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Vagus nerve stimulation and cancer survival

The vagus nerve, also known as the vagal nerves, are the main nerves of your parasympathetic nervous system. This system controls specific body functions such as your digestion, heart rate and immune system. These functions are involuntary, meaning you can’t consciously control them. Source: Cleveland Clinic

Source: 2023 Review article published in Cancer Medicine

Vagus nerve stimulation (VNS) is any method such as the use of electrical current, manual touch, mindfulness meditation, or deep breathing exercise to stimulate the branches of vagus nerve.

The vagus nerve serves a two-way means of carrying information from the body to the brain and vice-versa.

Some of the methods of administering non-invasive VNS include electrical, manual touch, respiratory stimulation of the peripheral branches of the vagus nerve, and mindfulness meditation.

Electrical stimulation is applied to the skin of the ear or neck.

For the VNS using manual touch, an area at the neck is pressed or electrically stimulated.

For the respiratory stimulation of the vagus nerve, slow-deep breathing is used to stimulate the diaphragmatic branch of the vagus nerve.

For the mindfulness meditation, it is a stress-coping technique that promotes relaxation and elevates heart rate variability (HRV).


How does VNS help?

Several important mechanisms have been identified: oxidative stress reduction; inhibition of inflammatory response and inhibition of sympathetic activity.

Oxidative stress reduction

VNS reduces oxidative stress via silent information regulator 1 that helps in the regulation of cell proliferation, differentiation, apoptosis, and metabolism.

Anti-inflammatory effect

When inflammation persists for a very long period of time, prolonged tissue damage occurs, which in turn induces cellular proliferation, a precursor for cancers.

Vagus nerve stimulation (VNS) is known to reduce systemic inflammatory response.

Inhibition of sympathetic activity

High vagal activity is related to good prognosis and increased chance of survival in patients with various forms of cancers such as colon, pancreatic, lung, and breast cancers.

This is because high vagal activity inhibits sympathetic nervous system activity. In contrast, the absence of vagal nerve activity promotes tumor growth and reduces cell survival, which in turn promotes invasion and migration of cancer cells/

Other roles of VNS in non-invasive cancer.

Non-invasive VNS has also been reported to help reduce postoperative ileus [ also called functional bowel obstruction ] when given for 20 min prior to anesthesia in patients who had laparoscopic radical resection of colorectal cancer.

It was also reported to help reduce the severity of peripheral neuropathy induced by chemotherapy.

In addition, it helps improve cancer-related fatigue, lymphopenia, and quality of life.

Furthermore, the positive association between depression and anxiety and incidence of cancer and all-cause mortality; and the increased risk of depression among patients with cancer are also factors that can be considered as mechanisms through which VNS plays a role in the treatment of cancer.

This is because VNS is used in the management of depression, which by implication helps improve a symptom associated with cancer and reduce the risk of developing it.

This systematic review says: Thus, we conclude that a relatively high vagus nerve activity predicts better prognosis in several cancers, independent of important prognostic factors such as age, cancer stage, or treatments. The experimental evidence from animal research confirms this conclusion and provides evidence for a causal relationship between an intact vagus nerve and slower tumor progression or between vagal activation via Semapimod, and less metastasis.

[Semapimod is an inhibitor of proinflammatory cytokine production]

This Review Article says:
Studies have also demonstrated that multiple forms of meditation can alter the parasympathetic component of HRV and can have a positive effect on cardiac autonomic tone. Similarly, relaxation therapy and HRV biofeedback, both behavioural methods, can significantly increase the parasympathetic component of HRV, reflecting an increase in vagus nerve activity…An increased efferent vagus nerve activity has been observed after administration of semapimod, demonstrating its vagal activating potential.

This 2023 study says:
In relapsed/refractory diffused large B-cell lymphoma we found that HRV [Heart Rate Variability]…was a predictor of survival independent of confounders. Patients with higher HRV had 4.85 times greater chances of surviving compared to those with low HRV independent of multiple confounders, including disease severity… For Multiple Myeloma, we found that HRV… was a predictor of Progression Free Survival independent of confounders. Patients with higher HRV had 5.23 times greater chances of not progressing compared to those with low HRV.

These results demonstrate the consistency of the prognostic role of the vagus nerve in two different hematologic cancers.

Moreover, the results of the present study are in line with previous studies showing the prognostic role of HRV in solid cancers, such as colon, breast, pancreas, and liver cancer, and in line with systematic reviews and a meta-analysis showing the independent prognostic role of HRV in cancer. Our results extend these results to two types of blood cancer, which raises the hypothesis that the vagus may affect blood cancer prognosis through a systemic mechanism.


Page updated 2023
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