The hormonal decline during menopause increases women's risk of chronic diseases. D-limonene, a monoterpene found in the human diet, possesses biological properties related to hypolipemic, antioxidant, anti-inflammatory, and gut microbiota-modulating activities, primarily observed in preclinical studies. Postprandial responses include physiological adaptations to the stress of a nutrient surplus, providing an opportunity to assess metabolic resilience, being a suitable strategy for exploring post-menopause-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 induce marked differences in postprandial responses to the dietary challenge. The supplementation with D-limonene induced no alterations in serum lipid/lipoprotein profile or glycemia/insulinemia. D-limonene supplementation did not affect the transient postprandial inflammatory response regarding changes in gene expression of peripheral blood mononuclear cells (PBMC) and circulating inflammatory markers. Nevertheless, D-limonene reduced postprandial levels of lithocholic acid, a 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 claim that short-term D-limonene supplementation beneficially affects the postprandial metabolism of postmenopausal women.Graphical
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