Oxidative stress and human diseases: Origin, link, measurement, mechanisms, and biomarkers.

Oxidative stress has been related increasingly to the onset and/or progression of a growing number of human diseases. However, large studies on supplementation with anti-oxidants for prevention or treatment of different pathologies have yielded contradictory and mostly negative results, as documented by numerous meta-analyses and clinical trials. Here we analyze in detail the findings of these studies and discuss major aspects that, in our opinion, are likely to be responsible for these confounding data. With the belief that a clear correlation between disease and oxidative stress is far from being proven for most pathological conditions, our argument focuses on the following points: i) choice of biomarker(s) and/or the biological system(s) for the analyses; ii) pitfalls in pre-analytical and analytical methods for assessing oxidative stress; and iii) scientific misconduct. Eventually, suggestions aiming to obtain more convergent results on this topic are provided.