Calcium homeostasis as a food-science framework linking food-derived nutrients and bioactive compounds to glucose regulation and metabolic health.

Calcium homeostasis is increasingly recognized as a mechanistic hub linking food-derived nutrients, bioactive compounds, gut-derived signals, and host glucose regulation. However, existing reviews have generally examined dietary bioactives, the gut microbiota, or metabolic disorders separately, without establishing calcium signaling as an integrated food-science framework. This review critically evaluates current evidence on how food-derived nutrients and bioactive compounds influence calcium homeostasis and calcium-dependent signaling in metabolically relevant tissues, including intestinal enteroendocrine cells, pancreatic β-cells, liver, adipose tissue, and skeletal muscle. Particular attention is given to food sources, gut microbiota interactions, food matrix effects, processing and storage influences, and the physiological relevance of dietary exposure. Available evidence indicates that selected food components may modulate calcium-sensing receptor signaling, transient receptor potential channels, voltage-gated calcium influx, endoplasmic reticulum calcium handling, and gut-derived mediators such as short-chain fatty acids and bile acid-related pathways. These mechanisms may influence incretin secretion, insulin secretion, insulin sensitivity, inflammatory tone, and hepatic glucose metabolism. However, the strength of evidence varies substantially across food components, tissues, and experimental models, and many reported effects rely on isolated compounds, nonphysiological doses, or limited in vivo validation. Current knowledge is also constrained by insufficient consideration of the food matrix, bioaccessibility, host-microbial cometabolism, and realistic consumption conditions, particularly the use of non-physiological in vitro concentrations and the lack of validation in whole-food matrices under realistic intake scenarios. Positioning calcium homeostasis as a food-science mechanism may improve the interpretation of the metabolic health effects of food components and help identify physiologically achievable calcium-signaling targets, matrix-aware formulations, and consumption-relevant strategies for functional food design.