From bitter toxins to bioactive assets: redefining quinolizidine alkaloids in Lupinus spp.

Lupins ( Lupinus spp.) are climate-resistant grain legumes gaining attention as sustainable protein sources. However, their use in the human diet is limited by quinolizidine alkaloids (QAs), a class of nitrogenous secondary metabolites. QAs represent a nutritional paradox: They are central to plant defence mechanisms, yet confer toxicity and bitterness that compromise food safety and consumer acceptance. Recent findings suggest that at sub-toxic concentrations, certain QAs may exert bioactivities that could be important for metabolic regulation. Thus, the sustainable integration of lupins into food systems depends on whether QAs are considered as undesirable contaminants or redefined as bioactive phytochemicals with dose-dependent functional potential. Significant methodological progress has been made over the last five years. Advances in high-resolution techniques and metabolomics have expanded the structural catalogue of QAs, facilitated species- and genotype-specific chemotyping and allowed first conclusions on biosynthesis. At the technological level, novel processing methods have improved the efficiency of QA removal while maintaining protein quality and, in some cases, have enabled the selective extraction of alkaloids for potential valorisation. This review critically synthesises recent advances in QA chemistry, biosynthesis, analytical methodologies, toxicology, processing strategies and emerging bioactivities. Despite this progress, major challenges remain, including the lack of standardised analytical protocols, insufficiently defined sensory thresholds, fragmented regulatory frameworks and the absence of clinical validation. Future research should shift from exclusive alkaloid elimination towards controlled modulation and selective valorisation to establish lupins as safe, multifunctional crops contributing to food security, human health and sustainable agriculture. • QAs pose safety risks and offer bioactive potential in lupin-based foods. • Lack of harmonised QA limits hinders regulatory clarity and risk assessment. • Green debittering and biorefineries enable co-valorisation of lupin alkaloids. • Nanodelivery and functional foods expand QA use beyond detoxification. • Omics and toxicokinetics support predictive models for QA safety evaluation.