Differential effects of voluntary exercise and Totum-448, a plant-based formulation, in a hamster model of MASLD.

Lifestyle interventions constitute first-line strategies for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), with dietary modification and increased physical activity forming the core evidence-based approaches. In this framework, plant-based supplements are being investigated as potential adjunctive strategies. Totum-448, a polyphenol-rich plant formulation, has shown promising effects in preclinical studies. Here, we evaluated the effects of Totum-448, voluntary exercise (Vex), and their combination in a hamster model of MASLD. Fifty-four male golden Syrian hamsters were fed either a normal diet (ND) or a Western diet (WD) for six weeks. WD-fed animals were then randomized to receive WD alone, WD supplemented with Totum-448 (5% w/w), WD with Vex, or WD with both interventions for an additional five weeks. We hypothesized that only the combined intervention would elicit measurable benefits. Contrary to this hypothesis, distinct effects were observed for each intervention: Totum-448 reduced circulating lipid levels and downregulated hepatic markers of inflammation and fibrosis, whereas Vex improved body composition, increased energy expenditure, and reduced hepatic lipid content. No significant improvements were detected in histological markers of inflammation or fibrosis. The combined intervention did not provide additional benefits beyond those of the individual interventions. In conclusion, Totum-448 and Vex exert complementary effects in MASLD. Although no additive effects were observed, the combined intervention provided the broadest overall protection by preserving the benefits of each intervention alone. These findings support the relevance of combining exercise with plant-based nutritional strategies in the management of MASLD.