Abstract
Multicomponent dietary supplements are commonly compared by ingredient count and labeled milligrams, whereas finished-product performance is determined by molecular identity, free con-centration, tissue delivery, and biological response. This critical integrative review introduces net-work-appropriate exposure as a design principle linking four decisions: what to provide, how much to provide, how to deliver it, and what to prioritize or omit. The framework treats the formulation matrix, dose ratio, host state, and time as joint determinants of effective exposure. Literature was organized across gastrointestinal transformation, mineral and nutrient competition, tolerable upper intake levels, precision nutrition, mixture interactions, analytical compatibility and assay develop-ment, and four connected functional domains: the barrier-microbiota-immune interface, redox and extracellular-matrix homeostasis, mitochondrial bioenergetics, and membrane-cofactor signaling. Six cumulative evidence stages organize progression from product identity through gastrointestinal transformation, plausible local or systemic exposure, target engagement, reproducible phenotype, and human outcomes with safety. A rational dose window integrates target-relevant exposure with saturation, competition, tolerability, interaction, clearance, and established intake limits, while ana-lytical validity is embedded across every stage. Together, these elements define a testable product-level architecture for the design, evaluation, and translation of multicomponent dietary supple-ments.