Acute Music-Frequency Exposure Modulates Salivary Stress and Neurotrophic Markers in Young Adults: A Randomized Controlled Trial

Background: The exam period is a period full of intense stress and anxiety that deeply affects cognitive and physiological responses for university students. Listening to music has the potential to protect cellular health and alleviate the negative effects of stress by affecting individuals' mood, and cognitive functions. This study aimed to investigate the differential effects of 528 and 432 Hz music frequencies on salivary BDNF, CREB, and GRP78 levels in young adults, along with their association with cognitive performance under exam-related stress. Methods: A total of 162 healthy university students were randomly assigned to three groups: no music (control), 528 Hz instrumental music, and 432 Hz instrumental music. Participants listened to music for 20 min, after which saliva samples were collected and analyzed for brain-derived neurotrophic factor (BDNF), glucose-regulated protein 78 (GRP78) and cyclic AMP response element-binding protein (CREB) levels using ELISA. Cognitive performance was assessed using the Stroop word-color test administered by medical doctor. Results: Exposure to 528 Hz music significantly increased salivary BDNF (3.84 [2.76–4.13]) and CREB levels (1.5 [1.38–1.59]) compared to control (p < 0.05), whereas GRP78 levels were elevated in the 432 Hz group (0.51 [0.47–0.58]) (p < 0.05). No significant differences were observed between groups in Stroop test performance. Conclusion: These findings suggest that specific music frequencies elicit distinct biological responses under exam-related stress, even in the absence of immediate cognitive performance differences. Salivary neurotrophic and stress-related biomarkers may offer valuable non-invasive insights into music's neuromodulatory effects. Trial Registration: ClinicalTrials.gov identifier: AMU-EC-8522.