Potential Side Effects of Vitamin E Supplementation
High-dose vitamin E supplementation can increase the risk of bleeding, particularly in patients taking anticoagulant medications, and may potentially increase the risk of hemorrhagic stroke at doses exceeding 400 IU/day. 1
Common Side Effects and Safety Profile
- Vitamin E has a relatively low toxicity profile compared to many medications, with most supplementation being well-tolerated at recommended doses 1
- The Tolerable Upper Limit for vitamin E supplementation in adults is set at 1000 mg (approximately 1500 IU) of any form of supplementary α-tocopherol 1
- Oral supplementation with doses between 60-800 IU/day (55-727 mg/day) for periods ranging from 30 days to 4 months has shown no consistent adverse effects on health parameters including bleeding time, antibody production, and creatinine concentrations in healthy adults 1
Serious Side Effects and Risks
Bleeding Risk
- Vitamin E supplements may induce bleeding risks due to their effect on platelet aggregation and blood clotting 1
- Daily supplementation with 1000 IU (670 mg) of RRR-α-tocopherol for 12 weeks has been shown to decrease γ-carboxylation of prothrombin, a vitamin K-dependent factor in the coagulation cascade 1
- Patients receiving warfarin therapy should avoid vitamin E supplements or be closely monitored if they do take them 2
- Vitamin E should be discontinued in the perioperative period for any patient requiring surgery due to increased bleeding risk 2
Stroke Risk
- Meta-analyses investigating vitamin E's effect on stroke subtypes found a decrease in ischemic stroke (RR 0.90, P=0.02), but an increase in hemorrhagic stroke (RR 1.22, P=0.045) 1
- This risk appears to be dose-dependent, with higher doses posing greater risk 3
Mortality Risk
- Some meta-analyses have suggested a potential increase in all-cause mortality in patients taking high-dose vitamin E supplements (RR 1.04; 95% CI, 1.01–1.07) 1
- However, other analyses show that vitamin E at doses ≤400 IU/day had no effect on all-cause mortality, and dosages <150 IU/day may actually slightly decrease mortality 1
Cancer Risk
- Vitamin E use has been associated with an increased risk of prostate cancer with an absolute risk of 1.6 per 1000 person-years 1
- This risk should be discussed with patients prior to initiating treatment, particularly in men with risk factors for prostate cancer 1
Special Populations and Contraindications
- Individuals taking anticoagulant drugs like warfarin should not take vitamin E supplements without medical supervision due to the increased risk of bleeding 1, 2
- Vitamin E supplementation is contraindicated in patients with vitamin K deficiency due to potential exacerbation of blood coagulation defects 4
- Smokers should avoid vitamin E supplementation due to potential negative effects on vitamin C, and vitamin E should never be administered in conjunction with beta-carotene in this population 2
- Patients with retinitis pigmentosa or requiring vitamin A therapy should avoid vitamin E supplementation 2
- Caution is advised in patients with heart failure, coagulation disorders, or history of stroke 3
Drug Interactions
- Potential interactions exist between high-dose vitamin E (≥300 mg/day) and several medications 5:
- For most other drugs, interactions with vitamin E are unlikely, even at higher doses 5
Dosing Considerations
- For most adults, vitamin E supplements ≤1600 IU (1073 mg RRR-α-tocopherol or equivalent) appear to be safe 1, 6
- Vitamin C supplements of ≤2000 mg/day are generally safe when taken with vitamin E 6
- In clinical settings requiring vitamin E supplementation, such as long-standing fat malabsorption (e.g., short bowel syndrome), a dose of 200 mg/day has been shown to improve neurological symptoms after a few months 1