Very-Low-Energy Ketogenic Therapy Modulates the Metabolic–Antioxidant Axis in Patients with Obesity and Type 2 Diabetes: A Non-Randomized Clinical Trial

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Abstract

Background: Oxidative stress and chronic inflammation contribute to the pathogenesis of obesity and type 2 diabetes (T2D), yet the effects of dietary interventions on endogenous antioxidant defences remain poorly defined. This is a non-randomized study evaluates the effects of very-low-energy ketogenic therapy (VLEKT), compared with a Mediterranean diet (MedD) and a control group, on antioxidants, metabolic, and inflammatory markers. Materials and Methods: Thirty adults with obesity and T2D were assigned to VLEKT (n = 10), MedD (n = 10), or control (n = 10) for 90 days. Metabolic parameters, inflammatory cytokines, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were assessed. Longitudinal changes were analyzed using linear mixed models. Results: VLEKT exhibited significant reductions in body weight, fat mass, HbA1c, and HOMA-IR. SOD activity increased in the VLEKT group, whereas no significant changes were observed in MedD. Changes in SOD were inversely associated with changes in HOMA-IR. GPx showed a less consistent response pattern, while inflammatory markers did not differ between groups. Conclusions: VLEKT was associated with substantial metabolic improvement accompanied by a selective modulation of antioxidant enzyme activity. The increase in SOD activity and its association with HOMA-IR suggest a link between metabolic and redox adaptations in subjects with obesity and T2D.

Tini, Sabrina, Stefano Celano, Stella Pigni, Elena De Palma, Hilal Irem Ozdemir, Tommaso Raiteri, Alessandro Antonioli, Jessica Baima, Valentina Antoniotti, Marina Caputo, and et al. 2026. "Very-Low-Energy Ketogenic Therapy Modulates the Metabolic–Antioxidant Axis in Patients with Obesity and Type 2 Diabetes: A Non-Randomized Clinical Trial" Antioxidants 15, no. 7: 844. https://doi.org/10.3390/antiox15070844

https://www.mdpi.com/2076-3921/15/7/844

Posted Jul 11, 2026, 1:22 PM UTC

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