Associations between modifiable lifestyle behaviours and plasma biomarkers of oxidative stress, inflammation and NAD+ metabolism in an apparently healthy human cohort

Abstract

Non-communicable diseases (NCDs) such as cardiovascular disease and diabetes are major causes of morbidity and mortality worldwide. Accumulated evidence strongly supports the view that unhealthy lifestyle behaviours are common underlying promoters of the change in biochemistry resulting in the development of NCDs. Early identification of the biochemical anomalies through which lifestyle behaviours drive the disease process, may be a key to developing early intervention strategies to prevent or subvert NCD development. Importantly, a growing body of evidence suggests that lifestyle-associated activation of oxidative and inflammatory processes are primary drivers of the cell and tissue damage which underpin the development of several NCDs. It is hypothesised that the presence of, often subclinical, oxidative and inflammatory processes silently drive the disease process during the long prodromal stage of disease. Therefore, using a cross sectional design, the studies presented in this thesis investigated, whether it is possible to a) identify changes in oxidative stress status and inflammatory activation in individuals with no clinical signs of disease and, b) where present, ascertain whether these changes were associated with lifestyle behaviours previously linked to the development of NCDs. The data presented in this thesis shows significant relationships between oxidative stress and inflammatory biomarkers of disease-free subjects and their individual or composite lifestyle behaviours. These findings indicate that significant biochemical shifts in oxidative and inflammatory processes are detectable in apparently healthy individuals and are associated with lifestyle-related behaviours. It was also observed that these changes in oxidative and inflammatory processes were significantly associated with other established NCD risk indicators such as the Framingham risk score and carotid intima media thickness. Correlation with disease risk markers at this early stage, when no clinical symptoms are yet manifest, suggests that quantification of oxidative stress and inflammatory biomarkers during the disease-free stage may have clinical relevance as a timely indicator of the presence of subclinical biochemical changes portending the development of disease. Early identification of subclinical disease processes through monitoring of these subclinical indicators may therefore enable earlier and more efficient strategies to prevent NCD development.