Whether vitamin E supplementation exerts protective effects in patients with cardiovascular disease is uncertain. The Cambridge Heart Antioxidant Study revealed that daily supplementation with 400 to 800 mg of vitamin E was associated with an increase in fatal cardiovascular events but a decrease in nonfatal infarctions in patients with coronary atherosclerosis. The Alpha-Tocopherol, Beta Carotene Cancer Prevention study showed that 50 mg of vitamin E daily did not produce a significant change in cardiovascular events among smokers. Investigators of the GISSI-Prevenzione trial evaluated the effects of supplemental vitamin E and n-3-polyunsaturated fatty acids (n-3-PUFA), alone and in combination, in patients with a history of myocardial infarction (MI).

The 3.5-year study included 11,324 patients who sustained an MI in the previous three months. Patients were randomly assigned to receive daily dietary supplementation with 1 g of n-3-PUFA (2,836 patients), 300 mg of vitamin E (2,830 patients), both vitamin E and n-3-PUFA (2,830 patients) or no supplement (2,828). Patients continued on their usual preventive cardiac therapies. Serum lipid levels were determined during follow-up visits at 6, 12, 18, 30 and 42 months. Follow-up visits also included a clinical assessment and administration of a dietary information questionnaire. Compliance was checked by medication reviews every three months.

Supplemental n-3-PUFA was found to significantly lower the risk of death. Two-way analysis of the data (i.e., PUFA therapy versus no PUFA therapy) revealed that the relative risk of death, nonfatal MI and nonfatal stroke decreased by 10 percent in patients who received n-3-PUFA therapy. On four-way analysis (i.e., efficacy of PUFA, vitamin E, combined therapy and control), PUFA therapy was associated with a 20 percent reduction in the relative risk for cardiovascular death, nonfatal MI and nonfatal stroke. No such benefit was found with vitamin E.

No increase in the incidence of cancer was found in patients receiving n-3-PUFA or vitamin E. Gastrointestinal upset was reported by fewer than 5 percent of patients receiving the supplements.

The authors conclude that supplementation with 1 g of n-3-PUFA daily for 3.5 years significantly reduced the risk of death, nonfatal MI and stroke in patients with a previous MI. Conversely, vitamin E in a dosage of 300 mg daily did not provide a protective effect in the population studied. They note that this daily dosage of vitamin E, although lower than that used in other studies, is well in excess of dietary levels, even in patients who regularly ingest a Mediterranean type of diet.