Cardiovascular disease is caused by atherosclerosis , a complex process in which fatty deposits, called atheromas or plaques, damage the lining of arteries, causing them to narrow and harden. High levels of low-density lipoproteins (LDLs) in the blood play an important role in the development of atherosclerotic plaques. Scientists believe that in order for LDL to contribute to the development of atherosclerosis, it must combine with oxygen in a multi-step process referred to as oxidation . This theory has triggered a great deal of research into a range of dietary constituents that may minimize the oxidation of LDL and limit the resulting atherosclerotic damage to arterial walls.

One promising constituent is a famous group of substances known as antioxidants. The two antioxidants that have received the most attention are vitamin E and beta-carotene , which is easily transformed by the body into vitamin A . In the past, observational studies (studies that observe and describe outcomes, but are not powered to determine cause and effect) have provided support for the potential health benefits of these antioxidant vitamins.

However, a new analysis of randomized clinical trials, published in the June 14, 2003 issue of The Lancet , suggests that the routine use of antioxidents not only fails to significantly reduce the risk of cardiovascular death or stroke , but, in the case of beta-carotene, may pose a potential health risk to some patients.

About the study

The researchers conducted a thorough search of the medical literature to identify all of the randomized controlled trials involving the use of antioxidant vitamins for the prevention of cardiovascular disease or its complications. For beta-carotene, the researchers identified 12 trials in total, eight of which involved individuals without known CVD (primary prevention) and four of which involved patients with CVD (secondary prevention). For vitamin E, seven trials were identified, the majority of which were secondary prevention trials. All of the trials were large, involving at least 1,000 patients.

The findings

The vitamin E trials involved a combined total of 81,788 patients and the beta-carotene trials involved a combined total of 138,113 patients. The researchers found that vitamin E did not significantly lower the risk for cardiovascular death or stroke compared with placebo (11.3% versus 11.1% respectively). The researchers also found that beta carotene actually led to a small, but significant increase in mortality from any cause (7.4% versus 7.0% respectively) and a slight (but statistically non-significant) increase in the risk of cardiovascular death.

How does this affect you?

The researchers concluded that neither supplement is effective for the prevention of cardiovascular disease or its complications, and that some patients receiving the beta-carotene supplement may have actually increased their risk of CVD. Therefore, the researchers determined that they could not support the routine use of vitamin E supplements for the prevention of CVD.

The researchers also stated that they could not support supplementation with beta-carotene under any circumstances. While this view is unlikely to be shared by many of their colleagues, the researchers went on to recommend that the use of vitamin supplements containing beta-carotene be actively discouraged, and that all clinical studies involving beta-carotene be discontinued due to its potential health risks to the participants.

The researchers concede, however that there are some important limitations to their study. For example, the small negative health effect noted for beta-carotene was driven by two studies in which the patients were at high risk for lung cancer, and past studies have shown that high doses of beta-carotene in smokers can indeed increase their risk for heart disease and stroke.

In addition, some researchers believe that antioxidants are more effective in inhibiting the early stages of atherosclerosis (plaque formation) than in preventing symptoms in the later stages of the disease. Therefore, the researchers concede that further study of the effects of vitamin E in primary prevention studies may be warranted.

It is important to note that all of the trials in the meta-analysis were conducted using vitamin supplements. Antioxidant rich foods may provide other beneficial nutrients such as flavonoids and lycopenes that are not present in oral vitamin supplements. It is also possible that the natural form of the vitamins found in food may have biological activity or potency that is different from synthetic supplements. There is currently no evidence that eating foods rich in antioxidant nutrients is harmful in any way.

The initial enthusiasm for antioxidant supplementation was based largely on observational studies. The recent publication of numerous controls trials, however, has raised many doubts about their beneficial health effects. As we watch yet another magic bullet go bust we must face, once again, the unsurprising truth that diet and exercise are the only real weapons we have in the battle against too much food and too much fat.