Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism

Clin Rheumatol. 2018 Feb;37(2):505-514. doi: 10.1007/s10067-017-3618-5. Epub 2017 Apr 8.


A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

Keywords: Brain; Clinical trials and methods; Endocrine; Gastrointestinal; Hormones; Metabolic disease; Metabolomics; Rheumatoid arthritis; Study design.

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Arthritis, Rheumatoid / metabolism*
  • C-Peptide / blood*
  • Calorimetry, Indirect
  • Cross-Over Studies
  • Energy Metabolism / physiology*
  • Female
  • Follicle Stimulating Hormone / blood
  • Human Growth Hormone / blood
  • Humans
  • Luteinizing Hormone / blood
  • Middle Aged
  • Postprandial Period / physiology*
  • Prolactin / blood
  • Thyrotropin / blood
  • Vagus Nerve Stimulation*


  • C-Peptide
  • Human Growth Hormone
  • Adrenocorticotropic Hormone
  • Prolactin
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Thyrotropin