Safety Profile
Known Safety Concerns
- Anticoagulant -- significant interaction with warfarin and antiplatelets
- High dose associated with increased all-cause mortality (HOPE-TOO trial)
- Increased hemorrhagic stroke risk at doses above 400 IU per day
- UL 1,000 mg per day of alpha-tocopherol
Contraindications
- Anticoagulant -- significant interaction with warfarin and antiplatelets
- High dose associated with increased all-cause mortality (HOPE-TOO trial)
Interactions
Information not yet available for this ingredient profile.
Evidence and Scientific Findings
Ingredient Overview
The natural form of alpha-tocopherol with approximately 2x the bioavailability of the synthetic dl-form. Higher doses are associated with increased all-cause mortality and hemorrhagic stroke risk per multiple meta-analyses. Has anticoagulant properties clinically relevant with warfarin. UL is 1,000 mg per day. High-dose supplementation is not recommended without medical supervision.
Biological and Chemical Classification
- Scientific Name
- d-alpha-tocopherol
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: Vitamin
- Evidence consistency: High consistency across studies (100%)
- Anticoagulant -- significant interaction with warfarin and antiplatelets
- High dose associated with increased all-cause mortality (HOPE-TOO trial)
- Increased hemorrhagic stroke risk at doses above 400 IU per day
- UL 1,000 mg per day of alpha-tocopherol
The available scientific evidence for Vitamin E (d-alpha Tocopherol) 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: 24 მარ 2026, 07:53
Evidence Distribution
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Observational / other LOW evidence YELLOWMembrane-anchoring engineering mediated the self-assembly of multifunctional nanocarriers: An efficient platform for astaxanthin delivery. ↗Si J et al.. Membrane-anchoring engineering mediated the self-assembly of multifunctional nanocarriers: An efficient platform for astaxanthin delivery.. Colloids Surf B Biointerfaces. 2026. PMID:41747347.PMID 41747347 ↗Journal Colloids Surf B BiointerfacesYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41747347/
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Observational / other LOW evidence YELLOWPreparation, Characterization, Pharmacokinetics, and Anti-Idiopathic pulmonary fibrosis activity of Bisdemethoxycurcumin liposomes. ↗Wang K et al.. Preparation, Characterization, Pharmacokinetics, and Anti-Idiopathic pulmonary fibrosis activity of Bisdemethoxycurcumin liposomes.. Eur J Pharm Biopharm. 2026. PMID:41605301.PMID 41605301 ↗Journal Eur J Pharm BiopharmYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41605301/
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Observational / other LOW evidence YELLOWHyaluronate-coated TPGS-g-chitosan nanoparticles for rheumatoid arthritis therapy: pharmaceutical development, anti-inflammatory activities, and bone regeneration studies. ↗Monika et al.. Hyaluronate-coated TPGS-g-chitosan nanoparticles for rheumatoid arthritis therapy: pharmaceutical development, anti-inflammatory activities, and bone regeneration studies.. Int J Biol Macromol. 2026. PMID:41317765.PMID 41317765 ↗Journal Int J Biol MacromolYear 2026Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41317765/
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Observational / other LOW evidence YELLOWSerum Liposoluble Vitamins (A, D, E) in Dogs with Chronic Biliary Tract Diseases Versus Healthy Dogs. ↗Habermaass V et al.. Serum Liposoluble Vitamins (A, D, E) in Dogs with Chronic Biliary Tract Diseases Versus Healthy Dogs.. Vet Sci. 2025. PMID:41472173.PMID 41472173 ↗Journal Vet SciYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41472173/
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Observational / other LOW evidence YELLOWBiomimetic Nanomicelles: Utilizing Peptide Transporters to Overcome Corneal Barrier for Treating Fungal Infection. ↗Sathe P et al.. Biomimetic Nanomicelles: Utilizing Peptide Transporters to Overcome Corneal Barrier for Treating Fungal Infection.. Mol Pharm. 2025. PMID:41115049.PMID 41115049 ↗Journal Mol PharmYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41115049/
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Observational / other LOW evidence YELLOWReinforced plant-derived lipid nanoparticles for oral precise epigenome editing in colonic diseases. ↗Gao Q et al.. Reinforced plant-derived lipid nanoparticles for oral precise epigenome editing in colonic diseases.. Sci Adv. 2025. PMID:41004579.PMID 41004579 ↗Journal Sci AdvYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/41004579/
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Observational / other LOW evidence YELLOWRedox-responsive self-targeting carrier-free nanotherapeutic agent with ROS storm for enhancing tumor oxidative stress. ↗Fu X et al.. Redox-responsive self-targeting carrier-free nanotherapeutic agent with ROS storm for enhancing tumor oxidative stress.. Colloids Surf B Biointerfaces. 2025. PMID:40882575.PMID 40882575 ↗Journal Colloids Surf B BiointerfacesYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40882575/
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Observational / other LOW evidence YELLOWAnticancer Activity of Paclitaxel-Loaded Mesoporous Silica Nanoparticles in B16F10 Melanoma-Bearing Mice. ↗Lee J et al.. Anticancer Activity of Paclitaxel-Loaded Mesoporous Silica Nanoparticles in B16F10 Melanoma-Bearing Mice.. Pharmaceutics. 2025. PMID:40871063.PMID 40871063 ↗Journal PharmaceuticsYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40871063/
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Observational / other LOW evidence YELLOWGlucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy. ↗Wang R et al.. Glucose-functionalized redox-responsive dihydroartemisinin prodrug nanosystem for targeted malaria therapy.. Int J Pharm X. 2025. PMID:40809063.PMID 40809063 ↗Journal Int J Pharm XYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40809063/
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Observational / other LOW evidence YELLOWSafety evaluation of d-u03b1-tocopheryl polyethylene glycol-1000 succinate (Vitamin E TPGS) as a food additive. ↗Castle L et al.. Safety evaluation of d-u03b1-tocopheryl polyethylene glycol-1000 succinate (Vitamin E TPGS) as a food additive.. EFSA J. 2025. PMID:40791650.PMID 40791650 ↗Journal EFSA JYear 2025Study type Observational / otherEvidence strength LOW evidencePubMed link https://pubmed.ncbi.nlm.nih.gov/40791650/
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 E (d-alpha Tocopherol). 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 moderate safety concern. Caution is advised, particularly at high doses or in sensitive populations.
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 Moderate classification for Vitamin E (d-alpha Tocopherol)
A score of 4.0 places this ingredient in the Moderate 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.