We examined the feasibility of using the neofunctional deep breathing (NDB) technique to reduce the allostatic load following the Trier Social Stress Test (TSST). Forty-four healthy subjects were randomised into experimental and control groups. Following the TSST procedure, participants underwent either a single session of NDB or an attention control intervention. The Procomp Infinity Biofeedback system measured breath per minute (BPM), respiratory amplitude, HRV linear domains, skin conductance, and trapezius muscle electromyographic activity. Cortisol and cytokine salivary concentrations, perceived stress, and anxiety levels were also assessed. These parameters were combined into an allostatic load index (ALI) to measure the intervention's effect. This pilot RCT demonstrated the feasibility of the study design and practicality of the intervention. The NDB group showed reduced ALI, increased respiratory abdominal amplitude, decreased BPM, increased HRV indicating parasympathetic activation, and decreased cortisol and inflammatory cytokines. This study highlighted the feasibility of testing the NDB technique in reducing allostatic load through a neurobiological and anti-inflammatory response after exposure to psychosocial stress. This protocol can represent a non-invasive therapeutic adjutant in disorders related to a dysregulation of the HPA axis or to an inflammatory state. Trial Registration: NCT04102813.
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