비타민B12 (메틸코발라민)

Efficacy of Oral Vitamin B-12 at 1000 μg Compared with 2000 μg on Neuropathic Outcomes in Patients with Diabetic Peripheral Neuropathy and Low Serum Vitamin B-12: a Randomized Clinical Trial.

1. J Nutr. 2026 Mar;156(3):101368. doi: 10.1016/j.tjnut.2026.101368. Epub 2026 Jan 16. Efficacy of Oral Vitamin B-12 at 1000 μg Compared with 2000 μg on Neuropathic Outcomes in Patients with Diabetic Peripheral Neuropathy and Low Serum Vitamin B-12: a Randomized Clinical Trial. Mansour A(1), Am

Comparative efficacy of biweekly preventive supplementation, with multiple micronutrients and iron folic acid or iron folic acid alone, on hemoglobin concentrations and anemia prevalence in children aged 6-59 months: a randomized controlled trial in rural India.

1. Am J Clin Nutr. 2026 May;123(5):101281. doi: 10.1016/j.ajcnut.2026.101281. Epub 2026 Mar 19. Comparative efficacy of biweekly preventive supplementation, with multiple micronutrients and iron folic acid or iron folic acid alone, on hemoglobin concentrations and anemia prevalence in children aged 6-59 months: a randomized controlled trial in rural India. Upadhyay RP(1), Chowdhury R(1), Mundra S(1), Taneja S(2), Jacob M(3), Kapil U(4), Bavdekar A(5), Bhandari N(1). Author information: (1)Society for Applied Studies, New Delhi, India. (2)Society for Applied Studies, New Delhi, India. Electronic address: sunita.taneja@sas.org.in. (3)Department of Biochemistry, Christian Medical College, Vellore, India. (4)Department of Clinical Epidemiology, Institute of Liver and Biliary Sciences, New Delhi, India. (5)Department of Pediatrics, KEM Hospital Research Centre, Pune, India. 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). Copyright © 2026 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.ajcnut.2026.101281 PMID: 41862001 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest RPU reports financial support was provided by Indian Council of Medical Research. All other authors report no conflicts of interest.

Maternal supplementation of vitamin B(12) in predominantly vegetarian pregnant women improves their vitamin B(12) status and the neurodevelopment of their infants: the MATCOBIND multicentric double-blind randomised control trial.

2. BMJ Paediatr Open. 2026 Mar 18;10(1):e004112. doi: 10.1136/bmjpo-2025-004112. Maternal supplementation of vitamin B(12) in predominantly vegetarian pregnant women improves their vitamin B(12) status and the neurodevelopment of their infants: the MATCOBIND multicentric double-blind randomised control trial. Nagpal J(1), Mathur M(2)(3), Rawat S(4), Singhal A(5), Pant R(6), Shah A(6), Nixon L(7), Mishra VK(3), Nagrath D(3), Heys M(5), Cortina-Borja M(5), Michie C(8), Gautam J(6), Karmacharya SB(9), Rai S(6), Lakhanpaul M(10)(11). Author information: (1)Department of Pediatrics & Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, Delhi, India. (2)Queen Mary University of London Faculty of Medicine and Dentistry, London, UK. (3)Public Health Foundation of India, New Delhi, India. (4)Department of Clinical Epidemiology, Sitaram Bhartia Institute of Science and Research, New Delhi, Delhi, India. (5)UCL Great Ormond Street Institute of Child Health, London, UK. (6)Paropakar Maternity and Women's Hospital, Kathmandu, Nepal. (7)Wolfson Institute of Population Health, UCL, London, UK. (8)University College London, London, UK. (9)Department of Neonatology, Paropakar Maternity and Women's Hospital, Kathmandu, Nepal. (10)UCL Great Ormond Street Institute of Child Health, London, UK m.lakhanpaul@ucl.ac.uk. (11)Nottingham University NHS Trust, Nottingham, UK. 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. DOI: 10.1136/bmjpo-2025-004112 PMCID: PMC13034390 PMID: 41850742 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: No, there are no competing interests.

Complex Effects of B-Vitamin Combinations on Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials over Three Decades.

3. Nutrients. 2026 Mar 5;18(5):842. doi: 10.3390/nu18050842. Complex Effects of B-Vitamin Combinations on Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials over Three Decades. Ren R(1), Yang A(2), Chow A(3), Wang K(4), Wang S(5), Leo C(6), Lu Y(7)(8), Li M(9). Author information: (1)College of Pharmacy, University of Minnesota, Minneapolis, MN 55415, USA. (2)Dartmouth College, Hanover, NH 03755, USA. (3)College of Arts and Science, New York University, New York, NY 10012, USA. (4)University of Washington School of Medicine, 1959 NE Pacific St., Seattle, WA 98195, USA. (5)NYU Langone Hospital-Long Island, Mineola, NY 11501, USA. (6)Duke Raleigh Hospital, a Campus of Duke University Hospital, School of Medicine, Duke University, Durham, NC 27708, USA. (7)College of Pharmacy, University of Minnesota, Hennepin Healthcare System, Minneapolis, MN 55415, USA. (8)Department of Pharmacy, Hennepin Healthcare System, Minneapolis, MN 55415, USA. (9)Brigham and Women's Hospital, Boston, MA 02115, USA. 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 do not confer consistent benefit for major cardiovascular outcomes but may reduce stroke and MACE in selected primary prevention populations, suggesting that baseline cardiovascular risk and regional folic acid fortification modify treatment effects and should guide future trial design and clinical use. DOI: 10.3390/nu18050842 PMCID: PMC12986992 PMID: 41830012 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.

Combined B-vitamin supplementation on homocysteine and vascular outcomes in coronary heart disease: a meta-analysis.

4. Ann Med. 2026 Dec;58(1):2622208. doi: 10.1080/07853890.2026.2622208. Epub 2026 Jan 30. Combined B-vitamin supplementation on homocysteine and vascular outcomes in coronary heart disease: a meta-analysis. Guo L(1), Shi X(2), Wang G(3), Han W(1), Ding R(1), Wang S(4), Yuan D(3). Author information: (1)Department of Pharmacy, The 7th People's Hospital of Zhengzhou, Zhengzhou, Henan Province, People's Republic of China. (2)Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China. (3)Clinical Trial Institution for Drugs, The 7th People's Hospital of Zhengzhou, Zhengzhou, Henan Province, People's Republic of China. (4)School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China. 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. DOI: 10.1080/07853890.2026.2622208 PMCID: PMC12862861 PMID: 41615824 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Improved HDL, LDL and total cholesterol levels following a 3-month administration of Mentha spicata leaf extract and Amaranthus caudatus seed flour extracts, flavonoids and B vitamins. A placebo-controlled, double-blind, randomized clinical trial.

5. Nutr Metab Cardiovasc Dis. 2026 Mar;36(3):104470. doi: 10.1016/j.numecd.2025.104470. Epub 2025 Nov 14. Improved HDL, LDL and total cholesterol levels following a 3-month administration of Mentha spicata leaf extract and Amaranthus caudatus seed flour extracts, flavonoids and B vitamins. A placebo-controlled, double-blind, randomized clinical trial. Di Minno A(1), Morone MV(2), Cordara M(3), Buccato DG(2), De Lellis LF(2), Ullah H(4), Piccinocchi R(5), Larsen DS(6), Baldi A(2), Piccinocchi G(7), Xiao X(8), Sacchi R(9), Daglia M(10). Author information: (1)Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131, Naples, Italy; CEINGE-Biotecnologie Avanzate, Via Gaetano Salvatore 486, 80145, Naples, Italy. (2)Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131, Naples, Italy. (3)School of Medicine, University of Milano-Bicocca, 20126, Milan, Italy. (4)School of Pharmacy, University of Management and Technology, Lahore, 54000, Pakistan. Electronic address: hammadrph@gmail.com. (5)Anaesthesia and Resuscitation A. U. O. Luigi Vanvitelli, Via Santa Maria di Costantinopoli, 80138, Naples, Italy. (6)School of Chemical Sciences, The University of Auckland, Auckland, 1010, New Zealand. (7)Comegen S.C.S., Società Cooperativa Sociale, Viale Maria Bakunin 41, 80125, Naples, Italy. (8)School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China. (9)Applied Statistic Unit, Department of Earth and Environmental Sciences, University of Pavia, Viale Taramelli 24, 27100, Pavia, Italy. (10)Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131, Naples, Italy; International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China. Electronic address: maria.daglia@unina.it. 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. Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.numecd.2025.104470 PMID: 41519619 [Indexed for MEDLINE]

Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment.

6. Brain Behav Immun. 2026 Mar;133:106259. doi: 10.1016/j.bbi.2026.106259. Epub 2026 Jan 5. Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment. Stiernborg M(1), Yang LL(2), Skott E(3), Giacobini M(4), Melas PA(5), Debelius JW(6), Lavebratt C(7). Author information: (1)Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden. (2)Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; Department of Neurology, Huazhong University of Science and Technology, Tongji Medical College, Union Hospital, Wuhan, China. (3)Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden. (4)Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; PRIMA Child and Adult Psychiatry, Stockholm, Sweden. (5)Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden; Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm, Sweden. (6)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. (7)Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden. Electronic address: catharina.lavebratt@ki.se. 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-synthesis module, in children on psychostimulant medication, for the gut ecosystem and host intestine remain to be elucidated. Synbiotic 2000 influenced the taxonomy and functionality of the fecal microbiome and increased plasma SCFA levels towards normal. Further research is warranted to explore the clinical implications of microbiome modulation in the treatment of ADHD. Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.bbi.2026.106259 PMID: 41500324 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania.

7. Gates Open Res. 2025 Sep 17;8:95. doi: 10.12688/gatesopenres.15991.2. eCollection 2024. Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania. Lweno O(1), Reynolds VS(2), Barberio MD(3), Klatt KC(4), Mugusi S(5), Gopalakrishnan M(6), Lukmanji Z(1), Al-Beity FMA(7), Ahmadzia HK(8)(9), Arcot A(10), Gallagher K(11), Martin LA(10), Rahnavard A(12), Gernand AD(10), Langevin B(6), Masanja H(1), Smith ER(2)(3). Author information: (1)Ifakara Health Institute, Dar es Salaam, Tanzania. (2)Department of Global Health, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA. (3)Department of Exercise and Nutrition Science, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA. (4)Department of Nutritional Sciences and Toxicology, University of California Berkeley, Berkeley, California, 94720, USA. (5)Department of Clinical Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. (6)Center for Translational Medicine, School of Pharmacy, University of Maryland Baltimore, Baltimore, Maryland, 21201, USA. (7)Department of Obstetrics and Gynecology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. (8)Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The George Washington University, Washington, District of Columbia, 20052, USA. (9)Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Inova Health System, Falls Church, VA, 22042, USA. (10)Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA. (11)Ross and Carol Nese College of Nursing, The Pennsylvania State University - University Park Campus, University Park, Pennsylvania, 16802, USA. (12)Computational Biology Institute, Departments of Biostatistics and Bioinformatics, The Milken Institute School of Public Health, The George Washington University, Washington, District of Columbia, 20052, USA. 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. DOI: 10.12688/gatesopenres.15991.2 PMCID: PMC12759048 PMID: 41488590 [Indexed for MEDLINE] Conflict of interest statement: No competing interests were disclosed.

Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial.

8. Clin Epigenetics. 2026 Jan 3;18(1):21. doi: 10.1186/s13148-025-02041-5. Nutritional status-dependent DNA methylation modifications on adipose tissue in systemic lupus erythematosus women following folic acid and vitamin B12 supplementation: a randomized double-blind placebo-controlled trial. da Mota JCNL(1)(2), Carvalho LM(1)(2), Souza LL(1)(2), Ribeiro AA(1)(2), Pinhel MAS(3)(4), Nonino CB(4), Godoy AL(5), Borba EF(6), Hounkpe BW(6), Gualano B(1)(2)(6)(7), Nicoletti CF(8)(9)(10). Author information: (1)Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. (2)Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. (3)Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. (4)Division of Nutrition and Metabolism, Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. (5)Department of Orthopedic Surgery, Institute of Orthopedics and Traumatology (IOT), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil. (6)Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil. (7)Laboratory of Assessment and Conditioning in Rheumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. (8)Applied Physiology and Nutrition Research Group, School of Physical Education and Sport and Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. carolina.nicoletti.ferreira@usp.br. (9)Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil. carolina.nicoletti.ferreira@usp.br. (10)Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil. carolina.nicoletti.ferreira@usp.br. 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 detectable changes. These findings suggest that obesity may create an "epigenetic resistance" to micronutrient interventions, highlighting the importance of precision nutrition strategies in autoimmune disease management. TRIAL REGISTRATION: NCT05097365. © 2026. The Author(s). DOI: 10.1186/s13148-025-02041-5 PMCID: PMC12866419 PMID: 41484640 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee of the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, Sao Paulo, Brazil (CAAE: 47317521.8.0000.0068). Eligible patients were informed about all the details of the project and signed the Informed Consent Form. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests.

Trial protocol: DOLFIN trial: Developmental Outcomes of Long-term Feed Supplementation in Neonates-A UK multicentre, blinded, stratified, randomised controlled trial.

9. Trials. 2025 Dec 29;26(1):592. doi: 10.1186/s13063-025-09253-3. Trial protocol: DOLFIN trial: Developmental Outcomes of Long-term Feed Supplementation in Neonates-A UK multicentre, blinded, stratified, randomised controlled trial. Andrew MJ(1)(2), Embleton N(3)(4), Hardy P(5), Johnson S(6), Juszczak E(7), Ledbury H(3), Pearson C(8), Rivero-Arias O(5), Francisco AA(5), Berrington J(4)(9), Bradley P(4), Bradley PJ(10), Cole C(5), Court K(3), Hurd M(5), King A(5), Linsell L(5), Murray D(5), O'Connor HM(5), Roehr CC(5), Stalker V(5), Stanbury K(5), Wahengbam UD(5), Welsh R(5), Wiles J(5), Parr JR(3)(4). Author information: (1)Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK. morag.andrew@newcastle.ac.uk. (2)Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, UK. morag.andrew@newcastle.ac.uk. (3)Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK. (4)Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, UK. (5)National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Oxford, UK. (6)Department of Population Health Sciences, University of Leicester, Leicester, UK. (7)Nottingham Clinical Trials Unit, School of Medicine, University of Nottingham, Nottingham, UK. (8)Portsmouth Hospitals University National Health Service Trust, Portsmouth, UK. (9)Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK. (10)Bliss, 1st Floor North, 10-18 Union Street, London, SE1 1SZ, UK. 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 powered and will be analysed separately. DISCUSSION: Findings from the DOLFIN trial will inform international neonatal and infant nutritional and feeding policy and practice. Learnings from the trial will inform the design and delivery of future neonatal nutritional intervention trials. TRIAL REGISTRATION: ISRCTN62323236. Registered 16 May 2022, https://www.isrctn.com/ISRCTN62323236 . © 2025. The Author(s). DOI: 10.1186/s13063-025-09253-3 PMCID: PMC12752120 PMID: 41462322 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Ethics approval and consent to participate {24}: The DOLFIN trial has received approval from the MHRA and the NHS Health Research Authority (Ethics Ref: 22/SW/0009) and the South West–Central Bristol Research Ethics Committee. Informed consent will be obtained for all participants. Trust Confirmation of Capacity and Capability will be secured at each participating site. The CI or their delegate will submit the Annual Progress Report, End of Trial Notification, and Final Report to key stakeholders, including the Funder (NIHR HTA), MHRA, REC, HRA, host organisation, and Sponsor. Consent for publication {32}: Not applicable. This trial protocol does not involve the use of any personal details, images, videos, or other materials that would require consent from participants or their authorised surrogates. Competing interests {28}: PH is a member of the NIHR Health Technology Assessment Funding Committee (commissioning). NE declares research funding paid to his institution for NIHR portfolio adopted trials from Prolacta Biosciences US, Nutricia Early Life Nutrition, ELGAN pharma, and Neokare UK but did not receive personal fees. NE has received speaker’s honoraria from Nestle Nutrition Institute and for providing consultancy advice to legal firms involved in class action for necrotising enterocolitis in the US; these monies have been donated to charity. NE has provided non-remunerated advice to the WHO, ESPGHAN, and BAPM in the areas of human milk and nutrition for preterm infants. MA declares speaker honoraria from Nestle Nutrition Institute and ESPGHAN conference travel and accommodation costs for the presentation of the Dolphin RCT findings from Nutricia UK, and symposia speaker travel and accommodation costs from Danone Research and Innovation centre.

The Effect of Vitamin B-12 Supplementation During Pregnancy on Early Motor Performance: Secondary Analyses From a Double-Blinded Randomized Controlled Trial.

10. J Nutr. 2026 Feb;156(2):101305. doi: 10.1016/j.tjnut.2025.101305. Epub 2025 Dec 27. The Effect of Vitamin B-12 Supplementation During Pregnancy on Early Motor Performance: Secondary Analyses From a Double-Blinded Randomized Controlled Trial. Kvestad I(1), Ulak M(2), McCann A(3), Chandyo RK(4), Hysing M(5), Schwinger C(6), Ranjitkar S(7), Ueland PM(8), Basnet S(2), Strand TA(9). Author information: (1)Regional Centre for Child and Youth Mental Health and Child Welfare, NORCE, Norwegian Research Centre, Bergen, Norway; Women's Clinic, Innlandet Hospital Trust, Lillehammer, Norway. Electronic address: inkv@norceresearch.no. (2)Child Health Research Project, Department of Child Health, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal. (3)Women's Clinic, Innlandet Hospital Trust, Lillehammer, Norway; Bevital AS, Bergen, Norway. (4)Department of Community Medicine, Kathmandu Medical College, Kathmandu. (5)Department of Psychosocial Science, Faculty of Psychology, University of Bergen, Bergen, Norway. (6)Department of Disease Burden, Norwegian Institute of Public Health, Norway. (7)Child Health Research Project, Department of Child Health, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal; Department of Psychosocial Science, Faculty of Psychology, University of Bergen, Bergen, Norway. (8)Bevital AS, Bergen, Norway. (9)Centre for International Health, University of Bergen, Norway; Department of Research, Innlandet Hospital Trust, Lillehammer, Norway. 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). Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.tjnut.2025.101305 PMCID: PMC12975383 PMID: 41461260 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest The authors report no conflict of interest.

Effect of Maternal Vitamin B(12) Status and Supplementation on Child Neurodevelopment and Cognition: A Systematic Review.

11. Curr Nutr Rep. 2025 Dec 20;14(1):128. doi: 10.1007/s13668-025-00720-6. Effect of Maternal Vitamin B(12) Status and Supplementation on Child Neurodevelopment and Cognition: A Systematic Review. Bonifácio DB(1), Pena FB(1), Dias KA(1), Abrantes LCS(1), Oliveira LA(1), Pereira SMS(1), Fialho TC(1), de Lana VS(1), Araújo SP(1), de Carvalho IMM(1), Della Lucia CM(2). Author information: (1)Department of Nutrition and Health, Universidade Federal de Viçosa, Avenida PH Rolfs, s/n. Viçosa, Viçosa, MG, 36570-900, Brazil. (2)Department of Nutrition and Health, Universidade Federal de Viçosa, Avenida PH Rolfs, s/n. Viçosa, Viçosa, MG, 36570-900, Brazil. cmdellalucia@ufv.br. 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. DOI: 10.1007/s13668-025-00720-6 PMID: 41420666 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Financial Support: This study was funded by Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Code 001), by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Competing interests: The authors declare no competing interests.

Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial.

12. Eur J Nutr. 2025 Dec 19;65(1):9. doi: 10.1007/s00394-025-03814-7. Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial. Zerback T(1), Koeder C(2)(3), Weder S(1), Sputtek A(4), Eckert GP(5), Keller M(1). Author information: (1)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. (2)Institute for Prevention and Cancer Epidemiology (IPE), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110, Freiburg im Breisgau, Germany. christiankoeder@gmail.com. (3)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. christiankoeder@gmail.com. (4)MVZ Medical Laboratory Bremen GmbH, 28359, Bremen, Germany. (5)Institute of Nutritional Sciences, Justus-Liebig University, 35392, Giessen, Germany. 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). DOI: 10.1007/s00394-025-03814-7 PMCID: PMC12717231 PMID: 41417236 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: T.Z., S.W., C.K., A.S., and G.P.E. declare no conflict of interest. M.K. is the managing director of the Research Institute of Plant-Based Nutrition (IFPE) which received funding from Watson Nutrition for conducting the study. Ethical approval: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethics committee of the Faculty of Medicine of the University of Giessen (57/22). Consent to participate: Written consent was obtained from all subjects involved in the study.

The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis.

13. Medicine (Baltimore). 2025 Dec 12;104(50):e46564. doi: 10.1097/MD.0000000000046564. The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis. Xie M(1)(2)(3)(4), Qing X(1), Huang H(1), Zhang J(2)(3)(4). Author information: (1)Department of Obstetrics and Gynecology, Chengdu Qingbaijiang District People's Hospital, Chengdu, China. (2)Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China. (3)The Joint Laboratory for Reproductive Medicine of Sichuan University, The Chinese University of Hong Kong, Chengdu, China. (4)Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, Chengdu, China. 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 studies and the short duration of treatment, more RCTs with high-quality, long-term duration and pregnancy outcomes are needed for further validation. Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/MD.0000000000046564 PMCID: PMC12708167 PMID: 41398893 [Indexed for MEDLINE] Conflict of interest statement: The authors have no funding and conflicts of interest to disclose.

Association between hemoglobin levels and mild cognitive impairment in generally healthy European community-dwelling older adults: a 3-year prospective analysis of the DO-HEALTH trial.

14. Am J Clin Nutr. 2026 Feb;123(2):101114. doi: 10.1016/j.ajcnut.2025.11.005. Epub 2025 Nov 13. Association between hemoglobin levels and mild cognitive impairment in generally healthy European community-dwelling older adults: a 3-year prospective analysis of the DO-HEALTH trial. Wieczorek M(1), Funk J(2), Mattle M(1), Gängler S(1), Egli A(1), Kressig RW(1), Manz MG(3), Bischoff-Ferrari HA(4); DO-HEALTH Research group. Author information: (1)Department of Geriatrics and Acute Aging Medicine Felix Platter, University of Basel, Basel, Switzerland; Swiss Campus for Healthy Longevity, University of Basel, Basel, Switzerland. (2)Department of Geriatrics and Acute Aging Medicine Felix Platter, University of Basel, Basel, Switzerland. (3)Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, University of Zurich, Zurich, Switzerland. (4)Department of Geriatrics and Acute Aging Medicine Felix Platter, University of Basel, Basel, Switzerland; Swiss Campus for Healthy Longevity, University of Basel, Basel, Switzerland; University of Zurich, Zurich, Switzerland. Electronic address: HA.Bischoff-Ferrari@felixplatter.ch. 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. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.ajcnut.2025.11.005 PMID: 41241003 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest HAB-F reports financial support was provided by EMPIRIS Foundation. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.

Intravenous Methylcobalamin-Induced Anaphylactic Shock: A Case Report.

1. Curr Drug Saf. 2026 Jun 12. doi: 10.2174/0115748863468407260605062252. Online ahead of print. Intravenous Methylcobalamin-Induced Anaphylactic Shock: A Case Report. Ravi A(1), R L(2), J SJUC(1). Author information: (1)Department of Pharmacy Practice, Sri Ramakrishna Institute of Paramedical Sciences College of Pharmacy, Coimbatore, 641044, India. (2)Department of Obstetrics and Gynaecology, Sri Ramakrishna Multi-specialty Hospital, Coimbatore, 641044, India. 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 cardiopulm

Targeted Micronutrient Supplementation in Diabetic Retinopathy With MTHFR Polymorphisms: Biomarker Shifts and Clinical Uncertainty.

2. Cell Biochem Funct. 2026 Jun;44(6):e70243. doi: 10.1002/cbf.70243. Targeted Micronutrient Supplementation in Diabetic Retinopathy With MTHFR Polymorphisms: Biomarker Shifts and Clinical Uncertainty. Msa M(1). Author information: (1)MSAM Clinic, Bredstedt, Germany. 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

Oral vitamin B₁₂ after total gastrectomy for gastric cancer: mapping the evidence.

3. Gastric Cancer. 2026 Jun 13. doi: 10.1007/s10120-026-01745-8. Online ahead of print. Oral vitamin B₁₂ after total gastrectomy for gastric cancer: mapping the evidence. Rogaczewski P(1), Janiak M(1), Durślewicz J(2)(3), Koper K(1)(4), Borowczak J(4)(5). Author information: (1)Department of Oncological Surgery, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Toruń, Poland. (2)Department of Tumor Pathology and Pathomorphology, Prof. Franciszek Łukaszczyk Oncology Centre, Bydgoszcz, Poland. justyna.durslewicz@pbs.edu.pl. (3)Department of Animal Biotechnology and Genetics, Faculty of Animal Breeding and Biology, Bydgoszcz University of Science and Technology, Bydgoszcz, Poland. justyna.durslewicz@pbs.edu.pl. (4)Clinical Department of Oncology, Prof. Franciszek Łukaszczyk Oncology Centre, Bydgoszcz, Poland. (5)Faculty of Medicine, Bydgoszcz University of Science and Technology, Bydgoszcz, Poland. 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 cance

Protective role of methylcobalamin (Vit B12) and pyridoxine (Vit B6) combination against teratogenic effects induced by lead in chick embryo.

4. Toxicol Rep. 2026 May 27;16:102280. doi: 10.1016/j.toxrep.2026.102280. eCollection 2026 Jun. Protective role of methylcobalamin (Vit B12) and pyridoxine (Vit B6) combination against teratogenic effects induced by lead in chick embryo. Idrees R(1), Kanwal MA(1), Ahmad SN(2), Ahmad KR(1), Ahmad W(1), Ghazanfar N(1), Inayat I(1), Khalid M(1), Suleman S(1). Author information: (1)Department of Zoology, University of Sargodha, Sargodha, Punjab, Pakistan. (2)Department of Zoology, University of Chakwal, Chakwal, Pakistan. 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 d

Ultrasound-guided Hydrodissection and Integrated Rehabilitation for Postsurgical Common Peroneal Nerve Entrapment.

5. J Vis Exp. 2026 May 12;(231). doi: 10.3791/71088. Ultrasound-guided Hydrodissection and Integrated Rehabilitation for Postsurgical Common Peroneal Nerve Entrapment. Gao L(1), Ye J(1), Zheng Y(1), Ye B(1), Ye X(1), Xu H(1), Zhi Y(1), Pan R(2). Author information: (1)Wenzhou TCM Hospital of Zhejiang Chinese Medical University. (2)Wenzhou TCM Hospital of Zhejiang Chinese Medical University; 80805110@qq.com. 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

A Case of Pernicious Anemia Induced by Atezolizumab in Hepatocellular Carcinoma and Renal Cell Carcinoma.

6. Am J Case Rep. 2026 May 10;27:e952800. doi: 10.12659/AJCR.952800. A Case of Pernicious Anemia Induced by Atezolizumab in Hepatocellular Carcinoma and Renal Cell Carcinoma. Sugimoto T(1), Kanemori G(1), Kanehira H(2), Kitao A(2), Nagatani Y(3). Author information: (1)Department of Hematology and Oncology, Kita-Harima Medical Center, Ono, Hyogo, Japan. (2)Department of Hematology and Oncology, Kita-Harina Medical Center, Ono, Hyogo, Japan. (3)Department of Oncology and Hematology, Kobe University Hospital, Kobe, Hiyogo, Japan. 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 def

Cobalt complexes in biology and medicine: enzymatic functions, pharmacological applications, and health challenges.

7. J Biol Inorg Chem. 2026 May 5. doi: 10.1007/s00775-026-02149-w. Online ahead of print. Cobalt complexes in biology and medicine: enzymatic functions, pharmacological applications, and health challenges. Motieiyan E(1), Motahari R(2), Aliabadi A(3)(4), Khaksar S(5), Abdolmaleki S(6). Author information: (1)Department of Chemistry, Payame Noor University, P. O. BOX, Tehran, 19395-4697, Iran. (2)Pharmaceutical Sciences Research Center, School of Pharmacy, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. (3)Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. (4)Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. (5)Department of Chemistry, School of Science and Technology, The University of Georgia, Tbilisi, Georgia. s.khaksar@ug.edu.ge. (6)Department of Chemistry, School of Science and Technology, The University of Georgia, Tbilisi, Georgia. sara.abdolmaleki19@gmail.com. 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-containi

Efficacy and safety of Mudan granules for treatment of diabetic peripheral neuropathy: a multicenter, double-blind, placebo-controlled, randomized, clinical trial.

8. J Ethnopharmacol. 2026 Sep 15;368:121754. doi: 10.1016/j.jep.2026.121754. Epub 2026 Apr 30. Efficacy and safety of Mudan granules for treatment of diabetic peripheral neuropathy: a multicenter, double-blind, placebo-controlled, randomized, clinical trial. Jin D(1), Gao Q(1), Zhang Y(1), Xiao X(2), Li Y(3), Yu S(4), Wang Y(5), Deng W(6), Zhao Z(7), Song Z(8), Liu P(9), Li Y(10), Piao C(11), Wang X(12), Zhang Q(13), Lian F(14), Tong X(15). Author information: (1)Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. (2)Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. (3)Beijing Hospital, Beijing, 100730, China. (4)Affiliated Hospital of Liaoning University of traditional Chinese Medicine, Shenyang, 110000, China. (5)The Affiliated Hospital of Qingdao University, Qingdao, 266000, China. (6)The Fourth People's Hospital of Chongqing, Chongqing, 400014, China. (7)Zhengzhou Yihe Hospital, Zhengzhou, 450047, China. (8)Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, 300134, China. (9)The Third Hospital of Xi'an, The Affiliated Hospital of Northwest University, Xi'an, 710021, China. (10)Huashan Hospital Fudan University, Shanghai, 200040, China. (11)Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, 518000, China. (12)The First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130012, China. (13)Tianjin Medica

Self-Assembled Quercetin-Mecobalamin Nanoparticles Mitigate Ischemic Stroke Injury via Enhanced Neuroprotection and Microglial Modulation.

9. ACS Biomater Sci Eng. 2026 May 11;12(5):2606-2618. doi: 10.1021/acsbiomaterials.5c01855. Epub 2026 Apr 24. Self-Assembled Quercetin-Mecobalamin Nanoparticles Mitigate Ischemic Stroke Injury via Enhanced Neuroprotection and Microglial Modulation. Zhang T(1)(2)(3), Fan S(1)(2)(3)(4), Ji H(1)(2)(3), Liu W(2)(3), Chen X(1)(2)(3), Fu D(1)(2)(3). Author information: (1)Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. (2)Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan 430022, China. (3)Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. (4)Department of Anesthesiology, First Affiliated Hospital of Shihezi University, Shihezi 832002, China. 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, un

Sustainable steps forward in vitamin B(12)-catalysis.

10. Chem Commun (Camb). 2026 May 14;62(37):9309-9324. doi: 10.1039/d6cc01062h. Sustainable steps forward in vitamin B(12)-catalysis. Nandi S(1), Szabó KF(1), Gryko D(1). Author information: (1)Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland. dorota.gryko@icho.edu.pl. 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. DOI: 10.1039/d6cc01062h PMID: 41960710 [Indexed for MEDLINE]

Investigating weak axial ligation in corrinoids by X-ray absorption spectroscopy: Implications for corrinoid iron-sulfur protein.

11. J Inorg Biochem. 2026 Aug;281:113323. doi: 10.1016/j.jinorgbio.2026.113323. Epub 2026 Apr 3. Investigating weak axial ligation in corrinoids by X-ray absorption spectroscopy: Implications for corrinoid iron-sulfur protein. Zhao K(1), Abernathy MJ(1), Griffith C(2), Kountz DJ(2), Esckilsen D(2), Ragsdale SW(3), Sarangi R(4). Author information: (1)Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA. (2)Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. (3)Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: sragsdal@umich.edu. (4)Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA. Electronic address: ritis@slac.stanford.edu. 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

Vitamin B(12) Biomanufacturing.

1. Adv Biochem Eng Biotechnol. 2026 Jul 30. doi: 10.1007/10_2026_338. Online ahead of print. Vitamin B(12) Biomanufacturing. Zhang D(1)(2)(3)(4), Wang H(5)(6), Kang Q(5)(6). Author information: (1)Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. zhang_dw@tib.cas.cn. (2)National Technology Innovation Center of Synthetic Biology, Tianjin, China. zhang_dw@tib.cas.cn. (3)University of Chinese Academy of Sciences, Beijing, China. zhang_dw@tib.cas.cn. (4)State Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. zhang_dw@tib.cas.cn. (5)Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. (6)National Technology Innovation Center of Synthetic Biology, Tianjin, China. 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. Ne

Adjuvant mecobalamin for anti-VEGF therapy in retinal vein occlusion: protocol of a single-centre, randomised, double-blinded controlled trial.

2. BMJ Open. 2026 Jul 22;16(7):e111209. doi: 10.1136/bmjopen-2025-111209. Adjuvant mecobalamin for anti-VEGF therapy in retinal vein occlusion: protocol of a single-centre, randomised, double-blinded controlled trial. Liu KY(#)(1)(2)(3)(4), Luo QY(#)(1)(2)(3)(4), Li ZY(1)(2)(3)(4), Xiao RY(5), Zeng C(1)(2)(3)(4), Zhang XD(1)(2)(3)(4), Liu SL(#)(6)(2)(3)(4), Deng WL(#)(6)(2)(3)(4), Zhang YL(#)(6)(2)(3)(4). Author information: (1)Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. (2)Chongqing Key Laboratory of Prevention and Treatment of Major Blinding Diseases, Chongqing, People's Republic of China. (3)Chongqing Eye Institute, Chongqing, People's Republic of China. (4)Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, People's Republic of China. (5)Department of Ophthalmology, University-Town Hospital of Chongqing Medical University, Chongqing, China. (6)Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China 202674@hospital.cqmu.edu.cn dengwenli@hospital.cqmu.edu.cn shulinliu_cmu@163.com. (#)Contributed equally 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 ef

Sensory Ataxia Mimicking Diabetic Neuropathy in a Long-Term Metformin User: A Case Report From Korea.

3. Cureus. 2026 Jun 11;18(6):e110704. doi: 10.7759/cureus.110704. eCollection 2026 Jun. Sensory Ataxia Mimicking Diabetic Neuropathy in a Long-Term Metformin User: A Case Report From Korea. Park J(1). Author information: (1)Medicine, Sacheon City Public Health Center, Sacheon, KOR. 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. Copyright © 2026, Park et al. DOI: 10.7759/cureus.110704 PMCID: PMC13356922 PMID: 42438661 Conflict of interest statement: Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all aut

A Retrospective Comparative Study of Sodium Ferulate Combined With Methylcobalamin for Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer.

4. Br J Hosp Med (Lond). 2026 Jun 22;87(6):55138. doi: 10.31083/BJHM55138. A Retrospective Comparative Study of Sodium Ferulate Combined With Methylcobalamin for Oxaliplatin-Induced Peripheral Neuropathy in Patients With Colorectal Cancer. Min B(1), Wan L(2), He H(1), Chen J(1), Jian Z(3), Chen R(3). Author information: (1)Department of Anesthesiology, Qianxi People's Hospital, 551599 Bijie, Guizhou, China. (2)Department of Pain, Qianxi People's Hospital, 551599 Bijie, Guizhou, China. (3)Department of Anesthesiology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, 550001 Guiyang, Guizhou, China. 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 = 1

Delusional parasitosis with shared psychotic features secondary to vitamin B12 deficiency and mild cognitive impairment: a case report.

5. BMC Psychiatry. 2026 Jun 27. doi: 10.1186/s12888-026-08334-0. Online ahead of print. Delusional parasitosis with shared psychotic features secondary to vitamin B12 deficiency and mild cognitive impairment: a case report. Bando C(1), Okamoto N(2), Chibaatar E(1), Ide S(3), Yoshimura R(1)(4), Ikenouchi A(1)(5). Author information: (1)Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, 8078555, Japan. (2)Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, 8078555, Japan. nokamoto@med.uoeh-u.ac.jp. (3)Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, 8078555, Japan. (4)St. Lucia's Hospital, Kurume, 8300047, Japan. (5)Medical Center for Dementia, Hospital of the University of Occupational and Environmental Health, Kitakyushu, 8078556, Japan. 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 environ

A Case of Nutritional Optic Neuropathy Caused by Vitamin B12 and Folate Deficiency Presenting With Bitemporal Hemianopia-Like Visual Field Defects.

6. Cureus. 2026 May 24;18(5):e109561. doi: 10.7759/cureus.109561. eCollection 2026 May. A Case of Nutritional Optic Neuropathy Caused by Vitamin B12 and Folate Deficiency Presenting With Bitemporal Hemianopia-Like Visual Field Defects. Ueda N(1), Kitamura Y(1), Baba T(1). Author information: (1)Ophthalmology, Chiba University, Chiba, JPN. 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

Blood-activating and collateral-unblocking traditional Chinese medicine formulas combined with mecobalamin for peripheral neuropathy in type 2 diabetes: a systematic review and Bayesian network meta-analysis.

1. Front Endocrinol (Lausanne). 2026 Sep 16;17:1888494. doi: 10.3389/fendo.2026.1888494. eCollection 2026. Blood-activating and collateral-unblocking traditional Chinese medicine formulas combined with mecobalamin for peripheral neuropathy in type 2 diabetes: a systematic review and Bayesian network meta-analysis. Liu Z(#)(1), Wang Y(#)(1), Hu A(#)(1), Jia S(1), Wu T(1), Fu Y(1), Zheng H(2), Sun L(1)(3). Author information: (1)Department of Nephrology and Endocrinology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China. (2)School of Nursing, Beijing University of Chinese Medicine, Beijing, China. (3)Department of Nephrology, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China. (#)Contributed equally 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 pl

Isolated Parosmia Caused by Vitamin B12 Deficiency.

2. Intern Med. 2026 Sep 1. doi: 10.2169/internalmedicine.7232-26. Online ahead of print. Isolated Parosmia Caused by Vitamin B12 Deficiency. Handa H(1), Uzawa A(1), Shu N(2), Mori M(1), Kuwabara S(1)(3). Author information: (1)Department of Neurology, Graduate School of Medicine, Chiba University, Japan. (2)Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan. (3)Research Institute of Disaster Medicine, Chiba University, Japan. 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. DOI: 10.2169/internalmedicine.7232-26 PMID: 42686568

Sensory ataxia associated with vitamin B(12) deficiency and hypocalcaemia in a patient with 'hikikomori' syndrome.

3. BMJ Case Rep. 2026 Aug 27;19(8):e275337. doi: 10.1136/bcr-2026-275337. Sensory ataxia associated with vitamin B(12) deficiency and hypocalcaemia in a patient with 'hikikomori' syndrome. Hashimoto T(1), Kubota M(2), Nakasone Y(3), Aizawa T(3). Author information: (1)Department of Neurology, Aizawa Hospital, Matsumoto, Nagano Prefecture, Japan sinke-dr@ai-hosp.or.jp. (2)Department of Neurology, Aizawa Hospital, Matsumoto, Nagano Prefecture, Japan. (3)Diabetes Center, Aizawa Hospital, Matsumoto, Nagano Prefecture, Japan. 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 ma

High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications.

4. Neurodegener Dis Manag. 2026 Aug 27:1-12. doi: 10.1080/17582024.2026.2713755. Online ahead of print. High-dose methylcobalamin in amyotrophic lateral sclerosis: mechanistic rationale, translational evidence, and clinical implications. da Silva AA(1), Pupe CCB(1), Dos Santos JCC(1). Author information: (1)Programa de Pós-Graduação em Neurologia e Neurociências, Universidade Federal Fluminense, UFF, Rio de Janeiro, Brazil. 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 translatio

Revisiting the hematological manifestations of vitamin B12 deficiency.

5. Front Nutr. 2026 Aug 12;13:1898533. doi: 10.3389/fnut.2026.1898533. eCollection 2026. Revisiting the hematological manifestations of vitamin B12 deficiency. Parakh N(1), Dewan P(2). Author information: (1)Department of Hematology, Bone Marrow Transplantation and Cellular Therapy, Vardhman Mahavir Medical College and Safdarjung Hospital, Guru Gobind Singh Indraprastha University, New Delhi, India. (2)Department of Pediatrics, University College of Medical Sciences, University of Delhi, New Delhi, India. 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