Vitamin E toxicity is very rare and supplements are widely considered to be safe. The National Academy of Sciences has established the daily tolerable upper intake level for adults to be 1,000 mg of vitamin E, which is equivalent to 1,500 IU of natural vitamin E or 1,100 IU of synthetic vitamin E.⁵¹

In a double-blind study of healthy elderly people, supplementation with 200 IU of vitamin E per day for 15 months had no effect in the incidence of respiratory infections, but increased the severity of those infections that did occur.⁵² For elderly individuals, the risks and benefits of taking this vitamin should be assessed with the help of a doctor or nutritionist.

In contrast to trials suggesting vitamin E improves glucose tolerance in people with diabetes, one trial reported that 600 IU per day of vitamin E led to impairment in glucose tolerance in obese people with diabetes.⁵³ The reason for the discrepancy between reports is not known.

In a double-blind study of people with established heart disease or diabetes, participants who took 400 IU of vitamin E per day for an average of 4.5 years developed heart failure significantly more often than did those taking a placebo.⁵⁴ Hospitalizations for heart failure occurred in 5.8% of those in the vitamin E group, compared with 4.2% of those in the placebo group, a 38.1% increase. Considering that some other studies have shown a beneficial effect of vitamin E against heart disease, the results of this study are difficult to interpret. Nevertheless, individuals with heart disease or diabetes should consult their doctor before taking vitamin E.

A review of 19 clinical trials of vitamin E supplementation concluded that long-term use of large amounts of vitamin E (400 IU per day or more) was associated with a small (4%) but statistically significant increase in risk of death.⁵⁵ Long-term use of less than 400 IU per day was associated with a small and statistically nonsignificant reduction in death rates. This research has been criticized because many of the studies on which it was based used a combination of nutritional supplements, not just vitamin E. For example, the adverse effects reported in some of the studies may have been due to the use of large amounts of zinc or synthetic beta-carotene, and may have had nothing to do with vitamin E. It is also possible that long-term use of large amounts of pure alpha-tocopherol may lead to a deficiency of gamma-tocopherol, with potential negative consequences. For that reason, some doctors recommend that people who need to take large amounts of vitamin E take at least part of it in the form of mixed tocopherols.