Vitamin B12 (Methylcobalamin)

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM) and is associated with substantial morbidity, mortality, and healthcare costs. Vitamin B-12 plays a critical role in nerve protection and regeneration. However, clinical evidence regarding the effectiveness and optimal dose of vitamin B-12 supplementation for managing DPN in individuals with low serum vitamin B-12 levels remains inconclusive. OBJECTIVES: The aim of this study is to compare the effects of 2 different daily doses of oral vitamin B-12 supplementation on neuropathic parameters in patients with DPN and low serum vitamin B-12. METHODS: This 16 wk, randomized controlled trial enrolled adults with T2DM, DPN, and low serum vitamin B12 levels (<200 pg/mL). Patients were randomly assigned (1:1) to receive either 1000 μg or 2000 μg of oral vitamin B12 (methylcobalamin) daily. The primary outcomes were changes in neuropathic parameters, assessed by the numerical rating scale (NRS), Michigan neuropathy screening instrument examination (MNSIE), and neuropathy disability score (NDS). Secondary outcomes included serum B-12 levels and metabolic parameters. RESULTS: Of the 35 participants randomly assigned, 32 completed the 16-wk trial. Serum vitamin B-12 levels increased significantly in both groups, with a greater rise noted in the 2000 μg group (P = 0.049). Both the 1000 μg and 2000 μg groups experienced significant improvements in neuropathy symptoms. Mean ± SD NRS scores decreased from 7.00 ± 2.03 to 5.60 ± 2.19 (P = 0.016) in the 1000 μg group, and from 6.18 ± 2.40 to 4.42 ± 2.50 (P = 0.007) in the 2000 μg group. Similarly, MNSIE scores improved from 5.70 ± 1.66 to 5.22 ± 1.99 (P = 0.033) and from 5.40 ± 1.68 to 4.47 ± 2.25 (P = 0.022), respectively. No significant difference in these neuropathic outcomes was observed between groups. The NDS remained unchanged in both groups (P > 0.05). In addition, the 1000 μg dose was associated with significant improvements in hemoglobin A1c levels, whereas the 2000 μg dose was linked to a significant decline in estimated glomerular filtration rate. CONCLUSIONS: In patients with DPN and low serum vitamin B-1

BACKGROUND: Anemia affects more than two-thirds of children aged <5 y in India, despite biweekly iron folic acid (IFA) supplementation under the Anemia Mukt Bharat national program. Multiple micronutrient (MMN) deficiencies may also contribute to the presence of anemia, but the incremental benefit of MMN supplementation in addition to IFA remains unclear. OBJECTIVES: We aimed to compare the efficacy of biweekly preventive supplementation with MMNs plus IFA compared with IFA alone on hemoglobin concentrations and prevalence of anemia in children aged 6-59 mo. METHODS: In this individually randomized, open-label trial, eligible children received biweekly supplementation with either MMN plus IFA (intervention) or IFA alone (control) for 100 doses over 50 wk. Primary outcomes were mean hemoglobin concentration and anemia prevalence. Secondary outcomes included serum ferritin, soluble transferrin receptor, vitamin B12, folate, and zinc. RESULTS: Among 1300 children enrolled (648 intervention and 652 control), supplementation compliance exceeded 75%. At the endline, the mean hemoglobin was slightly higher in the intervention group [adjusted mean difference, 0.12 g/dL; 95% confidence interval (CI): 0.00, 0.25]. The prevalence of anemia was 17.6% in the intervention group and 24.0% in the control group (adjusted relative risk, 0.72; 95% CI: 0.58, 0.90). No significant differences were observed in serum biomarkers of iron status or other micronutrients. CONCLUSIONS: Biweekly supplementation with MMN plus IFA resulted in a modest increase in hemoglobin concentrations and a relative reduction in anemia prevalence compared with IFA alone, particularly in older children. Lack of improvement in biochemical markers and a small rise in hemoglobin concentrations suggest that a reduction in the prevalence of anemia may be driven by shifts near diagnostic thresholds, rather than meaningful physiological benefits. MMN adds minimal value where IFA adherence is already high. The study was registered at Clinical Trial Registry of India as #CTRI/2020/10/028299 (https://ctri.nic.in/Clinicaltrials/login.php).

BACKGROUND: Vitamin B12 deficiency is common in populations with limited animal-source foods and has been linked to delayed infant neurodevelopment and adverse pregnancy outcomes. Evidence on the benefits of maternal B12 supplementation for improving infant neurodevelopment remains mixed, particularly in low-income and middle-income countries where deficiency is prevalent. METHODS: This double-blind, randomised controlled trial was conducted in two tertiary maternity care centres in India and Nepal. Pregnant women in their first trimester, following a vegetarian diet, were enrolled and randomised to receive either a daily oral supplement of 250 µg (group A) or 50 µg (group B) of methyl-cobalamin from enrolment to 6 months post partum. The primary outcomes were infant neurodevelopment assessed at 9-12 months using the Development Assessment Scale of Indian Infants and biochemical B12 status in mothers and infants measured through blood tests. RESULTS: 531 mothers completed the study (group A n=255; group B n=276). There were no significant differences in baseline characteristics between mothers at both centres or in groups A and B. Mental developmental quotients (DQs) were higher in the infants of group A: 103.7 (7.7) than group B: 101.7 (8.8); p=0.008). This corresponds to a mean difference of 7.8 centiles (p=0.007). Mean motor DQs were not significantly different between the groups. Maternal vitamin B12 levels rose from the first to third trimester in both groups, with a larger increase in group A (104.9 pg/mL (SD 159.1)) than group B (47.5 pg/mL (SD 118.0)), p<0.001. Holotranscobalamin levels improved similarly (p<0.001). All infant levels of vitamin B12 were within the normal range. Newborn anthropometry, APGAR scores and morbidity profiles were similar in both groups (p>0.05). Serum ferritin, vitamin D and folate were similar (p>0.05). CONCLUSIONS: Daily supplementation with 250 µg of vitamin B12 during pregnancy in vegetarian mothers significantly improved infant mental DQ and maternal B12 status compared with a 50 µg dose. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group.

Background and Purpose: The effects of B-vitamin combinations on the prevention of cardiovascular diseases, such as myocardial infarction (MI) and stroke, remain controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) over three decades to evaluate the association between B-vitamin combinations and mortality and arterial thrombotic outcomes. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for RCTs with minimal duration over 24 months published between January 1996 and November 2025. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Random-effects models were used in this meta-analysis to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Results: Thirteen randomized trials enrolling 68,363 participants across both primary and secondary prevention populations were included. B-vitamin combinations were associated with a nonsignificant reduction in stroke and 3-point major adverse cardiovascular events (MACE) (stroke: RR 0.91, 95% CI 0.81-1.04; MACE: RR 0.93, 95% CI 0.86-1.01). No significant effects were observed for all-cause mortality (RR 1.01, 95% CI 0.96-1.06), cardiovascular mortality (RR 0.97, 95% CI 0.88-1.07), or MI (RR 0.97, 95% CI 0.91-1.03). In primary prevention populations, B-vitamin combinations were associated with significant reductions in stroke (RR 0.79, 95% CI 0.68-0.93) and MACE (RR 0.80, 95% CI 0.69-0.92). A modest reduction in MACE was also observed in secondary prevention populations (RR 0.91, 95% CI 0.83-0.99). Between-study heterogeneity was minimal to low for ischemic outcomes, supporting the robustness of these estimates, whereas substantial heterogeneity was observed for mortality outcomes in secondary prevention populations. Conclusions: The evidence is limited by heterogeneity in trial populations, vitamin formulations and doses, and outcome definitions, with substantial between-study inconsistency for mortality outcomes and imprecision in subgroup estimates derived from a small number of contributing trials. Overall, B-vitamin combinations d

OBJECTIVE: Hyperhomocysteinemia (Hcy) independently predicts coronary heart disease (CHD) and adverse cardiovascular events. Although folic acid plays a key role in Hcy metabolism, the effect of combined B-vitamin supplementation (folic acid, VB6, and VB12) on clinical outcomes in CHD remains uncertain. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception through April 2025 using MeSH terms including "folic acid," "vitamin B6," "vitamin B12," "coronary heart disease," and "homocysteine." A random-effects model was used for meta-analysis. RESULTS: Thirteen studies involving 14,539 participants were included in the meta-analysis (7,338 patients treated with folic acid combined with vitamin B complex and 7,301 controls). Combined B-vitamin supplementation significantly reduced serum Hcy levels [mean difference: -2.36; 95% confidence interval (CI): (-3.09 to -1.62); p < 0.01] compared with any single-nutrient regimen. The incidence of vascular restenosis was lower in the intervention group than in the control group (risk ratio: 0.65; 95% CI: 0.44-0.95; p < 0.05). However, no significant differences were observed in the incidence of major cardiovascular events (p = 0.78) or cardiovascular-related mortality (risk ratio: 0.96; 95% CI: 0.85-1.07; p = 0.44). CONCLUSION: Combined B-vitamin supplementation effectively lowers serum Hcy levels and the incidence of vascular restenosis in patients with CHD. However, its impact on cardiovascular events and mortality remains inconclusive. Plain Language Summary: Meta-analysis of 13 RCTs (n = 14,539): combined B vitamins lower serum HcyCombined B-vitamin supplementation lowers vascular restenosis in CHD patientsExerts no significant impact on major CV events or mortalityHcy-lowering appears CHD-specific; broader CV benefits remain unproven.

BACKGROUND AND AIMS: We have evaluated the efficacy and tolerability of two food supplements (FS) containing flavonoids (naringin and hesperidin); same doses of B3, B6, B9 and B12 vitamins, and two different doses of a blend of Mentha spicata leaf extract and Amaranthus caudatus seed flour, in subjects with borderline high total (TC) and low-density lipoprotein cholesterol (LDL-C) levels. METHODS AND RESULTS: 114 Participants (18-70 years) with TC levels 200-239 mg/dL, (5.18-6.19 mmol/L) and LDL-C (<159 mg/dL) were randomised into three groups to receive for 90 days the lowest (n = 38, Treatment A), the highest dose of the FS (n = 38 - Treatment B), or placebo (n = 38). Treatment B was associated with a significant reduction in LDL-C (∼31.5 mg/dL;-22%) and TC (∼19.5 mg/dL; -9%), along with an increase in high-density lipoprotein cholesterol (HDL-C). The greater efficacy of Treatment B containing the highest dose of vegetable extracts is likely attributable to its higher M. spicata extract content, as judged by high-resolution mass spectrometry analysis of the preparation. CONCLUSION: The combination of different FS ingredients with different mechanisms of action can be a valuable strategy for improving lipid profiles in subjects with borderline high TC and LDL-C levels.

The effect of psychostimulant medication in ADHD on the gut microbiome remains unknown. Oral Synbiotic 2000, comprising multiple lactic acid bacteria and dietary fibers, reduces psychiatric symptoms and plasma immune markers in ADHD, but its impact on the gut microbiome is unexplored. This study aimed to (i) study the fecal bacterial microbiome, focusing on species and bacterial gene modules, in ADHD patients and neurotypical controls, and (ii) examine microbiome changes attributable to Synbiotic 2000. Fecal samples were collected from 147 participants at baseline, and 106 completers at follow-up from a randomized placebo-controlled trial of Synbiotic 2000 conducted in children and adults with ADHD. At baseline, adult samples were compared to those of 52 adult controls, and patients on psychostimulants were compared to those not on psychostimulants in adults and children separately. The fecal microbiome was sequenced using shallow shotgun sequencing and analyzed for diversity and differential abundance using machine learning. Plasma short-chain fatty acids (SCFAs) and serum vitamin B12 levels were measured. At baseline, adult ADHD patients had significantly different abundances of four species compared to controls. In children, those on psychostimulants exhibited a higher abundance of species from the genus Prevotella, alongside a lower abundance of the vitamin B12-synthesis module, M00122, than those not on such medication. The lower M00122 abundance was associated with a looser stool consistency, implicating a shorter colonic transit time. Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children. However, looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time. There was a significant Synbiotic-specific effect on taxonomic and functional β-diversity, not only the increased abundance of the Synbiotic 2000 species. Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic group. In conclusion, distinct species were differently abundant in adults with ADHD compared to controls. The implications of the lower abundance of the vitamin B12-syn

BACKGROUND: Vitamin B12 is an essential cofactor for two enzymes that have critical functions in pregnancy, both for maternal health and fetal development. However, the optimal supplemental dosage and its correlation with vitamin B12 status during pregnancy remain inadequately understood due to limited data. METHODS: This is a single-blinded, stratified, dose-ranging trial of vitamin B12 supplementation that will be conducted at the Ifakara Health Institute Bagamoyo Clinical Trial Unit in Bagamoyo, Tanzania. We will enroll 40 pregnant participants (gestational age 25-28 weeks) and 10 non-pregnant participants, stratified based on baseline vitamin B12 status (sufficient and insufficient). Pregnant participants are sequentially assigned to one of three doses: 2.6, 10, and 50 µg for four weeks. At the highest dose, pregnant participants are randomized to receive 50 µg once a day (Q24H) or 25 µg twice a day (Q12H). The two lower doses (2.6 and 10 µg) are given Q24H. Non-pregnant participants will receive 2.6 µg Q24H. The trial includes a four week in-patient phase for daily assessment and controlled feeding, with pregnant participants assessed once postpartum. Primary endpoints include serum B12 concentrations, holotranscobalamin concentrations, and their ratio after four weeks of daily supplementation. DISCUSSION: This study aims to deepen our understanding of nutrient requirements in pregnancy by generating high-quality, high dimensional data. We will answer questions about how pre supplementation vitamin B12 status and dosage impact vitamin B12 saturable absorption and steady-state over the course of four weeks. Limitations include our inability to assess pharmacokinetic changes across gestation, the impact of vitamin B12 status or supplementation on pregnancy and fetal/newborn health, comparing vitamin B12 effects between pregnant and non-pregnant individuals above the recommended dietary allowance (2.6 µg), and comparing Q12H and Q24H dosing at 50 µg. This is the first controlled feeding study to be conducted in sub-Saharan Africa. REGISTRATION: ClinicalTrials.gov ( NCT05426395, 16/06/2022). Copyright: © 2025 Lweno O et al.

BACKGROUND: DNA methylation plays an important role in systemic lupus erythematosus (SLE) pathogenesis by regulating immune cell function and disease progression. Dietary factors, particularly methyl-donor micronutrients such as folic acid and vitamin B12, may influence DNA methylation patterns and autoimmune responses. However, their specific effects in SLE, especially in adipose tissue that is a key modulator of systemic inflammation, remain unclear. Given the high prevalence of obesity in SLE and its impact on disease severity, understanding the interaction between nutritional status, epigenetics, and immune dysregulation is crucial. This study examines whether folic acid and vitamin B12 supplementation modulate adipose tissue DNA methylation in female SLE patients, considering their nutritional status, to uncover potential mechanisms influencing disease progression and therapeutic response. This is a randomized, double-blind, placebo-controlled trial with premenopausal women with inactive SLE, classified as normal weight (NW, n = 23) or excess body weight (EBW, n = 27). Participants received daily supplementation of folic acid (400 mcg) and vitamin B12 (2000 mcg) or placebo for 12 weeks. Phenotypic characteristics and adipose tissue DNA methylation profiles were assessed before and after intervention using the Illumina EPIC BeadChip platform. RESULTS: Supplementation significantly increased serum folic acid and vitamin B12 levels in both groups (p < 0.05), with a greater rise observed in NW patients (p = 0.035). In the NW group, 120 differentially methylated CpG sites (DMCpGs) were identified post-intervention (74 hypermethylated and 46 hypomethylated sites). These genes were linked to autoimmunity, inflammatory metabolism, obesity, and metabolic health pathways. In contrast, no DMCpGs were detected in the EBW group, potentially due to obesity-related chronic inflammation or altered folic acid metabolism associated with excessive adipose tissue. CONCLUSION: Folic acid and vitamin B12 supplementation modulated DNA methylation in SLE depending on nutritional status. Epigenetic remodeling occurred exclusively in NW patients, whereas EBW patients showed no detec

BACKGROUND: Infants born extremely preterm (EP; < 28 weeks of gestation) or term born infants with hypoxic-ischemic encephalopathy (HIE) have increased risk of long-term cognitive and learning deficits. Early supplementation with long chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), choline, uridine-5'-monophosphate (UMP), and cytidine-5'-monophosphate (CMP), zinc, iodine, and vitamin B12 may improve cognitive and language outcomes in these populations. METHODS: This multicentre, blinded, stratified, randomised controlled trial, including an economic evaluation, will investigate the impact of nutritional supplementation on cognitive development in infants born EP or term born infants with HIE. The planned sample size is 1010 (538 EP, and 472 HIE) infants from up to 40 National Health Service neonatal units in the UK. The trial patient populations are infants born EP (preterm stratum) and term infants (born at or more than 35 weeks of gestation) with HIE who received therapeutic hypothermia (HIE stratum). Patient strata were chosen to include infants at high risk of adverse neurodevelopmental outcomes by virtue of EP birth, or HIE requiring therapeutic hypothermia. Infants are randomly assigned, in a 1:1 allocation ratio, to receive either the active supplement or a matched control, in addition to standard care. Families, clinical teams, investigators, and Clinical Trials Unit staff are blinded to allocation. Only the Senior Trials Programmer and Trial Statisticians have access to allocation information. The active supplement is a nutrient powder formulated to be mixed with breast milk, infant formula, or food, containing LCPUFAs (including DHA, EPA, and ARA), choline, UMP, CMP, zinc, iodine, and vitamin B12. Supplementation commences once infants achieve full milk feeds and continues until 12 months post-estimated date of delivery (EDD), with a daily dosage of 1 g per kilogram of body weight. The primary outcome is the Parent Report of Children's Abilities-Revised non-verbal cognitive scale at 24 months post-EDD. EP and HIE patient population comparisons have been appropriately power

BACKGROUND: In a recent double-blind randomized controlled trial (RCT) in Nepal, we found a negative effect of maternal vitamin B-12 supplementation during pregnancy on motor performance in their young infants. OBJECTIVES: The objective of this study is to examine whether the negative effect of the vitamin B-12 supplementation on motor performance in these infants aged 8 to 12 wk differed by baseline maternal characteristics. METHODS: These are secondary analyses of an RCT where 800 pregnant women were randomly assigned to receive vitamin B-12 or placebo from early pregnancy to 6 mo postpartum. The outcome was motor development measured by the test of infant motor performance (TIMP) in 712 infants at age 8 to 12 wk. We examined whether plasma markers of baseline maternal vitamin B-12 status [cobalamin, total homocysteine (tHcy), methylmalonic acid (MMA), and cB12], folate and hemoglobin concentration, and socioeconomic status (SES) modified the effect of vitamin B-12 on the TIMP scores. The subgrouping variables were categorized according to predefined cutoffs and included as interaction terms in generalized linear models, with treatment group as the exposure and TIMP scores (continuous and categorical) as the outcomes. RESULTS: Overall, the negative effect of the vitamin B-12 supplementation was observed in most subgroups. Except for plasma folate concentration (P-interaction = 0.015), the maternal baseline characteristics did not significantly modify the effect of vitamin B-12 supplementation on the TIMP scores. There was a tendency for a stronger negative effect of vitamin B-12 among infants of women with adequate baseline vitamin B-12 status (i.e. concentrations of cobalamin >220, tHcy <10, MMA <0.26, and cB12 values >-0.5) and with folate concentration in the lower tertile. CONCLUSIONS: The negative effect of vitamin B-12 supplementation on infant motor performance cannot be explained by any subgroup specific effects. However, the effect appears to be more pronounced in mothers with adequate B-12 status. This trial was registered at clinicaltrials.gov as NCT03071666 (https://www. CLINICALTRIALS: gov/study/NCT03071666).

PURPOSE OF REVIEW: This review aims to systematically evaluate clinical and observational studies that assessed the influence of maternal vitamin B12 supplementation and status on child neurodevelopment and cognition. Vitamin B12 plays an essential role in fetal neurodevelopment. However, to date, no study has focused on gathering conclusions about the effect of supplementation and maternal levels of vitamin B12 on neurodevelopment, focusing on child cognition. Therefore, the databases consulted included PubMed, Scopus, Web of Science, and Embase. The PRISMA guideline was used to conduct and report the review, and the risk of bias was assessed using the Cochrane risk-of-bias tool (version 2) (RoB 2) for randomized controlled trials and Risk of Bias in Non-randomized Studies - of interventions (ROBINS-I). The PROSPERO registration number is CRD42023476614. RECENT FINDINGS: Eleven studies were reviewed, including four randomized controlled trials and seven observational studies. The results demonstrated that maternal vitamin B12 supplementation has an impact on the cognitive and language domains in children up to 42 months of age. Observational studies have also reported an association between maternal vitamin B12 levels and overall neurodevelopment in children under two years of age. This systematic review highlights the importance of assessing maternal vitamin B12 levels during pregnancy, considering potential adverse effects on child neurodevelopment. Given the limited number of included studies, particularly clinical trials, further research is required to clarify the findings of this review. © 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PURPOSE: The aim of the MultiVeg study, a double-blind, randomised controlled trial (RCT), was to investigate the nutritional status of healthy vegans following 4 months of multinutrient supplementation. METHODS: A double-blind, RCT was conducted with 72 vegan adults (19-57 years) in Germany. Data on anthropometric parameters, dietary nutrient intake, and nutritional status were collected. The nutritional status of the participants was assessed at baseline and after 4 months. The results were compared between groups using ANCOVA. The results for vitamins and choline are presented here. RESULTS: After adjustment for baseline values, age, sex, and multiple testing, no significant between-group differences in biomarker concentration changes from baseline to 4 months were observed for vitamin A, retinol-binding protein, transthyretin, beta-carotene, methylmalonic acid, homocysteine, choline, total osteocalcin, carboxylated and undercarboxylated osteocalcin, and folate. In contrast, significant between-group differences in changes were observed for flavin adenine dinucleotide (FAD), serum vitamin B12, holotranscobalamin, and the combined vitamin B12 status indicator (cB12) after adjustment. CONCLUSION: A multinutrient supplement containing 82 µg of vitamin B12 per day significantly positively affected vitamin B12 blood biomarkers in healthy vegans. REGISTRATION: This study was registered in the German Clinical Trials Register (DRKS00028151). © 2025. The Author(s).

BACKGROUND: Low folate levels in women of childbearing age can cause various health issues. Additionally, low perinatal folate concentrations are a significant cause of neural tube defects. Currently, folic acid supplements mainly consist of folic acid and the active form of folate. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness and safety of the active form of folate in women of childbearing age. METHODS: We searched the published literature in PubMed, Medline, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Randomized controlled trials (RCTs) were obtained to assess the effects of the active form of folate versus folic acid in women of childbearing age. The random or fixed effects model was used to analyze the data in meta-analysis. The results were expressed as standardized mean differences or risk ratios along with their corresponding 95% confidence intervals. RESULTS: Eleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes. However, there were no significant differences in homocysteine, vitamin B12, and betaine. In addition, subgroup analyses showed a significant increase in plasma folate and erythrocyte folate in the active form of folate supplementation group, specifically in subgroups with dosage ≥0.4 mg, intervention of the active form of folate supplementation versus the equimolar mass of folic acid, and intervention duration ≥12 weeks. CONCLUSION: Active form of folate supplementation might contribute to higher plasma folate, erythrocyte folate, and subsequent pregnancy rates, lower unmetabolized folic acid, and lower incidence of adverse pregnancy outcomes in women of childbearing age. Due to the limitation in the quality of involved stud

BACKGROUND: Although numerous cross-sectional studies have examined the relationship between anemia and cognitive impairment or dementia in older adults, data from larger longitudinal studies, especially in generally healthy older adults, are limited. OBJECTIVES: To investigate the associations between baseline hemoglobin levels, anemia, and mild cognitive impairment (MCI) over 3 y in generally healthy older adults. METHODS: This is an observational analysis of the 3-y DO-HEALTH trial, a double-blind, randomized controlled trial including 2157 European community-dwelling adults age 70+. Cognition was assessed at baseline, 12, 24, and 36 mo using the Montreal Cognitive Assessment (MoCA). MCI was defined as a MoCA score <26 at 2 consecutive time points. The exposures were the quintiles of hemoglobin levels and anemia at baseline. Logistic regression models based on generalized estimating equations controlled for age, sex, prior falls, study site, treatment allocation, body mass index, number of comorbidities, smoking status, use of iron supplements, alcohol consumption, renal function, and vitamin B12 levels. RESULTS: A total of 2150 participants were included in the analyses (mean age of 74.9 y; 61.7% females). Compared with the lowest quintile, participants in all higher quintiles had a significantly lower odds of MCI: 2nd = 34% lower odds of MCI [odds ratio (OR) = 0.66; 95% confidence interval (CI): 0.47, 0.93; P = 0.02], 3rd = 39% (OR = 0.61; 95% CI: 0.43, 0.86; P = 0.005), 4th = 44% (OR = 0.56; 95% CI: 0.39, 0.82; P = 0.003), and 5th = 36% (OR = 0.64; 95% CI: 0.43, 0.97; P = 0.03). For anemia, there was no association with the odds of MCI over time. CONCLUSIONS: Baseline hemoglobin levels >130 g/L were associated with reduced odds of MCI over 3 y. Although this study does not establish causality, it suggests further investigations in monitoring and managing hemoglobin levels, even in generally healthy older adults. This trial was registered at clinicaltrials.gov as NCT01745263.

BACKGROUND: Methylcobalamin is a naturally occurring, active form of Vitamin B12. Vitamin B12 is essential for the growth and development of healthy nerves and red blood cell production. Usually, the requirement of vitamin B12 is increased in thyrotoxicosis due to increased utilization and accelerated turnover imposed by increased metabolism. Vitamin B12 is generally well-tolerated and widely used in clinical settings. Parenteral vitamin B12 treatment in hospitalized patients is considered an effective therapy regardless of its etiology. CASE PRESENTATION: Herein, we report the case of a 26-year-old female patient admitted to the Obstetrics and Gynaecology department. She received a slow intravenous methylcobalamin injection on the 4th day of admission for his complaints. Then, she was administered with 2nd dose of intravenous methylcobalamin, after which she developed anaphylactic shock immediately. To address these serious adverse effects, the patient was administered Critical care with cardiopulmonary resuscitation without further delay. The patient had a spontaneous return of circulation within a few minutes of high-quality cardiopulmonary resuscitation. After treatment, the patient recovered and was discharged from the hospital. CONCLUSION: Anaphylactic shock, after slow intravenous methylcobalamin injection, is an uncommon but potentially serious adverse effect. The purpose of this case report is to highlight the importance of this rare but serious life-threatening adverse effect. To our knowledge, this is the first reported case of intravenous methylcobalamin-induced anaphylactic shock. Physicians and healthcare teams should be cautious while administering methylcobalamin to patients, especially via the intravenous route.

Disturbances in one-carbon metabolism, endothelial signaling, oxidative stress, and coagulation balance are central features of diabetes-associated microvascular disease, and targeted micronutrient supplementation-including L-methylfolate, methylcobalamin, pyridoxal-5'-phosphate, antioxidants, and thiol donors-may modulate homocysteine remethylation, endothelial function, and angiogenic signaling. In a 6-month pilot study of ten patients with type 2 diabetes, mild diabetic retinopathy, and MTHFR polymorphisms, micronutrient supplementation was associated with a 23% reduction in serum homocysteine, a 47% decrease in plasma VEGF, and a 15% increase in D-dimer, biomarker shifts that are mechanistically consistent with modulation of homocysteine metabolism, oxidative stress, endothelial signaling, and fibrin turnover. Interpretation of these findings is limited by the small sample size, absence of a control group, lack of functional vascular or imaging endpoints, and incomplete coagulation assessment, as D-dimer elevations alone cannot distinguish enhanced fibrin clearance from increased thrombotic risk. While homocysteine-lowering effects were biochemically evident, they should be contextualized within prior large-scale trials demonstrating discordance between total homocysteine reduction and cardiovascular outcomes, and consideration of downstream metabolites, such as homocysteine-thiolactone, N-homocysteinylated proteins, and S-adenosylhomocysteine, may provide additional mechanistic insight. Collectively, these findings are hypothesis-generating, reflecting biochemical engagement of relevant vascular pathways rather than confirmed clinical benefit, and underscore the need for future randomized, genotype-stratified studies incorporating serial biomarker and functional assessments to establish the physiological and therapeutic relevance of targeted micronutrient interventions in diabetic microvascular disease. © 2026 John Wiley & Sons Ltd.

BACKGROUND: Patients who undergo total gastrectomy lose the ability to produce intrinsic factor and require lifelong supplementation to prevent vitamin B12 deficiency. While oral B12 has emerged as a potential alternative to parenteral therapy, data remain limited, and most clinicians still favor intramuscular injections. This scoping review aimed to map the current evidence on the efficacy, safety, and implementation of oral vitamin B12 supplementation in patients after total gastrectomy for gastric cancer. METHODS: We included peer-reviewed studies reporting outcomes of oral vitamin B12 supplementation after total gastrectomy. A systematic literature search was conducted in scientific databases, including articles published up to November 2025. The reference lists of included articles were screened manually. Extracted data were synthesized narratively. The review was conducted in accordance with the PRISMA-ScR guidelines. RESULTS: Seven studies (n = 449, including 310 patients receiving oral B₁₂) were included. Most used mecobalamin at daily doses of 500-1500 µg. Oral B12 consistently normalized serum levels and alleviated symptoms in the majority of patients. Comparative studies showed that, in terms of biochemical response, oral supplementation was not inferior to parenteral therapy. However, symptom monitoring was inconsistent, follow-up durations were generally short (< 6 months), and only one study was randomized. Standardized clinical outcome measures were rarely used, and data from Western populations were limited. Heterogeneity in dosing regimens and B12 formulations further limited comparability across studies. CONCLUSIONS: Oral B12 appears to be a feasible route of supplementation after total gastrectomy, but current evidence is limited by heterogeneity, underreporting of clinical outcomes, and lack of long-term follow-up. High-quality trials with standardized outcome measures are warranted. © 2026. The Author(s).

Environmental contamination through heavy metals poses significant health risks and cause detrimental effects on embryonic development of humans and animals. This study investigates the teratogenic effects induced by lead - one of poisonous heavy metals, and rescuing potential of combined dose of vitamin B6 and vitamin B12 in golden black breed of domestic chicken embryos. Experiments were carried out on 200 fertilized eggs. Eggs were weighed and distributed into four groups (50 eggs each). 1. Control group 0.1 mL of patent drinking water 2. Vit-B6 + Vit-B12 combination group 0.05 mL of 0.1 mg/kg vitamin B6 solution + 0.05 mL of 0.1 mg/kg vitamin B12 solution in patent drinking water. 3. Lead acetate group 0.1 mL of 5 mg/kg lead acetate solution in patent drinking water. 4. Lead acetate and Vit-B6 + Vit-B12 combination group 0.1 mL of solution containing 5 mg/kg lead acetate, 0.1 mg/kg vitamin B6 and 0.1 mg/kg vitamin B12 solution in patent drinking water. Recovery of embryos was performed on 14th day of incubation and embryos were preserved for further studies. Significant teratogenic effects were observed in lead treated group compared to control group. Microcephaly, exopthalomus eye, abnormal beak development, skewed spine, reduced neck length and torticollis were observed in lead treated group. Appendicular abnormalities include forelimb and hind limb amelia, meromelia in hind limbs. In some chick embryos agenesis and irregular development of claws was noted. Mortality rate was higher in lead group compared to control group. This study highlights vitamin B6 and vitamin B12 ameliorative effects against lead induced developmental abnormalities in chick embryo. © 2026 Published by Elsevier B.V.

Postoperative common peroneal nerve (CPN) entrapment is a common iatrogenic cause of foot drop, and an established rehabilitation protocol is currently lacking. This article provides a step-by-step visual demonstration of an integrated approach, combining ultrasound-guided hydrodissection with structured task-oriented rehabilitation. The protocol includes: (1) real-time ultrasound identification of CPN entrapment; (2) in-plane, multi-quadrant hydrodissection using a 5% dextrose, lidocaine, and mecobalamin injectate; and (3) a phased rehabilitation program initiated 24 h post procedure, comprising neural gliding, therapeutic ultrasound, neuromuscular electrical stimulation, and five task-oriented training modules. In the representative case, the leg-foot angle during maximal dorsiflexion effort demonstrated a 38° reduction (from 142° to 104°), and gait analysis showed restoration of heel-strike, push-off, and swing-phase foot clearance. Post-intervention EMG revealed reinnervation potentials in the tibialis anterior, peroneus longus, and extensor hallucis longus. This visually formatted, stepwise protocol demonstrates the feasibility of combining percutaneous nerve decompression with task-specific rehabilitation, offering a replicable framework for managing refractory postoperative CPN entrapment.

BACKGROUND Anemia derived from immune checkpoint inhibitor (ICI) is recognized as a systemic immune-related adverse event (irAE). However, only a few studies reported regarding pernicious anima (PA) or megaloblastic anemia induced by vitamin B12 (Vit.B12) deficiency after ICI treatment. Vit.B12 deficiency-induced PA remains unclear as an irAE. CASE REPORT We present a case of a 68-year-old man with hepatocellular carcinoma and renal cell carcinoma who developed Vit.B12 deficient megaloblastic anemia after the induction of atezolizumab-containing chemotherapy. Laboratory findings revealed hemoglobin of 6.1 g/dL with signs of hemolysis, gastric parietal cell antibody positivity, and gastrin level elevations. He tested negative for Helicobacter pylori antibodies. Upper gastrointestinal endoscopy showed atrophic mucosa that affected almost the entire stomach. The loss of gastric folds and marked vascular visibility were observed. We defined it as open type (O-3) atrophic gastritis, although histopathological examination was not performed. Based on these findings, the anemia was considered megaloblastic anemia induced by Vit.B12 deficiency (PA). The anemia demonstrated partial recovery (hemoglobin of 9.5 g/dL) with the resolution of hemolytic pattern after mecobalamin administration. We found that PA was associated with parietal cell antibody production triggered by atezolizumab, in which the removal of immune checkpoint brakes by atezolizumab may reveal this pathogenesis. Because PA is recognized as the progressive status of autoimmune gastritis, ICI treatment-induced PA is suggested to emerge at the late phase. CONCLUSIONS PA is indicated as a potential complication of ICI-containing chemotherapy. Measuring Vit.B12 levels is essential when encountering cases of anemia and gastritis during ICI treatment.

Cobalt is an essential trace element in biochemistry that plays a crucial role in the structure and function of several important biomolecules. In this review, vitamin B12 is discussed as one of the best-known examples in this area. Various forms of this vitamin, including methylcobalamin and adenosylcobalamin, play a crucial role in metabolic reactions in mammals and prokaryotes. It also discusses cobalt-containing enzymes that are essential for various biological processes. These enzymes are B12-dependent enzymes, which are well studied, and cobalt-containing enzymes, which are less well known, such as methionine aminopeptidase, nitrile hydratase, glucose isomerase, and prolidase. In addition to the significant role of cobalt complexes in biochemistry, these complexes are considered potent anticancer agents that can exert their antiproliferative effects through the production of ROS, cell cycle arrest, MMP breakdown, and induction of apoptosis in cancer cells. Cobalt complexes are also being explained here for their antimicrobial properties against a variety of pathogens, including bacteria, fungi, and viruses. Furthermore, examples of these complexes are presented as promising agents for the suppression of AD, which could be effective by binding to Aβ-peptides and preventing their aggregation, which is a central feature of the pathogenesis of AD, or by combating the oxidative damage associated with the disease, or even by interfering with the enzyme activities associated with this disease. Finally, the challenges related to the toxicity of cobalt and its compounds in medicine are discussed, and chelation therapy is considered an effective treatment for cobalt poisoning. © 2026. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).

ETHNOPHARMACOLOGICAL RELEVANCE: Mudan granules are Chinese patented medicines approved by the National Medical Product Administration, used to treat diabetic peripheral neuropathy (DPN) with Qi deficiency and collateral obstruction syndrome. However, placebo-controlled studies definitively establishing efficacy and safety are lacking. AIM OF THE STUDY: To evaluate the efficacy and safety of Mudan granules as an adjunct treatment for DPN with qi deficiency and collateral obstruction syndrome. METHODS: This multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial recruited patients from 13 clinical centers in mainland China. 400 participants were randomly assigned in a 1:1 ratio to either the Mudan (Mudan granules + mecobalamin) or control group (placebo + mecobalamin), and were reassessed after the 24-week intervention. The primary outcome was the Michigan Diabetic Neuropathy Score (MDNS). RESULTS: The complete analysis set comprised 357 participants. The mean baseline MDNS of the Mudan and control groups were 9.69 and 9.43, respectively. The mean change in MDNS from baseline to week 24 was -4.80 in the Mudan and -2.66 in the control group. Using a covariate-adjusted analysis of covariance model, the least squares mean for the Mudan and control groups were -4.74 (-5.33 to -4.15) and -2.72 (-3.33 to -2.11), respectively. There was a statistically significant difference between the two groups. After 24 weeks of follow-up, the Mudan group showed a significant improvement in MDNS compared to the control group. CONCLUSION: These findings suggest that Mudan granules may improve the clinical symptoms of DPN. Given this, Mudan granules may be helpful in the management of DPN.

Ischemic stroke is the key cause of increased disability and mortality in society. Quercetin (Qu), a natural compound with neuroprotective effects, shows promise for treating ischemic stroke. However, Qu's hydrophobicity may be an important factor limiting its therapeutic efficacy. Here, a novel quercetin nanodrug (Qu-Me NPs) is constructed by a facile self-assembly with mecobalamin (a FDA-approved drug for peripheral neuropathy), aiming to overcome the hydrophobicity and improve the bioavailability of Qu. Qu-Me NPs exhibits excellent dispersibility, uniform particle size, and stability in physiological media. Qu-Me NPs markedly attenuated infarct size, reduced neuroinflammation, and improved functional recovery at a 1/10 dose of free quercetin in the mouse middle cerebral artery occlusion (MCAO) model. Mechanistically, Qu-Me NPs modulated anti-inflammatory and antioxidative stress pathways, including suppression of microglial M1 polarization by the downregulation of Panx1 and attenuation of pro-inflammatory cytokine production (IL-1β, IL-6). These findings suggest that Qu-Me NPs is a new formulation of Qu, safe, and efficient therapeutic nanodrug for treating MCAO with a ready-to-be-clinically translated potential.

Vitamin B12, a naturally occurring cobalt complex, plays a vital role as a cofactor in biological processes for adenosylcobalamin- and methylcobalamin-dependent enzymes, where it is essential in DNA synthesis, neurological function, or red blood cell formation. Beyond its biological significance, vitamin B12 exhibits unique reactivity: in the presence of suitable reagents, it forms Co-alkyl complexes that, under light irradiation or thermal activation, generate C-centered radicals that engage in reactions with various SOMOphiles and electrophiles. The feature review highlights catalytic properties of this native cobalt-complex, with particular emphasis on emerging strategies that address the growing demand for more sustainable chemical processes. Remaining challenges and potential future directions are also discussed.

Corrinoid iron‑sulfur protein (CFeSP) is the methyltransferase in the Wood-Ljungdahl pathway, yet the geometric and electronic structure that enables its higher catalytic efficiency relative to small-molecule analogs remains a subject of debate. While axial ligation is known to tune the reactivity of B12-dependent enzymes, weak interactions in "base-off" species like methylated CFeSP (Me-CFeSP) have been difficult to define using standard structural probes, despite that solution-phase spectroscopy has suggested their presence. Here we utilize Co K-edge X-ray absorption spectroscopy (XAS) and theoretical analysis (DFT, TD-DFT, and QM/MM) to investigate a series of methylated corrinoids: methylcobalamin, methylcobinamide, and Me-CFeSP. Our results show that despite similar Co-CH3 bond distances across these species, the Co K-pre-edge feature undergoes a diagnostic increase in intensity and a shift to lower energy. Our analysis reveals that these spectral signatures are driven by modulations in the trans-axial Co-ligand distance, and because of the lower symmetry of the corrin ring, the spectral signature of the trans-axial ligand is decoupled from the methyl group. These results provide additional quantitative evidence that Me-CFeSP in solution possesses a weakly bound trans-axial water ligand rather than a 5-coordinate structure estimated by recent structural and XAS studies. This subtle ligation modulates frontier orbital energies to lower the CoC bond dissociation energy, explaining, in part, the enhanced methyl transfer rates of CFeSP. Collectively, this work establishes a spectroscopic and computational basis for diagnosing unresolved axial ligation in corrinoids, suggesting that such interactions may be a widespread, yet underappreciated, feature in "base-off" B12 enzymology.

Vitamin B12 (cobalamin), as an essential cobalt-containing vitamin for the human body, boasts significant physiological functions and broad application in the pharmaceutical, animal feed, food, and cosmetic industries. It mainly exists in four forms: adenosylcobalamin, methylcobalamin, cyanocobalamin, and hydroxocobalamin (hydroxycobalamin). Cyanocobalamin, due to its chemical stability, serves as the primary industrial product form. Currently, microbial fermentation stands as the core method for industrial vitamin B12 production, with strains such as Pseudomonas denitrificans and Propionibacterium freudenreichii. Nevertheless, the production remains relatively low, which has become a key constraint for the industry's development. This chapter highlights the principal innovations and notable accomplishments of the research team, led by Zhang Dawei from the Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, in the domain of vitamin B12 biomanufacturing. By systematically reviewing the synthesis methods of vitamin B12, characteristics of industrial fermentation strains, metabolic engineering strategies, and fermentation technologies, this chapter clarifies the technical advantages and current development status of this field. Meanwhile, it analyzes the challenges encountered in the biomanufacturing process and the progress made in addressing them. Finally, it provides an overview of the global market pattern of vitamin B12 and the development trends of cost control. This comprehensive and in-depth review is expected to help readers gain a thorough and in-depth understanding of the vitamin B12 biomanufacturing. © 2026. The Author(s), under exclusive license to Springer Nature Switzerland AG.

INTRODUCTION: Retinal vein occlusion (RVO), a common retinal vascular disease, is frequently treated with anti-vascular endothelial growth factor (anti-VEGF) agents as first-line therapy. However, anti-VEGF monotherapy lacks neuroprotective effects, primarily targets vascular leakage and neovascularisation, and requires frequent long-term injections that impose substantial economic burdens. Therefore, combined therapeutic strategies that address both vascular pathology and neural damage are being explored. This article describes the protocol for evaluating mecobalamin (a widely used neuroprotective drug) in combination with anti-VEGF for the treatment of macular edema (ME). METHODS AND ANALYSIS: The study is a randomised, double-blind, placebo-controlled clinical trial that will enrol 120 patients with RVO from the First Affiliated Hospital of Chongqing Medical University. Participants will be randomly assigned (1:1) to an experimental group and a control group. The experimental group will receive intravitreal injections of conbercept plus oral mecobalamin for 6 months, while the control group will receive the same conbercept regimen plus a placebo for 6 months. All patients will undergo 1 year of follow-up after initial treatment, with visits at 1, 3, 6, 9 and 12 months. The primary outcome is the change in central subfield thickness from baseline to 1 year post initial treatment. Secondary outcomes consist of change in the best-corrected visual acuity from baseline over time, capillary density, cone photoreceptor distribution characteristics, mean light sensitivity and fixation stability, serum vitamin B12 levels, the number of treatments, frequency of injection (times per year), interval time, incidence and severity of adverse events (AEs) and serious AEs. Statistical analyses will use appropriate parametric and non-parametric tests for group comparisons, correlation analyses, and multivariate modelling. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of The First Affiliated Hospital of Chongqing Medical University (No. 2025-387-01). The results will be disseminated through conference presentations and publication in pe

A 66-year-old man with long-standing diabetes and prolonged metformin exposure presented with a 10-year history of distal paresthesia and progressive imbalance, previously attributed to diabetic neuropathy. Bedside examination demonstrated a positive Romberg sign, impaired distal joint position sense, and reduced vibration sense, suggesting sensory ataxia with posterior column involvement. Mild macrocytosis without anemia was identified. In a resource-limited primary care setting where confirmatory testing was not immediately available, empirical methylcobalamin was initiated. The patient subsequently reported resolution of paresthesia and substantial improvement in gait stability. This case highlights the importance of reassessing presumed diabetic neuropathy when bedside findings suggest an alternative and potentially reversible diagnosis.

AIMS/BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) is a common dose-limiting toxic effect of oxaliplatin-based chemotherapy for colorectal cancer (CRC), severely affecting patients' quality of life and treatment adherence. Currently, effective therapeutic options for OIPN are limited. This study aimed to investigate the clinical efficacy and safety of sodium ferulate combined with methylcobalamin in the treatment of OIPN in CRC patients. METHODS: In this retrospective cohort study, 280 CRC patients diagnosed with OIPN following oxaliplatin-based chemotherapy at Qianxi People's Hospital between January 2020 and December 2024 were enrolled. Based on treatment regimen, patients were assigned to an observation group (sodium ferulate combined with methylcobalamin, n = 152) or a control group (methylcobalamin alone, n = 128). All patients received basic nursing care. Treatment duration was 8 weeks for both groups. Outcomes compared between groups included National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) neurotoxicity grading, nerve conduction velocity (NCV), and quality of life (QoL) scores assessed before treatment, at 4 weeks, and at 8 weeks post-treatment. Clinical efficacy was evaluated after 8 weeks, and changes in hematological parameters and liver/kidney function indicators were monitored. RESULTS: Baseline characteristics were comparable between the two groups (p > 0.05). While no significant difference in neurotoxicity grading was observed at 4 weeks (p > 0.05), the observation group demonstrated significantly better NCI-CTCAE grades than the control group at 8 weeks (p < 0.05). NCV assessments revealed that motor and sensory NCVs of the median and common peroneal nerves in the observation group were significantly improved compared to both baseline levels and the control group at 4 and 8 weeks (p < 0.05). After 8 weeks, the overall clinical efficacy rate was significantly higher in the observation group (89.47%) than in the control group (67.97%) (p < 0.05). QoL scores across all functional domains (physical, role, cognitive, emotional, and social) were significantly better in the observation group compared t

BACKGROUND: Visual illusions are misperceptions of real external stimuli and, when persistent, may indicate underlying neurological or metabolic disorders. Delusional parasitosis is characterized by a fixed belief of infestation without medical evidence and may occur secondary to medical conditions. However, the relationship between visual illusion-related perceptual abnormalities and delusion formation, particularly in reversible metabolic states such as vitamin B12 deficiency, remains unclear. CASE PRESENTATION: An 80-year-old man presented with a persistent belief that mites infested his body and environment. His delusion was preceded by misinterpretation of real stimuli, including lint and skin debris, consistent with visual illusions. Cognitive assessment indicated mild cognitive impairment. His wife gradually came to share his delusional beliefs. Laboratory findings revealed marked vitamin B12 deficiency. Brain perfusion imaging demonstrated hypoperfusion in the medial occipital and parietal association cortices. Treatment with low-dose quetiapine and mecobalamin resulted in rapid resolution of visual illusions and subsequent disappearance of delusional parasitosis. Quetiapine was discontinued without relapse, and follow-up imaging showed improvement in cerebral perfusion. The wife's shared beliefs resolved following clinical improvement and separation. CONCLUSIONS: This case suggests that visual illusions due to reversible metabolic disturbances may precipitate delusional parasitosis in cognitively vulnerable individuals and highlights the importance of evaluating all suspected patients and closely associated individuals. © 2026. The Author(s).

Nutritional optic neuropathy is a rare condition caused by vitamin B12 or folate deficiency. It typically presents with subacute bilateral vision loss and central visual field defects, whereas a presentation resembling bitemporal hemianopia is uncommon. A 70-year-old man living alone presented with gradually worsening bilateral vision loss over four months. His best-corrected visual acuity (BCVA) had decreased to 20/400 in the right eye (OD) and 20/200 in the left eye (OS). Optical coherence tomography showed widespread thinning of the ganglion cell complex, with preservation of the peripapillary retinal nerve fiber layer. Humphrey 30-2 perimetry revealed bitemporal hemianopia-like defects, raising suspicion of a chiasmal lesion; however, contrast-enhanced MRI was normal. Serum vitamin B12 and folate levels were low (66 pg/mL and 3.4 ng/mL), leading to a diagnosis of nutritional optic neuropathy. The patient started oral methylcobalamin (1.5 mg/day) and folic acid (10 mg/day), along with smoking cessation counseling. After three weeks of treatment, vitamin levels normalized, and approximately 15 weeks later, BCVA improved to 20/30 in OD and 20/40 in OS, with significant recovery of visual fields. Nutritional optic neuropathy may rarely cause bitemporal hemianopia-like visual field defects. In patients with subacute bilateral vision loss, assessing diet and smoking history, along with measuring vitamin B12 and folate levels, is important.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a leading cause of neuropathic pain, disability and lower-limb amputation, and the pharmacological options currently available do little to reverse established nerve injury. Compound traditional Chinese medicine preparations that activate blood circulation and unblock the collaterals have shown promise as add-on therapy to neurotrophic treatment, improving nerve conduction and relieving symptoms, but head-to-head comparisons between individual formulas are lacking. METHODS: PubMed, Embase, the Cochrane Library, CNKI, Wanfang and other databases were searched to July 2026 for randomised controlled trials comparing a blood-activating, collateral-unblocking formula plus mecobalamin with mecobalamin alone in adults with type 2 diabetes and peripheral neuropathy. The primary outcome was the Toronto Clinical Scoring System (TCSS); secondary outcomes were motor and sensory conduction velocity (MCV, SCV) of the median and common peroneal nerves, together with adverse events. Mean differences (MD) and 95% credible intervals were estimated in a Bayesian random-effects model, and ranking distributions were summarised as the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed with RoB 2 and certainty of evidence with CINeMA (Confidence in Network Meta-Analysis). RESULTS: Nineteen randomised controlled trials (2,090 participants) were included. All were conducted in China, and most nodes were informed by a single trial. Relative to mecobalamin alone, most add-on regimens improved TCSS and nerve conduction velocity. Credible intervals excluded zero for 9 of 12 formulas for TCSS, 7 of 14 for median nerve MCV, 3 of 14 for median nerve SCV, 5 of 14 for peroneal nerve MCV and 8 of 9 for peroneal nerve SCV. By SUCRA, Yiqi Huashi Tongbi Formula ranked first for TCSS (90.3%; MD -3.49, 95% CrI -5.17 to -1.81), Shengyang Sanhuo Decoction for median nerve MCV (85.6%; MD 4.16, 95% CrI 1.58 to 6.78), Xiaoma Zhitong Capsule for median nerve SCV (84.4%; MD 4.19, 95% CrI 0.88 to 7.58), Modified Buyang Huanwu Decoction for peroneal nerve MCV (79.2%; MD 3.78, 95% CrI 0.83 to 6.72) and Jiangtang Tongluo Tablet for pe

Vitamin B12 deficiency classically presents with neurological or hematological abnormalities. Prior reports have shown that vitamin B12 deficiency also causes olfactory dysfunction when patients have concurrent neurological or hematologic findings. To our knowledge, this is the first case of isolated parosmia caused by vitamin B12 deficiency in the absence of neurological/hematological abnormalities or structural sinonasal disease. A 20-year-old man presented with a 3-month history of parosmic symptoms. Nasal endoscopy, brain MRI, and neurological examinations were normal. A laboratory evaluation demonstrated marked vitamin B12 deficiency without hematologic abnormalities, and oral methylcobalamin led to the complete resolution of parosmia within 3 months. Clinicians should consider vitamin B12 deficiency as a reversible cause of olfactory dysfunction.

A man in his 40s presented with progressive gait instability and distal sensory disturbance after 2 years of 'hikikomori' syndrome associated with a depressive state. Neurological examination demonstrated severe sensory ataxia with sensory-dominant polyneuropathy. Serum vitamin B12 was markedly reduced (56 pg/mL), accompanied by elevated homocysteine levels (19.1 nmol/mL). Evaluation of calcium metabolism demonstrated hypocalcaemia due to vitamin D deficiency with secondary hyperparathyroidism. Sunlight exposure combined with methylcobalamin treatment improved both neurological symptoms and serum calcium levels. Repeated measurements during 4 years of follow-up demonstrated a strong positive association between serum vitamin B12 and corrected calcium levels. This case suggests that prolonged social withdrawal and reduced sunlight exposure may contribute to concurrent vitamin D and vitamin B12 deficiencies and that resultant hypocalcaemia may contribute to vitamin B12 deficiency. © BMJ Publishing Group Limited 2026. No commercial re-use. See rights and permissions. Published by BMJ Group.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder characterized by selective degeneration of upper and lower motor neurons, driven by converging mechanisms including glutamatergic excitotoxicity, mitochondrial dysfunction, oxidative stress, calcium dyshomeostasis, impaired RNA metabolism, and neuroinflammation. In the absence of effective disease-modifying therapies, high-dose methylcobalamin has emerged as a candidate intervention based on its pleiotropic neurobiological effects. A structured literature search was conducted in PubMed/MEDLINE and ScienceDirect to identify peer-reviewed studies published between January 2017 and December 2025 addressing the mechanistic, preclinical, and clinical effects of methylcobalamin in ALS. Preclinical evidence suggests that methylcobalamin modulates homocysteine metabolism, supports S-adenosylmethionine-dependent methylation pathways, preserves mitochondrial integrity, attenuates oxidative stress, and promotes axonal regeneration. Experimental and translational findings further indicate that its therapeutic effects may be strongly dose dependent, particularly under ultra-high-dose regimens capable of overcoming limitations in central nervous system delivery. Clinical trials evaluating ultra-high-dose methylcobalamin demonstrate a potential attenuation of functional decline in patients treated during early disease stages, although effects on survival and respiratory outcomes remain inconsistent. This narrative review integrates molecular mechanisms, experimental evidence, biomarker research, and clinical trial data to examine the translational relevance, stage dependency, and therapeutic implications of high-dose methylcobalamin in ALS.

Vitamin B12 (cobalamin) deficiency remains a significant problem affecting both children and adults and is associated with a wide range of hematological manifestations that are largely preventable with timely diagnosis and treatment. Vitamin B12 deficiency can present with variable hematological, neuropsychiatric, and mucocutaneous changes. Hematological abnormalities are among the most common presentations. The classical peripheral blood smear shows macrocytosis with oval macrocytes, anisopoikilocytosis, and hypersegmented neutrophils. Anemia may be accompanied by leukopenia and thrombocytopenia due to ineffective hematopoiesis. Bone marrow examination typically reveals hypercellularity with erythroid hyperplasia and large megaloblasts exhibiting open chromatin and nuclear-cytoplasmic asynchrony as a result of defective DNA synthesis. Ineffective erythropoiesis leads to intramedullary destruction of hematopoietic precursors, resulting in elevated lactate dehydrogenase, indirect hyperbilirubinemia, and reduced haptoglobin, thereby mimicking hemolytic anemias. Abnormal red cells and megaloblasts that enter the circulation have a shortened lifespan, leading to megaloblastic anemia, with reticulocyte counts that are inappropriately low for the degree of anemia. In pediatric patients, manifestations may be severe, particularly in infants born to cobalamin-deficient mothers. Presentations include profound anemia, pancytopenia, failure to thrive, recurrent infections, and bleeding manifestations due to thrombocytopenia, often misdiagnosed as aplastic anemia or myelodysplasias. Pigmentary changes in the form of hyperpigmentation of knuckles, oral mucosa and rarely Addisonian pigmentation have been described. In older children, isolated anemia or bicytopenia with subtle macrocytosis may delay diagnosis. Severe presentations, seen in approximately 10% of cases, include pancytopenia, hemolytic anemia, and pseudothrombotic microangiopathy, which may mimic hematological malignancies or thrombotic microangiopathies. Early recognition is crucial, as vitamin B12 replacement leads to rapid and often complete hematological recovery.