Humans depend on oxygen to produce energy, but oxygen also has the potential to generate so-called oxygen radicals, which may cause oxidative stress and disease. Markers of oxidative stress have been correlated with cardiovascular disease, cancer, diabetes, and other conditions. Because of these associations, antioxidant supplements are taken by millions of people; however, none of the antioxidants tested in randomized clinical trials have demonstrated any benefit. On the contrary, some of them may cause harm.
This is because oxygen radicals not only trigger disease but also perform many important functions in the body, such as for immune defense and hormone synthesis. Thus anti-oxidants will interfere with both healthy and disease-triggering oxygen molecules.
"Oxidative stress could be important in some conditions and only in a small proportion of patients," said Prof. Ghezzi. "It can be targeted in a totally different manner, with drugs targeted only at those sources of oxygen molecules that are triggers of disease and leave the healthy ones alone," added Prof. Schmidt. The review is published the British Journal of Pharmacology.
The theory stating that oxidative stress (OS) is at the root of several diseases is extremely popular. However, so far, no antioxidant is recommended or offered by healthcare systems neither approved as therapy by regulatory agencies that base their decisions on evidence-based medicine (EBM). This is simply because, so far, despite many preclinical and clinical studies indicating a beneficial effect of antioxidants in many disease conditions, randomised clinical trials have failed to provide the evidence of efficacy required for drug approval.
In this review, we discuss the levels of evidence required to claim causality in preclinical research on OS, the weakness of the oversimplification associated with OS theory of disease and the importance of the narrative in its popularity. Finally, from a more translational perspective, we discuss the reasons why antioxidants acting by scavenging reactive oxygen species (ROS) might not only prevent their detrimental effects but also interfere with essential signalling roles. We propose that ROS have a complex metabolism and are generated by different enzymes at diverse sites and with different timing. Aggregating this plurality of systems in a single theory of disease may not be the best way to develop new drugs, and future research may need to focus on specific oxygen-toxifying pathways rather than on non-specific ROS scavengers. Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories (open data), as this will allow big data approaches or meta-analyses without the blinders of the publication bias.
bron: ScienceDaily https://www.sciencedaily.com/releases/2016/07/160719094130.htm 21-7-2016
Pietro Ghezzi, Vincent Jaquet, Fabrizio Marcucci, Harald H.H.W. Schmidt. The oxidative stress theory of disease: levels of evidence and epistemological aspects. British Journal of Pharmacology, 2016; DOI: 10.1111/bph.13544
p.s. ik zal vanavond of morgen een deel van de citaten vertalen naar het Nederlands