Oxidomics of Human Plasma Reveals Lower Oxidized Lipids After Acute Intake of Polyphenol-Enriched Flaxseed Oil: A Randomized Crossover Exercise Trial

Abstract

Dietary antioxidants offer protection against oxidative bursts caused by high-intensity physical exercise. However, their acute effects on specific lipid oxidation products, especially oxidized phosphatidylcholine (oxPC) and oxysterols, remain underexplored in human plasma. Nineteen female participants underwent a crossover study involving pre-exercise intake of either polyphenol-enriched flaxseed oil (FO) or water (control), followed by standardized high-intensity interval training (HIIT). Plasma collected at four time points (pre- to post-HIIT) was analyzed via targeted LC-MS/MS for oxPCs and oxysterols and untargeted lipidomics using LC-QTOF-MS. FO significantly suppressed the postexercise rise in oxPCs (e.g., SONPC, KOOA-PC, KDdiA-PC) and nonenzymatically formed oxysterols (7-ketocholesterol, 7β-hydroxycholesterol). Orthogonal PLS-DA showed obvious postexercise group separation between FO-consuming subjects versus control. Untargeted lipidomics revealed broader remodeling of the phospholipidome in the FO group. This study provides novel evidence that polyphenol-rich FO acutely mitigates lipid peroxidation, supporting its potential as a nutritional strategy for oxidative stress management.