Cocrystals of β-Sitosterol with Propionic Acid Improve Postprandial Lipid Response and Long-Term Adaptation to Obesogenic Diets in Hamsters, Surpassing the Effects of Commercial β-Sitosterol

Objectives: This study investigated the short- and long-term metabolic effects of two β-sitosterol with propionic acid cocrystals (CCA and CCB) compared with commercial β-sitosterol in male hamsters. Methods: Five experiments were conducted, including three acute and two chronic dietary interventions. Acute experiments evaluated the metabolic response to a single dose of commercial β-sitosterol (S) or its cocrystals (513 mg/kg) administered with a pork-fat load following 40% caloric restriction. Blood samples were collected before and 5 h after the lipid challenge. Long-term studies assessed daily supplementation with CCA (264 mg/kg) or CCB (at two doses, 114 and 342 mg/kg) during exposure to high-fat (HF) or Western diets (WD), respectively, for 21 days. Results: Acutely, CCA attenuated postprandial triglyceride increases in adult animals, while CCB induced a reduced rise in postprandial cholesterol across the three studies compared to S. Young animals treated with CCA and CCB exhibited a reduction in postprandial glucose levels. Long-term, in HF-fed hamsters, CCA lowered plasma cholesterol and triglyceride levels on day 14 and, at the endpoint, decreased liver weight and increased circulating sitosterol levels, unlike its commercial counterpart. In WD-fed animals, CCB supplementation dose-dependently elevated plasma sitosterol levels. At the low dose, CCB treatment reduced body weight gain and cholesterol increase and improved adipocyte morphology, whereas the high dose reduced diet-induced hepatic detrimental outcomes, showing a stronger hepatoprotective effect compared to S-treated animals. Together, these results indicate improved postprandial lipid handling in the short-term and a modulation of metabolic adaptation to obesogenic diets in the long-term. Conclusions: β-sitosterol with propionic acid cocrystals improved metabolic responses more effectively than commercial β-sitosterol, enhancing bioavailability and potential therapeutic value against diet-induced metabolic disturbances.