Vitamin B12 Supplementation Research Articles

Riboflavin ameliorates intestinal inflammation via immune modulation and alterations of gut microbiota homeostasis in DSS-colitis C57BL/6 mice.

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1β, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.

Vitamin B12, fatty acids EPA and DHA during pregnancy and lactation in women with a plant-based diet

Pregnancy and lactation represent a complex stage from a nutritional point of view, since energy, protein and micronutrient requirements increase during these stages. The literature describes that a well-planned plant-based diet can be sufficient in energy, macronutrients and micronutrients, with the exception of vitamin B12 and possibly n3 polyunsaturated fatty acids, mainly EPA and DHA. During the last few years, adherence to this diet has increased rapidly in the population, so the main objective of this article is to review the current evidence on the intake and concentrations of vitamin B12, EPA and DHA during pregnancy and lactation in women following a plant-based diet. A literature search was performed in PubMed, Scopus, Web of Science and Ovid MedLine using free terms and MESH. Eleven articles were selected in this review. Well-planned vegetarian and vegan diets, with adequate supplementation of vitamin B12, EPA and DHA, are compatible during pregnancy and lactation, being a positive predictor of their content in breast milk. A similar situation was observed in plasma levels in women supplemented with B12. However, it is important to continue with research in this area that considers an adequate dietary anamnesis, integral evaluation of nutritional status, estimation of nutritional requirements and an individualized nutritional plan.

Vitamin B6 and diabetes and its role in counteracting advanced glycation end products.

Naturally occurring forms of vitamin B6 include six interconvertible water-soluble compounds: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PLP is the catalytically active form which works as a cofactor in approximately 200 reactions that regulate the metabolism of glucose, lipids, amino acids, DNA, and neurotransmitters. Most of vitamers can counteract the formation of reactive oxygen speciesand the advanced glycation end-products (AGEs) which are toxic compounds that accumulate in diabetic patients due to prolonged hyperglycemia. Vitamin B6 levels have been inversely associate with diabetes, while vitamin B6 supplementation reduces diabetes onset and its vascular complications. The mechanisms at the basis of the relation between vitamin B6 and diabetes onset are still not completely clarified. In contrast more evidence indicates that vitamin B6 can protect from diabetes complications through its role as scavenger of AGEs. It has been demonstrated that in diabetes AGEs can destroy the functionality of macromolecules such as protein, lipids, and DNA, thus producing tissue damage that result in vascular diseases. AGEs can be in part also responsible for the increased cancer risk associated with diabetes. In this chapter the relationship between vitamin B6, diabetes and AGEs will be discussed by showing the acquired knowledge and questions that are still open.

A novel and apparent de novo ALAS2 missense variant associated with congenital sideroblastic anemia.

Congenital sideroblastic anemia (CSA) constitutes a group of inherited erythropoietic disorders. Some affect mainly or exclusively erythroid cells; other syndromic forms occur within multisystem disorders with extensive nonhematopoietic manifestations. In this study, we have performed clinical and molecular investigations on a 10-year-old boy suspected of having CSA. Routine blood examination, peripheral blood and bone marrow smears, and serum iron tests were performed. Gene mutation analysis was conducted using whole-exome sequencing (WES) and the results were confirmed using Sanger sequencing. Furthermore, the functional impact of the identified variant was assessed/predicted with bioinformatics methods. The patient presented with severe microcytic anemia (hemoglobin, 50 g/L), iron overload and ring sideroblasts in the bone marrow. Moreover, WES revealed the presence of a hemizygous missense variant in ALAS2 (c.1102C > T), changing an encoded arginine to tryptophan (p. Arg368Trp). This variant was verified via Sanger sequencing, and neither of the parents carried this variant, which was suspected to be a de novo variant. Using in silico analysis with four different software programs, the variant was predicted to be harmful. PyMol and LigPlot software showed that the p. Arg368Trp variant may result in changes in hydrogen bonds. The patient was treated with vitamin B6 combined with deferasirox. After 6 months, the hemoglobin increased to 99 g/L and the serum ferritin decreased significantly. We report a novel pathogenic variant in the ALAS2 gene (c.1102C > T:p. Arg368Trp), which caused CSA in a 10-year-old boy. Mutational analysis is important in patients with CSA when family history data are unavailable. Anemia due to the ALAS2 Arg368Trp variant responds to pyridoxine supplements.

Dietary Pyridoxine Requirements of Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

A 10-week feeding trial was conducted to investigate the dietary pyridoxine requirements of coho salmon (Oncorhynchus kisutch) post-smolts with an initial mean body weight of 180.22 ± 0.41 g. Seven diets were prepared with gradient pyridoxine levels of 0.32, 1.25, 2.56, 4.08, 8.24, 16.02, and 32.32 mg/kg, respectively, and each diet was assigned to three replication groups of 10 fish. The results revealed that coho salmon fed the diet with pyridoxine supplementation gained more final body weight (FBW), specific growth rate (SGR), and better feed conversion ratio (FCR). FBW and SGR of the fish fed the diet with 8.24 mg/kg pyridoxine were significantly higher than those of the other groups (P < 0.05). An inverse trend was observed for FCR, which was the lowest in fish fed the diet with 8.24 mg/kg pyridoxine. The gradient pyridoxine levels did not yield any statistically (P > 0.05) significant impact on the whole-body composition including moisture, ash, crude lipid, and crude protein. The hepatic pyridoxine concentration, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities increased significantly with dietary pyridoxine levels increasing from 0.32 to 4.08 mg/kg (P < 0.05) and plateaued after that (P > 0.05). The coho salmon fed the diet with 8.24 mg/kg pyridoxine achieved the maximum superoxide dismutase and catalase, as well as the minimum total cholesterol, triglyceride, and malondialdehyde. Broken line analysis of SGR, FCR, AST, and ALT activities reflected the optimal dietary pyridoxine requirements for coho salmon post-smolts from 3.92 to 7.08 mg/kg diet.

Vitamin B12 Supplementation Improves Oocyte Development by Modulating Mitochondria and Yolk Protein in a Caffeine-Ingested Caenorhabditis elegans Model.

Vitamin B12 is an essential cofactor involved in the function of two enzymes: cytosolic methionine synthase and mitochondrial methylmalonic-CoA mutase. In our previous studies, caffeine (1,3,7-trimethylxanthine), the most popular bioactivator, was shown to reduce yolk protein (vitellogenin) and fertility in a Caenorhabditis elegans model. Based on the previous finding that methionine supplementation increases vitellogenesis in C. elegans, we investigated the role of vitamin B12 in methionine-mediated vitellogenesis during oogenesis in caffeine-ingested animals (CIA). Vitamin B12 supplementation improved vitellogenesis and reduced oxidative stress by decreasing mitochondrial function in CIA. Furthermore, the decreased number of developing oocytes and high levels of reactive oxygen species in oocytes from CIA were recovered with vitamin B12 supplementation through a reduction in mitochondrial stress, which increased vitellogenesis. Taken together, vitamin B12 supplementation can reverse the negative effects of caffeine intake by enhancing methionine-mediated vitellogenesis and oocyte development by reducing mitochondrial stress.

Effects of Vitamin B 12 Supplementation on Cognitive Function in Survivors of Hemorrhagic Stroke

Background: Hemorrhagic stroke often leads to significant cognitive deficits in survivors. Vitamin B12 plays a crucial role in neurological functions, suggesting its potential in cognitive recovery post-stroke. This retrospective cohort study explored the impact of Vitamin B12 supplementation on cognitive function in hemorrhagic stroke survivors, a subject that holds substantial importance in stroke rehabilitation and patient care. Objective: The primary objective was to evaluate the effectiveness of Vitamin B12 supplementation in improving cognitive function, as measured by MMSE and MoCA scores, in adults who have recently survived a hemorrhagic stroke. Methods: The study included 75 adults diagnosed with hemorrhagic stroke within the last six months. Participants were administered a daily oral dose of 1000 mcg of Vitamin B12 for three months. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at the start and end of the supplementation period. Additionally, Vitamin B12 levels were measured at baseline and after three months to gauge the physiological uptake of the supplement. Results: The study observed significant improvements in cognitive function, with the MMSE score increasing by an average of 2.2 (p=0.0463) and the MoCA score by 5.8 (p=0.0410). There was also a notable average increase of 400 pg/mL in Vitamin B12 levels (p&lt;0.05). The supplementation was generally well-tolerated, with only 8% of participants reporting minor adverse effects, a rate not statistically significant (p&gt;0.05). Conclusion: The study provides preliminary evidence that Vitamin B12 supplementation may positively impact cognitive function in survivors of hemorrhagic stroke. However, due to the study's limitations, further extensive research is necessary to corroborate these findings and to deepen our understanding of the role of Vitamin B12 in post-stroke cognitive recovery.

A Comprehensive Examination of Vegan Lifestyle in Italy.

The popularity of veganism and plant-based diets is rapidly increasing worldwide, including in Italy, where more individuals and families are adopting this lifestyle. However, medical and health professionals often lack the necessary knowledge and are skeptical about this diet despite the scientific evidence. It is important for them to provide support and expertise to those following this diet. The survey evaluated various aspects of the lifestyle of Italian vegans living in Italy and abroad, including food frequency, vitamin and mineral supplementation, relationship with medical and health professionals, and perceived difficulties in daily life. The emphasis was on potentially critical aspects for those following this dietary choice. A cross-sectional survey was conducted in Italy between March and April 2022. A questionnaire was distributed through social media platforms such as Instagram, Facebook, and Telegram, and 2180 Italian adults who follow a vegan diet completed it. The survey found that most of the vegan population surveyed were female, showed a greater sensitivity to ethical issues, were aware of the need for vitamin B12 supplementation, and followed healthy-eating guidelines. It is evident that despite the increasing popularity of plant-based diets, many medical and health professionals remain cautious and hesitant to recommend them.

Medical management of vegetarian and vegan children in France: Medical practices and parents’ perceptions

ObjectivesDespite a significant increase in the prevalence of vegetarianism and veganism in children in France, data on the care pathway of these children are scarce. This study aimed to describe the characteristics of the medical follow-up of vegan/vegetarian children, to evaluate the medical practices, and to analyze the perceptions of parents. Materials and methodsThis was a double cross-sectional survey. One questionnaire was sent to parents of vegetarian/vegan children, and the other to French doctors (pediatricians or general practitioners). ResultsA total of 241 vegetarian families responded to the study and nearly one quarter (n = 67, 28 %) were unsatisfied with the medical follow-up of their child. Parents considered that their child's diet was responsible for refusing a medical consultation in 11 % (n = 27) of cases. In almost one third of cases (n = 70, 29 %), participants declared that the doctor was unaware of their child's diet. Vitamin B12 supplementation was commonly used (n = 195, 81 %), mainly by self-medication, and laboratory testing was performed for 30 % (n = 72) of children. Regarding the questionnaire for doctors, most of the participants (n = 318/501, 63 %) reported having vegetarian/vegan children in their cohort. A few of them (n = 70, 14 %) declared they did not systematically screen for meat and fish consumption during consultations. Doctors caring for vegetarian/vegan children had 27 % correct answers to questions regarding the nutrition guidelines. Overall, 36 % of them (n = 117) systematically referred the child to a specialist. ConclusionThe medical follow-up of vegetarian/vegan children in France is very heterogeneous. Parents and doctors alike stressed the need to develop reliable sources of knowledge. A systematic screening of the diet and a referral to a specialist could help to improve the management of vegetarian/vegan children.

Supplementing semen extenders with a combination of phosphorus and vitamin B12 Improves post-thawed cryopreserved rooster semen quality.

Semen cryopreservation is an important technique for preserving the genetic material of numerous species. However, frozen semen is highly susceptible to sperm DNA damage and reduced motility, resulting in decreased fertility. The standard method for cryopreservation and several approaches have not been elucidated. This study aimed to determine the effects of supplementing rooster semen extender with a combination of phosphorus and vitamin B12 on cryopreserved semen quality. Semen was collected weekly via dorso-abdominal massage from 57 Burmese × Vietnam-crossbred Thai native roosters aged 1-3 years. In total, 139 semen samples were collected, pooled, and diluted to 200 million sperm per dose. The pooled sample was divided into six experimental groups: a control group (0.00%) diluted with modified Beltville Poultry Semen Extender (BPSE) and five treatment groups diluted with modified BPSE supplemented with phosphorus and vitamin B12 at concentrations 0.02, 0.04, 0.06, 0.08, and 0.10%, respectively. The semen samples were frozen and evaluated at 0, 15, and 30 min after thawing. Sperm kinematic parameters were determined using a computer-assisted sperm analysis system. Sperm quality was evaluated by measuring sperm viability, mitochondrial activity, acrosome integrity, and plasma membrane integrity. Statistical analyses were performed using a general linear mixed model (MIXED) in SAS. Factors in the statistical model were experimental groups, time after thawing, and interaction between experimental groups and time after thawing. Total and progressive motilities were greater in semen supplemented with 0.04% phosphorus and vitamin B12 compared with those in the control (p < 0.05). At 15 min post-thawing, VCL, VAP, and HPA in the 0.04% phosphorus and vitamin B12 supplementation group was greater than that in the control (p < 0.05). Phosphorus and vitamin B12 supplementation did not affect sperm kinematics at 0 and 30 min after thawing (p > 0.05). All the sperm parameters that were tested for the 0.04% phosphorus and vitamin B12 supplementation group in modified BPSE were the highest at all the timepoints after thawing. Thus, supplementing frozen semen extender with 0.04% phosphorus and vitamin B12 increased sperm motility, sperm kinematic parameters, and sperm quality.

An examination of relationships between vitamin B12 status and functional measures of peripheral neuropathy in young adult vegetarians.

Prevalence rates for vitamin B12 deficiency in U.S. adult vegetarians may exceed 30%, which is concerning given the role for this vitamin in numerous nervous system functions, including the synthesis of myelin sheaths. Defective myelin synthesis and repair are directly linked to peripheral neuropathy; yet, few investigations have examined how physical indicators of peripheral neuropathy (e.g., hand dexterity, vibration sensitivity and balance) are impacted in individuals adhering to vegetarian diets. This feasibility research explored the relationships between peripheral neuropathy and vitamin B12 status using a cross-sectional study design. In addition, a small pilot trial was conducted for limited-efficacy testing of vitamin B12 supplementation for reducing peripheral neuropathy. Healthy, able-bodied adults (n = 38; 19-40 years of age) reported exclusive adherence to a vegetarian or vegan diet for 3 years. Peripheral neuropathy was measured using a force plate for assessing balance, and a vibration sensitivity tester and pegboard tests to assess hand dexterity. Serum vitamin B12 and folate were measured using standard radioimmunoassay techniques. Twenty-six percent of the sample displayed deficient or marginal vitamin B12 status (serum vitamin B12 <221 pmol/L). Participants with adequate vitamin B12 status scored 10% higher on the Purdue pegboard assembly test and 20% higher on the left hand adjusted functional dexterity test in comparison to participants with marginal-to-deficient vitamin B12 status (p < 0.05). These data provide preliminary evidence that peripheral neuropathy can be detected in individuals with marginal-to-deficient vitamin B12 status.

Riboflavin supplements for blood pressure lowering in adults

Riboflavin supplements for blood pressure lowering in adults

Low vitamin B12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania.

Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2 , B6 , B9 and B12 , and vitamin C that were measured in blood samples from 820 SCD patients from Tanzania with no history of hospital admission, infections or painful episodes in the previous 30 days. We studied children (0-8 years), early adolescents (9-14 years), late adolescents (15-17 years) and adults (≥18 years). Severely low levels of vitamin B12 were observed across the four age groups. Despite the lowered vitamin B12 concentrations, total homocysteine concentrations were normal across both genders in all age groups. We found no significant gender-related differences between the other measured micronutrients. In this large SCD population, spanning the whole life cycle, a low level of vitamin B12 was consistently found across both genders and all age groups. Given the pivotal role of vitamin B12 in cellular metabolism, particularly in erythropoiesis, more studies are required to unravel how to better detect clinically relevant vitamin B12 deficiency among SCD patients, and thus to identify more precisely those who need supplementation of vitamin B12 .

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models.

Traumatic brain injury is a major cause of death and disability worldwide, affecting over 69 million individuals yearly. One-carbon metabolism has been shown to have beneficial effects after brain damage, such as ischemic stroke. However, whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation. The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury. PubMed, Web of Science, and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes. The search terms included combinations of the following words: traumatic brain injury, dietary supplementation, one-carbon metabolism, and B-vitamins. The focus of each literature search was basic science data. The year of publication in the literature searches was not limited. Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recovery of animals with traumatic brain injury compared to controls. However, this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delivery of vitamin supplementation post-traumatic brain injury. The details of supplementation post-traumatic brain injury need to be further investigated. Overall, we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems. Further investigation in a clinical setting should be strongly considered in conjunction with current medical treatments for traumatic brain injury-affected individuals.

197 The effects of pyridoxine supplementation during oocyte maturation on the in vitro production of pig embryos

197 The effects of pyridoxine supplementation during oocyte maturation on the in vitro production of pig embryos

Abstract A021: Nutrient competition in the tumor microenvironment alters NK cell metabolism in Pancreatic Cancer

Abstract Tumor cells present constant nutritional demand of macronutrients and micronutrients for their rapid growth needs. Often this nutrient limitation hampers the function of anti-tumor immune cells, which need basal energy levels to execute cytotoxic effects against malignant cells. Hence, we investigated nutrient limitation-induced metabolic alterations in NK cells that regulate the anti-tumor activity of NK cells. Using 2D cultures and PDAC organoid models, we demonstrate that pancreatic tumor cells exhaust vitamin B6 (VB6) in the co-culture milieu, causing reduced killing activity of NK cells. Additionally, we demonstrate that PDAC patients have significantly reduced plasma VB6 as compared to the healthy counterparts. This data aligns with the epidemiological studies showing that VB6 intake reduces the risk of pancreatic cancer incidence. Moreover, we noted a significant reduction in circulating VB6 in the pancreatic tumor-bearing mice as compared to healthy counterparts. Utilizing mass spectrometry-based metabolomics we noted that limitation of the VB6 prevents glycogen breakdown in NK cells. This was validated by follow up electron microscopy-based studies that demonstrated glycogen depots in NK cells that were very prominent upon inhibiting glycogenolysis. Metabolic tracing studies demonstrated that NK cells require VB6 for intracellular glycogen breakdown. Correspondingly, knocking down glycogen phosphorylase, a key enzyme involved in glycogen breakdown abrogated anti-tumoral NK cell function. Notably, supplementation of co-cultures in 2D and organoid models and in vivo orthotopic mouse models, with VB6 restored NK cell function against pancreatic tumor cells. In parallel, we observed dependence of tumor cell metabolism on VB6 for sustaining growth. Accordingly, we observed that tumor cells actively deplete VB6 in tumor microenvironments, as observed by comparing VB6 levels in circulation and in tumor interstitial fluids. Finally, we observed that VB6 supplementation in combination with inhibitors targeting VB6-driven metabolic pathway dependencies in tumor cells effectively enhances NK cell frequency and diminishes tumor burden in vivo. These studies demonstrate a novel role of glycogen breakdown as a critical energy source for activated NK cells and demonstrate, for the first time a key role of glycogenolysis in NK cell cytotoxic activities. Our results expand the understanding of the critical role of micronutrients (vitamin B6) in regulating cancer progression and anti-tumor immunity and open new avenues for developing NK cell-based immunotherapies for PDAC patients. Citation Format: Kamiya Mehla. Nutrient competition in the tumor microenvironment alters NK cell metabolism in Pancreatic Cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A021.

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

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

Anemia Outside the Box: Nonimmune Intramedullary Hemolytic Anemia Driven By Vitamin B12 Deficiency

Introduction: Vitamin B12 and folate deficiencies are common etiologies of macrocytic anemia, mostly encountered with chronic alcohol use, and uncommon for healthy individuals with unremarkable medical history. The pathogenesis of the resulting anemia is described by two possible mechanisms: either ineffective erythropoiesis, driven by vitamin B12 deficiency, or more rarely, via nonimmune intramedullary hemolysis. We present a very rare case of severe vitamin B12 deficiency leading to nonimmune intramedullary hemolysis and highlight the diagnostic evaluation and tailored management. Case Presentation: A 49-year-old female with history of depression, chronic alcohol use and chronic nitrous oxide inhalation, presented with lethargy, hypotension and fevers with visual hallucinations, and was subsequently admitted for acute encephalopathy. Findings on physical examination included diminished proprioception and diminished sensation to fine touch, pinprick and vibration of the lower extremities with distal hyperreflexia of the patellar and Achilles tendon reflexes bilaterally. Lab work was notable for leukopenia and macrocytic anemia with a significant drop in hemoglobin to 9.6 from a baseline of 13.2 within 5 months and MCV of 103. Extensive investigation of encephalopathy was undertaken, of which we note infectious workup, prompted by the septic presentation, which showed Staphylococcus aureus bacteremia. On the other hand, the patient's anemia was concurrently investigated. Hemolysis workup was positive (LDH 394 U/L; direct bilirubin 1.6 mg/dL; haptoglobin&amp;lt;8 mg/dL; reticulocyte count 6.1%); however, schistocytes were low on peripheral smear (Figures 1 and 2). As such, nonimmune intramedullary hemolysis was suspected. Further anemia workup revealed severe vitamin B12 deficiency (75 ng/L), consistent with the physical exam findings, but normal folate levels. Of note, methylmalonic acid levels and homocysteine were also elevated (respectively 4.39 nmol/mL, and 142 umol/L). The constellation of the clinical presentation and all the laboratory findings confirmed a nonimmune intramedullary hemolytic process, elicited by vitamin B12 deficiency. This deficiency was thought to be multifactorial, mainly caused by chronic alcohol abuse, in addition to persistent nitrous oxide use. It was also suggested that hemolysis could be a consequence of drug-induced carboxyhemoglobinemia (level was 9.4%), whereby carboxyhemoglobin can form during the binding and release of nitric oxide from hemoglobin. Treatment was focused on replacing vitamin B12 with 1000 mcg daily intramuscular injections for 7 days, then weekly thereafter for 4 weeks, followed by monthly injections. Improvement of hemoglobin to 11.1 with improvement of neurologic exam findings were noted prior to discharge. Conclusion: Nonimmune hemolytic anemia must be included in the differential diagnosis when evaluating patients with anemia concurrent with vitamin B12 deficiency, mostly encountered with chronic alcohol use. Vitamin B12 supplementation remains the key treatment to correct this rare, but serious outcome of vitamin B12 deficiency.

Awareness of the Effect of Vitamin B12 Deficiency on the Nervous System Among the General Population in Taif, Saudi Arabia.

Vitamin B12 is important for the health of the nervous system, its deficiency leads to various neurological manifestations such as visual problems, ataxia, peripheral neuropathy, dementia, etc. The deficiency can be caused by malnutrition, malabsorption, or increased demand. Early detection is important for the control and prevention of complications. In December 2021, a population-based cross-sectional survey was carried out among Saudi males and women at least 18 years old. There were 383 participants in the sample. An electronic survey distributed over social media was used to collect the data. SPSS version 28 was used to analyze the data. The majority of the respondents were female (88%). Most participants were aged 18-25 years (44%). Regarding participants' awareness and knowledge of vitamin deficiency, 64% were aware of vitamin B12 deficiency. 41.7% of participants knew about food sources of vitamin B12, 29.0% knew how to prevent it, and 30.0% took vitamin B12 supplements. (92.2%) of the participants were not following vegetarian or vegan diets. Difficulty concentrating accounted for the highest number of reported symptoms by the respondents (53.8%). This study recommends a scientific approach encouraging patients to self-report their B12 deficiency in medical institutions. In addition, a study about the relationship between B12 deficiency and other neurodegenerative disorders is also a recommendation of this study.

Evaluation of the response to vitamin B12 supplementation in patients with atrophy in sleeve gastrectomy materials

Evaluation of the response to vitamin B12 supplementation in patients with atrophy in sleeve gastrectomy materials