Introduction
Vitamin E is a fat-soluble vitamin that functions primarily as an antioxidant in the human body. It exists in eight different forms (four tocopherols and four tocotrienols), with alpha-tocopherol being the most biologically active form in humans. While primarily obtained through diet, vitamin E is also available as a dietary supplement and prescription medication for specific deficiency states.
Mechanism of Action
Vitamin E's primary mechanism of action involves its function as a chain-breaking antioxidant that prevents the propagation of free radical reactions in biological membranes. It donates a hydrogen atom from its chromanol ring to lipid peroxyl radicals, forming a tocopheryl radical that is relatively stable and can be regenerated back to active vitamin E through interaction with other antioxidants like vitamin C. Additionally, vitamin E demonstrates anti-inflammatory properties, inhibits platelet aggregation, and enhances immune function through various cell signaling pathways.
Indications
FDA-approved indications:- Treatment of vitamin E deficiency in patients with abetalipoproteinemia
- Prevention and treatment of vitamin E deficiency in patients with chronic cholestasis, hepatic disease, short bowel syndrome, or cystic fibrosis
- Antioxidant supplementation (controversial efficacy)
- Potential reduction in cardiovascular risk (no conclusive evidence)
- Neurological conditions (limited evidence)
- Eye health (limited evidence for age-related macular degeneration)
- Skin conditions (topical application)
Dosage and Administration
Standard dosing:- Adults: 60-75 IU daily for supplementation; 60-75 IU/day up to 100 IU/kg/day for deficiency treatment
- Children: 1 IU/kg/day for prevention; 1 IU/kg/day up to 100 IU/kg/day for treatment
- Oral administration with food to enhance absorption
- Available forms: capsules, tablets, liquid drops, topical formulations
- Prescription forms: Aquasol E (water-miscible form) for malabsorption conditions
- Renal impairment: No dosage adjustment required
- Hepatic impairment: Use with caution in severe impairment
- Pregnancy: Recommended dietary allowance is 15 mg (22.4 IU) daily
- Lactation: Recommended dietary allowance is 19 mg (28.4 IU) daily
Pharmacokinetics
Absorption: Requires bile salts for absorption; occurs in small intestine via passive diffusion (20-60% absorption efficiency) Distribution: Distributed via chylomicrons and lipoproteins; stored primarily in adipose tissue, liver, and muscle Metabolism: Hepatic metabolism via cytochrome P450 system; extensive first-pass metabolism Elimination: Primarily excreted in bile and feces; urinary excretion minimalContraindications
- Hypersensitivity to vitamin E or any component of the formulation
- Concurrent use with anticoagulant therapy in high doses (relative contraindication)
- Vitamin K deficiency (high doses may exacerbate bleeding tendency)
Warnings and Precautions
- High doses (>400 IU/day) associated with increased all-cause mortality in some meta-analyses
- May increase risk of hemorrhage, particularly at doses >800 IU/day
- Use with caution in patients with bleeding disorders or scheduled for surgery
- May impair hematologic response to iron therapy in children
- Synthetic form (dl-alpha-tocopherol) has approximately half the biological activity of natural form (d-alpha-tocopherol)
Drug Interactions
Significant interactions:- Anticoagulants (warfarin, heparin, direct oral anticoagulants): Increased risk of bleeding
- Cyclosporine: Vitamin E may increase cyclosporine levels
- Statins: Possible reduced efficacy with concomitant high-dose vitamin E
- Iron supplements: May require separation of administration by 2-4 hours
- Chemotherapeutic agents: Theoretical interference with oxidative mechanisms
Adverse Effects
Common effects (usually with high doses >400 IU/day):- Nausea
- Diarrhea
- Abdominal cramps
- Fatigue
- Headache
- Increased bleeding risk
- Impaired wound healing (controversial)
- Necrotizing enterocolitis in premature infants (with IV formulation)
- Increased risk of prostate cancer (SELECT trial findings)
- Hypervitaminosis E syndrome with very high doses: blurred vision, weakness, dizziness
Monitoring Parameters
- Serum vitamin E levels (normal range: 5-20 μg/mL)
- Coagulation parameters (PT/INR) if on anticoagulant therapy
- Liver function tests in patients with hepatic impairment
- Hematologic parameters in patients with bleeding tendencies
- Ophthalmologic examination with long-term high-dose therapy
Patient Education
- Take with food to enhance absorption
- Do not exceed recommended dosage without medical supervision
- Report any signs of bleeding (unusual bruising, blood in stool/urine)
- Inform all healthcare providers about vitamin E supplementation
- Store in a cool, dry place away from light
- Natural and synthetic forms have different potencies (check labels)
- Food sources include nuts, seeds, vegetable oils, and green leafy vegetables
- Discontinue at least 2 weeks before elective surgery
References
1. Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. National Academies Press, 2000. 2. Traber MG. Vitamin E regulatory mechanisms. Annu Rev Nutr. 2007;27:347-362. 3. Klein EA, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556. 4. Miller ER 3rd, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142(1):37-46. 5. Brigelius-Flohé R, Traber MG. Vitamin E: function and metabolism. FASEB J. 1999;13(10):1145-1155. 6. Sokol RJ. Vitamin E deficiency and neurological disease. Annu Rev Nutr. 1988;8:351-373. 7. FDA prescribing information for Aquasol E. 8. Natural Medicines Comprehensive Database. Vitamin E Professional Monograph. Accessed 2023.
