Oxidative stress: a concept in redox biology and medicine Original paper

What was reviewed?

This mini review revisits the oxidative stress concept in medicine and redox biology, tracing its origin (coined in 1985) and explaining why the term remains influential yet frequently misapplied. Sies emphasizes that oxidative stress should be understood as a shift in redox balance—not a vague label for “bad things involving oxygen.” The review highlights how modern redox biology has moved beyond a simplistic “free radicals cause disease” narrative toward mechanistic work on redox signaling, compartment-specific redox control, and molecular “redox switches” (especially reversible cysteine oxidation in proteins). A major theme is methodological and conceptual rigor: clinicians and researchers should specify which oxidant is involved (e.g., hydrogen peroxide rather than generic “ROS”) and avoid overinterpreting nonspecific surrogate measures such as total antioxidant capacity.

Who was reviewed?

Rather than evaluating a defined patient cohort, this article synthesizes evidence across chemistry, biochemistry, physiology, and translational medicine, spanning experimental models (cells, organisms), human biomarker literature, and clinical trials of antioxidant supplementation. It also integrates landmark conceptual and methodological developments in the field, including the evolution from an original definition of oxidative stress (prooxidant–antioxidant imbalance) to an updated framework that explicitly includes disruption of redox signaling and control. The review draws on broad biomedical contexts—such as inflammation, infection-related micronutrient deficiencies (e.g., selenium), and chronic metabolic disease—illustrating how oxidative stress is invoked across conditions, sometimes appropriately and sometimes as an imprecise placeholder for unknown mechanisms.

Most important findings

The review’s central finding is that the oxidative stress framework is most useful when tied to specific redox chemistry and molecular targets. Sies argues that indiscriminate phrasing (“cells were exposed to oxidative stress”) obscures biology; experiments expose systems to defined oxidants, and clinical interpretations should likewise specify the relevant redox components. A second key point is that antioxidant defense is dominated by enzymatic systems rather than small-molecule antioxidants, helping explain why large clinical trials focused on one or two antioxidant vitamins often underperformed expectations. The most clinically actionable insight is that global, nonspecific measurements (notably total antioxidant capacity in plasma) are poor proxies for organismal redox state; instead, patterns of antioxidant enzyme activity and discrete oxidative damage products provide more interpretable signals. Finally, the review highlights the rise of redox signaling via reversible cysteine modifications and its integration with phosphorylation-based signaling—positioning redox biology as a mechanism-rich discipline rather than a catch-all explanation. Notably, the paper does not address microbiome composition or microbial signatures; any microbiome relevance is indirect (e.g., oxidative stress as a host milieu factor that could influence microbial ecology, rather than a reported microbial association).

Key implications

For clinicians, this review is a caution against treating “oxidative stress” as a diagnosis or a universal causal pathway. The practical implication is to demand biochemical specificity: when oxidative stress is proposed in a disease model, ask which oxidants, which targets, which compartment, and which adaptive responses are involved—and whether validated biomarkers support that claim. Therapeutically, the review helps explain why blanket antioxidant supplementation often fails: redox systems are networked, regulated, and compartmentalized, so simplistic “more antioxidants” strategies can miss the biology. For microbiome-focused practice and databases, the paper contributes conceptually by clarifying host redox state as an environmental selector, but it provides no direct microbial taxa, functional pathways, or microbiome signatures suitable for curation.

Citation

Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biology. 2015;4:180-183. doi:10.1016/j.redox.2015.01.002