Beyond bitterness: a comprehensive review of limonoid debittering, bioavailability, metabolic regulation, and potential biological significance of bitterness

Limonoids are the primary contributors to the delayed bitterness in citrus juice, yet they also exhibit potent antioxidant, anti-inflammatory, metabolic regulatory, cardioprotective, detoxifying, and anti-aging activities. However, their intense bitterness and low oral bioavailability, along with limited understanding of how bitterness relates to bioactivity, substantially limit their application in functional foods and nutritional supplements. This review systematically summarises current debittering technologies, the bioavailability of limonoids, their multi-target health benefits, interactions with other bioactive compounds, and their affinity for human bitter taste receptors (TAS2Rs). The main conclusions are as follows: i) resin adsorption remains the predominant industrial debittering strategy, whereas enzymatic and microbial approaches offer higher selectivity and milder processing conditions; ii) although systemic absorption of limonoids is low, gut-mediated effects and local intestinal exposure are biologically meaningful; and iii) even at low bioavailable doses, limonoids can improve metabolic homeostasis, protect multiple organs, and extend lifespan in experimental models, primarily through AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2)-dependent pathways. Overall, this review links bitter taste modulation with functional enhancement and provides a conceptual framework and practical guidance for the development of low-bitterness, high-value citrus products enriched in limonoids.