Vitamin B12 Deficiency Manifesting As Pancytopenia, Lymphadenopathy, and Fever: A Clinical Mimic of Hematologic Malignancies.

Pancytopenia is a complex medical condition characterized by decreased levels of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). It can arise from impaired production, peripheral destruction, or a combination of both. The causes of pancytopenia range from reversible factors like infections and medication reactions to irreversible conditions. Vitamin B12 deficiency is a notable reversible cause that can take years to manifest in adults due to stored reserves. However, deficiencies caused by impaired absorption, especially due to the lack of intrinsic factors (IFs), can lead to rapid deterioration within two to five years. A healthy 39-year-old male with an athletic lifestyle presented with symptoms such as dizziness, nausea, vomiting, palpitations, and fainting over a few days. These symptoms were preceded by weeks of persistent body aches, headaches, weakness, daily fevers, chills, and night sweats. Vital signs were stable. The physical examination revealed conjunctival pallor and lymphadenopathy in the submandibular and superficial cervical regions. Initial blood tests showed normocytic anemia (Hgb 4.9, MCV 80), leukopenia (2.99), thrombocytopenia (142), and elevated liver enzymes (AST 199, ALT 96, and total bilirubin of 2.04). The peripheral smear showed tear-drop cells and hypochromic cells. The initial impression was hematologic malignancy, including but not limited to leukemia, lymphoma, or myelofibrosis given clinical findings such as B-symptoms like night sweats, neck lymphadenopathy, and subjective daily fever, along with pancytopenia. The patient received a bolus of normal saline and a transfusion of two units of packed RBCs. CT scans of the chest, abdomen, and pelvis showed no adenopathy or splenomegaly. Although initial clinical assessment pointed toward a potential hematologic malignancy, comprehensive testing, including SPEP, reticulocyte count/fraction, serum folate, and serum vitamin B12, revealed only severe vitamin B12 deficiency, with a level of less than 150, with the presence of IF antibodies. Treatment involved intensive in-patient vitamin B12 injections followed by a detailed outpatient regimen. The patient completed a daily dose of vitamin B12 injections for seven consecutive days, followed by weekly injections for the next four weeks. Subsequent laboratory results demonstrated an increase in WBC count to 8.39, Hgb level to 13.2, and PLT count of 249, indicating a continued positive response to the vitamin B12 replacement therapy. In summary, pancytopenia poses a diagnostic challenge that demands careful evaluation of patient data and comprehensive testing. Vitamin B12 deficiency, which encompasses pernicious anemia (PA), is among the reversible factors to consider. This aspect holds significance before opting for more invasive measures like a bone marrow biopsy. Nutritional deficiencies need to be considered first as differentials in pancytopenia, even in the absence of typical signs of vitamin B12 deficiency (like macrocytosis and hypersegmented neutrophils) and in the presence of compelling clinical indications pointing to a hematologic malignancy.

Long-Term Use of Nitrous Oxide Resulting in Vitamin B12 Deficiency Causing Cervical Myelopathy.

Nitrous oxide, commonly known as laughing gas, gained popularity in the medical field as an anesthetic. It also causes euphoria and acts as an anxiolytic in the human body. However, there is limited information available on its toxicity, particularly its neurotoxicity, which has been emerging in younger populations using it for recreational purposes. Here, we present a case of a young patient with subacute combined degeneration secondary to vitamin B12 deficiency from chronic use of nitrous oxide.

Vitamin B12 deficiency misdiagnosed as TTP: What can we learn from it?

The case report by Dwyre et al. shows that vitamin B12 deficiency may be misdiagnosed as acute thrombotic thrombocytopenic purpura. Together with similar observations, this underlines that acquired vitamin B12 deficiency-besides the inherited disorder of intracellular cobalamin metabolism, cbl C disease-should be listed as a separate entity of the thrombotic microangiopathies. Commentary on: Dwyre et al. Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19625.

Recreational Nitrous Oxide Causing Deep Vein Thrombosis and Subacute Combined Degeneration: Whip It Real Good.

Nitrous oxide (N2O) has been thought to be a harmless recreational substance by public perception, but it has been linked to subacute combined degeneration (SACD) due to induction of a functional vitamin B12 deficiency via oxidation and inactivation of the cobalt ion in its molecular structure. N2O has been rising in popularity due to several factors including accessibility, low cost, and low perceived risk, leading otherwise healthy people to develop what used to be a neurological disease experienced by select patient populations with dietary restrictions or medical conditions leading to low levels of vitamin B12. Vitamin B12 plays a crucial role in many cellular processes, and loss of functional vitamin B12 cannot be detected by measuring it directly. Substrates from its metabolic pathways such as homocysteine and methylmalonic acid must be measured to check its functional status. Vitamin B12 deficiency also leads to a hypercoagulable state due to the build-up of homocysteine in the blood. We present the case of a 26-year-old male who had reportedly used N2O for six months leading to SACD and a popliteal deep vein thrombosis. The options for treatment are abstaining from substance use and vitamin B12 supplementation; however, full recovery after SACD develops is unlikely and patients may be left with permanent neurological dysfunction from N2O use.

Microangiopathic thrombocytopenia caused by vitamin B12 deficiency responding to plasma exchange.

A young adult African American female presented with normocytic microangiopathic haemolytic anaemia, elevated lactate dehydrogenase and thrombocytopenia. The patient responded to therapeutic plasma exchanges (TPE) for presumed thrombotic microangiopathy caused by thrombotic thrombocytopenic purpura (TTP). After relapsing, the patient was found to have pancytopenia, megaloblastic bone marrow and low vitamin B12 consistent with pernicious anaemia, which improved with intramuscular B12 and discontinuation of TPE. B12-deficient macrocytosis was not seen at presentation due to concomitant alpha-thalassaemia. Initial clinical/laboratory improvement is attributed to B12 present in TPE plasma. B12 deficiency can mimic TTP. Vigilance is needed regarding atypical presentations of pernicious anaemia.

Proximal Gastrectomy is Associated with Lower Incidence of Anemia and Vitamin B12 Deficiency Compared to Total Gastrectomy in Patients with Upper Gastric Cancer.

Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p<0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p<0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion: The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.

Single Low-Dose Methotrexate and Vitamin B12 Deficiency-Induced Pancytopenia Causing Fatality: A Case Report.

Methotrexate (MTX), a commonly used disease-modifying antirheumatic drug, is generally considered safe at low cumulative doses. However, severe pancytopenia can occur even with doses as low as 10 mg, as illustrated by a fatal case in an older adult with chronic kidney disease (CKI) and vitamin B12 deficiency. Despite the low dose and lack of folate supplementation, the patient developed severe mucositis and pancytopenia leading to fatal complications. This case underscores the challenges in diagnosing and managing MTX-induced pancytopenia, especially in patients with comorbidities such as CKI and vitamin B12 deficiency.

Vitamin B12 Deficiency Mimicking Thrombotic Thrombocytopenic Purpura: A Case Report and Review of Literature.

Vitamin B12 (cyanocobalamin) deficiency can lead to ineffective erythropoiesis, intramedullary hemolysis, and, in severe cases, neurologic deficits. Some of those findings are also features of thrombotic microangiopathies, specifically thrombotic thrombocytopenic purpura (TTP), and the distinction between both entities could sometimes be challenging. While the treatment of the former consists of enteral or parenteral repletion, the treatment of TTP is more complex and time-sensitive. For that reason, refining diagnostic strategies is crucial to avoid misdiagnosis and unnecessary interventions. Here is an example of a potential life-threatening hemolysis caused by vitamin B12 deficiency with acute onset neurologic symptoms, which resolved with B12 repletion.

Reversible Hyperpigmentation in a Patient With Vitamin B12 Deficiency.

Hyperpigmentation is a recognized sign of vitamin B12 deficiency that resolves after vitamin repletion. We present the case of a 58-year-old female with neuropsychiatric symptoms who developed progressive darkening of her hands and feet. A diagnosis of vitamin B12 deficiency secondary to pernicious anemia was made and her symptoms and hyperpigmentation resolved following vitamin repletion. Clinicians should consider vitamin B12 deficiency in the differential diagnosis of palmoplantar hyperpigmentation, as early treatment can avert permanent disability in these patients.

Vitamin B12 deficiency presenting as progressive blindness in a 33-year-old HIV-positive female patient on Efavirenz-based regimen: case report.

Optic neuritis is a rare presentation of vitamin B12 deficiency. We describe a 33-year-old female patient living with HIV presenting with progressive loss of vision for 1 week. She had a history of severe peripheral neuropathy that was managed with vitamin B12-containing tablets approximately three years before presenting with progressive loss of vision. On examination, she had no perception of light in the left eye and no perception of hand motion in the right eye. The fundus in her left eye had mild blurring of disc margins. Results from tests done showed a haemoglobin of 12.9g/dl, MCV 101fl, a serum vitamin B12 of 78pmol/l, and cytomegalovirus (CMV) test showed no active disease. She was diagnosed with optic neuritis and started on 30 mg tablets of prednisolone for 1 week with slight improvement. She was then started on vitamin B12 injections 1 mg daily for 10 days and thereafter, monthly for 6 months. She reported gradual improvement and regained her sight after 5 months treatment of with Vitamin B12 injections. Ophthalmic manifestations of vitamin B12 deficiency are not common and may present without haematological signs therefore, a high index of suspicion is required for early diagnosis and management of vitamin B12 deficiency.

An Uncommon Association: HLA-B27 Positivity in Conjunction With Pernicious Anemia - A Case Report and Literature Review.

Pernicious anemia, stemming from Vitamin B12 deficiency and autoimmune processes affecting intrinsic factor production, presents challenges in early diagnosis due to vague initial symptoms. This case report introduces a unique occurrence of pernicious anemia-induced peripheral neuropathy in a patient with concurrent HLA-B27 arthropathy, highlighting the complex interplay of autoimmune mechanisms. While HLA-B27 is not typically associated with pernicious anemia, the case underscores the importance of exploring specific HLA haplotypes in understanding the nuanced manifestation of autoimmune disorders. Comprehensive screening for anti-intrinsic factor and anti-parietal cell antibodies is crucial in individuals with signs of pernicious anemia, especially those with a history of HLA-B27 arthropathy, guiding tailored management strategies. This report contributes to the ongoing exploration of the intricate autoimmune landscape in pernicious anemia.

Multidisciplinary rehabilitation following recreational nitrous oxide (N2O) misuse: evaluating service provision and rehabilitation outcomes in a cohort with serious disability.

Purpose: Recreational nitrous oxide (N2O) misuse is increasing globally. Chronic misuse can cause neurological impairments that require rehabilitation, though literature characterising rehabilitation is limited. This study aimed to evaluate rehabilitation service provision for impairments resulting from N2O misuse. Methods: A retrospective audit of hospitalised patients referred for rehabilitation for N2O toxicity was conducted between 2015 and 2022 at a single metropolitan hospital. Data were collected via medical record audit and analysed via descriptive and non-parametric statistics. Results: 16 eligible cases were identified, aged 18-43 years (50% female/male), with increasing case frequency. 12 cases received inpatient rehabilitation episodes for multifactorial sensorimotor, cognitive and psychosocial impairments. Cases articulated diverse rehabilitation goals and received intervention from a median of 6 clinical disciplines. All cases required assistance to mobilise or perform self-care activities on admission. Functional Independence Measure (FIM) scores significantly improved with rehabilitation (median FIM 84[75-93] to 117[112-123], p < .001). Despite gains in independence, all cases required referral for ongoing rehabilitation post-discharge. Conclusions: Demand for inpatient rehabilitation for disabling N2O toxicity appears to be increasing. In this series, cases were young, exhibited serious impairments, and had multidisciplinary rehabilitation needs. Inpatient rehabilitation led to significant functional improvements, though ongoing disability was evident post-discharge.

There appears to be rising demand for multidisciplinary rehabilitation to manage neurological disabilities from recreational Nitrous Oxide (N₂O) misuse.Heavy N₂O misuse can cause serious impairments and activity limitations across sensorimotor, cognitive and psychosocial domains.Intensive, multidisciplinary rehabilitation can improve functional independence for people with disabling N₂O toxicity; specialist rehabilitation services should be involved in optimising care of this population.Ongoing disability and the need for longer-term rehabilitation and support following hospital discharge were evident in severe cases of N₂O toxicity.

A Case Report and Literature Review on Dietary Practices and Megaloblastic Anemia in a Young Female: Unraveling the Impact of Nutrition on Hematological Health.

Megaloblastic anemia, stemming from vitamin B12 or folate deficiencies, poses diagnostic challenges due to its diverse clinical presentation. We report a case of a 25-year-old female college student presenting with symptoms indicative of megaloblastic anemia, attributed to her recent adoption of a strict vegetarian and vegan diet. Clinical manifestations included dizziness, palpitations, blurred vision, vertigo, headaches, burning sensations, excessive sweating, mouth ulcers, and unintentional weight loss. Physical examination revealed pale palpebral conjunctiva and sweating on the palms and soles. Laboratory findings confirmed megaloblastic anemia secondary to vitamin B12 deficiency, with elevated mean corpuscular volume (MCV), reticulocyte count, serum methylmalonic acid (MMA), and homocysteine levels. Treatment with intramuscular cyanocobalamin injections and oral vitamin B12 supplementation led to symptomatic improvement and normalization of hematological parameters. This case underscores the crucial role of dietary habits in hematological health. Vegetarian and vegan diets, devoid of animal products rich in vitamin B12, increase the risk of deficiency. Early recognition and management of such deficiencies are imperative to prevent long-term complications. A literature review corroborates the association between vegetarianism/veganism and megaloblastic anemia risk. Healthcare providers should vigilantly assess dietary histories, particularly in patients with hematological abnormalities. Further research is warranted to explore strategies for optimizing nutrient intake in individuals adhering to vegetarian or vegan diets, aiming to mitigate the risk of nutritional deficiencies and associated complications.

Vitamin B12 Deficiency in Children and Adolescents: A Case for Revised Diagnostic Parameters.

BACKGROUND: Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications. CASE SUMMARY: Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years. The 13-year-old male patient had behavioral changes, gastrointestinal complaints, and sensory disturbances from an early age.Diagnosis: Both adolescents displayed B12 levels that were considered low-normal based on adult thresholds, complicating their diagnostic processes. Their diverse and atypical symptomatology required a comprehensive review of their medical and family histories, clinical symptoms, and risk factors.Intervention: Treatment included administration of hydroxocobalamin injections, complemented by dietary adjustments.Outcome: Both patients responded well to the treatment, showing significant improvements in their symptoms and overall quality of life. CONCLUSION: The main takeaway from these cases is the importance of tailoring diagnostic adequate thresholds and treatment plans to the pediatric population to address and manage B12 deficiency effectively. This approach can significantly enhance patient outcomes and prevent the progression of potentially severe complications in later life.

Plain language titleRevisiting Diagnostic Criteria for Vitamin B12 Deficiency in Children and Adolescents, a Case ReportPlain language summaryVitamin B12 deficiency is surprisingly common in kids and teenagers, but the problem is, only adult standards are available to diagnose it. Research shows that healthy children can have much different B12 levels than adults, meaning some kids with a deficiency might not get the help they need quickly. We share stories of 2 teenagers who suffered from B12 deficiency with very different symptoms, from extreme tiredness to mood changes and stomach issues. These cases show that diagnosing B12 deficiency can be difficult, especially with symptoms that don't fit the usual pattern. However, once they were properly diagnosed and treated adequate, these young people saw significant improvements in their health. These cases highlight the need for new standards tailored to children, to better identify and treat B12 deficiency early on, improving their quality of life.

Lack of Clinical Evidence Regarding the Guidelines for Vitamin B12 Deficiency: An Analysis From Literature and Recommendations From Clinical Practice.

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 titleAnalyzing the Lack of Research on Vitamin B12 Deficiency Guidelines: Insights from Studies and Clinical AdvicePlain language summaryThis 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.

Development of a Vitamin B12 Deficiency Patient-Reported Outcome Measure for Clinical Practice and Research.

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 titleDevelopment of a Vitamin B12 Deficiency Questionnaire for Clinical Practice and ResearchPlain language summaryThis 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.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients.

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.

Vitamin B12 Deficiency in Clinical Practice-Proceedings of the International B12 Conference, June 2023, Rotterdam.

This supplement of the Food and Nutrition Bulletin is dedicated to the proceedings of "the International B12 Conference in Clinical Practice," held in Rotterdam in June 2023. The conference brought together physicians, scientists, patient groups, and health care professionals with substantial expertise in diagnosing and treating vitamin B12 deficiency from many universities around the world. With a collective commitment to advancing clinical practice and improving patient outcomes, this event was instrumental in addressing the many complex and challenging aspects of vitamin B12 deficiency. The subjects explored at the conference ranged from the latest research findings to real-world case studies, spanning diverse medical disciplines, including pediatrics, obstetrics, neurology, internal medicine, gastroenterology, psychiatry, clinical chemistry, nutrition, public health, biomedical science, and nursing. The broad spectrum of disciplines reflects the multifaceted nature of vitamin B12 deficiency and underscores the necessity of a comprehensive and multidisciplinary approach to its diagnosis and treatment. This supplement aims to distill into a concise and accessible format the knowledge shared by stimulating and provocative presentations at the B12 Conference and to make the information available for the broader scientific and health care community. The compendium bridges the insights generated at the conference and the wider audience of health care practitioners, researchers, and policymakers who recognize the urgency of addressing the critical public health concerns surrounding vitamin B12 deficiency.

Plain language title Vitamin B12 Deficiency in Clinical Practice: Proceedings of an International B12 Conference Plain language summary This supplement focuses on vitamin B12, a crucial micronutrient essential for overall human health. It summarizes the proceedings of the "International B12 Conference in Clinical Practice," held in June 2023 in Rotterdam. The conference gathered experts from various fields, including physicians, scientists, patient groups, and health care professionals, to address the complexities of diagnosing and treating vitamin B12 deficiency. The content covers various topics, from the latest research findings to real-world case studies spanning diverse medical disciplines. The aim is to distill the conference's knowledge into an accessible format for the broader scientific and health care community. The supplement emphasizes the need for a comprehensive and multidisciplinary approach to address Vitamin B12 deficiency by bringing together insights from different disciplines. The manuscripts within the supplement delve into the intricacies of vitamin B12 deficiency offering a synthesis of research findings, clinical insights, and innovative approaches to diagnosis and treatment. The goal is to inspire further research, inform clinical practice, and ultimately improve patient care in the critical areas of nutrition and health care. The supplement expresses gratitude to conference contributors, attendees, and supporters who made the event and publication possible. It aims to contribute to preventing or treating B12 deficiency and improving patients' health and well-being. Whether at the beginning or end of life and all ages in between, addressing B12 deficiency can significantly enhance global health and quality of life.

Metformin-Induced Vitamin B12 Deficiency in Patients with Type 2 Diabetes: A Narrative Review with a Practical Approach for Screening, Diagnosing, and Managing Vitamin B12 Deficiency.

Metformin is the most widely used antihyperglycemic drug in patients with type 2 diabetes (T2D). Over the past 2 decades, several studies have highlighted a substantial increase in the risk of vitamin B12 deficiency in patients with T2D on metformin therapy. This can lead to several complications and induce or exacerbate peripheral neuropathy. Despite these data, there are no definite guidelines for screening, diagnosing, and treating vitamin B12 deficiency in patients with T2D on metformin therapy. Therefore, in this narrative review, we aimed to suggest a practical diagnostic and therapeutic strategy to address vitamin B12 deficiency in patients with T2D receiving metformin treatment. Clinical evidence supporting an increased risk of vitamin B12 deficiency in patients with T2D on metformin therapy and its risk factors and potential complications are also discussed.