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Background/purpose: Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA + /DG + /EOLP patients)., Methods: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA + /DG + /EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups., Results: We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA + /DG + /EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL), iron (< 60 μg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA + /DG + /EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA + /DG + /EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p < 0.001). Of 27 anemic GPCA + /DG + /EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA + /DG + /EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia., Conclusion: We conclude that GPCA + /DG + /EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA + /DG + /EOLP patients may sometimes have normocytic anemia or iron deficiency anemia., (Copyright © 2016. Published by Elsevier B.V.)

Disturbance in one-carbon (1-C) cycle occurs due to nutritional deficiencies (vitamin B12/folate) or specific genetic polymorphisms. This leads to altered levels of key 1-C metabolites such as SAM (s-adenosyl methionine), SAH (s-adenosyl homocysteine), methionine, homocysteine and MMA (methyl malonic acid). These 1-C metabolites are determinants of cellular methylation potential and epigenetic modifications of DNA which impairs metabolic pathways in several pathological diseases and developmental programming. Though methods were able to measure these analytes only independently, none of the methods detect simultaneously. Therefore we developed a method to measure these five 1-C metabolites in a single run using liquid chromatography tandem mass spectrometry (LC-MS/MS). We used stable isotopes dilution LC-MS/MS to measure the 1-C metabolites in human plasma. Blood samples were collected from pregnant women (n=30) at early gestation in the ongoing, multicentre, prospective PRiDE study. Linearity exhibited across the calibration range for all the analytes with the limit of detection (LOD) of 1.005nmol/l for SAM, 0.081nmol/l for SAH, 0.002μmol/l for methionine, 0.046μmol/l for homocysteine and 3.920nmol/l for MMA. The average recovery for SAM was 108%, SAH-110%, methionine-97%, homocysteine-91% and MMA-102%. The inter-assay CV for SAM was 7.3, SAH-5.6%, methionine-3.5%, homocysteine-7.0% and MMA-4.0%. The intra-assay CV for SAM was 8.7%, SAH-4.7%, methionine-5.4%, homocysteine-8.1% and MMA-6.1%. Pregnant women at early gestation with low B12 levels had significantly higher homocysteine, MMA, lower levels of methionine, SAM and SAM:SAH ratio and higher triglycerides. We developed a simple and rapid method to simultaneously quantify 1-C metabolites such as SAM, SAH, methionine, homocysteine and MMA in plasma by stable isotope dilution LC-MS/MS which would be useful to elucidate the epigenetic mechanisms related in the gene-nutrient interactions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The dietary intake of vitamin B12 among unsupplemented vegans is notably lower compared to both vegetarians and omnivores. Prolonged low intakes of vitamin B12, such as seen in those adhering to a vegan diet, lead to physiological deficiency of vitamin B12 and an elevated risk of B12‐related morbidity. However, while serum B12 serves as a conventional biomarker for assessing B12 status, its utility is limited given its sensitivity and specificity in ascribing physiological deficiency of B12 and the functional vitamin B12 status of those adhering to vegan diets is unclear. We conducted a systematic review and meta‐analysis using data based on the full panel of biomarkers of vitamin B12 status to test whether adherence to a vegan diet is associated with an elevated risk of functional vitamin B12 deficiency compared to vegetarian or omnivorous diets. In addition, subgroup analysis was carried out to look at the effect of vitamin B12 supplement use on B12 status among vegans. Our search identified 4002 records, of which 19 studies met the inclusion criteria for the systematic review and 17 studies were taken forward for the meta‐analysis. Meta‐analysis results revealed significantly lower serum B12, pmol/ (−0.72 [−1.26, −0.18]; p = 0.01) and elevated total homocysteine, μmol/L (tHcy) (0.57 [0.26, 0.89]; p < 0.001) concentrations, alongside elevated methylmalonic acid, nmol/L (MMA) (0.28 [−0.01, 0.57]; p = 0.06) and lower holotranscobalamin, pmol/ (HoloTC) (−0.42 [−0.91, 0.07]; p = 0.09) levels among vegan adults compared to omnivores, indicating increased functional B12 deficiency in addition to low vitamin B12 status in vegan adults. There were no differences between vegans and vegetarians in HoloTC (0.04 [−0.28, 0.35]; p = 0.814) or MMA (−0.05 [−0.29, 0.20]; p = 0.708), but differences were found in serum B12 (−0.25 [−0.40, −0.10]; p = 0.001) and for tHcy (0.24 [0.09, 0.39]; p = 0.002) concentrations. Subgroup analyses indicated that the use of vitamin B12 supplements among vegans contributes to significant improvements in all biomarker concentrations compared to their unsupplemented counterparts. Our findings underscore the need for improved strategies to redress poor vitamin B12 status with appropriate B12 supplementation use among those adhering to vegetarian and vegan diets. [ABSTRACT FROM AUTHOR]

Objective: Vitamin B12 deficiency, an essential vitamin for the human body, is common in Turkey, and infants are at risk in this regard. This study was intended to investigate the effect of vitamin B12 levels of breastfeeding mothers with infant vitamin B12 and homocysteine levels. Material and Methods: A total of 214 infants aged 1-6 months and their mothers who applied to the infancy outpatient clinic of İstanbul Medeniyet University Göztepe Training and Research Hospital were included in the study. In this study, vitamin B12 levels of the mothers, vitamin B12, folic acid, and homocysteine levels in the infants were primarily analyzed, and the associated risk factors were secondarily determined. Results: The rate of adequate vitamin B12 levels in infants was 20.09% (n=43), and the rate of normal homocysteine levels in mothers of infants with sufficient vitamin B12 and normal homocysteine levels was 383.93 pg/mL and 379.07 pg/mL. 66.27% sensitivity and 75.56% specificity were calculated when 220 pg/mL was taken as the vitamin B12 cut-off value, which predicts homocysteine elevation. Conclusion: This study predicted that only one in five infants had sufficient vitamin B12 levels, but if breastfeeding mothers had sufficient vitamin B12 levels, infants were much less likely to have vitamin B12 deficiency. Since adequate vitamin B12 levels are important for infants, especially in terms of neurodevelopment, we believe that it is necessary to evaluate pregnant women in our society in terms of vitamin B12 levels and to provide vitamin B12 support. [ABSTRACT FROM AUTHOR]

Background: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. Objectives: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. Results: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. Conclusion: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses. Plain language title: Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications? Plain language summary: It has been known for many decades that high doses of the B vitamin supplement, folic acid, can alleviate the anemia of vitamin B12 deficiency, at least temporarily. However, by alleviating the anemia, such folic acid supplements were said to "mask" the underlying vitamin B12 deficiency, thus allowing neurological damage to continue or possibly be exacerbated. Consequently, treating vitamin B12 deficiency with high dose folic acid was discontinued in the 1970s. The issue of whether folic acid supplements can exacerbate vitamin B12 deficiency reemerged in the 1990s with folic acid fortification of cereals and grains in the United States and Canada (and now in over 80 countries around the world) to prevent spina bifida and other birth defects. This narrative review summarizes the results of studies that have assessed the relationships between folic acid and folate and vitamin B12 status in patients and in populations. A recent hypothesis on how folic acid might exacerbate vitamin B12 deficiency is summarized, and recommendations to clinicians are made for increased vigilance in assessing vitamin B12 status in certain groups at risk of vitamin B12 deficiency, including older adults, people with gastrointestinal issues and other factors that cause vitamin B12 malabsorption, people with unexplained neurological problems, and people who follow vegan or vegetarian diets which are naturally low in vitamin B12. [ABSTRACT FROM AUTHOR]

Background: Adult vitamin B12 (B12) deficiency may present itself with nonspecific mainly neurological symptoms, and thus plasma biomarkers are often judged to be of major importance in the further diagnostic process. Four biomarkers are of special relevance: total B12, holotranscobalamin (the part of B12 bound to the active transport protein, transcobalamin, also named holoTC or active B12) and the 2 so-called metabolic markers that accumulate if B12 is lacking, methylmalonic acid (MMA) and homocysteine. Objective: This article briefly reviews the inherent limitation of biomarkers, discusses its use in establishing the diagnosis and cause of B12 deficiency, and when following or discontinuing treatment with B12. Methods: The review is based on published papers, but also on knowledge gained from working within the area. Conclusion: It is concluded that a combination of a B12 and a metabolic marker, for example, total B12 and MMA, may prove most useful in daily practice. An unexpectedly high level of total B12 is most often of no clinical importance, though sometimes related to the presence of underlying cancer. Measurement of total B12 is of limited value in patients on treatment with pharmacological doses of B12 but may be helpful if B12 treatment is discontinued. Plain language title: Vitamin B12-Related Blood Tests Plain language summary: Blood-testing is considered an important part of the diagnostic procedure in patients suspected to suffer from B12 deficiency. A deficiency is supported by a low level of plasma B12, and confirmed by a high level of methylmalonic acid, judged according to age and kidney function. Alternatively, a high level of homocysteine may support the diagnosis. Treatment of B12 deficiency is mainly guided by improvement of symptoms, with a very limited need for further blood testing. If B12-treatment is discontinued, B12 status should be judged every 6 months for approximately 2 years to detect a possible reoccurrence of a deficient state. An unexpected high level of plasma B12 is most often of no clinical implication. [ABSTRACT FROM AUTHOR]

Background: The incidence of gestational diabetes mellitus (GDM) has increased in recent decades. Established prevention methods for GDM include diet and exercise. Recent interest has focused on the roles of vitamin B12 and folate in the development of GDM. These micronutrients are essential for one-carbon metabolism, which is involved in many metabolic pathways. However, the study results were conflicting and varied by geographic area. Objectives: The aim of this study was to evaluate the relationship between GDM and vitamin B12 levels in our region. Methods: This case-control study enrolled 180 pregnant women at 24 - 28 weeks of gestation. Half of the participants had GDM, and the other half were healthy individuals. All participants attended outpatient pregnancy care clinics at Shiraz University of Medical Sciences from June 2020 to April 2021. Gestational age, age, and body mass index were matched between the two groups. Vitamin B12, folate, insulin, and homocysteine levels were measured in both groups and insulin resistance was calculated. The results were compared between the two groups, and the relationship between vitamin B12 levels and insulin resistance in each group was investigated. Results: Vitamin B12 deficiency was present in 15.6% of the women with GDM. There were no cases of vitamin B12 deficiency in the control group. The GDM group had lower vitamin B12 levels (365.22 ± 136.82 pg/mL vs. 496.08 ± 156.46 pg/mL, P = 0.001). There was a negative correlation between serum vitamin B12 level and insulin resistance index (P = 0.001, r = -0.62). Folate levels were higher in the GDM group (17.93 ± 3.66 ng/mL vs. 14.60 ± 5.32 ng/mL, P = 0.001), but these levels did not significantly relate to insulin resistance or GDM. Conclusions: In our region, there is a significant relationship between low levels of vitamin B12 and both insulin resistance and GDM, which suggests the need for larger studies and attention to the detection and treatment of vitamin B12 deficiency during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression. Aims and Objectives: To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD. Materials and Methods: Fifty‑nine patients with MDD were recruited based on ICD‑10 criteria. Severity of depression was assessed by HAM‑D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed. Results: Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 µmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW‑CV) varied significantly between the three groups of MDD patients. Patients consuming non‑vegetarian food had a significantly higher median value of serum vitamin B12. Conclusion: Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study. [ABSTRACT FROM AUTHOR]

Background: B12 deficiency, which can be seen in type 2 DM patients using metformin, can cause peripheral nerve damage that can easily be confused with peripheral neuropathy, a complication of diabetes. Therefore, early diagnosis is important in patients. Objective: In our study, we aimed to investigate benefit of Active B12 measurement in diagnosing B12 deficiency, as it might be a better alternative in follow-up of B12 levels in type 2 DM patients using metformin. Methods: Patients were divided into three groups according to their Total B12 levels: Deficient, Borderline and Sufficient. Homocysteine and Active B12 (holotranscobalamin) levels were studied with Chemiluminescent Microparticle Immunoassay (CMIA) for quantitative determination. Duration of use, daily metformin dose, and other parameters were collected from records and interviews. Results: A statistically significant positive correlation was found between Total B12 and Active B12 (r = 0.624, p = 0.000). A statistically significant negative correlation was found between metformin dose and Active B12 and Total B12 levels (r = -0.309, r = -0.212, respectively; p < 0.05). While effects of metformin dose and duration of use groups were not found statistically significant in binary logistic regression analysis for Total B12 groups, the OR value for Active B12 was found to be 5.575 (95% CI 1.456–21.343, p = 0.012). Conclusions: It is important to closely follow up Type2 DM patients with high daily metformin dose in terms of B12 deficiency. Active B12 is a significant predictor of B12 deficiency compared to other parameters. [ABSTRACT FROM AUTHOR]

Background/Aim: This study examines patients diagnosed with vitamin B12 deficiency in our department. Although rare, vitamin B12 deficiency is one of the causes of megaloblastic anemia, which can lead to negative outcomes in patients. We aim to promote earlier diagnosis to protect patients from these negative effects. Therefore, this study will contribute to raising awareness in the literature. Methods: Retrospectively, we included a total of 127 outpatient children, aged 0-18 years (0-215 months), who were diagnosed and treated for vitamin B12 deficiency at the Bagcilar Training and Research Hospital Child Health and Disease Clinic between October 2014 and February 2015. Results: Among the patients, 67 (53%) with vitamin B12 deficiency were female, while 60 (47%) were male, indicating a higher occurrence in girls. Vitamin B12 deficiency was most commonly observed in the age groups of 0-2 years and 12-17 years (adolescents). The mean vitamin B12 level was 168.1 (34.1) pg/mL, the mean hemoglobin level was 12 (1.9) g/dL, and the mean MCV (mean corpuscular volume) was 78.4 (8.1) fl. Anemia was observed in 38% of the patients, bicytopenia in 4%, neutropenia in 6%, thrombocytopenia in 9%, pancytopenia in 3%, and macrocytosis in 2%. Non-iron-deficient patients showed no difference in mean hemoglobin and RDW (red cell distribution width) when compared to irondeficient patients. However, their B12 levels were lower. The prevalence of iron deficiency did not differ between girls and boys. Comparing patients with vitamin B12 levels lower than 150 pg/mL to those with higher levels, there were no significant differences in average Hb, MCV, and RDW. Conclusion: It should be noted that macrocytic anemia is not exclusive to vitamin B12 deficiency. Vitamin B12 deficiency can manifest as normocytic anemia and should not be overlooked in biochemical assessments. It is recommended to conduct nationwide and regional prevalence studies to evaluate vitamin B12 deficiency as a public health issue and to develop new solutions accordingly. [ABSTRACT FROM AUTHOR]

The recreational use of nitrous oxide as laughing gas becomes a real public health issue among adolescents and young adults. Chronic use is deleterious and can lead to severe neurological disorders. Nitrous oxide inactivates vitamin B12, and the functional defect of vitamin B12 plays a major role in the pathogenesis of nitrous oxide-related neurological disorders. Here we report the case of a 22-year-old woman who came to the hospital after an unexplained loss of consciousness. She exhibited typical features of vitamin B12 or folate deficiency such as macrocytic anemia and hypersegmented neutrophils. However, serum concentrations of folate and vitamin B12 were normal. In contrast, circulating concentrations of total homocysteine and methylmalonic acid were significantly increased. These results clearly indicated a defect in vitamin B12 functions. The reason for this defect was clarified when she revealed that she had been consuming nitrous oxide recreationally for over a year. The present case points out the challenges in diagnosing vitamin B12 deficiency in the context of nitrous oxide abuse due to normal concentrations of total serum vitamin B12 in a significant proportion of cases. The medical community should be aware of how difficult it can be to interpret B12 status in this specific population. [ABSTRACT FROM AUTHOR]

Methylation is a ubiquitous and permanent key biochemical process playing a major role in gametogenesis and embryogenesis in relation to epigenetics and imprinting. Methylation relies on a unique cofactor S-Adenosyl Methionine: SAM. Release of the methyl group onto target molecules is followed by liberation of S-Adenosyl Homocysteine (SAH), and then homocysteine (Hcy), both potent inhibitors of the methylation process. Defective recycling of homocysteine, leading to Hyperhomocysteinemia, is mainly due to reduced activity of MTHFR (Methylene TetraHydroFolate Reductase). However, we described here, in a woman attending an ART program, a rather rare syndrome: The Folate trap syndrome. Due to vitamin B12 deficiency (malabsorption), Hcy cannot be recycled to methionine by the methionine synthase. Transmethylation activity is weak and leads to Hhcy (Hyperhomocysteinhemia). Her Hhcy, over 16µM, was resistant to 5MTHF (5 Methyltetrahydrofolate) associated with a support of the one carbon cycle, a classical efficient treatment for elevated homocysteine. Treatment with Methylcobalamine (associated with adenosyl Cobalamine) allowed a Hcy drop down to 10 µM. Knowing the pleiotropic negative impact of Hcy on gametes, embryos and pregnancy in general, we strongly recommend a Hcy dosage in both members of couples seeking treatment for pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of sublingual methylcobalamin for the treatment of vitamin B12 deficiency anemia in children. Methods: A single arm intervention study was conducted between November, 2020 and April, 2022 in children aged 1–12 years with vitamin B12 deficiency anemia. Children aged 1–6 years received a tablet of methylcobalamin (1500 mcg) by sublingual route every alternate day (three doses) while those aged 7–12 years received five such doses. Thereafter, one such sublingual tablet was given weekly and all participants were followed-up for 6 weeks. Results: 37 children with a mean (SD) age of 8.2 (4.1) years were treated and followed-up. On day 10, no child needed rescue therapy with parenteral methylcobalamin. After 6 weeks, the mean (SD) serum cobalamin increased from 123.3 (35.5) pg/mL to 507.3 (274.2) pg/mL (P<0.001), plasma homocysteine decreased from 48.9 (17.8) µmol/L to 16.3 (8.5) µmol/L (P<0.001), the mean (SD) hemoglobin increased by 2.3 (1.1) g/dL (P<0.001), and MCV decreased by 12.9 (6.8) fL (P<0.001). 67.6% children persisted to have anemia, albeit majority of them had mild or moderate anemia. There were no unsolicited side-effects reported. Conclusion: Sublingual methylcobalamin is effective for the treatment of vitamin B12 deficiency anemia in children; although, the duration of treatment needs to be longer than six weeks. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 is a water-soluble vitamin with important cellular functions; it is an essential vitamin. The aim of this study is to determine the B12 levels of children in the period from the 6th month when they start taking additional foods to the age of seven (preschool children) and the risk factors affecting them. Methods: One hundred pediatric patients aged 6–72 months who were diagnosed with vitamin B12 deficiency and their parents who agreed to attend Istanbul Atlas University, Medical Faculty, "Medicine Hospital" Pediatric Clinic between September 2022 and June 2023 were prospectively included in this study. Results: B12 deficiency was significantly higher in the 6–11 (25%)-month group than in the 12–23 (5.8%)- and 24–47 (2.8%)-month groups. Homocysteine levels were highest in those with insufficient B12 levels compared to the other groups. There was no statistically significant difference in weekly dairy and meat consumption levels between age groups. B12 levels were lower in the 6–11-month group than in the other groups. Homocysteine levels were highest in those with insufficient B12 levels (<200 pg/mL (148 pmol/L)). Folic acid levels were lower in the 24–47-month and 48–72-month groups than in the 6–11-month and 12–23-month groups. Conclusions: The results obtained in this study showed that low vitamin B12 and increased homocysteine levels seem to be important risk factors in preschool children, especially from the 6th month when they start consuming additional foods. The diagnosis of B12 deficiency can be confirmed by elevated serum total homocysteine levels, which are evidence of functional cobalamin deficiency. [ABSTRACT FROM AUTHOR]

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Background: COVID-19 disease affects the respiratory and cardiovascular systems. Vitamin B12 has been associated with A1AT, one of the protective factors of lung tissue, and homocysteine among the cardiovascular risk factors. Therefore we suggest that low vitamin B12 levels are associated with a disposition to COVID-19 infection. This study aims to determine whether there is a relationship between COVID-19 infection and serum vitamin B12 levels. Methods: This research is a case-control study. Seventy-six people with COVID-19 constituted the case group. Seventy- six people without COVID-19 formed the control group. Vitamin B12 and homocysteine levels of 152 patients included in the study were analyzed. Results: The odds ratio for vitamin B12 was 0.99 (0.978- 0.995). When the value of the vitamin B12 variable decreases by one unit, the risk of COVID-19 increases by 1%. The odds ratio for homocysteine was 1.81 (1.414-2.325). When the value of the homocysteine variable increases by one unit, the risk of COVID-19 increases by 1.81 times. According to ROC analysis, when serum vitamin B12 is below 222.5 ng/L and homocysteine is above 13.7 irmol/L, it may increase the risk of COVID-19. Conclusions: We suggest that patients with low vitamin B12 levels and high homocysteine levels are more severely affected by COVID-19 infection. [ABSTRACT FROM AUTHOR]

Da ein Vitamin-B12-Mangel zu sehr unterschiedlichen Symptomen führen kann, dauert es bei vielen Patient:innen jahrelang, bis endlich eine Diagnose gestellt wird. Mit dem Gesamt-Vitamin-B12, Holotranscobalamin, Homocystein und Methylmalonsäure stehen vier Biomarker für die Diagnostik zur Verfügung, die einzeln verwendet nur eine eingeschränkte Aussagekraft haben. Wichtig für die Diagnose und die Entscheidung für eine Therapie ist neben der Anamnese und den klinischen Symptomen auch das Vorhandensein von Risikofaktoren. [ABSTRACT FROM AUTHOR]

Abstract Objective Measurement of total vitamin B12 (vit B12) concentration raised concerns over early detection of vit B12 deficiency due to its clinical unreliability. In this present article we aimed to assess the efficacy of holo-transcobolamin (active vit B12) for true evaluation of vit B12 deficiency. Methods This retrospective study included 100 participants referred for vit B12 assay. Serum total vit B12, active vit B12 and homocysteine were estimated. Results Our study showed 59% of the total participants with vit B12 deficiency (185 ± 64.62 pg/ml) and 18% with hyper-cobalaminemia (1666.9 ± 367.13 pg/ml) based on their total vit B12 concentrations. A comparative study on total vit B12 and active vit B12 was done which reflected a striking disparity in results. Active vit B12 reported 28.8% patients with vit B12 deficiency (19.8 ± 17.48 pg/ml) and only 16.6% patients with hyper-cobalaminemia (224.14 ± 10 pg/ml). Active vit B12 appeared to be more sensitive (82.35% vs 65%) and specific (46.6% vs. 43.8%) diagnostic marker compared to total vit B12. Pearson Correlation study indicated a strong positive correlation (r = 0.695 at p

The recreational use of nitrous oxide (N2O) as "laughing gas" is a growing problem. The chronic toxicity of N2O is mainly due to its ability to oxidize vitamin B12, making it dysfunctional as a cofactor in metabolic pathways. This mechanism plays a major role in the development of neurological disorders in N2O users. The assessment of vitamin B12 status in N2O users is important but challenging due to the lack of decrease in total vitamin B12 in most cases despite genuine vitamin B12 functional deficiency. Other biomarkers, such as holotranscobalamin (holoTC), homocysteine (tHcy) and methylmalonic acid (MMA), are interesting candidates to properly assess vitamin B12 status. Here, we conducted a systematic review of case series in order to assess the prevalence of abnormal values of total vitamin B12, holoTC, tHcy and MMA in recreational N2O users, which is an important prerequisite for determining the best screening strategy in future guidelines. We included 23 case series (574 N2O users) from the PubMed database. Total circulating vitamin B12 concentration was low in 42.2% (95% confidence interval 37.8–46.6%, n = 486) of N2O users, while 28.6% (7.5–49.6%, n = 21) of N2O users had low circulating concentrations of holoTC. tHcy levels were elevated in 79.7% (75.9–83.5%, n = 429) of N2O users, while 79.6% (71.5–87.7%, n = 98) of N2O users had increased concentrations of MMA. In summary, the increases in tHcy and MMA were the most prevalent abnormalities, and should be measured alone or in combination in symptomatic N2O users rather than total vitamin B12 or holoTC. [ABSTRACT FROM AUTHOR]

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2-78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0-88.0%), unsteady gait (58%; 48.2-67.8%), and weakness (43%; 33.1-52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9-83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 15 µmol/L (90.3%; 79.3-100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4-100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency.

Background: Vitamin B12 is an important vitamin for metabolism and affects many mechanisms in the body including neuronal migration, DNA synthesis, neurotransmitter synthesis, brain and cognitive development. Increased oxidative stress in the body leads to the damage of the child development, but also plays a crucial role in the pathogenesis of many diseases encountered in the childhood period. Our aim is to investigate whether or not B12 deficiency is associated with dynamic thiol/disulfide homeostasis in adolescent patients. Methods: This is a case-controlled observational study consisting of 45 adolescent patients with vitamin b12 deficiency and a control group consisting of 45 healthy adolescent. Patients between 11 and 18 ages who applied to the outpatient clinic for the first time with one of the complaints of headache were selected due to their decreased school performance, dizziness, and fatigue. Hemogram, vitamin B12, homocysteine levels and oxidative stress parameters such as native and total thiol disulfide levels and ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were measured from the patients. Results: Vitamin B12 level was found to be significantly lower in vitamin B12 deficiency group (p < 0.001). The serum disulfide level was found to be 27.5 ± 8.38 in the case group and 20.5 ± 8.36 in the control group (p < 0.001). In the multiple linear regression analysis, it was determined that the independent variables of native thiol, homocysteine and disulfide levels effected of vitamin B12 levels (p < 0.001, p < 0.001, p < 0.005 respectively; R2 = 0.62). Conclusion: The results obtained in terms of the effect of vitamin B12 deficiency on oxidative stress in adolescents are remarkable. The increase in oxidative stress parameters in the patient group may also suggest that oxidative stress plays a vital role in vitamin B12 deficiency in adolescence. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cobalamin) is essential for normal metabolic function, and even moderate deficiency of this vitamin has negative health effects. Vitamin B12 is found in animal foods, and as vegetarian diets are increasingly popular in Western countries, one might expect a higher prevalence of vitamin B12 deficiency in the Nordic population. Setting recommendations for vitamin B12 intake has proven to be difficult, as uptake of vitamin B12 varies substantially, the clinical deficiency symptoms are often diffuse, and there is no clear agreement on the decision limits for vitamin B12 deficiency. Vitamin B12 deficiency is reported to be particularly common among pregnant women and infants, despite the fact that less than 1% of Norwegian pregnant women have a cobalamin intake below the Nordic Nutrition Recommendations 2012-recommended level of 2.0 µg/day. In addition, the assumption that breast milk contains sufficient vitamin B12 for optimal health and neurodevelopment during the first 6 months of life does not comply with the high prevalence of insufficient vitamin B12 status in this age group. Recommended intakes of vitamin B12 vary among age groups and must be based on markers of cobalamin status, indicating an optimal intracellular biochemical status, and not merely absence of clinical signs of vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the evidence for whether habitual or different levels of experimental intake of vitamin B12 from diet and supplements is sufficient to ensure adequate B12 status in groups most susceptible to vitamin B12 deficiency. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Scopus up to 21 May 2021, for intervention studies, prospective cohort studies and case-control studies assessing B12 intake from diet and/or supplements in relation to B12 status (s/p-B12, holotranscobalamin, methylmalonic acid, homocysteine or breastmilk B12). Cross-sectional studies were eligible for studies conducted during pregnancy and lactation. Included populations were children (0-18 years), young adults (18-35 years), pregnant or lactating women, older adults (≥65 years) and vegans or vegetarians. Study selection, data extraction and risk of bias assessment were conducted by two assessors independently. The evidence was synthesized qualitatively and classified according to the World Cancer Research Fund. Results: The searches yielded 4855 articles of which 89 were assessed in full text and 18 included. Three studies were conducted during pregnancy and three during lactation or infancy -- all observational. Eight studies were conducted among older adults; most were interventions among B12-deficient participants. Four studies were eligible for vegetarian and vegans, all interventions. The strength of evidence that habitual B12 intake or an intake in line with the current Nordic recommended intake (RI) is sufficient to ensure adequate status was considered Limited -- no conclusion for all included populations. Conclusion: Evidence is insufficient to assess if or which level of B12 intake is sufficient to maintain adequate status for all included populations. Population-based cohort studies and low-to-moderate dose interventions that address this question are highly warranted. [ABSTRACT FROM AUTHOR]

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• The majority of significant hyperhomocysteinemia was due to remethylation defects. • c.609G>A is the most prevalent mutation in MMACHC gene in Malaysian patients. • CBS (c.402del, c.1333C>T and c.1031T>G), MTHFR genes (c.266T>A and c.1249del) were possibly novel. • Compliance to treatment can be challenging in managing patients detected via high-risk screening. • Chronic hyperhomocysteinemia and hypermethioninemia had a negative clinical outcome. Hyperhomocysteinemia can be due to various abnormalities of the complex interaction of methionine, folate and vitamin B12. It has been known to be a cardiovascular risk factor. This study aims to review the clinical presentation, underlying causes and clinical outcome in paediatric patients diagnosed with significant hyperhomocysteinemia in Malaysia. Data were obtained from the medical records and the laboratory information system. Paediatric patients with significant hyperhomocysteinemia were identified from a selective high-risk screening of 96,721 patients, performed between 2010 and 2022. Inclusion criteria for the study were paediatric patients with significant hyperhomocysteinemia (>40 µmol/L). Sixteen patients were identified. The average total homocysteine (tHcy) and methionine were 269 µmol/L and 499 µmol/L in cystathionine β-synthase deficiency (CBS), 127 µmol/L and 29 µmol/L in patients with remethylation defects and 390 µmol/L and 4 µmol/L in congenital B12 deficiency. We found c.609G>A as the most prevalent mutation in MMACHC gene and possible novel mutations for CBS (c.402del, c.1333C>T and c.1031T>G) and MTHFR genes (c.266T>A and c.1249del). Further subclassification revealed CBS was 5/16 patients (31 %), remethylation defects was 9/16 (56 %) and congenital B12 deficiency was 2/16 (13 %). All patients received standard treatment and regular monitoring of the main biomarkers. The average age at the time of diagnosis were 9.2 years (CBS) and 1.2 years (remethylation defects). Congenital B12 deficiency had slight delay in milestones, remethylation defects had mild to moderate learning disabilities, CBS had variable degree of intellectual disability, delayed milestones, ophthalmological abnormalities, and thrombosis at an early adolescent/adulthood. The majority of significant hyperhomocysteinemia in Malaysian children was due to remethylation defects. Screening for hyperhomocysteinemia in Malaysian children is recommended for earlier treatment and improved clinical outcome. [ABSTRACT FROM AUTHOR]

Aim: Risk factors for vitamin B12 deficiency in infants are not fully understood. The aim of the study was to assess predictors of total homocysteine and methylmalonic acid analysed in newborn screening dried blood spots. Methods: In a Norwegian case control study, we analysed total homocysteine and methylmalonic acid in newborn screening dried blood spots of 86 infants clinically diagnosed with vitamin B12 deficiency during 2012–2018. Results were compared to 252 healthy infants and 400 dried blood spot controls. Medical records were reviewed, and mothers completed questionnaires. Results: Both total homocysteine and methylmalonic acid were significantly higher on newborn screening dried blood spots in infants later clinically diagnosed with vitamin B12 deficiency than controls. Multiple regression analysis showed that the dose of nitrous oxide during labour was the strongest predictor for total homocysteine level in newborn screening dried blood spots for all infants, with larger effect in infants later clinically diagnosed with vitamin B12 deficiency than controls. Conclusion: Nitrous oxide dose during labour was a predictor for total homocysteine and may impact the interpretation of total homocysteine analysis in newborn screening. Nitrous oxide is suggested as a contributing risk factor for infants prone to develop vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (B12 normal folic acid-deficient, BNFD) was associated with an increased expression of microRNA-675 (miR-675) in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2) expression was decreased under folic acid-deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD and BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid-deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus. [ABSTRACT FROM AUTHOR]

Objective: Measurement of total vitamin B12 (vit B12) concentration raised concerns over early detection of vit B12 deficiency due to its clinical unreliability. In this present article we aimed to assess the efficacy of holo-transcobolamin (active vit B12) for true evaluation of vit B12 deficiency. Methods: This retrospective study included 100 participants referred for vit B12 assay. Serum total vit B12, active vit B12 and homocysteine were estimated. Results: Our study showed 59% of the total participants with vit B12 deficiency (185 ± 64.62 pg/ml) and 18% with hyper-cobalaminemia (1666.9 ± 367.13 pg/ml) based on their total vit B12 concentrations. A comparative study on total vit B12 and active vit B12 was done which reflected a striking disparity in results. Active vit B12 reported 28.8% patients with vit B12 deficiency (19.8 ± 17.48 pg/ml) and only 16.6% patients with hyper-cobalaminemia (224.14 ± 10 pg/ml). Active vit B12 appeared to be more sensitive (82.35% vs 65%) and specific (46.6% vs. 43.8%) diagnostic marker compared to total vit B12. Pearson Correlation study indicated a strong positive correlation (r = 0.695 at p < 0.01) hence justified use of the two methods. Conclusion: We claim that active vit B12 is a much more reliable biomarker than total vit B12 for early diagnosis of vit B12 deficiency. [ABSTRACT FROM AUTHOR]

Black cohosh is a readily available dietary supplement currently marketed as a remedy for dysmenorrhea and menopausal symptoms and is one of the top-selling herbal supplements in the United States. Black cohosh extract (BCE) was nominated to the National Toxicology Program (NTP) by the National Cancer Institute and the National Institute of Environmental Health Sciences due to its widespread use and lack of animal toxicity studies. Results of the NTP BCE subchronic mouse toxicity study revealed a dose-dependent, non-regenerative decrease in the erythron with an increase in the mean corpuscular volume (macrocytosis). Howell-Jolly bodies, or micronuclei, were significantly increased. These particular changes indicated an ineffective erythropoiesis consistent with a condition known as megaloblastic anemia. Megaloblastic anemia is due to disruptions in DNA synthesis during hematopoiesis and can be a result of an inherited or drug-induced disorder or a consequence of folate or cobalamin deficiency. Subsequent mouse studies revealed hematological and biochemical changes that were consistent with a functional cobalamin deficiency. This article will review basic mechanisms and laboratory features of megaloblastic anemia. The results of our studies including morphological abnormalities of the erythron and biomarkers of folate and cobalamin deficiencies, as well as hepatic microarray gene changes, are also discussed. [ABSTRACT FROM AUTHOR]

Optimal vitamin B 12 status is important for vascular health. Vascular endothelial (VE) cadherin is an adherent junction protein involved in the maintenance of a functional endothelium. We hypothesized that vitamin B 12 deficiency can negatively affect markers of vascular function, such as VE-cadherin. Within a human intervention study, we explored the possible association between cobalamin status (i.e., vitamin B 12 , holotranscobalamin, and homocysteine) and VE-cadherin (as marker of vascular health) in vegetarians/vegans (VEG) with B 12 deficiency. The associations were evaluated at baseline and after 90-day supplementation with 2000 µg/wk of vitamin B 12. On the whole, an inverse association between VE-cadherin and holotranscobalamin (P =.014) and a positive association between VE-cadherin and homocysteine (P =.041) was documented at baseline. VEG women showed higher levels of VE-cadherin compared with VEG men (P =.044), suggesting an increase in endothelial permeability. The intervention with vitamin B 12 restored serum vitamin levels and improved the overall cobalamin status, whereas it did not affect VE-cadherin levels. The inverse association between holotranscobalamin and VE-cadherin was also maintained after intervention in women, corroborating the strong correlation between these 2 parameters. The results obtained seem to suggest a possible association between cobalamin status and VE-cadherin even if the intervention with B 12 failed to positively affect VE-cadherin levels. Thus, further studies are needed to corroborate these findings and clarify the contribution of a vitamin B 12 intervention on VE-cadherin levels in this target population. This trial was registered at ISRCTN registry (ISRCTN75099618). The deficiency of vitamin B 12 and the consequent alteration of serum holotranscobalamin, homocysteine, and methylmalonic acid can alter vascular functionality in vegetarian/vegan subjects. The inverse association found between vitamin B 12 status and vascular endothelial-cadherin, makes this a candidate biomarker of vascular health in vegetarian/vegan subjects. [Display omitted] [ABSTRACT FROM AUTHOR]

Recreational nitrous oxide (N2O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N2O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose‐dependent nature of chronic N2O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management. [ABSTRACT FROM AUTHOR]

Objective: Vitamin B12 is crucial for cell metabolism, deoxyribonucleic acid synthesis and cell proliferation. Hematological neurological systems are known to be affected in vitamin B12 deficiency. The aim of this study was to research the effects of vitamin B12 deficiency on kidney function parameters. Material and Methods: Thirty-four children with vitamin B12 deficiency and 36 sex and age-matched healthy controls were included in the study. Complete blood count, serum urea, creatinin, vitamin B12, holotranscobalamin, methyl malonic acid, homocysteine, ferritin, folate and estimated glomerular filtration rate were recorded. Additionally, spot urine protein, microalbumin and neutrophil gelatinase-associated lipocalin were measured. Results: Kidney function parameters were normal for childrens that participated the study. Serum kidney function parameters adjusted for age also showed no significant difference between the two groups. No correlation was found between serum vitamin B12 and neutrophil gelatinase-associated lipocalin; however, a negative correlation was detected between neutrophil gelatinase-associated lipocalin and holotranscobalamin (r =-0.24, p =0.045). Holotranscobalamin was substantially lower in the group with vitamin B12 deficiency (p<0.001). Conclusion: No negative influence of B12 deficiency on kidney function was found in non-anemic children. [ABSTRACT FROM AUTHOR]

Abstract Background Alteration of vitamin B12 metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B12 deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B12) related disorders, both genetic and acquired conditions. Methods A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated. Results During the period 2015–2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B12 deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia. Conclusions When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B12 deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.

Aim: Nowadays, insufficiency and deficiency of vitamin B12 and folate are seen as an important health problem. The purpose of the present study was to determine the frequency of vitamin B12 and folate deficiencies in pregnant women and their babies at birth. Materials and Methods: The study group consisted of 117 pregnant women and their single, term babies in İzmir Ege Maternity Hospital. Analysis of vitamin B12, folate and homocysteine levels were performed from venous blood samples which were obtained from the mother and cord blood at birth. Additionally, a questionnaire using a face-to-face interview method was performed with the pregnant women included in this study. The mean duration of pregnancy was 39.1±0.89 weeks and the mean age of the mothers was 28.2±6.2 years. Results: Vitamin B12 deficiency (<130 pg/mL) was present in 88.9% of mothers and 56% of babies. Folate deficiency (<4 ng/mL) was found in 6.8% of mothers, but not found in any babies. The homocysteine levels were high (>8 µmol/L) in 58.1% of mothers and 63.2% of babies. There was a significant correlation between maternal and cord blood vitamin B12, folate and homocysteine levels (p<0.01). However, there was no correlation between maternal vitamin B12 and homocysteine levels (p=0.016, p=0.354). Conclusion: Low maternal vitamin B12 levels are strongly associated with low cord blood vitamin B12 levels. This data reveals that vitamin B12 deficiency which can occur from the neonatal period is a preventable public health problem. Pregnant women and physicians should be made aware of the importance of vitamin B12 intake during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Cobalamin C (cblC), a vitamin B12 processing protein, plays a crucial role in metabolism for the conversion of homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA. CblC deficiency, an inborn error of cobalamin processing, is a rare cause of atypical hemolytic-uremic syndrome (aHUS) and results in hyperhomocysteinemia and methylmalonic aciduria. Both substances are thought to contribute to thrombotic microangiopathy (TMA) in cblC deficiency patients. However, the roles of homocysteine and methylmalonic acid (MMA) in these patients remain unclear. We want to shed more light on the contributions of homocysteine and MMA levels as contributing factors for thrombotic microangiopathy (TMA)/aHUS by a follow-up of a cblC deficiency patient over 6 years. Case diagnosis: A 27-day-old Hispanic female presented with abnormal C3-carnitine on her newborn screen, poor feeding, decreased activity, and oligouria. She was diagnosed with cblC deficiency after laboratory results revealed elevated serum homocysteine, and serum MMA along with genetic testing showing a homozygous pathogenic frameshift variant in MMACHC. The patient developed aHUS and acute kidney injury (AKI), which resolved after appropriate therapy. Over 6 years, she continued to have normal kidney function with no thrombocytopenia despite persistently elevated homocysteine and MMA levels. Conclusion: We question the roles of homocysteine and MMA as causative of aHUS/TMA in cblC deficiency as they remained elevated during follow-up but did not result in aHUS/TMA or AKI. Hyperhomocysteinemia and/or MMA caused by other metabolic diseases do not result in aHUS/TMA or AKI. This suggests that other nephrotoxic factors may trigger aHUS/TMA in cblC patients. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency can present with neurologic and psychiatric symptoms without macrocytic anaemia. We describe a case of late-onset cobalamin C deficiency which typically presents with normal serum vitamin B12 concentrations, posing an additional diagnostic challenge. A 23-year-old woman with decreased muscle strength and hallucinations was diagnosed with 'catatonic depression' and admitted to a residential mental health facility. She was referred to our hospital for further investigation 3 months later. Heteroanamnesis revealed that the symptoms had been evolving progressively over several months. Magnetic resonance imaging (MRI) of the brain showed diffuse symmetrical white matter lesions in both hemispheres. Routine laboratory tests including vitamin B12 and folic acid were normal except for a slight normocytic, normochromic anaemia. Over the next 6 weeks her symptoms deteriorated, and she became unresponsive to stimuli. A new MRI scan showed progression of the white matter lesions. The neurologist requested plasma homocysteine (Hcys) which was more than 8 times the upper limit of normal. Further testing revealed increased methylmalonic acid and the patient was diagnosed with adult-onset cobalamin C deficiency. This case illustrates that Hcys and/or methylmalonic acid should be determined in patients presenting with neuropsychiatric symptoms suggestive of vitamin B12 deficiency with a normal serum vitamin B12 to rule out a late-onset cobalamin C deficiency. [ABSTRACT FROM AUTHOR]

Background: Obsessive–compulsive disorder (OCD) a complex neuropsychiatric disorder, is characterized by irresistible obsessive thinking and compulsive behavior. Folate is a member of water-soluble vitamins in the human body and sustains many normal daily activities (e.g., exercise, sleep, and memory). Homocysteine, a sulfur-containing non-essential amino acid, has been investigated in numerous psychiatric disorders (e.g., OCD). Vitamin B12 is a type of complex organic compound with cobalt contained. Moreover, vitamin B12 and folate deficiency and high levels of homocysteine were found to have an effect on brain functions and also lead to non-specific psychiatric symptoms. Objectives: This study aimed to confirm the epidemiological evidence of OCD and investigate whether vitamin B12, folate, and homocysteine have an effect on the etiology of OCD. Methods: A systematic search was conducted on eight databases (i.e., PubMed, Embase, Web of Science, the Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database), and the retrieval time was up to March 2021. The available articles involving patients with OCD with/without abnormal serum levels of vitamin B12, folate, and homocysteine were comprehensively reviewed and analyzed. Results: A total of 5 studies involving 309 patients were included in this meta-analysis, including 172 cases in the experimental group and 137 in the control group. The content of folate in the OCD group was not significantly different from that in the control group (SMD = −0.089, 95%CI −0.755 to 0.577, p = 0.794). And serum homocysteine was significantly higher in the patients with OCD (SMD = 1.132, 95%CI 0.486 to 1.778, p = 0.001). Vitamin B12 was significantly lower in patients with OCD (SMD = −0.583, 95%CI −0.938 to −0.229, p = 0.001). Conclusions: This meta-analysis shows serum high levels of homocysteine, low levels of vitamin B12, and normal folate level are closely correlated with OCD. However, high-quality case-control studies should be further conducted to explore the correlation between serum levels of vitamin B12, folate, homocysteine, and OCD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display%5frecord.php?ID=CRD42021262161; PROSPERO (Number CRD#42021262161). [ABSTRACT FROM AUTHOR]

A 27-year-old man presented with altered mental status and unilateral right lower limb swelling. Brain imaging and cerebrospinal fluid analysis were unremarkable. He reported history of nitrous oxide misuse after he recovered from his delirium. The diagnosis of drug induced psychosis was made. The right lower limb swelling was found to be due to extensive deep vein thrombosis. In another case, a 21-year-old woman presented with headache, vomiting and dipoplia. Brain imaging showed extensive cerebral venous sinus thrombosis. She also misused nitrous oxide. Both cases had low-normal vitamin B12 and elevated methylmalonic acid, consistent with nitrous oxide misuse. The woman was found to have elevated homocysteine because of functional vitamin B12 deficiency. Homocysteine was not measured in the man. Raised homocysteine is associated with increased thrombosis risk. Fourteen cases of nitrous oxide misuse associated arterial and venous thrombosis have been reported. These two cases highlighted the importance of inquiring about recreational drug use in young patients who presented with apparently unprovoked venous thromboembolism. [ABSTRACT FROM AUTHOR]

To compare vitamin B12, homocysteine, and anti-parietal cell antibody (APCA) levels between children with ASD and controls, paired in terms of age, sex, and socioeconomic level. The research group consisted of 69 children, 36 with ASD and 33 controls. The severity of ASD was determined using the Childhood Autism Rating Scale (CARS). Serum vitamin B12, homocysteine and human anti-parietal cell levels were analysed using enzyme-linked immunosorbent assay. The serum vitamin B12 and homocysteine levels in children with ASD were lower than in the control group, but there was no significant difference in terms of APCA levels. Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism. However, it is believed that these parameters should be analysed in a wider population to clarify their effect on the aetiology of ASD. We hypothesised that low levels of vitamin B12 and homocysteine levels reported in previous studies might be associated with APCA levels. The homocysteine and B12 levels were found to be significantly lower in children with ASD. There was no significant difference in serum APCA levels. No significant relationship was found between B12 levels and APCA. Given all these findings, it can be stated that vitamin B12 deficiency is not associated with an absorption-related mechanism due to the presence of APCA. Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism. In future studies, it will be beneficial to investigate other mechanisms that may cause vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]

BACKGROUND: Retinal venous occlusive diseases have been recognized as a major cause of ocular morbidity. Hyperhomocysteinemia could be a potentially modifiable risk factor. OBJECTIVE: To determine the association of hyperhomocysteinemia with central and hemi-central retinal vein occlusion (CRVO and HCRVO), the correlation of serum levels of homocysteine with Vitamin B12 and folate levels and the association of Vitamin B12 deficiency with hyperhomocysteinemia. METHODS: In this case–control study, patients with CRVO and HCRVO, and age- and gender-matched controls without CRVO and HCRVO, who met the eligibility criteria, were enrolled after obtaining informed consent. Data obtained from participants using a questionnaire, complete ophthalmological examination and relevant investigations, including estimation of serum homocysteine, Vitamin B12 and folate levels, were collated and analyzed. RESULTS: Thirty-nine cases with CRVO and HCRVO and 39 age- and gender-matched controls were studied. We found a significant association of hypertension (P < 0.01), hyperlipidemia (P = 0.01), and abnormal blood profile (P < 0.01) with retinal vein occlusion. There was no statistically significant association of hyperhomocysteinemia with CRVO and HCRVO (P = 0.81). However, we found a high prevalence of both hyperhomocysteinemia (43.58% of cases and 53.84% of controls; P = 0.81) and Vitamin B12 deficiency (23.08% of cases and 38.46% of controls; P = 0.14) in cases and controls, without a statistically significant difference between the two groups with respect to both parameters. Our study also found a negative correlation of serum levels of homocysteine with Vitamin B12 (Pearson correlation co-efficient − 0.3874, P = 0.0005), and folate (Pearson correlation coefficient − 0.3886, P = 0.0004) of the study participants. Among the study participants (n = 78), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (2.26–21.72) times those of patients without Vitamin B12 deficiency (P = 0.001). Similarly, among the cases (CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 7.0 (1.22–40.09) times those of patients without Vitamin B12 deficiency (P = 0.029). In the control group also (non-CRVO, n = 39), the odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were 6.67 (1.47–30.21) times those of patients without Vitamin B12 deficiency (P = 0.014). CONCLUSION: Hyperhomocysteinemia was not found to be an independent risk factor for retinal vein occlusion in our study. However, we found a high prevalence of hyperhomocysteinemia and Vitamin B12 deficiency in both cases and controls, without a statistically significant difference between the two groups with respect to both parameters. We also found a negative correlation of serum homocysteine levels with Vitamin B12 and folate levels. The odds of patients with Vitamin B12 deficiency having hyperhomocysteinemia were seven times those of patients without Vitamin B12 deficiency. Hypertension, hyperlipidemia, and abnormal blood profile had a significant association with CRVO and HCRVO. Many of the systemic risk factors for retinal vein occlusions are found to be associated with elevation of serum homocysteine levels, which may be part of a final common pathway in bringing about a state of accelerated atherosclerosis, leading to CRVO or HCRVO. Therefore, lowering serum levels of homocysteine by Vitamin B12 and folate supplementation could have a role in the prevention of these diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD. Case presentation We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation. Conclusions Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

Background: Recreational N2O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders. Methods: Patients with N2O‐related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. Results: The principal clinical manifestations of N2O‐related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = −0.309, p =.014), which disappeared after linear regression. An interval of less than 6 months between initial N2O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ2 = 6.40, p =.01). Thirty‐eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p <.01; r = 0.346, p <.01; r = 0.477, p <.01; r = 0.324, p <.01). Conclusions: The significant inverse correlation between initial vitamin B12 levels and clinical severity could aid prognosis prediction in patients with N2O‐related neurological disorders. Spinal MRI abnormalities were not related to clinical severity but depended on the time interval between initial N2O abuse and hospitalization. Anxiety and depression were common comorbidity in these patients, and their severity increased with the intensity of clinical impairment and/or serum homocysteine levels. [ABSTRACT FROM AUTHOR]

Nitrous oxide, also known as 'laughing gas', is one of the most widely used recreational drugs among teenagers in the UK. Copious inhalation of nitrous oxide may increase intra-alveolar pressure, resulting in barotrauma secondary to alveolar rupture. Pneumomediastinum and subcutaneous emphysema are common clinical findings in nitrous oxide-associated barotrauma. Prolonged nitrous oxide misuse may inactivate vitamin B12 through the alteration of its metabolism, causing demyelination of the central and peripheral nervous system. A spectrum of neurological manifestations has been reported, including peripheral neuropathy, myelopathy and subacute combined degeneration of the spinal cord. Medical therapies and psychosocial interventions aiming at nitrous oxide cessation are important treatment steps to achieve partial or complete recovery from the adverse effects associated with inhalation of nitrous oxide. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance. To investigate the prevalence of hyperhomocysteinemia (S -tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children. In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants. Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia. We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms. • S -tHcy > 8 μmol/L was associated with tremor and excessive sleep. • 10% of infants had clinically relevant S -tHcy>8 μmol/L suggestive of clinical B12 deficiency. • 78% of infants with S -tHcy > 8 μmol/L did not show clinically relevant symptoms. • Sub-normal score on ASQ fine motor section was associated with higher S -tHcy. [ABSTRACT FROM AUTHOR]

The sources of bioavailable vitamin B12 are limited, and most of them are animal-derived. Chlorella vulgaris, a freshwater microalga, is known for immune system boosting, nutraceutical properties and presence of a natural form of vitamin B12. The present study focused on the in vivo evaluation of the Chlorella biomass as a source of bioavailable vitamin B12 to alleviate the vitamin B12 deficiency status of Wistar rats. Experimental animals were evaluated for the vitamin B12 deficiency-related circulatory marker (serum vitamin B12) and functional markers (plasma homocysteine and urinary methylmalonic acid), haematological and histological changes. The results showed that an increase of 2.4-fold in urinary methylmalonic acid (13.01 ± 0.89 µmoles moles of creatinine−1), 2.6-fold in plasma homocysteine (17.18 ± 3.57 µmole L−1), and 48% decrease in serum vitamin B12 levels (252.69 ± 1.46 pg mL−1) in vitamin B12 deficient group compared to control animals. The Chlorella biomass supplementation in the diet led to the restoration of the functional and circulatory markers, hematological parameters, and vitamin B12 content of kidney and liver to control levels. The Chlorella biomass supplementation increased the erythrocyte precursors and MAST cells in the bone marrow and also normalized the histological features of kidney, liver, and lung tissues. The results suggest that the vitamin B12 from the Chlorella biomass was bioavailable and facilitated the improvement of vitamin B12 status in deficient rats. [ABSTRACT FROM AUTHOR]

Abstract Background Recreational N2O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders. Methods Patients with N2O‐related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. Results The principal clinical manifestations of N2O‐related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = −0.309, p = .014), which disappeared after linear regression. An interval of less than 6 months between initial N2O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ2 = 6.40, p = .01). Thirty‐eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p