Vitamin B12 (Cobalamin)

BACKGROUND: Vitamin B12 (cobalamin) deficiency can result in irreversible structural brain changes if not treated appropriately. Long-term use of acid-lowering agents (ALA) has been linked to vitamin B12 deficiency, but results are inconsistent. AIM: To evaluate the association between prolonged ALA use and vitamin B12 deficiency by performing a meta-analysis. METHODS: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents, Cochrane Library, Google Scholar, Science Direct and Web of Science. Original data were abstracted from each study and used to calculate a pooled odds ratio and 95% confidence interval (95% CI). RESULTS: Of the articles reviewed, four case-control studies (4254 cases and 19,228 controls) and one observational study met full criteria for analysis. The long-term ALA use was significantly associated with development of vitamin B12 deficiency (hazard ratio 1.83, 95% CI: 1.36-2.46, P-value 0.00). CONCLUSION: Chronic use of ALA is a risk factor for developing vitamin B12 deficiency. Judicious prescribing of ALA and regular monitoring of vitamin B12 in patients who are inevitably on long-term ALA therapy are recommended. © 2015 Royal Australasian College of Physicians.

BACKGROUND: Folate deficiency can result in congenital neural tube defects and megaloblastic anaemia. Low folate levels may be due to insufficient dietary intake or inefficient absorption, but impaired metabolic utilization also occurs.Because B12 deficiency can produce a similar anaemia to folate deficiency, there is a risk that folate supplementation can delay the diagnosis of B12 deficiency, which can cause irreversible neurological damage. Folic acid supplements may sometimes therefore include vitamin B12 supplements with simultaneous administration of vitamin B12.Lesser degrees of folate inadequacy are associated with high blood levels of the amino acid homocysteine which has been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplementation can improve cognitive function in the elderly.However, any apparent benefit from folic acid which was given in combination with B12 needs to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function has therefore been published. OBJECTIVES: To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy or demented people, in preventing cognitive impairment or retarding its progress. SEARCH STRATEGY: Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 10 October 2007 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin and cyanocobalamin. This Register contains references from all major health care databases and many ongoing trials databases. In addition MEDLINE, EMBASE, CINAHL, PsychINFO and LILACS were searched (years 2003-2007) for additional trials of folate with or without vitamin B12 on healthy elderly people. SELECTION CRITERIA: All double-blind, placebo-controlled, randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: The reviewers independently appli

BACKGROUND: Folates are vitamins essential to the development of the central nervous system. Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. High blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms. There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function is being prepared. OBJECTIVES: To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing

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: 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 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.

Vitamin B12 is essential for neural function, red blood cell formation, and DNA synthesis, yet its deficiency persists as a global health burden driving megaloblastic anemia, neuropathy, and cognitive decline. Effective prevention is constrained by the vitamin's susceptibility to degradation during processing, storage, and cooking, its intricate absorption physiology, and the failure of conventional diagnostic and supplementation strategies to address the diverse underlying causes of deficiency. This review introduces a closed-loop smart nutrition system that integrates monitoring, intelligent diagnosis, and precision supplementation to overcome these challenges, shifting B12 management from a generalized one size fits all model toward dynamic, personalized health interventions. We critically survey emerging sensors and wearable devices capable of frequent B12 status assessment, discuss the application of artificial intelligence for deficiency diagnosis and tailored dietary guidance, and examine advanced delivery platforms including

The agri-food industry generates large quantities of by-products, e.g., fruit pomace from juice and wine production, which represent underutilized sources of valuable compounds. The popularity of plant-based foods is steadily increasing due to growing concerns about human health, animal welfare, and environmental sustainability, highlighting the need for vitamin B12 fortification - plants cannot synthesize this essential micronutrient. This challenge is particularly relevant given the growing prevalence of B12 deficiency and its associated health risks. The aim of this study was to enrich pomace from blue honeysuckle berries, strawberries, and grapes with B12 via co-fermentation using Propionibacterium freudenreichii DSM 20271 and Lactiplantibacillus plantarum ATCC 10241 (selected based on screening tests, including the co-existence test of P. freudenreichii-different LAB species), and to optimize the pomace matrix for cobalamin biosynthesis in co-culture conditions. The pomace matrices were characterized with respect to carbon and nitrogen sources, as well as cobalamin biosynthesis precursors, including cobalt, riboflavin, and niacin. Nearly complete utilization of available carbon sources was observed in all matrices. B12 (13.91-39.71 μg/kg) and propionic acid (0.73-4.31 g/kg) were produced in all pomace-based media. Optimization experiments indicated that strawberry and grape pomace were the most suitable substrates for B12 synthesis, whereas propionic acid production was primarily associated with strawberry pomace. These findings demonstrate the feasibility of using co-cultures of propionic acid and lactic acid bacteria to enrich fruit pomace with B12. This approach offers a promising strategy for developing B12-fortified plant foods from fermented and edible fruit pomace, thereby supporting sustainable development and zero-waste principles.

Recreational nitrous oxide (N2O) use has increased in recent years and is an increasingly recognized cause of functional vitamin B12 deficiency with associated neurological and systemic complications. This systematic review and meta-analysis summarizes published case reports and case series describing the clinical, biochemical, and neurodiagnostic features of N2O-induced B12 deficiency. A comprehensive literature search of PubMed and Embase using the terms "nitrous oxide" and "B12" identified 458 publications. After exclusion of non-English and inaccessible articles, 257 studies were included, comprising 462 individual case reports and 1,291 patients from aggregated case series. Data extracted included demographics, duration of N2O exposure, clinical presentation, laboratory values (hemoglobin, mean corpuscular volume (MCV), serum B12, me

Age-related renal function decline may contribute to other physiological alterations. This study aimed to examine the associations of kidney function, assessed by estimated glomerular filtration rate (eGFR), and nutritional factors with homocysteine levels in community-dwelling older adults. This cross-sectional study enrolled participants aged ≥ 65 years. Demographic characteristics were collected using questionnaires. Biochemical parameters, including homocysteine, folic acid, vitamin B12, and metabolic disorder indicators, were measured, and eGFR was calculated and categorized into three groups. Homocysteine concentrations were significantly higher in the low and moderate eGFR groups compared with the high eGFR group (median: 16.9 vs. 11.9 vs. 9.3 μM, p < 0.01). Regression analyses indicated that each 1-unit decrease in eGFR was associated with higher homocysteine (β = -0.13, p < 0.01). Conversely, higher folic acid (β = -0.29, p < 0.01) and vitamin B12 (β = -0.003, p < 0.01) levels were significantly associated with lower homocysteine concentrations. These associations remained significant after mutual adjustment, indicating distinct effects of renal function and nutritional factors on homocysteine levels. Moreover, homocysteine levels were positively correlated with waist circumference (r = 0.38, p < 0.01) and triglycerides (r = 0.18, p < 0.05) and inversely correlated with high-density lipoprotein cholesterol (r = -0.27, p < 0.01). The results suggest that renal function and nutritional status are independently associated with homocysteine levels and may contribute to metabolic risk profiles in older adults.

BACKGROUND: Cobalamin (vitamin B₁₂) is synthesized only by certain bacteria and archaea and is rarely found in plant-derived foods because plants neither synthesize nor require this cofactor. The edible duckweed Wolffia globosa Mankai is unusual in containing bioavailable cobalamin, suggesting a microbial origin. However, how cobalamin biosynthetic capacity is organized within angiosperm-associated microbiomes remains large

Observational studies have suggested associations between micronutrient status and recurrent aphthous ulcers (RAU); however, the causal nature of these relationships remains unclear. This study aimed to evaluate the genetically predicted associations between circulating micronutrients and RAU using a Mendelian randomization (MR) approach. We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from individuals of European ancestry. Genetic instruments for 15 micronutrients, including folic acid, zinc, and vitamin B12, were obtained from the IEU OpenGWAS database, while RAU outcome data (5394 cases) were derived from the FinnGen consortium. The inverse variance weighted (IVW) method was used as the primary analysis, complemented by weighted median, MR-Egger, and sensitivity analyses to assess heterogeneity and horizontal pleiotropy. The IVW analysis indicated a nominally significant association between genetically predicted

Fire smoke inhalation represents a major cause of acute mortality in fire incidents, with hydrogen cyanide being a critical contributor to rapid systemic toxicity. This study aimed to establish a controlled smoke inhalation model to characterize cyanide-dominant exposure and to evaluate the prophylactic efficacy of a nebulized antidote combination under acute conditions. A reproducible smoke chamber system was developed to generate cyanide-rich toxic atmospheres. C57BL/6 mice were exposed to controlled

Methylmalonic acidemia is an autosomal recessive genetic disorder primarily caused by defects in methylmalonyl-CoA mutase and cobalamin (vitamin B12) metabolism. These defects disrupt the tricarboxylic acid cycle and oxidative phosphorylation, leading to the abnormal accumulation of metabolic products such as methylmalonic acid, propionic acid, and methylcitric acid. This accumulation results in damage to multiple systems, including the nervous, hepatic, and renal systems. Tethered cord syndrome results from pathological spinal cord traction due to congenital/acquired factors, causing conus medullaris malposition, neuronal degeneration, and progressive sensorimotor deficits. This report details a diagnostically complex case highlighting an unusual clinical intersection between these two conditions. © 2026 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Ribonucleotide reductases (RNRs) catalyze one of the central biochemical reactions, giving rise to deoxyribonucleotides, the building blocks of DNA. Due to their importance in cellular metabolism, this class of enzymes has been extensively studied over five decades. One aspect that has been neglected so far is the substrate specificity in terms of noncanonical nucleotides. While some of these compounds are physiologically relevant, many non-natural nucleotides are important in medical science, biotechnology and synthetic biology. In this study, we investigated the substrate specificity of two thermostable RNRs for a broad range of natural and non-natural nucleotides, in order to define the substrate promiscuity of this class of enzymes. Both enzymes were capable of converting all canonical nucleotides and a variety of other nucleotides. Generally, the enzymes were more likely to convert substrates with modifications of already existing functional groups of the nucleobase core structure. Our results show the potential and limitations for the biotechnological application of RNRs. In addition, they improve our understanding of the natural nucleot

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

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 canc

12. medRxiv [Preprint]. 2026 Jun 4:2026.06.03.26354855. doi: 10.64898/2026.06.03.26354855. Heterozygous MMACHC burden variants are associated with higher circulating vitamin B12 in the All of Us Research Program. Cai L, DeBerardinis RJ. Heterozygous carriers of autosomal recessive disease variants are conventionally considered unaffected, yet population-scale genomic datasets reveal subclinical carrier phenotypes. MMACHC encodes a cobalamin-processing protein whose biallelic loss causes cobalamin C deficiency, an inborn error of intracellular cobalamin metabolism. We performed an unbiased quantitative phenome-wide association screen in All of Us Research Program v8 to identify phenotypes associated with rare heterozygous MMACHC burden variants. Serum/plasma vitamin B12 was the top quantitative association. Carriers had higher circulating B12 than non-carriers in adjusted analyses, but also higher homocysteine, suggesting that elevated circulating B12 does not reflect improved intracellular cobalamin function. Carriers were less likely to fall below conventional B12 insufficiency thresholds, indicating a potential diagnostic blind spot. A pathway-wide rare-variant gene-burden (All-by-All) gene-burden analysis placed this finding in broader biological context. Burdens in genes related to circulating B12 binding or intestinal absorption were associated with lower circulating B12. In contrast, burdens in several genes involved in cellular delivery and intrace

This exploratory study investigated the interactive effects of dietary fat content and methyl-donor supplementation on genome-wide DNA methylation in adipose tissue of female lupus-prone NZBWF1/J mice. Thirty mice were randomly assigned to four groups for 12 weeks in a 2 × 2 factorial design: standard diet (SD, n = 7), high-fat diet (HFD, n = 7), standard diet supplemented (SDS, n = 8), and high-fat diet supplemented (HFDS, n = 8). The standard diet provided 4.2 kcal/g and the high-fat diet 6.6 kcal/g. Supplemented diets contained 8 mg/kg folic acid and 50 µg/kg vitamin B12. After a 10-h fast, subcutaneous adipose tissue was collected for genome-wide DNA methylation analysis using the Infinium Mouse Methylation BeadChip, followed by differential methylation and pathway enrichment analyses. The high-fat diet induced a distinct methylation profile with 90 differentially methylated CpGs (p < 0.05, Δβ ≥ 0.05). Enrichment analyses did not identify significantly overrepresented pathways. Diet × supplementation interaction analysis identified 31 CpGs with significant interaction effects (p < 0.01). Pathway enrichment analysis revealed overrepresentation of the IL-17 signaling pathway. Only one CpG overlapped between HFD-associated and interaction-associated loci, indicating largely distinct epigenetic responses to diet and supplementation. A high-fat diet induces widespread epigenetic remodeling in adipose tissue, while folic acid and vitamin B12 supplementation modulates inflammatory epigenetic pathways in a diet-dependent manner. © 2026 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.

BACKGROUND/OBJECTIVES: Iron deficiency (ID) can occur before anemia and may impair performance, recovery, and hematological function, particularly in athletes. Female basketball players may be especially vulnerable due to high training demands and sex-specific iron losses. Therefore, this study aimed to compare nutrient intake and hematological and iron status biomarkers between ID and non-ID female basketball players, and to examine diet-biomarker correlations. METHODS: Twenty-four female basketball players completed the study. Athletes were stratified by ferritin, with ID defined as <30 μg/L, resulting in 12 athletes per group. Dietary intake was assessed using a 48 h food record. Energy, macronutrients, fiber, iron, calcium, folate, vitamin B12, and vitamin C intakes were analyzed. Blood biomarkers included red blood cells (RBCs), hemoglobin (HGB), hematocri

Background/Objectives: Maternal intake of methyl-group donors (MGD) during pregnancy may influence fetal development, yet its role in in vitro fertilization (IVF) pregnancies remains poorly understood. The aim of the present study was to investigate maternal intake of MGDs during late pregnancy and its association with neonatal outcomes in IVF versus spontaneously (S) conceived pregnancies. Methods: We assessed third-trimester, daily maternal intake of MGD (folate, betaine, choline, methionine, and folic acid) using a validated food-frequency questionna

BACKGROUND: Inflammation may bias the estimation of burden of certain micronutrient deficiencies; however, few studies have examined the magnitude and direction of this bias in school-age children and adolescents. OBJECTIVES: Associations between biomarkers of inflammation [C-reactive protein (CRP) and α-1-acid-glycoprotein (AGP)] and multiple micronutrient biomarkers [serum folate (SFO), red blood cell folate (RBC folate), serum vitamin B12, serum 25(OH)D, and serum zinc] were examined in children aged 5 to 19 y. METHODS: This analysis included 13 cross-sectional surveys of children (n = 46,363) from 12 countries with ≥1 micronutrient biomarker of interest, CRP or AGP, and n > 100 per survey. Spearman rank correlations between each micronutrient and inflammation biomarker were calculated by survey. To examine the dose-response relationship between inflammation and micronutrient levels, geometric means of each micronutrient biomarker were plotted across deciles of AGP and CRP, stratified by age groups (5-9, 10-14, and 15-19 y), and overall (5-19 y). RESULTS: Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L) ranged from 2.7% to 29.6% by survey with medians ranging from 0.5 to 0.8 g/L for AGP and 0.2 to 1.9 mg/L for CRP. The prevalence of micronutrient deficiencies ranged from 0.1% to 87.7% for SFO, 0.1% to 24.4% for RBC folate, 0.5% to 54.8% for vitamin B12, 4.6% to 25.6% for serum 25(OH)D, and 0.6% to 57.3% for zinc, with median values from 4.2 to 45.5 nmol/L for SFO, 452.1 to 1000.0 nmol/L for RBC folate, 131 to 442 pmol/L for vitamin B12, 43.2 to 60.0 nmol/L for serum 25(OH)D, and 59.4 to 92.9 μg/dL for zinc. Associations between micronutrient biomarkers and AGP or CRP were weak (most absolute r < 0.2) with no clear pattern across positive, negative, and null associations. Geometric means of micronutrient biomarkers did not show clear patterns of association with CRP or AGP deciles, overall or stratified by sex or age group. CONCLUSIONS: With weak and inconsistent correlations between inflammation and select micronutrient biomarkers, these findings do not support the routine adjustment for inflammation when estimating folate, vitamin B12, vitamin D, or zi

Diatoms play a crucial role in aquatic ecosystems, yet the mechanisms underlying their long-term dominance remain poorly understood. This study investigated the relationship between diatom ecological persistence and their phycosphere bacterial communities by comparing the long-term dominant species Cyclotella atomus with the short-term dominant species Ulnaria ulna. 16S rRNA gene sequencing combined with predictive functional profiling revealed that the bacterial community associated with C. atomus was more diverse, stable, and interconnected than that associated with U. ulna. Taxonomic analysis identified key bacterial taxa such as Gemmatimonas, Sphingobium, and Pseudorhodoferax enriched in C. atomus. Co-occurrence network analysis demonstrated higher microbial interaction complexity in C. atomus, enhancing functional redundancy and ecosystem stability. Functional predictions indicated significant enrichment in carbohydrate metabolism (glycosaminoglycan degradation, pentose/glucose interconversion) and stress response pathways (betaine biosynthesis, xenobiotic metabolism by cytoc

BACKGROUND: Hydroxocobalamin (OHCbl), the most effective form of vitamin B12 containing cobalt (Co) as its core component, is the mainstay therapy for cobalamin C (cblC) defect, yet long-term Co exposure and safety signals remain incompletely characterized. METHODS: We retrospectively analyzed 379 cblC patients receiving OHCbl therapy. Among them, 270 had prognostic data and 99 had laboratory and Co measurements. Adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Regression models identified determinants of Co levels and associations of OHCbl dosage, treatment duration, and Co concentration with routine laboratory parameters, potential ADRs and prognosis. RESULTS: Median treatment duration was 76.70 months and median OHCbl dosage was 1.07 mg/kg/week; Median blood Co concentration was 22.53 μg/L. Although 53.54% of patients having Co >20.00 μg/L, no severe Co toxicity was observed

INTRODUCTION: B-vitamins and herbal supplements such as Passiflora incarnata have demonstrated potential benefits for cognitive and neurological functions. This study aims to evaluate the neural and biochemical effects of high-dose vitamin B multivitamin supplementation, with and without P. incarnata, in healthy adults using multimodal neuroimaging and biomarker assessments. METHODS AND ANALYSIS: This is a phase I/II, randomised, double-blind, placebo-controlled clinical trial involving 108 healthy adults aged 30-55 years, allocated to three groups: (A) high-dose vitamin B multivitamin supplementation with P. incarnata; (B) high-dose vitamin B multivitamin supplementation alone; and (C) placebo. Participants will take two tablets daily for 24 weeks. The primary outcomes are changes in default mode network connectivity assessed using resting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging, together with safety outcomes including vital signs, clinical laboratory parameters and adverse event monitoring. Secondary outcomes include regional brain metabolite concentrations measured by proton magnetic resonance spectroscopy and plasma biomarkers of one-carbon metabolism, including vitamin B6, vitamin B12, folate and homocysteine. ETHICS AND DISSEMINATION: Ethics approval was granted by the Medical Research Ethics Committee, Ministry of Health Malaysia (NMRR-19-379-46101 (ISR); Protocol Number: Exec B). Results will be disseminated through peer-reviewed publications and scientific conferences. TRIAL REGISTRATION NUMBER: ACTRN12622001150730. © Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

Vitamin B12 deficiency is a common yet frequently underrecognized nutritional disorder with important public health implications, particularly in low- and middle-income countries where maternal deficiency, vegetarian dietary practices, and food insecurity are prevalent. In children, deficiency may lead to irreversible neurodevelopmental impairment, growth failure, and hematological abnormalities, making early recognition essential. The clinical spectrum ranges from asymptomatic biochemical deficiency and isolated macrocytic anemia to developmental regression, seizures, movement disorders, peripheral neuropathy, and pancytopenia, with neurological manifestations often preceding hematological changes. Diagnosis requires integration of clinical features with laboratory evaluation, including complete blood count, peripheral smear, serum vitamin B12 estimation, and functional biomarkers such as methylmalonic acid and homocysteine, which improve diagnostic accuracy in borderline or atypical cases. Molecular testing has expanded the identification of inherited disorders affecting vitamin B12 absorption and metabolism, enabling timely lifelong manag

BACKGROUND: Peripheral neuropathy (PN) is one of the most common disorders of the peripheral nervous system, affecting around 10% of the general adult population. PN results in pain, paraesthesia, and sensory loss, negatively impacting patients' quality of life. The condition is characterised by damage to peripheral nerves and is often linked to risk factors, among which diabetes is the most common cause. The incidence rate of patients suffering from PN has significantly increased in the last three decades, yet there are currently no pharmacological treatments to reverse or prevent the development of PN. Therefore, neurotropic B vitamins, specifically vitamins B1, B6, and B12, which are essential for protecting nerves from damage, nerve regeneration, and maintaining nerve health, are promising treatment options. Other biofactors with therapeutic potential a

Organohalide-respiring bacteria (OHRB) are key mediators of chlorinated solvent detoxification in anoxic groundwater, yet their practical application is often constrained by vitamin B₁₂ (cobalamin) auxotrophy and the requirement for strictly controlled anoxic and nutrient conditions. Here, we report the enrichment and characterization of a Trichlorobacter-dominated consortium (NB-12) that sustains efficient dihaloelimination of halogenated alkanes under minimal nutrient and relaxed anoxic constraints. The NB-12 enrichment completely transformed 1,2-dichloroethane (1,2-DCA) to ethene within 40 h (≥3.3 μmol h⁻¹) and also dechlorinated 1,2-dichloropropane and 1,1,2-trichloroethane, as well as debrominated 1,2-dibromoethane and 1,2-dibromopropane. Exogenous vitamin B₁₂ supplementation did not enhance dechlorination kinetics or product yields. Amplicon sequencing and metagenomic analyses identified Trichlorobacter lovleyi as the dominant population (>60% relative abundance) and revealed a complete anaerobic cobalamin biosynthesis pathway in the corresponding metagenome-assembled genome, indicating corrinoid autonomy at the community level. Notably, the NB-12 consortium retained sustained dehalogenation activity in non-sterile, unbuffered, and oxygen-leaky mesocosms prepared using only tap water, trace elements, and lactate-conditions mimicking challenging in situ environments. Field bioaugmentation using this "low-input" inoculant resulted in successful aquifer colonization and a reduction in 1,2-DCA concentrations in contaminated groundwater. Together, these results demonstrate that corrinoid-autonomous, Trichlorobacter-dominated enrichments can relax key physiological and operational constraints of OHR-based remediation, expanding the applicability of low-input, cost-effective strategies for in situ treatment of halogenated alkane-contaminated groundwater.

ObjectivesTo investigate the prevalence of hypo- and hypercobalaminemia in a cohort of cats with diverse disease pathologies and to assess associations with signalment and disease characteristics.MethodsResidual blood from cats presented to a large veterinary referral hospital during a 24-month period was used for serum B12 quantification. All cats requiring blood collection as part of diagnostic investigations were eligible for inclusion regardless of clinical presentation. Serum B12 concentration was assessed according to signalment, body weight, body condition score, primary affected body system and type of disease pathology as derived from the clinical notes.ResultsA total of 229 cats were enrolled: 128 male (119 neutered, 9 entire) and 101 female (88 neutered, 13 entire). Of these, 176 were domestic shorthair or longhair, and 53 were purebred. The median age was 9.9 years and median body weight 4.1 kg. Of the 229 cats, 80 (34.9%) had high, 86 (37.6%) normal, 18 (7.9%) borderline, and 45 (19.7%) low serum B12. Median serum B12 concentration was higher in cats aged <8.0 years than ≥8.0 years, and there w

BACKGROUND: Despite the well-established relationship between micronutrient deficiencies and cirrhosis, little is known of micronutrient deficiencies among ambulatory patients with cirrhosis awaiting liver transplant (LT). We aimed to characterize micronutrient deficiencies among patients with cirrhosis awaiting LT and assess their association with frailty, a complication with high morbidity and mortality. METHODS: Ambulatory adult patients with cirrhosis awaiting LT from June 2024 to March 2025 were tested for micronutrient deficiencies in clinical practice. Multivariable modeling was used to assess the association between frailty and micronutrient deficiencies. RESULTS: Of 275 patients, the median (IQR) age was 60 (51-66) years and 114 (42%) were women. Median MELD 3.0 (IQR) was 17 (12-22), and 64 (23%) were frail. Micronutrient deficiencies were common, especially of zinc, vitamin D/E/B12, and selenium. Compared to patients who were not frail, frail patients were

Plant pathogens colonize multiple plant-associated habitats throughout their life cycle, encountering distinct nutrient conditions and microbial communities. l-methionine is required for bacterial growth and environmental adaptation. However, how plant pathogens coordinate l-methionine biosynthetic pathways to adapt to different plant-associated environments remains poorly understood. Here, using the plant pathogen Xanthomonas campestris pv. campestris strain XC1 as a model, we show that three homocysteine methyltransferase pathways allow XC1 to catalyze the final step of l-methionine biosynthesis using different methyl donors and cofactors under different environmental conditions. Bioinformatic and transcriptional analyses identified three homocysteine methyltransferase-associated operons in XC1, mesMXD, mmuPM, and metHRHaHb, corresponding to the MesD-, MmuM-, and MetHaHb-dependent pathways, respectively. MesD uses an endogenously synthesized methyl donor and functions as the dominant homocysteine methyltransferase under l-methionine-limiting conditions, supporting bacterial growth, intracellular l-methionine accumulation, and full virulence. Furthermore, MmuM enables XC1 to use plant-derived S-methylmethionine for l-methionine biosynthesis, whereas MetHaHb enables XC1 to use vitamin B12 supplied by a neighboring bacterium for l-methionine biosynthesis in co-culture. Expression analyses showed that mesMXD was the only homocysteine methyltransferase-associated operon that responded to l-methionine availability, and its expression also decreased when S-methylmethionine- or vitamin B12-dependent pathways supported l-methionine biosynthesis. Comparative genomic analysis further showed that the three-homocysteine methyltransferase configuration is conserved in Xanthomonas and is also present in other plant-associated bacteria. Together, these findings show that a plant pathogen can coordinate endogenous, plant-derived, and microbially supported homocysteine methyltransferase pathways to maintain l-methionine biosynthesis, providing a metabolic strategy for adaptation to plant-associated environments.

BACKGROUND: Several lines of evidence suggest that vitamin B6 has potential as an antidepressant. It plays a crucial coenzyme role in the synthesis of the neurotransmitters serotonin, gamma-aminobutyric acid (GABA) and dopamine, which are central to mood regulation, and it has been shown that increasing availably of vitamin B6 above normal levels increases concentrations of serotonin and GABA. Furthermore, epidemiological evidence points to vitamin B6 deficiency as a risk factor for depression, and to high vitamin B6 levels as protective. Therefore, we asked whether taking 100 mg vitamin B6 as pyridoxine daily for 1 month would reduce depression symptoms, measured with the Depression, Anxiety and Stress Scales (DASS) questionnaire, which also assesses anxiety and stress. METHODS: We recruited 267 participants from the general population (215 female) and double blind randomised them to receive either placebo, vitamin B6 or vitamin B12 (1000 µg). Using baseline DASS scores, we divided participants into a group classified as having mild or more severe depression symptoms at baseline (N = 58) and a larger group classified as non-depressed. RESULTS: Only within the former group, vitamin B6 produced a selective reduction in depression symptoms compared to placebo or vitamin B12 with a very large effect size (partial η 2 = 0.20). We also found evidence that participants whose DASS depression scores narrowly failed to meet criterion for moderate depression (N = 52) experienced a slightly smaller but still statistically substantial reduction in symptoms (partial η 2 = 0.17). We repeated the analysis procedure for anxiety and stress scores but found no significant effects. CONCLUSIONS: We have shown that high-dose vitamin B6 has therapeutic potential for depression, and large-scale clinical trials with patients should now be conducted to determine whether these findings from our mostly female sample generalise to males, to quantify the dose-response relationship, and to evaluate its potential as an adjunct to existing treatments versus monotherapy, and to elucidate which factors, for example, presence of inflammation, predict responsiveness to the intervention.

Update of Res Sq. 2025 Nov 17:rs.3.rs-8077579. doi: 10.21203/rs.3.rs-8077579/v1. mRNA splicing represents a fundamental level of gene regulation that alters proteomic diversity and cellular state. Its dysfunction can profoundly rewire metabolism, yet underlying mechanisms remain elusive. Here, we investigate Verheij syndrome, caused by mutations in core splicing factor PUF60, using a Caenorhabditis elegans model, human cell lines, and patient-derived samples. We demonstrate that RNP-6/PUF60 deficiency disrupts splicing of genes governing one-carbon metabolism and phospholipid remodeling, impairing S-adenosylmethionine/S-adenosylhomocysteine cycling and phosphatidylcholine synthesis. These perturbations trigger the integrated stress response and compromise mTORC1 signaling, causing developmental growth defects. Vitamin B12 supplementation restores metabolic balance by reactivating S-adenosylmethionine-dependent phospholipid remodeling and mTORC1 activity, effectively rescuing Verheij-like phenotypes. Similar responses arise from perturbing another splicing factor, PRP-19. Mechanistically, intron retention of nhr-114/HNF4 transcription factor drives these phenotypes, while restoring its splicing rescues them. Our findings implicate vitamin B12-dependent one-carbon metabolism as a metabolic modulator with therapeutic potential to mitigate Verheij syndrome and other spliceosomopathies. © 2026. The Author(s).

OBJECTIVES: Guidelines recommend routine biochemical screening for vitamin B12 deficiency in metformin users. However, these recommendations are based on non-specific and outdated definitions of vitamin B12 deficiency. Using contemporary diagnostic criteria, we compared prevalence in metformin users with non-users. METHODS: In this cross-sectional study, we included adults with diabetes (type 1, 2, other types) attending 2 outpatient clinics in Denmark, March 2024 to October 2025. Exposure was current use of metformin. B12 deficiency was defined by plasma B12 ≤ 250 pmol/L and elevated serum methylmalonic acid. Crude and adjusted prevalence differences (aPDs) and ratios (aPRs) were estimated using binomial regression. RESULTS: Among 3958 participants (median age 54 years, 57% male) prevalence of vitamin B12 deficiency was 2.3% in current users and 1.3% in non-users (aPD of 0.7% [95% confidence interval [CI]: -0.32 to 1.7]; aPR of 1.56 [95% CI: 0.92 to 2.63]). In patients with type 2 diabetes (n = 1,338, median age 62 years, 61% male) prevalence was 2.3% versus 2.0% (aPD of 0.38% [95% CI: -1.9 to 1.1]; aPR of 1.21 [95% CI: 0.55 to 2.66]). CONCLUSION: Vitamin B12 deficiency was uncommon with no meaningful excess risk among metformin users. Thus, routine screening may be redundant.

The gut microbiota, as a vital micro-ecological system within the human body, plays a crucial role in regulating diverse physiological functions. Recent research has increasingly demonstrated its close association with the occurrence and progression of anemia. This review summarizes current understanding of how the gut microbiota influences iron metabolism, vitamin synthesis-particularly vitamin B12-and immune modulation, all of which are key factors in the pathogenesis of anemia. We explore the mechanisms by which dysbiosis of the gut microbiota contributes to anemia development, including disruptions in nutrient absorption and inflammatory responses. Furthermore, we analyze recent clinical studies that investigate the relationship between gut microbiota alterations and different anemia subtypes. By integrating the latest basic and clinical research findings, this review aims to provide a comprehensiv

BACKGROUND: Septic shock is characterized by severe circulatory failure, microvascular dysfunction, and metabolic derangement. Methylene blue (MB) and vitamin B12 (VB12) have each shown potential benefit in vasodilatory shock, but the biological effects of their combined use remain unclear. METHODS: A rat model of LPS-induced septic shock was used to evaluate the effects of combined MB and VB12 pretreatment. Transcriptomic analysis of carotid artery tissue was performed to identify treatment-responsive genes and pathways. Expression of KCNMB1, PRKG1, and PRKG2 was assessed by immunohistochemistry, western blotting, and RT-qPCR. Hemodynamic parameters, circulating injury markers, inflammatory cytokines, oxidative stress indices, and histological changes in major organs were also evaluated. RESULTS: Combined MB and VB12 treatment was associated with lower expression of KCNMB1, PRKG1, and PRKG2 and reduced cGMP levels compared with the model group. The combined treatment also partially improved hemodynamic abnormalities, reduced

BACKGROUND: Adequate vitamin B12 (B12) concentrations are essential for optimal pregnancy development. The COVID-19 pandemic may have compromised adequate B12 intake. However, evidence on maternal B12 status and its predictors during the pandemic is scarce. This study aimed to assess serum total B12 (sB12) concentrations in the first or second trimester, and to identify maternal lifestyle, obstetric, and dietary predictors of B12 status among pregnant Chilean w

BACKGROUND: Vitamin B12 deficiency is common in older adults, atrophic gastritis, and after bariatric surgery, and can cause irreversible neurological injury. Oral, sublingual, and intramuscular routes all correct serum concentrations, yet whether any route is superior for clinically meaningful outcomes is unclear, and international guidelines diverge. This consensus was convened to define where evidence is adequate, where it is lacking, and the priority research questions. METHODS: This was a modified Delphi consensus study. The RAND/UCLA Appropriateness Method was applied through a two-stage process of 2 electronic rounds and an in-person meeting in São Paulo, Brazil. Panellists were recruited between 1 July 2025 and 15 July 2025. Thirty statements were voted on, presented as 31 graded items, using a binary (agree or disagree) format with a priori percentage-agreement grades (A+, 100%; A, 90%-99.9%; B, 80%-89.9%; C, 70%-79.9%; and D, 66%-69.9%). Draft statements, informed by a systematic review, were rated anonymously by a Brazilian multidisciplinary panel of 20 experts across haematology, gastroenterology, endocrinology, bariatric surgery, and geriatric medicine/neurology. Of 20 experts invited, all 20 agreed to participate and completed the electronic rounds (100%); 16 (80%) attended the in-person meeting. Patient representatives (n = 2) participated as non-voting observers. Grade A (at least 90% agreement) was the stopping rule. This consensus was not registered. FINDINGS: In total, 30 statements across 6 modules were agreed, comprising 31 separately graded items as statement 1 was presented in two parts (1a and 1b); 22 of 31 items (71%) reached grade A+ (100% agreement) and 9 of 31 (29%) reached grade A (90%-99.9%). All routes were judged capable of normalising serum vitamin B12, but none showed proven superiority for symptom resolution, neurological recovery, functional status, or quality of life. Evidence gaps were greatest after bariatric surgery, in older adults with cognitive impairment or frailty, and in pernicious anaemia. Dosing, monitoring, and response definitions varied substantially. INTERPRETATION: Vitamin B12 replacement across all routes rem

BACKGROUND: Vitamin B12 deficiency, commonly attributed to malabsorption, presents significant clinical consequences including hematological and neurological manifestations. Helicobacter pylori infection, a prevalent global pathogen, has been implicated in gastric pathology that may compromise vitamin B12 absorption through various mechanisms including gastric atrophy and impaired intrinsic factor production. This study aimed to evaluate the association between H. pylori infection and vitamin B12 deficiency. METHODS: A retrospective study was conducted at Thumbay Hospital, Ajman, UAE, involving 110 patients who underwent testing for both H. pylori (via urea breath test) and vitamin B12 levels using consecutive sampling of eligible patients tested during the study period. Patients with positive H. pylori results comprised the case group (n=60), while those with negative results served as controls (n=50). H. pylori positivity was defined by the assay's manufacturer cut-off (delta-over-baseline ≥2.4‰), and vitamin B12 deficiency was defined as a serum concentration below 200

Mechanochemical integration of vitamin B12 (B12) with microscale zero-valent iron (mZVI) (i.e., B12-mZVIbm) markedly enhances reductive dechlorination, but the origin of this enhancement remains unclear. Here we show that the performance gain of B12-mZVIbm arises from interfacial restructuring rather than immobilization alone. Systematic characterization revealed that mechanochemical synthesis immobilized B12 on mZVI via the formation of abundant FexN species, including γ'-Fe4N and ε-Fe2+xN, while preserving the structural integrity of B12 and shifting the cobalt center toward the catalytically active Co(

INTRODUCTION: Serum cobalamin (vitamin B12) is routinely measured to diagnose deficiency, while elevated concentrations have been associated with malignancy, renal and liver impairment. Limited data on these associations exists in South African populations. This study aimed to characterise laboratory utilisation of serum cobalamin testing and assess the association between elevated serum cobalamin concentrations and malignancy in a South African population. MATERIALS AND METHODS: A retrospective analysis of serum cobalamin tests performed over five years was undertaken to describe laboratory utilisation. A retrospective cohort study of tests performed over three years was conducted to investigate associations between elevated serum cobalamin concentrations and pathological comorbidities, including histologically or cytologically confirmed malignancy diagnosed within three years of measurement. Patients with serum cobalamin concentrations of 145-569 pmol/L were defined as the unexposed group, while those with concentrations >569 pmol/L were defined as the exposed group. RESULTS: A total of 1561 tests from patients admitted to Tygerberg Hospital between 2017 and 2019 were included, comprising an unexposed group (n = 791) and an exposed group (n = 770). Higher serum cobalamin concentrations were observed in males and individuals with renal or liver impairment (p < 0.001), as well as those with histologically or cytologically confirmed malignancy (p = 0.011). Log-binomial regression demonstrated an adjusted relative risk (aRR) (95% confidence interval) for malignancy of 1.84 (1.22-2.79; p = 0.004) among individuals with elevated cobalamin concentrations, increasing to 3.12 (1.91-5.08; p < 0.001) for concentrations between 1000 and 1467 pmol/L, and 2.07 (1.20-3.56; p = 0.008) for solid malignancies. CONCLUSION: In South African individuals without cobalamin supplementation, elevated serum cobalamin concentrations were independently associated with malignancy. Elevated concentrations should therefore increase the clinical index of suspicion for underlying malignancy, particularly solid tumours.

INTRODUCTION: We aimed to compare total serum vitamin B12 measurements across four immunoassay platforms, establish method-specific reference intervals, evaluate the clinical impact of a uniform deficiency cut-off, and assess associations between total vitamin B12 and holotranscobalamin (holoTC). MATERIALS AND METHODS: Residual serum samples from 220 apparently healthy adults undergoing routine health check-ups were analyzed. Total vitamin B12 was measured on Beckman, Abbott, Siemens, and Roche platforms. Beckman analyses used the updated Access Vitamin B12 II calibrator introduced in December 2024. Holotranscobalamin was measured on the Abbott system. Reference intervals were derived using non-parametric methods according to CLSI EP28-A3c guidelines. Method comparison was performed using Passing-Bablok regression and concord

Pernicious anemia is a chronic autoimmune disease characterized by impaired of vitamin B12 absorption and deficiency. Current diagnostic approaches rely on laboratory biomarkers with limitations in sensitivity and specificity, leading to diagnostic uncertainty and potentially delayed and/or suboptimal treatment. The 2024 NICE guidelines acknowledge that treatment frequency should be guided by individual symptom response rather than current one-size-fits-all schedules; however, the symptom heterogeneity underpinning this recommendation remains poorly characterized. We conducted secondary analysis of symptom survey data from 1,117 members of the Pernicious Anaemia Society (PAS) collected between August 2010 and November 2012. We applied latent class analysis (LCA) to 46 self-reported indicators comprising demographic characteristics, symptoms, and comorbid conditions, to identify distinct symptom-based subtypes and assess whether such subgroups can inform more tailored management of PA. Associations between symptom subtypes and diagnostic test results, age when symptoms first started, symptom duration, and treatment satisfaction were examined using chi-square and Fisher's exact tests. The best model included three distinct symptom subtypes: High Burden (n = 334, 29.9%), Moderate Burden (n = 613, 54.9%), and Low Burden (n = 170, 15.2%). The High Burden subtype exhibited fatigue (99.4%), cognitive dysfunction (97.9% memory loss), neurological manifestations (95.5% clumsiness), and suicidal thoughts (41.6%). Intrinsic factor antibody (IFA) status did not differ significantly across subtypes (χ 2 = 1.04, df = 2, p = 0.593). Age at symptom onset differed significantly across subtypes (p = 0.002), with the Low Burden subtype overrepresented in older age groups. The High Burden subtype had the longest diagnostic delays (56.9% >2 years). Standard three-monthly injections showed low satisfaction across all classes (High Burden: 8.5%, Moderate Burden: 23.7%, Low Burden: 30.7%). Symptom-based stratification identifies clinically meaningful subgroups independent of IFA status, supporting tailored, symptom-guided treatment rather than the current piecemeal approach. The invers

A method for the accurate determination of vitamin B12 (cobalamin) in infant formula was developed using isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS). As an internal standard, a [13C7]-cyanocobalamin isotope-labeled analogue was used. Because of the hygroscopic property of cobalamins, the concentration of the cyanocobalamin standard solution was determined via quantitative nuclear magnetic resonance (qNMR) spectroscopy and further validated by capillary electrophoresis with ultraviolet detection as an independent technique. The cobalamins contained in infant formula were converted to cyanocobalamin in the presence of cyanide. Incomplete conversion of cobalamins was observed, and the residual amount of hydroxocobalamin was quantified to obtain the total amount of cobalamins. The expanded measurement uncertainty ranged from 1.7% to 2.4%, accounting for the contribution of residual hydroxocobalamin. Recovery, calculated by comparing the measured CN-Cbl concentration with the gravimetric fortification level, ranged from 101 to 103%. Both intra- and inter-day RSDs were below 1%. The method was applied to commercially available infant formula, with cobalamin concentrations ranging from 31.0 to 40.6 µg/kg. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

Vitamin B12 deficiency can cause preventable but potentially irreversible neurological injury in infancy, whereas unexpectedly elevated total vitamin B12 creates a different diagnostic challenge. This review outlines a phenotype-guided approach to both findings, emphasizing the mother-infant dyad. Infant deficiency commonly reflects low maternal status, including unrecognized malabsorption despite an omnivorous diet. Neurological manifestations may precede anemia or macrocytosis. Methylmalonic acid and total homocysteine therefore help resolve borderline or clinically discordant vitamin B12 results, although interpretation requires age-specific reference intervals and consideration of renal function. Symptomatic infants generally require prompt parenteral replacement, while selected asymptomatic infants with nutritional deficiency may respond to supervised oral treatment. Newborn screening can identify affected mother-infant dyads but does not exclude deficiency developing later during breastfeeding. Elevated total vitamin B12 most commonly reflects supplementation or altered transport, clearance, or assay characteristics, and should not be equated with toxicity. Persistent unexplained elevation warrants targeted clinical and laboratory assessment. CONCLUSION: Integrating clinical phenotype, maternal evaluation, functional biomarkers, and cautious interpretation of elevated concentrations may reduce delayed treatment and unnecessary investigations in infancy and early childhood. WHAT IS KNOWN: • Infant vitamin B12 deficiency may cause irreversible neurological injury without macrocytic anemia. • Maternal vitamin B12 status strongly influences fetal stores and breastfed-infant risk. WHAT IS NEW: • A phenotype-led framework integrates infant deficiency, maternal assessment, newborn screening, and unexpectedly elevated vitamin B12. • Functional biomarkers help distinguish intracellular deficiency from isolated high total vitamin B12, which is not equivalent to toxicity. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Recently, we have described the first supermolecular nanoentities of vitamin B12 analogues, i.e., monocyano forms of heptabutyl cobyrinate, which are unique nanoparticles with emerging optical and catalytic properties and rapid response to gaseous toxins highly dangerous to humans. However, the following questions remain: why do all the studied properties change dramatically in supermolecules, and can their structures provide an answer to this question? Herein, we present the first evidence obtained from X-ray diffraction analysis of supermolecules of organometallic compounds. They were created by a nanoarchitectonic approach using directed self-assembly of vitamin B12 derivatives in layers at the air-water interface in a confined space at the nanolevel. The Bragg peaks indicated that two types of supermolecular structures can be formed in Langmuir-Schaefer (LS) films: molecular stacks twisted into

BACKGROUND: Excessive intake of exogenous vitamin A during pregnancy has been associated with congenital malformations. This experimental study aimed to evaluate whether vitamin B12, folic acid, and L-carnitine exert a protective or contributory effect on malformations induced by hypervitaminosis A. METHODS: Thirty-five healthy adult female Wistar albino rats and seven male rats were used. Pregnant rats received vitamin A alone or in combination with vitamin B12, folic acid, or L-carnitine for 21 consecutive days (GD 0-21). At the end of gestation, neonates were evaluated for gross congenital malformations. Brain, liver, and eye tissues were excised and processed for histopathological and morphometric analyses. RESULTS: No gross external malformations were observed in any group; however, significant growth restriction and multi-organ histopathological alterations were detected in the offspring. Histological examination revealed interstitial edema in brain tissue and retinal detachment in the eye. Hepatic alterations included sinusoidal dilatatio

Unaccompanied minor refugees (UMRs), particularly from regions like Syria, Eritrea, and Iraq, face significant healthcare challenges in the Netherlands. Their unique medical and psychosocial needs necessitate a culturally sensitive diagnostic approach and coordinated care. Chronic conditions linked to nutritional deficiencies, such as celiac disease, are of particular concern. Celiac disease is an immune-mediated disorder triggered by gluten, leading to inflammation and malabsorption in the intestines. We present a case of a 16-year-old Eritrean UMR who, after a lengthy migration, arrived with anemia, gastrointestinal issues, and nutritional deficiencies. Diagnostic tests revealed anemia, intramedullary hemolysis, and vitamin B12 deficiency, with endoscopy confirming celiac disease and chronic gastritis. Treatment included

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 p

BACKGROUND: Serum vitamin B12 is among the most frequently ordered laboratory tests, and both low and high concentrations have been linked to cancer and mortality. However, the full dose-response shape and the contribution of reverse causation remain unclear. OBJECTIVES: We aimed to characterize the dose-response shape and temporal structure of the associations of serum vitamin B12 with cancer incidence and all-cause mortality. METHODS: We conducted a retrospective propensity score-matched cohort study of 3,950,497 adults from the TriNetX global collaborative network (169 health care organizations, 19 countries, 2006-2020). Adults were classified into 6 baseline serum vitamin B12 strata, with the 400-600 pg/mL stratum as the reference. Overall cancer incidence and all-cause mortality were assessed over 10 y. Dose-response, time-stratified, landmark, subgroup, and negative control analyses were performed to address reverse causation. RESULTS: Overall cancer incidence increased modestly above the reference [adjusted hazard ratio (aHR): 1.05-1.08], with no association in the deficiency range. All-cause mortality followed a J-shaped pattern, with elevations at both extremes. The elevated-end cancer association attenuated to near null after excluding the first 2 y of follow-up (>1000 pg/mL: aHR: 1.07‒1.02), whereas the deficiency-end mortality association showed the least attenuation (<200 pg/mL: aHR: 1.26 at 1 y to 1.18 at 10 y). CONCLUSIONS: Cancer incidence was modestly higher at elevated serum vitamin B12 concentrations but attenuated after exclusion of early events, whereas the mortality association at deficiency-range concentrations persisted. These observational findings do not justify discontinuing clinically indicated vitamin B12 therapy.

Host-microbe interactions extend beyond infection, involving microbial metabolites, such as short-chain fatty acids, vitamins, and other bioactive compounds, that influence host physiology and development. Using Caenorhabditis elegans, an excellent model organism for host-microbe interactions, we demonstrate that Salmonella Typhimurium significantly accelerates C. elegans growth through a vitamin B12-dependent mechanism affecting methionine metabolism. We measured the reproductive maturity of C. elegans via embryo and oocyte production in response to various Salmonella virulence factor mutants and Salmonella strains deficient in cobalamin, folate, and methionine synthesis pathways. We found that the Salmonella cbiB and metH genes are essential for rapid development in C. elegans. Moreover, the C. elegans metr-1 mutant, which lacks functional methionine synthase, did not exhibit increased reproductive maturity when fed on S. Typhimurium or Escherichia coli OP50 supplemented with vitamin B12. However, methionine supplementation rescued this phenotype, indica