비타민B12 (코발라민)

Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis.

1. Intern Med J. 2015 Apr;45(4):409-16. doi: 10.1111/imj.12697. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Jung SB(1), Nagaraja V, Kapur A, Eslick GD. Author information: (1)Prince of Wales Hospital, Sydney, Austra

Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people.

2. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD004514. doi: 10.1002/14651858.CD004514.pub2. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Malouf R(1), Grimley Evans J. Author information: (1)Department of Psychiatry, Oxfords

Folic acid with or without vitamin B12 for cognition and dementia.

3. Cochrane Database Syst Rev. 2003;(4):CD004514. doi: 10.1002/14651858.CD004514. Folic acid with or without vitamin B12 for cognition and dementia. Malouf M(1), Grimley EJ, Areosa SA. Author information: (1)Dept. of Clinical Geratology, Cochrane Dementia and Cognitive Improvement Group, Radclif

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).

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.

5. 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), Amrollahi Bioky A(1), Gerami H(2), Khorasanian AS(3), Esmaeili AH(4), Fateh HR(5), Aghaei Meybodi HR(6), Mohajeri-Tehrani MR(1), Safyari R(7), Adibi H(8), Sajjadi-Jazi SM(9). Author information: (1)Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. (2)Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (3)Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. (4)Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran. (5)Department of Physical Medicine and Rehabilitation, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. (6)Evidence Based Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. (7)Department of Internal Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. (8)Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. (9)Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mahmood.sajadi@gmail.com. BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM) and is associated with substantial morbidity, mortality, and healthcare costs. Vitamin B-12 plays a critical role in nerve protection and regeneration. However, clinical evidence regarding the effectiveness and optimal dose of vitamin B-12 supplementation for managing DPN in individuals with low serum vitamin B-12 levels remains inconclusive. OBJECTIVES: The aim of this study is to compare the effects of 2 different daily doses of oral vitamin B-12 supplementation on neuropathic parameters in patients with DPN and low serum vitamin B-12. METHODS: This 16 wk, randomized controlled trial enrolled adults with T2DM, DPN, and low serum vitamin B12 levels (<200 pg/mL). Patients were randomly assigned (1:1) to receive either 1000 μg or 2000 μg of oral vitamin B12 (methylcobalamin) daily. The primary outcomes were changes in neuropathic parameters, assessed by the numerical rating scale (NRS), Michigan neuropathy screening instrument examination (MNSIE), and neuropathy disability score (NDS). Secondary outcomes included serum B-12 levels and metabolic parameters. RESULTS: Of the 35 participants randomly assigned, 32 completed the 16-wk trial. Serum vitamin B-12 levels increased significantly in both groups, with a greater rise noted in the 2000 μg group (P = 0.049). Both the 1000 μg and 2000 μg groups experienced significant improvements in neuropathy symptoms. Mean ± SD NRS scores decreased from 7.00 ± 2.03 to 5.60 ± 2.19 (P = 0.016) in the 1000 μg group, and from 6.18 ± 2.40 to 4.42 ± 2.50 (P = 0.007) in the 2000 μg group. Similarly, MNSIE scores improved from 5.70 ± 1.66 to 5.22 ± 1.99 (P = 0.033) and from 5.40 ± 1.68 to 4.47 ± 2.25 (P = 0.022), respectively. No significant difference in these neuropathic outcomes was observed between groups. The NDS remained unchanged in both groups (P > 0.05). In addition, the 1000 μg dose was associated with significant improvements in hemoglobin A1c levels, whereas the 2000 μg dose was linked to a significant decline in estimated glomerular filtration rate. CONCLUSIONS: In patients with DPN and low serum vitamin B-12 levels, 16 wk of daily supplementation with either 1000 μg or 2000 μg of vitamin B-12 similarly improves neuropathic symptoms. Apart from higher serum B-12 levels, the 2000 μg dose did not offer additional neuropathic or metabolic benefits. Copyright © 2026 American Society for Nutrition. Published by Elsevier Inc. All rights reserved. DOI: 10.1016/j.tjnut.2026.101368 PMID: 41548600 [Indexed for MEDLINE] Conflict of interest statement: Conflicts of interest The authors report no conflicts of interest.

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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.