Vitamin B12 Supplementation Research Articles

Impact of Regulatory Action on Dose Maximalization for Vitamin B6 Dietary Supplements on the Reporting Pattern for Neuropathy.

Vitamin B6 deficiency is linked to neurological disorders. However, supplementation with high doses of vitamin B6 has also been linked to neuropathy as an adverse drug reaction. Review of cases from the Dutch Spontaneous Reporting System (SRS) and other data led to a regulatory action to lower the maximum daily dose (DD) of vitamin B6 in supplements to 21 mg/day from October 1, 2018. The aim of this study was to investigate if there was an effect of the regulatory action in 2018 on maximum daily dosage for vitamin B6 on the reporting pattern of neuropathy to the SRS in the Netherlands. We investigated trends in the number of reports received until December 31, 2023, DD mentioned in the reports, and the correlation between DD and plasma vitamin B6 levels. A change point analysis was used to get insight into the pattern of reports over time. Two hundred and twenty-four reports were included. After the regulatory action for dose maximization from October 2018, only one report mentions a dosage which is much higher than the recommended 21 mg DD. Only 15% of the variability in plasma levels mentioned in reports can be explained by the DD. Twelve statistical change points were noted, especially around some peaks in the reporting pattern for instance in 2018. However, from the second half of 2019, the number of reports on vitamin B6 and neuropathy per time period is lower and no change points were detected. Although our study has limitations, we clearly see an effect of regulatory action on the doses of vitamin B6 used in neuropathy reports. However, some cases describing neuropathy related to vitamin B6 supplementation with lower doses are still reported after the regulatory action in 2018. Therefore, the association between low-dose vitamin B6 products and neuropathy should be studied further.

Vitamin B6 Alleviates Aflatoxin B1-Induced Impairment of Testis Development by Activating the PI3K/Akt Signaling Pathway.

Aflatoxin B1 (AFB1) is a harmful environmental contaminant known to disrupt gut microbiota and cause health problems. In recent years, the role of vitamin B6 (VB6) in maintaining intestinal and reproductive health has attracted much attention. AFB1 has been found to damage the intestinal barrier and cause inflammation by disrupting the intestinal microbiota, particularly by increasing the abundance of Enterococcus. In mice treated with AFB1, serum metabolites were disturbed, VB6 serum levels were reduced, and testicular inflammation was exacerbated. Enterococcus exposure in mice leads to a reduction in serum VB6 levels, which is accompanied by intestinal and testicular damage. However, VB6 supplementation significantly ameliorated AFB1-induced intestinal and testicular injury. Transcriptomics and Western blotting showed that after AFB1 exposure, VB6 could increase the expression of phosphoinositide 3-kinase (PI3K) and kinase B (AKT) as well as their phosphorylated forms in the testes of mice. Based on the results, AFB1 leads to intestinal and testicular damage by disturbing the gut microbiota, and VB6 represents a potential therapeutic to counteract this damage. In conclusion, supplementation with adequate VB6 can ameliorate AFB1-induced intestinal and testicular damage, emphasizing the importance of VB6 intervention and providing a new perspective for the prevention and treatment of AFB1-related health issues.

Synergistically effects of n-3 PUFA and B vitamins prevent diabetic cognitive dysfunction through promoting TET2-mediated active DNA demethylation.

Diabetic cognitive dysfunction (DCD) refers to the cognitive impairment observed in individuals with diabetes. Epidemiological studies have suggested that supplementation with n-3 polyunsaturated fatty acid (PUFA) or B vitamins may prevent the development of diabetic complications. Post hoc studies indicate a potential synergistic effect of n-3 PUFA and B vitamins in preventing cognitive impairment. However, the precise effect and underlying mechanism of this combination on DCD remain unclear. In case-control study, we compared fatty acid composition of erythrocyte membrane and serum homocysteine levels between diabetic individuals with and without DCD. We found that insufficient levels of n-3 PUFA, along with elevated serum homocysteine, significantly increase the risk of developing DCD. Treatment with a combination of fish oil, folate, and vitamin B12 improved cognitive impairment and aberrant neuronal morphology in streptozotocin-induced DCD mice. Folic acid and vitamin B12 enhanced the efficiency of exogenous docosahexaenoic acid (DHA) transportation to the brain by preventing the accumulation of homocysteine and S-adenosylhomocysteine, thereby inhibiting neuronal apoptosis in diabetic brains. Furthermore, folic acid and vitamin B12 supplementation can provide sufficient 5-methylcytosine for diabetic brains by promoting DNA methylation, while increased DHA levels maintain TET-mediated active DNA demethylation in diabetic brains through enhancing TET2 function. Overall, our study provides novel insights into molecular mechanisms underlying the synergistic preventive effects of the combined supplementation with fish oil, folic acid and vitamin B12 on DCD, suggests that combining n-3 PUFA and B vitamins could be a promising strategy for preventing DCD among individuals with diabetes.

Vision loss as an initial clinical manifestation in a case of adolescent-onset MTHFR enzyme deficiency with a rare genetic mutation

Methylenetetrahydrofolate reductase (MTHFR) enzyme deficiency is a rare autosomal recessive disorder characterized by a wide range of mutations and highly variable clinical manifestations. Herein, we report a rare c.547C > T (p.Arg183Ter) mutation in a compound heterozygous state, presenting as adolescence-onset bilateral painless visual diminution, along with subtle gait abnormalities. An 11-year-old girl, previously diagnosed with bilateral ametropic amblyopia elsewhere, was found on initial evaluation to have normal ocular findings, normal retinal imaging, generalized reduced sensitivity of visual fields, and no evidence of any nerve conduction delay in either eye. Neuroimaging revealed multiple leucodystrophic lesions in the periventricular white matter in a symmetrical pattern. A hematological investigation revealed low vitamin B12, low folate, and moderate hyperhomocysteinemia. Genetic evaluation identified a rare pathogenic variant, c.547C > T (p.Arg183Ter), in a compound heterozygous state, along with a c. 973C > T (p.Arg325Cys) variant of uncertain significance in exons 4 and 6 of the MTHFR gene, respectively. She was treated with high doses of folic acid, vitamin B6, and vitamin B12 supplementation. A follow-up evaluation after 3 months revealed complete visual recovery, substantial improvement in the gait abnormalities, and regression of the leucodystrophic lesions. Late-onset MTHFR enzyme deficiency should be considered a possible cause in cases of bilateral, painless, progressive diminution of vision in the absence of a clinically detectable ocular cause, especially when accompanied by subtle or evident neurological manifestations, such as gait abnormalities. Additionally, this case report broadens the spectrum of MTHFR pathogenic mutant variants.

Analysis of Supplement Consumption of Pregnant Women with Orofacial Cleft in Children at RSAB Harapan Kita Jakarta

Congenital abnormalities remain a leading cause of death in toddlers, with a global death rate of 8.7 per 1000 live births in 2016. Cleft lip, a congenital birth defect, has an incidence rate in Indonesia that increases by an average of 7,500 cases per year. One of the exogenous factors influencing the occurrence of orofacial clefts (OFC) is maternal supplement intake. This study aimed to assess the relationship between maternal supplement consumption and the incidence of OFC in children and identify the dominant factors in maternal supplement intake. The study employed an observational analytic method with a case-control approach, involving 70 maternal samples calculated using the Lemshow formula. Data for the case group were obtained from mothers who underwent treatment at RSAB Harapan Kita Jakarta. The sampling method used was non-probability convenience sampling, and the data were analyzed using univariate, bivariate, and multivariate methods. The results showed a tendency for supplement consumption and maternal zinc requirements to increase the risk of OFC in children. However, a significant relationship was found between the timing of supplement consumption and the adequacy of folic acid, Vitamin B6, and Vitamin B12 supplements. In the multivariate analysis, the dominant risk factors were the need for folic acid and zinc in mothers. Based on the study results, it is recommended that local government regulations consider these factors to optimize the management and prevention of non-syndromic OFC in children, especially in Jakarta.

Clinical and Hematological Characteristics of Vitamin B12 Deficiency and Evaluation of the Therapeutic Response to Vitamin B12 Supplementation.

Background Vitamin B12 deficiency, or cobalamin deficiency, is common among populations with low consumption of animal-based products, mainly in India, due to religious and socioeconomic factors, which significantly increase the deficiency rate. The condition has been characterized by a wide range of clinical and hematological symptoms, mainly affecting the blood and nervous system. This study aims to assess the clinical and hematological characteristics of patients with vitamin B12 deficiency and assess the therapeutic response to supplementation with vitamin B12. Methodology This two-year, in-hospital study was conducted at K. J. Somaiya Medical College and Hospital. The study involved 180 patients aged between 18 and 70 years with hemoglobin below 13 g/dL for males, less than 12 g/dL for females, and serum vitamin B12 levels below 250 pg/mL. Data on demographic and clinical characteristics of the patients, along with hematological parameters, including complete blood count, peripheral smear, reticulocyte count, and bone marrow examination, were collected. Each patient received six intramuscular injections per week of 1,000 µg of vitamin B12. The hematological parameters were measured at different follow-up intervals, and the therapeutic response was measured using the one-way analysis of variance. We employed Pearson's correlation coefficient to investigate the relationship between the severity of anemia and vitamin B12 level. Results The study showed a higher prevalence of male patients, accounting for 105 (58.3%) of the sample, with the majority of patients aged between 46 and 60 years, totaling 70 (38.9%). Common comorbidities included hypertension in 60 (33.3%) and diabetes in 45 (25%) patients. The most frequently reported symptom was fatigue, present in 120 (66.7%) patients, followed by neurological symptoms such as tingling and numbness in the extremities reported by 98 (54.4%) patients. Baseline hematological assessments indicated macrocytic anemia, with a mean hemoglobin level of 9.7 g/dL and an elevated mean corpuscular volume (MCV) of 104.7 fL. At the end of six weeks of vitamin B12 therapy, there were notable improvements, with hemoglobin levels rising to 12.6 g/dL, MCV decreasing to 91.3 fL, and reticulocyte count increasing to 2.1%. A strong positive correlation was observed between hemoglobin levels and serum vitamin B12 concentrations (r = 0.75, p < 0.001). Conclusions Vitamin B12 deficiency leads to clinical and hematological abnormalities, including macrocytic anemia and neurological symptoms. This study demonstrates that vitamin B12 supplementation effectively reverses these abnormalities, improving both hematological and neurological outcomes. Given the prevalence of deficiency, routine screening and supplementation are recommended, particularly for at-risk populations such as vegetarians and older adults. Further research is needed to assess the long-term effects of supplementation, particularly its potential role in reducing cardiovascular risk in individuals with vitamin B12 deficiency.

Rare but relevant: Nitrous oxide and peripheral neurotoxicity, what do we know?

Nitrous oxide (N2O), used medically as an anaesthetic, has gained popularity as a recreational drug, with rising prevalence particularly among young adults. While its reinforcing and addictive potential remains debated, N2O is proven to be neurotoxic, especially with prolonged, heavy use, which is often unexpected for users. The neurotoxicological mechanism underlying N2O-induced neurotoxicity involves inactivation of vitamin B12 (cobalamin), which disrupts methionine synthesis, essential for maintaining the myelin sheath. This can result in demyelinating diseases, including generalized demyelinating polyneuropathy (GDP). Clinical incidence of N2O-induced peripheral neuropathy is largely unknown, although some research suggests it is not uncommon. Treatment includes immediate cessation of N2O use and vitamin B12 supplementation. Although this treatment often reverses damage, residual symptoms such as limb weakness may persist. Additionally, genetic and dietary factors, such as vitamin B12 deficiency, may heighten individual vulnerability for N2O's detrimental effects.

Pyridoxine supplementation before puberty ameliorates MAM-induced cognitive and sensorimotor gating impairments.

Schizophrenia is a kind of neurodevelopmental mental disorder in which patients begin to experience changes early in their development, typically manifesting around or after puberty and has a fluctuating course. Environmental disturbances during adolescence may be a risk factor for schizophrenia-like deficits. As a better treatment option, preventive intervention prior to schizophrenia may be more beneficial than direct treatment. More effective stress-relieving interventions during the critical puberty period may prevent schizophrenia-like neuronal changes and the transition to schizophrenia in adulthood. Pyridoxine deficiency alters the function of NMDA (n-methyl-D-aspartic acid) receptors and plays a key role in learning and memory. In this study, we prepared a progeny model of schizophrenia by exposing pregnant rats to methoxymethanol acetate (MAM) on gestational day 17. The offspring rats were injected intraperitoneally with pyridoxine daily from birth to prepuberty PND12-PND21), and behavioral changes in the offspring rats were observed in adulthood. Cannabinoid receptor interacting protein 1 (CNRIP1) and cannabinoid receptor-1 (CB1R), which regulate memory, cognitive and motor activity, were detected in the prefrontal cortex (PFC) and hippocampus of the offspring rats, and the cell proliferation in the hippocampal dentate gyrus (DG) was also observed. The results showed that the MAM rats spent less time the open arm in the elevated plus maze test, decreased discrimination coefficient in novel object recognition test, and decreased prepulse inhibition, while the MAM rats supplemented with pyridoxine in prepuberty did not show any of the above abnormal behavioral changes in adulthood. By examining related proteins in the PFC and hippocampus, we found that only CB1R protein expression was downregulated in the PFC, whereas CNRIP1 expression was not only elevated in the hippocampus, but also significantly increased in pyridoxine- supplemented MAM rats. Meanwhile, pyridoxine supplementation alleviated the reduction of doublecortin (DCX)-positive cells and Ki67-positive cells in MAM rats. These results indicate that prepuberty pyridoxine supplementation has a positive effect on the prevention of cognitive deficits and sensorimotor gating impairment in MAM-induced schizophrenia-like rats, accompanied by changes in the CB1R and CNRIP1 expression in PFC and hippocampus, as well as the regeneration of neurons in the DG region.

Hypertension may lead to cognitive dysfunction in older adults via methylmalonic acid: evidence from NHANES 2011–2014 population

BackgroundAn enriched understanding is necessary concerning the association between hypertension and cognitive impairment in older adults, particularly regarding the potential underlying mechanisms at a biological level. This study aimed to explore the mediating role of methylmalonic acid (MMA) in the hypertension-cognition link in the older population.MethodsA total of 2762 adults (age > = 60 years) from the National Health and Nutrition Examination Survey (NHANES) 2011–2014 participated. Cognitive function was assessed using a combination of the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word List Learning Test. Self-reported hypertension diagnosis, antihypertensive medications use, and blood pressure examinations were used to identify hypertension. Serum MMA (sMMA) levels were collected. Weighted multiple linear regressions and mediation analysis were applied. A subgroup analysis by sex and age was performed.ResultsAfter adjusting for potential confounding factors, we observed a significant mediating effect of the sMMA level in the hypertension-cognition link, accounting for 11.14% (95% CI 4.09%-14.00%, p < 0.001) of the relationship in older adults. The proportion mediated by the sMMA level in the relationship between hypertension and cognitive function was higher in males (15.23%, 95%CI 1.32%-27.00%, p < 0.001) than in females (6.61%, 95%CI 2.12%-10.00%, p < 0.001). This mediating effect of sMMA was observed only in individuals aged 68 years and older (11.31%, 95%CI 3.80%-16.00%, p < 0.001), with no significant mediation detected in those younger than 68 years.ConclusionHypertension may lead to cognitive dysfunction in older adults through MMA. Apart from its role as a biomarker reflecting vitamin B12, MMA may act as an independent neurotoxin capable of inducing brain injury and cognitive impairment. Addressing MMA accumulation, such as through Vitamin B12 supplementation, may have a potential to mitigate hypertension-induced cognitive decline in older adults. Special attention could be paid to hypertensive males with an advanced age (> = 68) to address MMA-related cognitive decline.

Child Neurology: Five-Year Update on Siblings With Riboflavin Transporter Deficiency: Stable Visual and Neurologic Status With Continued Riboflavin Therapy.

Riboflavin transporter deficiency (RTD), previously referred to as Brown-Vialetto-Van Laere syndrome, is caused by pathogenic variants in the SLC52A1, SLC52A2, or SLC52A3 genes, resulting in RTD types 1, 2, and 3, respectively. Researchers estimate an occurrence of approximately 1 in 1,000,000. There is only one case of type 1 described in medical literature. Type 2 is characterized by muscle weakness in the arms and neck, vision loss, hearing impairment, and sensory ataxia. In type 3, vocal cord paralysis is more common and muscle weakness is more generalized. In 2018, we described a case of a 6-year-old girl with RTD type 2 who made remarkable visual recovery after initiation of treatment with oral riboflavin and coenzyme Q10 supplementation. The patient's younger brother began the same treatment regimen after genetic testing confirmed that he carried the same genetic variant. In this report, we update the visual and neurologic status in these siblings 5 years after our initial report and 7.5 years after initiation of riboflavin treatment.

An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.

X-linked sideroblastic anemia (XLSA) is a congenital anemia caused by mutations in ALAS2, a gene responsible for heme synthesis. Treatments are limited to pyridoxine supplements and blood transfusions, offering no definitive cure except for allogeneic hematopoietic stem cell transplantation, only accessible to a subset of patients. The absence of a suitable animal model has hindered the development of gene therapy research for this disease. We engineered a conditional Alas2-KO mouse model using tamoxifen administration or treatment with lipid nanoparticles (LNP) carrying Cre-mRNA and conjugated to an anti-CD117 antibody. Alas2-KOBM animals displayed a severe anemic phenotype characterized by ineffective erythropoiesis (IE), leading to low numbers of red blood cells (RBC), hemoglobin (Hb), and hematocrit (HCT). In particular, erythropoiesis in these animals showed expansion of polychromatic erythroid cells, characterized by reduced oxidative phosphorylation, mitochondria's function, and activity of key Tricarboxylic Acid (TCA) cycle enzymes. In contrast, glycolysis was increased in the unsuccessful attempt to extend cell survival despite mitochondrial dysfunction. The IE was associated with marked splenomegaly and low hepcidin levels, leading to iron accumulation in the liver, spleen, and bone marrow and the formation of ring sideroblasts. To investigate the potential of a gene therapy approach for XLSA, we developed a lentiviral vector (X-ALAS2-LV) to direct ALAS2 expression in erythroid cells. Infusion of BM cells with 0.6-1.4 copies of the X-ALAS2-LV in Alas2-KOBM mice improved CBC levels, tissue iron accumulation, and survival rates. These findings suggest our vector could be curative in XLSA patients.

Development of a riboflavin-responsive model of riboflavin transporter deficiency in zebrafish.

Riboflavin transporter deficiency (RTD) is a rare and progressive neurodegenerative disease resulting from the disruption of RFVT2- and RFVT3- mediated riboflavin transport caused by biallelic mutations in SLC52A2 and SLC52A3, respectively. The resulting impaired mitochondrial metabolism leads to sensorimotor neurodegeneration and symptoms including muscle weakness, respiratory difficulty, and sensorineural deafness. Although over 70% of patients with RTD improve following high-dose riboflavin supplementation, remaining patients either stabilise or continue to deteriorate. This may be due to the rapid excretion of central nervous system (CNS) riboflavin by organic anion transporter 3 (OAT-3), highlighting the need for alternative or supplemental RTD treatments. Probenecid is a promising therapeutic candidate for RTD due to its known inhibitory effect on OAT-3. Therefore, this study aimed to generate morpholino-mediated knockdowns of human SLC52A3 ortholog slc52a3 in zebrafish larvae for use in therapeutic screening of riboflavin and probenecid. Knockdown of slc52a3 resulted in an RTD-like phenotype indicative of altered neurodevelopment, hearing loss, and reduced mobility. This RTD-like phenotype overlaps with the phenotype of CRISPR/Cas9-mediated knockout of slc52a3 in zebrafish, is maintained following slc52a3 morpholino + p53 morpholino co-injection, and is rescued following slc52a3 morpholino + human SLC52A3 mRNA co-injection, indicating specificity of the knockdown. Riboflavin treatment alone ameliorates locomotor activity and hearing ability in slc52a3 morphants. Riboflavin and probenecid co-treatment provides an additional small benefit to hearing but not to locomotion. Our findings demonstrate that this model recapitulates both the RTD phenotype and the riboflavin-responsiveness of RTD patients, and possible therapeutic benefit conferred by probenecid warrants further investigation.

Efficacy in prenatal vitamin B12 supplementation preventing vitamin B12 deficiency in exclusively breastfed infants

Efficacy in prenatal vitamin B12 supplementation preventing vitamin B12 deficiency in exclusively breastfed infants

Unusual presentation of Evans syndrome with hypokalemic paralysis during pregnancy, management and outcome

Background: Evans Syndrome (ES) is a rare autoimmune disorder characterized by autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Its occurrence in association with Sjögren’s Syndrome (SS) during pregnancy, compounded by hypokalemic paralysis, is exceedingly rare. Case Description: A 24-year-old primigravida at 17 weeks of gestation presented with limb weakness due to hypokalemic paralysis. She had a history of ES and SS diagnosed prior to conception, managed initially with corticosteroids and vitamin B12 supplementation. During pregnancy, she experienced hypokalemia, renal tubular acidosis, and moderate anemia, which were managed effectively with potassium, bicarbonate, prednisolone, and hydroxychloroquine. The pregnancy was monitored closely, culminating in a cesarean delivery of a healthy baby at 39 weeks. Postpartum care included transfusions and anticoagulation therapy. Both mother and baby showed favorable outcomes without major complications. Conclusion: The coexistence of ES and SS during pregnancy, further complicated by hypokalemic paralysis, presents unique challenges. Early diagnosis, multidisciplinary management, and close monitoring are pivotal in achieving successful maternal and neonatal outcomes.

Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases.

Elevated plasma homocysteine (Hcy) is associated with an increased risk of developing neurodegenerative diseases; however, its relationship with the apolipoprotein E (APOE) ε4 allele has not been well characterized. Participants clinically diagnosed with Alzheimer's disease or mild cognitive impairment (AD/MCI), frontotemporal dementia, Parkinson's disease, or cerebrovascular disease were stratified by the presence of the APOE ε4 allele. Volumetric magnetic resonance imaging, plasma amyloid/tau/neurodegeneration biomarkers, and cognitive performance were quantified. Across all diagnostic groups, Hcy was associated with lower brain parenchymal fraction and greater neurofilament light chain in APOE ε4 non-carriers only. In AD/MCI, Hcy was associated with phosphorylated tau 217 in APOE ε4 non-carriers, but not in carriers. Exploratory analyses revealed interactions between Hcy and APOE ε4 on memory and visuospatial function. Hcy may contribute to neurodegeneration depending on the presence of the APOE ε4 allele and specific disease processes. Trials on vitamin B12 supplementation may consider stratifying by APOE genotype. Highlights Homocysteine (Hcy) was associated with neurodegenerative biomarkers across disease groups. Relationships with Hcy were predominantly found in apolipoprotein E (APOE) ε4 non-carriers. In Alzheimer's disease, associations between Hcy and phosphorylated tau 217 were found in APOE ε4 non-carriers only. Significant interactions existed between Hcy and APOE ε4 status on cognition.

Vitamin B12 concentrations vary greatly in milk donated to a large provincial milk bank, and are influenced by supplementation and parity

Feeding parent's milk with supplemental donor milk (DM) is the optimal way to feed very low birth weight (VLBW) infants instead of formula; however, suboptimal neurodevelopment persists. This is believed due, in part, to suboptimal nutrition. Given vitamin B12's role in neurodevelopment and increased adoption of plant-based diets among females of child-bearing age, we aimed to determine the adequacy of vitamin B12 in DM (n=380 donors) and associated donor characteristics. Vitamin B12 was measured in consecutive raw DM donations received at the milk bank from March 2020-2021 using a validated competitive chemiluminescent enzyme immunoassay (IMMULITE 2000, Siemens). Donor characteristics were obtained from screening records and associations with milk vitamin B12 concentrations explored using a generalized additive model. Donors were 32±4 years old (mean±SD), and DM was expressed 98±85 days postpartum. Vitamin B12 concentrations in DM had a median (25th, 75th percentile) of 232 (149, 373) pmol/L; 64% had concentrations <310pmol/L (common cut-off for inadequacy in healthy term-born infants). In a multivariable analysis, donors consuming a vitamin B12-containing supplement had higher DM vitamin B12 (β±SE: 80.3±25.4pmol/L; p=0.020) compared to those not taking a supplement. Primiparous donors had higher DM vitamin B12 than multiparous donors (36.7±18.2pmol/L greater; p=0.044). No associations were observed for other donor characteristics. Milk donated to a large human milk bank showed evidence of suboptimal vitamin B12; levels were associated with both donor vitamin B12-containing supplement use and parity. Further research as to whether and when milk bank donors are recommended to consume a supplement and the benefits and risks of routine vitamin B12 supplementation of DM-fed infants is warranted.

Efficacy of Thiamine (Vitamin B1) on Post-acute COVID-19 Syndrome: An Open-Label, Randomized, Controlled Trial

Background: Thiamine (vitamin B1) has the potential to influence the severity of various diseases by enhancing immune function. However, its role in the manifestations of coronavirus disease 2019 (COVID-19) remains inadequately understood. Objectives: This study aimed to investigate the efficacy of thiamine in alleviating symptoms of post-acute COVID-19 syndrome. Methods: In this open-label, randomized, controlled trial, 66 recovered COVID-19 patients experiencing post-acute COVID-19 syndrome were enrolled. Participants were randomly assigned to two groups: An intervention group receiving vitamin B1 alongside supportive therapy and a control group receiving supportive therapy alone. Symptom frequency and severity were monitored weekly over a nine-week period as study outcomes. Data were analyzed using SPSS. Results: The mean age of participants was 49.35 ± 13.83 years. Findings showed that vitamin B1 administration significantly shortened the duration for symptom improvement compared to the control group, with effects observed within two weeks (P &lt; 0.0001). Unlike the control group, many symptoms—including myalgia, anosmia, ageusia, fatigue, and sleep disturbances—showed improvement after five weeks of vitamin B1 supplementation (P &lt; 0.05). From the seventh week onwards, the recovery rate in the vitamin B1 group was twice that of the control group. Conclusions: Our findings indicate that vitamin B1 administration can significantly reduce the duration of post-acute COVID-19 syndrome. For post-acute COVID-19 patients, vitamin B1 supplementation along with appropriate supportive therapy is recommended to enhance recovery rates.

Late-onset drug-resistant epilepsy in pyridoxamine 5′-phosphate oxidase deficiency: a case report

BackgroundPyridoxamine 5′-phosphate oxidase deficiency is a rare inborn error of vitamin B6 metabolism that presents with drug-resistant epileptic seizures. However, the condition is responsive to supplementation with the active vitamin B6 metabolite pyridoxal 5′-phosphate and, in some cases, pyridoxine. Case presentationIn this case report, a 10-year-old Iranian male of Fars ethnicity came to a regional hospital in Tehran, Iran with a chief complaint of tic-like movement. He had a history of unintentional, repetitive, and stereotypic movements of both arms since the age of 4 years. The physical examination depicted facial dimorphism. During admission, the patient experienced habitual hypermotor seizures and generalized tonic–clonic seizures. Ictal electroencephalography demonstrated a generalized background attenuation and bursts of generalized, predominantly left-sided, biphasic spike-wave complexes. Whole-genome sequencing revealed a pyridoxamine 5′-phosphate oxidase deficiency as the underlying cause of the drug-resistant seizures, resulting in a low serum level of pyridoxal 5′-phosphate. The patient underwent pyridoxine supplementation therapy, which ultimately resolved his seizures. At 6 months, he was seizure free.ConclusionPhysicians ought to be aware of manifestations of vitamin B6 deficiency such as mimicking tic and consider it in the differential for drug-resistant epilepsy.

NCMP-05. CLINICAL AND RADIOGRAPHIC IMPROVEMENT WITH REPLACEMENT OF FOLATE METABOLITES IN A PATIENT WITH INTRATHECAL METHOTREXATE-INDUCED MYELOPATHY

Abstract Methotrexate (MTX)-induced myelopathy is a rare but serious adverse effect of intrathecal (IT) MTX, which may mimic subacute combined degeneration (SCD). MTX disrupts the normal synthesis of methionine, which plays an important role in maintaining myelin sheath integrity, resulting in degeneration of the dorsal columns. This degeneration does not respond to classic treatment with vitamin B12 and folate supplementation, unlike SCD. Here, we describe a case of a 45-year-old woman with Philadelphia-positive B-cell acute lymphoblastic leukemia treated with hyperCVAD regimen with ponatinib, who after 14 doses of prophylactic IT MTX, developed progressive lower extremity weakness, paresthesias, gait instability, saddle anesthesia, and bowel/bladder dysfunction. Her neurologic exam was also notable for diffuse hyporeflexia. The onset of symptoms followed a diarrheal infection, and an initial MRI spine showed no evidence of abnormal enhancement. She was initially treated with intravenous immunoglobulins for presumed acute inflammatory demyelinating polyneuropathy. She then re-presented one week later with progressively worsening symptoms. A repeat MRI spine revealed a new longitudinally extensive T2 hyperintense signal within the dorsal columns from T7 to T12. CSF results were notable for mild pleocytosis and increased myelin basic protein; the latter of which is often seen in MTX-induced myelopathy. The patient received high-dose administration of key metabolites of the methyl-transfer pathway including S-adenosylmethionine (PO 400mg three times daily), folinate (IV 20mg four times daily), cyanocobalamin (PO 1000mcg once daily) and methionine (PO 5mg once daily) for 7 days. This treatment regimen resulted in both clinical and radiographic improvement. Subsequent MRI spine demonstrated complete resolution of the abnormal signal in the thoracic cord. This case highlights (1) the diagnostic complexity of IT MTX-induced myelopathy (2) the role response to treatment plays in uncovering this diagnosis, and (3) how the replacement of folate metabolites facilitates both radiographic and clinical improvement in IT MTX-induced myelopathy.

Assessment of Vitamin B12 Efficacy on Cognitive Memory Function and Depressive Symptoms: A Systematic Review and Meta-Analysis.

Vitamin B12 is significant for DNA synthesis, red blood cell formation, and nervous system function. Inadequate vitamin B12 levels may result in a higher risk of depression, necessitating the need for supplementation to improve mood and cognitive function. However, the use of vitamin B12 supplementation varies across studies. This review aims to evaluate the effect of vitamin B12 supplementation on cognitive memory function and depressive symptoms among participants who may have mild cognitive impairment (MCI). This review adhered to the Cochrane Handbook and PRISMA guidelines. A comprehensive search was conducted across PubMed, CENTRAL, Medline, and Ovid, with no constraints on geography or demographics, up to August 31, 2024. Only randomized controlled trials (RCTs) were included. Data on study characteristics, treatment details, and outcomes were extracted. The risk of bias was assessed using the revised Cochrane ROB2 tool. A meta-analysis of the effect of vitamin B12 on cognitive memory and depression was conducted using Jamovi software (The jamovi project (2024).jamovi(Version 2.5) [Computer Software]. Retrieved from https://www.jamovi.org). Statistical significance was set at p < 0.05. The results yielded 483 records that were screened based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Excluding duplicates and irrelevant studies, the meta-analysis finally included nine RCTs. For cognitive memory function, eight of the nine included studies were analyzed, showing an average standardized mean difference of -0.03 (95% confidence interval (CI): -0.07 to 0.01), indicating no significant effect of vitamin B12 supplementation (p = 0.1801) and no significant heterogeneity. Regarding depressive symptoms, three of the nine included studies were analyzed, yielding an average standardized mean difference of -0.01 (95% CI: -0.0773 to 0.0525), also showing no significant effect (p = 0.708). These results suggest that vitamin B12 complex supplementation has an insignificant effect on cognitive function and depressive symptoms in the general population. However, further research is needed to explore the conditions under which B12 is most effective, providing clearer guidelines for its use in clinical practice.