Study of the D-limonene effects on lipid metabolism and postprandial glycemic response in postmenopausal women

The hormonal decline that occurs during menopause increases the risk of chronic diseases in women. D-limonene is a monoterpene commonly found in the human diet with biological properties related to hypolipemic, antioxidant, anti-inflammatory, and gut microbiota-modulating activities, mostly observed in preclinical studies. Postprandial responses include physiological adaptations to the stress of a nutrient surplus, providing an opportunity to assess metabolic resilience. This strategy is a suitable tool for exploring postmenopause-associated metabolic alterations. Here, we investigated the effects of D-limonene supplementation (2 g/day) on postprandial metabolism in postmenopausal women (n = 9) challenged with a standardized mixed meal in a 3-week single-arm clinical study. Our findings revealed that D-limonene did not exhibit marked differences in postprandial responses to the dietary challenge. The supplementation with D-limonene induced no alterations in the lipid/lipoproteins profile (LDL-, HDL- and total cholesterol, non-esterified fatty acids, triglycerides), nor in the glycemia/insulinemia. Furthermore, the transient postprandial inflammatory response was not affected by D-limonene supplementation in terms of changes in gene expression of peripheral blood mononuclear cells (PBMC) and circulating inflammatory markers. Nevertheless, D-limonene reduced postprandial levels of lithocholic acid, a major gut microbiota-derived bile acid, and regulated the plasma concentrations of selected amino acids, carbohydrate metabolism-derived metabolites and organic acids. In conclusion, our data do not support the notion that short-term D-limonene supplementation beneficially affects the postprandial metabolism of postmenopausal women