Life requires oxygen. This runs the risk that, when oxygen leaks out from normal metabolism, ‘reactive oxygen species’ (ROS) are formed, which – when too high– trigger disease. This state, called oxidative stress, has been suggested as a major cause of major diseases representing most causes of death, such as cardiovascular diseases and cancer. The famous scientist Linus Pauling – twice Nobel Prize winner (chemistry and peace) – was a pioneer in addressing the connection of disease and oxidative stress. Unfortunately, his idea of using excessive amounts of vitamin C to reduce oxidative stress is not clinically efficient. Indeed, clinical trials using antioxidants as therapeutics have been failures, sometimes even with side effects. Still, the concept oxidative stress, probably also thanks to Linus Pauling, is very popular. Up to half the population in high-income countries uses vitamin supplements, often marketed as antioxidants. It is like the Popeye-spinach story, where a health halo around the vegetable was constructed and still believed even when research indicated that the iron in spinach has poor bioavailability.
One reason why antioxidants cannot work is the double-edged role of ROS being both potentially mediators of disease and essential signalling molecules. An excess of ROS can damage cells, but ROS are also essential for the immune system. Thus, a deficiency in ROS can result in similarly harmful effects. Accordingly, the roles of ROS in health and disease need to be completely re-defined and much better understood before safe applications are possible. EU-ROS will apply completely different approaches: First, instead of letting ROS form and then trying to delete them, EU-ROS will identify their disease-relevant sources and prevent their formation or specifically repair the damage caused by ROS. Second, EU-ROS will differentiate beneficial roles of ROS.