Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin

Abstract

Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single‐blinded randomized cross‐over protocols, blood glucose levels, plasma concentrations of insulin, C‐peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor‐heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0–2.5 mA, 30 min) or sham‐taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects ( n = 16) were fasted throughout the protocol and in a second protocol, subjects ( n = 10) received a high‐calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham‐taVNS. No significant effects of taVNS on heart rate variability and baroreceptor‐heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: −115.5 ± 28.3 pg/ml vs. sham‐taVNS: −51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow‐up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.

Non-invasive vagus nerve stimulation decreases vagally mediated heart rate variability

“…An important factor that might modulate the effectiveness of taVNS in regulating cardiovascular function is the body's metabolic state (Kozorosky et al, 2022;Sclocco et al, 2019;Szulczewski, 2022). After the caloric load, we found that taVNS decreased HF-HRV and RMSSD further amplifying the reduction in RMSSD and HF-HRV induced by the milkshake.…”

“…In addition, small sample sizes (Wolf et al, 2021, meta-analysis: median(N) = 30, range(N) = 7-60 of taVNS studies with within-subject design), lack of a common stimulation protocol, appropriate baseline measurements, and adequate control conditions may contribute to discrepancies across studies. Likewise, other physiological factors, such as the respiratory rate or hormonal balance (Kozorosky et al, 2022;Sclocco et al, 2019;Szulczewski, 2022), interact with the effect of taVNS, indicating a complex interplay between physiological states and taVNS-induced changes. To summarize, pressing questions about the differential effects of taVNS at the left vs. the right ear and the emerging evidence of interactions with metabolic state (Altınkaya et al, 2023;Vosseler et al, 2020) call for additional studies on cardiovascular effects.…”

Pediatric Vagus Nerve Stimulation: Case Series Outcomes and Future Directions

“…35 One key aspect of patient selection relates to recent discoveries that VNS has a myriad of effects—systemically and neurologically—which are only now becoming apparent. In addition to VNS′ well-documented and U. S. Food and Drug Administration–approved indication for depression, 36 early reports document therapeutic benefit in seemingly unrelated and comorbid disorders in patients with epilepsy including autism spectrum disorder, 37 obesity, 38 heart failure, 39 and rheumatoid arthritis. 40 As our understanding of the role of VNS in these and other disorders evolves, it will be important to consider these factors as well when identifying surgical candidates for VNS implantation.…”

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications

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