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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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemical fortification and dose supplementation of vitamin B12 are widely implemented to combat deficiency symptoms. However, in situ, fortification of vitamin B12 in food matrixes can be a promising alternative to chemical fortification. The present study aimed to produce vitamin B12‐rich, probiotic guava juice fermented with Levilactobacillus brevis strain KU15152. Pasteurized fresh guava juice was inoculated with 7.2 log CFU mL−1L. brevis strain KU15152 and incubated for 72 h at 37 °C anaerobically. The antioxidants, total phenolic compounds, vitamin B12 production, sugars, organic acids, pH and viable count were analyzed at 24, 48 and 72 h of incubation. The fermented juice was stored at 4 °C, and the changes in its functional properties were analyzed at 7‐day intervals up to 28 days of storage. RESULTS: During fermentation, the bacteria cell count was increased from 7.01 ± 0.06 to 9.76 ± 0.42 log CFU mL−1 after 72 h of fermentation and was decreased to 6.94 ± 0.34 CFU mL−1 during storage at 4 °C after 28 days. The pH, total soluble solids, crude fiber, citric acid and total sugars decreased, while titratable acidity, total protein, antioxidants, phenolic compounds and lactic acid contents increased during fermentation. The fermented guava juice exhibited higher 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS)) radical scavenging activities (85.97% and 75.97%, respectively) at 48 h of fermentation. The concentration of active vitamin B12 in the sample reached 109.5 μg L−1 at 72 h of fermentation. However, this concentration gradually decreased to 70.2 μg L−1 during the storage period. During storage for 28 days at 4 °C, both the fermented and control guava juices exhibited a decline in antioxidant and phenolic compound concentrations. Furthermore, the addition of 20% honey and guava flavor enhanced the organoleptic properties and acceptability of fermented guava juice. CONCLUSION: The value‐added fermented guava juice could be a novel functional food product to combat vitamin B12 deficiency. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin B12 is an essential micronutrient involved in various metabolic processes, including DNA synthesis and neurological function. B12 deficiency can lead to significant hematological and neurological disorders. This study aimed to evaluate changes in serum vitamin B12 levels in patients admitted to the internal medicine department over the past 5 years and examine their relationship with admission diagnosis. Methods: This retrospective study included 500 patients hospitalized in the Internal Medicine Department at University of Health Sciences Turkey, İstanbul Training and Research Hospital between January 2020 and 2024. Patient data were obtained from the hospital information system and categorized according to demographic variables, reason for hospitalization, chronic diseases, vitamin B12 supplementation, metformin use, and serum vitamin B12 levels. Results: The study cohort comprised 500 patients with a mean age of 63.1 years. No significant differences in B12 levels were found between different age groups or genders, nor across the years studied. However, patients hospitalized for pancreatitis and those using metformin had significantly lower B12 levels (p<0.05), whereas patients in palliative care or those with malignancies had significantly higher levels (p<0.05). The use of vitamin B12 supplements was correlated with significantly higher serum B12 levels (p<0.05). Conclusion: The serum vitamin B12 levels of patients admitted to the internal medicine department remained stable over the past 5 years. However, certain subgroups, such as patients with pancreatitis, malignancies, and metformin use, exhibited significant variations in B12 levels. Regular monitoring of B12 levels in high-risk groups, such as patients with diabetes receiving metformin, is recommended to prevent deficiency-related complications. Elevated B12 levels in patients with cancer should prompt further investigation into the underlying malignancies. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency is usually simple to diagnose. However, our patient demonstrates that in difficult cases, the ordinary clinician may need a transdisciplinary approach. The finding of a double haploinsufficiency as a possible cause of vitamin B12 deficiency in our patient, illustrates the usefulness of performing large panel clinical exome sequencing. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report emphasizes the crucial need to include vitamin B12 deficiency in the differential diagnosis of hemolytic anemia, despite its rarity as a presentation. The case illustrates that non‐immune hemolytic anemia can occur secondary to severe vitamin B12 deficiency, which can be effectively treated with vitamin B12 supplementation. Early recognition and comprehensive evaluation are essential for identifying this uncommon yet significant cause of hemolysis, ensuring prompt and appropriate treatment to improve patient outcomes. [ABSTRACT FROM AUTHOR]

ABSTRACT: Purpose: Undernutrition in children is a critical worldwide concern that hampers both their physical and cognitive growth. The nutritional status of school-going children and adolescents remains insufficiently addressed with no comprehensive data. This is the first study from the Himalayan foothills that aims to assess the clinical and laboratory aspects of anemia with micronutrient status in undernourished children above the age of five along with association of clinical features with anemia severity. Materials and Methods: A cross-sectional study was conducted involving children aged 5-18 years with undernutrition in a tertiary hospital in North India over eighteen months. We observed the prevalence of anemia, its morphological type, micronutrient status, clinical features, and demographic parameters of these children. The association of various clinical features and anthropometric parameters with the severity of anemia was determined. Results: Of the 200 children who were enrolled in the study, 77% were found anemic, with the proportion of mild, moderate, and severe anemia being 18.2%, 46.8%, and 35%, respectively. Iron (67%) was the most common micronutrient deficient in these children with a significant number suffering from vitamin B12 (53.9%) deficiency. Folic acid deficiency was relatively low (10.4%). Body mass index (P = 0.009), fatigability (P = 0.001), pallor (P ≤ 0.001), poor academic performance (P = 0.023), and knuckle hyperpigmentation (P = 0.018) were significantly associated with the severity of anemia. Conclusion: Despite the significant tread in various aspects of human development, undernutrition and anemia remain a formidable challenge, especially in developing countries. A high proportion of anemia in undernutrition indicates the gravity of the issue, yet not received the deserved attention. [ABSTRACT FROM AUTHOR]

Introduction: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDS) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing loss or DM. Case Presentation: We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy, and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing-based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later hemoglobin levels and bone marrow morphology had normalized. Conclusion: Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS. [ABSTRACT FROM AUTHOR]

This document explores the relationship between antiepileptic drugs (AEDs), folate, one-carbon metabolism, genetics, and epigenetics. It highlights the potential complications that can arise from AEDs interfering with folate metabolism, such as cognitive, mood, and psychiatric issues. The document also discusses the risks associated with the use of valproate, a commonly used AED, and emphasizes the importance of folic acid supplementation during pregnancy, especially for women taking AEDs. Further research is needed to fully understand the mechanisms involved and develop preventive measures. The document does not provide any specific recommendations or conclusions. [Extracted from the article]

The identification of vitamin B12 (B12) deficiency in the newborn may prevent neurological damage and a delay in the normal growth. In this study we characterized the incidence of B12 deficiency in newborns, the costs associated to the clinical diagnosis and management, and the relevance to optimize the use of cobalamin biomarkers during treatment follow-up.Starting from a continuous case series of 146,470 screened newborns (November, 1st 2021- December, 3rd 2023), the Regional Reference Laboratory for Neonatal Screening identified 87 newborns having altered levels of biomarkers of cobalamin metabolism measured by Newborn Screening. These subjects were confirmed with a nutritional B12 deficiency of maternal origin by performing the serum B12 measurements and plasma homocysteine (Hcy) both on the newborns and respective mothers. A cost analysis was performed to characterize the costs/year of identifying and managing B12 deficiency cases.At baseline, median (interquartile range) serum B12 levels of 185.0 (142.3–246.0) ng/L and threefold increased plasma Hcy concentrations above the normal level confirmed a severe condition of deficiency in the newborns. After intramuscular B12 supplementation, serum B12 measured at the first follow up visit showed a fivefold increase, and the levels of Hcy returned to normal. From the healthcare perspective, the costs for diagnosing and managing all newborns with B12 deficiency is 188,480 €/year.Preventing B12 depletion in newborns lowers healthcare costs and likely improves their health outcomes. Further studies are however required to address the clinical pathway to identify, treat and monitor pregnant women with marginal and low B12 status, in order to achieve these goals. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin B12 is an essential micronutrient involved in various metabolic processes, including DNA synthesis and neurological function. B12 deficiency can lead to significant hematological and neurological disorders. This study aimed to evaluate changes in serum vitamin B12 levels in patients admitted to the internal medicine department over the past 5 years and examine their relationship with admission diagnosis. Methods: This retrospective study included 500 patients hospitalized in the Internal Medicine Department at University of Health Sciences Turkey, İstanbul Training and Research Hospital between January 2020 and 2024. Patient data were obtained from the hospital information system and categorized according to demographic variables, reason for hospitalization, chronic diseases, vitamin B12 supplementation, metformin use, and serum vitamin B12 levels. Results: The study cohort comprised 500 patients with a mean age of 63.1 years. No significant differences in B12 levels were found between different age groups or genders, nor across the years studied. However, patients hospitalized for pancreatitis and those using metformin had significantly lower B12 levels (p

Objective: This systematic review and meta-analysis aimed to evaluate the vitamin B12 status and intake of Seventh-day Adventists following a plant-based diet and compare it with omnivore controls to investigate their susceptibility for vitamin B12 deficiency. Data Source: Peer-reviewed articles were identified through a comprehensive search in PubMed, Scopus, and Google Scholar databases from inception up to the year 2024 using specific keywords related to vitamin B12 and Seventh-day Adventists. Study Inclusion and Exclusion Criteria: Observational studies published in the English language were included if they reported on vitamin B12 status or intake among plant-based Adventists and compared it with omnivore controls who may or may not have been Adventists. Studies that did not present distinguishable results for vegetarian/vegan from omnivore Adventists or only reported on food item intake without specific vitamin B12 data were excluded. Data Extraction: Two independent reviewers extracted data on study characteristics, vitamin B12 intake, and serum levels using a customised data extraction form, resolving discrepancies through consultation with a third reviewer. Data Synthesis: A meta-analysis was conducted using random-effect models due to anticipated heterogeneity, without any subgroup analysis due to the low number of studies. Sensitivity analysis was performed using the 'leave-on-out' method to assess individual study influence on overall effect size and heterogeneity. Results: Four studies met inclusion criteria, encompassing 1994 participants. Meta-analysis showed no significant differences in serum vitamin B12 levels (MD: −9.85 pmol/L; 95% CI: −45.64 to 25.94 pmol/L; P = 0.54, I2 = 50%) or daily intake (MD: 3.31 mcg/d; 95% CI: −4.70 to 11.32 mcg/d; P = 0.42, I2 = 90%) between plant-based Adventists and omnivore controls, although there was high heterogeneity between the studies. Conclusion: Adventists following a vegan or vegetarian diet did not demonstrate increased risk of vitamin B12 deficiency due to the widespread consumption of fortified foods and supplements. The findings underscore the importance of supplementation and the consumption of fortified foods for maintaining adequate B12 status among vegan or vegetarian Adventists but highlight the need for further studies to confirm these observations in diverse geographical areas. [ABSTRACT FROM AUTHOR]

Background: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition. Case presentation: In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS. Conclusions: In this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy. [ABSTRACT FROM AUTHOR]

Background: Metformin, widely used in diabetes treatment, is linked to reduced cobalamin (vitamin B12) levels, potentially exacerbating diabetic peripheral neuropathy (PN) and increasing the risk of lower limb amputations. Studies suggest that black individuals might be less prone to vitamin B12 deficiency, but the impact of metformin on vitamin B12 levels in this group is unclear. Objective: This study investigated the prevalence of vitamin B12 deficiency in diabetics on metformin and examined the relationship between metformin use and PN. Methods: A retrospective review of patient records from Edendale Hospital's diabetes clinic in Pietermaritzburg (January 1, 2017, to December 31, 2018) was conducted. Patients over 18 years of black descent with documented vitamin B12 levels were included. The study extracted data on diabetes treatment, vitamin B12 levels, and PN indicators. Results: Of 668 patients, 558 met the criteria. Metformin was used by 341 patients (61.1%), alone or with other treatments, while 217 (38.9%) did not use metformin. Glycaemic control was similar in both groups (median HbA1C 9.4% (IQR 7.8–11.0) in metformin users vs. 9.46% (IQR 7.1–11.0) in non-users, p = 0.80). Absolute vitamin B12 deficiency was equally rare in both groups (6 [1.8%] in metformin users vs. 4 [1.8%] in non-users, p = 1.0), but metformin users had significantly lower median vitamin B12 levels (299.0 pmol/l vs. 340.0 pmol/l in non-users, p < 0.05). PN prevalence was similar in both groups (31.7% in metformin users vs. 25.1% in non-users, p = 0.12). However, those with borderline-low vitamin B12 levels (≤ 269 pmol/l) had a higher risk of PN (OR 1.6; 95% CI: 1.1–2.3, p = 0.015). Conclusion: Metformin users showed lower median serum vitamin B12 levels than non-users, with an association between metformin use and borderline-low vitamin B12 levels. Higher metformin doses correlated with lower vitamin B12 levels, yet a direct link between metformin use and PN was not established. [ABSTRACT FROM AUTHOR]

Aims: Nutritional vitamin B12 deficiency remains a significant public health issue. This study aimed to compare the efficacy of an oral combination of thiamine, pyridoxine, cyanocobalamin, and parenteral cyanocobalamin treatment among adolescents with nutritional vitamin B12 deficiency. Methods: This retrospective study included patients aged 12-18 years who applied to University of Health Sciences Türkiye, Gülhane Training and Research Hospital General Pediatrics Polyclinic between 2018 and 2019, and serum vitamin B12 levels were measured before and after parenteral or oral combination of thiamine, pyridoxine, and cyanocobalamin treatment. Results: Of the subjects with post-treatment serum vitamin B12 levels above the target level of 200 pg/mL, parenteral cyanocobalamin was given to 34 patients with a median age of 16 years [interquartile range (IQR), 14 to 16 years], and girls (52.9%), and oral cyanocobalamin was given to 51 patients with a median age of 15 years (IQR, 13 to 16 years), and girls (58.8%). The mean serum vitamin B12 levels before parenteral and oral cyanocobalamin treatment were 150.32±6.49 pg/mL parenteral and 132.35±4.67 pg/mL in oral replacement groups (p>0.05). The mean serum vitamin B12 levels after parenteral and oral cyanocobalamin treatments were 566.0±62.77 pg/mL and 463.1±36.97 pg/ mL, respectively (p>0.05). Both parenteral and oral cyanobalamin treatments caused a significant increase in serum vitamin B12 levels compared with before treatment (p<0.001 for both). Conclusions: In adolescents with nutritional vitamin B12 deficiency, an oral combination of thiamine, pyridoxine, and cyanocobalamin may be preferred to parenteral cyanocobalamin because it is non-invasive and provides an increase in serum vitamin B12 levels similar to parenteral cyanocobalamin treatment. [ABSTRACT FROM AUTHOR]

Pernicious anaemia is a rare condition which is classed as an autoimmune disease. It is most frequently diagnosed in those over the age of 60, but can occur at any age. It presents with variable symptoms, many of which are shared with those of other diseases, making the condition difficult to diagnose, leading to missed diagnosis and a greater risk of complications. This article gives an overview of its diagnosis, management, and complications, with the aim of helping general practice nurses (GPNs) and non-medical prescribers recognise symptoms and get early treatment, reducing the risk of long-term adverse effects and improving quality of life for all those affected by this complex disease. [ABSTRACT FROM AUTHOR]

Background: Data have shown that vitamin B12 has immunomodulatory effects via different pathways, which could influence the pathophysiology of sepsis. The objective of this study was to investigate whether vitamin B12 levels, assessed by the measurement of holotranscobalamin (HTC), total vitamin B12 (B12), and methylmalonic acid (MMA, which accumulates in case of B12 deficiency), are associated with the development of sepsis in patients with onset of bacterial infection. Methods: This was a single-center, prospective observational pilot study. Adult patients who presented to the emergency department with bacterial infection confirmed by a positive microbiological culture result were included in the study and followed up for 6 days to assess whether they developed sepsis or not. The primary objective was to compare HTC concentration in patients who developed sepsis to those who did not develop sepsis. Secondary objectives were the evaluation of B12 and MMA concentrations in those two groups. Multiple logistic regression models were used, with presence of sepsis as the outcome variable, and HTC, B12, and MMA concentrations as predictor variables, separately, and adjusted for potential confounders. Results: From 2019 to 2022, 2131 patients were assessed for eligibility, of whom 100 met the inclusion criteria. One patient was excluded from the analysis due to missing data. Of the 99 patients, 29 developed sepsis. There was no evidence for an association between HTC or B12 concentration and the development of sepsis (OR 0.65, 95% CI 0.31–1.29, p = 0.232, OR 0.84, 95% CI 0.44–1.54, p = 0.584, respectively). There was an association between MMA concentration and the development of sepsis, with a positive effect, i.e. with increasing MMA, the odds for sepsis increased (OR 2.36, 95% CI 1.21–4.87, p = 0.014). This association remained significant when adjusted for confounders (OR 2.72, 95% CI 1.23–6.60, p = 0.018). Conclusions: Our study found an association between elevated MMA concentration and the development of sepsis. We did not find an association between HTC and B12 concentrations and the development of sepsis. Further, larger studies are warranted, as it could lead to interventional trials investigating whether B12 supplementation provides a clinical benefit to patients with infection or sepsis. Trial registration: The study was registered on ClinicalTrials.gov under the identifier NCT04008446 on June 17, 2019. [ABSTRACT FROM AUTHOR]

Vitamin B12, or cobalamin, is an essential nutrient required for diverse physiological functions secondary to its role as a critical cofactor for two mammalian enzymes, methionine synthase and methylmalonyl‐CoA mutase. While essential throughout all life stages, several pathways that require vitamin B12, including hematopoiesis, myelination, and DNA/histone methylation, are particularly critical during pregnancy and fetal development. This narrative review aims to describe vitamin B12 in pregnancy, with emphasis on the placenta's role in ensuring adequate nutrition of the fetus and impacts of vitamin B12 deficiency on placental development and function. Our literature search included preclinical model systems and human cohorts and interventions. Our review identified evidence of B12 deficiency resulting in impaired placental development, greater placental inflammation, and modulation of placental docosahexaenoic acid concentration, collectively suggestive of vitamin B12 deficiency as a determinant of both maternal and fetal health outcomes. Heterogeneity in study design complicated generalization of findings. Future studies should consider selecting a B12 marker that is relatively stable across pregnancy, such as holotranscobalamin, while accounting for important confounders such as maternal folate. [ABSTRACT FROM AUTHOR]

Background: The prevalence of vitamin B12 deficiency is found to coexist in hypothyroid patients, causing the persistence of symptoms concomitant to both diseases even on adequate thyroxine supplementation. Aims & Objectives: To assess the prevalence of Vitamin B12 deficiency among hypothyroid patients. Materials & Methods: A cross sectional study was conducted among 50 patients. Haemoglobin (Hb), mean corpuscular volume (MCV), anti thyroid antibodies, thyroid function tests and vitamin B12 levels were measured. In Mean age was 42.4 years. 36(72%) were females and rest 14 were males. Vit B12 defiency was seen in 31(62%) patients with mean TSH of 4.3 was seen. 72% of them were already receiving levothyroxine therapy with mean dose of 98.4μg was seen. Conclusion: There is a high (62%) prevalence of B12 deficiency in hypothyroid patients. Just the symptoms are not a good guide to determining presence of B12 deficiency. Screening for vitamin B12 levels should be undertaken in all hypothyroid patients, irrespective of their thyroid antibody status. [ABSTRACT FROM AUTHOR]

Aim: Vitamin B12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B12 dosage regimens in elderly vitamin B12‐deficient patients. Methods: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 μg cobalamin. Total vitamin B12, holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90. Results: Both dosage regimens resulted in a rapid increase of vitamin B12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B12 of 1090 pmol/L (reference 350‐650 pmol/L) concentration after 14 days. Following weekly administration, B12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B12 of 717 pmol/L after 90 days. Conclusions: Intranasal vitamin B12 administration is an effective and suitable way to replenish and sustain vitamin B12 levels in elderly patients. [ABSTRACT FROM AUTHOR]

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Objective: Vitamin B12 deficiency, an essential vitamin for the human body, is common in Turkey, and infants are at risk in this regard. This study was intended to investigate the effect of vitamin B12 levels of breastfeeding mothers with infant vitamin B12 and homocysteine levels. Material and Methods: A total of 214 infants aged 1-6 months and their mothers who applied to the infancy outpatient clinic of İstanbul Medeniyet University Göztepe Training and Research Hospital were included in the study. In this study, vitamin B12 levels of the mothers, vitamin B12, folic acid, and homocysteine levels in the infants were primarily analyzed, and the associated risk factors were secondarily determined. Results: The rate of adequate vitamin B12 levels in infants was 20.09% (n=43), and the rate of normal homocysteine levels in mothers of infants with sufficient vitamin B12 and normal homocysteine levels was 383.93 pg/mL and 379.07 pg/mL. 66.27% sensitivity and 75.56% specificity were calculated when 220 pg/mL was taken as the vitamin B12 cut-off value, which predicts homocysteine elevation. Conclusion: This study predicted that only one in five infants had sufficient vitamin B12 levels, but if breastfeeding mothers had sufficient vitamin B12 levels, infants were much less likely to have vitamin B12 deficiency. Since adequate vitamin B12 levels are important for infants, especially in terms of neurodevelopment, we believe that it is necessary to evaluate pregnant women in our society in terms of vitamin B12 levels and to provide vitamin B12 support. [ABSTRACT FROM AUTHOR]

Introduction: Depression is common in patients with diabetes and it is known to be twice as frequent in patients with diabetes, as in the general population. Metformin, an anti-diabetic agent is commonly used in type 2 diabetes mellitus as a first line drug and long-term metformin treatment is a known pharmacological cause of vitamin B12 deficiency. Low serum B12 status in the general population is associated with a significant risk of depressive symptoms. Metformin has also been known to enhance antidepressant efficacy and improve cognition in preclinical studies. Objective: The aim of this study was to determine the association of metformin usage, serum vitamin B12 and depression in patients with type 2 diabetes. Methods: This cross sectional study was carried out from September 1st 2022 to October 31st 2022. Sociodemographic data was collected. Serum B12 was estimated and depression was diagnosed based on the Patient Health Questinnaire-9. Results: there was a strong negative correlation between serum B12 status and depression as assessed by PHQ-9 p≤0.000005. There was a moderate negative correlation between metformin dosage and serum B12 status p≤0.01. Conclusion: This study shows a significant negative relation between vitamin B12 and Patient Health Questionnaire-9 scores which indicate that lower the vitamin B12 value, higher is the PHQ-9 score that implies severity of depression. Similarly a negative correlation was observed between metformin dosage and serum vitamin B12 that implies larger doses of metformin tend to decrease the serum vitamin B12 levels. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is a very common nutritional deficiency in developing countries and is known to cause neurologic manifestations. However, relationship of Serum Vitamin B12 levels with appearance of neurologic manifestations remain unclear. Aim: To study the relationship of serum vitamin B12 levels with neurological manifestations in children 6 month to 5 years having vitamin B12 deficiency (using a cut-off 250 pg/dl). Methods: This observational analytical study included a single centre cohort of 80 children with Vitamin B12 deficiency (<250 picogram/dl) children aged between 6 months and 5 years in whom clinical manifestations were analysed. In all these children MRI brain was also performed. Results: Out of 80 cases enrolled, 49 (61.25%) were males and 31 (38.75%) were girls. 51(63.75%) cases were between 6 to 15 months. 38(47.50%) cases had severe vitamin B12 deficiency (<100 pg/dl) and remaining 42(52.50%) had mild to moderate vitamin B12 deficiency (100-250 pg/dl). 65% (52/80) cases presented with neurological manifestations and had significantly lower levels of serum vitamin B12 (90.86±58.78pg/dl) as compared to those not having Neurologic manifestations. Conclusion: Based on this study it is recommended that serum vitamin B12 levels between 160 to 250 pg/dl, between 90-160 pg/dl and <90 pg/dl should be categorised as mild, moderate and severe vitamin B12 deficiency states respectively. Early diagnosis and treatment is important to prevent neurological morbidity in these patients. [ABSTRACT FROM AUTHOR]

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger–Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency. [ABSTRACT FROM AUTHOR]

Cobalamin (Vitamin B12) is a cofactor for many enzymes, including those in bacteria, archaea, algae, and mammals. In humans, cobalamin deficiency can lead to pernicious anaemia as well as gastrointestinal and neurological disorders. In contrast to marine ecosystems, there is a great paucity of information on the role of soils and terrestrial plants in the supply of cobalt and cobalamin to microorganisms and animals. The content of cobalt cations in most soils is usually sufficient to maintain growth, and the density of cobalamin-producing soil prokaryotes is high in comparison to water bodies. The cobalt content of most soils is usually sufficient in comparison with water, and the density of cobalamin-producing soil prokaryotes is high. Therefore, terrestrial plants are an important cobalt source for cobalamin-producing rumen and gut prokaryotes. The major source of cobalamin for most other animals is the meat of ruminants as well as other animal-derived products, bacteria in insects, and coprophagy, e.g., by rodents. In addition, faecal deposits, and fertilizers as well as soil bacteria add to the cobalamin supply. However, those archaea and bacteria that do not produce cobalamin obtain this coenzyme or its analogues from the environment. Therefore, presence or absence of cobalamin-producing species in soil affects the whole soil microbiome. However, our knowledge concerning microbial producers and consumers of cobalamin in soils is still limited, despite some recent advances. The main reasons are a low cobalamin content in soils and challenging methods of determination. In this regard, advanced analytical knowledge and technical equipment are required, which are usually unavailable in soil laboratories. This review provides relevant methodological information on sample homogenization, extraction, concentration, and purification as well as analysis of cobalamin. [ABSTRACT FROM AUTHOR]

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The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60–35.40) vs. 22.95 mg/dL (17.60–33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678–1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG—33.8%, GA—50.2%, and AA—16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Vitamin B12 deficiency is common and is more frequent in low- and middle-income countries with a poor or inadequate diet of animal foods. In Ethiopia, researches related to the status of micronutrients in children are limited. Therefore, this study aimed to assess the prevalence of vitamin B12 deficiency and associated factors among primary school children. Methods: A cross-sectional study design was conducted from January 10-February 30/2023. A total of 514 students were selected using a systematic random sampling technique. Face-to-face interviews using a structured questionnaire, document review, anthropometric measurement, and laboratory studies were implemented to collect data. Data was analyzed by STATA version 14 and summarized by using frequency tables and graphs. Logistic regression analysis was done to identify factors associated with vitamin B12 Deficiency. Results: About 34% of the students were found to have vitamin B12 deficiency. Not Consuming animal products (AOR = 1.83, 95% CI:1.20–2.79) and low body mass index (AOR = 1.62, 95% CI:1.05–2.47) were associated with vitamin B12 deficiency. Conclusions: The study revealed a notable high deficiency of vitamin B12 in primary school students. Consumption of animal products and BMI were identified as statically significant associated factors with serum concentration of vitamin B12. [ABSTRACT FROM AUTHOR]

Background: Metformin 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. Aim: The 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. Method: For 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. Results: A 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. Conclusion: Younger 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. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is a critical medical condition that, if left untreated, can lead to severe symptoms and potentially serious and life-threatening complications. Clinical guidelines are designed to provide a standardized approach to diagnosis and treatment, aiming for consistency and effectiveness. However, it is well-established that not all patients fit into general guidelines. Objective: To investigate the clinical relevance of the submitted research to support these protocols for diagnosing and treating a B12 deficiency. Approach: Conducting a literature review of the references focused and used on diagnosing and treating vitamin B12 deficiency in adults and children. Results: No robust clinical trial nor RCT has been found to back up the current protocols. The research used is primarily based on assumptions rather than solid clinical evidence. Conclusion: Existing guidelines for vitamin B12 deficiency need to be significantly revised and improved through clinical research, clinical experience by experts in the field with input from patient groups worldwide. Plain language title: Analyzing the Lack of Research on Vitamin B12 Deficiency Guidelines: Insights from Studies and Clinical Advice Plain language summary: This study dives into Vitamin B12 deficiency, stressing its serious health impacts and potential life-threatening complications when not treated. The study aims to investigate the scientific articles supporting these guidelines and their clinical relevance, conducting an in-depth analysis of literature references. The manuscript investigates and criticizes current guidelines for B12 deficiency, pointing out 4 key issues reported by patients and clinicians worldwide. The results are grouped into 4 sections: Maintenance Dose Protocol: The study questions the adequacy of maintenance doses every few months, highlighting a lack of clinical evidence and challenging the idea of sufficient liver stores. Oral Supplementation Protocol: The effectiveness of oral supplements is questioned due to inconclusive trials, focusing on raising blood values rather than assessing actual clinical outcomes. Diagnosing B12 Deficiency in Children: Guidelines neglect B12 deficiency in children despite significant differences in B12 levels between adults and healthy kids, potentially leading to underdiagnosis and unnecessary suffering. Delay in Diagnosis and Treatment: Factors like a lack of awareness and diverse symptoms contribute to delays, emphasizing the ongoing challenge of standardizing B12 assays. In the discussion, the manuscript argues that awareness of guidelines is low, and evidence-based guidelines may lack practical relevance. It suggests a significant revision of guidelines based on robust clinical evidence, advocating for personalized treatment, patient monitoring tools, controlled trials, and age-related healthy levels. Recognizing diverse patient needs and implementing individualized therapies are crucial for improving care for those with vitamin B12 deficiency, emphasizing the importance of early recognition and intervention. [ABSTRACT FROM AUTHOR]

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered. [ABSTRACT FROM AUTHOR]

Background: It is difficult to recognize vitamin B12 deficiency and to evaluate the effect of B12 treatment due to a broad range of variable clinical symptoms overlapping with other diseases and diagnostic biomarkers that quickly normalize during treatment. This poses a risk of delay in diagnosis and a challenge to uniformly monitor the effect of B12 treatment. There is a need for a new clinical outcome measure suitable for clinical practice and clinical evaluation studies. Objective: To develop a Patient-Reported Outcome Measure (PROM) which measures the severity of vitamin B12 deficiency symptoms. Methods: The B12 PROM was developed by (1) gathering input from experts and literature review to define a construct and develop a conceptual model, (2) processing input from health care providers, scientists, and patients to develop items and response options, and (3) improving items based on the feedback from laypersons, test interviews, semi-structured cognitive interviews with patients, and forward and backward translation (ENG-NL). Results: The B12 PROM includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Cognitive interviews demonstrated good comprehensibility and comprehensiveness. Conclusions: This study is the first step in the development of a disease-specific PROM for vitamin B12 deficiency to measure the burden of symptoms. Further validation and reliability testing are necessary before the PROM can be applied in clinical practice and research. Plain language title: Development of a Vitamin B12 Deficiency Questionnaire for Clinical Practice and Research Plain language summary: This study is the first step in the development of a questionnaire for vitamin B12 deficiency to measure the severity of vitamin B12 deficiency symptoms. The questionnaire includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Interviews with patients demonstrated good comprehensibility and comprehensiveness of the questionnaire. Further testing is necessary before the questionnaire can be applied in clinical practice and research. [ABSTRACT FROM AUTHOR]

Background: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. Objectives: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. Results: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. Conclusion: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses. Plain language title: Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications? Plain language summary: It has been known for many decades that high doses of the B vitamin supplement, folic acid, can alleviate the anemia of vitamin B12 deficiency, at least temporarily. However, by alleviating the anemia, such folic acid supplements were said to "mask" the underlying vitamin B12 deficiency, thus allowing neurological damage to continue or possibly be exacerbated. Consequently, treating vitamin B12 deficiency with high dose folic acid was discontinued in the 1970s. The issue of whether folic acid supplements can exacerbate vitamin B12 deficiency reemerged in the 1990s with folic acid fortification of cereals and grains in the United States and Canada (and now in over 80 countries around the world) to prevent spina bifida and other birth defects. This narrative review summarizes the results of studies that have assessed the relationships between folic acid and folate and vitamin B12 status in patients and in populations. A recent hypothesis on how folic acid might exacerbate vitamin B12 deficiency is summarized, and recommendations to clinicians are made for increased vigilance in assessing vitamin B12 status in certain groups at risk of vitamin B12 deficiency, including older adults, people with gastrointestinal issues and other factors that cause vitamin B12 malabsorption, people with unexplained neurological problems, and people who follow vegan or vegetarian diets which are naturally low in vitamin B12. [ABSTRACT FROM AUTHOR]

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

Background: An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption. Objective: This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency. Methods: A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency. Results: Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. 'Titration' of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections. Conclusions: This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free. Plain language title: Diagnosis and Treatment of Vitamin B12 Deficiency Plain language summary: The number of people who are at risk of developing a deficiency of vitamin B12 is steadily increasing. B12 deficiency can develop when people consume too few B12-containing foods of animal origin, or when they develop a form of B12 malabsorption. B12 deficiency can lead to serious complications so prevention and early treatment are essential. Diagnosing B12 deficiency can be challenging: the symptoms vary from patient to patient, and the methods used to measure B12 in the blood, or certain biomarkers associated with B12 metabolism, such as holo-transcobalamin, methylmalonic acid, and total homocysteine are unreliable. When people do not consume enough B12-containing foods, supplementation with B12 tablets is needed. In the case of B12 malabsorption, intramuscular injections of B12 are mandatory. The usual treatment with B12 is starting with injections of 1000 µg hydroxocobalamin twice weekly or on every other day for a period of up to 5 weeks or longer, until all symptoms have disappeared, and thereafter, the frequency of injections is gradually reduced. There is, however, a large group of people who require more frequent administration to become and remain symptom-free: this may range from daily or twice weekly to every 2 to 4 weeks. [ABSTRACT FROM AUTHOR]

Background: An optimal cobalamin status is necessary for normal neurodevelopment. Objective: To give a description of the epidemiology, pathophysiology and diagnostic challenges related to cobalamin insufficiency in neonates and infants in order to prevent its occurence. Results: Inadequate cobalamin status is prevalent among neonates and young infants, due to a high prevalence of maternal cobalamin deficiency, exclusive breastfeeding for extended periods and late introduction of animal food. Cobalamin insufficiency is associated with delayed neurodevelopment and subtle clinical symptoms like feeding difficulties, regurgitations and constipation in young infants. Early diagnosis and treatment of impaired cobalamin status is important to prevent neurologic damage. Conclusion: Clinical suspicion of cobalamin insufficiency in infants should infer immediate biochemical testing and a plasma total homocysteine > 5.0 µmol/L indicate cobalamin insufficiency in need of intramuscular treatment with hydroxycobalamin, followed by introduction of animal food after 4 months of age. Plain language title: Vitamin B12 Is Important for Normal Development in Young Children Plain language summary: Vitamin B12, also called cobalamin, is found only in animal-sourced food. As low-meat, vegetarian, and vegan diets are increasingly popular in Western countries, vitamin B12 deficiency has become common, also in pregnant women and babies. Vitamin B12 status is essential for normal development and adequate levels of this vitamin is particularly important during pregnancy and the first years of life. In pregnancy, vitamin B12 is transferred from the mother to the fetus, so the baby has a store of this vitamin at birth. However, if the mother has vitamin B12 deficiency or the baby is born premature or with a low birth weight, the vitamin store may be insufficient and the baby may develop vitamin B12 deficiency. Maternal vitamin B12 status is important as long as the baby is exclusively breastfed. Breast milk contains vitamin B12, but the concentration decreases after 4 to 6 weeks and may be too low to support the baby until animal-sourced foods are introduced. The vitamin B12 content in formula milk is higher than in breast milk, and vitamin B12 deficiency is more common in exclusively breastfed babies. Vitamin B12 deficiency is associated with diffuse symptoms in small babies and may be difficult to detect, and the diagnosis have a mean delay of 4 months in this age-group. Typical symptoms are regurgitations or spitting up, constipation, problems with feeding and swallowing, and delayed psychomotor development. Suspicion of vitamin B12 insufficiency in babies should prompt immediate biochemical testing. Plasma total homocysteine is a metabolic marker of vitamin B12 status and can be measured in a blood sample from the baby. A level >5.0 µmol/L indicates probable vitamin B12 insufficiency and the baby should receive vitamin B12 supplementation, followed by introduction of animal-sourced foods at 3 to 4 months of age. [ABSTRACT FROM AUTHOR]

Background: Adult vitamin B12 (B12) deficiency may present itself with nonspecific mainly neurological symptoms, and thus plasma biomarkers are often judged to be of major importance in the further diagnostic process. Four biomarkers are of special relevance: total B12, holotranscobalamin (the part of B12 bound to the active transport protein, transcobalamin, also named holoTC or active B12) and the 2 so-called metabolic markers that accumulate if B12 is lacking, methylmalonic acid (MMA) and homocysteine. Objective: This article briefly reviews the inherent limitation of biomarkers, discusses its use in establishing the diagnosis and cause of B12 deficiency, and when following or discontinuing treatment with B12. Methods: The review is based on published papers, but also on knowledge gained from working within the area. Conclusion: It is concluded that a combination of a B12 and a metabolic marker, for example, total B12 and MMA, may prove most useful in daily practice. An unexpectedly high level of total B12 is most often of no clinical importance, though sometimes related to the presence of underlying cancer. Measurement of total B12 is of limited value in patients on treatment with pharmacological doses of B12 but may be helpful if B12 treatment is discontinued. Plain language title: Vitamin B12-Related Blood Tests Plain language summary: Blood-testing is considered an important part of the diagnostic procedure in patients suspected to suffer from B12 deficiency. A deficiency is supported by a low level of plasma B12, and confirmed by a high level of methylmalonic acid, judged according to age and kidney function. Alternatively, a high level of homocysteine may support the diagnosis. Treatment of B12 deficiency is mainly guided by improvement of symptoms, with a very limited need for further blood testing. If B12-treatment is discontinued, B12 status should be judged every 6 months for approximately 2 years to detect a possible reoccurrence of a deficient state. An unexpected high level of plasma B12 is most often of no clinical implication. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history. Plain language title: A case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaints Plain language summary: Vitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery. [ABSTRACT FROM AUTHOR]

Background: The incidence of gestational diabetes mellitus (GDM) has increased in recent decades. Established prevention methods for GDM include diet and exercise. Recent interest has focused on the roles of vitamin B12 and folate in the development of GDM. These micronutrients are essential for one-carbon metabolism, which is involved in many metabolic pathways. However, the study results were conflicting and varied by geographic area. Objectives: The aim of this study was to evaluate the relationship between GDM and vitamin B12 levels in our region. Methods: This case-control study enrolled 180 pregnant women at 24 - 28 weeks of gestation. Half of the participants had GDM, and the other half were healthy individuals. All participants attended outpatient pregnancy care clinics at Shiraz University of Medical Sciences from June 2020 to April 2021. Gestational age, age, and body mass index were matched between the two groups. Vitamin B12, folate, insulin, and homocysteine levels were measured in both groups and insulin resistance was calculated. The results were compared between the two groups, and the relationship between vitamin B12 levels and insulin resistance in each group was investigated. Results: Vitamin B12 deficiency was present in 15.6% of the women with GDM. There were no cases of vitamin B12 deficiency in the control group. The GDM group had lower vitamin B12 levels (365.22 ± 136.82 pg/mL vs. 496.08 ± 156.46 pg/mL, P = 0.001). There was a negative correlation between serum vitamin B12 level and insulin resistance index (P = 0.001, r = -0.62). Folate levels were higher in the GDM group (17.93 ± 3.66 ng/mL vs. 14.60 ± 5.32 ng/mL, P = 0.001), but these levels did not significantly relate to insulin resistance or GDM. Conclusions: In our region, there is a significant relationship between low levels of vitamin B12 and both insulin resistance and GDM, which suggests the need for larger studies and attention to the detection and treatment of vitamin B12 deficiency during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. Methods and findings: Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. Conclusions: Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study. Using data from India, Chakrabarti and colleagues evaluate whether higher open defecation levels diminished the protection provided by deworming against anaemia or micronutrient deficiencies. Author summary: Why was this study done?: Deworming is recommended to tackle soil-transmitted worm infections in low- and middle-income countries (LMICs), but the effectiveness of deworming provided on a large scale varies significantly. Sanitation levels across communities are likely to influence the impact of deworming in populations due to high rates of reinfection, but no studies have investigated these links. Despite well-intended programs intended to eliminate open defecation in India, this behavior persists in certain communities. This study was done to test whether higher open defecation levels diminished the protection provided by deworming against anemia or micronutrient deficiencies among Indian children and adolescents. What did the researchers do and find?: We used a cross-sectional dataset (sample size 105,060 individuals) representative of Indian children and adolescents to look at links between open defecation, deworming, anemia, and micronutrient deficiencies. We found that deworming coverage remains low in India, especially among young children and adolescents out of school, indicating the need for enhanced and expanded deworming interventions. After accounting for the influence of age, sex, wealth, education, diet, and season, dewormed children in areas without open defecation had lower rates of anemia (28% lower), iron deficiency (22% lower), and folate deficiency (31% lower); however, in communities with open defecation, dewormed children showed similar deficiency levels as those not dewormed. What do these findings mean?: Our findings suggest that open defecation diminishes the protection provided by deworming medication against anemia and micronutrient deficiencies in India. The findings highlight the importance of sequencing sanitation interventions such as behavior change campaigns before deworming initiatives in high open defecation communities. This study cannot establish causation because the statistical models were based on observing associations at a single point in time rather than tracking changes over time. [ABSTRACT FROM AUTHOR]

Introduction: Altered DNA methylation pattern in sperms has been associated with infertility in males demonstrating defective spermatogenesis or low semen quality. Vitamin B-12, by affecting 1-carbon metabolism pathways, might alter the DNA methylation pattern. We aimed to study the correlation of serum vitamin B12 levels with aberrant DNA methylation in infertile male patients. Methods: A cross-sectional study was conducted on 17 oligozoospermic infertile males (WHO criteria, 2010) and 10 healthy fertile males. Serum vitamin B12 levels were estimated using the chemiluminescence method. Global methylation was determined using the ELISA system (Imprint Methylated DNA Quantification Kit, Sigma–Aldrich). The levels of global DNA methylation were calculated and compared relative to the methylated (100%) control DNA provided with the kit. Results: Mean serum vitamin B12 concentration in the control group was higher than that of the case group. This difference in serum vitamin B12 concentration in both groups was found statistically significant. Although the results of this study show that oligozoospermic men have relatively lower global DNA methylation as compared to normozoospermic control, the values could not reach a statistically significant level. A small positive correlation was found between serum vitamin B12 levels and percent methylation defect (r = 0.14) but was statistically insignificant. Conclusion: Our study concludes that oligozoospermic infertile males have a significant deficiency of vitamin B12 as compared to normozoospermic fertile males. This study did not find any significant difference in global DNA methylation between the two groups. The present study does not suggest any correlation between serum vitamin B12 level and percent DNA methylation. [ABSTRACT FROM AUTHOR]

Background: Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression. Aims and Objectives: To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD. Materials and Methods: Fifty‑nine patients with MDD were recruited based on ICD‑10 criteria. Severity of depression was assessed by HAM‑D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed. Results: Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 µmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW‑CV) varied significantly between the three groups of MDD patients. Patients consuming non‑vegetarian food had a significantly higher median value of serum vitamin B12. Conclusion: Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study. [ABSTRACT FROM AUTHOR]

This article provides an overview of the potential impact of metformin, a medication commonly used for type 2 diabetes, on vitamin B12 levels and deficiency. The authors conducted a comprehensive review of various studies and guidelines published between 2010 and 2021. The evidence suggests that long-term use of metformin is associated with decreased vitamin B12 concentrations, and higher doses of metformin may increase the risk of B12 deficiency. The authors recommend regular monitoring of vitamin B12 levels in patients taking metformin to prevent and treat deficiency. The article also discusses the prevalence of B12 deficiency in patients on metformin therapy and highlights the importance of managing this side effect to improve patients' quality of life. The document includes a list of references that can be helpful for library patrons researching the effects of metformin on vitamin B12 levels and related health conditions. [Extracted from the article]

Background. The vitamin b12 in type 2diabetes mellitus. Patients using metformin or not on metformin-a cross sectional study. Methods: Data was collected from T2DM patients attending Department of General medicine of Sree Mookambika Institute of Medical Sciences, Kanyakumari, TamilNadu from march 2022 to September 2023. data collected from 110 patients with type 2 diabetes mellitus on metformin and patients not on metformin(dose and duration) Age group (18to 80 years). Results: The age group didn't shows significant p value. The Pearson chi square for age is 8.057, p=0.089. The sex also shows no significant p value(Pearson chi square=0.131, p=0.717) Mathew c pflipse et al, shows high prevalence of vitamin b12 deficiency among 22% of diabetes with metformin therapy. In our study also had almost same percentage of the metformin group patients affected. Ting et al, noticed that the metformin duration are main factors for Vitamin B12 deficiency. This is similar to our study and shows association between duration of metformin and with B12 levels. Conclusion: In the study, metformin therapy for >2 years had shows significant vitamin B12 deficiency and less than 6 months has no significant vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

Background Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. Combination medicines and pure methylcobalamin seems to improve symptoms rather than electrophysiologic outcomes in individuals with diabetic peripheral neuropathy. The aim of present study was to assess the effect of Vitamin B supplementation for diabetic peripheral neuropathy. Methods The present cross-sectional study was conducted at department of general medicine among 100 patients with diabetic peripheral neuropathy who visited during the study period of one year. Patients were divided into two groups (group B and group P). The entire neuropathy and laboratory test were done. With IBM SPSS v25.0, statistical analyses were carried out. Results There were no significant differences between the group B and group P regarding demographics, anthropometric and laboratory measurements. Vitamin B12 levels significantly increased in the group B from 237.8±70.3 pmol/L at baseline to 775.8±234.2 pmol/L at follow-up. In the group B, there was a significant improvement in the vibration perception threshold (VPT), MNSIQ, pain score, quality of life (QoL), sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and electrochemical skin conductance in feet (ESCF) during the follow-up (p =0.001, p = 0.003, p = 0.0001, p = 0.0001, and p = 0.013, respectively). Conclusion Patients with DN who received an oral methylcobalamin treatment for a whole year had improvements in their QoL, pain score, sudomotor function, plasma B12 levels, and all neurorophysiological markers; however, CARTS and MNSIE did not show any improvement. [ABSTRACT FROM AUTHOR]

Metformin-associated vitamin B12 deficiency is a well-established side effect, especially in patients taking higher doses of metformin or who have existing risk factors. Severe deficiency causes a wide range of systemic disorders. Gait instability, which leads to frequent falling, is usually an underrecognized side effect. Older patients are more likely to develop chronic subdural hematoma even with minor trauma. We present a case of 84-year-old man with type 2 diabetes mellitus with acute-on-chronic subdural hematoma from frequent falls. Metformin therapy at dose of 1700 mg/day was given for more than 25 years. He had been in his usual state of health until 10 months ago when he began to have frequent fallings and fatigue. Physical examination in this admission revealed new-onset impaired vibratory sensation and proprioception in both feet and positive Romberg test. Subsequent evaluations demonstrated undetectable plasma vitamin B12 level and elevated plasma homocysteine. Improvement in neurological symptoms occurred within 1 week of vitamin B12 replacement and surgical hematoma evacuation. This case highlights the importance of awareness and periodic monitoring of vitamin B12 status among older patients taking metformin. [ABSTRACT FROM AUTHOR]

Introduction Vitamin B12 deficiency can lead to hematological findings, neurological symptoms, and neurodevelopmental delay. The aim of this study was to investigate the impact of vitamin B12 deficiency on the neurodevelopment of children. Materials and Methods This study included 89 children aged between 6 and 24 months without any complaints; 44 of these were evaluated in the study group (serum vitamin B12 <300 pg/mL) and 45 in the control group (serum vitamin B12 ≥300 pg/mL). Denver Developmental Screening Test II (DDST-II) and the Social Communication Area Screening Test (SCAST) were evaluated in each participant. Results The mean vitamin B12 level in the study group was 206.11 ± 9.1 pg/mL, and in the control group, it was 540.65 ± 24.1 pg/mL. When DDST-II results were analyzed, the rate of getting suspicious and abnormal results in the study group was significantly higher compared with the control group (p = 0.001). The rate of the "risky" SCAST results of the cases was found to be statistically significantly higher in the study group than in the control group (p = 0.003). Vitamin B12 values of patients with suspicious or abnormal DDST-II results and with risky SCAST results were found to be statistically significantly lower than those with normal neurodevelopmental screening tests results (p = 0.001 and p = 0.001, respectively). Conclusion Vitamin B12 deficiency can lead to neurodevelopmental delay in children, even in the absence of neurological and hematological symptoms or complaints, which highlights the importance of early detection and intervention of vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

Over the last decades, low vitamin B12 status has been reported in individuals with type 2 diabetes mellitus (T2DM). Metformin, the first-line therapy for lowering blood glucose, is the main driving factor behind this association. Although the relationship between vitamin B12 deficiency and metformin is well established, results of studies on the exact effect of the dose and duration of the therapy remain inconsistent. Additionally, a lack of consensus on the definition of vitamin B12 deficiency adds to the conflicting literature. The objectives of this review were to analyze and synthesize the findings on the effects of metformin dose and duration on vitamin B12 status in patients with T2DM and to outline the potential mechanisms underlying metformin's effect on vitamin B12. Metformin therapy has adversely affected serum vitamin B12 concentrations, a marker of vitamin B12 status. The metformin usage index (a composite score of metformin dose and duration) might serve as a potential risk assessment tool for vitamin B12 screening in patients with T2DM. Considering the health implications of suboptimal vitamin B12 status, vitamin B12 concentrations should be monitored periodically in high-risk patients, such as vegans who are receiving metformin therapy for T2DM. Additionally, it is prudent to implement lifestyle strategies concurrent with metformin therapy in individuals with T2DM, promoting an overall synergistic effect on their glycemic control. [ABSTRACT FROM AUTHOR]

Background: There are limited data relating to the effects of metformin‐associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well‐characterised community‐based cohorts. Aims: To assess inter‐relationships between metformin therapy, vitamin B12 deficiency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes. Methods: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total ≥80 and ≤200 pmol/L, active ≥23 and ≤35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses. Results: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum concentration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treatment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose‐dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90–316) for >2000 mg daily compared with no treatment; P < 0.001), there was no significant association between vitamin B12 status and DSPN, anaemia (haemoglobin ≤130 g/L males, ≤120 g/L females), haemoglobin concentration or mean corpuscular volume (P ≥ 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency. Conclusions: Since nutritional sources likely attenuate metformin‐associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin‐treated patients. [ABSTRACT FROM AUTHOR]