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

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Abstract

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.

Graphical abstract

This graph summarizes the different aspects covered in the review article. Changes from native to oxidized LDL play a central role in human (patho)physiology, such as for the transition from full health to metabolic and cardiovascular diseases and other disorders. These changes can be monitored by biomarkers of oxidized LDL, including (i) a “challenge test” model, such as the ex vivo LDL resistance to a defined oxidative stress (e.g., by copper(II) ions), (ii) markers of “current status”, such as in vivo circulating oxidized LDL, along with oxysterols and 4-hydroxynonenal (HNE), and (iii) fingerprints of an “immune response” to oxidized LDL, such as (auto)antibodies against oxidized LDL. These biomarkers have been reviewed at life stages from infancy to older age, in healthy subjects, including athletes and smokers, as well as patients with different metabolic, cardiovascular and a variety of other diseases. A major focus of research addressed the effects of bioactive compounds in human intervention studies, including single vitamins and trace elements and combinations thereof, as well as different fruits, vegetables and oils known to contain bioactive compounds. Taken together, a valuable resource of comprehensive information has accumulated which may be useful for selecting informative biomarkers for human intervention studies and health claim support.

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