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.

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.

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.

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.

National and regional population attributable fractions for anemia risk factors (iron, folate, and vitamin B12) in Belize: potential impact of fortification.

Objective: To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods: A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15-49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results: The overall prevalence of anemia (hemoglobin <12 g/dL) was 21.2% (95% CI [18.7, 25.3]). The prevalence of anemia was significantly greater among women with iron deficiency (59.5%, 95% CI [48.7, 69.5]) compared to women without iron deficiency (15.2%, 95% CI [12.2, 18.3]; aPR 3.9, 95% CI [2.9, 5.1]). The three nutritional deficiencies examined contributed to 34.6% (95% CI [22.1, 47.1]) of the anemia cases. If all these nutritional deficiencies could be eliminated, then an estimated 5 953 (95% CI [3 807, 8 114]) anemia cases could be prevented. Conclusions: This study suggests that among women of child-bearing age in Belize, anemia cases might be reduced by a third if three modifiable nutritional risk factors (iron, RBCF, and vitamin B12 deficiencies) could be eliminated. Fortification is one potential strategy to improve nutritional status and reduce the burden of anemia in this population.

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.

Prevalence of vitamin B 12 deficiency and associated factors among primary school children: North East Ethiopia: multicenter cross-sectional study.

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.

A Rare Cause of Vitamin B12 Deficiency in the Pediatric Age.

Vitamin B12 plays an important role in DNA synthesis, hematopoiesis, and neuronal mechanisms, and its deficiency can be associated with insufficient intake or poor absorption and autoimmune and genetic diseases. Although rare, excessive, and chronic alcohol consumption may also justify a deficiency in this vitamin. We present a case of a 17-year-old Iraqi adolescent refugee in Portugal with a deficiency of vitamin B12 due to excessive and chronic alcohol consumption. Although intramuscular (IM) supplementation with cyanocobalamin is the most used, it was decided to initiate oral supplementation. After four months, vitamin B12 levels were replenished. With this clinical case, we aim to raise awareness of the cause of cyanocobalamin deficiency, which although rare in pediatric age should be considered in adolescents, given the possibility of risky behaviors in this age group. Additionally, given the therapeutic options, we have found that oral administration of vitamin B12 has been effective, as reported in the literature.

Vision Loss as a Presenting Symptom of Vitamin B12 Deficiency.

Nutritional optic neuropathy is a rare and often overlooked factor leading to bilateral, symmetrical, and gradual visual impairment. This condition falls within the category of metabolic neuropathies. We documented a case involving bilateral nutritional optic neuropathy attributed to pancytopenia associated with vitamin B12 deficiency. A healthy 65-year-old Indian woman reported a bilateral, progressive, painless decline in vision over the past six months. She had a history of reduced oral intake for the preceding year and denied experiencing any gastrointestinal or constitutional symptoms. Bilateral visual acuity was 1/60. Examination revealed pale optic discs with attenuated vessels in both eyes and a cup-disc ratio of 0.3. The blood analysis showed low indices and a deficiency in serum vitamin B12. Despite undergoing treatment, her vision remained impaired due to the chronic nature of the condition. This case highlights the importance of identifying visual symptoms in an elderly woman experiencing malnutrition caused by inadequate dietary habits, which leads to bilateral nutritional optic neuropathy.

Effect of calcium supplementation on reversing metformin-based inhibition of vitamin B12 bioavailability in healthy adults using a [13C] cyanocobalamin tracer - A pilot study.

BACKGROUND & AIMS: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B12 (B12) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B12 absorption using a novel stable isotope [13C] cyanocobalamin tracer. METHODS: A pilot crossover study was conducted to estimate the bioavailability of B12 in healthy subjects, using [13C] cyanocobalamin as a tracer. In the study, [13C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC). RESULTS: Seven participants completed all three experiment days. The mean B12 bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B12 bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003). CONCLUSION: B12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B12 deficiency needs to be further studied.

Exploring the Nexus: A Systematic Review on the Interplay of the Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T Genotype, Hyperhomocysteinemia, and Spontaneous Cervical/Vertebral Artery Dissection in Young Adults.

Ischemic strokes (IS) in young adults often evade early detection, resulting in delayed diagnosis until complications arise. Cervical/vertebral artery dissection, a significant contributor to these strokes, presents with symptoms such as migraine with aura, severe headache, and neck pain, commonly overlooked due to their nonspecific nature. This review investigates early indicators of artery dissections, emphasizing their importance in diagnosis and exploring the correlation between methylenetetrahydrofolate reductase (MTHFR) gene C677T genotype polymorphism, hyperhomocysteinemia (HHCY), and IS in young adults. This systematic review encompasses a thorough analysis of 11 papers, including four observational studies, three case reports, three narrative reviews, and one experimental study, involving 4,840 patients aged 18-45 years. Findings reveal HHCY as a significant contributor to vascular damage and tissue ischemia leading to IS. The MTHFR gene C677T genotype polymorphism is closely associated with HHCY, often contributing to underdiagnosed strokes in young adults. Cervical/vertebral artery dissection may manifest as initial symptoms of neck pain or headache, remaining undiagnosed until imaging is conducted. Importantly, the review suggests that MTHFR gene polymorphism can be mitigated through simple supplementation with vitamin B12 and folates, serving as a valuable tool for primary prevention. Additionally, betaine, a methyl donor, was explored in severe MTHFR gene polymorphism cases resistant to conventional supplementation. In conclusion, recognizing the significance of early signs and symptoms, along with a high clinical suspicion, is crucial for preventing catastrophic outcomes, mortality, and morbidity associated with IS in young adults lacking traditional risk factors. The MTHFR gene C677T genotype polymorphism, a potential genetic cause, can be easily managed with simple measures but is often overlooked or underdiagnosed.

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study.

BACKGROUND: The absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy. OBJECTIVES: We aimed to assess the efficacy of oral vitamin B12 supplementation in PA. METHODS: We enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid-to-creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 µg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration. RESULTS: We included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297-485) compared with 148 (116-213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9-29.8) compared with 18.6 (13.7-46.8) µmol/L; P < 0.0001], and pMMA [0.24 (0.16-0.38) compared with 0.56 (0.28-1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms. CONCLUSIONS: Oral supplementation with 1000 µg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

Impact of Prevalent Dietary Pattern on Serum Vitamin B12 Status and Its Association With Inflammation Among Reproductive Age Women.

SCOPE: Association between vitamin B12 deficiency (VB12D) and dietary patterns being well documented has bearing on obstetrics and neonatal outcomes. However, relationship between VB12D and serum inflammatory markers (IMs), particularly in vegetarian diet and Polycystic ovary syndrome (PCOS), remains elusive. This cross-sectional study assesses VB12D and IMs among reproductive age women consuming different diets. METHODS AND RESULTS: Nonvegetarian (PCOS, n = 104; healthy, n = 148) and vegetarian women (PCOS n = 112; healthy, n = 186) are for evaluated clinical, biochemical, hormonal assessment, inflammatory, and four vitamin B 12 (VB12) markers. VB12D is defined by Fedosov's wellness quotient (4cB12). Using 4cB12, prevalence of VB12D is discerned in 54.4% (PCOS: 72.1%; healthy 36.5%) and 93.4% (PCOS: 95.9%; healthy: 91.9%) among nonvegetarians and vegetarians, respectively. Vegetarian PCOS women depict lowest median (interquartile range [IQR]) of serum B12 76.2(72.6) pg mL-1, holotranscobalamine (HTC) 37.9(11.3) and highest homocysteine (HCY) 40.32(6.0) µmol L-1, methylmalonic acid (MMA) 352.26(156.7) nmol L-1 with highest Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and IMs (Monocyte chemoattractant protein 1 (MCP-1), High sensitivity C-reactive protein (hs-CRP), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 6 (IL-6)). Significant correlation of serum hs-CRP, TNF-α, and IL-6 with VB12 markers is observed. CONCLUSION: The VB12D is rampant among reproductive age women that gets exacerbated by PCOS or vegetarian diet. It is directly correlated with magnitude of proinflammatory markers. The results carry substantial implications for public health policies aimed at improving preconception maternal VB12 status for better future pregnancy and offspring outcomes.

Serum Vitamin B12 Deficiency in Chronic Hemodialysis Patients.

Introduction Essential vitamins like folate and vitamin B12 are crucial for many physiological functions. Patients with renal failure undergoing regular hemodialysis in the general population may experience harmful effects from vitamin B12 deficits. Therefore, this study aimed to determine the frequency of vitamin B12 deficiency in hemodialysis patients and its association with other clinical parameters. Methods This cross-sectional study was conducted at the dialysis unit of Patel Hospital and Lifeline Hospital, Karachi, using a non-probability consecutive sampling technique after obtaining ethical approval from Lifeline Hospital (LLH/HR/02-22). The study duration was six months, from January 10, 2023, to July 22, 2023. A total of 135 adult renal failure patients with ages >18 and <70 years on maintenance hemodialysis for >1 year were included in the study. The chi-square test was used to determine the association between vitamin B12 deficiency and age and gender. A p-value of 0.05 was considered statistically significant. Results The study findings showed that out of 135 patients, 82 (60.7%) were males and 53 (39.3%) were females, with a mean age of 50.80 ± 10.03 years. The duration of hemodialysis was approximately 1-2 years in 98 (72.6%) patients, 2-3 years in 27 (20.0%) patients, and 3-4 years in only 9 (6.7%) patients. The mean serum vitamin B-12 levels were 411.61 ± 224.95 pg/ml, with 30 (22.2%) of the subjects being deficient. In terms of duration of hemodialysis, there was a significant association (p= 0.013). Between patients with normal 4 (4%) and deficient 5 (17%) vitamin B12 and 3-4 years of hemodialysis. Conclusion In this study, we found that a significant proportion of patients on chronic hemodialysis had vitamin B12 deficiency. Moreover, vitamin B12 deficiency was significantly associated with duration of hemodialysis. Therefore, we recommend periodic vitamin B12 testing in hemodialysis patients to avoid any associated complications.

Pernicious Anemia Unveiled: Unusual Hemolytic Complications and Clinical Implications.

Pernicious anemia (PA) is an autoimmune condition resulting in impaired vitamin B12 absorption that commonly presents with gastritis and neurological symptoms. In rare cases, associated vitamin B12 deficiency can contribute to significant red blood cell lysis, and patients can present with PA-induced pseudo-thrombotic microangiopathy (TMA) hemolytic anemia. This case describes a 59-year-old male presenting with a two-week history of gastrointestinal pain with bleeding who had anemia and hemodynamic instability on initial evaluation. After the endoscopy/colonoscopy did not reveal any active sources of bleeding and packed red blood cells failed to stabilize the patient, it was found that he had low serum B12 with anti-intrinsic factor and anti-parietal cell antibodies. A coordinated clinical approach, including parenteral cyanocobalamin and daily oral folic acid supplementation, stabilized the patient, highlighting the importance of distinguishing PA-induced pseudo-TMA from true TMA hemolytic anemia.

Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis. METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

Adult Vitamin B12 Deficiency-Associated Pseudo-Thrombotic Microangiopathy: A Systematic Review of Case Reports.

Cobalamin-deficient thrombotic microangiopathy or vitamin B12 deficiency presenting as pseudo-thrombotic microangiopathy is a rare disorder that can be misdiagnosed as thrombotic thrombocytopenic purpura. Patients with this condition are at risk of receiving unnecessary plasmapheresis with a potential delay in appropriate therapy with vitamin B12 supplementation. There are no established diagnostic criteria for this condition in clinical practice. We performed a systematic review of case reports published between January 2018 and January 2023 to analyze the clinical characteristics, risk factors, and patterns of laboratory markers to improve the diagnostic criteria for this condition.

A Case Report of Simultaneous Intracranial Hemorrhage and Cerebral Venous Sinus Thrombosis in a Young Indian Male: Diagnostic and Therapeutic Challenges.

This case report discusses the intricate diagnostic and therapeutic challenges faced by a 23-year-old Indian male who presented with altered consciousness, a holo-cranial headache, right-sided hemiparesis, and subsequent neurological symptoms. The patient's dietary habits, leading to vitamin B12 and folic acid deficiencies resulting in hyperhomocysteinemia, along with binge alcohol drinking leading to dehydration, were identified as the main causes of cerebral venous sinus thrombosis (CVST) in this case. The case was complicated by an additional cerebral hemorrhage. The patient received a comprehensive treatment regimen involving antiepileptic medications, intravenous fluids, and anticoagulation therapy. A decline in the Glasgow Coma Scale score prompted further interventions. Collaborative decision-making, involving neurologists, neurosurgeons, and the patient's relatives, steered the treatment course, ultimately favoring continued medical management over decompression surgery. Notably, the patient exhibited remarkable progress in mobility, achieving the ability to walk with support by the end. This case report contributes valuable insights to the understanding of CVST, emphasizing the significance of nutritional considerations, especially in vegetarians, and underscoring the importance of thorough diagnostic evaluations in complex clinical scenarios.