A randomized vagus nerve stimulation study demonstrates that serum aldosterone levels decrease with age in women, but not in men.

In this randomized, sham-controlled study, we explored the effects of acute transcutaneous vagus nerve stimulation (tVNS) on serum aldosterone in 20 younger (21-26 years) and 19 older (40-70 years) healthy participants. Blood samples were collected on two different days before and after a 20-min application of active tVNS at the inner tragus or sham stimulation of the earlobe. Irrespective of the stimulation mode, aldosterone levels decreased from pre- to post-stimulation in both the young (active: β = - 1.610 (- 2.855, - 0.365), p = 0.022; sham: β = - 0.857 (- 2.102, 0.388), p = 0.257) and the old cohort (active: β = - 1.969 (- 3.234, - 0.703), p = 0.005; sham: β = - 1.334 (- 2.600, - 0.069), p = 0.063). Although this decline was significant during active tVNS, the difference in estimated β-coefficients between active and sham stimulation was not statistically significant in either cohort. Nevertheless, aldosterone concentrations showed a significant interaction effect between sex and age (p = 0.001). Among all study participants, younger women (23.3 ± 1.6 years) had the highest mineralocorticoid levels (pre active: 172.1 ± 102.0 pg/ml, pre sham: 214.3 ± 82.3 pg/ml), whereas the lowest were observed in older females (59.4 ± 9.4 years) (pre active: 104.9 ± 85.8 pg/ml, pre sham: 81.1 ± 53.8 pg/ml). This post hoc analysis did not suggest that active auricular tVNS reduces serum aldosterone levels compared to sham stimulation in healthy subjects. However, serum aldosterone levels differed among subjects depending on their age and sex, irrespective of tVNS.