Resveratrol: metabolism, biological mechanisms, and potential side effects

Resveratrol, a natural stilbenoid found in grapes, berries, and other plants, has attracted significant scientific interest due to its broad spectrum of reported health benefits, including antioxidant, anti-inflammatory, anti-aging, and cardioprotective properties. This review synthesizes current knowledge on resveratrol, exploring its complex pharmacokinetics — characterized by high absorption but low oral bioavailability resulting from extensive presystemic metabolism—and its multifaceted mechanisms of action. We detail the activation of key signaling pathways such as SIRT1, AMPK, Nrf2, and PGC-1α, which mediate its effects on mitochondrial biogenesis, antioxidant defense, and metabolic homeostasis. A special focus is placed on the crucial role of gut microbiota in metabolizing resveratrol into active derivatives like dihydroresveratrol and lunularin, which contribute significantly to its biological effects and modulate gut health. Paradoxically, the review also addresses the compound’s potential adverse effects, examining how its oxidation into a reactive quinone form can lead to pro-oxidant effects, genotoxicity, disruption of cellular signaling, and endocrine disruption. This comprehensive analysis underscores the dual nature of resveratrol, highlighting both its therapeutic potential and the dose-dependent risks that must be considered for its future application in nutrition and medicine.