Scientists overturn accepted theory of disease

The current thinking that oxygen free radicals are responsible for the development of numerous diseases, including cancer and arthritis, may be a red herring, says a team of UK scientists.

Their study, which challenges the theory behind drug development worth millions of dollars, would also call into question the use of antioxidants to counter the build-up of free radicals.

The paper, published in today's issue of Nature (vol 427, no 6977, p853) may hold profound implications for the nutraceutical industry. The researchers say that all the theories relating to the cause of disease by oxygen free radicals and the therapeutic value of antioxidants must be re-evaluated.

It is currently held that oxygen free radicals, which are atoms or groups of atoms produced by white blood cells, are responsible, if produced in excess, for the production of conditions such as arthritis, arteriosclerosis and many others, including cancer.

Since the 1970s, the pharmaceutical industry has sought to develop drugs to stop the production of free radicals and mop them up with antioxidants (substances capable of preventing the oxidation of organic molecules) to help treat such diseases.

The nutraceutical industry has focused on prevention, working on the theory that stopping production or fighting the build-up of free radicals with antioxidants, such as vitamin C or E, could hold off certain diseases as well as the ageing process.

The University College London (UCL) team categorically discounts the primary evidence upon which this theory is based, and suggests that instead we need to look at other potential treatments, specifically treatments impacting the regulation of enzymes released from neutrophil leukocytes, the most numerous of the white blood cells.

"White blood cells produce oxygen free radicals, and the process by which they do so is essential for the efficient killing of microbes," says author Professor Tony Segal of the Centre for Molecular Medicine within UCL's department of medicine.

"However, people in whom this process is defective are prone to severe, chronic and often fatal infections. This fact has led to the presumption that the oxygen free radicals themselves are highly toxic, and that if they can kill organisms as tough as bacteria and fungi they can also damage human tissues," he explained.

Free radicals are believed to be promoted by many agents, including smoking and atmospheric pollutants, and have been implicated in the production of conditions that include cancer, arthritis, and many other conditions caused by an initial inflammation in which these neutrophil leukocytes accumulate.

"However, our work shows that the basic theory underlying the toxicity of oxygen radicals is flawed," said Segal.

The researchers discovered that it is not free radicals that give white blood cells their destructive power, but enzymes which effectively digest foreign invaders. Production of these enzymes is triggered by the flow of the mineral potassium within the cell.

But when the scientists blocked this process, the cells were unable to fight pathogens, showing that free radicals may not be toxic as thought.

The researchers argue that millions of dollars have been "misspent by the pharmaceutical industry in chasing the red herring of the involvement of oxygen free radicals in the causation of many diseases".

"Many patients might be using expensive antioxidant drugs based upon completely invalid theories as to their therapeutic potential," added Segal.

There are many categories of natural compounds that have been shown to have antioxidant actions. Aside from vitamins E and C, carotenoids such as lycopene and lutein, astaxanthins such as those found in berries and some minerals like selenium have all been studied for their potential to reduce risk of disease. And growing sales of natural antioxidants in supplement or functional foods reflect that the consumer may have seen some benefit from such ingredients.

While the growth in antioxidants in the overall food segment is relatively small at 3.4 per cent in Europe, supplements and fortified foods will become the fastest growing section of the carotenoids market, growing from 18.2 per cent of the overall segment in 2003 to 27.0 per cent in 2010, making it the second largest revenue generator behind animal feed, predicts Frost & Sullivan.

Polyphenols, also traditionally employed as natural food colouring agents, will also grow based on research showing their health benefits.