Can different pathophysiological mechanisms and risk factors leading to various diseases be linked with altered transmission of signals by one common pathway? The present article provides evidence for the hypothesis that adequate vagal nerve activity reduces the risk of major diseases, via common basic mechanisms and interim risk factors. These diseases include cardiovascular disease, cancer, Alzheimer's disease and the metabolic syndrome. Three basic mechanisms contribute to such illnesses: local oxidative stress and DNA damage, inflammatory reactions and excessive sympathetic responses, all of which are inhibited by vagal nerve activity. Efferent vagal activity that can be non-invasively measured by HRV (heart rate variability), derived from an ECG, is inversely related to all three basic mechanisms, to various risk factors (e.g. diabetes and dyslipidaemia) and, more broadly, to the diseases as well. Finally, vagal activity is proposed to moderate the effects of risk factors on developing such illnesses. By proposing an integrative neurobiological model of major diseases, identifying people at risk for, and treating patients with, such diseases may be done more efficiently. People with low HRV may be identified and subsequently treated by vagus nerve activation to possibly prevent or treat such illnesses. This proposed disease paradigm may have important preventative and therapeutic implications, whose clinical effects need to be investigated.

Global burden of diseases (GBD) includes non-communicable conditions such as cardiovascular diseases, cancer and chronic obstructive pulmonary disease. These share important behavioral risk factors (e.g., smoking, diet) and pathophysiological contributing factors (oxidative stress, inflammation and excessive sympathetic activity). This article wishes to introduce to medicine and public health a new paradigm to predict, understand, prevent and possibly treat such diseases based on the science of neuro-immunology and specifically by focusing on vagal neuro-modulation. Vagal nerve activity is related to frontal brain activity which regulates unhealthy lifestyle behaviors. Epidemiologically, high vagal activity, indexed by greater heart rate variability (HRV), independently predicts reduced risk of GBD and better prognosis in GBD. Biologically, the vagus nerve inhibits oxidative stress, inflammation and sympathetic activity (and associated hypoxia). Finally, current non-invasive methods exist to activate this nerve for neuro-modulation, and have promising clinical effects. Indeed, preliminary evidence exists for the beneficial effects of vagal nerve activation in diabetes, stroke, myocardial infarction and possibly cancer. Thus, we propose to routinely implement measurement of HRV to predict such GBD in populations, and to test in randomized controlled trials effects of non-invasive vagal nerve activation on prevention and treatment of GBD, reflecting possible neuro-modulation of health.

The vagus or “wandering” nerve is the main branch of the parasympathetic nervous system (PNS), innervating most internal organs crucial for health. Activity of the vagus nerve can be non-invasively indexed by heart-rate variability parameters (HRV). Specific HRV parameters predict less all-cause mortality, lower risk of and better prognosis after myocardial infarctions, and better survival in cancer. A non-invasive manner for self-activating the vagus is achieved by performing a slow-paced breathing technique while receiving visual feedback of one’s HRV, called HRV-biofeedback (HRV-B). This article narratively reviews the biological mechanisms underlying the role of vagal activity and vagally mediated HRV in hypertension, diabetes, coronary heart disease (CHD), cancer, pain, and dementia. After searching the literature for HRV-B intervention studies in each condition, we report the effects of HRV-B on clinical outcomes in these health conditions, while evaluating the methodological quality of these studies. Generally, the levels of evidence for the benefits of HRV-B is high in CHD, pain, and hypertension, moderate in cancer, and poor in diabetes and dementia. Limitations and future research directions are discussed.

Type 2 diabetic mellitus (T2DM) is a common chronic disease and a substantial risk factor of other fatal illnesses. At its core is insulin resistance, where chronic low-level inflammation is among its main causes. Thus, it is crucial to modulate this inflammation. This review paper provides scientific neuroimmunological evidence on the protective roles of the vagal nerve in T2DM. First, the vagus inhibits inflammation in a reflexive manner via neuroendocrine and neuroimmunological routes. This may also occur at the level of brain networks. Second, studies have shown that vagal activity, as indexed by heart-rate variability (HRV), is inversely related to diabetes and that low HRV is a predictor of T2DM. Finally, some emerging evidence shows that vagal nerve activation may reduce biomarkers and processes related to diabetes. Future randomized controlled trials are needed to test the effects of vagal nerve activation on T2DM and its underlying anti-inflammatory mechanisms.

Background. The vagus nerve may slow tumor progression because it inhibits inflammation. This study examined the relationship between a new vagal neuroimmunomodulation (NIM) index and survival in fatal cancers. Method. We retroactively derived markers of vagal nerve activity indexed by heart rate variability (HRV), specifically the root mean square of successive differences (RMSSD), from patients’ electrocardiograms near diagnosis. The NIM index was the ratio of RMSSD to C-reactive protein levels (RMSSD/CRP). Sample 1 included 202 Belgian patients with advanced pancreatic cancer (PC), while sample 2 included 71 Belgian patients with non-small cell lung cancer (NSCLC). In both samples, we examined the overall survival, while in sample 2, we additionally examined the survival time in deceased patients. Results. In PC patients, in a multivariate Cox regression controlling for confounders, the NIM index had a protective relative risk (RR) of 0.68 and 95% confidence interval (95% CI) of 0.51–0.92. In NSCLC patients, the NIM index also had a protective RR of 0.53 and 95% CI of 0.32–0.88. Finally, in NSCLC, patients with a higher NIM index survived more days (475.2) than those with lower NIM (285.1) (p<0.05). Conclusions. The NIM index, reflecting vagal modulation of inflammation, may be a new independent prognostic biomarker in fatal cancers.

The SIX Cs model, a neuropsychological framework for psychological first aid, addresses acute stress responses that may lead to functional failure and heighten the risk for posttraumatic stress disorder. Unlike emotional interventions, this model prioritizes Cognitive Communication to diminish emotional overwhelm and bolster cognitive functioning. It introduces a Challenge for active engagement, Control for cognitive management of situations, Commitment from the helper to reduce loneliness, and Continuity to ensure narrative coherence. This study evaluates the SIX Cs model's effectiveness in an experimental setup to alleviate acute stress reaction symptoms. Sixty-three participants voluntarily participated. They were randomly assigned to the SIX Cs intervention (experimental) or to supportive emotional expression (control). They listened to a 3-min audio recording of a real emergency 911 phone call. Interventions were provided before and after listening to the recording. Before, immediately after, and 5 min later (recovery), participants' anxiety, heart rate variability, and mental resilience levels were measured. For all three outcomes, the Time × Group interactions were statistically significant. Follow-up analyses revealed that the SIX Cs participants showed lower anxiety and less reductions in heart rate variability and resilience than controls immediately after the stressor. Furthermore, the SIX Cs participants recovered faster on all three outcomes compared to controls. The results demonstrate the superior effect of the psychological first aid based SIX C's protocol over control in all outcomes, immediately after a simulated stressor and 7 min later as well as possible contribution for posttraumatic stress disorder risk reduction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).