An oral nutritional supplement with TRPM8 agonists as a cooling flavor improved swallowing function in post-stroke patients with oropharyngeal dysphagia

Post-stroke patients with OD (PSOD) show impaired oropharyngeal sensory function, impaired safety during voluntary swallow (VS) and a critical reduction of spontaneous swallowing frequency (SSF), increasing the risk of aspiration of oropharyngeal secretions. Our aim was to evaluate the effect of oropharyngeal sensory stimulation on the VS and SSF in chronic PSOD patients using a cooling sensation flavoring (TRPM8 agonists) in an oral nutritional supplement (ONS) drink and comparing it with a control ONS. We performed a prospective, crossover, interventional and open-label clinical study on 50 PSOD patients. Patients were randomized into two groups, which differed from each other according to the order in which the ONS were administered: (1) Group A (n = 25): 1st visit, cooling sensation (active) + 2nd visit, control; and (2) Group B (n = 25): 1st visit, control + 2nd visit, active. The swallowing function was evaluated pre and post administration of each product using the volume-viscosity swallowing test (V-VST) for the VS, including the prevalence of impaired safety and efficacy, and SSF (swallows/minute). A saliva sample before and after the administration of control and active ONS' was collected to quantify substance P (SP) and calcitonin gen-related peptide (CGRP) by using ELISA. We observed that mean basal SSF in PSOD was low (0.29 ± 0.21 swallows/min). PSOD patients showed a significant increase in SSF (51.6%, p < 0.0001), a 22% (p = 0.0449) reduction in the prevalence of impaired safety during VS and a 15% (p = 0.0453) increase in the concentration of salivary SP after the administration of the active ONS. In contrast, no significant changes were observed after the administration of the control product. The order of administration did not affect the results. In conclusion, the TRPM8 compound included in the active ONS facilitates sensory perception, enhancing the peripheral release of SP and improving SSF and safety of swallow during VS in PSOD, which suggests both cortical, and brainstem enhancement of swallow responses.