Metabolic Syndrome Disrupts the Association Between Serum Malondialdehyde and Lipoprotein Subclasses

Malondialdehyde (MDA) is a widely used biomarker of lipid peroxidation, yet its relationships with lipoprotein subclasses remain poorly explored, particularly in metabolic syndrome (MS). We investigated associations of free MDA measured by the TBARS assay (MDA-TBARS) and total MDA quantified by high-performance liquid chromatography (MDA-HPLC) with NMR spectroscopy-measured lipoprotein subclasses in 65 healthy volunteers (HV) and 65 patients with MS. MDA-HPLC concentrations were higher than MDA-TBARS, and the two measures were strongly correlated. Free MDA levels were significantly elevated in MS, whereas total MDA did not differ between groups. In HV, MDA-TBARS showed positive relationships with VLDL and IDL, as well as triglyceride enrichment of LDL, IDL, and HDL, and a negative relationship with levels and cholesterol content of small, dense HDL, as well as cholesterol and phospholipid content of LDL subclasses. MDA-HPLC only showed a positive association with VLDL levels in HV. In contrast, no significant associations between MDA and lipoproteins were observed in MS. Multivariable analyses confirmed that lipoprotein profiles were able to discriminate between low and high MDA levels in HV, but not in patients with MS. In conclusion, interactions between oxidative stress and lipoproteins are strongly context dependent, being preserved in health but disrupted in MS, with free MDA emerging as a more informative marker of lipoprotein-associated lipid peroxidation.