Vitamin B12
Also known as: Cobalamin, Cyanocobalamin, Methylcobalamin, Adenosylcobalamin, Hydroxocobalamin, Vitamin B-12
This ingredient is classified as unclassified risk (GIRI score: 1.0/10).
Safety Profile
Known Safety Concerns
- Deficiency risk in vegans; impaired absorption with metformin; confirm active Methylcobalamin form
Contraindications
- Deficiency risk in vegans; impaired absorption with metformin; confirm active Methylcobalamin form
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
Vitamin B12 (cobalamin) is an essential water-soluble vitamin required for DNA synthesis (one-carbon methylation cycle), myelin sheath maintenance (neurological function), red blood cell formation (megaloblastic anaemia prevention), and energy metabolism via methylmalonyl-CoA mutase. Available in multiple forms: Cyanocobalamin (synthetic, stable, widely used), Methylcobalamin (biologically active, no conversion required — preferred for neurological conditions), Adenosylcobalamin (mitochondrial form), and Hydroxocobalamin (used clinically for cyanide poisoning treatment). Deficiency is common in vegans and vegetarians (dietary B12 is exclusively in animal products), elderly (reduced gastric intrinsic factor), and metformin users (B12 absorption impaired by metformin — monitor annually). Generally very safe even at high doses — water-soluble and renally excreted. No established UL (Tolerable Upper Intake Level) set by EFSA or IOM. Confirm active Methylcobalamin form on product label — particularly important for vegan supplement lines. Rare anaphylaxis with parenteral administration.
Biological and Chemical Classification
Information not yet available for this ingredient profile.
Mechanism of Action
Information not yet available for this ingredient profile.
Clinical Evidence of Effectiveness
Information not yet available for this ingredient profile.
Pharmacokinetics
Information not yet available for this ingredient profile.
Recommended Dosage
Information not yet available for this ingredient profile.
SETI — Scientific Evidence Transparency Index
Executive Summary — Ingredient Assessment
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or RCT)
- Main clinical benefit observed: Vitamins & Minerals
- Evidence consistency: High consistency across studies (100%)
- Deficiency risk in vegans; impaired absorption with metformin; confirm active Methylcobalamin form
The available scientific evidence for Vitamin B12 indicates notable safety signals that warrant caution. Use should be considered carefully and monitored, particularly in sensitive populations or alongside other medications.
Total SETI Score
High risk| Evidence quality | 10/40 |
| Evidence consistency | 20/20 |
| Safety signals | 0/20 |
| Study recency | 10/10 |
| Evidence transparency | 10/10 |
Evidence Summary
- 10 studies reviewed
- 0 high-quality studies (meta-analysis or systematic review)
- 0 studies identified benefits or no safety concern (GREEN)
- 10 studies reported limited or advisory safety evidence (YELLOW)
Evidence Policy
Only peer-reviewed scientific literature indexed in PubMed or comparable databases is included in this evaluation. Commercial websites, blogs, and marketing materials are excluded. All references include direct traceable links to source documents.
Last updated: 06 აპრ 2026, 12:09
Evidence Distribution
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Observational / other LOW evidence YELLOWCeliac Disease Unveiled by Palmoplantar Pigmentation. ↗Jain A. Celiac Disease Unveiled by Palmoplantar Pigmentation.. Am J Med. 2026. PMID:41936991.PMID 41936991 ↗Journal Am J MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41936991/
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Observational / other LOW evidence YELLOW[Thrombotic microangiopathy caused by vitamin B12 and folate deficiency (pseudo-TMA)]. ↗Ku00f3bor K et al.. [Thrombotic microangiopathy caused by vitamin B12 and folate deficiency (pseudo-TMA)].. Orv Hetil. 2026. PMID:41936033.PMID 41936033 ↗Journal Orv HetilYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41936033/
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Observational / other LOW evidence YELLOWRapidly Progressive Dementia Secondary to Vitamin B12 Deficiency: A Case Report. ↗Xu R et al.. Rapidly Progressive Dementia Secondary to Vitamin B12 Deficiency: A Case Report.. Curr Alzheimer Res. 2026. PMID:41935355.PMID 41935355 ↗Journal Curr Alzheimer ResYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41935355/
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Observational / other LOW evidence YELLOWMaternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions. ↗Connor KL et al.. Maternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions.. J Physiol. 2026. PMID:41935021.PMID 41935021 ↗Journal J PhysiolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41935021/
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Observational / other LOW evidence YELLOWSaliva as a Matrix for Primary Care: Feasibility and Scoping of its Use for Assessment of Nutrition and Inflammation. ↗Fahim SM et al.. Saliva as a Matrix for Primary Care: Feasibility and Scoping of its Use for Assessment of Nutrition and Inflammation.. Adv Nutr. 2026. PMID:41933704.PMID 41933704 ↗Journal Adv NutrYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41933704/
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Observational / other LOW evidence YELLOWPerception and acceptance of micronutrient-Fortified Bouillon among Non-Index Household Members: A longitudinal sub-study nested within a randomized trial in Northern Ghana. ↗Kyereh FK et al.. Perception and acceptance of micronutrient-Fortified Bouillon among Non-Index Household Members: A longitudinal sub-study nested within a randomized trial in Northern Ghana.. PLoS One. 2026. PMID:41931601.PMID 41931601 ↗Journal PLoS OneYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41931601/
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Observational / other LOW evidence YELLOWCase Report: Marchiafava-Bignami disease: anti-parietal cell antibodies as a potential etiological factor in a novel case presentation. ↗Zhang J et al.. Case Report: Marchiafava-Bignami disease: anti-parietal cell antibodies as a potential etiological factor in a novel case presentation.. Front Mol Biosci. 2026. PMID:41930251.PMID 41930251 ↗Journal Front Mol BiosciYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41930251/
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Observational / other LOW evidence YELLOWEvaluation of Vitamin B12 Deficiency Among Patients with Type 2 Diabetes Mellitus on Metformin at Hoima Regional Referral Hospital, Uganda. ↗Ali HO et al.. Evaluation of Vitamin B12 Deficiency Among Patients with Type 2 Diabetes Mellitus on Metformin at Hoima Regional Referral Hospital, Uganda.. Diabetes Metab Syndr Obes. 2026. PMID:41924591.PMID 41924591 ↗Journal Diabetes Metab Syndr ObesYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41924591/
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Observational / other LOW evidence YELLOWSex-Specific Heart Rate Variability Associations With Vitamin B12, Folate, and Iron Status. ↗u00d6zyau015far M et al.. Sex-Specific Heart Rate Variability Associations With Vitamin B12, Folate, and Iron Status.. Rev Cardiovasc Med. 2026. PMID:41923733.PMID 41923733 ↗Journal Rev Cardiovasc MedYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41923733/
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Observational / other LOW evidence YELLOWCharacteristics of women who fast during pregnancy: Findings from Kuwait Birth Cohort Study. ↗Al-Taiar A et al.. Characteristics of women who fast during pregnancy: Findings from Kuwait Birth Cohort Study.. Br J Nutr. 2026. PMID:41919344.PMID 41919344 ↗Journal Br J NutrYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41919344/
Score Transparency
0 of 10 approved references (score saturates at 10). More peer-reviewed studies = stronger evidence base.
Method: Q = number of approved references ÷ 10 (capped at 1.0)
Limited — mostly case reports or animal studies
Method: L = mean study-level weight across approved references. Level 1 (meta-analysis / systematic review) = 1.0; Level 2 (RCT) = 0.8; Level 3 (cohort/case-control) = 0.6; Level 4 (case report) = 0.4; Level 5 (animal / in-vitro) = 0.2.
Mixed or neutral — roughly equal benefit and risk signals
Method: D = (sum of risk-scored references − sum of benefit-scored references) ÷ total evidence score, then scaled from [−1, 1] to [0, 1]. 0.0 = pure benefit; 0.5 = neutral; 1.0 = pure risk.
One or more monitoring-level safety signals active
Method: S = 0.5 (neutral baseline) + sum of active signal severity deltas ÷ 10. Severity deltas: Critical = +2.0, High = +1.5, Moderate = +1.0, Low = +0.5. Capped at 1.0.
Final GIRI Score for Vitamin B12. Risk level thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
Full methodology & data sources
The GIRI Score is computed entirely from structured data — no editorial scoring or subjective weighting is applied at any step.
- References: Only approved references are counted. Each reference is assigned an evidence level (L1–L5) and a direction (risk / neutral / benefit) by the reference manager or AI classifier.
- Safety Signals: Sourced from regulatory agencies (FDA, EMA, Health Canada, TGA, and others) and pharmacovigilance databases. Only active signals count toward the score.
- Formula version: GIRI Score v3.7.0 — Q × L × D × S × 10.
- Limitations: The score reflects published evidence and recorded signals as of the last update date. It is not a clinical risk assessment and should not replace advice from a qualified healthcare professional.
Risk Level Classification
Based on available regulatory signals and scientific evidence, this ingredient presents a low safety concern under normal conditions of use.
0–3.0
3.0–5.5
5.5–7.5
7.5–10
The score pin shows exactly where this ingredient falls on the fixed risk scale.
What drove the Low classification for Vitamin B12
A score of 1.0 places this ingredient in the Low band. Thresholds: Low 0–3.0 · Moderate 3.0–5.5 · High 5.5–7.5 · Critical 7.5–10.
0 approved references.
Limited — mostly case reports or animal studies (Level 4–5).
Neutral or mixed — benefit and risk signals roughly balanced.
No active signals — S component is at neutral baseline (0.5), contributing no extra risk weight.
No major regulatory restrictions or advisories recorded across monitored jurisdictions (FDA, EMA, Health Canada, TGA, and others).
How are the Low / Moderate / High / Critical thresholds defined?
The four risk levels are fixed score bands. A score is assigned to exactly one level based on where it falls:
| Level | Score | Meaning |
|---|---|---|
| LOW | 0.0 – 2.9 | Sparse or predominantly beneficial evidence. No active safety alerts. |
| MODERATE | 3.0 – 5.4 | Mixed signals — some risk alongside benefit. Caution at high doses or in sensitive groups. |
| HIGH | 5.5 – 7.4 | Multiple studies or regulatory alerts documenting adverse effects. Professional oversight recommended. |
| CRITICAL | 7.5 – 10 | Regulatory restrictions in one or more major jurisdictions. Serious documented harm. Avoid without specialist supervision. |
Thresholds are fixed constants (GIRI_Score_Utils::LEVEL_THRESHOLDS). They do not change per ingredient and are never subject to editorial adjustment.