into its own. They were going to identify more and more of these one-to-one correlations between exposures and disease, and, in their fervent imaginations, with simple interventions and cautionary advice they were going to save whole nations of people. This dream was very much not realised, as it turned out to be a bit more complicated than that.
Two large trials of antioxidants were set up after Peto’s paper (which rather gives the lie to nutritionists’ claims that vitamins are never studied because they cannot be patented: in fact there have been a great many such trials, although the food supplement industry, estimated by one report to be worth over $50 billion globally, rarely deigns to fund them). One was in Finland, where 30,000 participants at high risk of lung cancer were recruited, and randomised to receive either ?-carotene, vitamin E, or both, or neither. Not only was there an increase in death from lung cancer among the people receiving the supposedly protective ?-carotene supplements, compared with placebo, but the vitamin group also showed increased death from prostate and gastric cancers.
The results of the other trial were almost worse. It was called the ‘Carotene and Retinol Efficacy Trial’, or ‘CARET’, in honour of the high ?-carotene content of carrots. It’s interesting to note, while we’re here, that carrots were the source of one of the great disinformation coups of World War II, when the Germans couldn’t understand how our pilots could see their planes coming from huge distances, even in the dark. To stop them trying to work out if we’d invented anything clever like radar (which we had), the British instead started an elaborate and entirely made-up nutritionist rumour. Carotenes in carrots, they explained, are transported to the eye and converted to retinal, which is the molecule that detects light in the eye (this is basically true, and is a plausible mechanism, like those we’ve already dealt with): so, went the story, doubtless with much chortling behind their excellent RAF moustaches, we have been feeding our chaps huge plates of carrots, to jolly good effect.
Anyway. Two groups of people at high risk of lung cancer were studied: smokers, and people who had been exposed to asbestos at work. Half were given ?-carotene and vitamin A, while the other half got placebo. Eighteen thousand participants were due to be recruited throughout its course, and the intention was that they would be followed up for an average of six years; but in fact the trial was terminated early, because it was considered unethical to continue it. Why? The people having the antioxidant tablets were 46 per cent more likely to die from lung cancer, and 17 per cent more likely to die of any cause, than the people taking placebo pills. This is not news, hot off the presses: it happened well over a decade ago.
Since then the placebo-controlled trial data on antioxidant vitamin supplements has continued to give negative results. The most up-to-date Cochrane reviews of the literature pool together all the trials on the subject, after sourcing the widest possible range of data using the systematic search strategies described above (rather than ‘cherry-picking’ studies to an agenda): they assess the quality of the studies, and then put them all into one giant spreadsheet to give the most accurate possible estimate of the risks of benefits, and they show that antioxidant supplements are either ineffective, or perhaps even actively harmful.
The Cochrane review on preventing lung cancer pooled data from four trials, describing the experiences of over 100,000 participants, and found no benefit from antioxidants, and indeed an increase in risk of lung cancer in participants taking ?-carotene and retinol together. The most up-to-date systematic review and meta-analysis on the use of antioxidants to reduce heart attacks and stroke looked at vitamin E, and separately ?-carotene, in fifteen trials, and found no benefit for either. For ?-carotene, there was a small but significant increase in death.
Most recently, a Cochrane review looked at the number of deaths, from any cause, in all the placebo- controlled randomised trials on antioxidants which have ever been performed (many of which looked at quite high doses, but perfectly in line with what you can buy in health-food stores), describing the experiences of 230,000 people in total. This showed that overall, antioxidant vitamin pills do not reduce deaths, and in fact they may increase your chance of dying.
Where does all this leave us? There was an observed correlation between low blood levels of these antioxidant nutrients and a higher incidence of cancer and heart disease, and a plausible mechanism for how they could have been preventive: but when you gave them as supplements, it turned out that people were no better off, or were possibly
More interesting is how uncommon it is for people even to be aware of these findings about antioxidants. There are various reasons why this has happened. Firstly, it’s an unexpected finding, although in that regard antioxidants are hardly an isolated case. Things that work in theory often do not work in practice, and in such cases we need to revise our theories, even if it is painful. Hormone replacement therapy seemed like a good idea for many decades, until the follow-up studies revealed the problems with it, so we changed our views. And calcium supplements once looked like a good idea for osteoporosis, but now it turns out that they probably increase the risk of heart attacks in older women, so we change our view.
It’s a chilling thought that when we think we are doing good, we may actually be doing harm, but it is one we must always be alive to, even in the most innocuous situations. The paediatrician Dr Benjamin Spock wrote a record-breaking best-seller called
But of course, there is a more mundane reason why people may not be aware of these findings on antioxidants, or at least may not take them seriously, and that is the phenomenal lobbying power of a large, sometimes rather dirty industry, which sells a lifestyle product that many people feel passionately about. The food supplement industry has engineered itself a beneficent public image, but this is not borne out by the facts. Firstly, there is essentially no difference between the vitamin industry and the pharmaceutical and biotech industries (that is one message of this book, after all: the tricks of the trade are the same the world over). Key players include companies like Roche and Aventis; BioCare, the vitamin pill company that media nutritionist Patrick Holford works for, is part-owned by Elder Pharmaceuticals, and so on. The vitamin industry is also – amusingly – legendary in the world of economics as the setting of the most outrageous price-fixing cartel ever documented. During the 1990s the main offenders were forced to pay
Whenever a piece of evidence is published suggesting that the $50-billion food supplement pill industry’s products are ineffective, or even harmful, an enormous marketing machine lumbers into life, producing spurious and groundless methodological criticisms of the published data in order to muddy the waters – not enough to be noteworthy in a meaningful academic discussion, but that is not their purpose. This is a well-worn risk-management tactic from many industries, including those producing tobacco, asbestos, lead, vinyl chloride, chromium and more. It is called ‘manufacturing doubt’, and in 1969 one tobacco executive was stupid enough to commit it to paper in a memo: ‘Doubt is our product,’ he wrote, ‘since it is the best means of competing with the “body of fact” that exists in the minds of the general public. It is also the means of establishing a controversy.’
Nobody in the media dares to challenge these tactics, where lobbyists raise sciencey-sounding defences of their products, because they feel intimidated, and lack the skills to do so. Even if they did, there would simply be a confusing and technical discussion on the radio, which everyone would switch off, and at most the consumer would hear only ‘controversy’: job done. I don’t think that food supplement pills are as dangerous as tobacco – few things are – but it’s hard to think of any other kind of pill where research could be published showing a possible increase in death, and industry figures would be wheeled out and given as easy a ride as the vitamin companies’ employees are given when papers are published on their risks. But then, of course, many of them have their own slots in the media to sell their wares and their world view.
The antioxidant story is an excellent example of how wary we should be of blindly following hunches based on laboratory-level and theoretical data, and naively assuming, in a reductionist manner, that this must automatically map onto dietary and supplement advice, as the media nutritionists would have us do. It is an object lesson in what an unreliable source of research information these characters can be, and we would all do well to remember this story the next time someone tries to persuade us with blood test data, or talk about molecules, or theories based on vast, interlocking metabolism diagrams, that we should buy their book, their wacky diet, or their bottle of pills.
