Research

Vitamin B12

153 peer-reviewed studies curated from PubMed and Semantic Scholar.

36
Meta-analyses
29
Systematic reviews
42
RCTs
46
Other studies
Meta-analyses (24%)
Systematic reviews (19%)
RCTs (27%)
Observational (6%)

Studies

Sorted by quality and recency

2025·Nutrients·Edith Valdez-Martínez, Horacio Márquez-González, Ricardo Ramírez-Aldana, et al

The Controversial Issue of Hypervitaminosis B12 as Prognostic Factor of Mortality: Global Lessons from a Systematic Review and Meta-Analysis.

Meta-analysisn = 69,610

Meta-analysis of 28 studies with 69,610 participants examining hypervitaminosis B12 as a prognostic factor for all-cause mortality. High serum levels of B12 marginally increased mortality risk among chronic disease patients and hospitalized individuals, but results were not statistically significant. The study suggests potential artefacts in the association between high B12 levels and mortality.

PubMedRead on PubMed
2025·Nutrients·Lirong Nie, Xinru Liu, Xiaoxue Li, et al

Beyond Folate: The Emerging Role of Maternal Vitamin B12 in Neural Tube Development.

Meta-analysisn = 6,614Womens Health

A systematic review and meta-analysis of 38 studies with 2316 NTD cases and 4298 controls investigated the role of maternal vitamin B12 in neural tube development. The analysis found that lower vitamin B12 levels were associated with a higher occurrence of neural tube defects, independent of folate levels, suggesting the importance of vitamin B12 supplementation alongside folic acid for NTD prevention.

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2025·Frontiers in pharmacology·Marta Mazur, Artnora Ndokaj, Claudia Salerno, et al

Efficacy of sublingual and oral vitamin B12 versus intramuscular administration: insights from a systematic review and meta-analysis.

Systematic reviewn = 6,098Nutrition

This systematic review and meta-analysis evaluated the effectiveness of sublingual and oral vitamin B12 administration compared to intramuscular injections for improving serum cobalamin and reducing homocysteine levels. The study included 16 studies with a total of 6,098 participants and found that all administration routes significantly increased serum cobalamin and reduced homocysteine levels, with no significant differences between the routes. The findings suggest that sublingual and oral B12 supplementation are as effective as intramuscular injections.

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2025·European journal of clinical nutrition·Yunfeng Yu, Tongyi Zhou, Liu Li, et al

Acupoint injection increases the efficacy of vitamin B12 for diabetic neuropathy: a meta-analysis and trial sequential analysis.

Meta-analysisn = 1,688

Meta-analysis and trial sequential analysis of 20 RCTs involving 1688 participants evaluated the efficacy of vitamin B12 acupoint injections for diabetic neuropathy. Acupoint injection significantly improved clinical effectiveness and nerve conduction velocities compared to other administration routes, without increasing adverse events.

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2025·Clinical diabetes : a publication of the American Diabetes Association·Nattawat Poolsawatkitikool

Effectiveness of Vitamin B1-6-12 Supplementation Compared With Vitamin B12 and Gabapentin in Patients With Diabetic Peripheral Neuropathy.

RCTn = 237

RCT of 237 patients with diabetic peripheral neuropathy comparing vitamin B1-6-12, vitamin B12, and gabapentin. Gabapentin showed superior improvement in pain outcomes, but vitamin B1-6-12 remains a cost-effective alternative with fewer side effects.

Semantic ScholarRead on Semantic Scholar
2025·Nutrition reviews·Meenakshi Sachdeva, Abhishek Purohit, Meenakshi Malik, et al

Comparison of Efficacy and Safety of Parenteral vs Oral Route of Vitamin B12 Supplementation for the Treatment of Vitamin B12 Deficiency Anemia in Children: A Systematic Review.

Systematic reviewNutrition

Systematic review comparing the efficacy and safety of parenteral vs oral vitamin B12 supplementation in children with vitamin B12 deficiency anemia. Limited evidence from a single RCT suggests the parenteral route is more efficacious, but the study is at high risk of bias.

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2025·Frontiers in nutrition·Yaqi Yin, Ziming Zhao, Xu Wang, et al

Effects of folic acid with vitamin B12/vitamin B6 intervention on serum homocysteine metabolism and complications in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

Systematic reviewNutrition

Systematic review and meta-analysis of 29 RCTs evaluating folic acid combined with B vitamins (B12 and B6) on serum homocysteine levels and complication risk in type 2 diabetes patients. Folic acid plus vitamin B12 significantly reduced homocysteine levels and decreased the incidence of complications.

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2025·Journal of oral rehabilitation·Danielle Soley Batista, Gabriela Aparecida Winkert Manfron, Diulia Pereira Bubna, et al

Nutritional Outcomes of Overdentures vs. Complete Dentures in Older Edentulous Adults: A Systematic Review and Meta-Analysis.

Meta-analysisNutrition

Systematic review and meta-analysis comparing nutritional outcomes of implant-supported overdentures versus conventional complete dentures in older edentulous adults. Overdenture users showed significantly higher vitamin B12 levels at 6-month follow-up, but no consistent differences for albumin or folate. Overall evidence was moderate for vitamin B12 and albumin, and low for folate.

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2025·Oxidative medicine and cellular longevity·Tesfaye Engdaw Habtie, Alemu Birara Zemariam, Betelhem Walelgn Dagnaw, et al

The Immunomodulatory Effect of Vitamin B12 in Pernicious Anemia: A Systematic Review.

Systematic reviewImmunity

Systematic review of RCTs evaluating the impact of vitamin B12 (methylcobalamin/cyanocobalamin) on immune function in pernicious anemia patients. Vitamin B12 administration significantly increased CD3, CD8+, and CD19 cell levels, improved NK cell activity, and decreased the CD4/CD8 ratio, suggesting enhanced immunity.

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2024·Irish journal of medical science·Omar Ahmed Abdelwahab, Ahmed Abdelaziz, Sherein Diab, et al

Efficacy of different routes of vitamin B12 supplementation for the treatment of patients with vitamin B12 deficiency: A systematic review and network meta-analysis.

Meta-analysisn = 4,275Nutrition -

This systematic review and network meta-analysis evaluated the efficacy of oral, intramuscular, and sublingual routes of vitamin B12 supplementation in 4275 patients. The intramuscular route ranked highest for increasing vitamin B12 levels, but differences between routes were not statistically significant. No significant differences were found among administration routes for hemoglobin levels or other CBC parameters.

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2024·American journal of health promotion : AJHP·Robert K Janko, Irmgard Haussmann, Ashok Patel

Vitamin B12 Status in Vegan and Vegetarian Seventh-Day Adventists: A Systematic Review and Meta-Analysis of Serum Levels and Dietary Intake.

Meta-analysisn = 1,994Nutrition -

This systematic review and meta-analysis evaluated vitamin B12 status and intake among Seventh-day Adventists following a plant-based diet compared to omnivore controls. The analysis of four studies with 1994 participants found no significant differences in serum vitamin B12 levels or daily intake between the groups, highlighting the role of fortified foods and supplements in maintaining adequate B12 status.

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2024·Clinical nutrition ESPEN·Maria Eduarda Rodrigues Alves Dos Santos, Karollainy Gomes da Silva, Ana Patrícia da Silva Souza, et al

Relationship between vitamin B12 levels and motor development: A systematic review.

Systematic reviewn = 1,559Brain Health

Systematic review investigating the influence of reduced vitamin B12 levels on infant motor development and the effects of supplementation. The review included eight studies with a total of 1,559 participants, showing that low vitamin B12 levels may affect motor development and that supplementation could enhance motor aspects in healthy children.

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2024·BMC gastroenterology·Guangxu Zhu, Xuguang Jiao, Shengjie Zhou, et al

Can proximal gastrectomy with double-tract reconstruction replace total gastrectomy? a meta-analysis of randomized controlled trials and propensity score-matched studies.

Meta-analysisn = 1,154Nutrition

This meta-analysis compared proximal gastrectomy with double-tract reconstruction to total gastrectomy with Roux-en-Y reconstruction in patients with gastric cancer. Proximal gastrectomy showed better outcomes in hemoglobin levels and reduced need for vitamin B12 supplementation, with comparable survival rates and complication profiles to total gastrectomy.

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2024·Nutrition bulletin·Ali Niklewicz, Luciana Hannibal, Martin Warren, et al

A systematic review and meta-analysis of functional vitamin B12 status among adult vegans.

Meta-analysisNutrition

This systematic review and meta-analysis examined functional vitamin B12 status among adult vegans compared to vegetarians and omnivores. It found that vegans have significantly lower serum B12 and elevated homocysteine levels, indicating increased functional B12 deficiency. The use of vitamin B12 supplements among vegans significantly improved biomarker concentrations.

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2024·Aging·Chih-Ying Lee, Lung Chan, Chaur-Jong Hu, et al

Role of vitamin B12 and folic acid in treatment of Alzheimer's disease: a meta-analysis of randomized control trials.

Meta-analysisBrain Health

Meta-analysis of randomized control trials assessing vitamin B12 and folic acid supplementation in Alzheimer's disease patients. Vitamin B12 and folic acid improved MMSE scores but did not significantly affect ADAS-Cog scores or daily life function. Blood homocysteine levels were significantly decreased.

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2024·Women's health (London, England)·Juan R Ulloque-Badaracco, Ali Al-Kassab-Córdova, Enrique A Hernández-Bustamante, et al

Homocysteine, vitamin B12, and folate circulating levels in women with and without polycystic ovary syndrome: A systematic review and meta-analysis.

Meta-analysisWomens Health

Systematic review and meta-analysis of 75 studies examining homocysteine, vitamin B12, and folate levels in women with and without PCOS. Patients with PCOS had higher homocysteine levels, while no significant differences were observed in vitamin B12 and folate levels.

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2023·Archives of gerontology and geriatrics·Kefeng Liu, Zhirong Yang, Xiaojing Lu, et al

The origin of vitamin B12 levels and risk of all-cause, cardiovascular and cancer specific mortality: A systematic review and dose-response meta-analysis.

Meta-analysisn = 92,346Longevity Heart Health

Systematic review and dose-response meta-analysis of 22 cohort studies with 92,346 individuals examining the relationship between serum vitamin B12 levels and mortality. Higher serum vitamin B12 concentrations were associated with increased all-cause mortality, particularly in older adults, and showed mixed evidence for cardiovascular mortality.

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2023·Frontiers in Endocrinology·Juan R. Ulloque-Badaracco, Enrique A. Hernández-Bustamante, Esteban A. Alarcón-Braga, et al

Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis

Meta-analysisn = 87,988

This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and homocysteine levels with metabolic syndrome (MetS). Higher vitamin B12 levels were inversely associated with MetS, while higher homocysteine levels were associated with MetS. Folate levels were not significantly associated with MetS.

Semantic ScholarRead on Semantic Scholar
2023·Frontiers in endocrinology·Vicente A Benites-Zapata, Felipe L Ignacio-Cconchoy, Juan R Ulloque-Badaracco, et al

Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis.

Meta-analysisn = 28,597Hormone Health

Systematic review and meta-analysis assessing vitamin B12 levels in patients with thyroid disorders. Patients with hypothyroidism had lower vitamin B12 levels compared to healthy participants, while no significant differences were found for hyperthyroidism, autoimmune thyroid disease, or subclinical hypothyroidism.

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2023·Expert review of gastroenterology & hepatology·Arup Choudhury, Anuraag Jena, Vaneet Jearth, et al

Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis.

Meta-analysisn = 2,852Nutrition

Systematic review and meta-analysis examining the risk of vitamin B12 deficiency in proton pump inhibitor (PPI) users compared to non-users. The pooled odds ratio indicated a slightly higher risk of deficiency among PPI users, but significant heterogeneity and low pooled OR suggest the association is unclear.

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2023·Epigenetics·Giulietta S Monasso, Thanh T Hoang, Giulia Mancano, et al

A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation.

Meta-analysisn = 2,420

Meta-analysis of epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy and cord blood with DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at multiple CpGs, with some associations persisting in children aged 4-10 years. Associations with birth weight, gestational age, and childhood cognitive skills were noted for some CpGs.

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2023·The Journal of nutrition·Rukman Manapurath, Tor A Strand, Ranadip Chowdhury, et al

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6-7 Years: A Follow-Up of a Randomized Controlled Trial.

RCTn = 791Heart Health

Follow-up of a randomized controlled trial investigating the effect of vitamin B12 and/or folic acid supplementation in early childhood on cardiometabolic risk markers after 6-7 years. Combined supplementation resulted in lower tHcy concentrations and vitamin B12 was associated with a lower leptin-adiponectin ratio, suggesting persistent beneficial metabolic effects.

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2023·Current medical imaging·Ali Alghamdi

Structural and Functional Brain Changes Associated with Vitamin B12 Deficiency using Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

Meta-analysisBrain Health

Systematic review and meta-analysis assessing structural and functional brain changes associated with vitamin B12 deficiency using MRI. The review found a connection between vitamin B12 deficiency and abnormal brain changes across different age groups, with improvements observed post-vitamin B12 treatment.

PubMedRead on PubMed
2023·Nutrition reviews·Christopher F Jensen

Vitamin B12 levels in children and adolescents on plant-based diets: a systematic review and meta-analysis.

Meta-analysisNutrition

Systematic review and meta-analysis evaluating vitamin B12 levels in children and adolescents on plant-based diets. Found significantly lower vitamin B12 levels in those on vegan and macrobiotic diets compared to omnivorous peers, indicating a risk of deficiency.

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2023·Current diabetes reviews·Rabie Khattab, Mayar Albannawi, Dua'a Alhajjmohammed, et al

Metformin-Induced Vitamin B12 Deficiency among Type 2 Diabetes Mellitus' Patients: A Systematic Review.

Systematic reviewNutrition

Systematic review examining the effect of metformin on vitamin B12 deficiency in type 2 diabetes mellitus patients. The review found a positive correlation between metformin intake and vitamin B12 deficiency, with increased homocysteine and decreased folate levels. It recommends regular measurement of vitamin B12 levels during long-term metformin treatment.

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2022·BMC pregnancy and childbirth·Jin He, Dongmei Jiang, Xianwei Cui, et al

Vitamin B12 status and folic acid/vitamin B12 related to the risk of gestational diabetes mellitus in pregnancy: a systematic review and meta-analysis of observational studies.

Meta-analysisn = 10,595Womens Health

Systematic review and meta-analysis of 10 studies with 10,595 pregnant women assessing the association between vitamin B12 and folic acid levels and the risk of gestational diabetes mellitus (GDM). Vitamin B12 deficiency was associated with a higher risk of GDM, while elevated vitamin B12 levels may decrease the risk. The role of excess folic acid and low vitamin B12 levels in GDM occurrence is controversial.

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2022·Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Nan Hu, Xubiao Wang

The level of homocysteine in amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Meta-analysisn = 812

Systematic review and meta-analysis investigating the levels of homocysteine, folic acid, and vitamin B12 in ALS patients compared to controls. The study found no significant difference in plasma levels of homocysteine, folic acid, or vitamin B12 between ALS patients and controls, but CSF levels of homocysteine were significantly higher in ALS patients.

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2022·Nutrition and health·Cummins-Williams Kirsty, Hickson Mary, Jonathan Sumner

The Relationship of Cobalamin and/or Folate to the Patient-Centred Outcomes in Multiple Sclerosis: A Systematic Review and Meta-analysis.

Meta-analysisn = 616

Systematic review and meta-analysis examining the relationship of vitamin B12 and folate concentrations to cognitive function, fatigue, physical function, quality of life, and homocysteine levels in MS patients. No significant differences in folate and cobalamin concentrations were found between MS patients and healthy controls, but MS patients had higher homocysteine levels. Results were inconclusive due to high heterogeneity.

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2022·Diabetes & metabolic syndrome·Samuel Pratama, Brigitta Cindy Lauren, Wismandari Wisnu

The efficacy of vitamin B12 supplementation for treating vitamin B12 deficiency and peripheral neuropathy in metformin-treated type 2 diabetes mellitus patients: A systematic review.

Systematic reviewn = 506Nutrition Inflammation

Systematic review of 7 clinical trials with 506 participants assessing vitamin B12 supplementation in metformin-treated type 2 diabetes mellitus patients. The review found significant increases in serum vitamin B12 levels and reductions in homocysteine, but mixed results on neuropathy symptoms.

Semantic ScholarRead on Semantic Scholar
2022·Frontiers in psychiatry·Sirui Yan, Hailong Liu, Yaqiong Yu, et al

Changes of Serum Homocysteine and Vitamin B12, but Not Folate Are Correlated With Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis of Case-Control Studies.

Systematic reviewn = 309Brain Health

Systematic review and meta-analysis of 5 case-control studies involving 309 patients with OCD. The analysis found significantly higher serum homocysteine levels and lower vitamin B12 levels in OCD patients, while folate levels were not significantly different from controls.

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2022·Journal of Bone and Mineral Research·M. Clements, M. Heffernan, M. Ward, et al

A 2‐Year Randomized Controlled Trial With Low‐Dose B‐Vitamin Supplementation Shows Benefits on Bone Mineral Density in Adults With Lower B12 Status

RCTn = 205Joint Bone Health

A 2-year RCT investigated the effect of low-dose B-vitamins on bone mineral density (BMD) in adults aged ≥50 years with lower B12 status. The intervention increased serum folate, B12, and plasma pyridoxal-5-phosphate but had no overall effect on BMD. However, it reduced BMD decline in participants with lower baseline B12 status.

Semantic ScholarRead on Semantic Scholar
2022·Archives of medical research·Xiaoyue Yang, Rui Hu, Yajun Zhu, et al

Meta-analysis of Serum Vitamin B12 Levels and Diabetic Retinopathy in Type 2 Diabetes.

Meta-analysis

Meta-analysis of 15 studies assessing the association between serum vitamin B12 levels and diabetic retinopathy in type 2 diabetes. Results showed significantly reduced serum vitamin B12 levels in patients with diabetic retinopathy, with variations in association by ethnicity.

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2022·Nutrition reviews·Kamila S Batista, Vanessa M Cintra, Paulo A F Lucena, et al

The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle-gut-brain axis and implications for SARS-CoV-2 infection.

Meta-analysisImmunity Brain Health Gut Health

This comprehensive review discusses the role of vitamin B12 as adjunct therapy for viral infections, particularly COVID-19, focusing on the muscle-gut-brain axis. It highlights vitamin B12's potential to balance immune responses and improve symptoms like pain, memory loss, and impaired concentration. The review calls for larger RCTs to determine optimal vitamin B12 supplementation strategies.

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2022·Emergency medicine Australasia : EMA·Pierce Marsden, Aakriti A Sharma, Joe-Anthony Rotella

Review article: Clinical manifestations and outcomes of chronic nitrous oxide misuse: A systematic review.

Systematic review

Systematic review of chronic nitrous oxide misuse, focusing on clinical manifestations and outcomes. Neurological symptoms were common, with functional B12 deficiency identified as a cause despite normal serum B12 levels. B12 replacement was the treatment of choice, with partial recovery reported.

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2021·Nutrients·Stefan Markun, Isaac Gravestock, Levy Jäger, et al

Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.

Meta-analysisn = 6,276Brain Health -Mood -Energy -

Systematic review and meta-analysis of 16 RCTs with 6276 participants assessing the effects of vitamin B12 and B complex supplementation on cognitive function, depressive symptoms, and fatigue. No evidence was found for an effect on cognitive function or depressive symptoms, and only one study reported on fatigue, making analysis impossible.

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2021·Nutrition research (New York, N.Y.)·Renu Bala, Rachna Verma, Priyanka Verma, et al

Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses.

Meta-analysisn = 153Womens Health

The study analyzed plasma folic acid, vitamin B12, and homocysteine levels in 83 females with early pregnancy loss (EPL) and 70 healthy pregnant females. Results showed that low vitamin B12 and hyperhomocysteinemia are significant risk factors for EPL, with a higher risk when combined. Meta-analysis confirmed these findings.

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2021·Arquivos de gastroenterologia·Débora Silva Costa, Marina P Guahnon, Fernanda Braga Seganfredo, et al

VITAMIN B12 AND HOMOCYSTEINE LEVELS IN PATIENTS WITH NAFLD: A SYSTEMATIC REVIEW AND METANALYSIS.

Meta-analysis

Systematic review and meta-analysis of serum vitamin B12 and homocysteine levels in patients with NAFLD. No difference in vitamin B12 levels between NAFLD patients and controls, but homocysteine levels were higher in NAFLD patients, suggesting it could be a marker for liver damage.

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2021·Frontiers in endocrinology·Rishikesh V Behere, Anagha S Deshmukh, Suhas Otiv, et al

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.

Systematic reviewWomens Health Womens Health Brain Health Brain Health Nutrition Nutrition

Systematic review of 46 studies on maternal vitamin B12 status during pregnancy in India. High prevalence of vitamin B12 deficiency is linked to higher risks of NTDs, pregnancy complications, lower birth weight, and adverse offspring health outcomes. Vitamin B12 supplementation showed beneficial effects on offspring neurocognitive development.

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2021·International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience·Farah Wahbeh, Mange Manyama

The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review.

Systematic reviewWomens Health

Systematic review of 40 studies examining the role of vitamin B12 deficiency and genetic risk factors in the etiology of neural tube defects (NTDs). The review found decreased vitamin B12 levels in mothers and infants in NTD groups compared to controls, and links between genetic variants and increased NTD risk.

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2020·Journal of alternative and complementary medicine (New York, N.Y.)·Ratree Sawangjit, Suntana Thongphui, Wanida Chaichompu, et al

Efficacy and Safety of Mecobalamin on Peripheral Neuropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Meta-analysisn = 1,707

Systematic review and meta-analysis of 15 RCTs with 1707 patients assessing mecobalamin's efficacy and safety on peripheral neuropathy. Mecobalamin in combination was more effective than active control for clinical therapeutic efficacy and nerve conduction velocities, but not for pain or neuropathic symptoms. No serious adverse events were reported.

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2020·Nutrients·Ilan Sela, Anat Yaskolka Meir, Alexander Brandis, et al

Plant-Based Protein Contains Bioactive Vitamin Band Is Well Absorbed in Humans.

RCTn = 294Nutrition

The study examined the presence of bioactive vitamin B12 compounds in the aquatic plant Mankai and its absorption in humans. In the 18-month DIRECT-PLUS weight-loss trial, participants consuming a Mankai-containing green Mediterranean/low-meat diet showed a 15.4% increase in serum B12 levels compared to control and Mediterranean diet groups.

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2020·BMJ Open·T. Sanz-Cuesta, E. Escortell-Mayor, I. Cura-González, et al

Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12)

RCTn = 283Nutrition

Pragmatic, randomised, non-inferiority trial comparing oral versus intramuscular vitamin B12 administration in 283 patients aged ≥65 years with vitamin B12 deficiency. Both administration routes were effective at 8 weeks, but differences were observed at 52 weeks, with intramuscular administration showing slightly higher efficacy. Most patients preferred the oral route.

Semantic ScholarRead on Semantic Scholar
2020·Nutrients·Thomas Julian, Rubiya Syeed, Nicholas Glascow, et al

B12 as a Treatment for Peripheral Neuropathic Pain: A Systematic Review.

Systematic review

Systematic review of 24 articles evaluating vitamin B12 as a treatment for neuropathic pain. The review suggests some evidence for the therapeutic effect of B12 in treating post-herpetic neuralgia and painful peripheral neuropathy.

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2019·Endocrine·Eleni Kouroglou, Panagiotis Anagnostis, Alexandros Daponte, et al

Vitamin B12 insufficiency is associated with increased risk of gestational diabetes mellitus: a systematic review and meta-analysis.

Meta-analysisn = 1,810Womens Health

Systematic review and meta-analysis of six studies examining the association between vitamin B12 deficiency and gestational diabetes mellitus (GDM) in pregnant women. Women with GDM had lower vitamin B12 levels, and vitamin B12 deficiency was associated with a higher risk of developing GDM.

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2019·Journal of clinical oncology : official journal of the American Society of Clinical Oncology·Christine B Ambrosone, Gary R Zirpoli, Alan D Hutson, et al

Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221).

RCTn = 1,134Longevity

Prospective study of 1,134 breast cancer patients in a chemotherapy trial assessing dietary supplement use. Antioxidant supplements and vitamin B12 use were associated with increased hazard of recurrence and poorer survival outcomes. Iron use during chemotherapy was also linked to recurrence.

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2018·Complementary therapies in medicine·J Y Wang, Y H Wu, S J Liu, et al

Vitamin B12 for herpetic neuralgia: A meta-analysis of randomised controlled trials.

Meta-analysisn = 383

Meta-analysis of four RCTs with 383 participants evaluating vitamin B12 supplementation in postherpetic neuralgia (PHN) patients. Vitamin B12 significantly decreased pain scores and improved quality of life compared to placebo, with moderate quality evidence.

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2017·American journal of epidemiology·Tormod Rogne, Myrte J Tielemans, Mary Foong-Fong Chong, et al

Associations of Maternal Vitamin B12 Concentration in Pregnancy With the Risks of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analysis of Individual Participant Data.

Meta-analysisn = 11,216Womens Health Nutrition

Systematic review and meta-analysis of 18 studies with 11,216 observations evaluating maternal vitamin B12 levels in pregnancy. B12 deficiency was associated with a higher risk of low birth weight and preterm birth, though no linear association was found with birth weight. A linear association was observed with preterm birth risk.

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2015·Public health nutrition·Nai-Hui Sun, Xuan-Zhang Huang, Shuai-Bo Wang, et al

A dose-response meta-analysis reveals an association between vitamin B12 and colorectal cancer risk.

Meta-analysisn = 10,601Longevity

This meta-analysis evaluated the association between vitamin B12 intake and colorectal cancer (CRC) risk, including 17 studies with 10,601 patients. It found a significant inverse association between dietary vitamin B12 intake and CRC risk, suggesting vitamin B12 may aid in cancer prevention, particularly at higher intake levels.

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2015·Scientific reports·Peirong Huang, Fenghua Wang, Birendra Kumar Sah, et al

Homocysteine and the risk of age-related macular degeneration: a systematic review and meta-analysis.

Meta-analysisn = 1,072

Systematic review and meta-analysis evaluating the association between plasma total homocysteine (tHcy) and B vitamin levels with age-related macular degeneration (AMD) risk. The analysis included 11 studies for tHcy and 3 studies for folic acid and vitamin B12. Results showed elevated tHcy and decreased vitamin B12 levels in AMD cases, suggesting tHcy as a risk modulator for AMD.

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2013·The British journal of nutrition·Derek Obersby, David C Chappell, Andrew Dunnett, et al

Plasma total homocysteine status of vegetarians compared with omnivores: a systematic review and meta-analysis.

Meta-analysisn = 3,230Nutrition

This systematic review and meta-analysis compared plasma homocysteine and serum vitamin B12 levels between vegetarians and omnivores. It found that vegetarians, particularly vegans, are at greater risk of vitamin B12 deficiency, which is inversely related to plasma homocysteine levels. The study highlights the need for reliable vitamin B12 supplementation to address elevated homocysteine levels in vegetarians.

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2012·The British journal of nutrition·Fiona O'Leary, Margaret Allman-Farinelli, Samir Samman

Vitamin B₁₂ status, cognitive decline and dementia: a systematic review of prospective cohort studies.

Systematic reviewn = 14,325Brain Health

Systematic review of 35 cohort studies (n=14,325) assessing the association between vitamin B12 status and cognitive decline in older adults. No association was found with serum vitamin B12 concentrations, but newer biomarkers showed associations with increased risk of cognitive decline or dementia.

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2011·BMC geriatrics·Janneke P van Wijngaarden, Rosalie A M Dhonukshe-Rutten, Natasja M van Schoor, et al

Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence.

RCTn = 2,919Joint Bone Health

The B-PROOF study is a randomized double-blind placebo-controlled trial investigating the effect of vitamin B12 and folic acid supplementation on osteoporotic fracture incidence in 2919 elderly subjects with elevated homocysteine levels. The study aims to assess bone health, physical performance, nutritional status, and other health markers over two years.

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2010·BMC geriatrics·Wendy P J den Elzen, Gerda M van der Weele, Jacobijn Gussekloo, et al

Subnormal vitamin B12 concentrations and anaemia in older people: a systematic review.

Systematic reviewn = 16,185

Systematic review evaluating the association between subnormal vitamin B12 concentrations and anaemia in older people. The review included 25 studies, with inconsistent results from observational studies and no effect of vitamin B12 supplementation on haemoglobin concentrations in RCTs. Evidence of a positive association is limited and inconclusive.

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2026·Clinical epigenetics·Jhulia C N L da Mota, Lucas M Carvalho, Leticia L Souza, et al

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.

RCTn = 50Inflammation

This randomized, double-blind, placebo-controlled trial studied the effects of folic acid and vitamin B12 supplementation on DNA methylation in adipose tissue of premenopausal women with inactive SLE. The study found that supplementation significantly increased serum levels of both vitamins, with DNA methylation changes observed only in normal weight patients, suggesting obesity may create an 'epigenetic resistance' to micronutrient interventions.

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2024·Frontiers in Nutrition·N. Memon, G. Conti, E. Brilli, et al

Comparative bioavailability study of supplemental oral Sucrosomial® vs. oral conventional vitamin B12 in enhancing circulatory B12 levels in healthy deficient adults: a multicentre, double-blind randomized clinical trial

RCTNutrition

A multicentre, double-blind randomized clinical trial compared the bioavailability of Sucrosomial® vitamin B12 to conventional B12 supplements in healthy deficient adults. Sucrosomial® B12 was significantly more effective in increasing and maintaining higher serum B12 levels across all time points, surpassing the deficiency-borderline threshold within 24 hours of the first dose.

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2023·Journal of developmental origins of health and disease·Satyajeet P Khare, Ayush Madhok, Indumathi Patta, et al

Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA).

RCTn = 88Nutrition

The Pune Rural Intervention in Young Adolescents (PRIYA) trial studied the effects of vitamin B12 and multi-micronutrient supplementation on gene expression in cord blood mononuclear cells. The intervention improved maternal micronutrient nutrition and revealed 75 differentially expressed genes related to mitotic processes. Neonates in the B12+MMN group had the highest ponderal index.

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2022·European journal of nutrition·Annick P M van Soest, Ondine van de Rest, Renger F Witkamp, et al

DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial.

RCTn = 191Brain Health

Post-hoc analysis of the B-proof trial with 191 adults aged 65 or older, examining the effect of B-vitamin supplementation (400 µg folic acid and 500 µg vitamin B12) on cognitive ageing. The study found that the efficacy of B-vitamin supplementation in slowing cognitive decline was greater in participants with higher baseline plasma DHA levels.

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2022·Nutrition and health·Jaineet Singh Chhabra, Amandeep Juneja, Yana Etkin, et al

The effect of nutrition on stroke risk: A systematic review.

Systematic review

Systematic review analyzing the impact of nutritional intervention on stroke risk. Multiple studies showed an inverse relationship between consumption of vegetables and fruits and stroke risk. Vitamin B12 or a combination of B Vitamins was the most common supplement studied in stroke prevention, with one RCT showing B12 correlated with lower CIMT in healthy vegetarians.

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2021·The journal of prevention of Alzheimer's disease·H Chen, S Liu, B Ge, et al

Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial.

RCTn = 101Brain Health Inflammation

Randomized, single-blind, placebo-controlled trial of folic acid and vitamin B12 supplementation in 101 Alzheimer's disease patients. The supplementation improved cognitive performance and reduced inflammation markers compared to placebo.

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2021·Nutrients·Triantafyllos Didangelos, Eleni Karlafti, Evangelia Kotzakioulafi, et al

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial.

RCTn = 90

This randomized, double-blind, placebo-controlled trial investigated the effect of oral methylcobalamin (vitamin B12) supplementation in 90 patients with diabetic neuropathy over one year. The active group showed significant improvements in neurophysiological parameters, sudomotor function, pain score, and quality of life compared to the control group.

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2020·Complementary therapies in medicine·Swayamjeet Satapathy, Debapriya Bandyopadhyay, Binod Kumar Patro, et al

Folic acid and vitamin B12 supplementation in subjects with type 2 diabetes mellitus: A multi-arm randomized controlled clinical trial.

RCTn = 80Nutrition Hormone Health

This randomized, multi-arm, open-label clinical trial investigated the effects of folic acid and vitamin B12 supplementation on glycaemic control, insulin resistance, and serum lipid profile in 80 patients with type 2 diabetes. Groups receiving vitamin B12 showed significant improvements in HbA1c, plasma insulin, insulin resistance, and serum adiponectin compared to standard treatment. Serum homocysteine declined significantly in all supplementation groups, but no improvement in lipid profile was noted.

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2019·Lancet (London, England)·Donat R Spahn, Felix Schoenrath, Gabriela H Spahn, et al

Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.

RCTn = 505Nutrition

This RCT assessed the effect of a combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid on reducing RBC transfusions in patients with anaemia or isolated iron deficiency undergoing cardiac surgery. The treatment significantly reduced RBC transfusions and improved haemoglobin levels compared to placebo.

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2019·Medicine·Yubin Xu, Na Zhang, Shanshan Xu, et al

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy: A systematic review and meta-analysis (PRISMA-compliant article).

Meta-analysis

Systematic review and meta-analysis examining the effects of phenytoin monotherapy on serum levels of homocysteine, folate, and vitamin B12 in patients with epilepsy. Results showed increased homocysteine and decreased folate and vitamin B12 levels in phenytoin-treated patients compared to controls.

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2018·Transactions of the Royal Society of Tropical Medicine and Hygiene·Alexander J Layden, Kristos Täse, Julia L Finkelstein

Neglected tropical diseases and vitamin B12: a review of the current evidence.

Systematic review

This systematic review evaluates the evidence on the role of vitamin B12 in the etiology of neglected tropical diseases (NTDs). It includes ten studies, focusing on vitamin B12 status and helminthic infections, with limited research on vitamin B12 interventions in NTDs. The review highlights the need for larger prospective human studies to understand vitamin B12's role in NTD risk and severity.

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2017·Obesity surgery·H J M Smelt, S Pouwels, J F Smulders

Different Supplementation Regimes to Treat Perioperative Vitamin B12 Deficiencies in Bariatric Surgery: a Systematic Review.

Systematic reviewNutrition

Systematic review of different supplementation regimes to treat perioperative vitamin B12 deficiencies in bariatric surgery. The review suggests that 350 µg oral vitamin B12 is an appropriate dose to correct low levels in many patients, though further research is needed.

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2015·PLoS ONE·I. Kvestad, S. Taneja, T. Kumar, et al

Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial

RCTn = 422Brain Health

Randomized, double-blind trial of vitamin B12 and folic acid supplementation in 422 young North Indian children. Supplementation improved gross motor and problem-solving skills, particularly in stunted children, those with high plasma homocysteine, or younger than 24 months.

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2015·Internal medicine journal·S B Jung, V Nagaraja, A Kapur, et al

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

Meta-analysisBrain Health

Systematic review and meta-analysis evaluating the association between long-term use of acid-lowering agents and vitamin B12 deficiency. The analysis included four case-control studies and one observational study, finding a significant association between prolonged ALA use and vitamin B12 deficiency.

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2014·PloS one·Qilin Liu, Sheyu Li, Heng Quan, et al

Vitamin B12 status in metformin treated patients: systematic review.

Meta-analysisNutrition

Systematic review analyzing the effects of metformin on vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. Results showed that serum vitamin B12 concentrations were significantly lower in patients treated with metformin compared to those who received placebo or rosiglitazone, indicating a dose-dependent reduction of vitamin B12 by metformin.

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2013·Annals of nutrition & metabolism·Esmée L Doets, Paulette H In 't Veld, Anna Szczecińska, et al

Systematic review on daily vitamin B12 losses and bioavailability for deriving recommendations on vitamin B12 intake with the factorial approach.

Systematic reviewn = 52Nutrition

Systematic review of literature on daily losses and bioavailability of vitamin B12 to derive intake recommendations for adults and elderly. Pooled analysis showed daily losses of 0.13% of total body store, with absorption ranging from 4.5% to 83% depending on the source. Suggested vitamin B12 intake to compensate for losses ranges from 3.8 to 20.7 µg.

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2013·Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery·Shounak Majumder, Jose Soriano, Allan Louie Cruz, et al

Vitamin B12 deficiency in patients undergoing bariatric surgery: preventive strategies and key recommendations.

Systematic reviewNutrition

Systematic review of vitamin B12 deficiency in patients undergoing bariatric surgery, exploring the pathophysiology and effectiveness of various vitamin B12 formulations. Intramuscular vitamin B12 is the gold standard for deficiency, with high-dose oral cyanocobalamin considered for certain patients. Lower-dose daily supplementation may suffice for those undergoing restrictive procedures.

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2012·Epidemiologic reviews·Esmée L Doets, Janneke P van Wijngaarden, Anna Szczecińska, et al

Vitamin B12 intake and status and cognitive function in elderly people.

Systematic reviewBrain Health -

This systematic review evaluates the relationship between vitamin B12 intake and cognitive function in adults and elderly people. The review found no association or inconsistent associations between vitamin B12 intake and cognitive function, with meta-analysis showing no association between serum/plasma vitamin B12 levels and risk of dementia or cognitive scores.

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2010·European journal of nutrition·Snorri B Rafnsson, Ponnusamy Saravanan, Raj S Bhopal, et al

Is a low blood level of vitamin B12 a cardiovascular and diabetes risk factor? A systematic review of cohort studies.

Systematic reviewHeart Health Longevity

Systematic review of cohort studies assessing the association between low blood vitamin B12 levels and the risk of cardiovascular diseases and diabetes. Limited evidence was found that vitamin B12 deficiency increases the risk of mortality and morbidity from these conditions. The review suggests that current data do not support vitamin B12 supplementation for reducing these risks.

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2010·Expert opinion on pharmacotherapy·Emmanuel Andrès, Helen Fothergill, Mustapha Mecili

Efficacy of oral cobalamin (vitamin B12) therapy.

Systematic reviewNutrition

Systematic review evaluating the efficacy of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency. Evidence from randomized studies and cohort studies suggests oral cobalamin treatment can adequately treat deficiency, improving serum vitamin B12 levels and hematological parameters.

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2008·Drugs & aging·Emmanuel Andrès, Thomas Vogel, Laure Federici, et al

Update on oral cyanocobalamin (vitamin B12) treatment in elderly patients.

Systematic reviewNutrition

This systematic review evaluates the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. It confirms the efficacy of oral cobalamin therapy in treating cobalamin deficiency, avoiding the discomfort and cost of injections.

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2008·The Cochrane database of systematic reviews·Reem Malouf, John Grimley Evans

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

Systematic reviewBrain Health Mood -

Systematic review of eight RCTs examining folic acid supplementation, with or without vitamin B12, on cognitive function and mood in elderly people. No consistent evidence of benefit was found for unselected healthy or cognitively impaired older people. However, folic acid improved cognitive function in healthy elderly with high homocysteine levels and enhanced response to cholinesterase inhibitors in Alzheimer's patients.

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2005·Acta neurologica Taiwanica·Yu Sun, Mei-Shu Lai, Chien-Jung Lu

Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials.

Systematic review

Systematic review of seven randomized controlled trials assessing the effectiveness of vitamin B12 and methylcobalamin on diabetic neuropathy. Both forms showed beneficial effects on somatic symptoms like pain and paresthesia, with inconsistent effects on vibration perception and electrophysiological measures. More high-quality trials are needed to confirm these effects.

PubMedRead on PubMed
2003·The Cochrane database of systematic reviews·R Malouf, A Areosa Sastre

Vitamin B12 for cognition.

Meta-analysisBrain Health -

Meta-analysis of randomized double-blind trials assessing the effect of vitamin B12 supplementation on cognitive function in people with dementia and low serum vitamin B12 levels. The analysis found no statistically significant evidence of treatment effect on cognitive function compared to placebo.

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2003·The Cochrane database of systematic reviews·M Malouf, Evans J Grimley, Sastre A Areosa

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

Systematic reviewBrain Health -Mood -

Systematic review of randomized controlled trials examining the effects of folic acid supplementation, with or without vitamin B12, on cognition and mood in elderly healthy and demented people. The review found no beneficial effect of folic acid on cognition or mood, though folic acid plus vitamin B12 was effective in reducing serum homocysteine concentrations.

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2002·JAMA·Guido Schnyder, Marco Roffi, Yvonne Flammer, et al

Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial.

RCTn = 553Heart Health

Randomized, double-blind placebo-controlled trial of 553 patients evaluating the effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcomes after percutaneous coronary intervention. The therapy significantly decreased the incidence of major adverse events, primarily due to a reduced rate of target lesion revascularization.

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2000·Seminars in thrombosis and hemostasis·H P Willems, M den Heijer, G M Bos

Homocysteine and venous thrombosis: outline of a vitamin intervention trial.

RCTn = 600

The VITRO trial is a multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of homocysteine-lowering therapy using folic acid, vitamin B12, and vitamin B6 in 600 patients with a history of idiopathic deep vein thrombosis or pulmonary embolism. The trial aims to assess the recurrence of venous thrombosis.

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2025·The American journal of clinical nutrition·Sol Maja G Bjørkevoll, Maria O'Keeffe, Carolien Konijnenberg, et al

Infant vitamin B12 status and its predictors - cross-sectional baseline results from an ongoing randomized controlled trial.

Cross-sectionaln = 644Nutrition

Cross-sectional baseline results from an ongoing RCT describing vitamin B12 status in Norwegian infants aged 6-15 weeks using multiple biomarkers. A substantial proportion of infants showed biochemical signs of low vitamin B12 status, particularly among partially and exclusively breastfed infants compared to nonbreastfed infants.

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2025·Rhinology·M Kawabata, E Mori, N Yanagi, et al

Olfactory disorder after COVID-19 vaccination.

Systematic reviewn = 16

Systematic review of 16 cases of olfactory disorders following COVID-19 vaccination. Symptoms included anosmia, parosmia, hyposmia, ageusia, and dysgeusia, appearing within one week of vaccination. Treatments included vitamin B12, multivitamins, olfactory training, Kampo formula, and corticosteroids. No direct causal relationship between vaccination and olfactory disorders was established.

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2023·Nutricion hospitalaria·Li Zhou, Xue Bai, Jiagui Huang, et al

Vitamin B12 supplementation improves cognitive function in middle aged and elderly patients with cognitive impairment.

Case-controln = 115Brain Health

Prospective case-control study of 115 middle aged and elderly patients with cognitive impairment, comparing vitamin B12 supplementation to control. Vitamin B12 group showed significant improvement in cognitive performance, particularly in attention, calculation, and visual-constructional ability.

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2021·International Journal of Environmental Research and Public Health·Michela Cirillo, R. Fucci, Sara Rubini, et al

5-Methyltetrahydrofolate and Vitamin B12 Supplementation Is Associated with Clinical Pregnancy and Live Birth in Women Undergoing Assisted Reproductive Technology

Observationaln = 269Womens Health

Retrospective study of 269 Caucasian women undergoing ART, comparing vitamin B complex (5-methyltetrahydrofolate, vitamin B12, vitamin B6) supplementation to folic acid alone. Vitamin B complex was associated with higher rates of clinical pregnancy and live birth.

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2019·Aging clinical and experimental research·Ayman Zant, Hussain M Awwad, Jürgen Geisel, et al

Vitamin B12-fortified toothpaste improves vitamin status in elderly people: a randomized, double-blind, placebo-controlled study.

RCTn = 92Nutrition

RCT of 92 elderly subjects using vitamin B12-enriched toothpaste versus placebo to improve vitamin B12 status. The vitamin B12 group showed higher serum concentrations of vitamin B12 and holotranscobalamin, and lower plasma total homocysteine levels, indicating improved vitamin B12 status.

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2019·Nutrients·Ann-Kathrin Lederer, L. Hannibal, Manuel Hettich, et al

Vitamin B12 Status Upon Short-Term Intervention with a Vegan Diet—A Randomized Controlled Trial in Healthy Participants

RCTn = 53Nutrition

RCT with 53 healthy omnivore subjects randomized to a vegan or meat-rich diet for 4 weeks. The vegan diet led to a significant decrease in holo-TC, a biomarker of vitamin B12 status, while other metabolites remained unaffected. The study highlights the impact of a vegan diet on vitamin B12 metabolism.

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2018·Molecular nutrition & food research·Chanachai Sae-Lee, Sarah Corsi, Timothy M Barrow, et al

Dietary Intervention Modifies DNA Methylation Age Assessed by the Epigenetic Clock.

RCTn = 57Longevity

The study assessed DNA methylation patterns in intervention studies with folic acid + vitamin B12 and monomeric and oligomeric flavanols (MOF) in 44 and 13 participants, respectively. Folic acid + vitamin B12 increased global DNA methylation in unmethylated regions and reduced epigenetic age in women with the MTHFR 677CC genotype. MOF decreased methylation in highly methylated regions.

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2015·Clinical Epigenetics

The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects

RCTn = 87

This study was part of a randomized, placebo-controlled trial investigating the effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. The intervention group showed differential methylation in several regions compared to placebo, with significant changes in genes implicated in carcinogenesis and early embryonic development.

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2010·New Zealand veterinary journal·J M Furlong, J R Sedcole, A R Sykes

An evaluation of plasma homocysteine in the assessment of vitamin B12 status of pasture-fed sheep.

RCTn = 112Nutrition

RCT evaluating plasma homocysteine, methylmalonic acid, and vitamin B12 levels in pasture-fed sheep to assess vitamin B12 status and supplementation responsiveness. Supplemented lambs showed 40% greater liveweight gain compared to unsupplemented lambs. Homocysteine levels were not a reliable indicator of vitamin B12 deficiency or supplementation response.

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2008·Stroke·Marit S Nenseter, Thor Ueland, Kjetil Retterstøl, et al

Dysregulated RANK ligand/RANK axis in hyperhomocysteinemic subjects: effect of treatment with B-vitamins.

RCTHeart Health

The study examined the role of the RANKL/RANK axis in hyperhomocystinemia and the effect of B-vitamin supplementation. Folic acid treatment reduced gene expression of RANKL/RANK, and a combination of folic acid, vitamin B12, and vitamin B6 significantly lowered serum levels of soluble RANKL in hyperhomocysteinemic individuals, suggesting potential cardiovascular benefits.

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2006·Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer·Peter Ellis, Angela M Davies, William K Evans, et al

The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a systematic review and practice guideline.

Systematic review

Systematic review and practice guideline on chemotherapy for advanced malignant pleural mesothelioma. Recommends chemotherapy with pemetrexed and cisplatin, supplemented with vitamin B12 and folic acid, for improved response rates and survival.

PubMedRead on PubMed
2003·Journal of clinical oncology : official journal of the American Society of Clinical Oncology·Nicholas J Vogelzang, James J Rusthoven, James Symanowski, et al

Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.

RCTn = 456

Phase III RCT comparing pemetrexed plus cisplatin with cisplatin alone in 456 patients with malignant pleural mesothelioma. The pemetrexed/cisplatin arm showed superior survival time, time to progression, and response rates. Folic acid and vitamin B12 were added to reduce toxicity, significantly reducing toxicities without affecting survival.

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2003·Journal of internal medicine·Robert Clarke, Georgina Harrison, Sue Richards, et al

Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia.

RCTn = 149Brain Health -

RCT of 149 people at high risk of dementia, testing low-dose aspirin, folic acid plus vitamin B12, and vitamins E plus C. B-vitamins lowered plasma homocysteine by 30%, and antioxidant vitamins lowered isoprostane excretion by 26%. No effect on cognitive function was detected.

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2003·Journal of nephrology·Joyce M Gonin, Hien Nguyen, René Gonin, et al

Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.

RCTn = 114Heart Health -

Two prospective studies in hemodialysis patients tested high doses of folic acid, vitamins B6 and B12, intravenous folinic acid, and serine for hyperhomocysteinemia. Despite significant increases in plasma folate and vitamin B12, there was no significant change in total homocysteine levels, indicating these treatments were ineffective at lowering tHcy.

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2002·The British journal of nutrition·Frédéric Guay, J Jacques Matte, Christiane L Girard, et al

Effects of folic acid and vitamin B12 supplements on folate and homocysteine metabolism in pigs during early pregnancy.

RCT

The study investigated the effects of folic acid and vitamin B12 supplements on folate and homocysteine metabolism in gestating sows. Folic acid supplementation tended to decrease uterine and plasma homocysteine levels in occidental sows, while vitamin B12 supplementation increased plasma vitamin B12 concentrations but did not affect uterine or plasma composition. The study highlights the potential role of folic acid in reducing uterine homocysteine and the high levels of vitamin B12 in uterine secretions.

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1998·Arteriosclerosis, thrombosis, and vascular biology·M den Heijer, I A Brouwer, G M Bos, et al

Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers.

RCTn = 316Heart Health

RCT assessing the effects of vitamin supplementation on plasma homocysteine levels in 89 patients with venous thrombosis and 227 healthy volunteers. High-dose multivitamin supplements containing folic acid, hydroxycobalamin, and pyridoxine normalized homocysteine levels in most individuals, with folic acid alone showing similar efficacy.

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1996·British journal of obstetrics and gynaecology·N J Wald, A D Hackshaw, R Stone, et al

Blood folic acid and vitamin B12 in relation to neural tube defects.

Systematic reviewn = 135Womens Health

The study analyzed blood folic acid and serum vitamin B12 levels in relation to neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review. Results showed lower levels of folic acid and vitamin B12 in affected pregnancies, but no significant association was found between serum B12 and neural tube defects after adjusting for folic acid.

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1993·Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih·B Yu

Treatment of herpes zoster: recombinant alpha-2a-interferon versus acyclovir and vitamin therapy. Clinical Study Group on Interferon.

RCTn = 305

RCT comparing the efficacy of recombinant alpha-2a-interferon, acyclovir, and vitamin therapy (B12, B1, B2) in treating herpes zoster in 305 patients. Both interferon and acyclovir reduced pain and symptom duration more effectively than vitamin therapy. Side effects were noted in the interferon group.

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2025·Molecules·Magdalena Krawczyk-Coda, A. Zgoła-Grześkowiak, E. Stanisz

Quality of Vitamin B12 Supplements Regarding Vitamin Assay and Content of Heavy Metals

Study

The study describes a methodology for quantifying vitamin B12 in supplements using UV-Vis spectrophotometry and LC-MS/MS. It found discrepancies in the content or form of vitamin B12 in three out of ten supplements and assessed metal impurities, finding no risk from metals but highlighting the need for stricter quality control.

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2024·Inorganics·Rozan H Mehder, Elena de la Torre-Rubio, Isabel de la Cueva-Alique, et al

Fluorescent Vitamin B12–Platinum(II) Derivatives as Potential Metallotheranostic Agents for the Treatment and Imaging of Tumors

Study

The study reports on the design of fluorescent vitamin B12–metal conjugates for tumor-specific delivery of therapeutic and diagnostic agents. Two novel fluorescent cyanocobalamin–platinum(II) derivatives were generated, showing enhanced capability to inhibit cell viability compared to inactive metal precursors and non-fluorescent analogues.

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