Vitamin B12 Supplementation Research Articles

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.

Evaluation of the ameliorative potential of Nutritional Dietary supplementation of vitamin B12 following chronic tramadol hydrochloride exposure induced hyperlipidemia, atherogenic indices, and hepato-renal dysfunction by downregulating redox imbalance, NO/iNOS/NF-κB response, caspase-3- activation and DNA fragmentation in rat’s model

Vitamin B12 is an essential water-soluble vitamin, commonly found in a variety of foods. The present study investigated the effect of Vitamin B12 on tramadol-induced hepatorenal dysfunctionand DNA fragmentation in rats. Thirty-two (32) adult male Sprague–Dawley rats were randomized into four groups of eight (n=8) rats each. Group A served as control and was given 1 ml normal saline, group B received 50 mg /kg body weight (bwt) of tramadol (TRM), group C received 0.5 mg/kg bwt of vitamin B12 (VB12) and group D received 50 mg /kg bwt TRM and 0.5 mg/kg bwt of VB12 through gastric gavage daily for 8 weeks. The biomarkers of hepatorenal damage, antioxidant enzyme activities, myeloperoxidase (MPO), nitric oxide (NO), inducible nitric oxide synthase (iNOS), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO), lipid profile, tumour necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-ĸB), interleukin-1 β (IL-1β) interleukin-6 (IL-6) and caspase-3 activity, cardiovascular risk indices, total ATPase, protein thiols, DNA fragmentation and liver and kidney histology were assessed.The increase in biomarkers of hepatorenal toxicity by TRM was alleviated by VB12. Also, the decrease in antioxidant status as well as the elevation in RONS and LPO were assuaged in rats cotreated with TRM and VB12. In addition, TRM-mediated increases in TNF-α, IL-1β, IL-6, NF-kB and caspase-3 activity were significantly diminished in the liver and kidney by VB12. Hepatorenal histopathological lesions were alleviated by VB12.Vitamin B12 therefore, assuaged TRM-induced oxidative stress, inflammation and caspase-3 activation in the liver and kidney.

An Adenosylcobalamin Specific Whole-Cell Biosensor.

Vitamin B12 (cobalamin) is essential for human health and its deficiency results in anemia and neurological damage. Vitamin B12 exists in different forms with various bioactivity but most sensors are unable to discriminate between them. Here, a whole-cell agglutination assay that is specific for adenosylcobalamin (AboB12), which is one of two bioactive forms, is reported. This biosensor consists of Escherichia coli that express the AdoB12 specific binding domain of CarH at their surface. In the presence of AdoB12, CarH forms tetramers, which leads to specific bacterial cell-cell adhesions and agglutination. These CarH tetramers disassemble upon green light illumination such that reversion of the bacterial aggregation can serve as internal quality control. The agglutination assay has a detection limit of 500 nм AdoB12, works in protein-poor biofluids such as urine, and has high specificity to AdoB12 over other forms of vitamin B12 as also demonstrated with commercially available supplements. This work is a proof of concept for a cheap and easy-to-readout AdoB12 sensor that can be implemented at the point-of-care to monitor high-dose vitamin B12 supplementation.

The effect of acute oral pyridoxine supplementation on peripheral chemoreflex sensitivity in human hypertension

ATP has been identified as an important signalling molecule in the carotid body. Animal models of hypertension have uncovered that ATP transmission via purinergic (P2) receptors increases carotid body tonicity and sensitivity, which drives sympathetic outflow and elevates blood pressure. A naturally occurring metabolite of pyridoxine (Vitamin B6), namely pyridoxal-5-phosphate, is a non-selective P2X receptor antagonist. In this study we tested the hypothesis that oral administration of pyridoxine reduces peripheral chemoreflex sensitivity and blood pressure in human hypertension. 14 treated hypertensive patients (4 men, 71±5 yr, 27±6 kg·m -2 , 156±19/83±8 mmHg) completed a double-blind placebo-controlled crossover study with either oral pyridoxine (600 mg) or placebo. Two-hours later, minute ventilation (V̇ E ), end-tidal partial pressures of oxygen and carbon dioxide (P ET O 2 and P ET CO 2 ), mean arterial pressure (MAP), and heart rate (HR) were recorded during an isocapnic hypoxic rebreathing protocol (target P ET O 2 45mmHg). Cardiorespiratory responses were taken as the change from baseline to peak rebreathing (final 15s). Arterial oxygen saturation (S a O 2 ) was calculated from P ET O 2 using the Severinghaus equation, and peripheral chemoreflex sensitivity taken as ΔV̇ E divided by ΔS a O 2 . Baseline V̇ E (13.02±3.26 vs. 12.68±4.13 L·min -1 , P=0.616), MAP (109±11 vs. 104±10 mmHg, P=0.058), and HR (63±11 vs. 62±8 BPM, P=0.463), were not different between pyridoxine and placebo conditions, respectively. The ΔV̇ E response to isocapnic hypoxia tended to be blunted with pyridoxine compared to placebo (6.88±3.94 vs. 9.87±7.69 L·min -1 ; P=0.188), but this did not reach statistical significance. Similarly, peripheral chemoreflex sensitivity was not different with pyridoxine compared to placebo (-0.46±0.31 vs. -0.64±0.49 L·min -1 ·% -1 , P=0.148). However, individuals with a higher peripheral chemoreflex sensitivity in the placebo condition, displayed a more marked reduction in peripheral chemoreflex sensitivity following pyridoxine (R 2 =0.63, P=0.005). While HR and MAP increased during isocapnic hypoxia (both P&lt;0.001), the magnitude of this response did not differ with pyridoxine or placebo administration. In this preliminary study, oral pyridoxine lowered neither blood pressure nor peripheral chemoreflex sensitivity in human hypertension. However, oral pyridoxine did lower peripheral chemoreflex sensitivity in those hypertension patients in whom baseline peripheral chemoreflex sensitivity (i.e., placebo condition) was highest. It is possible that oral pyridoxine supplementation may be beneficial for those hypertensive patients who exhibit overactivation of their peripheral chemoreflex. Health Research Council of New Zealand (Ref# 19/687), the University of Auckland Faculty Research Development Fund, and the New Zealand Lottery Grants Board (R-LHR-2021-153114). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pseudo-Orthostatic Tremor as a Manifestation of Vitamin B12 Deficiency: A Case Report

Vitamin B12 deficiency has long been known to present with various neurological manifestations, but only rarely presents as movement disorders, especially in adults. We present the case of a 30-year-old vegan male presenting with tremors on both legs when standing which was relieved by vitamin B12 supplementation. To the best of our knowledge, this is the first documented case of slow orthostatic tremor or pseudo-orthostatic tremor caused by vitamin B12 deficiency. Key words: Vitamin B12 Deficiency, Cobalamin, Vegan, Movement Disorders, Tremor, Orthostatic Tremor, Shaky-leg Syndrome, Electromyography

Onset of Mania by Vitamin B12 Injection in a 52-Year Old Patient with Refractory and Resistant Depression

Vitamin B12 affects and modify the function of multiple organ systems. Its deficiency may cause psychiatric symptoms in addition to hematologic, gastrointestinal, and neurologic manifestations. The present case study aims to report a patient with vitamin B12 deficiency who coexisted with resistant and persistent depression, and experienced mania phase after the replacement of vitamin B12. For a patient with refractory and resistant depression and evidence or a risk factor for vitamin B12 deficiency, it is required to check plasma levels and monitor psychiatric symptoms during vitamin B12 supplementation. There are some manifestations of B12 deficiency including bipolar disorder, mood lability, irritability, and psychosis due to deficiency but we didn’t find case report about induce of psychiatric presentation follow correction of vitamin B12 deficiency .

Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway

AimTo examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action. MethodsMice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury. ResultsWe found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury. ConclusionHigh doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

Prevalence of Vitamin B12 Deficiency in Type 2 Diabetes Mellitus Patients on Metformin Therapy.

Background Long-term metformin treatment in individuals with type 2 diabetes mellitus causes vitamin B12 insufficiency, which is typically neglected, undetected, and under-treated. A severe deficit may cause life-threatening neurological problems. This study assessed the prevalence of vitamin B12 deficiencies among T2DM patients and its factors at a tertiary hospital in the Tamil Nadu district of Salem. Materials and Methods This is an analytical cross-sectional study conducted in a tertiary care hospital in the Salem district, Tamil Nadu, India. Patients with type 2 diabetes mellitus who were prescribed metformin at the outpatient department of general medicine took part in the trial. Our research instrument was a structured questionnaire. We used a questionnaire containing information on sociodemographic characteristics, metformin use among diabetic mellitus patients, diabetes mellitus history, lifestyle behaviors, anthropometric measurement, examination findings, and biochemical markers. Prior to administering the interview schedule, each participant's parents provided written informed consent. A thorough medical history, physical exam, and anthropometric examination were performed. Data were entered in Microsoft Excel (Microsoft Corporation, Redmond, WA) and analyzed using SPSS version 23 (IBM Corp., Armonk, NY). Results Among the study participants, we diagnosed nearly 43% of diabetes cases in participants between the ages of 40-50 years, while we diagnosed 39%aged under 40 years. Nearly 51% had diabetes for 5-10 years, while only 14% had diabetes for over 10 years. In addition, 25% of the study sample had a positive family history of type 2 diabetes. Nearly 48% and 13% of the study group had been on metformin for 5-10 years and >10 years, respectively. The majority, 45%, were found to take 1000 mg of metformin per day, whereas just 15% take 2 g per day. In our study, the prevalence of vitamin B12 insufficiency was 27%, and nearly 18% had borderline levels. The duration of diabetes mellitus, the duration of metformin intake, and the dose of metformin were statistically significant (p-value = 0.05) among the variables associated with diabetes mellitus and vitamin B12 deficiency. Conclusion The results of the study show that a deficiency in vitamin B12 increases the likelihood that diabetic neuropathy would worsen. Therefore, individuals with diabetes who take larger dosages of metformin (more than 1000mg)for an extended period must have their vitamin B12 levels monitored often. Preventative or therapeutic vitamin B12 supplementation can mitigate this issue.

Normal Outcome With Prenatal Intervention for Riboflavin Transporter Defect

BackgroundRiboflavin transporter deficiency is a rare but severe neurometabolic disorder. MethodsWe report two siblings with pathogenic variants in SLC52A3 gene, resulting in riboflavin transporter 3 deficiency. ResultsThe first sibling was diagnosed at age 11 months with severe respiratory compromise and regression of developmental milestones. His symptoms significantly improved with riboflavin supplementation therapy. The younger sibling was diagnosed by antenatal genetic analysis; riboflavin supplementation was initiated in utero and continued from birth. Now at age two years, he remains clinically asymptomatic despite genetic confirmation of riboflavin transporter deficiency. ConclusionsAntenatal riboflavin supplementation is a safe and effective treatment for the prevention of symptomatic manifestations of riboflavin transporter deficiency.

The effect of vitamin B12 supplementation during pregnancy on infant growth and development in Nepal: a community-based, double-blind, randomised, placebo-controlled trial

Vitamin B12 is required for healthy infant growth and development, but low and marginal vitamin B12 status is endemic in low-income and middle-income countries. We aimed to measure the effect of vitamin B12 supplementation from early pregnancy until 6 months post partum on infant growth and neurodevelopment. In this community-based, double-blind, placebo-controlled trial, we randomly assigned (1:1) 800 pregnant women (aged 20-40 years) who were up to 15 weeks pregnant-recruited from home visits and outpatient departments at three hospitals in Nepal-to daily supplementation with 50 μg oral vitamin B12 or placebo until 6 months postpartum. Independent scientists generated the list that linked allocation to participants' study identification number. Participants were masked to group assignment and all investigators were masked until data cleaning was completed. The primary outcomes were length-for-age Z score (LAZ) at age 12 months and the cognitive composite score of the Bayley Scales of Infant and Toddler Development (3rd edition) at age 6 months and 12 months. The primary and secondary outcomes, including adverse events, were assessed in the intention-to-treat population, for all participants with available outcome data. This trial is registered with ClinicalTrials.gov, NCT03071666. 800 eligible pregnant women were enrolled in the trial between March 28, 2017, and Oct 15, 2020, with 400 women randomly assigned to each group. Follow-up was completed on May 18, 2022. At baseline, 569 (71%) of 800 women had plasma vitamin B12 indicating low or marginal status (<221 pmol/L). We found no effect of vitamin B12 on the primary outcomes. The mean LAZ at age 12 months were -0·57 (SD 1·03) in the B12 group and -0·55 (1.03) in the placebo group (366 infants in the vitamin B12 group vs 363 infants in the placebo group) with a mean difference of -0·02 (95% CI -0·16 to 0·13). The mean cognitive composite scores were 97·7 (SD 10·5) in the B12 group and 97·1 (10·2) in the placebo group, with a mean difference of 0·5 (95% CI -0·6 to 1·7) measured in 364 and 361 infants. Stillbirths or infant deaths occurred in three (1%) of 374 women in the vitamin B12 group and nine (2%) of 379 women in the placebo group. Although vitamin B12 deficiency was prevalent in our study population and vitamin B12 supplementation from early pregnancy substantially improved vitamin B12 status, supplementation did not improve infant growth or neurodevelopment. Our findings support the current WHO recommendations of no routine vitamin B12 supplementation during pregnancy. Research Council of Norway.

Efficacy of maternal vitamin B12 supplementation for improving infant outcomes in settings with high deficiency

Efficacy of maternal vitamin B12 supplementation for improving infant outcomes in settings with high deficiency

Abstract 1840: Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression

Abstract Deregulation of cytotoxic CD8+ T cells is a feature of the aging process with important consequences for anti-tumor immunity and consequently affects tumor initiation, progression, and response to immunotherapies. However, our understanding of how the aging process affects CD8+ T cells remains incomplete. Vitamin B12 deficiency is also a feature of old age caused by a well-recognized decrease in vitamin absorption. Interestingly, clinical studies have reported a significant decline in CD8+ T cells in individuals with vitamin B12 deficiency, suggesting that vitamin B12 levels might be a mechanistic link between aging and deregulation of CD8+ T cells. An important and often overlooked consequence of vitamin B12 deficiency is an elevation of methylmalonic acid (MMA) in circulation. Our laboratory has previously established a critical role for age-induced MMA in promoting progression into metastatic disease of breast and lung cancers, which coincided with a robust immunosuppressive signature. Here, we demonstrate that exposure of CD8+ T cells to MMA or culture of CD8+ T cells in the absence of vitamin B12 reduces T cell activation, thereby decreasing T cell numbers and effector function. Conversely, supplementation of vitamin B12 on CD8+ T cells isolated from old mice enhances their ability to activate and increases T cell numbers. Evaluation of the effects of MMA on the CD8+ T cells metabolome revealed a decrease in antioxidant levels, including a pronounced reduction in vitamin C and reduced glutathione, which were accompanied by an increase in both superoxide and hydrogen peroxide, suggesting that an increase in reactive oxygen species might be the link between MMA and CD8+ T cell dysfunction. Together, these results put forward the idea that MMA is an important regulator of immune cell function and that supplementation of vitamin B12 in older people and individuals diagnosed with vitamin B12 deficiency may function as an important strategy to improve immune cytotoxic responses and thereby increase anti-cancer immunosurveillance and the effectiveness of certain immunotherapies. Citation Format: Joanne D. Tejero, Stanislav Drapela, Juan Fernandez-Garcia, Sarah-Maria Fendt, Didem Ilter, Ana P. Gomes. Methylmalonic acid accumulation suppresses CD8+ T cell activation and contributes to age-induced immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1840.