Taste Modulation by Umami Compounds: Mechanisms, Sensor-Based Evaluation, and Pharmaceutical Applications in Bitterness Suppression.

Bitterness of oral active pharmaceutical ingredients (APIs) remains a major barrier to patient adherence, particularly in pediatric and geriatric populations. Conventional taste-masking strategies primarily rely on formulation-based approaches, but do not always sufficiently suppress activation of bitter taste pathways. Increasing attention has focused on taste-modulating compounds, including umami substances, which reduce bitterness through multiple stages of taste processing, including peripheral receptor responses, perceptual taste interactions, and central sensory integration. This review provides an integrated overview of umami-mediated bitterness suppression from molecular, sensory, neural, and analytical perspectives. Interactions between TAS2R bitter receptors and T1R1/T1R3 umami receptors, including possible downstream signaling convergence and sensory integration mechanisms, are discussed in relation to bitterness suppression. Representative umami compounds, including monosodium glutamate (MSG) and umami peptides, have been reported to suppress the bitterness of several bitter APIs, suggesting potential applicability beyond compound-specific taste-masking strategies. Recent advances in electronic taste-sensing technologies, particularly lipid/polymer membrane-based systems, enable quantitative evaluation of bitterness modulation. Because taste sensors primarily reflect peripheral physicochemical interactions rather than central sensory processing, this review further discusses the potential utility of the bitterness sensor BT0 for evaluating the peripheral component of bitterness suppression, drawing primarily on studies using MSG and representative umami peptides. Collectively, current evidence suggests that umami-mediated taste modulation may provide a rational framework for improving oral pharmaceutical palatability.