[img_inline align=”right” src=”http://padnws01.mcmaster.ca/images/lonn.jpg” caption=”Eva Lonn, professor of medicine, Michael G. DeGroote School of Medicine.”]Vitamin E does not work to prevent cardiovascular incidents in people who have diabetes or cardiovascular conditions, say McMaster researchers in a paper to be published in the March 16 issue of the Journal of the American Medical Association (JAMA).

The study, an extended follow-up of the HOPE trial, which began in 1993 and looked at the role of ACE inhibition and vitamin E in cardiovascular prevention, explored the role of vitamin E supplements in preventing cancer, heart disease and stroke in a high-risk population. In the extended follow-up, researchers focused more on cancer than in the original analysis. The study found no benefits for vitamin E and identified potential harmful effects.

The trial findings surprised the principal investigator, Eva Lonn, professor of medicine at the Michael G. DeGroote School of Medicine, McMaster University and a cardiologist at Hamilton Health Sciences. “When we designed the trial, we expected this intervention, vitamin E supplements, to be beneficial,” she said. “We were surprised that there were no benefits and, even more so, that there were detrimental effects.”

Lonn says that there has been a great interest from both the scientific community and the general public about the potential role of vitamin E in the prevention of cancer and cardiovascular diseases.

“Oxidative stress has been linked both to cancer and atherosclerosis, which is the process causing heart disease and stroke. Vitamin E is a potent, naturally-occurring antioxidant and, therefore, at the time when we planned this study, it appeared attractive both in cancer chemo-prevention as well as in the prevention of cardiovascular diseases.”

Experimental data derived from laboratory studies has suggested that vitamin E might prevent cancer and atherosclerosis. There have also been large observational epidemiological studies, which suggested that people taking vitamin E supplements might have a lower risk for cancer and cardiovascular diseases. However, such studies can be biased, as individuals who take vitamin supplements may have other behaviours that may enhance their general health.

“Therefore, we felt that there was a need for a large randomized controlled trial to study this question,” said Lonn. The study was co-ordinated by the Population Health Research Institute, McMaster University and involved 267 centres in Canada, the United States, Mexico, Europe and South America.

More than 9,500 participants took part of the study between 1993 and 1999. They were 55 or older at times, with evidence of vascular disease or diabetes and additional risk factors. Patients were randomized to receive 400 international units (IU) of vitamin E per day or a placebo. The first stage of the study was completed in 1999.

“At that time,” said Lonn, “We analyzed the affect of vitamin E on cardiovascular outcomes and no significant differences were noted. We decided to extend the study for an additional two and a half years because some data from other investigations had suggested that vitamin E may need a longer duration of treatment to be effective.”

Therefore, the trial was extended. At that the end of the study extension, effects of vitamin E on cancer and on cardiovascular events were analyzed. There was no significant benefit on cancer and on most cardiovascular outcomes, such as heart attack, stroke or death related to cardiovascular causes. However, increased rates of heart failure were observed in patients treated with vitamin E and an echocardiographic substudy conducted in close to 500 study participants demonstrated a small decrease in the function of the left ventricle, the main cardiac chamber, in study participants who received vitamin E.

“We do not have a precise explanation for our findings,” said Lonn. “There is, however, a significant body of literature suggesting that vitamin E may actually become a pro-oxidant when placed in an oxidative milieu. It has also been suggested that high doses of vitamin E, much higher than those provided by a balanced diet, may disturb the usual balance of antioxidants in diets.

“The required daily allowance of vitamin E is 15 mg per day. Thus, 400 IU per day, which is similar to 400 mg per day, represents over a twenty-fold increase of the required daily allowance of vitamin E. It is possible that when vitamin E is administered in very large pharmacological doses other naturally occurring antioxidants, such as gamma tocopherol, may be displaced.”

“Based on our study,” said Lonn, “we recommend that people with established heart disease or stroke or with diabetes and other risk factors should not take vitamin E supplements routinely. The focus should remain on a balanced diet rich in fruits and vegetables. This is a recommendation for the general population as well as for individuals similar to those studied in our trial.

“Those individuals who already had a heart attack or a stroke should also take the medications prescribed by their physicians regularly such as aspirin, lipid-lowering drugs, beta-blockers and ACE inhibitors, which have been proven to decrease cardiovascular risk.

“An additional recommendation from our study is the need for a carefully conducted randomized trial to evaluate the potential role for vitamins and complementary medicines. There is a tendency to accept such natural interventions readily. Both the general public, as well as physicians, often believe that even if there is no definitive proof for benefit, there is no harm associated with vitamins or other natural products.

“Our study demonstrates that the potential for risk exists. The focus should remain on a healthy diet, regular exercise and, for individuals at high risk, medications as prescribed by their physicians.”