New research shows that far from protecting us, antioxidant supplements, such as vitamins C and E, may actually increase the chance of developing cancer.
If, 15 years ago, you were au fait with the word antioxidant, then you probably had a chemistry degree. These days, you're almost certainly an expert on the subject yourself. Every time we read a magazine, turn on the TV or pop to the supermarket, we're bombarded by claims about the ability of these apparently miraculous chemicals to ward off serious illness and help us live longer. As a result, swathes of the public, in particular the "worried well", now expound knowledgeably about the "antioxidant power" of their purchases from the fruit and veg counter at Waitrose to neutralise the dangerous ''free radicals'' in our bodies.
But although "antioxidant good, free radical bad" has become the nutritional rallying cry of a generation, scientists say that worrying questions remain about the complex role the two interlinked chemicals play in our lives. This has been underlined by new research suggesting that, far from protecting us from harm, high doses of antioxidants can do significant damage to our bodies.
Scientists at the Cedars-Sinai Heart Institute in Los Angeles reported in the journal Stem Cells that high doses of antioxidant supplements, such as vitamins C and E, raised the risk of dangerous changes in human cells.
"In simple terms, by taking high amounts of antioxidant supplements, you may be increasing your chances of cancer," explained the team leader, Dr Eduardo Marbán.
Confused? Before we turn to Dr Marbán's explanation, it's worth recapping what we do – and don't – know about free radicals and antioxidants. The starting point is that our bodies generate a class of molecules called free radicals, both as a by-product of our normal metabolic processes and as a result of contact with pollutants. These reactive molecules contain oxygen atoms with unpaired electrons. Since electrons have a very strong tendency to exist in a paired rather than an unpaired state, the free radicals indiscriminately "seek" to grab electrons from nearby molecules. These are then converted into secondary free radicals, setting up a chain reaction that damages our tissue.
In 1956, the Californian scientist Denham Harman proposed a theory that has dominated the field of ageing research ever since. His idea was that ageing is caused by an accumulation of "oxidative stress" – the damage to our cells done by free-radical forms of oxygen. These free radicals are thought to be harmful to our DNA – raising the risk of cancer – and also damaging to cholesterol molecules, creating a reactive form of the fatty molecule that can inflame our arteries, thereby leading to heart attacks and strokes.
Then, over the past few decades, came a series of population studies which suggested that people who ate lots of fruit and vegetables – which contain plenty of antioxidants – tend to live longer. Separate studies in the laboratory showed that antioxidants stopped oxidative chemical processes of the type thought to lie behind several diseases. People added one and one and made three: they assumed that ingesting high doses of these antioxidants, as supplements, would protect them from the diseases of old age.
The first cracks in this argument appeared in the 1990s, when a large clinical trial by the US National Cancer Institute made a surprising – and alarming – discovery. It found that the popular antioxidant supplement beta-carotene actually appeared to increase the risk of lung cancer in those predisposed to the disease. By the middle of this decade, the initial excitement about vitamin E's ability to prevent heart disease, and similar hopes that vitamin-C supplements could extend our lives, had also withered away. "The simple message is: 'Don't buy antioxidant supplements, because they won't do you any good'," says Dr David Gems of University College London's Institute of Healthy Ageing. "The oxidative stress theory is looking very shaky. It is clearly not the only driver of the ageing process."
But it is not just the benefits of antioxidants that have come under attack. The other half of the equation, namely the idea that free radicals must be neutralised at all costs, has also been challenged. These reactive molecules actually play a vital role in our immune systems by killing tumour cells and invading pathogens. Researchers at Nijmegen University in the Netherlands have suggested that giving antioxidants to people with cancer might actually be counterproductive, given that patients will need free radicals to dispose of proliferating tumour cells.
On a subtler level, Professor Malcolm Jackson of University of Sheffield argues that a certain level of free radicals may be needed to stimulate the production of our own internal – and highly effective – antioxidants. These include the superoxide dismutase, a molecule honed by million of years of evolution to mop up free radicals in the body.
Still, there is a considerable leap from this concept to the idea that high doses of antioxidants can actually increase the risk of cancer. Which brings us back to the striking findings published in Stem Cells last week. Dr Marbán and his team accidentally discovered the danger of excessive antioxidant doses while trying to find a way to reduce the genetic abnormalities that occur when growing cardiac stem cells for experimental heart treatments in vitro.
These cultures typically contain very high levels of oxygen, which means that the cells are at high risk of oxidative damage. To limit this, he recently added antioxidant supplements recommended by a technical supplier. But to his surprise, he found this increased the level of genetic damage. The same thing happened when he added the antioxidant vitamins C and E, at the same levels commonly reached by people on high-dose supplements.
Dr Marbán thinks that at such high levels, the antioxidants impede the enzyme that corrects the errors that occur frequently when DNA is duplicated during cell division. Indeed, he has shown that a mix of vitamins C and E could also impede the enzyme that repairs our DNA from doing its job.
Tellingly, he repeated the experiment using unnaturally high levels of the antioxidants produced by the body itself, such as catalase. Again, the cancer-fighting DNA repair enzyme was hindered. "This suggests to us that it was the antioxidant properties, rather than peculiar chemical properties of these two vitamins, that prevented DNA repair," he says.
And back in the real world? "Taking one multivitamin a day is fine, but a lot of people take way too much because they think if a little is good, a lot must be better," Dr Marbán says. "That is just not the case. The simple message for consumers is: eat as much fruit and vegetables as you like. You can't overdose on antioxidants in your diet. But supplements can take you into the danger zone."
Yet if the value of antioxidant supplements is at best uncertain, the evidence for the life-prolonging benefits of a diet rich in fruit and vegetables seems clear. The challenge now is to explain why they work in this form but appear to fail as isolated key chemicals.
Apart from the question of dosing, experts suggest that antioxidants might work best in combination with other nutrients and protective chemicals that are present in fruit and vegetables. Or perhaps it's that eating lots of fruit and veg means you have less room for junk food. It's certainly something to reflect on the next time you find yourself perusing the ever-growing ranks of antioxidant supplements in the pharmacy or health-food shop. Instead of time-release vitamin pills, buy yourself an apple.
