Vitamin/Ancillary

Vitamin B12

Research Reagent · Laboratory Use Only

Quick Answer

What does research show about Vitamin B12's role in neurological and metabolic health?

Research indicates Vitamin B12 (cobalamin) is essential for DNA synthesis, myelin sheath maintenance, and one-carbon metabolism. Studies published in PubMed-indexed journals link B12 deficiency to peripheral neuropathy, megaloblastic anaemia, and elevated homocysteine. B12 functions as a cofactor for methionine synthase and methylmalonyl-CoA mutase, supporting neurological integrity and red blood cell formation.

PMID42042873↗DOI10.1038/nrgastro.2010.105↗⟳ Reconstitution Calculator
Scientific AbstractPMID 42042873 · 2010

Background Objectives

Vitamin B12 deficiency is a common but often underdiagnosed complication in patients with type 2 diabetes (T2D) undergoing long-term metformin therapy. Accurate early prediction could enable targeted screening and timely intervention. This study aimed to develop and interpret a machine learning model for predicting vitamin B12 deficiency in metformin-treated patients with T2D, using eXtreme Gradient Boosting (XGBoost).

Methods

A retrospective cross-sectional study was conducted at a single endocrinology centre (La Rabta University Hospital, Tunis, Tunisia). Patients with T2D treated with metformin for at least three years were included (n = 257); those with conditions independently affecting vitamin B12 metabolism were excluded. Vitamin B12 deficiency was defined as a serum B12 level below 150 pmol/L or a borderline level (150-221 pmol/L) with concurrent hyperhomocysteinemia (>15 μmol/L). XGBoost was selected after comparison with Logistic Regression (L2), Random Forest, and Support Vector Machine on the same 5-fold stratified cross-validated pipeline. Hyperparameters were optimized via Bayesian search (100 iterations × 5-fold stratified cross-validation), with the Matthews correlation coefficient (MCC) as the primary optimization metric to account for class imbalance. Model interpretability was achieved using SHapley Additive exPlanations (SHAP). Discrimination and calibration were assessed on an independent test set using bootstrap 95% confidence intervals (2000 resamples).

Results

Of 257 patients, 95 (37.0%) presented with vitamin B12 deficiency. On the independent test set (n = 52), the optimized XGBoost model achieved an ROC-AUC of 0.671 [95% CI: 0.514-0.818], sensitivity of 0.737 [95% CI: 0.533-0.938], specificity of 0.545 [95% CI: 0.375-0.710], MCC of 0.273 [95% CI: 0.018-0.517], and a Brier Score of 0.259. SHAP analysis identified HbA1c, microalbuminuria, autonomic neuropathy, BMI, DN4 score, and fasting glucose as the most influential predictors. Nonlinear SHAP interaction plots revealed an increased predicted risk in patients with low HbA1c combined with a high cumulative metformin dose.

Conclusions

The XGBoost-SHAP framework provided interpretable predictions of vitamin B12 deficiency in patients with T2D on metformin, identifying key clinical profiles for targeted screening. External multi-centre validation is required before clinical deployment.

Source:10.1038/nrgastro.2010.105
Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Vitamin B12 Deficiency in Metformin-Treated Type 2 Diabetes?

Vitamin B12 deficiency is a common metabolic complication in patients with type 2 diabetes (T2D) undergoing long-term metformin therapy, defined as serum B12 levels below 150 pmol/L or borderline levels (150–221 pmol/L) with concurrent hyperhomocysteinemia. This study developed a machine learning prediction model to enable early identification and targeted clinical intervention in at-risk populations.

Mechanism of Action

Metformin impairs vitamin B12 absorption through effects on gastric calcium-dependent ileal B12 binding and disruption of intrinsic factor signaling in the terminal ileum. Long-term exposure (≥3 years) reduces serum B12 concentrations and elevates homocysteine metabolism, a marker of functional B12 deficiency. The interplay between glycemic control (HbA1c), cumulative metformin dosage, and diabetic microvascular complications (microalbuminuria, autonomic neuropathy) further modulates B12 bioavailability and cellular uptake.

Observed Laboratory Results

  • Model discrimination: XGBoost achieved ROC-AUC of 0.671 [95% CI: 0.514–0.818] with sensitivity of 0.737 and specificity of 0.545 on independent test set (n=52), outperforming Logistic Regression, Random Forest, and Support Vector Machine classifiers.

  • Deficiency prevalence: 95 of 257 patients (37.0%) met criteria for vitamin B12 deficiency, with diagnosis confirmed by serum B12 <150 pmol/L or borderline levels with hyperhomocysteinemia (>15 μmol/L).

  • Key predictive interactions: SHAP analysis identified HbA1c, microalbuminuria, autonomic neuropathy, BMI, DN4 neuropathy score, and fasting glucose as top predictors; nonlinear interaction plots revealed increased predicted risk in patients with low HbA1c combined with high cumulative metformin dose.

Clinical Implications

The XGBoost-SHAP framework provides interpretable risk stratification for vitamin B12 deficiency screening in T2D populations on chronic metformin therapy. However, external multi-centre validation is required before clinical deployment.

Clinical Research Parameters
10 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

Registered Clinical Trials
ClinicalTrials.gov ↗
NCT07268508 ↗
RECRUITINGN/An=60

Impact of a Pro-diversity Gut Microbiota Diet After a Bariatric Surgery on Gut Microbiota, Eating Behaviour and Sensory Function

Bariatric surgery is the most effective treatment for long-term weight loss and reducing obesity-related health risks. It alters the gastrointestinal tract as well as metabolic and hormonal functions, influencing eating behaviour. However, weight loss outcomes and long-term maintenance vary between patients, likely due to changes in the gut microbiota. Dietary recommendations aimed at improving mi

Study Interventions
Nutritional counseling
Primary Endpoints
Microbiota diversity 12 months after surgery
Study Period
2025-11-05 → 2029-04-05
NCT03544671 ↗
COMPLETEDN/An=220

Effect of Vitamin D3 Supplementation in Children From 12 to 30 Months of Age.

Background Vitamin D (VD) is essential for calcium absorption, bone health and growth in children. In a national representative sample authors found mean serum concentration of 25-Hydroxi-Vitamin-D (25-OH-D) of 59 nmol/L, in children \< 5 y of age. Prevalence deficiency of VD under 50 nmol/L was 33%, which means that 3 million preschool- age children have VD deficiency in Mexico. Additionally, les

Study Interventions
Vitamin D
Primary Endpoints
Chanche in 400UI,of vitamin D2 over 25-Hidroxi Vitamin D; Chanche in 800UI,of vitamin D2 over 25-Hidroxi Vitamin D
Study Period
2016-09-15 → 2017-12-21
NCT03372447 ↗
COMPLETEDPhase IVn=13

Megadose of Hydroxocobalamin for the Treatment of Pernicious Anemia

Demonstrate the effectiveness of a single dose of a multivitamin complex for the treatment of megaloblastic anemia

Study Interventions
Hydroxocobalamin 10,000mcg, Thiamin 100mg, Pyridoxine 50mg
Primary Endpoints
Hematologic response; Duration of hematologic response
Study Period
2017-12-27 → 2019-12-01
NCT00727571 ↗
COMPLETEDN/An=815

LEARN-6™: A Prospective, Observational Nursing Home Study

This is a prospective, multicenter, observational, hypothesis-generating study exploring mobility, Quality of Life and other physical performance measures among older, long-term stay Nursing Home residents with CKD, with versus without anemia. Enrolled patients will participate in the study up to a total of 26 weeks and be assessed at Weeks 1, 2, 14 and 26/End of Study. Based upon Week 1 hemoglobi

Study Interventions
Observations
Primary Endpoints
Total Distance Walked or Wheeled in a Maximum of 10 Minutes at Each Visit
Study Period
2006-09 → 2008-07
NCT07021248 ↗
RECRUITINGPhase IVn=249

A Randomized Controlled Trial Evaluating the Impact of Procedure-Specific Bariatric Supplements on Micronutrient Status and Vitamin B6 Hypervitaminosis Following Metabolic and Bariatric Surgery

Obesity is a complex, multifactorial chronic disease with an escalating global incidence, impacting over 650 million adults worldwide. It is closely linked to a variety of metabolic, cardiovascular, and musculoskeletal diseases, and is a leading contributor to preventable morbidity and mortality. Metabolic and Bariatric Surgery (MBS) stands out as the most effective long-term intervention for obes

Study Interventions
Elan Believe, Elan Compass, Elan Supreme
Primary Endpoints
The prevalence of vitamin B6 hypervitaminosis
Study Period
2025-06-15 → 2026-06
NCT07050342 ↗
NOT YET RECRUITINGN/An=84

Evaluation of the Specialized Clinic for Nutrition and Mental Health: A Pilot Study

The goal of this observational pilot study is to learn how personalized nutrition-focused care can help people with mental and psychosomatic health problems. This study takes place in Europe's first outpatient clinic that focuses on how diet affects mental well-being. The main questions the study aims to answer are: Does care at this clinic help lower participants' stress levels over one year?

Study Interventions
Personalized Nutrition-Based Psychosomatic Care
Primary Endpoints
Change in perceived stress levels measured by the Perceived Stress Scale (PSS-10)
Study Period
2025-12-01 → 2028-12-01
NCT04170205 ↗
UNKNOWNN/An=450

Causes Associated With Small Fiber Neuropathy (SFN).

Small fiber neuropathy (SFN) is an injury of cutaneous nerve fibers, mainly by a decrease in their density within the cutaneous tissue. The symptomatology associated with this SFN is broad with symptoms that are essentially sensory, but also autonomic. The etiologies of SFN are numerous (diabetes, drug, infectious, immunological...) and clinically non-specific, justifying a broad etiological asses

Primary Endpoints
Prevalence of etiologies associated with SFN
Study Period
2019-11-15 → 2020-04-30
NCT05211375 ↗
RECRUITINGPhase IIIn=130

Comparisons of Metabolic Effect of Sleeve Gastrectomy With Duodenojejunal Bypass and Sleeve Gastrectomy (MEDUSA): A Multicenter Randomized Controlled Trial

In this study, the effects of SG with DJB and SG alone for the treatment of type 2 diabetes mellitus (T2DM) will be compared in patients other than the two groups at both extremes who are expected to show excellent effects of metabolic surgery with SG alone (mild T2DM) and who need SG with DJB (severe T2DM). This study is to target patients with poor blood sugar control despite current medical tr

Study Interventions
Duodenojejunal bypass, Sleeve gastrectomy
Primary Endpoints
Complete remission rate of type 2 diabetes
Study Period
2022-01-03 → 2036-01-03
NCT06175130 ↗
COMPLETEDN/An=846

Cross-sectional Dietary Intake Survey on Ivorian School-Aged Children and Women of Reproductive Age

A cross-sectional dietary intake study was conducted with 423 Ivorian school aged children (SAC, 6-12 years) and 423 women of reproductive age (WRA, 15-49 years) from four cities, recruited by two-stage random sampling.

Primary Endpoints
Mean usual nutrient intake per day
Study Period
2021-02-01 → 2021-02-28
NCT04740346 ↗
RECRUITINGN/An=886

Survival Rates and Quality of Life According to Follow-up Period After Gastrectomy for Gastric Cancer (STOFOLUP)

This study is a multi-center, prospective, randomized controlled study. The aim of this study is to compare survival rates and to observe quality of life and nutritional status according to follow-up period in patients who underwent radical gastrectomy for stage 2 or 3 gastric cancer.

Study Interventions
Computed tomography, Chest X-ray, and blood test
Primary Endpoints
3-year overall survival
Study Period
2021-07-05 → 2026-06-30
Research Compliance Notice

All data presented on this page is for laboratory research purposes only. Vitamin B12 is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 42042873) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.

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