Impact of Daily High Ergosterol Intake for 14 Weeks in Ovariectomized Rats on Cholesterol and Vitamin D₃ Biosynthesis...

Postmenopausal women are at a higher risk of developing dyslipidemia and osteoporosis due to estrogen deficiency, necessitating regular vitamin D supplementation and the use of cholesterol inhibitors, respectively, to prevent these conditions. Despite current treatments, alternatives are needed to address both conditions simultaneously. Ergosterol, a precursor of vitamin D₂, is a fungal sterol converted to brassicasterol by 7-dehydrocholesterol reductase, a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D₃) into cholesterol. Our previous research demonstrated that ergosterol decreases cholesterol levels and increases 7-dehydrocholesterol levels in human HepG2 hepatoma cells. Furthermore, we reported that ergosterol increases vitamin D₂ levels, inhibits the cholesterol biosynthetic pathway, and potentially promotes vitamin D₃ biosynthesis in male rats fed a high-fat and high-sucrose diet. In this study, we investigated the effects of daily high ergosterol intake on cholesterol, vitamin D₂, and D₃ biosynthetic pathways in ovariectomized (OVX) rats using GC-MS and LC with tandem mass spectrometry. OVX rats treated with ergosterol for 14 weeks exhibited significantly decreased plasma cholesterol levels and markers of cholesterol absorption, such as the plant sterol sitosterol. Furthermore, 7-dehydrocholesterol levels increased in these rats compared to untreated OVX rats. We observed that 1α, 25-dihydroxyvitamin D₃ levels slightly increased in OVX rats treated with ergosterol. Additionally, ergosterol improved bone strength and increased OVX-induced bone resorption. These results indicate that daily ergosterol intake may aid in the simultaneous prevention of dyslipidemia and osteoporosis in postmenopausal women.