LAUSR

OBJECTIVE We previously showed that a training intervention comprising a combination of meditation, exposure to cold and breathing exercises enables voluntary activation of the sympathetic nervous system, reflected by profoundly increased plasma epinephrine levels, and subsequent attenuation of the lipopolysaccharide (LPS)-induced inflammatory response. Several elements of the intervention may contribute to these effects, namely two different breathing exercises (either with or without prolonged breath retention) and exposure to cold. We determined the contribution of these different elements to the observed effects. METHODS Forty healthy male volunteers were randomized to either a short or an extensive training in both breathing exercises by either the creator of the training intervention or an independent trainer. The primary outcome was plasma epinephrine levels. In a subsequent study, 48 healthy male volunteers were randomized to cold exposure training, training in the established optimal breathing exercise, a combination of both, or no training. These 48 participants were subsequently intravenously challenged with 2 ng/kg LPS. The primary outcome was plasma cytokine levels. RESULTS Both breathing exercises were associated with an increase in plasma epinephrine levels, which did not vary as a function of length of training or the trainer (F(4,152) = 0.53, p = 0.71 and F(4,152) = 0.92, p = 0.46, respectively). In the second study, the breathing exercise also resulted in increased plasma epinephrine levels. Cold exposure training alone did not relevantly modulate the LPS-induced inflammatory response (F(8, 37) = 0.60, p = 0.77), whereas the breathing exercise led to significantly enhanced anti-inflammatory and attenuated pro-inflammatory cytokine levels (F(8, 37) = 3.80, p = 0.002). Cold exposure training significantly enhanced the immunomodulatory effects of the breathing exercise (F(8, 37) = 2.57, p = 0.02). CONCLUSION The combination of cold exposure training and a breathing exercise most potently attenuates the in vivo inflammatory response in healthy young males. Our study demonstrates that the immunomodulatory effects of the intervention can be reproduced in a standardized manner, thereby paving the way for clinical trials.Trial registration:ClinicalTrials.gov identifiers: NCT02417155 and NCT03240497.