Vitamin B12 Supplementation Research Articles

Association of serum homocysteine, folate, and vitamin B12 and mood following the Swank and Wahls elimination dietary interventions in relapsing-remitting multiple sclerosis: Secondary analysis of the WAVES trial.

Depression and anxiety are common psychiatric comorbidities among people with multiple sclerosis (MS). Emerging data suggest abnormal serum homocysteine, vitamin B12, and folate levels in people with MS, which are related to a range of neurological disorders, including mood and mental illnesses. Evidence suggests that dietary interventions could affect mood disorders via several pathways. This study aimed to evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets, along with a supplement regimen, on mood as assessed by Hospital Anxiety and Depression Scale (HADS), and Mental Health Inventory (MHI). The secondary objective was to identify changes in serum levels of homocysteine, folate, and vitamin B12 and the association and mediation effects between their changes and HADS and MHI scores and their subscales among people with relapsing-remitting MS (RRMS). In a previously conducted randomized parallel-arm trial, participants with RRMS (n=77) were randomly allocated to either the Swank or Wahls diets at baseline and followed for 24 weeks. Blood was drawn at four study visits spaced 12 weeks apart: (1) run-in, (2) baseline, (3) 12 weeks, and (4) 24 weeks. Serum vitamin B12, folate, and homocysteine were analyzed. HADS and MHI questionnaires were also completed by participants at the four study visits to assess symptoms of depression and anxiety, behavioral control and positive affect respectively. Significant improvement in severity of depression (HADS-D) and anxiety (HADS-A) symptoms, MHI total, and MHI subscores were seen at 12 and 24 weeks in each diet group. Further, a significant within-group reduction in serum homocysteine and a significant increase in serum vitamin B12 level were observed in both groups at 12 and 24 weeks compared to corresponding baseline values (p≤0.05 for all). All participants exceeded the analytical maximum threshold for folate of 20nmol/L at 12 and 24 weeks. Changes in serum levels of homocysteine and vitamin B12 were not associated with and did not mediate changes in HADS depression, anxiety, MHI total and four subscales scores (p>0.05). Participants on both Swank and Wahls dietary interventions, including folate and vitamin B12 supplements, showed significant improvement in mood. However, the favorable effects of both diets on mood were not associated with or mediated by the effect of the diets on serum levels of homocysteine, folate, and vitamin B12 (p>0.05).

P11-008-23 Efficacy of Different Routes of Vitamin B12 Supplementation for the Treatment of Patients With Vitamin B12 deficiency: A Systematic Review and Network Meta-analysis

P11-008-23 Efficacy of Different Routes of Vitamin B12 Supplementation for the Treatment of Patients With Vitamin B12 deficiency: A Systematic Review and Network Meta-analysis

Diagnosis and Management of Nitrous Oxide Poisoning: A Case Report

Background: Chronic nitrous oxide (N2O) poisoning induces irreversible inactivation of vitamin B12, affecting two biochemical reactions essential for the proper functioning of the body. The prognosis is excellent when adequately and quickly treated. We present the case of a 23-year-old Caucasian woman with symptoms caused by chronic N2O inhalation. Case Presentation: A 23-year-old Caucasian woman was admitted to the emergency department with complaints of confusion and gait disturbance. Following an in-depth history and laboratory tests, chronic N2O poisoning was confirmed, and vitamin B12 supplementation was initiated promptly. Conclusion: Our case demonstrated the clinical presentation and biological changes typical of N2O poisoning. The misuse of N2O is prevalent due to the easy accessibility of cylinders over-the-counter since a few years. Recreational misuse of N2O has been observed in young populations. It is important to raise awareness among emergency physicians and nursing staff regarding increases in their consumption. Treatment involved vitamin B12 supplementation and long-term addiction monitoring

Involuntary Movements in Cobalamin Deficiency.

Neurologic problems are frequently described in infants with nutritional vitamin B12 (cobalamin) deficiency.Major neurologic consequences of infantile cobalamin deficiency include delays or regression in neurodevelopment and the occurrence of involuntary movements METHODS: We reviewed the medical records of infants with cobalamin deficiency and divided infants with involuntary movements into two groups as those, who developed involuntary movements during vitamin B12 supplementation (Group I) and those, who developed involuntary movements prior to supplementation therapy (Group II). We evaluated a total of 32 infants with the diagnosis of cobalamin deficiency. Involuntary movements were observed in 12 out of 32 infants. Group I and Group II consisted of 6 infants each. Of the infants with involuntary movements, five were exclusively breastfed until the time of diagnosis. The majority of infants in Group II had choreoathetoid movements; twitching and myoclonus in the face, tongue, and lips, and tremor in the upper extremities. These involuntary movements disappeared in one to three weeks after clonazepam therapy. In Group I; shaking movements, myoclonus, tremor, and twitching or protrusion were observed in patients' hands, feet, tongue, and lips on the 3rd-5th day of cobalamin supplementation. These involuntary movements disappeared within 5-12 days of clonazepam therapy. Recognition of nutritional cobalamin deficiency is important to perform a differential diagnosis of the condition from seizures or other causes of involuntary movements and avoid aggressive therapy and over treatment.

Anemia Due to Familial Vitamin B12 Deficiency: About 3 Cases

Vitamin B12 deficiency is a rare pathology in the paediatric population, most often due in our Moroccan context to a deficiency in intake. However, in rarer cases, it may be the result of an inborn anomaly in cobalamin transport or metabolism. A well-codified diagnostic approach can clarify the nature of the deficiency and adapt therapeutic options. We report 03 pediatric cases of three brothers treated for vitamin B12 deficiency. Diagnosed at 8, 4 and 3 years of age, they all presented with a severe anemic syndrome and delayed stature, two of them had seizures, and the elder brother was also delayed at school. Given the familial nature of the disease and the presence of proteinuria in 2 patients, Imerslund-Grasbëck disease was suspected in our patients. Treatment was based on parenteral vitamin B12 supplementation, with good clinical and biological progression in our patients. Vitamin B12 deficiency is a metabolic emergency and should be considered in the presence of hematological and neurological disorders. Although Imerslund-Gräsbeck disease is rare, it should be suspected and proteinuria investigated.

320-OR: ADA Presidents' Select Abstract: Risk Factors for Distal Symmetrical Polyneuropathy (DSPN) in the Diabetes Prevention Program (DPP) and the DPP Outcomes Study (DPPOS)

Objective: To evaluate how DSPN differs across the randomized DPP treatment groups and is associated with diabetes (DM) status, DM duration, and cumulative glycemic exposure. Methods: In the DPP, adults ≥25 years of age at high risk for DM (n=3234) were randomized to determine the effects of intensive lifestyle modification (ILS) or metformin (MET) compared to placebo (PLA) on incident diabetes. After DPP ended, participants were invited to join the DPPOS during which metformin was continued in those randomized to receive it. DSPN was rigorously assessed in 1,792 participants at DPPOS year 17 based on both symptoms and signs (pinprick, vibration, and monofilament). Multivariable logistic regression models were used to determine whether DSPN was associated with randomized treatment group, DM status and duration, and cumulative glycemic exposure. Results: At 21 years following DPP randomization, 66% had developed DM with median duration of 15 years. The prevalence of DSPN did not differ by DPP treatment group (21.5%, 21.5% and 21.9% in ILS, MET and PLA, respectively), but was slightly lower for those at risk for DM (19.6%) vs. those with DM (22.7%). There was a significant effect modification by age of the association between DPP treatment group and DSPN (p<0.05): the odds ratio (OR) for DSPN with ILS vs PLA decreased by 3.7% (95% CI 0.6-6.7) with each 1 year increase in age. MET vs. PLA was not associated with DSPN and age did not influence the null association. In models adjusted for treatment group, demographics, cardiometabolic risks, and low vitamin B12 or B12 supplement use, DSPN was associated with DM status (OR 1.40, p<0.001 vs. no DM), greater DM duration (OR 1.04 per 1 year, p<0.001), and higher time-weighted HbA1c (OR 1.85 per 1% increase, p<0.001). Conclusions: The likelihood of DSPN was higher for those with DM, longer DM duration, and higher cumulative glycemic exposure. Although ILS did not prevent DSPN overall, there were ILS benefits with increasing age. Disclosure C.Lee: Employee; Pfizer Inc. N.White: None. W.H.Herman: Advisory Panel; National Committee for Quality Assurance, Consultant; Merck Sharp & Dohme Corp., Other Relationship; National Institutes of Health, American Diabetes Association. D.Research group: None. A.Ciarleglio: None. S.Edelstein: None. J.P.Crandall: Research Support; Abbott Diabetes. D.Dabelea: None. R.B.Goldberg: None. S.E.Kahn: Advisory Panel; Anji Pharmaceuticals, Bayer Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Other Relationship; Novo Nordisk. W.C.Knowler: None. M.Ma: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (UDK048489, UDK048339, UDK048377, UDK048349, UDK048381, UDK048468, UDK048434, UDK048485, UDK048375, UDK048514, UDK048437, UDK048413, UDK048411, UDK048406, UDK048380, UDK048397, UDK048412, UDK048404, UDK048387, UDK048407, UDK048443, UDK048400)

Riboflavin ameliorates pathological cardiac hypertrophy and fibrosis through the activation of short-chain acyl-CoA dehydrogenase

Short-chain acyl-CoA dehydrogenase (SCAD), the rate-limiting enzyme for fatty acid β-oxidation, has a negative regulatory effect on pathological cardiac hypertrophy and fibrosis. FAD, a coenzyme of SCAD, participates in the electron transfer of SCAD-catalyzed fatty acid β-oxidation, which plays a crucial role in maintaining the balance of myocardial energy metabolism. Insufficient riboflavin intake can lead to symptoms similar to short-chain acyl-CoA dehydrogenase (SCAD) deficiency or flavin adenine dinucleotide (FAD) gene abnormality, which can be alleviated by riboflavin supplementation. However, whether riboflavin can inhibit pathological cardiac hypertrophy and fibrosis remains unclear. Therefore, we observed the effect of riboflavin on pathological cardiac hypertrophy and fibrosis. In vitro experiments, riboflavin increased SCAD expression and the content of ATP, decreased the free fatty acids content and improved PE-induced cardiomyocytes hypertrophy and AngⅡ-induced cardiac fibroblasts proliferation by increasing the content of FAD, which were attenuated by knocking down the expression of SCAD using small interfering RNA. In vivo experiments, riboflavin significantly increased the expression of SCAD and the energy metabolism of the heart to improve TAC induced pathological myocardial hypertrophy and fibrosis in mice. The results demonstrate that riboflavin improves pathological cardiac hypertrophy and fibrosis by increasing the content of FAD to activate SCAD, which may be a new strategy for treating pathological cardiac hypertrophy and fibrosis.

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation

We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT). We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings. Furthermore, we included a longitudinal PSC cohort (n= 158) sampled prior to and serially afterLT, and cohorts of people with inflammatory bowel disease (IBD) without PSC (n= 51) or with primary biliary cholangitis (PBC) (n= 100), as disease controls. We used Cox regression to measure the added value of PLP to predict outcomes before and after LT. In different cohorts, 17-38% of people with PSC had PLP levels below the biochemical definition of a vitamin B6 deficiency. The deficiency was more pronounced in PSC than in IBD without PSC and PBC. Reduced PLP was associated with dysregulation of PLP-dependent pathways. The low B6 status largely persisted after LT. Low PLP independently predicted reduced LT-free survival in both non-transplanted people with PSC and in transplant recipients with recurrent disease. Low vitamin B6 status with associated metabolic dysregulation is a persistent feature of PSC. PLP was a strong prognostic biomarker for LT-free survival both in PSC and recurrent disease. Our findings suggest that vitamin B6 deficiency modifies the disease and provides a rationale for assessing B6 status and testing supplementation. We previously found that people with PSC had reduced gut microbial potential to produce essential nutrients. Across several cohorts, we find that the majority of people with PSC are either vitamin B6 deficient or have a marginal deficiency, which remains prevalent even after liver transplantation. Low vitamin B6 levels strongly associate with reduced liver transplantation-free survival as well as deficits in biochemical pathways dependent on vitamin B6, suggesting that the deficiency has a clinical impact on the disease. The results provide a rationale for measuring vitamin B6 and to investigate whether vitamin B6 supplementation or modification of the gut microbial community can help improve outcomes for people with PSC.

Vitamin B12-Multifaceted In Vivo Functions and In Vitro Applications.

Vitamin B12 plays a key role in DNA stability. Research indicates that vitamin B12 deficiency leads to indirect DNA damage, and vitamin B12 supplementation may reverse this effect. Vitamin B12 acts as a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase, which are involved in DNA methylation and nucleotide synthesis. These processes are essential for DNA replication and transcription, and any impairment can result in genetic instability. In addition, vitamin B12 has antioxidant properties that help protect DNA from damage caused by reactive oxygen species. This protection is achieved by scavenging free radicals and reducing oxidative stress. In addition to their protective functions, cobalamins can also generate DNA-damaging radicals in vitro that can be useful in scientific research. Research is also being conducted on the use of vitamin B12 in medicine as vectors for xenobiotics. In summary, vitamin B12 is an essential micronutrient that plays a vital role in DNA stability. It acts as a cofactor for enzymes involved in the synthesis of nucleotides, has antioxidant properties and has potential value as a generator of DNA-damaging radicals and drug transporters.

Cross sectional study of vitamin B12 supplementation in Slovak and Czech vegans.

The number of vegans in the world is growing and in Slovakia and the Czech Republic they make up 1% of the population. Vegan diet excludes all foods of animal origin and vegans who do not use vitamin B12 supplements are at risk of the vitamin B12 deficiency. The aim of this study was to determine what proportion of Czech and Slovak vegans use vitamin B12 supplements regularly, irregularly or not at all and what is their supplemental cobalamin intake. The research involved 1337 self-identified vegans from Slovakia and the Czech Republic who were interviewed using the CAWI (Computer-Assisted Web Interview) method. Participants were recruited by posts in veganism-themed social media groups. Out of 1337 vegans 55.5% supplemented cobalamin regularly, 32.54% irregularly and 11.97% were not supplementing. Rate of not supplementing individuals was 5.04% higher in Slovaks than in Czechs. Short-term vegans had a significantly higher rate of not supplementing individuals (17.99%) compared to medium-term (8.37%) and long-term vegans (7.50%). Mean weekly cobalamin intake from supplements was 2938.34±2566.60 μg in regularly supplementing vegans compared to 1630.31±1949.27 μg in irregularly supplementing vegans, particularly due to the lower weekly supplementation frequency among irregularly (2.93) compared to regularly supplementing vegans (5.27). The rate of supplementation in Slovak and particularly Czech vegans was higher than in other countries. The number of not supplementing individuals was significantly higher among short-term vegans, indicating that there is still a need for education on the importance of adequate and regular cobalamin supplementation, especially in new vegans. Our results support the hypothesis that the reason for higher rate of cobalamin deficiency in irregularly compared to regularly supplementing vegans is the lower cobalamin intake caused by lower supplementation frequency.

Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-Area Puerto Ricans

BackgroundVitamin B12 involves several physiological functions, and malabsorption is reported with medication use. ObjectivesStudies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults. MethodsThis analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45–75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users. ResultsAt baseline, we observed an association between metformin use (β = –0.069; P = 0.03) and concomitant ALA and metformin use (β = –0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency. ConclusionsThese results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.

As3MT via consuming SAM is involved in arsenic-induced nonalcoholic fatty liver disease by blocking m6A-mediated miR-142-5p maturation

Arsenic, a common environmental hazard, is a risk factor for nonalcoholic fatty liver disease (NAFLD). However, the mechanism remains unclear. Here, we found that chronic exposure to environmental-related doses of arsenic disturbed fatty acid and methionine metabolism in mice, caused liver steatosis, increased arsenic (3) methyltransferase (As3MT), sterol regulatory element binding protein 1 (SREBP1) and lipogenic gene levels, and decreased N6-methyladenosine (m6A) and S-adenosylmethionine (SAM) levels. Mechanistically, arsenic blocks m6A-mediated miR-142-5p maturation by consuming SAM via As3MT. miR-142-5p was involved in arsenic-induced cellular lipid accumulation by targeting SREBP1. SAM supplementation or As3MT deficiency blocked arsenic-induced lipid accumulation by promoting the maturation of miR-142-5p. Moreover, in mice, folic acid (FA) and vitamin B12 (VB12) supplementation blocked arsenic-induced lipid accumulation by restoring SAM levels. Arsenic-exposed heterozygous As3MT mice showed low liver lipid accumulation. Our study demonstrates that SAM consumption caused by arsenic, through As3MT, blocks m6A-mediated miR-142-5p maturation, thereby elevating the levels of SREBP1 and lipogenic genes, leading to NAFLD, which provides a new mechanism and biological insights into the therapy of NAFLD induced by environmental factors.

Medicinal Effect of Pyridoxine - Magnesium for the Cure of Autism Spectrum Disorder

Dietary interventions involving the use of magnesium and vitamin B6 supplements are considered the most commonly employed therapeutic approach for autism spectrum disorder (ASD). However, there is currently a lack of investigation into the medicinal efficacy of vitamin and mineral supplementation in improving ASD symptoms. Nonetheless, several researchers have observed a prevalence of nutritional and metabolic abnormalities among individuals with autism. While there is some evidence suggesting that nutrient and mineral supplementation may enhance these fundamental physiological processes, further research is necessary to establish their effectiveness. This review aims to explore potential direct and indirect contributions of metabolism to the primary symptoms of autism, as well as provide evidence regarding nutritional deficiencies and metabolic dysfunction. The present review systematically investigates the existing body of evidence regarding the utilization of high-dose vitamin B6-mg supplementation for the therapeutic intervention in individuals, encompassing both pediatric and adult populations, diagnosed with autism spectrum disorder

Markers of Vitamin B12 Status in Relation to Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Cognitive Performance.

The association between markers of vitamin B12 status and cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), which precede cognitive impairment, has been investigated by only a few small studies and results have been inconsistent. The aim of this study was to investigate the associations of vitamin B12-related markers with CSF biomarkers of AD and cognitive performance. Data included 462 patients aged 40 to 94 years referred to the Memory Clinic of the Ulm University Hospital, Ulm, Germany. Vitamin B12, holotranscobalamin (HoloTC), homocysteine (tHcy), and methylmalonic acid (MMA) have been measured. CSF values of amyloid β42 (Aβ42 ) and total-tau have been assessed in 227 participants. CERAD battery was administered to examine the cognitive status, and different domains were derived. Regression models were used to investigate the associations. In the multi-adjusted model, higher levels of MMA were associated with raised CSF total-tau values: the odds ratios (ORs) 95% confidence intervals (CIs) were 3.25 (95% CI = 1.35-7.76) for the highest quartile of MMA compared to the lowest. Furthermore, moderately increased MMA were related to lower Aβ42 levels: the ORs and 95% CIs were 3.06 (95% CI = 1.22-7.67) for the third quartile of MMA compared to the lowest. All B12 indicators except B12 itself were related to several cognitive domains, such as episodic memory and executive functioning. Markers of vitamin B12 may be independent predictors of CSF biomarkers of AD and cognitive functioning, with MMA showing the most consistent effects. Randomized controlled trials are needed to determine the importance of vitamin B12 supplementation on slowing structural brain changes and cognitive decline. ANN NEUROL 2023;94:223-231.

Should we follow the guidelines on vitamin B12 deficiency and diabetes? A retrospective analysis of data from middle eastern population

ABSTRACT Background Vitamin B12 is a micronutrient required for hematopoietic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been recognized in patients with type 2 diabetes mellitus. One of the adverse effects of long-term metformin use is vitamin B12 malabsorption. Aim of the study was to assess the state of vitamin B12 deficiency in people with type 2 diabetes and to ascertain the relationship between vitamin B12 status, metformin use and peripheral neuropathy. It is a retrospective study that was conducted on 8040 subjects included 2126 type 2 diabetic patients, and 5914 nondiabetic individuals. Personal information, medical history, including metformin and multivitamin therapy use as well as the existence of clinical peripheral neuropathy, were all included data. For the purpose of measuring the amount of vitamin B12, blood samples were taken. Serum B12 levels <200 pg/ml was defined as B12 deficiency. Results Vitamin B12 deficiency was detected in 12.9% of diabetic group and 19.9% of control group. The mean value of vitamin B12 level between diabetic (563 ± 470.6 pg/ml) and non-diabetic (429.7 ± 310.9 pg/ml) showed a high significant difference, p value <0.001. The vitamin B12 levels were higher in people with diabetes. Vitamin B12 deficiency was not associated with metformin intake or diabetic neuropathy. Conclusions Vitamin B12 level was significantly higher in diabetic compared to nondiabetic individuals. Neither peripheral neuropathy, anemia nor metformin therapy was associated with vitamin B12 deficiency. Vitamin B12 supplementation is not recommended as a routine practice in people with diabetes. This is contrary to the common practice that is sometimes done. The cost of supplementation can be used to provide more beneficial services and drugs for these people.

A RARE TREATABLE CAUSE OF ADULT ONSET SPASTIC PARAPARESIS

pastic paraparesis refers to weakness and stiffness of both lower limbs caused by lesions affecting the Pyramidal tract. It could be due to genetic or acquired etiology. Genetic causes include leukodystophies, Heriditary Spastic Paraplegia (HSP), metabolic disorders etc,. Acquired causes include B12 and folate deficiency , infections like HTLV-1 virus, HIV, neurosyphilis , vascular malformations and so on. Here we encounter a rare treatable cause of spastic paraparesis. A 28 year old male born out of 3o Consanguinous parents with normal developmental history came with insidious onset slowly progressive spastic paraparesis for the past 4 years. Initially at onset he noticed difficulty in getting up from squatting position, which was associated with stiffness of lower limbs. Then he noticed there was slippage of slippers while walking and he was aware about it. Physical examination revealed marfanoid Habitus ,increased tone and exaggerated reflexes involving both lower limbs .Motor power was MRC Grade 4/5 in both lower limbs in both proximal and distal muscles. Ocular Examination revealed Ectopia Lentis. MRI Spine screening was normal. MRI Brain revealed symmetric T2/FLAIR hyperintensities involving periventricular and deep white matter of bilateral frontoparietal region. Possibilities of Primary demyelinating diseases and genetic/degenerative leukoencephalopathies were considered. CSF examination was normal and oligoclonal bands were absent. Clinical Exome sequence testing was done in suspicion of Adult onset leukodystrophy which showed Homozygous MTHFR gene mutation on exon4. Plasma Homocysteine levels were elevated ( 60 µmol/L).Patient was started on Oral Vitamin B12 1500mcg/day, Folic acid and pyridoxine supplementation. Patient showed symptomatic improvement and is under follow up. MTHFR deficiency in adults is a mimicker of leukodystrophies and other white matter disease. It is a potentially treatable disease. Before considering degenerative diseases like HSP, treatable diseases should be considered.

Vitamin B12 Deficiency and Peripheral Neuropathy in patients with Type 2 Diabetes Mellitus Treated with Metformin. An integrative review

Background/Purpose: Type 2 diabetes mellitus (T2DM) is a worldwide pathology with several complications, and 50% of patients with T2DM develop peripheral neuropathy (PN) in the long term. The present study aimed to review the literature on the association between PN and vitamin B12 deficiency in patients with T2DM treated with metformin. Materials and methods: A literature review was carried out in the PubMed Central, Cochrane, Scielo, Scopus and Embase databases, from 2015 to 2021. We found 755 studies, of which 16 were included. Results: The serum level of vitamin B12 was lower in individuals with at least one neurological symptom. Treatment with metformin was associated with reduced serum vitamin B12 levels, and its use was defined as a probable cause of PN due to reduced vitamin B12. Studies that performed supplementation with methylcobalamin demonstrated significant improvement in neuropathic symptoms. Vitamin B12 supplementation therapy for diabetic patients undergoing metformin treatment has been suggested. Conclusion: Deficiency of vitamin B12 associated to metformin can be considered a risk factor for PN. Periodically evaluation of serum levels of vitamin B12 is recommended for patients on metformin treatment.

Folate and vitamin B12 usual intake and biomarker status by intake source in United States adults aged ≥19 y: NHANES 2007–2018

BackgroundFolate and vitamin B12 are important biomarkers of nutritional status of populations. ObjectivesThis study aims to estimate folate and vitamin B12 usual intakes among United States adults and examine folate and vitamin B12 biomarker status by intake source. MethodsWe analyzed data for United States adults aged ≥19 y from National Health and Nutrition Examination Survey 2007–2018 (n = 31,128), during which time voluntary corn masa flour (CMF) fortification was started. Usual intake was estimated using the National Cancer Institute method. Folate intake included folate from natural foods and folic acid from 4 sources: enriched cereal grain products (ECGPs), CMF, ready-to-eat cereals (RTEs), and folic acid–containing supplements (SUP). Vitamin B12 intake was mainly from food and supplements. ResultsThe median natural food folate intake (222 μg dietary folate equivalents (DFE)/d) was below the estimated average requirement (EAR) of 320 μg DFE/d. The proportions of those who consumed folic acid from ECGP/CMF only, ECGP/CMF + RTE, ECGP/CMF + SUP, and ECGP/CMF + RTE + SUP were 50%, 18%, 22%, and 10%, respectively. Median usual folic acid intakes (μg/d) were 236 (IQR: 152, 439) overall and 134, 313, 496, and 695 in the ECGP/CMF only, ECGP/CMF + RTE, ECGP/CMF + SUP, and ECGP/CMF + RTE + SUP folic acid consumption groups, respectively. Overall, 2.0% (95% CI: 1.7%, 2.3%) of adults, all of whom used folic acid supplements, consumed greater than the tolerable upper intake level (UL) of 1000 μg/d folic acid. The median usual vitamin B12 intake (μg/d) was 5.2 for vitamin B12 supplement nonusers and 21.8 for users. Consumption of RTE and/or supplements with folic acid was associated with higher serum and red blood cell folate concentrations. Vitamin B12 supplement users had significantly higher serum vitamin B12 concentrations. ConclusionsFolic acid fortification plays a critical role in helping United States adults meet the folate EAR. At current fortification levels, United States adults who do not consume supplements do not have the usual folic acid intake exceeding the UL.

Status of Vitamin B12, Zinc, Copper, Selenium, Manganese, Molybdenum and Cobalt in Severe Acute Malnutrition.

To define the vitamin B12 levels and other micronutrients status in severe acute malnutrition (SAM) children. This was a prospective hospital based cross-sectional study. Children with severe acute malnutrition as per WHO criteria. (i) Pernicious anemia (ii) Autoimmune gastritis (iii) SAM children on exclusive vitamin B12 supplementation. All enrolled children underwent a detailed clinical history, general physical examination with more emphasis on clinical features of vitamin B12 and other micronutrients deficiencies. Three ml of venous blood was collected to estimate vitamin B12 and other micronutrients. Primary outcome was percentage of deficiency of serum vitamin B12, zinc, copper, selenium, manganese, molybdenum and cobalt in SAM children. Fifty children were included in the study. The mean age of children was 15.60±12.90 mo with male to female ratio 0.85:1. The common clinical presentation in order of frequency were upper respiratory infection (URI) symptoms 35 (70%), hepatomegaly 24 (48%), Hyperpigmentation17 (34%), angular cheilitis 14 (28%), tremors 11 (22%), edema 07 (14%), and hypotonia 05 (10%). Anemia was found in 44 (88%) children. Prevalence of vitamin B12 deficiency was 34%. Other micronutrient deficiencies observed were cobalt 24 (100%), copper 05 (12%), zinc 04 (9.5%), and molybdenum 03 (12.5%). No statistical significance was found between clinical symptoms and levels of vitamin B12 with different age and sex. Prevalence of low vitamin B12 and cobalt were more common than other micronutrients.

Premature farrowing and stillbirths in two organic sow farms due to riboflavin deficiency

BackgroundRiboflavin deficiency can lead to premature farrowing, stillborn piglets, weak-born piglets and neonatal death. Riboflavin (vitamin B2) is considered essential for reproductive function. The longer the period on riboflavin-deficient diets, the more severe the clinical signs become. Litter size as well as body size of piglets can also be considered risk factors that may contribute to the problem.Case presentationThis case report involved two organic farms of 320 (farm A) and 250 sows (farm B). Between 2019 and 2020, premature farrowing with weak-born or stillborn piglets and severe intra-litter mortality, ranging from 60 to 100% were observed. Investigations for infectious causes of reproductive disease, drinking water quality and general feed composition were performed, but showed no significant results. Feed composition was subsequently evaluated more in detail. Riboflavin levels were very low specifically 1.25 mg/kg of diet (3.75 mg/kg of diet is the NRC minimum recommended level). Riboflavin as a vitamin complex supplement (B complex) was administered to sows one month before the farrowing date and this led to a rapid improvement of the problem such that no stillbirth or intra-litter mortality was observed.ConclusionsThe clinical presentation, the low riboflavin levels in the feed below the recommended levels for gestating sows and the effectiveness of the riboflavin supplementation, led to an ex juvantibus diagnosis of this deficiency condition. This case report highlights that riboflavin deficiency during gestation should be considered in case of premature parturition and stillborn litters.