Effects of a Chilean Hazelnut-Supplemented Diet on Oxidative Stress and Cytokine Expression in PBMCs of Hypercholesterolemic Adults: A Randomized Controlled Trial

Background/Objectives: Hypercholesterolemia is characterized by alterations in lipid metabolism, oxidative stress, and inflammatory status. Nuts have been shown to mitigate these alterations; however, limited evidence is available regarding their effects in the Chilean population using a native nut species. This study aimed to assess the impact of a six-month Chilean-adapted Mediterranean diet supplemented with Gevuina avellana Molina, compared with a low-fat regimen, on oxidative stress and inflammatory markers in peripheral blood mononuclear cells (PBMCs) from adults with hypercholesterolemia. Methods: A randomized controlled trial was conducted with a 6-month nutritional intervention. Of 106 hypercholesterolemic adults randomized, 81 completed the study, allocated to two groups: one following a Chilean diet supplemented with Chilean hazelnuts (n = 47) and the other a low-fat diet (n = 34) (ClinicalTrials.gov: NCT07087704). Oxidative stress markers and inflammatory markers in PBMCs were assessed as secondary outcomes. In PBMCs, reactive oxygen species (ROS) production and the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GRd) were analysed, along with oxidative damage markers (malondialdehyde, carbonyls, and nitrotyrosine) and gene expression (SOD, CAT, GRd, IL-10, and TNF-α). Results: Both dietary interventions were associated with similar improvements in PBMC redox status, characterized by reduced oxidative damage and enhanced antioxidant defence capacity. Malondialdehyde and carbonyl levels decreased in both groups following the dietary intervention. In addition, antioxidant enzyme activities increased, with SOD showing a concomitant increase in gene expression level, whereas CAT gene expression decreased despite enhanced enzymatic activity. No significant differences between groups were observed for the assessed oxidative stress, antioxidant, or inflammatory markers. Conclusions: A Chilean diet supplemented with Chilean hazelnuts and a low-fat diet produced similar improvements in PBMC redox status in hypercholesterolemic adults. These findings suggest that improving dietary fat quality and increasing antioxidant-rich food intake may contribute to favourable changes in cellular redox homeostasis, although the specific contribution of Chilean hazelnuts requires further investigation.