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

Vitamin B₁₂Deficiency and Depression in the Elderly

To determine the role of vitamin B12 deficiency in pernicious anemia and the efficacy of oral vitamin B12 replacement therapy given regardless of the etiology, and to compare the endoscopic and pathological findings in patients diagnosed with vitamin B12 deficiency. The study included 216 patients, aged 18 - 65 years, diagnosed with vitamin B12 level < 200 pg/mL between May 2015 and May 2016. Evaluation was made of the demographic characteristics of the patients, diseases, drugs used, dietary habits, previous use of vitamin B12 replacement therapy, family history of vitamin B12 deficiency, laboratory test values, and neurological symptoms present at the time of presentation. Endoscopy was applied to all the patients included in the study. Anti-parietal cell antibody (APCA) and anti-intrinsic factor antibody (AIFA) analyses were applied to all patients. Evaluation was made of a total of 216 patients diagnosed with vitamin B12 deficiency, comprising 145 (67.1%) females and 71 (32.9%) males. The mean vitamin B12 level of the patients was determined as 127 pg/mL at the time of presentation and 334 pg/mL after treatment. APCA positivity was determined in 40 (18.5%) patients, and AIFA positivity in 5 (2.3%) patients. Atrophy was determined endoscopically in 53 (24.5%) patients and pathologically in 90 (41.7%). Helicobacter pylori positivity was determined in 196 (90.7%) patients. A diagnosis of pernicious anemia (PA) was made in 4 (1.9%) patients (patients with AIFA positivity or APCA accompanied by corpus atrophy). APCA positivity was determined but not corpus atrophy in 36 (16.7%) patients and these cases were accepted as suspected pernicious anemia. In this study of 216 patients with vitamin B12 deficiency, stomach pathologies which could cause vitamin B12 deficiency (atrophic gastritis, HP, PA) and the responses to oral replacement therapy were investigated. As vitamin B12 absorption plays a role in the pathogenesis. Vitamin B12 deficiency can lead to atrophic gastritis, and this was determined with biopsy in 41.7% of the patients. APCA positivity was determined in 18.5% of the patients investigated with respect to autoimmune atrophic gastritis (pernicious anemia) and AIFA positivity in 2.3%. A diagnosis of PA was made in 4 (1.9%) patients from autoimmune marker positivity and the presence of corpus atrophic gastritis. HP was determined in 90.7% of the patients with vitamin B12 deficiency, and although no correlation was determined between HP and atrophy, HP positivity was determined in 84 (93.3%) of the patients with pathological atrophy. From the time of diagnosis, the patients in the study were prescribed 1,000 µg/day vitamin B12. At the 40-day follow-up examination, a significant increase was observed in the vitamin B12 levels of 92.5% of the patients. At the end of the study, as oral replacement therapy was seen to be effective to a great extent, even in patients with PA, it was concluded that for patients not responding to oral replacement therapy, it would be appropriate to apply parenteral vitamin B12 treatment. In developing countries such as Turkey, the role of HP infection in vitamin B12 deficiency must be kept in mind. The incidence of atrophic gastritis and pernicious anemia is higher than expected in vitamin B12 deficiency. Thus, it can be concluded that it is appropriate to investigate patients with vitamin B12 deficiency with respect to atrophic gastritis and PA, and oral replacement therapy should be the first stage in the treatment of vitamin B12 deficiency.

We carefully read the article published in the European Journal of Neurology entitled “How to distinguish Guillain-Barré syndrome from nitrous oxide-induced neuropathy: a 2-year, multicenter, retrospective study” [1]. We aim to propose suggestions regarding the use of vitamin B12 as a biomarker of nitrous oxide (N2O) intoxication. Fortanier et al. established criteria to define the Guillain-Barré syndrome (GBS)-like group; however, clinical symptoms of N2O exposure vary. Clinical and cerebrospinal fluid analysis can be available rapidly and guide treatment decisions. In case of uncertainty between GBS and N2O-induced neuropathy, intravenous immunoglobulins must be initiated for critical patients, without waiting for biological laboratory test results. Clinical symptoms of N2O exposure are related to the functional inactivation of vitamin B12 by oxidation of its cobalt ion [2]. This oxidation prevents the formation of methylcobalamin, resulting in a decrease in methionine synthase activity which converts homocysteine into methionine. A similar action is suspected for MMA-CoA mutase, which converts methylmalonic acid (MMA) into succinyl-CoA (Figure 1). Fortanier et al. only focused on the significance of serum vitamin B12 measurement, a routine laboratory test providing results within a few hours. However, as N2O leads to functional inactivation of vitamin B12, quantitative deficiency is secondary and inconsistent [3]. In N2O abuse, vitamin B12 is neither specific (prevalence of about 25% in the general population) nor sensitive: only about 50% of N2O consumers exhibit vitamin B12 deficiency [1, 3]. Functional exploration of vitamin B12 with plasma homocysteine and MMA gives informative results. These measurements were conducted but not discussed by the authors. However, as vitamin B12, homocysteine can be measured rapidly [4]. Homocysteine increases rapidly, and it is a sensitive biomarker for recent N2O consumption [3]. As reported by Fortanier et al., the majority of patients (96.2%) have elevated plasma homocysteine levels [1]. However, homocysteine lacks specificity: it also rises in cases of vitamin B9 or B12 deficiency, renal or hepatic insufficiency, hypothyroidism, and in certain metabolic disorders. Plasma MMA is a reliable marker of functional vitamin B12 deficiency. Plasma MMA lacks sensitivity in N2O intoxication as its elevation is not consistent, but is correlated with the clinical severity [3]. Plasma MMA is more specific than homocysteine in the assessment of vitamin B12 deficiency as it is independent of vitamin B6 and B9 status, but rises in cases of renal insufficiency and in certain metabolic diseases. In the context of N2O abuse, high plasma homocysteine suggests recent consumption, and plasma MMA can aid evaluation of the clinical severity [5]. Vitamin assays (B6, B9, B12) may uncover nutritional deficiencies. Consequently, it is important to exclude other causes of homocysteine or MMA elevation. The European Federation of Laboratory Medicine is in the process of formulating guidelines concerning the use of biological parameters for initial evaluation and follow-up of N2O intoxication (https://www.eflm.eu/site/page/a/1832). Data sharing is not applicable to this article as no new data were created or analyzed in this study.

BackgroundThe 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. ObjectivesWe aimed to assess the efficacy of oral vitamin B12 supplementation in PA. MethodsWe 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. ResultsWe 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. ConclusionsOral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

Editor, In neuro-ophthalmology, vitamin B12 deficiency is a known cause for bilateral visual loss because of an optic neuropathy. Traditionally, the diagnosis of vitamin B12 deficiency has been based on clinical symptoms and on the determination of serum vitamin B12 levels. However, more recent studies have given evidence that measurements of serum methylmalonic acid (MMA) and homocysteine (HC) are more sensitive in the determination of a deficient state for vitamin B12 at tissue level (Savage et al. 1994; Stabler 1995). MMA and HC are metabolites that accumulate when the vitamin B12-dependent enzymatic reactions in human cells dysfunction. The aim of the present case series is to draw attention within the ophthalmologic community to the new insights in detection of vitamin B12 deficiency. We present a case series of seven patients with a bilateral optic neuropathy and an elevated MMA and/or HC level as evidence of a vitamin B12 deficiency. The patients were seen at our department between January 2009 and December 2010. Whenever a vitamin B12 level was determined to exclude a vitamin B12 deficiency as the cause of the bilateral optic neuropathy, serum MMA and, in most cases, HC were also measured. The values of serum vitamin B12, MMA and HC are shown in Table 1. In only three patients, the serum vitamin B12 level was below the established norm set by the laboratory. Present literature recommends measuring MMA and/or HC whenever vitamin B12 is below 200 or 300 pmol/l (Stabler 1995; Oh & Brown 2003). However, had we followed these recommendations, still three patients with a deficient state for vitamin B12 would have been missed. All patients received vitamin B12 substitution therapy. In the four patients where we repeated the measurement of MMA and HC after treatment, the metabolites normalized indicating that the abnormal levels of metabolites were indeed caused by the vitamin B12 deficiency. Two of the patients with an apparent normal B12 serum level had a history of alcohol abuse. Lambert et al. (1997) reported on patients suffering from alcoholic liver cirrhosis. These patients had normal to elevated serum vitamin B12, probably due to intracellular release of stored vitamin B12 from damaged liver cells. But they also had elevated MMA and HC, indicating a vitamin B12 deficiency at tissue level. They suggested poor cellular penetration of vitamin B12 owing to a deficit or malfunction of binding protein as an explanation for their results. Another striking finding in the present series is that two of seven patients had a pathogenic mutation for Leber hereditary optic neuropathy (LHON). LHON and optic neuropathy as a result of vitamin B12 deficiency have clinical similarities, and both diseases have their origin in mitochondrial metabolism. So it is conceivable that a subclinical vitamin B12 deficiency can trigger the expression of optic neuropathy in LHON patients. Reports on patients with both a LHON mutation and vitamin B12 deficiency have been published in the past (Pott & Wong 2006). The earliest descriptions of optic neuropathy in vitamin B12 deficiency are in patients with pernicious anaemia. However, this classical entity did not occur in any of the patients presented in this study. Two patients had proven macrocytosis, without anaemia. Five patients did not have macrocytosis or anaemia. Accompanying neurological symptoms were only present in two patients. The present results again point out that macrocytosis or neurological symptoms are not a requisite finding to suspect a vitamin B12 deficiency. In conclusion, the results of this study confirm that measurement of only vitamin B12 serum level will miss neuro-ophthalmologic patients with an actual deficiency. One should always measure MMA and HC levels when a vitamin B12 deficiency is suspected.

Comparison between Weekly Intravenous Versus Daily Oral Vitamin B12 Supplementation in Vitamin B12 Deficiency Anemia [Courage-12]: A Randomized, Open Label, Single Centre Study

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with vitamin B12 deficiency

79-Year-Old Woman With Forgetfulness

Does Cell Size Matter?: Utilizing Mean Cell Volume in Hospitalized Patients As a Screen to Determine Common Causes of Anemia Including Iron Deficiency Anemia, Vitamin B12 and Folate Deficiency

Vitamin B12 deficiency in childhood and adolescence

Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

BackgroundBoth vitamin B6 deficiency and vitamin B12 deficiency can present with symptoms that appear like polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, with painful peripheral neuropathy and sensorimotor dysfunction. There are rare reports of an association between vitamin B12 deficiency and POEMS syndrome, and even rarer reports of an association between vitamin B6 deficiency and POEMS syndrome. To our knowledge, this is the first described case with deficiencies in both vitamin B6 and vitamin B12 in association with POEMS syndrome.Case presentationA man in his 40s presented with fatigue, imbalance, and painful numbness and tingling. Initial evaluation revealed low vitamin B12 level, and he received oral and IV supplementation for one month with an improvement in vitamin B12 levels, but without improvement in symptoms. Further evaluation revealed both a vitamin B6 deficiency and an IgA lambda monoclonal spike, prompting further investigation and an eventual diagnosis of POEMS syndrome. He underwent an autologous stem cell transplant and has had improvement in his symptoms.ConclusionsPatients with POEMS syndrome may have symptoms that are difficult to distinguish from deficiencies in vitamin B6 or vitamin B12. Management of POEMS should include screening of vitamin B6 and B12 to ensure other possible associated causes of symptoms are appropriately treated.

Vitamin B12 deficiency in infants secondary to maternal deficiency: A case series of seven infants

Anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in oral lichen planus patients with vitamin B12 deficiency.

to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom. a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l. the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels. the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.