Vitamin E

Introduction Overview

Generic Name

Vitamin E

Brand Name

Aqua-E, Aqua-E Concentrate, Aquasol E, Aquavite-E, Aqueous Vitamin E, E-400 Clear, Vitamin E Pure dl-Alpha, Xcellent E

Dosage Form

Oral capsule, oral liquid, oral solution, oral tablet, oral and topical oil

Drug Class

Vitamins

Pharmacokinetics

Absorption:
Vitamin E is primarily absorbed in the small intestine via a passive diffusion mechanism enhanced by bile salts and pancreatic secretions. Its absorption efficiency depends on the presence of dietary fat, as vitamin E is a fat-soluble antioxidant. Factors such as bile salt concentration, fat content in the diet, and pancreatic enzyme activity significantly influence absorption rates. Malabsorption syndromes, cholestatic liver diseases, or conditions like cystic fibrosis can impair absorption, leading to deficiency. Upon intestinal absorption, vitamin E is incorporated into chylomicrons for lymphatic transport.

Distribution:
After absorption, vitamin E is transported in chylomicrons via the lymphatic system into the bloodstream. It is distributed widely to tissues, with highest concentrations in adipose tissue, liver, skin, and muscles. Vitamin E is incorporated into very low-density lipoproteins (VLDL) and subsequently into low-density lipoproteins (LDL) and high-density lipoproteins (HDL), facilitating delivery to peripheral tissues. The tocopherol transfer protein (TTP) in the liver selectively binds alpha-tocopherol, regulating plasma and tissue levels. Vitamin E accumulates mainly in cellular membranes, where it acts to protect polyunsaturated fatty acids against oxidative damage.

Metabolism:
Vitamin E undergoes hepatic metabolism whereby it is initially hydroxylated by cytochrome P450 enzymes, particularly CYP4F2, leading to the formation of water-soluble metabolites excreted in bile and urine. The liver preferentially metabolizes and excretes non-alpha-tocopherol forms more rapidly, maintaining alpha-tocopherol as the predominant circulating form. Metabolic processes regulate vitamin E’s bioavailability and are influenced by genetic variations in metabolic enzymes and hepatic function.

Elimination:
Vitamin E metabolites are eliminated primarily via feces following biliary excretion. Renal elimination of vitamin E is minimal due to its lipophilicity. The half-life of alpha-tocopherol ranges between 13 to 62 hours, subject to dose, formulation, and individual metabolic rate. The enterohepatic circulation contributes to prolonged presence in the body. Impairments in bile flow or liver function may alter elimination kinetics, affecting plasma levels and biological activity.

Dosage Forms

Available Dosage Forms:
- Oral capsule: 33.5 mg, 90 mg, 100 international units (IU), 180 mg, 200 IU, 325 mg, 400 IU, 1000 IU, dl-alpha 400 IU, dl-alpha 1000 IU, with mixed tocopherols 1000 IU, with mixed tocopherols 200 IU, with mixed tocopherols 400 IU.
- Oral liquid: 75 IU (50 mg)/mL of d-alpha tocopherol with tocopherols and tocotrienols.
- Oral solution: 15 IU/0.3 mL.
- Oral tablet: 100 IU.
- Oral and topical oil: 100 IU/0.25 mL.

Dosages for Adults and Adolescents:
- For vitamin E deficiency (e.g., abetalipoproteinemia), doses approximately 100 mg/kg body weight or 5 to 10 grams of alpha-tocopherol per day are used.
- Dietary supplement RDA for adults (≥19 years) is 15 mg alpha-tocopherol (equivalent to 22.4 IU).
- Tolerable Upper Intake Level (UL) for adults is 1000 mg alpha-tocopherol (1500 IU) daily.

Specific Patient Populations:
- Pediatric dosing varies by age group with RDAs from 4 mg (6 IU) for infants 0–6 months up to 15 mg (22.4 IU) for adolescents 14–18 years.
- Pediatric ULs range from 300 mg (450 IU) for ages 1–8 years to 800 mg (1200 IU) for ages 14–18 years.
- Pregnant and breastfeeding women should consult with healthcare providers as dose requirements may differ.
- Patients with malabsorption syndromes or lipid metabolism disorders might require higher doses, tailored by clinical monitoring.
- Caution advised in patients with increased bleeding risk or on anticoagulant therapy; avoid doses exceeding recommended UL without supervision.

Mechanism Of Action

Vitamin E primarily acts as a potent lipid-soluble antioxidant, protecting cell membranes from oxidative damage by scavenging reactive oxygen species (ROS) and free radicals. Its molecular structure allows donation of hydrogen atoms from the hydroxyl group of the chromanol ring to lipid radicals, thus terminating lipid peroxidation chain reactions within polyunsaturated fatty acid residues of membrane phospholipids. This stabilizes cellular membranes and prevents oxidative degradation of lipids, proteins, and DNA.

At the cellular level, vitamin E localizes predominantly within lipid bilayers of membranes and lipoproteins, where it intercepts lipid peroxyl radicals, converting them into stable lipid hydroperoxides. This antioxidant action preserves membrane fluidity and integrity and modulates signal transduction pathways involved in inflammation and cell proliferation.

Biochemically, vitamin E influences gene expression and enzymatic activity linked to antioxidant defense systems, such as upregulation of glutathione peroxidase activities and modulation of protein kinase C activity. These biochemical interactions contribute to its potential roles in immune function regulation and inhibition of platelet aggregation.

Clinically, the antioxidant property of vitamin E has been associated with protection against oxidative stress-related pathologies, including neurodegenerative diseases, cardiovascular disorders, and certain inflammatory conditions. Comparative studies indicate vitamin E’s mechanism contrasts with other antioxidants like vitamin C, which act in aqueous environments, whereas vitamin E functions within lipid domains. Clinical trials assessing vitamin E supplementation have shown mixed outcomes, with efficacy depending on the disease context, dose, and formulation used.

Pharmacological Actions

Functions as a potent lipid-soluble antioxidant preventing oxidative damage in cell membranes.
Protects polyunsaturated fatty acids in cellular membranes from lipid peroxidation.
Stabilizes cell membranes and preserves membrane fluidity.
Modulates immune function by influencing lymphocyte proliferation and humoral responses.
Inhibits platelet aggregation and reduces thrombosis risk via biochemical pathways.
Regulates gene expression related to antioxidant defense enzymes.
Interacts with other antioxidants to maintain redox balance within cells.
Influences enzyme activities such as protein kinase C, affecting cell growth and differentiation.
Potentially protects against neurodegenerative and cardiovascular diseases due to antioxidant properties.
May improve microcirculation and vascular endothelial function.
Contributes to skin health through topical antioxidant effects.
Possesses anti-inflammatory properties by modulating cytokine production.
Supports red blood cell membrane stability, reducing hemolysis.
Enhances cellular repair mechanisms by preventing oxidative DNA damage.
May aid in mitigating photoaging and ultraviolet light–induced skin damage.

Therapeutic Or Clinical Uses

Treatment and prevention of vitamin E deficiency caused by various etiologies such as abetalipoproteinemia and fat malabsorption syndromes.
Dietary supplementation to meet recommended daily allowances in populations with inadequate intake.
Adjunct therapy in ataxia with vitamin E deficiency to improve motor control.
Supportive treatment in neurological disorders with oxidative stress components, e.g., Alzheimer's disease and tardive dyskinesia (experimental/alternative use).
Potential antioxidant therapy in nonalcoholic fatty liver disease to reduce oxidative injury.
Complementary management in beta-thalassemia to mitigate oxidative hemolysis.
Use in prevention of age-related macular degeneration as a nutritional supplement.
Supportive treatment in disorders like glucose-6-phosphate dehydrogenase deficiency to reduce hemolytic risk.
Alternative medicine use in premenstrual syndrome and menstrual pain (limited evidence).
Investigational use in reducing risk of bleeding in intracranial hemorrhage.
Potential role in managing symptoms of osteoarthritis and Parkinson's disease (research ongoing).
Topical application for skin disorders such as eczema and prevention of scarring post-surgery.
Adjunctive use in peripheral neuropathy and muscle disorders such as ALS (experimental).
Supportive care in cardiovascular disease through antioxidant mechanisms (limited conclusive evidence).
Exploratory uses in diverse conditions including asthma, dementia, depression, diabetes, and inflammatory bowel disease (unproven efficacy).

Side Or Adverse Effects

Nausea frequently noted at higher doses.
Bleeding complications including easy bruising, nosebleeds, and bleeding gums due to its anticoagulant properties.
Fatigue or feeling tired reported with elevated vitamin E intake.
Headache as a common mild side effect.
Allergic reactions characterized by hives, facial swelling, and respiratory difficulty are rare but potentially severe.
Increased risk of hemorrhagic stroke or bleeding in brain with excessive dosing.
Potential interactions may amplify bleeding risk when combined with anticoagulants.
Gastrointestinal disturbances such as abdominal cramps or diarrhea occasionally observed.
Hypotension or blood pressure alterations in susceptible individuals.
Muscle weakness reported rarely in case studies.
Rare dermatological reactions with topical formulations including rash or irritation.
Long-term high-dose use may interfere with vitamin K absorption and function.
Overdose can lead to hemorrhagic complications necessitating emergency intervention.
Excessive doses may alter thyroid hormone levels and metabolism.
Risk of drug interactions increasing adverse effects with other supplements or medications.

Precautions

Use with caution in individuals with bleeding disorders or those on anticoagulant or antiplatelet therapy.
Avoid concomitant administration with other supplements that affect coagulation, such as garlic, ginkgo, or omega-3 fatty acids without medical supervision.
Consult healthcare providers before use in presence of chronic diseases such as diabetes, cancer, cardiovascular disease, or kidney impairment.
Pregnant and breastfeeding women should seek medical advice for appropriate dosing and safety.
Careful dosing required in pediatric populations to avoid toxicity.
Discontinue vitamin E at least two weeks prior to surgical or dental procedures to reduce bleeding risk.
Monitor for signs of allergic reactions especially with topical preparations.
Avoid use with orlistat within two hours before or after vitamin E ingestion due to absorption interference.
Patients with retinitis pigmentosa or vitamin K deficiency should use under close medical supervision.
Avoid concurrent use of multiple vitamin E products to prevent overdose.
Evaluate risk-benefit balance if prescribing in individuals with history of stroke or cardiovascular disease.
Store oral liquids refrigerated after opening to maintain stability and potency.
Quality and purity may vary in over-the-counter supplements; source reputable products.
Use caution when combined with medications metabolized via cytochrome P450 pathways potentially affecting vitamin E metabolism.
Regular clinical monitoring is advised during high-dose therapy.

Warnings

Vitamin E supplementation may increase the risk of bleeding, especially in high doses or when combined with blood-thinning medications.
Not approved by the FDA for treatment of medical conditions; efficacy for many uses remains unproven.
Avoid unsupervised use in children; doses should be directed by healthcare professionals.
High doses may mask symptoms of vitamin K deficiency, leading to critical bleeding issues.
Discontinue use and seek emergency care if signs of allergic reactions occur: hives, swelling, difficulty breathing.
Taking multiple vitamin or mineral supplements concurrently without medical advice may cause adverse effects.
Use with caution in patients with cardiovascular conditions due to potential for altered hemostasis.
Vitamin E may reduce the efficacy of chemotherapeutic agents or interfere with cancer therapies.
Overdose symptoms include severe bleeding, requiring emergency evaluation.
Supplements may be contaminated or inconsistent in dosage; select products from reputable manufacturers.
Avoid use in combination with or shortly after administration of orlistat due to absorption issues.
Patients should inform healthcare providers about vitamin E use prior to surgical procedures.
Potential interactions with a wide range of prescription, OTC, and herbal drugs necessitate professional consultation.
Pregnancy and breastfeeding safety profiles are not well established; use only under medical supervision.
Excessive intake over prolonged periods may increase all-cause mortality according to some meta-analyses, warranting cautious use.

Contraindication

Known hypersensitivity or allergic reaction to vitamin E or formulation components.
Active bleeding disorders or patients with uncontrolled hemorrhagic conditions.
Patients on concurrent anticoagulant or antiplatelet therapy without appropriate medical supervision.
Vitamin K deficiency due to risk of exacerbated bleeding.
Before surgical or invasive procedures where vitamin E’s anticoagulant effect may increase bleeding risk unless discontinued as recommended.
History of hemorrhagic stroke or intracranial bleeding events without thorough risk assessment.
Children without medical indication or supervision.
Concurrent use with high-dose omega-6 fatty acid therapy without monitoring.
Severe liver disease impairing vitamin E metabolism and clearance.
Use contraindicated in patients with certain rare metabolic disorders affecting fat absorption and vitamin E distribution without specialist oversight.
Patients with certain inherited thrombophilic or platelet function disorders without specialist evaluation.
Absence of medical need or supplementation beyond UL without professional advice.
Known intolerance to any excipients in the vitamin E formulation.
Use in conditions with increased risk of clotting abnormalities should be contraindicated unless benefits outweigh risks.
Contraindicated in combination with selumetinib without medical supervision due to interaction potential.

Drug Interactions

Increased risk of bleeding when combined with anticoagulants such as warfarin, coumadin, Jantoven, or antiplatelet agents like clopidogrel (Plavix), aspirin, dipyridamole, ticlopidine, and alteplase.
Potential reduced absorption when taken concurrently with orlistat (alli, Xenical) if administered within 2 hours.
Additive anticoagulant effect and bleeding risk when used with herbal supplements affecting coagulation such as garlic, ginkgo biloba, ginger, horse chestnut, red clover, saw palmetto, and turmeric.
Interaction with omega-6 fatty acid supplements, possibly affecting coagulation and vitamin E metabolism.
Potential alteration in cytochrome P450 enzyme activity affecting metabolism of certain drugs and vitamin E levels.
May interfere with chemotherapeutic agents and reduce their efficacy (specific drugs require monitoring).
Possible interference with statins and niacin used for cholesterol management in antioxidant pathways.
Interaction with vitamin K antagonists increasing anticoagulant effect; mandates INR monitoring.
Combination with corticosteroids may alter antioxidant defenses.
Potential for diminished absorption or efficacy when co-administered with mineral oils and cholestyramine due to sequestration.
Synergistic or antagonistic effects with other fat-soluble vitamins such as vitamins A and D.
May interact with drugs affecting lipid metabolism or transport such as fibrates and bile acid sequestrants.
Avoid concurrent use with certain experimental agents such as selumetinib unless closely supervised.
Interactions with cyclosporine and tacrolimus may alter immunosuppressant levels.
Patients should disclose all medications and supplements to healthcare providers to avoid unidentified interactions.

Preparations Of The Drug

Aqua-E: oral capsules and liquids containing various concentrations of natural and synthetic vitamin E forms.
Aquasol E: aqueous vitamin E injectable and oral formulations primarily based on d-alpha-tocopherol.
Aqueous Vitamin E: water-dispersible formulations for enhanced bioavailability.
Vitamin E Pure dl-Alpha: synthetic racemic mixture of alpha-tocopherol in capsule or oil form.
Topical vitamin E oils: used for dermatologic application in preventing scars and oxidative skin damage.
Oral tablets available in standardized dosages (e.g., 100 IU tablets) for dietary supplementation.
Capsule forms with mixed tocopherols providing broader spectrum antioxidant activity.
Oral solutions and drops formulated for pediatric administration and ease of dosing.
Natural (d-alpha-tocopherol) and synthetic (dl-alpha-tocopherol) preparations differing in bioactivity and potency.
Concentrated solutions designed for treatment of deficiency states with high-dose regimens.
Combination formulations with other vitamins for broad-spectrum nutritional supplementation.
Pharmaceutical preparations compliant with regulatory quality standards ensuring purity and stability.
Herbal supplement forms marketed under various brand names with variabilities in concentration and excipients.
Preservative-free and hypoallergenic topical oils suitable for sensitive skin applications.
Vitamin E formulations available as over-the-counter dietary supplements or prescription products depending on the country.