TRPM8 agonist cooling flavor in oral supplement improves swallowing function and safety in post-stroke dysphagia

Patients suffering from post-stroke oropharyngeal dysphagia (PSOD) often experience impaired oropharyngeal sensory function, leading to unsafe voluntary swallowing (VS) and a critical reduction in spontaneous swallowing frequency (SSF). This significantly increases the risk of aspiration of oropharyngeal secretions, a major cause of pneumonia and mortality. Current interventions often focus on compensatory strategies or muscle strengthening. Targeting sensory deficits, particularly through activation of TRPM8 receptors which detect cold and menthol, offers a novel approach to enhance sensory perception and potentially improve swallowing reflexes.

This prospective, crossover, interventional, and open-label clinical study enrolled 50 PSOD patients. Participants were randomized into two groups, receiving either an active oral nutritional supplement (ONS) containing TRPM8 agonists (cooling sensation) or a control ONS in a crossover design. Swallowing function was assessed pre and post-administration of each product using the volume-viscosity swallowing test (V-VST) for VS, evaluating impaired safety and efficacy, and measuring SSF (swallows/minute). Saliva samples were collected before and after administration to quantify substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations via ELISA.

Basal SSF in PSOD patients was notably low, averaging 0.29 ± 0.21 swallows/min. Following administration of the active ONS containing TRPM8 agonists, patients demonstrated significant improvements across multiple metrics. They experienced a 51.6% increase in SSF (p < 0.0001), indicating enhanced spontaneous swallowing. Furthermore, the prevalence of impaired safety during VS was reduced by 22% (p = 0.0449).

A 15% increase in salivary substance P (SP) concentration (p = 0.0453) was also observed after active ONS administration, suggesting a mechanism involving peripheral sensory nerve activation. In stark contrast, the control product yielded no significant changes in any measured parameters. The crossover design confirmed that the order of product administration did not influence these positive outcomes, reinforcing the direct effect of the TRPM8 agonist-enhanced ONS.