Circulating biomarkers of oxidative stress and antioxidant status in women with overweight and obesity following an 8-week energy-restricted ketogenic diet: Results from the randomized KETO-MINOX study.

BACKGROUND AND AIMS: Ketogenic diet (KD) has been proposed to improve oxidative stress through mechanisms related to nutritional ketosis; however, the relative contribution of ketosis and weight loss to redox adaptation remains unclear. This study aimed to evaluate the effects of an eight-week energy-restricted KD on circulating biomarkers of redox homeostasis in women with overweight and class I obesity.

METHODS

Eighty women were randomised to either an energy-restricted Mediterranean-style KD (KETO; n = 40) or an energy-restricted standard diet (STD; n = 40). Oxidative-stress, antioxidant-defence, and metabolic-stress biomarkers (FGF21 and GDF15) were assessed at baseline (T0), week 4 (T1), and week 8 (T2). A composite oxidative stress index (OSI) was calculated, and associations with inflammatory markers, ketone bodies, amino acids, and body composition were explored.

RESULTS AND

CONCLUSION

Sixty-six participants were included in the final analyses (KETO, n = 32; STD, n = 34). Both interventions induced significant changes in several redox-related biomarkers, with a marked rise in antioxidant capacity accompanied by a rise in 8-OHdG, and a net reduction in the composite OSI. No between-group difference survived correction for multiple testing at either time point; the early differences in ACW, PCL and total protein at week 4 were nominal only. Within-arm trajectories of FGF21 and GDF15 differed, but the randomised between-diet contrasts for both markers were non-significant. Principal component analysis revealed no distinct ketogenic redox phenotype. An eight-week energy-restricted KD did not provide detectable additional benefits for systemic redox homeostasis compared with a standard energy-restricted diet. The increase in antioxidant capacity was proportional to the degree of weight loss, whereas the OSI was not, indicating an absence of a KD-specific effect rather than establishing weight loss as the determinant of redox adaptation overall. The findings suggest that changes related to energy restriction and weight loss may be more important determinants of the observed redox adaptations than nutritional ketosis per se in women with overweight and obesity.

REGISTRATION NUMBER OF CLINICAL TRIAL: NCT05652972.