Ghezzi-HWWWSchmidtSRO.pdf (2.38 MB)
The oxidative stress theory of disease: levels of evidence and epistemological aspects
journal contribution
posted on 2023-06-09, 01:58 authored by Pietro Ghezzi, Vincent Jaquet, Fabrizio Marcucci, Harald H H W SchmidtThe 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 Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories (open data), as this will allow big data approaches or meta-analyses without the blinders of the publication bias.
History
Publication status
- Published
File Version
- Accepted version
Journal
British Journal of PharmacologyISSN
0007-1188Publisher
WileyExternal DOI
Issue
12Volume
174Page range
1784-1796Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-06-30First Open Access (FOA) Date
2017-08-05First Compliant Deposit (FCD) Date
2016-06-30Usage metrics
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