02Research · Supplement

Vitamin E

Measured against the 58-marker panel. Human studies found an effect on 13, no change in 14 and conflicting results on 0; 31 have no result yet.

Most studied for

Non-alcoholic steatohepatitis (NASH) - nondiabetic adults

Supported 13
No effect 14
Conflicting 0
No result yet 31

BOverall evidence grade

925Studies tracked

229Meta-analyses

449Randomized trials

01Read first

Who should be careful

From the dossier's safety review: 14 cautions and 19 interactions, 13 rated serious. They summarize research and labels; they are not advice for you.

Cautions14

SeriousDiabetic NASH — VE monotherapy not guideline-supportedGrade A
PIVENS explicitly excluded T2DM patients; VE may improve insulin sensitivity.
SeriousVery low birthweight (VLBW) premature infants — high-dose parenteral/enteral VEGrade B
supraphysiologic serum levels (>3.5 mg/dL) specifically correlated with hemorrhagic complications
SeriousBiliary obstruction (obstructive jaundice, primary biliary cholangitis, primary sclerosing cholangitis)Grade C
Bile salt deficiency abolishes micellar solubilization required for VE absorption; oral alpha-tocopheryl acetate/succinate essentially non-absorbable
SeriousAbetalipoproteinemia / familial hypobetalipoproteinemiaGrade C
Absence of apoB-containing lipoproteins eliminates chylomicron formation; TPGS partially bypasses via alternative absorption pathway

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SeriousActive hemorrhagic disorders (hemophilia A/B, von Willebrand disease, severe thrombocytopenia <50,000/μL)Grade C
VE inhibits platelet aggregation (PKC/TXA2) and potentiates vitamin K antagonism via tocopherylquinone; additive hemorrhagic risk in already-impaired hemostasis
SeriousPre-surgical period (≥7 days before elective surgery)Grade C
Antiplatelet activity and vitamin K antagonism increase intraoperative and post-operative bleeding risk.
SeriousVitamin K deficiency (nutritional or malabsorptive) — uncorrectedGrade C
Tocopherylquinone inhibition of vitamin K-dependent carboxylase is additive with pre-existing vitamin K deficiency.
SeriousPharmacological-dose supplementation (>400 IU/day) in first trimester of pregnancyGrade C
Supplemental VE >400 IU/day in early pregnancy associated with increased risk of congenital heart defects in observational studies.
SeriousCystic fibrosis without concomitant pancreatic enzyme replacement therapy (PERT)Grade C
Exocrine pancreatic insufficiency severely impairs fat digestion required for VE micellar incorporation; standard tocopheryl acetate shows <10% absorption without PERT
SeriousConcurrent use of TPGS formulation with calcineurin inhibitors (cyclosporine, tacrolimus) without therapeutic drug monitoringGrade C
TPGS inhibits P-glycoprotein and CYP3A4, increasing calcineurin inhibitor bioavailability and risk of nephrotoxicity and immunosuppressant toxicity
ModerateHistory of prostate cancer or significantly elevated PSA (>4.0 ng/mL) in malesGrade A
SELECT trial (n=35,533): alpha-tocopherol 400 IU/day significantly increased prostate cancer incidence (HR 1.17, p=0.008); effect emerged ~year 3 and persisted
ModerateHigh-dose long-term supplementation (>400 IU/day) in healthy adults without clinical indicationGrade B
SELECT (400 IU/day): prostate cancer increase in healthy males. Mechanism unclear but may involve pro-oxidant shift, gamma-tocopherol displacement.
ModerateHepatic failure (Child-Pugh C)Grade D
Severe hepatic dysfunction impairs TTP-mediated tocopherol retention, CYP4F2-mediated catabolism, and biliary metabolite excretion; coexisting coagulopathy means VK-antagonism from tocopherylquinone is amplified
MinorRenal impairment (eGFR <30 mL/min) — monitoring advisory, not absolute contraindicationGrade C
Parent tocopherol is not renally cleared (high protein binding, large Vd); CEHC metabolites are renally excreted (~50–100 mL/min clearance).

Interactions19

SeriousWarfarinGrade B
Tocopherylquinone metabolite inhibits vitamin K-dependent carboxylase (VKOR); additive impairment of coagulation factor synthesis (II, VII, IX, X).
SeriousCyclosporineGrade C
VE (particularly TPGS form) inhibits P-glycoprotein (ABCB1)-mediated efflux in intestinal epithelium, increasing cyclosporine bioavailability; TPGS also inhibits CYP3A4-mediated first-pass metabolism
SeriousCyclosporine / tacrolimusGrade C
VE (particularly TPGS form) inhibits P-glycoprotein (ABCB1)-mediated efflux in intestinal epithelium and inhibits CYP3A4-mediated first-pass metabolism; increases cyclosporine and tacrolimus bioavailability.
ModerateOrlistatGrade B
Orlistat inhibits intestinal lipase, reducing dietary fat absorption; fat-soluble vitamin absorption (A, D, E, K) proportionally reduced.

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ModerateAntiplatelet agents (aspirin, clopidogrel, ticagrelor, dipyridamole)Grade C
VE inhibits protein kinase C-mediated platelet aggregation via independent pathway; additive antiplatelet effect when combined with ADP-receptor or COX-1 inhibitors
ModerateVitamin K (phylloquinone, menaquinones)Grade C
Competitive antagonism at vitamin K-dependent carboxylase.
ModerateBile acid sequestrants (cholestyramine, colestipol, colesevelam)Grade C
Bind bile acids in intestinal lumen, reducing bile salt pool available for micellar solubilization of fat-soluble vitamins; VE absorption reduced by 30–50%
ModerateMineral oil (liquid paraffin)Grade C
Non-absorbed mineral oil dissolves fat-soluble vitamins in intestinal lumen, carrying them into fecal stream without absorption; chronic mineral oil use causes fat-soluble vitamin deficiencies (A, D, E, K)
ModerateChemotherapy agents with oxidative mechanism (cisplatin, doxorubicin, alkylating agents)Grade D
Several cytotoxic agents (anthracyclines, platinum compounds, alkylating agents) generate reactive oxygen species as part of their antitumor mechanism; concurrent antioxidant supplementation including VE may theoretically reduce cytotoxic efficacy by scavenging ROS
ModerateAnticoagulants — direct oral (rivaroxaban, apixaban, dabigatran, edoxaban)Grade D
VE antiplatelet activity (PKC inhibition, PGI2 potentiation) provides additive bleeding risk atop DOAC anticoagulation; unlike warfarin, no pharmacokinetic INR-mediated interaction, but pharmacodynamic additive hemorrhagic risk
ModerateCYP3A4-metabolized drugs with narrow therapeutic index (cyclosporine, tacrolimus, midazolam, sirolimus, certain tyrosine kinase inhibitors)Grade D
However, TPGS formulation of VE is a validated P-gp inhibitor and may modestly inhibit CYP3A4 at excipient-level concentrations — mechanistically distinct from tocopherol itself.
ModerateDirect oral anticoagulants (rivaroxaban, apixaban, dabigatran, edoxaban)Grade D
VE antiplatelet activity (PKC inhibition, TXA2 reduction) provides additive bleeding risk atop DOAC anticoagulation via pharmacodynamic mechanism; unlike warfarin, no INR-mediated pharmacokinetic interaction, but pharmacodynamic additive hemorrhagic risk.
ModerateChemotherapy agents with ROS-dependent cytotoxic mechanism (cisplatin, doxorubicin, bleomycin, alkylating agents)Grade D
Several cytotoxic agents generate reactive oxygen species as part of their antitumor mechanism (anthracyclines via semiquinone redox cycling; platinum compounds via mitochondrial oxidative stress).
MinorHMG-CoA reductase inhibitors (statins)Grade C
2001, HATS trial). Magnitude clinically debated.
MinorHMG-CoA reductase inhibitors (simvastatin, atorvastatin, lovastatin)Grade C
Antioxidant co-supplementation concern (HATS trial, Cheung 2001): multi-antioxidant cocktail (VE 800 IU + C 1000 mg + beta-carotene + selenium) appeared to blunt statin + niacin-mediated HDL2 rise, possibly by attenuating oxidative signaling required for HDL remodeling.…
MinorMetforminGrade D
No direct pharmacokinetic interaction established. Indirect context: NASH trials (PIVENS) used VE as monotherapy comparator to metformin-adjacent pathways.
MinorCYP4F2 substrate drugsGrade D
VE and its isoforms compete for CYP4F2-mediated omega-hydroxylation; CYP4F2 V433M variant carriers have reduced baseline CYP4F2 activity, compounding interaction
MinorCYP2D6 substrates with narrow therapeutic index (tamoxifen, codeine, tramadol, tricyclic antidepressants, metoprolol)Grade D
CYP2D6 is not a primary VE metabolism enzyme. The primary clinical consideration is PGx-mediated: CYP2D6 poor metabolizers on tamoxifen (requires CYP2D6 bioactivation to endoxifen) already have reduced active metabolite formation.
MinorQT-prolonging drugs (amiodarone, sotalol, haloperidol, certain fluoroquinolones, ondansetron, azithromycin)Grade D
(3) VE anti-arrhythmic properties have been proposed mechanistically (antioxidant protection of cardiac membrane ion channels) but clinical data are absent and VE is not an anti-arrhythmic drug.

02What it moves

27 markers studied

One row per marker on the panel that human studies measured. Open a row for the direction, who was studied, and the papers.

Blood sugar4 of 4 studied

HbA1cNo changeGrade A

Studies of Vitamin E found no change in HbA1c.

21 studies linked

Studied in: T2DM, Adult, Mixed sex

VE-MA-003 (MA of 14 RCTs, n=714): WMD −0.12% (95% CI −0.31 to +0.07), non-significant. Grade A null finding from well-powered MA. VE is not a glycemic control intervention.

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Fasting glucoseNo changeGrade B

Studies of Vitamin E found no change in fasting glucose.

2 studies linked

Studied in: Adult, Mixed sex, T2DM, Non diabetic

GRADE CORRECTION: Source study VE-MA-003 is a meta-analysis of 14 RCTs (n=714). Per pipeline rules ≥2 RCTs = grade A. Null finding from well-powered MA is grade A evidence of no effect, not B.

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Fasting insulinNo changeGrade B

Studies of Vitamin E found no change in fasting insulin.

0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: T2DM, NAFLD, Adult

Inconsistent results across trials; modest insulin reduction in some NAFLD subgroups not replicated in diabetic populations. Insufficient pooled data for grade A.

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HOMA-IRNo changeGrade A

Studies of Vitamin E found no change in HOMA-IR.

37 studies linked

Studied in: NAFLD, T2DM, Adult, Insulin resistant

VE-MA-001 (18 RCTs) and VE-MA-003 (14 RCTs): WMD −0.21 (95% CI −0.48 to +0.06), marginal non-significant trend. Multiple MA sources with consistent null finding = grade A.

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Lipids5 of 6 studied

LDL-CNo changeGrade A

Studies of Vitamin E found no change in LDL-C.

Meta-analysis or review · 48 studies linked

Studied in: NASH, Nondiabetic, Adult, Adolescent

DUPLICATE: Two ldl_c entries exist — one lowercase (from corey_2015/ahmadi_2014 with grade B) and one uppercase LDL_C (from MAs with grade B). Should be merged. Combined evidence from VE-MA-002, VE-MA-006, corey_2015, ahmadi_2014 yields grade A (null finding across ≥2 RCTs and multiple MAs).

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HDL-CNo changeGrade A

Studies of Vitamin E found no change in HDL-C.

Meta-analysis or review · 32 studies linked

Studied in: NASH, Nondiabetic, Adult, Us multi center

DUPLICATE: Two hdl_c entries — lowercase (grade B from corey_2015/ahmadi_2014) and uppercase HDL_C (grade B from MAs). Should be merged. Combined = grade A.

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TriglyceridesNo changeGrade A

Studies of Vitamin E found no change in triglycerides.

44 studies linked

Studied in: Adult, Mixed sex, NAFLD, NASH

WMD −0.09 mmol/L (ns) across meta-analyses. Consistent null across VE-MA-002, VE-MA-004, corey_2015, ahmadi_2014. Grade A null finding.

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Total cholesterolNo changeGrade A

Studies of Vitamin E found no change in total cholesterol.

33 studies linked

Studied in: Adult, Mixed sex, NASH, Adolescent

Consistent null from VE-MA-002 (22 RCTs), corey_2015, ahmadi_2014. VE is not a lipid-modifying intervention. Grade A null finding.

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Lp(a)LowersGrade B

Vitamin E lowers Lp(a).

Human trials · 1 study linked

The effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression of lipoprotein(a) and oxidized low-density lipoprotein, lipid profiles and biomarkers of oxidative stress in pati (2017)

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Inflammation3 of 5 studied

hs-CRPLowersGrade A

Vitamin E lowers hs-CRP.

Meta-analysis or review · Small effect · 40 studies linked

Studied in: NAFLD, Metabolic syndrome, Adult, Mixed sex

WMD −0.42 mg/L (95% CI −0.71 to −0.13) from VE-MA-001; high heterogeneity (I²=78%). Effect modest and inconsistent outside NAFLD populations. Publication bias signal detected in funnel plot.

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IL-6LowersGrade A

Vitamin E lowers IL-6.

Meta-analysis or review · Small effect · 25 studies linked

Studied in: NAFLD, Metabolic syndrome, Adult

WMD −0.68 pg/mL (95% CI −1.24 to −0.12) from VE-MA-005; I²=69%. NF-κB mechanism supports direction but heterogeneity limits confidence.

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TNF-αLowersGrade A

Vitamin E lowers TNF-α.

Meta-analysis or review · Small effect · 13 studies linked

Studied in: NAFLD, Adult, Mixed sex

WMD −2.1 pg/mL (95% CI −3.8 to −0.4) from VE-MA-005. Consistent with NF-κB suppression mechanism.

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Liver4 of 6 studied

ALTLowersGrade A

Vitamin E lowers ALT.

Moderate effect · 2 studies linked

Studied in: NAFLD, NASH, Adult, Mixed sex

Effect driven by hepatic indication; benefit in non-hepatic populations not established

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ASTLowersGrade A

Vitamin E lowers AST.

Moderate effect · 2 studies linked

Studied in: NAFLD, NASH, Adult, Mixed sex

Consistent across multiple meta-analyses; magnitude slightly smaller than ALT reduction

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GGTLowersGrade A

Vitamin E lowers GGT.

Meta-analysis or review · Moderate effect · 12 studies linked

Studied in: NASH, Nondiabetic, Hp2-2, Adults

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ALPLowersGrade A

Vitamin E lowers ALP.

Human trials · Small effect · 29 studies linked

Studied in: NASH, Nondiabetic, Hp2-2, Adults

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Kidney2 of 4 studied

CreatinineNo changeGrade A

Studies of Vitamin E found no change in creatinine.

Meta-analysis or review · 10 studies linked

Studied in: Adult, NAFLD, Cardiovascular, Hemodialysis

Serum creatinine unaffected in PIVENS (96 weeks), HOPE substudy, and SPACE hemodialysis trial. VE is not nephrotoxic at standard therapeutic doses. Nephroprotective signal in contrast-induced nephropathy context (tasanarong_2013).

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eGFRNo changeGrade A

Studies of Vitamin E found no change in eGFR.

Meta-analysis or review · 8 studies linked

Studied in: Adult, Cardiovascular, NAFLD

eGFR stable across VE intervention trials at doses up to 800 IU/day. No nephrotoxicity signal. Nephroprotective signal in specific acute kidney injury contexts (contrast-induced, cisplatin) does not translate to eGFR improvement in chronic supplementation.

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Blood and iron2 of 7 studied

HemoglobinNo changeGrade A

Studies of Vitamin E found no change in hemoglobin.

Meta-analysis or review · 9 studies linked

Studied in: Thalassemia, Sickle cell, Hemodialysis

VE may modestly improve hemoglobin in hemolytic anemias (thalassemia, sickle cell) by protecting RBC membranes. Not a primary hematopoietic effect. Insufficient pooled data for direction assignment in general population.

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PlateletsNo changeGrade B

Studies of Vitamin E found no change in platelets.

Human trials · 5 studies linked

Studied in: Adult

VE inhibits platelet aggregation (function) but does not affect platelet count. Platelet count stable across VE supplementation trials.

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Hormones1 of 5 studied

TestosteroneLowersGrade A

Vitamin E lowers testosterone.

Meta-analysis or review · 13 studies linked

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Oxidative stress4 of 4 studied

MDALowersGrade A

Vitamin E lowers MDA.

Large effect · 2 studies linked

Studied in: NAFLD, Adult, Mixed sex, General population

Most consistent biomarker effect across all indications; directly reflects chain-breaking antioxidant mechanism of action

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F2-isoprostanesLowersGrade A

Vitamin E lowers F2-isoprostanes.

Moderate effect · 1 study linked

Studied in: NAFLD, Adult, Mixed sex

F2-isoprostanes considered most reliable in vivo oxidative stress marker; corroborates MDA findings

Pervez MA, Khan DA, Ijaz A, Khan S et al. (2018)

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8-OHdGLowersGrade B

Vitamin E lowers 8-OHdG.

Moderate effect · 4 studies linked

Studied in: Adult, Oxidative stress, NAFLD

8-OHdG (8-hydroxy-2'-deoxyguanosine) is a DNA oxidative damage marker. VE supplementation reduces 8-OHdG in oxidative-stress-driven conditions, consistent with lipid peroxidation chain-breaking mechanism. 17 studies in corpus.

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GlutathioneRaisesGrade A

Vitamin E raises glutathione.

Meta-analysis or review · Moderate effect · 30 studies linked

Studied in: NAFLD, Adult, Hemodialysis

WMD +0.31 μmol/g Hb (95% CI +0.18 to +0.44) from VE-MA-005. Reflects glutathione sparing via reduced oxidative load. 475 studies in corpus.

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Body2 of 2 studied

Blood pressureNo changeGrade A

Studies of Vitamin E found no change in blood pressure.

Meta-analysis or review · 1 study linked

Rodrigo R, Korantzopoulos P, Cereceda M, et al. (2018)

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Weight and BMINo changeGrade A

Studies of Vitamin E found no change in weight and BMI.

Meta-analysis or review · 18 studies linked

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Also measured28 outcomes

Outcomes these studies measured that are not on the shared panel, so they are not on the map.

Waist CircumferenceLowersGrade A

Vitamin E lowers waist Circumference.