Antioxidant pills: worse than useless

Food chart
Foods high in antioxidants are known to contribute significantly to health—but if condensed into a pill, the story changes:
Cranberry capsules. Green tea extract. Effervescent vitamin C. Pomegranate concentrate. Beta carotene. Selenium. Grape seed extract. High-dose vitamin E. Pine bark extract. Bee spit.
You name it, if it’s an antioxidant, we’ll swallow it by the bucket-load. According to some estimates around half the adults in the US take antioxidant pills daily in the belief they promote good health and stave off disease. We have become antioxidant devotees. But are they doing us any good? Evidence gathered over the past few years shows that at best, antioxidant supplements do little or nothing to benefit our health. At worst, they may even have the opposite effect, promoting the very problems they are supposed to stamp out.
It’s little surprise that antioxidants have acquired a reputation as miracle health supplements. As long ago as the 1950s, scientists discovered that many diseases – including heart disease, strokes, cancer, diabetes, cataracts, arthritis and neurodegenerative disorders such as Parkinson’s and Alzheimer’s – were linked to damage caused by highly destructive chemicals called free radicals.
Free radicals are compounds with unpaired electrons that stabilise themselves by oxidising other molecules – including proteins, carbohydrates, lipids and DNA. In the process they often create more free radicals, sparking off a chain of destruction. Oxidative damage accompanies most, if not all, diseases and has even been proposed as a direct cause of some including lung cancer, atherosclerosis and Alzheimer’s.
Free radicals are an unavoidable hazard of being alive. We live in an oxygen-rich atmosphere, and radicals, particularly reactive oxygen species (ROS), are natural by-products of respiration. “One per cent of the oxygen we consume turns into ROS,” says biochemist Barry Halliwell from the National University of Singapore. “It doesn’t sound like much but humans are big animals and we breathe a lot. Over a year a human body makes 1.7 kilograms of ROS.” Exposure to X-rays, ozone, tobacco smoke, air pollutants, microbial infections, industrial chemicals and intensive exercise also trigger free radical production.
In the 1980s, however, a potential weapon against free radical damage appeared on the horizon. Scientists had known for a long time that people whose diets are rich in fruits and vegetables have a lower incidence of heart disease, diabetes, dementia, stroke and certain types of cancer – the very diseases that are associated with free radical damage. Now there was an explanation. Fruits and vegetables are a rich source of antioxidants that can neutralise free radicals by donating electrons to them.
Green plants are full of antioxidants for good reason. They are especially vulnerable to oxidative stress since they produce pure oxygen during photosynthesis. To protect themselves they manufacture an assortment of potent antioxidants.
And so a hypothesis was born: dietary antioxidants are free-radical sponges that can stave off the diseases of old age. It was a great idea. “Putting two and two together, scientists assumed that these antioxidants were protective, and that taking them as supplements or in fortified foods should decrease oxidative damage and diminish disease,” says Halliwell, who pioneered research into free radicals and disease. “It was simple: we said free radicals are bad, antioxidants are good.”
The concept helped spawn a colossal supplements industry. According to the US National Institutes of Health (NIH), more than half of US adults take some form of vitamin or mineral supplement at a total cost of $23 billion a year. The bewildering range of supplements on the shelves makes it hard to say how much of this expenditure goes on antioxidants, but the NIH says it is probably a “large proportion”. And their popularity just keeps on growing. SPINS, a market research firm based in San Francisco, estimates that the antioxidant market has grown by 18 per cent in the past year alone.
The best known antioxidants are vitamin E (also known by its chemical name tocopherol), vitamin C, and two broad classes of plant chemicals called polyphenols (including flavonoids) and carotenoids (including beta carotene and lycopene). Most supplements touted as antioxidants contain at least one of these, often as a pure chemical and sometimes as a concentrated plant extract.
Since the early 1990s scientists have been putting these compounds through their paces, using double-blind randomised controlled trials – the gold standard for medical intervention studies. Time and again, however, the supplements failed to pass the test. True, they knock the wind out of free radicals in a test tube. But once inside the human body, they seem strangely powerless. Not only are they bad at preventing oxidative damage, they can even make things worse. Many scientists are now concluding that, at best, they are a waste of time and money. At worst they could be harmful.
The first antioxidant to produce disappointing results was beta carotene. Once a star among supplements, beta carotene pills were recommended to smokers to protect them against lung cancer. This was largely based on the observation, made in the 1970s, that people who ate a lot of carrots – which contain large quantities of beta carotene – had some protection against cancer.
In 1992 researchers at the US National Cancer Institute set about testing beta carotene. They recruited more than 18,000 people at high risk of developing lung cancer, either because they smoked or had been exposed to asbestos, and gave around half of them beta carotene supplements. The trial was supposed to run for six years, but the researchers pulled the plug two-thirds of the way through after discovering, to their surprise and horror, that those taking supplements were faring worse than the controls. Their lung cancer rate was 28 per cent higher, and the overall death rate was up 17 per cent. “It was a shock. It not only did no good but had the potential to do harm,” Halliwell says.
The researchers couldn’t be sure that these increases were not caused by chance, and beta carotene capsules are still widely sold as an antioxidant. Further trials, though, have strengthened the evidence that beta carotene supplements not only fail to protect people against cancer but can also increase the risk of lung cancer in smokers. In May of this year an expert panel convened by the NIH concluded that there was no evidence to recommend beta carotene supplements for the general population, and strong evidence to recommend that smokers avoid it.
It’s a similar story with the world’s most popular antioxidant. Vitamin E shot to fame in the early 1990s, after two large studies involving more than 127,000 people in total found that those with a diet high in vitamin E were significantly less likely to develop cardiovascular disease. The first study followed 87,245 female nurses for eight years; it found that the top 20 per cent with respect to vitamin E consumption had a 41 per cent lower incidence of cardiovascular disease than the bottom 20 per cent (New England Journal of Medicine, vol 328, p 1444). The second study, involving 39,910 male health professionals, found a similar reduction in heart disease risk (New England Journal of Medicine, vol 328, p 1450).
The researchers, based at Harvard Medical School and Harvard School of Public Health, even had a plausible mechanism. Evidence was emerging that one of the causes of heart disease was free radical damage to LDLs, tiny packages of lipid and protein that circulate in the bloodstream, delivering fatty acids to cells. It turned out that adding vitamin E to blood samples in the test tube made LDL more resistant to oxidation. Perhaps this was how vitamin E prevented heart disease. “At the biochemical level, the rationale sounded so good – at that time,” says Roland Stocker, a biochemist at the University of New South Wales in Sydney, Australia.
Use of vitamin E supplements soared. In 1990, almost nobody took vitamin E; by the end of the decade an estimated 23 million US citizens were knocking back daily doses.
On the back of these positive results, other researchers set up large studies using vitamin E supplements. The results, however, have been almost universally disappointing. Only one experiment – the Cambridge heart antioxidant study (CHAOS) – found a positive effect, a 77 per cent reduced risk of heart attack. Several others found no protective effect and one even concluded that vitamin E increased the risk of heart failure.
There’s much more in the article. Worth reading, though behind a subscription wall. OTOH, New Scientist is well worth its subscription price. The article ends:
There’s yet another, more intriguing explanation. Among the leading sources of dietary antioxidants are tea and coffee, and there is some evidence that green tea in particular is linked with health benefits including reduced risk of cancer and cardiovascular disease. [White tea is even better. - LG] Oddly, though, Halliwell has discovered that tea and coffee are also bursting with reactive oxygen species in the form of hydrogen peroxide.
“Every time you drink a cup of coffee it’s a dilute bowl of hydrogen peroxide,” says Halliwell. The hydrogen peroxide is there because of the presence of the antioxidants – “antioxidants” is really just another way of saying reducing agent, which can react with oxygen in the water to produce hydrogen peroxide. Think platinum blond, and you get the picture of what you might be drinking.
But if free radicals are bad for us, how come coffee and tea might be beneficial? One possibility is that they can help nudge our own internal antioxidant systems into action. “There has been a considerable rethink as to what free radicals are doing,” says Malcolm Jackson, a biochemist at the University of Liverpool, UK. He believes that in the right quantities radicals can be positively health-enhancing, prompting our cells to fire up their own internal defence machinery: a battery of radical-busting enzymes such as catalase and superoxide dismutase. “Cells are very good at protecting themselves against minor stresses, as long as they are not excessive,” says Jackson. “The question is: should we be quenching free radicals at all?”
If it turns out that antioxidants in food work because they generate health-promoting quantities of free radicals, that would be an ironic turnaround. It may also explain why supplements and extracts don’t seem to work or may even be dangerous: the doses are too high, and produce too many free radicals.
For now, the advice is simple. “Stick to flavonoid-rich foods, red wine in moderation, tea, fruits and vegetables,” says Halliwell. “Don’t start taking high-dose supplements or heavily fortified foods, until we know more.”