Betaine supplementation modulates mitochondrial and redox-related adaptations in premenopausal women with overweight: a randomized controlled trial

The aim of this study was to investigate the effects of betaine supplementation on mitochondrial and redox-associated parameters in premenopausal women with overweight or obesity. We hypothesized that betaine enhances selected mitochondrial enzyme content and improves antioxidant defense. In this randomized controlled trial, premenopausal women with overweight or obesity were assigned to receive anhydrous betaine supplementation (3 g/d) or a placebo condition for eight weeks. Mitochondrial enzyme content was assessed in peripheral blood mononuclear cells (PBMCs), including citrate synthase (CS) and cytochrome c oxidase (COX). Redox-related parameters were evaluated in plasma; these included the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as oxidized glutathione (GSSG) concentration. Preintervention and postintervention measurements were compared between groups. A significant treatment × time interaction was observed for CS concentration in PBMCs ( p = 0.043). The pre-to-post change differed significantly between the betaine and placebo groups (between-group difference in change: 102.3 μg/mg protein, 95% CI 3.19 to 201.4), although the within-group pre–post changes were not statistically significant. No significant treatment × time interaction was observed for COX ( p = 0.326). Plasma CAT activity showed a significant treatment × time interaction ( p = 0.003, ηp 2 = 0.213) and increased significantly only in the betaine group. No significant effects were observed for SOD ( p = 0.825), GPx ( p = 0.359), or GSSG ( p = 0.693). Betaine supplementation may selectively influence PBMC mitochondrial-associated parameters and circulating antioxidant enzyme activities in premenopausal women with overweight or obesity. The differential change in CS between the betaine and placebo groups and the increase in plasma CAT activity warrant further investigation, particularly to determine their physiological significance and underlying mechanisms. https://clinicaltrials.gov/study/NCT06344377.