Redox Systems Biology of Nutrition and Oxidative Stress

Diet and nutrition contribute to both beneficial and harmful aspects of oxidative processes. The harmful processes, termed oxidative stress, occur with many human diseases. Major advances in understanding oxidative stress and nutrition have occurred with broad characterization of dietary oxidants and antioxidants, and with mechanistic studies showing antioxidant efficacy. However, randomized controlled trials in humans with free-radical-scavenging antioxidants and the glutathione precursor N-acetylcysteine have provided limited or inconsistent evidence for health benefits. This, combined with emerging redox theory, indicates that holistic models are needed to understand the interplay of nutrition and oxidative stress. The purpose of this article is to highlight how recent advances in redox theory and the development of new omics tools and data-driven approaches provide a framework for future nutrition and oxidative stress research. Here we describe why a holistic approach is needed to understand the impact of nutrition on oxidative stress and how recent advances in omics and data analysis methods are viable tools for systems nutrition approaches. Based on the extensive research on glutathione and related thiol antioxidant systems, we summarize the advancing framework for diet and oxidative stress in which antioxidant systems are a component of a larger redox network that serves as a responsive interface between the environment and an individual. The feasibility for redox network analysis has been established by experimental models in which dietary factors are systematically varied and oxidative stress markers are linked through integrated omics (metabolome, transcriptome, proteome). With this framework, integrated redox network models will support optimization of diet to protect against oxidative stress and disease.