Evidence Trace, complete trial record
In plain terms
In plain terms: Transcutaneous Vagus Nerve Stimulation has strong evidence from human clinical trials. The benefit shown in those trials is if that describes your situation.
Transcutaneous Vagus Nerve Stimulation
A
Replicated: replicated trials on a qualifying endpoint
The endpoint this grade is based on: Validated scale scored by a clinician blinded to treatment
The evidence as the record states it
Perioperative cognition, three sham-controlled trials from three Chinese centers: Zhou et al. (Aging Clin Exp Res, 2022; PMID 35809206), 124 older adults having joint replacement, auricular stimulation from 1 hour before anesthesia to the end of surgery; delayed neurocognitive recovery at 1 week in 10 percent against 27 percent with sham, with lower IL-6 and S100-beta; funded by the National Natural Science Foundation of China. Li et al. (Neuromodulation, 2026; PMID 42104979), 103 older patients having gastrointestinal tumor surgery, 30 minutes daily from the day before to day 4 after; postoperative cognitive dysfunction on the MoCA in 10.2 percent against 32.7 percent; registered retrospectively. Ma et al. (J Geriatr Oncol, 2026; PMID 42456197), 103 older adults after laparoscopic gastrointestinal tumor resection, double-blind; MoCA higher from day 7 through 3 months, by 2 to 3 points. Shi et al. (Clin Interv Aging, 2026; PMID 41835922): 150 patients aged 65 and over, stimulation during major non-cardiac surgery; postoperative delirium 12 against 25 percent, a related endpoint. Cognition in mixed samples: Liu et al. (Psychol Med, 2026; PMID 42339645), systematic review of 53 studies with 30 pooled, more than 1,500 participants; g 0.41 overall, strongest for executive function, across healthy and clinical samples, mostly short laboratory tasks with varied devices and sites. Ridgewell et al. (Neuropsychology, 2021; PMID 34043386): 19 studies in healthy adults, g 0.21, mainly executive function. Wang et al. (Brain Stimul, 2022; PMID 36150665): 52 patients with mild cognitive impairment, double-blind, acupoint-site sham; MoCA-Basic improved at 24 weeks, one trial. Autonomic: Souza et al. (Auton Neurosci, 2026; PMID 41506123), meta-analysis of 13 sham-controlled trials of which 6 used transcutaneous vagus stimulation; no significant effect on time- or frequency-domain heart rate variability. Soltani et al. (Clin Auton Res, 2023; PMID 37119426): systematic review of 21 studies in healthy people; results mixed, baroreflex sensitivity changed in 1 of 6 studies. Grade A on the perioperative use: a validated cognitive scale scored blind, replicated across three independent sham-controlled trials, none large and all from one country.
PMID 42339645 PMID 42104979 PMID 42456197 PMID 35809206 PMID 41835922 PMID 36150665 PMID 34043386 PMID 41506123 PMID 37119426
Evidence by specific use
Postoperative cognitive dysfunction in older adults having major surgery
Grade A
Three sham-controlled trials agree: Zhou et al. (2022; PMID 35809206) and Ma et al. (2026; PMID 42456197), both double-blind, and Li et al. (2026; PMID 42104979), with Shi et al. (2026; PMID 41835922) finding less postoperative delirium in 150 patients as a related endpoint. A validated cognitive scale scored without knowledge of allocation, replicated across independent groups, meets the written A definition. Limits stated beside the letter: all three trials are from one country and about 100 patients each, and one was registered retrospectively.
PMID 35809206 PMID 42104979 PMID 42456197 PMID 41835922
Cognitive test performance in healthy adults and mixed clinical samples
Grade C
Liu et al. (2026; PMID 42339645) pool 30 studies: g 0.41 overall, strongest for executive function, with no difference between clinical and healthy samples. Ridgewell et al. (2021; PMID 34043386) pool 19 studies in healthy adults: g 0.21. The studies are small, mostly single laboratory sessions, and differ in device, site, intensity and population, so no specific protocol has two independent positive trials: C.
PMID 42339645 PMID 34043386
Cognition in mild cognitive impairment
Grade C
Wang et al. (2022; PMID 36150665): double-blind trial, MoCA-Basic improved at 24 weeks against an acupoint-site sham. One trial, not repeated: C.
PMID 36150665
Heart rate variability in healthy adults
Grade D
Souza et al. (2026; PMID 41506123) pooled the sham-controlled trials and found no significant effect of transcutaneous vagus stimulation on heart rate variability; Soltani et al. (2023; PMID 37119426) found mixed results across 21 studies in healthy people, with baroreflex sensitivity changed in 1 of 6. Tested, no benefit shown: D on Route 2.
PMID 41506123 PMID 37119426
Why Grade A and not higher
Grade A requires a hard clinical endpoint or objectively measured functional outcome, independently replicated across at least two trials. Transcutaneous Vagus Nerve Stimulation meets that standard based on the trials cited above. A downgrade to Grade B would follow if replication attempts produced null results, if the effect size proved substantially smaller in a broader population, or if the studied dose proved impractical to sustain.
What this grade covers and what it does not
Grade A on postoperative cognitive dysfunction in older surgical patients. Three double-blind sham-controlled trials from three Chinese centers found less cognitive dysfunction on the Montreal Cognitive Assessment with auricular stimulation around surgery: Zhou et al. (2022; PMID 35809206), 124 patients, 10 against 27 percent; Li et al. (2026; PMID 42104979), 103 patients, 10 against 33 percent; Ma et al. (2026; PMID 42456197), 103 patients, MoCA 2 to 3 points higher through 3 months. A validated cognitive scale scored blind to allocation, replicated across independent groups, meets the written A definition. The limits are stated beside the letter: the trials are small, all from one country, and one was registered retrospectively. WHAT THIS GRADE DOES NOT COVER: cognition in healthy adults or mixed samples, Grade C, where pooled effects (Liu et al., 2026; PMID 42339645; Ridgewell et al., 2021; PMID 34043386) come from small, mostly single-session laboratory studies of different devices and sites; mild cognitive impairment, Grade C on one trial (Wang et al., 2022; PMID 36150665); heart rate variability in healthy adults, Grade D, tested and no benefit shown in pooled sham-controlled trials (Souza et al., 2026; PMID 41506123); mood, inflammatory or pain claims; implanted vagus nerve stimulation; and any specific consumer device, none of which was used in these trials.
What would move this grade
A null result in a well-powered independent replication trial, or evidence that the effect does not hold at a practically sustainable dose, would prompt downgrade to Grade B.
How to track whether this is working
The endpoint of the graded use: the Montreal Cognitive Assessment before and after surgery for the perioperative use; a cognitive test battery for cognition; resting heart rate variability only as a research measure, since pooled trials found no effect. Stimulation parameters (frequency, pulse width, current, site) at every session: auricular and cervical stimulation have different evidence and are not interchangeable.