she was initiated on intramuscular cyanocobalamin 1000 μg daily. The encephalopathy resolved and renal function improved. On day 6, ADAMTS13 activity was normal ruling out the diagnosis of TTP. Accordingly, plasmapheresis, steroids, and caplacizumab were discontinued. With continued aggressive B12 replacement, hemolysis resolved indicating severe vitamin B12 deficiency was the likely culprit of this patient's microangiopathic hemolytic anemia. This case serves to highlight the variable presentation of vitamin B12 deficiency. Severe vitamin B12 deficiency can even mimic TTP. If patients have markers of hemolysis, a low vitamin B12 level, and low reticulocyte count we should consider vitamin B12 deficiency as a likely cause of microangiopathic hemolytic anemia as early detection allows for early initiation of appropriate management. Vitamin B12 deficiency can be a cause of thrombotic microangiopathy.

Comparison of homocysteine, vitamin B12 and folic acid between rural and urban ageing Indians and its association with mild cognitive impairment and cardiovascular risk factors: a cross-sectional analysis.

The relationship between blood levels of homocysteine (HCY), vitamin B12, folic acid and cognitive impairment is inconclusive. Since HCY is an independent risk factor for cardiovascular diseases, understanding its association with Framingham risk score (FRS) may provide insight into the shared underlying mechanism between cardiovascular disease and cognitive impairment. Cross-sectional analyses utilized baseline data from two ongoing longitudinal studies: the Tata Longitudinal Study of Ageing (n = 923), an urban cohort, and Srinivaspura Ageing, NeuroSenescence and COGnition (n = 4239), a rural cohort. The study compared the HCY, vitamin B12 and folic acid levels across cohorts and normal versus mild cognitive impairment (MCI) participants. The association between HCY and cognitive status was established using regression models. Three models were analysed: model 1-unadjusted; model 2-adjusted for age, gender, smoking, alcohol consumption, diet, hypertension, cardiac illness, diabetes; and model 3-adjusted for variables in model 2 plus vitamin B12 and folic acid. Correlation was calculated between HCY and FRS. The urban cohort exhibited a significantly higher level of HCY [median (IQR) (17.70 (10.2) versus 14.70 (9.7); P < 0.001)], vitamin B12 (251 (231) versus 219 (138); P < 0.001) and folic acid (8.21 (8) versus 5.48 (4); P < 0.001) levels compared to rural cohort. HCY, vitamin B12 and folic acid levels did not differ significantly between normal and MCI participants in the urban cohort. In the rural cohort, among the age-gender matched MCI-normal, participants with normal cognition had higher levels of vitamin B12 (≥60 years) [227 (152) versus 217 (175); P = 0.03] and folic acid (<60 years) [5.91 (4) versus 5.40 (4); P = 0.04] compared to MCI. There was no association between HCY and cognitive status in both the cohorts, but there was a significant positive relationship between vitamin B12 deficiency and Clinical Dementia Rating-Sum of the Boxes (CDR-SOB), as well as folic acid deficiency and CDR-SOB in rural and urban cohorts, respectively, within a specific age group. A significant correlation was observed between FRS and HCY in the rural cohort (r = 0.17, P < 0.001), but not in the urban cohort. This study revealed significant differences in HCY, vitamin B12 and folic acid levels between the cohorts. In the rural cohort, participants with MCI had lower vitamin B12 and folic acid levels in a certain age group. Association between HCY and cognitive status was insignificant in both the cohorts. A small significant correlation between FRS and HCY was seen in the rural cohort.

Low concentration of serum vitamin B12 may be a strong predictor of large-artery atherosclerosis stroke: A case-control study

IntroductionIdentifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B12 with LAA stroke. MethodsInpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B12 concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B12 concentrations with LAA stroke, meanwhile adjusted for confounding factors. ResultsPatients with LAA stroke had significantly lower serum vitamin B12 concentrations in comparison to those of controls. In the fully adjusted model, vitamin B12 (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77–0.91), vitamin B12 < 200 pg/mL (OR=7.70, 95 %CI: 2.19–27.03) and vitamin B12 < 300 pg/mL (OR=4.19, 95 %CI: 1.82–9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B12 to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B12 concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine. ConclusionResults indicate that low concentration of serum vitamin B12 may be a strong predictor for the risk of LAA stroke.

Vitamin D, Folate, Vitamin B12, and Iron Status in Pregnant/Postpartum Old Order Anabaptist Women in Southwestern Ontario.

Purpose: To assess vitamin D, folate, vitamin B12, and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women.Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B12, and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007).Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes <EAR; 80% had folic acid supplement intakes >upper limit. One woman had low serum vitamin B12 (<148 pmol/L); serum vitamin B12 was high (>652 pmol/L) for 24%. None had vitamin B12 intakes <EAR; intakes were high compared to the recommended dietary intake. One woman had low hemoglobin; 13% had ferritin <15 μg/L. Thirteen percent had total iron intake <EAR.Conclusions: Overall, dietary intake and serum micronutrient status of OOA pregnant and postpartum women in our study were similar to those reported in previous studies of Canadian women. While some women had low intakes of vitamin D and iron, most had high intakes of folate and vitamin B12. These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.