Vitamin B12 deficiency is a significant clinical concern, often leading to pernicious anaemia and associated vascular dysfunction. Traditional supplementation methods face challenges such as poor absorption in patients lacking intrinsic factor, highlighting the need for alternative delivery strategies. This study investigates the use of dissolving microneedles for transdermal delivery of vitamin B12, evaluating both permeation efficiency and biological effects on endothelial cells. Microneedle arrays were fabricated using polyvinyl pyrrolidone (PVP K30) combined with either 7.5% or 15% trehalose dihydrate at two needle lengths (800 µM and 900 µM). Following mechanical characterisation, the optimal formulation and needle length were applied to excised murine skin in a Franz diffusion cell system to assess vitamin B12 permeation. Receiver media were collected and applied to EA.hy926 endothelial cells to evaluate trans-endothelial permeation and the effect of permeated B12 on TNF-α-induced inflammation by measuring IL-6 expression and reactive oxygen species (ROS) generation. Microneedles composed of PVP K30 with 15% trehalose at 900 µM length demonstrated superior mechanical properties and insertion efficiency. The Franz cell study revealed that over 24 h, approximately 25% of vitamin B12 permeated through murine skin. The permeated vitamin B12 efficiently traversed the endothelial cell barrier in vitro within 1.5 h and significantly suppressed TNF-α-induced IL-6 expression and ROS production in EA.hy926 cells. These findings suggest that PVP-trehalose dissolving microneedles provide a promising transdermal delivery platform for vitamin B12, capable of sustained release and effective biological activity. This approach holds potential as a minimally invasive treatment option for pernicious anaemia and related vascular complications.

Identifying individuals with vitamin B12 (B12) deficiency is challenging due to poor harmonization across total B12 assays. To establish clinically meaningful thresholds for the Roche assay, we characterized B12 concentrations associated with deficiency by comparing individuals with macrocytic anemia and other anemia subtypes or no anemia. We retrospectively analysed 10years of laboratory data from adults tested for total B12 and folate (Roche Cobas), homocysteine (Abbott Architect), and haematological parameters (Sysmex XE/XN). Individuals receiving vitamin supplementation or with isolated folate deficiency were excluded. Anemia subtypes (normocytic, microcytic, macrocytic) were classified using red blood cell count, hemoglobin concentration, and mean corpuscular volume relative to reference intervals. Among 5,147 subjects (median age 65years; 25th-75th percentile: 49-77), 36.8 % had anemia. Total B12 concentrations decreased by 2.3 ng/L for each 1 μmol/L increase in homocysteine and by 6.8 ng/L per decade of age increase (p<0.0001). Macrocytic anemia (9.4 % of subjects), was associated with a mean reduction of 18.6 ng/L in B12 levels compared with no anemia and microcytic anemia. Mean homocysteine concentrations rose progressively, from 15.9 to 21.5 μmol/L and then to 34.9 μmol/L, as total B12 concentrations fell in the intervals: 342-447 ng/L, 341-258 ng/L, and 257-<50 ng/L, respectively. Among individuals investigated for anemia, macrocytosis, a hallmark of B12 depletion, supports that total B12 concentrations≤257 ng/L measured using the Roche assay likely reflect severe deficiency. Levels between 258 and 341 ng/L may indicate early depletion and warrant confirmation through elevated homocysteine concentrations.

Patient Blood Management (PBM) is an evidence-based, multidisciplinary strategy that aims to optimize hemoglobin levels, to minimize perioperative blood loss, and to reduce avoidable transfusions. In military medicine, combat-related traumatic injuries (CRTI) pose specific challenges, as wounded soldiers frequently develop multifactorial anemia because of acute and chronic blood loss, inflammation, malnutrition, and delayed access to care. Although blood transfusions are a common treatment, they carry medical risks and represent a scarce, logistically demanding resource, especially in deployed or resource-limited settings. This case report illustrates the importance of early anemia screening, differentiation, and targeted treatment with a PBM framework in septic reconstructive surgery. A 32-year-old Ukrainian soldier was admitted to the Emergency Department of the Military Hospital Berlin, Germany. Eight months ago, the soldier sustained a blast injury with a femoral fracture and stabilization by external fixation in his home country. Diagnostic work-up detected chronic osteomyelitis and previously untreated iron deficiency. During ongoing surgical and antimicrobial treatment, the anemia progressed postoperatively but was successfully managed with intravenous and oral iron supplementation, without the need for blood transfusion. This case highlights the importance of structured anemia management in military surgery, even in young and otherwise healthy patients, to improve clinical outcomes while preserving limited resources. This aspect is of relevance during large-scale combat operations with high numbers of casualties. In this context, anemia management relies on the simple identification of underlying causes and correction of deficiencies in iron, vitamin B12, or folate when present, offering an effective and easily applicable strategy before resorting to blood transfusion.

Childhood anemia is a very common problem in India, out of which more than one-third is attributed to vitamin B12 deficiency. To follow up on a girl with recurrent anemia who was later diagnosed with hereditary intrinsic factor deficiency. An eight-year-old girl presented with recurrent anemia, easy fatigability, poor appetite, and abdominal pain for one month. The hemoglobin was 4.3 g/dL, and the peripheral smear showed a dimorphic picture. Serum vitamin B12 was severely low at <50 pg/mL. After a packed red blood cell transfusion, she was advised to take oral vitamin B12 and iron supplements. Her symptoms and vitamin B12 levels did not improve on follow-up, which led to suspicion of a congenital intrinsic factor deficiency (proven by whole exome sequencing). The child is currently doing well on monthly vitamin B12 injections. This case highlights the importance of considering rare inherited causes in a child with recurrent severe anemia, even in regions where nutritional deficiencies are common.

Background: Type 2 Diabetes Mellitus (T2DM) is a common metabolic disorder often associated with diabetic peripheral neuropathy manifested by pain, paresthesia and sensory impairment. The first line treatment for T2DM, metformin has been associated with decreased intestinal uptake of vitamin B12 with prolonged use. (de Jager et al., 2010; Reinstatler et al., 2012) Vitamin B12 deficiency may therefore play a role in the neurological dysfunction and aggravate neuropathic symptoms. However, the link between vitamin B12 levels and the severity of neuropathic pain in metformin-treated patients is still not adequately examined. Method: This is a cross-sectional observational study which was conducted at the Department of General Medicine, Guntur General Hospital (GGH), which is a tertiary care teaching hospital serving a diverse semi-urban and rural population. The study was carried out in a period of a year i.e. December 2023 - December 2024. Results: Mean age of participants was 61.1±10.6 years. Vitamin B12 deficiency was seen in 25.6% of the patients and clinical neuropathy (DN4 ≥ 4) was present in 33.6% of the cohort. Neuropathy was much more common in vitamin B12-deficient (81.2%) and normal vitamin B12 level patients (12.6%). Serum vitamin B12 levels had a significant inverse correlation with the VAS pain scores (rs= - 0.527, p &lt; 0.001). Multivariable regression confirmed that lower levels of vitamin B12 were an independent predictor of lower neuropathic pain levels. Conclusion: Vitamin B12 deficiency is seen in high percentages of metformin-treated patients with T2DM and is highly correlated with a greater level of neuropathic pain. Routine monitoring and supplementation may help to decrease neuropathic complications.

Premature graying of hair (PGH) is a significant concern for individuals, as it is frequently perceived as an indicator of advancing age and reduced vitality, and can lead to lower self-esteem and psychological distress. Deficiencies of vitamin B12, vitamin D3 and ferritin may be related to PGH. Nevertheless, data on the specific risk factors and biochemical parameters for PGH in India are relatively limited. This study was conducted to examine the various demographic and potential risk factors, along with biochemical variables linked to PGH. An analytical case-control study was conducted on patients attending the skin outpatient department with PGH. The control group comprised age- and gender-matched patients and attendants with other dermatoses. Various demographic factors and potential risk factors were documented and compared with control groups. Measurement of serum ferritin, calcium, hemoglobin, vitamin D3, vitamin B12, lipid profile, and thyroid profile was done and analyzed between the cases and controls. Males outnumbered females with a male-to-female ratio of 1.5:1. Most of the cases of PGH belonged to the age group of 15-25 years (71.5%). On binary multivariate regression analysis, statistically significant differences in family history, smoking and hair plucking compared to controls were noted. Additionally, the cases had considerably lower levels of serum ferritin (P = 0.020), vitamin B12 (P = 0.012), and vitamin D3 (P = 0.043). This study was done at a single center. We plan to conduct a multicentric study in the future. Recall bias may also be a limitation in the study. The patients were not followed-up after correction to assess it's effect. Identifying modifiable risk factors and correcting biochemical abnormalities may help in preventing and better managing patients with PGH.

Autoimmune gastritis (AIG) is an immune-mediated condition that affects the oxyntic mucosa of the stomach, leading to progressive atrophy and deficiencies in vitamin B12, iron and other micronutrients. Our understanding of the pathogenesis, clinical manifestations and management of AIG has improved in the past 20 years. Initially thought to be associated mainly with pernicious anaemia and limited to certain geographical areas, AIG is now recognized as a global disorder with a broad clinical spectrum, ranging from asymptomatic cases to gastrointestinal, haematological, neurological and gynaecological manifestations. The role of Helicobacter pylori in the development of AIG has been debated, with evidence suggesting that AIG might arise through distinct pathogenic pathways both related and unrelated to H. pylori infection. The risk of gastric adenocarcinoma in AIG has also been reassessed on the basis of studies exploring its natural history. Finally, novel insights have emerged regarding the characterization of 'potential AIG' and 'seronegative AIG', two distinct conditions that were previously overlooked. In this Review, we discuss the latest advances in the field of AIG.

Diabetic retinopathy (DR) is a leading cause of preventable vision loss, yet current therapies primarily address late, VEGF-driven vascular complications rather than early upstream drivers. Emerging evidence indicates that early DR originates from metabolic stress within the retinal neurovascular unit, where dysregulated lipid metabolism, oxidative stress, and inflammation precede visible microvascular damage. Disturbances in polyunsaturated fatty acid (PUFA) metabolism, together with related metabolic stressors such as elevated homocysteine (Hcy), drive lipid dysregulation, oxidative stress, and inflammation preceding visible microvascular damage, promoting endothelial dysfunction and blood–retinal barrier (BRB) breakdown. Hyperglycemia shifts retinal lipid composition toward oxidation-prone omega-6 PUFAs and activates lipoxygenase (LOX), cyclooxygenase (COX), and cytochrome P450 (CYP450) eicosanoid pathways. LOX-derived metabolites such as 12- and 15-HETE stimulate NADPH oxidase, disrupt tight junctions, and promote inflammatory signaling in endothelial and Müller cells. COX-2–driven prostaglandin E2 signaling increases vascular permeability, while CYP450 metabolites and their soluble epoxide hydrolase (sEH) derived products exert context-dependent effects on vascular integrity. Elevated Hcy further enhances oxidative stress and NF-κB activation, amplifying PUFA-mediated inflammatory signaling. These mechanisms identify modifiable upstream targets that complement glycemic control. Higher dietary omega-3 intake and lower omega-6:omega-3 ratios are associated with reduced DR risk, particularly in well-controlled diabetes. Omega-3–rich diets, exercise, and correction of folate and B-vitamin deficiencies may help improve systemic inflammation and retinal barrier integrity. Integrating lipid pathway modulation, nutritional support, and metabolic control with careful ocular monitoring may help slow the progression of DR before irreversible blindness occurs.

Biermer's disease, or pernicious anemia, is an autoimmune condition marked by vitamin B12 deficiency due to intrinsic factor antibodies targeting gastric parietal cells. The relationship between Biermer's disease and increased thrombotic risk, while uncommon, represents a critical clinical concern necessitating heightened diagnostic awareness for patients presenting with unexplained thrombotic symptoms. This report details the case of a 57-year-old Mediterranean male, with a prior diagnosis of Graves' disease, who developed splanchnic venous thrombosis. An extensive etiological investigation revealed mild hyperhomocysteinemia, associated with an undiagnosed Biermer's disease. Our case underscores a critical association between Biermer's disease, hyperhomocysteinemia, and venous thrombosis, emphasizing the imperative for further research elucidating their interconnected pathogenesis.

Leprosy primarily affects the skin and peripheral nerves, with neuropathy usually accompanying skin lesions. Rarely, neural involvement may precede cutaneous manifestations, leading to diagnostic delay. We report the case of a 36-year-old male presenting with bilateral lower limb sensory motor neuropathy initially attributed to Vitamin B12 deficiency. Despite normalization of B12 levels, symptoms persisted, and subsequent skin changes led to biopsy confirmation of borderline tuberculoid leprosy. This case emphasizes considering Hansen's disease in patients with unexplained neuropathy, particularly in the endemic regions, even before overt skin lesions appear.

Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM). Long-term use of metformin has been associated with vitamin B12 deficiency, which may lead to serious complications such as anaemia and neuropathy. Although international bodies have recommended screening for vitamin B12 deficiency in patients on long-term metformin, it is unclear how aware clinicians are of this adverse effect and to what extent such guidance is being followed in practice. A scoping review was conducted using Joanna Briggs Institute (JBI) methodology. Databases searched included MEDLINE, Medical Literature Analysis and Retrieval System Online (PubMed), British Nursing Index (BNI), Google Scholar, Cochrane, Embase, Web of Science and CINAHL, Cumulative Index to Nursing and Allied Health Literature (EBSCO) alongside searching for grey literature such as EThOS (Electronic Theses Online Service), DART (Digital Access to Research Theses) European and Kings College London Research Portal. Studies published in English from 1990 onwards were included if they addressed clinician awareness or screening practices. Data were extracted and summarised using a structured tool, with themes mapped visually. The literature search was conducted between 1 August 2025 and 1 November 2025 and included studies published from January 1990 onwards. 23 sources were included in the review. 7 studies directly assessed clinician awareness of metformin-associated vitamin B12 deficiency, all conducted outside the UK. Across 15 studies reporting screening practices, routine vitamin B12 monitoring was uncommon, with annual testing rates in general below 20% of eligible patients (range 2.6%-19.8%). In a large retrospective cohort study of patients on long-term metformin, 44.9% underwent vitamin B12 testing, with a mean delay of 990 days from treatment initiation. Screening was predominantly symptom-triggered rather than preventive, and older adults and other high-risk groups were consistently less likely to be tested. Reported barriers included lack of clinical prompts, competing priorities and testing costs. Clinician awareness of the link between long-term metformin use and vitamin B12 deficiency is present but inconsistently translated into practice. Screening practices remain suboptimal despite recent guideline updates. Interventions, such as checklists, prompts and updated training, may support improved adherence. However, no UK-based studies were identified, highlighting a gap in national evidence. Routine, risk-based screening in primary care could prevent significant morbidity associated with undiagnosed vitamin B12 deficiency in this population.

Vitamin B12 deficiency is classically associated with megaloblastic anemia and neurologic or neuropsychiatric manifestations; however, in rare cases, it may present with pancytopenia and laboratory features that mimic hemolytic anemia. Pernicious anemia is a common cause of vitamin B12 deficiency classically described in older adults of Northern European descent; however, it can occur across all ages and ethnic backgrounds, and demographic assumptions should not delay diagnosis. We report a 35-year-old African American man with no significant past medical history who presented with progressive weakness, decreased appetite, and fatigue. Initial laboratory evaluation revealed profound macrocytic anemia, thrombocytopenia, elevated lactate dehydrogenase, indirect hyperbilirubinemia, and low haptoglobin. Despite these findings, the reticulocyte response was inappropriately low, the direct antiglobulin test was negative, and the peripheral blood smear demonstrated no schistocytes, consistent with ineffective erythropoiesis rather than true hemolysis. Further evaluation revealed severe vitamin B12 deficiency with normal folate levels and positive intrinsic factor antibodies, and biopsy findings consistent with autoimmune metaplastic atrophic gastritis supporting a diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 resulted in rapid clinical and hematologic improvement, emphasizing the reversibility of hematologic manifestations with prompt therapy. This case highlights pernicious anemia as a reversible cause of pseudo-hemolytic anemia and underscores the importance of recognizing its distinguishing features to avoid unnecessary interventions such as plasma exchange or immunosuppressive therapy.

Background: Infantile Tremor Syndrome (ITS) is a rare yet clinically significant nutrition-related neurological disorder that is observed in most infants and young children in developing nations. Tremors, neurodevelopmental delay or deterioration, anemia, pigmented skin, and shaggy hair are characteristic feature. Increasing evidence suggests a strong association with vitamin B12 deficiency, particularly in exclusively breastfed infants born to nutritionally deficient mothers. We report a case of a 10-month-old female infant exhibited typical features of Infantile Tremor Syndrome with markedly low vitamin B12 levels despite normal growth, and showed significant clinical improvement after treatment. ITS should be considered in infants with tremors and developmental delay even with normal anthropometry, as early detection and vitamin B12 supplementation can prevent long-term neurodevelopmental complications. Keywords: Infantile tremor syndrome; Vitamin B12 deficiency; Nutritional rehabilitation; Neurodevelopmental delay.

Vitamin B12 testing is recommended for individuals with clinical signs and symptoms suggestive of B12 deficiency, and when there is reasonable clinical suspicion of deficiency due to risk factors (e.g. inadequate dietary intake, malabsorptive conditions). Where vitamin B12 testing is indicated, total serum B12 is typically the first-line test. Active B12 may be requested if total B12 results are indeterminate, or during pregnancy. If total or active B12 tests are inconclusive, methylmalonic acid or homocysteine testing may be considered; however, their concentrations may be elevated in other conditions. In individuals with confirmed B12 deficiency, B12 supplementation is required, with the choice of formulation, duration and dosage guided by the underlying cause and severity of the deficiency and patient preference.

Vitamin B12 deficiency is a common cause of normocytic or megaloblastic anemia. In 2.5% of cases, it can manifest as pseudo-thrombotic microangiopathy (pseudo-TMA), which mimics thrombotic thrombocytopenic purpura (TTP), an emergent hemolytic microangiopathy. This case report discusses a stable-appearing 45-year-old female with progressive fatigue, heavy menstrual bleeding, bleeding gums, and easy bruising. Laboratory testing demonstrated low vitamin B12 (121 pg/mL), pancytopenia, exaggeratedly elevated LDH, undetectable haptoglobin, low reticulocyte production index (RPI), and positive intrinsic factor antibody. She was diagnosed with pseudo-TMA. Unlike TTP, pseudo-TMA patients often appear clinically well and hemodynamically stable without renal or neurologic dysfunction. Other key differentiators of pseudo-TMA include progressive anemia, often with irregular red cell morphology; evidence of pancytopenia, neutropenia, and reticulocytopenia; and LDH levels exceeding 2500 units/L. While clinicians should maintain a low threshold for recognizing TTP as a hematologic emergency, they must also maintain awareness of pseudo-TMA to prevent misdiagnosis and unnecessary plasmapheresis and to optimize treatment.

Cobalt ion-enhanced chemiluminescence of boron-nitrogen co-doped carbon dots for sensitive detection of cobalt ions and vitamin B12.

Pregnancy-related anaemia significantly affects human development across life stages. In sub-Saharan Africa (SSA), country-specific epidemiological variations primarily driven by nutritional practices, socioeconomic factors and health-system disparities contribute to heterogeneity in prevalence, severity and adverse birth outcomes (ABOs). While anaemia and micronutrient deficiencies in pregnancy are well studied globally, comprehensive trimester-specific evidence and their associations with ABOs in SSA remain scarce. This review, therefore, examines the breadth and nature of existing evidence on these associations within SSA, thereby updating current knowledge and informing regionally tailored interventions and future research. A scoping review methodology will be employed due to the limited volume of literature addressing the specific research questions and population. The review will follow the Joanna Briggs Institute (JBI) framework, applying the population-concept-context approach. Comprehensive searches will be conducted across CINAHL, MEDLINE, Cochrane Library, Scopus, Google Scholar, EBSCO Open Dissertations and relevant organisational websites. The planned search period will span from 1 January 2016 to 31 December 2025. Two reviewers will independently screen and extract data using JBI-adapted protocols within the Rayyan review platform. Any discrepancies will be resolved via discussion with the research team. Findings will be synthesised narratively through descriptive content analysis and visual mapping.This review will include peer-reviewed studies and grey literature that investigate the associations between anaemia or deficiencies in iron, folate and vitamin B12 during pregnancy trimesters and ABOs in SSA. All relevant sources of evidence will be considered, regardless of study design or methodology, provided they report on women of reproductive age who experienced anaemia in any trimester and were subsequently identified with ABOs. Birth outcomes of interest include low birth weight, macrosomia, small or large for gestational age, preterm birth, post-term birth and stillbirth. Only sources published in English from 2016 onward will be included. The studies' quality will be evaluated using Cochrane's risk of bias assessment and mixed methods appraisal tools and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review. This scoping review will not require ethical approval as it will synthesise published data and reports. It has been registered with the Open Science Framework. This review does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to shape subsequent research, serving as a fundamental element of the evidence and knowledge mapping framework. As this study protocol was not reviewed by an ethics committee, the appropriate contact for research integrity matters is the Faculty of Health and Environmental Sciences, Auckland University of Technology.

Neurological Consequences of Infantile Vitamin B12 Deficiency - A Prospective Cohort Study.

Type 2 diabetes mellitus (T2DM) is an alarming public health challenge in the United Arab Emirates. Nevertheless, nutrition is a critical modifiable risk factor influencing T2DM. Therefore, this study will critically evaluate the key nutrition-related risk factors for type 2 diabetes (T2D) in the United Arab Emirates. A literature search was conducted via Scopus, PubMed, Cochrane Library, ScienceDirect, and Google Scholar. Potential articles were screened against prespecified eligibility criteria. Data were systematically extracted for subsequent analysis. Fifteen research articles were included in this review. T2D showed high prevalence rates (3.4%–22.2%) in the United Arab Emirates, and combined prediabetes/diabetes affected up to 42% of the United Arab Emirates nationals and residents. Several nutrition-related factors were associated with T2D burden, including carbohydrate-rich dietary patterns and widespread obesity (30.5%–40.7% across ethnic groups). An increase in each unit of body mass index increased the risk of T2DM by 1.017%, while central adiposity affected 63%–74% of the population across different ethnic groups. Additionally, diabetic patients exhibited Vitamin B12 deficiency and poor adherence to recommended dietary guidelines, particularly the United Arab Emirates Food-Based Dietary Guidelines (Burj Model) and the MyPlate meal pattern. However, structured interventions, including lifestyle modifications, resulted in glycated hemoglobin (HbA1c) reductions ranging from 0.3% to 2.0%, while dietary education programs demonstrated an average HbA1c improvement of 0.6%, reflecting enhanced glycemic control. Nutrition is both a modifiable risk factor and therapeutic target, with population-level initiatives and food policy interventions showing potential for diabetes prevention and management in the United Arab Emirates.

Background: Anemia is a major public health issue, particularly among women of reproductive age (WRA) in low- and middle-income countries (LMICs). Pakistan's National Nutrition Survey (NNS) 2011 showed a high prevalence of vitamin B12 (B12) and folate deficiency among WRA, necessitating further investigation in subsequent surveys. Methods: Blood samples from 31,828 WRA (15-49 years old) were collected using a stratified multi-stage sampling technique in NNS-2018. We conducted a secondary analysis using population-weighted logistic regression to assess the association of potential factors with B12 and folate deficiency. B12 (n = 4442) and folate (n = 12,662) samples were measured using an electrochemiluminescence immunoassay and a Centers for Disease Control and Prevention, USA (CDC)-approved microbiologic assay, respectively. Results: Folate deficiency was present in 44.7% WRA, and 20.2% had B12 deficiency. Provincial distribution was associated with folate deficiency, i.e., Sindh (OR = 1.140, 95% CI 1.018, 1.285), Baluchistan (OR = 1.237, 95% CI 1.052, 1.453), and Islamabad (OR = 1.524, 95% CI 1.109, 2.092), while B12 deficiency was prevalent in Islamabad (OR = 1.673, 95% CI 1.122, 2.497), Gilgit Baltistan (OR = 2.472, 95% CI 1.197, 5.106), and newly merged districts of KPK (OR = 1.584, 95% CI 0.977, 2.570). Rural residence (OR = 1.407, 95% CI 1.125, 1.760), obesity (OR = 1.649, 95% CI 1.282, 2.122), and overweight (OR = 1.560, 95% CI 1.262, 1.928) were associated with B12 deficiency. Conclusions: Our results show regional and demographic differences in the prevalence of folate and B12 deficiencies among WRA. This underscores the need for targeted nutritional interventions and further longitudinal studies to identify potentially associated factors.