Low B12 Levels Research Articles

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.

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Mediator Role of Frailty and Biological Deficits in Dementia Prognosis-Retrospective Cohort Study.

Background and Objectives: Dementia is increasing worldwide. This study aimed to examine the impact of comorbidity burden and frailty on dementia prognosis in patients with dementia. Materials and Methods: This retrospective cohort study was conducted with 47 patients with dementia who were followed for up to two years. The Modified Charlson Comorbidity Index (MCCI), Mini-Mental State Examination (MMSE-E), and Edmonton Fragility Scale were used besides laboratory and clinical findings. Results: The mean age of the 47 patients was 78.77 ± 12.44 years. During the follow-up period, MMSE-E scores were observed to improve in 50% of the patients. Initial MMSE-E scores were found to be lowest in men and patients with coronary artery disease or depression, while final MMSE-E scores were observed to be lowest in patients with depression and low vitamin B12 or vitamin D levels. The rates of decrease in MMSE-E scores in non-, moderately and severely frail patients were 21.4%, 55.6%, and 70.6%, respectively. There was a moderate negative correlation between MMSE-E scores and both comorbidity burden and frailty scores. The mediation analysis revealed that frailty was a complete mediator, and that comorbidity burden led to an increase in frailty and a decrease in MMSE-E scores. During the follow-up period, patients with moderate frailty, hypertension, diabetes mellitus, alcohol and tobacco use, low B12 levels, or hypothyroidism showed an increased risk of decrease in cognitive functions. Conclusions: There was a significant association between dementia prognosis and both frailty and biological deficits. We recommend the adoption of a syndemic approach in the follow-up of dementia, as we believe that the prevention of frailty and associated biological deficits will contribute to slowing dementia's clinical course.

Effect of treatment with sublingual vitamin B12 in patients with B12 deficiency

Introduction: The efficacy of the intramuscular administration of vitamin B12 is well established, but it is limited by the fact that it should be administered by a healthcare professional and the associated local injection site reaction. Aim: To investigate the effectiveness of sublingual vitamin B12 administration in patients with low serum B12 levels. Patients and Methods: This is a retrospective study including patients with low serum levels of B12 (&lt;200 pg/mL) and treated with 1000 μg/day sublingually (B12-SOLGAR®) for 3 months. Subjects’ main characteristics and personal history were recorded, as well as laboratory parameters before and 3 months after therapy initiation. Results: 314 patients (men: 43%, age: 64 [54-75] years) were included in this study. Most participants were on metformin (48%) and/or a proton pump inhibitor/H2 antagonist (50%). The administration of sublingual vitamin B12 was associated with a significant increase in serum B12 levels (from 182 [152-196] to 403 [312-590] pg/mL, p&lt;0.05). Likewise, a significant increase was also noted in the patients with very low vitamin B12 levels (&lt;100 pg/mL, n=21) (from 85 [74-92] pg/mL to 298 [294-340] pg/mL, p&lt;0.05). Furthermore, significant improvements in hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white blood cells, and platelets were observed. Conclusions: The sublingual administration of vitamin B12 (1000 μg/day) for 3 months in patients with low B12 serum levels results in significant increases of B12 levels and improves hematologic parameters, and thus may be considered as an alternative to the intramuscular administration.

Factors associated with an increased risk of vitamin B12 deficiency in patients with type 2 diabetes mellitus on metformin

ABSTRACTBackgroundMetformin is used to treat type 2 diabetes mellitus, but prolonged use has been associated with vitamin B12 deficiency. Many other factors have also been associated with vitamin B12 deficiency. Studies on the possible additive effect of risk factors for developing a vitamin B12 deficiency are lacking.AimThe objective of this study was to assess the correlation between other known risk factors for vitamin B12 deficiency among patients with type 2 diabetes mellitus prescribed metformin who had a vitamin B12 deficiency.MethodFor inclusion in this single‐centre, retrospective cohort study, patients needed to be at least 18 years old, diagnosed with type 2 diabetes, taking metformin for at least 2 years and actively taking metformin during the study period. The primary outcome was the rate of low B12 levels with metformin. Secondary outcomes were risk factors associated with B12 deficiency. The patient and clinical characteristics were compared between the two study groups using Student's t‐test for continuous variables and chi‐squared tests for categorical variables. This project was exempt due to the local policy requirements that constitute research by the University of Arkansas for Medical Sciences Institutional Review Board (IRB) (IRB Program Manager, 11 August 2021). The justification for this ethics exemption was as follows: the project was determined to be of minimal risk to privacy of subjects because the research team had mechanisms to protect the personal health identifiers from improper use or disclosure; to destroy the identifiers at the earliest opportunity consistent with the conduct of research, and provided assurance that the identifiers will not be re‐used or disclosed to any other person or entity, except as required by law, for authorised oversight of the research project, or for other research as permitted by the HIPAA regulations.ResultsA total of 387 patients were included in this study, from which 364 patients had a vitamin B12 deficiency. The cohort was an average 69‐years‐old and predominantly female (66%). No risk factors were associated with a higher incidence of B12 deficiency. Patient age (p = 0.0063) and time on metformin (p = 0.0144) were significantly and negatively correlated with B12 deficiency.ConclusionYounger age and shorter duration of metformin use may increase the risk of vitamin B12 deficiency. Although guidelines recommend occasional checks, only 21% of patients had vitamin B12 levels assessed during the study period.

Diet Pattern Analysis in Alzheimer's Disease Implicates Gender Differences in Folate-B12-Homocysteine Axis on Cognitive Outcomes.

Low plasma B12 and folate levels or hyperhomocysteinemia are related to cognitive impairment. This study explores the relationships among diet pattern, blood folate-B12-homocysteine levels, and cognition measurement in Alzheimer's disease (AD) while exploring whether a gender effect may exist. This cross-sectional study enrolled 592 AD patients (246 males, 346 females) and the demographic data, blood biochemical profiles, Mini-Mental State Examination (MMSE), and a Food Frequency Questionnaire (FFQ) for quantitative assessment of dietary frequency were collected. Structural Equation Modeling (SEM) was employed to explore the associations among dietary patterns, blood profiles, and cognition. A least absolute shrinkage and selection operator regression model, stratified by gender, was constructed to analyze the weighting of possible confounders. Higher MMSE scores were related to higher frequencies of coffee/tea and higher educational levels, body mass index, and younger age. The SEM model revealed a direct influence of dietary frequencies (skimmed milk, thin pork, coffee/tea) and blood profiles (homocysteine, B12, and folate) on cognitive outcomes. At the same time, the influence of dietary pattern on cognition was not mediated by folate-B12-homocysteine levels. In males, a direct influence on the MMSE is attributed to B12, while in females, homocysteine is considered a more critical factor. Dietary patterns and blood profiles are both associated with cognitive domains in AD, and there are gender differences in the associations of dietary patterns and the levels of B12 and homocysteine. To enhance the quality of dietary care and nutritional status for individuals with dementia, our study results still require future validations with multi-center and longitudinal studies.

B12 deficiency-related glossitis is highly associated with high gastrin-17 and low pepsinogen I.

The causes of vitamin B12 (B12) deficiency are varied and mainly related to gastric disorders. Glossitis is a common oral manifestation of B12 deficiency and is often first seen by dentists. This study aimed to investigate the correlation between B12 deficiency-related glossitis (B12-def glossitis) and gastric serum biomarkers [gastrin-17(G17), pepsinogen I (PGI), pepsinogen II (PGII), and anti-Helicobacter pylori (H. pylori) antibodies], and preliminarily discuss the etiology of B12-def glossitis. A cross-sectional study was conducted in patients complaining of glossodynia, burning sensation, or severe recurrent oral ulcers, but patients with a history of gastrectomy were excluded. All subjects underwent a uniform oral examination and hematological tests. Of 243 patients, 133 with B12-def glossitis were in the case group, and 110 with other oral mucosal diseases (non-glossitis) and normal B12 levels were in the control group. In the case group, 84.2% (112/133) showed high G17 and low PGI levels (G17hi PGIlow ). Univariate logistic regression showed that G17hi PGIlow was a high-risk factor for B12-def glossitis (OR: 92.44; 95% CI: 35.91, 238.02). Subgroup analyses in the case group showed that the G17hi PGIlow group presented with lower B12 levels and a lower positive rate of anti-H. pylori antibodies compared to the non-G17hi PGIlow group. Gastric serum biomarkers in patients with B12-def glossitis generally showed G17hi PGIlow , suggesting possible atrophy of gastric corpus and fundus mucosa. The G17hi PGIlow and non-G17hi PGIlow groups may represent different etiologies of B12 deficiency.

Prevalence and Time Trends of Low Serum B12 Levels and Inadequate B12 Dietary Intake in Lebanese Adults amidst the Food Insecurity Situation: Findings from a Nationally Representative Cross-Sectional Study.

Rising food insecurity (FI) and the increased prices of animal-based foods could compromise vitamin B12 (B12) intake and serum levels in food-insecure people. Our study aims to determine the prevalence of low levels of serum B12 and its inadequate dietary intake among a nationally representative sample of Lebanese adults aged 18 to 64 years, while exploring the impact of FI and identifying other potential predictors. The B12 intake was assessed using a food frequency questionnaire and the mean of two non-consecutive 24 h recalls. The B12 serum levels were also examined. To examine the time trends in the B12 serum levels and dietary intake, the data from a large representative digitized database of 6290 participants were collected, along with the examination of FAOSTAT food consumption data both before and during the economic crisis period. Our findings revealed that 47.3% of households in Lebanon experienced FI. The inadequate intake of B12 food sources was prevalent in 52.5% of participants, and 61.1% presented with low (23%) or intermediate (38.1%) levels of serum B12. The food-secure households had a higher proportion of B12 intake from meats (p = 0.004), while traditional foods contributed more to food-insecure households (p = 0.000). The participants who were female, unemployed, food-insecure, and had low dietary diversity were about two to three times more likely to have inadequate B12 intake. The predictors of low levels of serum B12 included residing in Beqaa (OR = 2.856 and 95% CI = 1.018-8.01) and having inadequate B12 intake (OR = 1.788 and 95% CI = 1.2-2.65). The findings from observing the time trends in the consumption and the serum levels of B12 indicate a considerable decline in the consumption of most animal-based foods compared to the pre-crisis period, associated with a decline in the serum levels of B12. In conclusion, an alarming prevalence of low dietary intake and low serum levels of B12 was revealed among Lebanese adults, and the indirect effect of FI on B12 serum levels mediated through B12 intake was inferred.

Importance of Raised Serum Homocysteine Levels in Ischemic Stroke Patients

Background: Around 5.5 million people die from stroke each year, making it the second leading cause of mortality worldwide. Increased homocysteine levels lead to early neurological deteriorations in ischemic stroke and may have an association with other risk factors of stroke. Objective: To determine how closely homocysteine levels are associated with other risk factors for ischemic stroke. Methods: This is a cross-sectional study, which was performed in the Department of Neurology, Liaquat National Hospital, Karachi from January to December 2021. All ischemic stroke patients of either gender above the age of 16 were included. Ischemic stroke was identified by neuroimaging MRI in patients presenting with focal neurological deficits lasting more than 24 hours. For statistical analysis, data was entered into SPSS version 21. Results: A total of 100 patients were included in the study with a mean age of 56.8 ± 15.6 years. Most of the patients were males (65%). Hypertension and diabetes were present in 76% and 42% of patients respectively. 45% of patients had homocysteine levels &lt;15 μmol/l while 55 % had raised homocysteine levels. Amongst them, 42% had levels of homocysteine in the range of 15-30 μmol/l (mild) whereas 13% had &gt;30 μmol/l homocysteine levels (intermediate). None of them had a level &gt;100 μmol (severe). On univariate analysis, the odds of increasing homocysteine levels were higher in males than females. Increasing B12 levels were associated with decreased odds of intermediate homocysteine levels. On the multivariable model after adjusting the model with other covariates, increasing B12 levels remained associated with homocysteine levels with a lower likelihood of intermediate homocysteine levels. Conclusion: According to the results of our study, there is a strong correlation between high homocysteine levels and low B12 levels, making homocysteine a substantial risk factor for ischemic stroke. Vitamin B12 has a major role in homocysteine pathomechanisms and its deficiency predisposes to hyperhomocysteinemia and hence stroke. Larger multicenter studies may be done to evaluate the role of B12 as a homocysteine-lowering agent both for the treatment and prevention of ischemic stroke.

Vitamin B12 Deficiency and Hemolytic Anemia Presenting As Pseudo Thrombotic Microangiopathy: A Systematic Review

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.

Low Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the ”Bambino Gesù Children Hospital”, a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = −0.31, p &lt; 0.001, BCa 95% −0.38, −0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = −0.33, p = 0.008, BCa 95% −0.53, −0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = −0.003 (−0.007, −0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and &lt;0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and &lt;0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.

Abstract 12719: The Association of High Vitamin B12 With Mortality Risks and Related Metabolisms Among Hypertensive Population

Background: The association of high serum vitamin B12 (B12) with mortality risks is not well studied, and its independence from related metabolites needs to be disentangled. This study aims to explore the association of high serum B12 levels with all-cause mortality and its interaction with serum folate and plasma total homocysteine (tHcy) among Chinese adults with hypertension. Methods: This large observational study obtained data from the China Stroke Primary Prevention Trial (CSPPT), a multi-center RCT. The study sample consisted of 9,695 hypertensive adults who were not exposed to B vitamin supplements at baseline and during follow-up. The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. Patients were stratified by B12 tertiles, and previously published cutoffs: B12 &lt; 299.52 pg/ml included patients with circulating B12 deficiency and sub-optimal deficiency; B12 &lt; 349.69 pg/ml with concomitant elevated tHcy determines B12 metabolic deficiency; B12 ≥ 349.69 ng/ml refers to those who are free from both circulating and metabolic B12 deficiency. Results: During the median follow-up time of 4.5 years, 284 deaths occurred. Compared to individuals with lower B12 levels, those with elevated B12 showed increased risk of all-cause mortality (hazard ratio (HR), 1.41 95%CI 1.07-1.85) and cardiovascular mortality (HR, 3.01; 95% CI 1.30-7.01). The association between elevated B12 and all-cause mortality risk appears robust in all tested subgroups. After excluding those with potential B12 metabolic deficiency, elevated B12 remains significantly and independently associated with all-cause mortality (HR, 1.36 95%CI 1.05, 1.76) and cardiovascular mortality (HR, 2.44 95%CI 1.15, 5.18). The Bayesian kernel machine regression results showed that higher B12 is associated with increased all-cause mortality risk independent of baseline folate and tHcy. Conclusion: Among Chinese adults with hypertension, elevated B12 levels is associated with increased risk of all-cause mortality, independent of baseline folate, tHcy, and other traditional risk factors. These findings, if further confirmed, have important implications for nutritional counseling and clinical recommendations on B vitamin therapy.

Cerebral venous thrombosis and B12 deficiency

Infants with prematurity and necrotizing enterocolitis (NEC) are at increased risk for short bowel syndrome and subsequent nutritional deficiencies. In particular, ileal resection is associated with vitamin B12 malabsorption, which interferes with normal myelination and homocysteine metabolism.1, 2 Vitamin B12 deficiency is associated with neurodevelopmental delay as well as hyperhomocysteinemia, which increases the risk for venous thrombosis.2, 3 This eight-year-old boy presented with severe headache, dehydration, and lethargy. He developed acute onset severe frontal headache followed by decreased oral intake, decreased urine output, and recurrent vomiting. The headache was dull and radiating to the back of his head. At the same time, he appeared to be sleepy and less active. These symptoms lasted for two to three days before he was brought to the primary doctor's office and then referred to the emergency department. On assessment, he was tired-looking and exhibited mild microcephaly, but his neurological examination was normal, as was an examination by an ophthalmologist. He experienced mild global developmental delay. He was born at 25 weeks gestational age and had a prolonged stay in the neonatal intensive care unit, complicated by NEC and a hemicolectomy with ileostomy and removal of ileocecal valve. He had low normal levels of B12 for several years prior to presentation and was not treated (151 pg/ml after surgery [normal 160-950]). Brain magnetic resonance imaging and magnetic resonance venography (MRV) showed filling defects in the inferior sagittal, straight, torcula, and proximal transverse sinuses consistent with cerebral venous sinus thrombosis (CVST) with no evidence of acute infarction (Figure 1). Dehydration was initially considered to be the cause. Enoxaparin sodium was started at 1 mg/kg every 12 h with the goal of anti-Xa level between 0.5 and 1.0 U/ml. The hypercoagulation evaluation was normal. The B12 level was 86 pg/ml. His hematocrit was 33.3, and his mean corpuscular volume (MCV) was 87.4. He was not treated at that time. He was discharged within a week after the repeat imaging remained stable with the goal to continue enoxaparin sodium for three months. After three months, he again developed headache and lethargy, and MRV showed a new thrombus. Enoxaparin was switched to warfarin. After a year of warfarin, the clot resolved but he still had headaches. Two B12 levels were obtained, both below 200. His anemia worsened (hematocrit 24.7) and his MCV increased to 96.9. The homocysteine level was 184 μmol/L (normal <11.4). At this point, he began B12 injections (1000 mcg daily for one week followed by monthly and then quarterly injections thereafter). His B12 levels normalized and remained normal throughout his course. The warfarin was discontinued and thrombus has not recurred. Our patient had a difficult-to-treat CVST secondary to a condition predisposing to nutritional deficiency. His chronic B12 deficiency was overlooked by his treating physicians until he presented with a profound deficiency with megaloblastic anemia. The association between B12 deficiency and CVST has been described in children with nutritional deficiency and megaloblastic anemia.4 Previous authors suggested that testing for hyperhomocysteinemia and with B12 supplementation should be considered in pediatric patients with CVST.5 The diagnosis becomes even more crucial in patients with conditions known that promote nutritional deficiencies, such as a history of NEC and ileal surgery. In such children, early recognition of vitamin B12 deficiency and timely vitamin supplementation may prevent the occurrence of CVST as well as other manifestations of B12 deficiency, such as developmental delay.6, 7 In this patient, the B12 deficiency was chronic. While it is difficult to prove that the deficiency caused the CVST, it likley played a substantial role. Hyperhomocysteinemia can damage the vascular endothelium, predisposing to thrombus formation.8, 9 Consequently, vitamin B12 deficiency is a potential risk factor in children with CVST. Fatemeh Mohammadpour Touserkani: Conceptualization; supervision; writing – original draft; writing – review and editing. Theodora Andriotis: Conceptualization; investigation; writing – original draft; writing – review and editing. Yaoping Zhang: Conceptualization; supervision; writing – original draft; writing – review and editing. Steven Pavlakis: Conceptualization; supervision; writing – original draft; writing – review and editing. We would like to thank the patient's parents for their consent for this publication. The authors declare no conflict of interest.

Co-Administration of Vitamins B12 and D During Pregnancy Have Strong Neuroprotective Effects in Parkinson Disease.

Parkinson's disease (PD) is a common disease whose pathophysiological mechanism is not well understood. Recent research studies have shown that PD patients have low serum levels of vitamins B12 and D. Therefore, in this study, the effects of supplementation with vitamins B12 and D on PD female mice as well as their fetuses were studied. After preparation of female mice and induction of Parkinson's by rotenone administration for 19days, rotarod test was used to confirm PD induction. During this time, supplementations with vitamins B12 and D were performed. On day 19, after confirmation of PD induction, half of the mice were killed and the other half were allowed to mate with males. Viability was measured by the MTT method, and apoptosis and necrosis of cerebellar neurons were measured by flow cytometry. The RT-PCR technique was used to evaluate the relative expressions of the bax, bcl-2, miR-211, and circRNA 0,001,518 genes. Data analysis was performed by the GraphPad Prism V.8 software. Co-administration of vitamins B12 and D resulted in highest viability percentage and greatest reduction in apoptosis and necrosis of cerebellar neurons in the female mice as well as their fetuses compared to the PD females. A decrease in the relative expression of the bax and miR-211 genes and an increase in bcl-2 expression were observed in the cerebellar tissue of PD mice receiving both vitamins. Vitamins B12 and D have neuroprotective effects on PD conditions. Therefore, co-administration of these two vitamins is recommended in PD patients during pregnancy.

Dermatologic Manifestations in Vitamin B12 Deficiency: A Review

Vitamin B12, also known as cobalamin, is a water-soluble vitamin primarily obtained from animal-based foods. It is crucial for hematopoietic cell formation, with methylcobalamin and adenosylcobalamin being its active forms. The metabolic process involves stomach release, binding to proteins, and absorption in the ileum with intrinsic factor. The liver stores B12, but deficiency can occur due to dietary, absorption, transportation, or metabolic issues. Causes of low B12 levels include dietary choices, gastrointestinal diseases, and medications likemetformin. Dermatological changes associated with deficiency, such as hyperpigmentation, can occur, possibly due to decreased glutathione and increased melanin production. Vitamin B12 deficiency has a wide range of symptoms, from asymptomatic to severe neurological impairments, but its dermatologic effects have been under-represented in literature.” Keywords: Vitamin B12 deficiency, dermatologic manifestations

Cognitive Decline Related to Diet Pattern and Nutritional Adequacy in Alzheimer's Disease Using Surface-Based Morphometry.

Dietary pattern (DP) results in nutrition adequacy and may influence cognitive decline and cortical atrophy in Alzheimer's disease (AD). The study explored DP in 248 patients with AD. Two neurobehavioral assessments (intervals 13.4 months) and two cortical thickness measurements derived from magnetic resonance images (intervals 26.5 months) were collected as outcome measures. Reduced rank regression was used to assess the groups of DPs and a linear mixed-effect model to explore the cortical neurodegenerative patterns. At screening, underweight body mass index (BMI) was related to significant higher lipid profile, impaired cognitive function, smaller cortical thickness, lower protein DP factor loading scores and the non-spouse caregiver status. Higher mini-mental state examination (MMSE) scores were related to the DP of coffee/tea, compared to the lipid/sugar or protein DP group. The underweighted-BMI group had faster cortical thickness atrophy in the pregenual and lateral temporal cortex, while the correlations between cortical thickness degeneration and high HbA1C or low B12 and folate levels were localized in the medial and lateral prefrontal cortex. The predictive model suggested that factors related to MMSE score were related to the caregiver status. In conclusion, normal or overweight BMI, coffee/tea DP group and living with a spouse were considered as protective factors for better cognitive outcomes in patients with AD. The influence of glucose, B12 and folate on the cortical degeneration was spatially distinct from the pattern of AD degeneration.

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

SYNERGISTIC EFFECT OF HIGH HOMOCYSTEINE AND LOW VITAMIN B12 LEVELS ON THE PREVALENCE OF ATRIAL FIBRILLATION IN HYPERTENSIVE PATIENTS

Objective: Atrial fibrillation (AF) is common arrhythmia in hypertensive patients. Besides hypertension, several other conditions are deemed to be associated with AF. High blood homocysteine levels (hyperhomocysteinemia) is a known risk factor for cardiovascular disease and are associated with vitamin B12 deficiency that possibly increase cardiovascular risk, as well. The present study assessed the possible effect of high homocysteine and low B12 levels on AF prevalence in hypertensive patients. Design and method: This retrospective study comprised all hypertensives referred to our institutions and had a blood sample measurement of homocysteine and B12 (n = 32800). The presence of sustained AF (SAF; Long-standing/Persistent or Permanent AF) was recorded with a resting electrocardiogram (ECG). Paroxysms of AF (PAF) were confirmed with previous relevant ECGs provided by the patient. The population was divided in quartiles according to homocysteine levels (groups 1, 2, 3 and 4 for increasing levels) and B12 levels (groups 1, 2, 3 and 4 for decreasing levels). The prevalence of AF (SAF and PAF) was calculated for each homocysteine and B12 quartile group as well as for each of the 16 homocysteine/B12 combination quartile subgroups. Results: The mean values for homocysteine were 13.3 ± 7.2 ?mol/l and for B12 525 ± 196 pg/ml. The prevalence of SAF, PAF and all-type AF (SAF and PAF) was 5.0%, 6.1% and 11.1%, respectively. For homocysteine quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 5.3%, 11.7%, 24.3% (pfor trend 0.049), PAF prevalence was 0.6%, 0.9%, 4.6%, 14.0% (pfor trend 0.090) and all-type AF prevalence was 3.2%, 5.4%, 11.5%, 22.2% (pfor trend 0.051), respectively. For B12 quartiles 1, 2, 3, 4, SAF prevalence was 2.9%, 6.4%, 11.0%, 20.2% (pfor trend 0.030), PAF prevalence was 2.5%, 5.1%, 7.7%, 9.0% (pfor trend 0.009) and all type-AF prevalence was 2.4%, 7.1%, 16.8% 21.0% (pfor trend 0.019), respectively. The synergistic effect of increasing homocysteine and decreasing B12 values on SAF, PAF and all-type AF prevalence is presented in Figure. Conclusions: High homocysteine levels and low vitamin B12 levels are individually and synergistically associated with the prevalence of AF in hypertensive individuals. Underlying mechanisms merit further examination.

Multiple myeloma with CNS involvement in the form of leptomeningeal carcinomatosis presenting as Vitamin B12 deficiency

A 75-year-old male presented with lower back pain, bilateral lower extremity weakness, decreased sensation to vibration and proprioception in lower extremities, anemia, and vitamin B12 deficiency. The MRI of the lumbar spine revealed extensive leptomeningeal carcinomatosis. Subsequently, the patient was diagnosed with multiple myeloma (MM) and B12 deficiency with negative intrinsic factor antibodies. MM can present as extramedullary hematopoiesis (EM) to involve the central nervous system (CNS). CNS involvement is rare and develops in only around 1% of MM patients. It carries a poor prognosis with less than 6 months survival. MM is thought to be associated with both B12 deficiency and pernicious anemia. Some studies have even suggested B12 deficiency as a possible marker for worsening disease and a prognostic factor. In our patient’s case, he had extensive CNS involvement at diagnosis of MM with very low B12 levels. The extent of his disease with extensive CNS involvement, which carries a poor prognosis, could possibly explain the very low levels of B12. This is the first reported case of a patient presenting with B12 deficiency found to have MM with leptomeningeal carcinomatosis at diagnosis. To the author’s knowledge, there is no literature investigating association between B12 deficiency at the time of diagnosis of MM with CNS complications. Furthermore, there are no established guidelines on treatment for leptomeningeal myelomatosis. We present this case with the effort to learn more about this disease in terms of response and overall survival.

An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes

ABSTRACT Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis. Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0–500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR). A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes. In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.