Total Antioxidant Capacity and Lipid Peroxidation in Health and Disease: A Systematic Review

Background: Oxidative stress — defined by the imbalance between reactive oxygen species (ROS) production and antioxidant defense capacity — is a pivotal pathophysiological mechanism in numerous chronic diseases. Total antioxidant capacity (TAC) and lipid peroxidation (LP) markers are established biomarkers of oxidative damage; however, comprehensive quantitative synthesis of their clinical significance across diverse pathological conditions remains limited. Objectives: To systematically review the alterations in total antioxidant capacity (TAC) and lipid peroxidation (LP) markers across diverse chronic disease states, evaluating their correlation, disease-specific patterns, and the comparative performance of TAC measurement methodologies, while identifying clinical and demographic factors modifying biomarker expression and providing evidence-based recommendations for clinical application and future research. Methods: Following PRISMA 2020 guidelines, comprehensive searches were conducted across PubMed, Scopus, Web of Science, Embase, and CENTRAL (2016 to March 2026). Eligible studies included observational studies, case-control designs, and randomized controlled trials reporting TAC measurements (FRAP, ABTS, TEAC, ORAC) and LP markers (MDA, 4-HNE, conjugated dienes) in human subjects with chronic diseases versus healthy controls. Two independent reviewers performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool. Results: From 8,247 deduplicated records, 156 studies met inclusion criteria, encompassing 42,389 participants across multiple chronic disease categories. Across all conditions, TAC was consistently and substantially decreased in disease states compared to healthy controls, with the most pronounced reductions in chronic kidney disease, cardiovascular disease, and diabetes mellitus. Lipid peroxidation markers showed consistent elevation across all pathological conditions examined. A strong inverse association was observed between TAC and LP markers across disease subgroups. FRAP demonstrated superior diagnostic performance compared to alternative TAC assays. Advancing age, longer disease duration, higher BMI, and greater comorbidity burden were identified as factors amplifying oxidative stress biomarker alterations. Conclusions: This systematic review provides robust evidence that decreased TAC and elevated lipid peroxidation are consistent biomarker signatures across diverse chronic diseases. The magnitude of these alterations correlates with disease type, severity, and key clinical covariates, supporting their utility as complementary diagnostic and monitoring tools. Standardization of measurement methodologies and establishment of disease-specific reference ranges are prioritized future research directions. Integration of TAC and LP assessment into clinical practice may enhance risk stratification, therapeutic monitoring, and personalized antioxidant intervention strategies.