Meta Information
ID:vitamin-e
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/dietary/high-fat-meal
Target name:
Meal Containing Fat
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As a fat-soluble vitamin, Vitamin E requires the presence of dietary fat and bile acids for proper absorption in the small intestine.
Actionable advice:
Vitamin E supplements should be taken with a meal that contains some fat (e.g., avocado, nuts, olive oil).
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
TP may be more bioavailable than TAc as intestinal hydrolysis and emulsification are not required.
Label source:
PubMed: Water-soluble all-rac α-tocopheryl-phosphate and fat-soluble all-rac α-tocopheryl-acetate are comparable vitamin E sources for swine. (PMID 29800244)
Action type:
informational_none
Target id:
/class/anticoagulants-antiplatelets
Target name:
Anticoagulants and Antiplatelets (e.g., Warfarin, Aspirin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin E has antiplatelet properties and can interfere with vitamin K-dependent clotting factors, significantly increasing the risk of bleeding when combined with these medications.
Actionable advice:
High-dose Vitamin E supplements (over 400 IU/day) should be avoided when taking blood-thinning medications; it is important to talk to a doctor.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The clinical significance of these changes warrants further investigation, but high doses of vitamin E may antagonize vitamin K.
Label source:
PubMed: Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. (PMID 15213041)
Action type:
avoid
Target id:
/procedure/surgery
Target name:
Upcoming Surgery
Severity:
major
Interaction type:
adverse
Nature:
temporal
Temporal spacing:
Hours before target:
336
Hours after target:
null
Description:
Due to its blood-thinning effects, Vitamin E can increase the risk of excessive bleeding during and after surgical procedures.
Actionable advice:
Vitamin E supplements should be discontinued at least 2 weeks before any scheduled surgery.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Because of the increased risk of bleeding, vitamin E should be discontinued in the perioperative period in any patient requiring surgery.
Label source:
PubMed: Current treatment options in cardiovascular medicine (2000)
Source url:
Exact phrase from label:
There is reason to believe that the extensive postoperative bleeding was due to vitamin E-induced inhibition of protein kinase C, which decreases platelet adhesion.
Label source:
PubMed: Ugeskrift for laeger (2005)
Source url:
Exact phrase from label:
A review of the medical literature on vitamin E found recent evidence demonstrating a marked decrease in platelet adhesiveness with megadose ingestion of vitamin E. It is concluded that this should be avoided in the perioperative period.
Label source:
PubMed: Archives of otolaryngology--head & neck surgery (1988)
Action type:
avoid
Target id:
/condition/bleeding-disorders
Target name:
Bleeding Disorders or Vitamin K Deficiency
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Individuals with pre-existing bleeding disorders or vitamin K deficiency are highly susceptible to the anticoagulant effects of Vitamin E, leading to a high risk of spontaneous bleeding.
Actionable advice:
Vitamin E supplementation should be avoided with a bleeding disorder or vitamin K deficiency.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
These risks are particularly significant for individuals with pre-existing health conditions such as heart failure, coagulation disorders, or a history of stroke.
Label source:
PubMed: Vitamin E (α-Tocopherol): Emerging Clinical Role and Adverse Risks of Supplementation in Adults. (PMID 40065887)
Action type:
avoid
Target id:
/condition/history-of-hemorrhagic-stroke
Target name:
History of Hemorrhagic Stroke
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to its anticoagulant properties, high-dose Vitamin E supplementation may increase the risk of a recurrent hemorrhagic stroke.
Actionable advice:
High-dose Vitamin E supplements should be avoided with a history of hemorrhagic stroke.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
An additional complication involves Vitamin E's anticoagulant effects, which have been shown to amplify the risk of bleeding when high-dose supplementation is combined with blood thinners such as warfarin and aspirin. Studies have linked high-dose Vitamin E supplementation to adverse outcomes, including enhanced risks of all-cause mortality, hemorrhagic stroke, cardiovascular events, and certain cancers.
Label source:
PubMed: Cureus (2025)
Source url:
Exact phrase from label:
With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.
Label source:
PubMed: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (2020)
Source url:
Exact phrase from label:
In this meta-analysis, vitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%. This differential risk pattern is obscured when looking at total stroke.
Label source:
PubMed: BMJ (Clinical research ed.) (2010)
Action type:
avoid
Target id:
/condition/retinitis-pigmentosa
Target name:
Retinitis Pigmentosa
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Clinical trial data suggests that high-dose Vitamin E supplementation (400 IU/day) may accelerate the progression of vision loss in individuals with retinitis pigmentosa.
Actionable advice:
Vitamin E supplements should be avoided with a diagnosis of retinitis pigmentosa.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSIONS: These results support a beneficial effect of 15,000 IU/d of vitamin A and suggest an adverse effect of 400 IU/d of vitamin E on the course of retinitis pigmentosa.
Label source:
PubMed: A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. (PMID 8512476)
Action type:
avoid
Target id:
/class/chemotherapy-radiation
Target name:
Chemotherapy and Radiation Therapy
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The potent antioxidant activity of Vitamin E may interfere with the efficacy of cancer treatments that rely on generating oxidative stress to destroy malignant cells.
Actionable advice:
High-dose antioxidant supplements, including Vitamin E, are best avoided during cancer treatment unless approved by an oncologist.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
DUBs promote cancer cell survival and drug resistance by modulating the ubiquitination, stability, and functional activity of central ferroptosis regulators, thereby enabling tumor cells to evade oxidative stress and treatment-induced cytotoxicity.
Label source:
PubMed: Deubiquitinases at the crossroads of ferroptosis and cancer therapy: mechanisms and therapeutic potential. (PMID 42171907)
Action type:
avoid
Target id:
/condition/prostate-cancer-risk
Target name:
High Risk for or History of Prostate Cancer
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The SELECT trial found that supplementation with 400 IU/day of synthetic Vitamin E was associated with an increased risk of prostate cancer in healthy men.
Actionable advice:
Men, especially those with a family history of prostate cancer, should avoid high-dose Vitamin E supplementation.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.
Label source:
PubMed: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). (PMID 21990298)
Action type:
avoid
Target id:
/intervention/vitamin-k2
Target name:
Vitamin K
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of Vitamin E (typically >800 IU/day) can antagonize the action of Vitamin K, impairing the synthesis of blood clotting factors and increasing bleeding risk.
Actionable advice:
High doses of Vitamin E are best avoided with Vitamin K deficiency or other bleeding risk factors.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
Taking vitamin E with vitamin K might keep vitamin K from working as it should.
Label source:
Anecdotal: Mayo Clinic
Action type:
avoid
Target id:
/class/statins
Target name:
Statins (especially when combined with Niacin)
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High-dose antioxidant cocktails containing Vitamin E have been shown to blunt the beneficial HDL-cholesterol-raising effects of statin and niacin combination therapy.
Actionable advice:
It is important to talk to a doctor about high-dose Vitamin E use while taking statins, particularly with niacin.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Results of a previous small study (n = 44) suggested that either a combination of an antioxidant cocktail [800 IU/day 2R,4'R,8'R-(RRR)-AT plus 1 g vitamin C, 25 mg beta-carotene, and 100 microg selenium] or individual antioxidant vitamins combined with simvastatin-niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N alone.
Label source:
PubMed: High-dose alpha-tocopherol therapy does not affect HDL subfractions in patients with coronary artery disease on statin therapy. (PMID 17234730)
Action type:
informational_none
Target id:
/class/bile-acid-sequestrants
Target name:
Bile Acid Sequestrants (e.g., Cholestyramine)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
These medications bind to bile acids in the intestine, which can also bind to and prevent the absorption of fat-soluble vitamins like Vitamin E.
Actionable advice:
Vitamin E is best taken at least 4 hours before or 4 hours after a bile acid sequestrant.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The routine administration of fat-soluble vitamins appears unnecessary but it is prudent to measure prothrombin time and serum vitamins A and E at intervals.
Label source:
PubMed: The effect of cholestyramine on intestinal absorption. (PMID 1168607)
Action type:
separate
Target id:
/intervention/orlistat
Target name:
Orlistat (Alli, Xenical)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Orlistat is a weight-loss drug that blocks the absorption of dietary fat, which consequently reduces the absorption of fat-soluble Vitamin E.
Actionable advice:
Vitamin E doses and Orlistat should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
STUDY OBJECTIVES: To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents.
Label source:
PubMed: Effects of orlistat on fat-soluble vitamins in obese adolescents. (PMID 12126214)
Action type:
separate
Target id:
/class/immunosuppressants
Target name:
Cyclosporine
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High doses of Vitamin E (especially as TPGS, a water-soluble form) can enhance the absorption of cyclosporine, potentially leading to toxic blood levels of the drug.
Actionable advice:
High-dose Vitamin E is best avoided when taking cyclosporine; it is important to talk to a doctor before combining them.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Improvement of cyclosporin absorption was sought by means of oral coadministration of d-alpha-tocopheryl-polyethylene-glycol-1000 succinate (TPGS), a water-soluble form of vitamin E which can form micelles.
Label source:
PubMed: Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. (PMID 1676779)
Action type:
avoid
Target id:
/intervention/vitamin-c
Target name:
Vitamin C
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin C can regenerate the antioxidant capacity of Vitamin E after it has neutralized a free radical, effectively recycling it for further use.
Actionable advice:
Taking Vitamin C and Vitamin E together can enhance their overall antioxidant effect.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Glutathione facilitates the regeneration of other antioxidants, such as vitamin C and vitamin E, through redox cycling.
Label source:
PubMed: Glutathione in Skin Aging and Tissue Regeneration: A Systematic Review of Molecular Mechanisms, Redox Modulation, and Biomedical Implications. (PMID 41900080)
Action type:
informational_none
Target id:
/intervention/selenium
Target name:
Selenium
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Selenium is a crucial component of the antioxidant enzyme glutathione peroxidase, which works in concert with Vitamin E to protect cell membranes from oxidative damage.
Actionable advice:
Co-administration of selenium and Vitamin E supports a comprehensive antioxidant defense system.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Selenium atom represents an integral component of the enzyme active site of different forms of glutathione peroxidase, which catalyzes conversion of hydrogen peroxide and organic hydroperoxides into the water and corresponding alcohols.
Label source:
PubMed: Selenium - its role in physiology and endocrinology and as organoselenium compounds in oncology: A minireview. (PMID 39572874)
Action type:
informational_none
Target id:
/intervention/coenzyme-q10
Target name:
Coenzyme Q10 (CoQ10)
Severity:
minor
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Both Vitamin E and CoQ10 are lipid-soluble antioxidants that protect mitochondrial and other cellular membranes from lipid peroxidation.
Actionable advice:
Taking Vitamin E with CoQ10 provides complementary antioxidant protection within cell membranes.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Plasma level of vitamin E (32.4 +/- 4.3 vs. 22.1 +/- 3.6 umol/L) and high density lipoprotein cholesterol (1.26 +/- 0.43 vs. 1.12 +/- 0.32 mmol/L) showed significant (p < 0.05) increase whereas thiobarbituric acid reactive substances, malondialdehyde (1.9 + 0.31 vs. 3.1 + 0.32 pmol/L) and diene conjugates showed significant reduction respectively in the CoQ group compared to control group.
Label source:
PubMed: Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. (PMID 12841346)
Action type:
informational_none
Target id:
/intervention/iron-supplements
Target name:
Iron Supplements (especially inorganic forms)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Inorganic iron (like ferrous sulfate) can promote the oxidation and destruction of Vitamin E in the digestive tract, potentially reducing its bioavailability.
Actionable advice:
Doses of Vitamin E and inorganic iron supplements are best separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Although vitamin E-deficient muscle was found to be more susceptible to peroxidative damage when stressed with iron and ascorbic acid, it was not possible to demonstrate that the damage occurring during contractile activity was mediated by free radicals.
Label source:
PubMed: Ciba Foundation symposium (1983)
Source url:
Exact phrase from label:
LDL oxidation was assessed by measuring the formation of conjugated dienes at 234 nm and oxidised lipids (cholesteryl linoleate hydroperoxide and 7-ketocholesterol) by HPLC. As expected, LDL enriched with α-tocopherol was oxidised more slowly than control LDL by Cu2+ at pH 7.4, but was not protected against oxidation by Cu2+ or Fe3+ or a low concentration of Fe2+ at pH 4.5 (it was sometimes oxidised faster by α-tocopherol with Cu2+ or Fe3+ at pH 4.5).
Label source:
PubMed: Free radical research (2020)
Source url:
Exact phrase from label:
Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment.
Label source:
PubMed: Chemistry and physics of lipids (2022)
Action type:
separate
Target id:
/class/anticonvulsants
Target name:
Enzyme-Inducing Anticonvulsants (e.g., Phenytoin, Phenobarbital)
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Certain older anticonvulsant medications can increase the metabolic breakdown of Vitamin E in the liver, potentially leading to lower serum levels over time.
Actionable advice:
If on long-term anticonvulsant therapy, consider monitoring Vitamin E levels with your doctor.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The serum vitamin E levels were lower in the handicapped than in controls. Among the handicapped, those treated with anticonvulsants showed much lower levels of serum vitamin E than those untreated.
Label source:
PubMed: Pediatric pharmacology (New York, N.Y.) (1980)
Source url:
Exact phrase from label:
The serum vitamin E level was 0.58 +/- 0.18 mg/dl in the treated and 0.67 +/- 0.17 mg/dl in the untreated children, indicating significantly lower levels in the treated patients (p less than 0.005).
Label source:
PubMed: Developmental pharmacology and therapeutics (1982)
Source url:
Exact phrase from label:
Five-day treatment with PB (75 mg/kg/day, IP) caused a significant increase in liver LPO levels (P less than 0.01), a decrease in plasma LPO levels (P less than 0.02), and a significant decrease in liver VE levels (P less than 0.05). It is suggested that PB plays an important role in lipid peroxidation in the liver by interfering with VE metabolism.
Label source:
PubMed: Pediatric pharmacology (New York, N.Y.) (1986)
Action type:
monitor
Target id:
/intervention/vitamin-a
Target name:
High-Dose Vitamin A
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Very high doses of Vitamin A can interfere with the absorption of other fat-soluble vitamins, including Vitamin E, as they compete for similar absorption pathways.
Actionable advice:
Very high doses of both Vitamin A and Vitamin E are generally best not taken simultaneously.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Vitamin A also significantly decreased the uptake of the other FSVs but, conversely, its uptake was not impaired by vitamins D and K and even promoted by vitamin E.
Label source:
PubMed: Food chemistry (2015)
Source url:
Exact phrase from label:
Concentrations of plasma alpha-tocopherol peaked earliest with D-alpha-tocopherol supplementation alone at 12 to 20 h after supplementation, but simultaneous supplementation with retinyl acetate resulted in lower plasma alpha-tocopherol concentrations.
Label source:
PubMed: Journal of dairy science (1997)
Source url:
Exact phrase from label:
Chicks were fed diets containing three levels of tocopherol, and control or high levels of retinyl palmitate for at least 24 days. Glutathione peroxidase activity in erythrocytes, plasma and liver was enhanced in tocopherol-depleted chicks, and in chicks fed high dietary vitamin A.
Label source:
PubMed: The Journal of nutrition (1982)
Action type:
avoid