For years the evidence was coming in showing that extra antioxidants worked very well. One group who seemed to be benefiting were smokers, who have a very high exposure to oxidants, which are also created when anything, from bacon to tobacco, is burnt. Beta-carotene, the stuff in carrots, was coming up trumps in thousands of studies linking a high intake, or high blood levels to low disease risk, particularly of cancer. For example, a ten-year study of several thousand elderly people in Europe, conducted by the Centre for Nutrition and Health at the National Institute of Public Health and the Environment in the Netherlands, found that the higher the beta-carotene level, the lower the overall risk of death, especially from cancer. Eating probably the equivalent of a carrot a day (raising blood level by 0.39mcmol/l) meant cutting cancer risk by a third.
Heart disease, the biggest western killer, was being linked to oxidative damage to cholesterol and the arteries and vitamin E, a fat-based antioxidant, was the best contender for protecting your arteries. The signs were good. The New England Journal of Medicine published two studies the first of which involved 87,200 nurses. Those taking in 67mg or more of vitamin E for more than two years had 40 per cent less fatal and non-fatal heart attacks compared to those not taking vitamin E supplements.
In another study, 39,000 male health professionals taking 67mg of vitamin E for the same length of time had a 39 per cent reduction in heart attacks. Then, the first placebo-controlled trial, carried out by researchers at the UK’s Cambridge University Medical School in 1996, gave some 2,000 people vitamin E or a placebo. Those given vitamin E had a 75 per cent reduced risk of a non-fatal heart attack. The research showed vitamin E to be almost four times as effective as aspirin in reducing heart attacks. But then in the mid-nineties this positive picture began to change when the results began to come in from a number of studies that had been set up to test the effects of giving smokers, and people with heart disease, antioxidants, especially beta-carotene and vitamin E respectively. The first to rock the antioxidant boat, the CARET trial by the National Cancer Institute, was published in 1996. It found a small, non-significant increased incidence of lung cancer in smokers given beta-carotene, and an equivalent decreased incidence in non-smokers taking the supplement.
Then, another trial reported an increased risk for smokers given beta-carotene. Male smokers were given either vitamin E, vitamin E plus beta-carotene, or beta-carotene on its own. The first two groups showed no significant change, but the beta-carotene-only group showed an increased risk. Once again, giving beta-carotene on its own to smokers shows up as very slightly raising the risk of cancer. Although the negative effect was small it has been confirmed by some more recent studies. For example, a study in which people received radiation therapy for head and neck cancer found that those given supplements of beta-carotene and vitamin E during radiation therapy who continued to smoke increased their risk of a cancer recurrence and death, while those who did not smoke didn’t. Other studies have also found an increased risk among smokers taking supplements and a decreased risk among non-smokers. The question is why? What does this mean for smokers?
The second nail in the coffin for antioxidants were results of trials giving vitamin E to those with cardiovascular disease. All was looking good with vitamin E until 2000, when around 20,000 people with cardiovascular disease were given vitamins (600mg of vitamin E, 250mg of vitamin C and 20mg of beta-carotene) or placebos in a large-scale double-blind trial. This trial was part of a much larger study testing the effects of statin drugs. It found no difference in those taking the vitamins versus the placebos, but statins performed well in comparison. Then, things got worse for vitamin E. An American study, the HOPE (Heart Outcomes Prevention Evaluation) trial, published in the New England Journal of Medicine, hinted at a slight increased risk of heart attack in heart patients who were on medication and taking vitamin E. The trial was extended for a further 2.5 years and, in 2005, the results of what was called the HOPE2 trial were published in the Annals of Internal Medicine, showing a slight increased risk of heart attack in heart patients who were on medication and taking vitamin E. This prompted a review of all trials in which vitamin E had been given to people with cardiovascular disease. The results showed that vitamin E, in higher doses, seemed to increase mortality, while at lower doses, seemed to decrease mortality.
The overall conclusion was that ‘vitamin E supplementation did not affect all-cause mortality’ – in other words, the same number of people overall died in the group that took vitamin E as did in the group that didn’t. But as with beta-carotene, there was a group that did slightly worse (those on a high dose, above 268mg), and a group that did slightly better (on a low dose, below 268mg). Either way, though, the results looked pretty damning. The effect of taking vitamin E, for these people, was not that greatly positive or negative – and certainly not as positive as the preventive power of giving vitamin E to reasonably healthy people. The question is why, and why the difference between the high and low doses?
What none of the negative studies or the hostile press stories have commented on, however, is the very interesting finding that the apparent risk of taking an antioxidant on its own seems to vanish when you also take a multivitamin. For example, the recent Cochrane Review by Bjekalovic  (which was also published in the Journal of the American Medical Association last February  ) found that people who took BOTH multivitamin AND antioxidant supplements showed no increased risk, and in some cases, a significant decrease in ......
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