Oxidative Stress and Inflammation in the Heterogeneity of Metabolic Health : An Integrative Analysis of Biomarkers, Lifestyle Determinants, and Mechanistic Pathways

Metabolic health is determined by complex biological processes that extend beyond anthropometric indicators such as body mass index (BMI). Chronic low-grade inflammation and oxidative stress are key mechanisms linking metabolic dysfunction to cardiometabolic disease, but their interaction across metabolic health phenotypes and clinical conditions remains insufficiently understood.

This thesis aimed to characterize inflammatory and oxidative stress profiles across metabolic health phenotypes, assess the clinical relevance of associated biomarkers, and identify modifiable determinants of these pathways. An integrative approach combining epidemiological analyses, a clinical pilot study, and mechanistic in vitro experiments was applied. Biomarkers included IL-6, soluble IL-6 receptor, C-reactive protein, coenzyme Q10, oxidized CoQ10, markers of oxidative damage, antioxidant capacity, and advanced glycation end products. Dietary patterns, physical activity, and gut microbiota composition were also evaluated.

The findings indicate that metabolic health status explains differences in inflammatory and oxidative stress profiles more effectively than BMI alone. Individuals with comparable BMI values showed distinct biomarker patterns depending on their metabolic phenotype. Physical activity and adherence to micronutrient- and antioxidant-rich dietary patterns were associated with more favorable biomarker profiles. Reduced gut microbial diversity was observed in metabolically unhealthy individuals and was linked to inflammation- and oxidative stress-related markers. Furthermore, complementary in vitro experiments further showed that a natural antioxidant extract from Haematococcus pluvialis reduced oxLDL-induced lipid accumulation in macrophages, providing mechanistic support for the potential modulation of redox-sensitive inflammatory pathways.

Overall, these findings demonstrate that metabolic health heterogeneity is closely associated with interactions between inflammation and oxidative stress. They support phenotype-specific biomarker interpretation and personalized strategies for preventing and managing metabolic disorders.