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Alpha-tocopherol

AEMPS

Fat-soluble vitamin E

ATC code: A11HA03(Tocopherol (vit E))

Brand names: Aquasol E

Updated · Methodology

Indications

A

Vitamin E deficiency

First line

First-line treatment for confirmed vitamin E deficiency. Indications: cystic fibrosis with pancreatic insufficiency, abetalipoproteinaemia, paediatric cholestatic liver disease, short bowel syndrome, ataxia with vitamin E deficiency (AVED). AEMPS approves oral doses expressed in international units (IU): the baseline dose in deficiency is 50 IU/day (maximum 300 IU), while 200–400 IU/day is reserved for malabsorption syndromes, cystic fibrosis and cholestasis, under plasma alpha-tocopherol monitoring.

Sources

  1. Cochrane Database Syst Rev: Vitamin E supplementation in people with cystic fibrosis. (2020)
  2. AEMPS: Ficha tecnica de Auxina E (alfa-tocoferol) (2023)
  3. Schuelke M: Ataxia with Vitamin E Deficiency. (1993)
  4. Orphanet J Rare Dis: Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers. (2010)

ICD-10: E56.0 · ICD-11: 5B58

C

Non-alcoholic steatohepatitis (NASH)

Individual decision

The one evidence-based use of vitamin E. The PIVENS RCT (NEJM 2010) in non-diabetic adults showed resolution of steatohepatitis at 800 IU/day, though without improvement in fibrosis; the paediatric TONIC RCT (JAMA 2011) missed its primary endpoint of sustained ALT reduction. 2023 and --EASO guidelines list vitamin E as an option in biopsy-proven non-alcoholic steatohepatitis without diabetes, not as first-line therapy: weight loss and lifestyle come first. Long-term high doses are linked to increased all-cause mortality, so the decision is individual and made under hepatology supervision.

Sources

  1. N Engl J Med: Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis (PIVENS) (2010)
  2. JAMA: Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents (TONIC) (2011)
  3. Hepatology: AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease (2023)
  4. J Hepatol: EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease (2016)

ICD-10: K76.0 · ICD-11: DB92.1

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Anti-aging and longevity

Not recommended

Vitamin E is sold for rejuvenation, immunity and longevity. There is no evidence base. The 2012 Cochrane review of antioxidants and the 2005 Miller meta-analysis showed that high-dose alpha-tocopherol does not extend life and raises all-cause mortality with long-term use. The only evidence-based use of vitamin E, biopsy-confirmed non-alcoholic steatohepatitis, is covered in a separate card and has nothing to do with anti-aging. If vitamin E was recommended for rejuvenation, consider seeking a second opinion.

Sources

  1. Cochrane: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases (2012)
  2. EFSA: Scientific Opinion on the substantiation of health claims related to vitamin E and protection of DNA, proteins and lipids from oxidative damage (ID 160, 162, 1947), maintenance of the normal function of the immune system (ID 161, (2010)
  3. Ann Intern Med: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality (2005)
F

Primary cardiovascular prevention in individuals without established CVD

Not recommended

Vitamin E was promoted for years as an antioxidant protecting the heart and vessels. HOPE-TOO (JAMA 2005, over 7000 patients aged 55 and older with vascular disease or diabetes) tested 400 IU/day alpha-tocopherol vs placebo for seven years: no difference in cardiovascular events, but more hospitalisations for heart failure. The Miller meta-analysis (Ann Intern Med 2005, 135 967 patients) linked doses above 400 IU/day with higher all-cause mortality. The 2012 Cochrane review of antioxidants found no reduction in cardiovascular events and signalled higher all-cause mortality. If vitamin E was prescribed for the heart, consider seeking a second opinion.

Sources

  1. Ann Intern Med (Miller et al.): Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality (2005)
  2. JAMA: Effects of long-term vitamin E supplementation on cardiovascular events and cancer (2005)
  3. Cochrane: Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases (2012)
  4. Eur Heart J: 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice (2021)
  5. JAMA: Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial (2008)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Alpha-tocopherol is absorbed in the small intestine within chylomicrons and handled by alpha-tocopherol transfer protein in the liver, where it is secreted into the bloodstream within VLDL. Its primary role is antioxidant defence of lipid membranes: the molecule donates a hydrogen to the peroxyl radical of a lipid chain and breaks the lipid peroxidation cascade. The alpha-tocopherol radical is regenerated by ascorbic acid and ubiquinol. High plasma concentrations interfere with vitamin K-dependent gamma-carboxylation of clotting factors, which explains the bleeding risk at megadoses.

Safety

Contraindications

  • Hypersensitivity to tocopherol or excipients
  • Neonatal vitamin K deficiency without prior K correction
  • Concomitant anticoagulant therapy without INR monitoring

Serious adverse effects

  • Haemorrhagic complications at doses above 400 IU/day combined with anticoagulants
  • Increased haemorrhagic stroke risk with long-term high-dose intake
  • Increased all-cause mortality at doses above 400 IU/day long-term (Miller 2005 meta-analysis)

Common adverse effects

  • Nausea
  • Diarrhoea
  • Abdominal cramps
  • Fatigue and weakness
  • Headache

Pregnancy: can you take Alpha-tocopherol?

AEMPS summary of product characteristics (section 4.6): there are no or limited data on high doses of vitamin E in pregnant women. Controlled studies in pregnant women have shown no risk to the fetus from vitamin E, but doses above the recommended daily intake (15 mg alpha-tocopherol equivalents) should not be used in pregnancy. Auxina E 200 and Auxina E 400 should not be used during pregnancy, and as a precaution Auxina E 50 should also be avoided.

Breastfeeding: can you take Alpha-tocopherol?

Compatible at physiological doses. Hale L1 up to 200 mg/day, L3 above 400 IU/day. Alpha-tocopherol enters breast milk and supports neonatal nervous system maturation. High doses in nursing women provide no additional benefit to the infant.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Drug–drug interactions

1 pair found. Sorted from critical to minor.

ModerateWarfarinVitamin K antagonist anticoagulants

Mechanism

NIH ODS describes two routes: vitamin E inhibits platelet aggregation and antagonises vitamin K-dependent clotting factors. With anticoagulants, high doses raise bleeding risk, especially when vitamin K intake is low. The exact clinically relevant amount is not established, though it probably exceeds 400 IU per day.

Symptoms

Bleeding gums, nosebleeds, bruising. The risk rises in someone who eats few leafy greens and takes high-dose vitamin E on their own.

Management

The vitamin E label advises against 400 IU a day or more in general, except in specific disorders. With warfarin, high vitamin E doses (300 mg a day or more) can prolong prothrombin time, so prothrombin time is monitored and the warfarin dose adjusted if needed (vitamin E SmPC). When vitamin E is started or stopped, check coagulation more often: the Spanish warfarin SmPC requires close coagulation control whenever a concomitant medicine is started or stopped, and the US label () asks for more frequent INR monitoring.

Sources

Pair details →Warfarin →

Label mentions4 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • Moderateanticoagulantesclass named in the label
    «- Anticoagulantes orales , como dicumarol, acenocumarol, warfarina: posible aumento del riesgo de sangrado; la administración concomitante con grandes dosis de vitamina E (300 mg al día o mayores)…»

    AEMPS, section 4.5 · Open on CIMA

  • ModerateWarfarin
    «- Anticoagulantes orales , como dicumarol, acenocumarol, warfarina: posible aumento del riesgo de sangrado; la administración concomitante con grandes dosis de vitamina E (300 mg al día o mayores)…»

    AEMPS, section 4.5 · Open on CIMA

  • anticonceptivos hormonalesclass named in the label
    «- Estrógenos (incluido anticonceptivos orales): su administración concomitante con vitamina E puede aumentar el riesgo de trombosis.»

    AEMPS, section 4.5 · Open on CIMA

  • Orlistat
    «- Orlistat : podría reducir la absorción de la vitamina E; se recomienda separar su administración al menos 2 horas.»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Alpha-tocopherol used for?

Alpha-tocopherol is evaluated for the following indications with varying evidence strength: Vitamin E deficiency (evidence tier A), Non-alcoholic steatohepatitis (NASH) (evidence tier C), Primary cardiovascular prevention in individuals without established CVD (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Alpha-tocopherol?

Common side effects of Alpha-tocopherol (≥ 1 in 100): Nausea, Diarrhoea, Abdominal cramps, Fatigue and weakness, Headache. See the Safety section for uncommon and serious reactions.

Is Alpha-tocopherol safe during pregnancy?

AEMPS summary of product characteristics (section 4.6): there are no or limited data on high doses of vitamin E in pregnant women. Controlled studies in pregnant women have shown no risk to the fetus from vitamin E, but doses above the recommended daily intake (15 mg alpha-tocopherol equivalents) should not be used in pregnancy. Auxina E 200 and Auxina E 400 should not be used during pregnancy, and as a precaution Auxina E 50 should also be avoided.

Is Alpha-tocopherol compatible with breastfeeding?

Compatible at physiological doses. Hale L1 up to 200 mg/day, L3 above 400 IU/day. Alpha-tocopherol enters breast milk and supports neonatal nervous system maturation. High doses in nursing women provide no additional benefit to the infant.

Who should not take Alpha-tocopherol?

Alpha-tocopherol is contraindicated in: Hypersensitivity to tocopherol or excipients; Neonatal vitamin K deficiency without prior K correction; Concomitant anticoagulant therapy without INR monitoring. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

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