Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds.

Based on the significance of oxidized low-density lipoprotein (LDL) in health and disease, this review focuses on human studies addressing oxidation of LDL, including three lines of biomarkers, (i) ex vivo LDL resistance to oxidation, a "challenge test" model, (ii) circulating oxidized LDL, indicating the "current in vivo status", and (iii) autoantibodies against oxidized LDL as fingerprints of an immune response to oxidized LDL, along with circulating oxysterols and 4-hydroxynonenal as biomarkers of lipid peroxidation. Lipid peroxidation and oxidized LDL are hallmarks in the development of various metabolic, cardiovascular and other diseases. Changes further occur across life stages from infancy to older age as well as in athletes and smokers. Given their responsiveness to targeted nutritional interventions, markers of LDL oxidation have been employed in a rapidly growing number of human studies for more than 2 decades. There is growing interest in foods, which, besides providing energy and nutrients, exert beneficial effects on human health, such as protection of DNA, proteins and lipids from oxidative damage. Any health claim, however, needs to be substantiated by supportive evidence derived from human studies, using reliable biomarkers to demonstrate such beneficial effects. A large body of evidence has accumulated, demonstrating protection of LDL from oxidation by bioactive food compounds, including vitamins, other micronutrients and secondary plant ingredients, which will facilitate the selection of oxidation biomarkers for future human intervention studies and health claim support.