Abstract

Is our behavior driving many of our diseases? And, if so, have we been missing the boat with our treatment approaches and medicines? Is our poor gastrointestinal health (GI) affecting our behavior, mood and cognitive ability? Or, is our behavior affecting our GI health? This comprehensive review examines the profound connections between the vagus nerve, autonomic nervous system function, and whole-person health, integrating spiritual practices, lifestyle interventions, evidence-based botanical medicines, and modern vagus nerve stimulation technologies within the Mederi Care framework.

Introduction and Overview “What Happens in Vagus”

There is a new scientific language to understand how the spirit-mind control the body through effects on the vagus nerve and autonomic nervous system (ANS), immune cells, microbiome, stem cells, telomeres, DNA, and more.¹ The vagus nerve, also called pneumogastric nerve, cranial nerve X, the Wanderer or sometimes the Rambler, is the tenth of twelve (excluding CNS) paired cranial nerves. The vagus nerve, the major nerve of the parasympathetic nervous system, innervates several organs from the neck to the abdomen and interfaces with parasympathetic control of the heart, lungs and digestive tract.² 

The vagus nerve is the longest nerve in the human body, providing afferent information about visceral sensation, integrity and somatic sensations to the CNS via brainstem nuclei to subcortical and cortical structures. Its efferent arm influences GI motility and secretion, cardiac ionotropy, chronotropy and heart rate variability, blood pressure responses, bronchoconstriction and modulates gag and cough responses via palatine and pharyngeal innervation.³ 

Autonomic Nervous System: The Foundation of Health

The autonomic nervous system (ANS) is a very complex, multifaceted neural network that maintains internal physiologic homeostasis/allostasis.⁴ Allostasis is the process of achieving stability, or homeostasis, through physiological or behavioral change. This can be carried out by means of alteration in HPA axis hormones, the autonomic nervous system, cytokines, or a number of other systems, and is generally adaptive in the short term. Allostasis is essential in order to maintain internal viability amid changing conditions.⁵ 

Bidirectional Communication Networks

The vagal branches contain afferent (i.e. sensory) and efferent (i.e. motor) fibers contributing to a bidirectional communication between the visceral organs and the brain.⁶ The extensive vagal innervation of the body indicates that the vagus nerve has a multitude of physiological functions. Specifically, the gastrointestinal (GI) tract is densely innervated by the vagus nerve and the latter plays a crucial role in GI functions such as food intake, digestion, and GI barrier function.⁷ In addition, the vagus nerve has immunomodulatory properties suggesting that activation of the parasympathetic innervation of the GI tract could act as a new therapeutic tool to treat intestinal immune diseases.⁸ 

Functionally speaking, the vagus nerve is the longest nerve in the body which originates in the brainstem (as cranial nerve ten), travels all the way down to the tongue, vocal chords, goes to the neck and then passes around the digestive system, liver, spleen, pancreas, heart and lungs. The vagus nerve is the most important element of the parasympathetic nervous system, the one that calms you down.⁹ 

The Stress Response and Vagal Balance

Activation of your vagus nerve counteracts your sympathetic nervous system, the one that causes stress by activating your fight-or-flight response. Stimulating the vagus nerve is a quick and easy way to relieve anxiety. The vagal response reduces stress. It is the “yin” activator. It reduces our heart rate and blood pressure. It changes the function of certain parts of the brain, stimulates digestion, all those things that happen when we are relaxed.¹⁰ 

When you stimulate your vagus nerve, it releases an array of anti-stress enzymes and hormones such as acetylcholine, prolactin, vasopressin, and oxytocin.¹¹ Vagus nerve stimulation is associated with benefits such as improved memory, immune function, sleep, and higher levels of growth hormone. It can also help to regulate immune function – buffering inflammation, allergic responses, and even tension headaches.¹² 

Children with high-baseline vagus nerve activity are more cooperative and likely to give. This area of study is the beginning of a fascinating new argument about altruism: that a branch of our nervous system evolved to support such behavior.¹³ 

The Spiritual Dimension: Vagus Nerve and Consciousness

Central to Immunosurveillance, Longevity, and Regeneration

Metaphorically speaking, the deepest layer of the energetic body generated by the semiconductant nervous system tissue is the vagus nerve. The vagus nerve functions in the service of awakening (sub or super) consciousness and in immortality – the connection to Spirit. This system is described in the Tibetan Inner Fire meditations as well as in the Taoist, “shen” breathing practices.¹⁴ 

The vagus nerve is often referred to as the “Nerve of compassion” because when it’s active, it helps create the “warm-fuzzy feeling” that we feel in our chest when we get a hug or are moved by something like listening to an uplifting piece of music.¹⁵ 

The Sacred Heart Connection

At the heart of us, a physiologic connection and rhythm, exists between our divinity and our physical existence. I propose that the “Life force” itself animates the heart and this why the heart is intuitively so sacred to us. Many Catholic churches are called “Sacred Heart.” The German mystic, Rudolf Steiner (1861 to 1925), founder of the Anthroposophy movement, understood that one of the great transformations of science would come in the twenty-first century as people learned to comprehend the central role of the heart and began to examine life from the intuitive-interior–heart-centered perspective.¹⁶ 

Steiner explained that intuition is the convergence of the subjective (being-subconscious) and the objective (doing-conscious) of knowledge. It is a state of inspired consciousness whereby the objective takes place through the subjective.¹⁷ 

The Wandering Nerve Linking Heart and Mind

The vagus nerve’s function is to transmit information to and from the central nervous system (CNS) regarding control of the gastrointestinal, cardiovascular, and respiratory systems. It is comprised of approximately 80% afferent and 20% efferent fibers including A, B and C fibers classified by conduction velocity. Vagus neurons may involve visceral (cardiac, bronchopulmonary, gastrointestinal) or somatic (soft tissues, muscles of palate, pharynx) modulation.¹⁸ 

“The intuitive mind is a sacred gift and the rational mind is a faithful servant. We have created a society that honors the servant and has forgotten the gift.” –Albert Einstein¹⁹ 

Cultivating Interior Silence: The Poustinik Practice

To support my intention to live in daily communication with God, I practice being a poustinik. I was introduced to this ancient Eastern Christian tradition through one of my favorite books, Poustinia, Encountering God in Silence, Solitude and Prayer, written by the Catholic social activist Catherine Doherty.²⁰ The word poustinia means “desert,” and refers to a simple room where one goes alone to fast, pray, and commune with God. Catherine expanded the original idea of poustinia to become “poustinia of the heart,” where one can find communion with God in any locale, even in the midst of the busiest of lives. By cultivating a silent, still space within, this internal poustinia offers a personal, always available quiet place of connection with God.²¹ 

Anti-Inflammatory Pathways and Immune Modulation

The Cholinergic Anti-Inflammatory Pathway

There are two anti-inflammatory pathways of interest for VNS that interface between the nervous and immune systems: the hypothalamus-pituitary-adrenal (HPA) axis and the cholinergic anti-inflammatory pathway.²² The HPA axis is involved in coordinated neural, behavioral, and endocrine responses that provide an important first-line innate defense against infection and inflammation and help to restore homeostasis in the body.²³ 

The immune system acts as an important intermediary between the gut microbiota and the brain. The signaling mediators of the immune system – cytokines – can signal to the brain from the periphery via the vagus nerve, or they can access the brain directly via the circumventricular organs (regions of the blood-brain barrier that are relatively permeable).²⁴ The gut microbiota are capable of modulating the peripheral inflammatory response, which can affect brain function and behavior. The vagus nerve is responsible for mediating the beneficial effects of probiotics on physiological mechanisms such as wound healing.²⁵ 

Key Communication Pathways of the Microbiota-Gut-Brain Axis

There are numerous mechanisms through which the bacterial commensals in our gut can signal to the brain. These include activation of the vagus nerve, production of immune mediators and microbial metabolites (i.e. short-chain fatty acids [SCFAs]), and enteroendocrine cell signaling.²⁶ Through these routes of communication, the microbiota–gut–brain axis controls central physiological processes, such as neurotransmission, neurogenesis, neuroinflammation and neuroendocrine signaling.²⁷ 

The Gut-Brain Connection: Historical Perspective and Modern Understanding – Darwin’s Early Observations

It has long been appreciated that the gastrointestinal (GI) tract and the central nervous system (CNS) interact. For example, Charles Darwin wrote in his classic The Expression of the Emotions in Man and Animals (1872): “The manner in which the secretions of the alimentary canal and of certain other organs…are affected by strong emotions, is another excellent instance of the direct action of the sensorium on these organs, independently of the will or of any serviceable associated habit.”²⁸ 

And Claude Bernard noted that the brain and the heart interacted through the pneumogastric nerve “…so that,” as Darwin wrote, “under any excitement there will be much mutual action and reaction between these…²⁹ But for many of us, the modern era elucidating how the GI tract and CNS interacted can be traced to the work of Gibbs and Smith. These authors clearly showed that the satiety effect of peripherally administered cholecystokinin was mediated through the vagus nerve.³⁰ 

Stress and Microbiome Balance

Stress has a significant influence on the balance of intestinal microflora. Moore et al. found, “The composition of the flora was not significantly affected by drastic changes in diet, but statistically significant shifts in the proportions of some species were noted in individuals under conditions of anger or fear stress.”³¹ 

Recently, a new neural connection has been reported between sensory cells of the gut epithelium and the nervous system that mediates signals from the gut to the brain. The gut senses and its environment, relays those signals to the brain, and the brain influences the gut.³² 

Bidirectional Communication Networks

There is a bidirectional information network between the gut microbiota and the brain. Researchers are finding evidence that irritation in the gastrointestinal system may send signals to the central nervous system (CNS) that trigger mood changes.³³ Our gut and brain ‘talk’ to each other, so therapies, including herbal medicine, that help one may help the other. Gut microbiota is changing with human development and influenced by various stress factors.³⁴ 

Some evidence has shown that stress in the first few years of life could lead to the change of microbiota, and this change is a risk factor for stress-related disorders in adulthood.^35,36 

Feeding the Microbiota-Gut-Brain-Immune System Axis

Nutritional Psychiatry and the Mederi Care Approach

The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites.³⁷ This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, targeting the modulation of the gut microbiota, nervous system, and endocrine system together is the Mederi Care novel approach for the treatment of various neuropsychiatric, digestive and immune conditions.³⁸ And, in particular, the microbiota is poised to play a key role in nutritional interventions for maintaining brain health.³⁹ 

Neurotransmitter Production by Gut Microbes

Gut microbes are capable of producing most neurotransmitters found in the human brain.⁴⁰ Evidence is accumulating to support the view that gut microbes influence central neurochemistry and behavior.⁴¹ Irritable bowel syndrome is regarded as the prototypic disorder of the brain-gut-microbiota axis that can be responsive to probiotic therapy.⁴² Translational studies indicate that certain bacteria may have an impact on stress responses and cognitive functioning.⁴³ Manipulating the gut microbiota with psychobiotics, prebiotics, or even antibiotics offers a novel approach to altering brain function and treating gut-brain axis disorders, such as depression and autism.⁴⁴ 

There is now strong evidence from animal studies that gut microorganisms can activate the vagus nerve and that such activation plays a critical role in mediating effects on the brain and behavior.⁴⁵ The vagus appears to differentiate between non-pathogenic and potentially pathogenic bacteria even in the absence of overt inflammation and vagal pathways mediate signals that can induce both anxiogenic and anxiolytic effects, depending on the nature of the stimulus.⁴⁶ 

The Anti-Inflammatory Reflex

Certain vagal signals from the gut can instigate an anti-inflammatory reflex with afferent signals to the brain activating an efferent response, releasing mediators including acetylcholine that, through an interaction with immune cells, attenuates inflammation.⁴⁷ This immunomodulatory role of the vagus nerve may also have consequences for modulation of brain function and mood.⁴⁸ What is currently lacking are relevant data on the electrophysiology of the system. Certainly, important advances in our understanding of the gut-brain and microbiome-gut-brain axis will come from studies of how distinct microbial and nutritional stimuli activate the vagus and the nature of the signals transmitted to the brain that lead to differential changes in the neurochemistry of the brain and behavior.⁴⁹ 

Understanding the induction and transmission of signals in the vagus nerve may have important implications for the development of microbial-or nutrition based therapeutic strategies for mood disorders.⁵⁰ Vagus nerve stimulation normalizes an elevated HPA axis (CRH, ACTH, and Cortisol).^51,52 

Vagus Nerve as a Predictor of Health Outcomes

The Neuroimmunological Paradigm

Global burden of diseases (GBD) includes noncommunicable conditions such as cardiovascular diseases, cancer and chronic obstructive pulmonary disease.⁵³ These share important behavioral risk factors (e.g., smoking, diet) and pathophysiological contributing factors (oxidative stress, inflammation and excessive sympathetic activity).⁵⁴ 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 neuroimmunology and specifically by focusing on vagal neuromodulation.⁵⁵ Vagal nerve activity is related to frontal brain activity which regulates unhealthy lifestyle behaviors.⁵⁶ 

Epidemiologically, high vagal activity, indexed by greater heart rate variability (HRV), independently predicts reduced risk of GBD and better prognosis in GBD.⁵⁷ Biologically, the vagus nerve inhibits oxidative stress, inflammation and sympathetic activity (and associated hypoxia).⁵⁸ Finally, current noninvasive methods exist to activate this nerve for neuromodulation, and have promising clinical effects.⁵⁹ Indeed, preliminary evidence exists for the beneficial effects of vagal nerve activation in diabetes, stroke, myocardial infarction and possibly cancer.⁶⁰ 

Thus, we propose to routinely implement measurement of HRV to predict such GBD in populations, and to test in randomized controlled trials effects of noninvasive vagal nerve activation on prevention and treatment of GBD, reflecting possible neuromodulation of health.⁶¹ 

The Vagus Nerve and Digestive Function

Autonomic Regulation of Digestion

Beginning in the brain, the vagus nerve travels down alongside the esophagus to the stomach and other gastrointestinal organs and is primarily responsible for autonomic regulation involved in heart, lung and gastrointestinal function.⁶² The vagus nerve controls much of the activity of the stomach, intestine and pancreas and plays a role in food processing, including:

1. Expansion of the stomach as food enters; contractions of the stomach to break food into smaller particles
2. Release of gastric acid required for food processing
3. Emptying of the stomach contents into the small intestine
4. Secretion of digestive pancreatic enzymes that enable absorption of calories
5. Controlling sensations of hunger, satisfaction and fullness⁶³ 

The Nervous System and Chronic Disease

The last three decades have witnessed the recognition of a significant relationship between the autonomic nervous system and chronic disease, including cardiovascular and cancer mortality.^64-66 

Sympathetic and Parasympathetic Innervation in Cancer

The autonomic nervous system, consisting of sympathetic and parasympathetic/vagal nerves, is known to control the functions of any organ, maintaining whole-body homeostasis under physiological conditions. Recently, there has been increasing evidence linking sympathetic and parasympathetic/vagal nerves to cancers.^67,68 

Human and animal studies have revealed that sympathetic and parasympathetic/vagal nerves innervate the cancer microenvironment and alter cancer behavior.⁶⁹ The sympathetic nerves have cancer-promoting effects on prostate cancer, breast cancer, and melanoma. On the other hand, while the parasympathetic/vagal nerves have cancer-promoting effects on prostate, gastric, and colorectal cancers, they have cancer-suppressing effects on breast and pancreatic cancers.⁷⁰ These neural effects may be mediated by β-adrenergic or muscarinic receptors and can be explained by changes in cancer cell behavior, angiogenesis, tumor-associated macrophages, and adaptive antitumor immunity.⁷¹ 

Sympathetic nerves innervating the tumor microenvironment promote cancer progression and are related to stress-induced cancer behavior.⁷² The parasympathetic/vagal nerves have variable (promoting or suppressing) effects on different cancer types.⁷³ Approaches directed toward the sympathetic and parasympathetic/vagal nerves can be developed as a new cancer therapy.⁷⁴ 

Interleukin-6 is a keystone cytokine,⁷⁵ linked to many of the known hallmarks of cancer that comprise the malignant phenotype of glioblastoma, including: 1 angiogenesis; 2) chemoresistance; 3) heterogeneity; 4) immunosuppression; 5) tumor-promoting inflammation; 6) invasion; 7) proliferation; 8) senescence- SASP and 9) stemness– making IL-6 an attractive target for 10) cytokine reduction using VNS 

A ClinicalTrials.gov search on 6.25.2023, updated on 7.22.24 reveals no prior or current clinical trials of VNS targeting IL-6, or other cytokines, for cancer control, including glioblastoma. 

Vagus nerve stimulation has been shown to slow the growth of certain cancers by enhancing the body’s immune response and regulating inflammation. This approach may improve survival outcomes in cancer patients by restoring normal metabolic functions and reducing systemic inflammation.⁷⁶ 

Key Findings of a Systemic and Comprehensive Review:

Analyzed 12 epidemiological studies looking at heart rate variability (the primary measure of vagus nerve activity) and cancer prognosis

• Higher initial vagal nerve activity correlates with better cancer outcomes and survival rates
• This relationship holds even when accounting for factors like cancer stage and treatment type
• The paper includes additional human cohort studies and animal experiments that provide stronger evidence for causation:
• Vagotomy (surgical removal of vagus nerve) accelerates tumor growth
• Vagal nerve stimulation improves cancer prognosis⁷⁷ 

Vagus Nerve Stimulation for Post-Surgery Fatigue in Elderly Colorectal Cancer Patients

Post-operative fatigue syndrome (POFS) causes exhaustion, sleep problems, depression, and anxiety after surgery, affecting recovery and quality of life. Research shows that surgery triggers inflammation, which contributes to these fatigue symptoms.

The vagus nerve can reduce inflammation by activating the body’s natural anti-inflammatory pathways. Both animal and human studies demonstrate that vagus nerve stimulation (VNS) effectively reduces inflammatory molecules that cause fatigue.

Given inflammation’s central role in POFS, we hypothesize that transcutaneous auricular vagus nerve stimulation (taVNS) could significantly reduce post-operative fatigue in elderly patients undergoing colorectal cancer surgery.⁷⁸ 

Cancer, Anxiety, and Depression: The Vagal Connection

Cancer is something that can cause a lot of anxiety in people. We often see people within the first month or so after their diagnosis, as they are still trying to cope with the news and figure out what their treatments are going to be and how they are going to get through treatment. After that, the most common things that we see are anxiety as well as depression.⁷⁹ 

Low vagus nerve activity is related to a worse cancer prognosis. The vagus nerve is one of the twelve cranial nerves that extends throughout the human body (larynx, trachea, esophagus, heart, lungs, stomach and abdominal organs) and performs a variety of important functions, such as stimulating the digestive system.⁸⁰ It is also the most important nerve of the parasympathetic nervous system, which means that it helps to calm your body after a stress response by, among other things, slowing down your heart rate and lowering your blood pressure.⁸¹ 

Vagus nerve activity can be measured using the heart rate variability (HRV) that is recorded in an ECG (electrocardiogram). Various clinical studies have shown that a higher HRV is related to an improved prognosis (longer survival rates or lower tumor markers) for different types of cancer.^82-84 

Clinical Studies on Vagal Activity and Cancer Prognosis

Recent studies suggest that vagal nerve activity, indexed by heart rate variability (HRV), could have a prognostic role in cancer.⁸⁵ Studies have tested the prognostic role of HRV in prostate cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical prospective design. HRV was derived from brief 10 sec ECGs obtained at approximately the time of diagnosis.⁸⁶ 

In prostate cancer patients, HRV significantly inversely predicted PSA levels at 6 and 24 months, independent of confounders. Furthermore, this was particularly significant in metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV did not predict overall survival and survival time, but it did positively predict survival time in patients under the age of 65, independent of confounders.⁸⁷ 

Vagus Nerve Activity and Cancer Staging

The parasympathetic system, and primarily the vagus nerve, informs the brain about multiple signals and returns the body to homeostasis. Recent studies have shown that vagal nerve activity independently predicts prognosis in cancer. When vagal nerve activity is high, cancer stage no longer predicts tumor burden.⁸⁸ 

Patients’ HRVs were derived from ECGs near diagnosis in colorectal cancer (CRC) and in prostate cancer (PC) patients. Outcomes included the tumor markers carcinoembryonic antigen (CEA) at 12 months for CRC and prostate-specific antigen (PSA) at 6 months for PC. As would be expected, initially advanced tumor stages of CRC or PC predicted higher tumor marker levels at follow-up than did early stages. However, this occurred only in patients with low, not high, vagal activity (HRV).⁸⁹ 

Furthermore, in patients with advanced tumor stage at diagnosis, high HRV predicted lower tumor marker levels than did low HRV, in both cancers. Estimating a cancer patient’s prognosis by determining his tumor stage needs to also consider the vagal nerve activity. This activity is easily measurable, and it determines in which subjects the tumor stage is prognostic. Importantly, higher vagal activity may even protect against the adverse effects of advanced cancer stage.⁹⁰ 

Vagal Nerve Activity in Metastatic Pancreatic Cancer

A study examining the relationship between vagal nerve activity, indexed by heart rate variability (HRV), and overall survival (OS) in patients (N=272) with advanced pancreatic cancer employed a “historical prospective” design. Patients with high HRV (>20 msec) survived on average more than double the days (133.5) than those with low HRV (64.0).

In a multivariate cox regression, higher initial HRV was significantly correlated with lower risk of death, independent of confounders including age and cancer treatments. This relationship was statistically mediated (accounted for) by CRP levels. Importantly, in patients who lived up to one month from diagnosis only, HRV was unrelated to CRP, while in patients surviving longer, HRV was significantly inversely related to CRP.

These results are in line with possible vagal nerve protection in a fatal cancer, and propose that the mechanism may involve neuroimmuno-modulation.⁹¹ 

Vagal Nerve Activity in Blood Cancers

A study examined the prognostic role of vagal nerve activity in patients with relapsed/refractory diffused large B-cell lymphoma (R/R-DLBCL) treated with chimeric antigen receptor cell therapy (CAR-T) and in patients with multiple myeloma (MM) undergoing an autologous hematopoietic cell transplantation (AutoHCT).

In DLBCL, HRV significantly predicted OS independently of confounders (e.g., performance status, disease status at cell therapy), hazard ratio (HR), and 95% confidence interval (HR = 0.20; 95%CI: 0.06–0.69). The prognostic role of disease severity was moderated by HRV: among severely disease patients, 100% died with low HRV, while only 37.5% died with high HRV.

In MM, HRV significantly predicted PFS (HR = 0.19; 95%CI: 0.04–0.90) independently of confounders. Vagal nerve activity independently predicts prognosis in patients with R/R-DLBCL and with MM undergoing cell therapy. High vagal activity overrides the prognostic role of disease severity.⁹² 

Therapeutic Potential of the Vagus Nerve in Cancer

Accumulating evidence points to a beneficial effect of vagus nerve activity in tumor development. The vagus nerve is proposed to slow tumorigenesis because of its anti-inflammatory properties mediated through ACh and the α7nAChR.⁹³ Since α7nAChRs are widely expressed by many types of immune cells we hypothesized that the vagus nerve affects the tumor microenvironment and anticancer immunity.⁹⁴ 

Direct evidence in studies using animal cancer models shows that vagus nerve stimulation alters immunological responses relevant to the tumor microenvironment. Also studies in pathologies other than cancer suggest a role for the vagus nerve in altering immunological responses relevant to anticancer immunity. These results provide a rationale to expect that vagus nerve stimulation, in combination with conventional cancer treatments, may improve the prognosis of cancer patients by promoting anticancer immunity.⁹⁵ 

Vagus Nerve Stimulation for Chemotherapy-Induced Neuropathy

Chemotherapy-induced painful peripheral neuropathy (CIPN) is a common adverse event in cancer patients, and there is still a lack of effective treatment.⁹⁶ Transauricular vagal nerve stimulation (taVNS) is a minimally invasive treatment for investigating efficacy for CIPN.

Twenty-seven patients with CIPN were randomly divided into a taVNS group (n = 14) and a sham stimulation (SS) group (n=13). Compared with the SS group, the NRS and AIS in the taVNS group were significantly lower. The impact lasted until D30. TaVNS can relieve chemotherapy-induced neuropathic pain in the short term, can improve sleep status and quality of life, and is expected to become a novel clinical treatment method for CIPN.⁹⁷ 

Vagus Nerve Stimulation in Parkinson’s Disease

Recent pathophysiological theories of Parkinson’s suggest that aggregated α-synuclein form in the gut and spread to nuclei in the brainstem via autonomic connections.⁹⁸ Noninvasive vagus nerve stimulation (nVNS), targeting efferent and afferent vagal projections, is a promising therapeutic tool to improve gait and cognitive control and ameliorate non-motor symptoms in people with Parkinson’s.⁹⁹ 

Evidence of nVNS as a novel therapeutic to improve gait in PD is preliminary, but early signs indicate the possibility that nVNS may be useful to target dopa-resistant gait characteristics in early PD.¹⁰⁰ The evidence for nVNS as a therapeutic tool is, however, limited and further studies are needed in both brain health and disease.¹⁰¹ 

Vagus Nerve Stimulation Relieves Insomnia

Vagus nerve stimulation (VNS) – delivered through devices or breathwork – may help people with insomnia by calming the nervous system and restoring natural sleep rhythms.

How VNS Affects Sleep

Insomnia often stems from hyperarousal – when the nervous system remains in fight-or-flight mode and can’t shift into the calm state needed for sleep. By stimulating the vagus nerve, VNS activates the parasympathetic “rest and digest” response, reducing stress and influencing brain areas that control sleep-wake cycles. It can also modulate GABA and serotonin, neurotransmitters critical for sleep regulation, and enhance deep sleep brain waves.

Mechanical Stimulation

A meta-analysis published in May in Neuromodulation¹⁰² found that transcutaneous auricular vagus nerve stimulation (taVNS) significantly relieved insomnia across six clinical trials involving over 300 patients. TaVNS improved sleep quality, reduced time to fall asleep, and extended sleep duration.

TaVNS delivers gentle electrical pulses through the skin of the outer ear. Unlike implanted devices – which carry risks like sleep apnea and heart complications – taVNS is non-invasive, affordable, and portable.

Benefits extend beyond short-term gains. A Chinese trial in JAMA Network Open¹⁰³ involving 72 participants showed that eight weeks of twice-daily taVNS improved sleep quality in chronic insomnia patients, with improvements lasting 12 weeks post-treatment. These sustained effects may result from taVNS reducing anxiety, depression, and fatigue – common insomnia contributors.

IBS and Open-Label Placebo Treatment

According to a 2010 study published in the journal PLoS One, placebos given without deception improved symptoms of irritable bowel syndrome (IBS). Despite the recognition of possible benefit, the use of a placebo without the patient’s knowledge poses an ethical problem for most clinicians. The new study examined the use of a placebo pill, given without deception, compared with no treatment in relieving symptoms of IBS.¹⁰⁴ 

Researchers followed 80 adults with IBS over the course of 3 weeks. Participants were randomly assigned to receive either placebo pills (two pills twice a day) or no treatment. The participants in the placebo group were informed that “placebo pills, made of an inert substance, like sugar pills, have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body healing processes.

The researchers found that the participants in the placebo group had significantly better scores in global improvement, severity of symptoms, and adequate relief than the no-treatment group at both the midpoint and the end of the study. In addition, the placebo group had a trend toward improvement in quality of life.

The researchers suggest that placebo treatments when administered without concealment, and with a plausible rationale of placebo’s potential effects, may produce beneficial responses in patients.¹⁰⁵ 

Vagus Nerve Stimulation Improves Symptoms and Comorbidities in Rosacea

A randomized, double-blind, sham-controlled trial investigated the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) in 72 adults with erythematotelangiectatic rosacea (ETR). Over a 3-week treatment period with 24-week follow-up, participants receiving taVNS demonstrated significant improvements in clinical erythema and telangiectasia (CEA) scores, with notable reductions in flushing, erythema, and associated systemic symptoms including anxiety, depression, insomnia, fatigue, and facial migraine. The intervention showed sustained remission and remarkably low adverse event rates, suggesting taVNS represents a promising, cost-effective therapeutic approach for managing ETR with potential broad-spectrum symptomatic benefits.¹⁰⁶ 

The Blood-Brain Barrier and Gut-Brain Communication

The blood-brain barrier (BBB) prevents the unrestricted exchange of substances between the central nervous system (CNS) and the blood. The BBB also conveys information between the CNS and the gastrointestinal (GI) tract through several mechanisms, and it is the BBB in mediating communication between the CNS and GI tract.¹⁰⁷ 

There are three mechanisms by which the blood-brain barrier (BBB) participates in gut–brain communication:

1. Direct transfer of peptides and regulatory proteins across the BBB
2. The ability of gastrointestinal (GI) hormones to alter the functioning of the brain endothelial cells which comprise the BBB
3. The ability of GI hormones to alter the secretion from the BBB of substances which have effects on feeding¹⁰⁸

Gut Immune System Development

Development of the gut immune system depends on gut microbiota. Lacking gut microbiota and low/lack of expression of toll-like receptors (TLRs) contribute to producing a neuroendocrine response to the pathogen in the gut.

Bacteria communicate with the host through a variety of ways, and the TLRs of the host cell play a key role in the communication between bacteria and host. There are ten kinds of TLRs in the human innate immune system, which have been identified as pattern recognition receptors. These receptors are a part of the innate immune system, which is the first step to produce cytokine response and is also widely distributed on neurons. Hence, neurons also respond to bacterial and viral components.¹⁰⁹ 

Heart Rate Variability and Vagus Nerve Measurement

The Pulse of Inflammation

In the brilliant scientific paper, ‘The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy,’ Dr. Jared M. Huston, Department of Surgery, Stony Brook University Medical Center discovered a neural control circuit that acts to keep the body’s cytokine production, and therefore inflammatory response, in check.¹¹⁰ 

There is now extensive experience using Heart Rate Variability measures in diverse disease syndromes and these data indicate that decreased vagus nerve activity is associated with increased morbidity and mortality.¹¹¹ 

Parasympathetic Heart Innervation

Parasympathetic innervation of the heart is mediated by the vagus nerve. Specifically, the vagus nerve acts to lower the heart rate.¹¹² The right vagus innervates the sinoatrial node. Parasympathetic hyperstimulation predisposes those affected to bradyarrhythmia. The left vagus when hyper-stimulated predisposes the heart to atrioventricular (AV) blocks.

Vagal tone is measured by tracking your heart rate alongside your breathing rate. Your heart-rate speeds up a little when you breathe in, and slows down a little when you breathe out. The bigger the difference between your inhalation heart-rate and your exhalation heart-rate, the higher your vagal tone. Higher vagal tone means that your body can relax faster after stress.¹¹³ 

Vasovagal Response

Activation of the vagus nerve typically leads to a reduction in heart rate, blood pressure, or both. This occurs commonly in the setting of gastrointestinal illness such as viral gastroenteritis or acute cholecystitis, or in response to other stimuli, including carotid sinus massage, Valsalva maneuver, or pain from any cause, particularly having blood drawn. When the circulatory changes are great enough, vasovagal syncope results.

Excessive activation of the vagal nerve during emotional stress, which is a parasympathetic overcompensation of a strong sympathetic nervous system response associated with stress, can also cause vasovagal syncope because of a sudden drop in blood pressure and heart rate. Vasovagal syncope affects young children and women more often. It can also lead to temporary loss of bladder control under moments of extreme fear.¹¹⁴ 

Drugs that inhibit the muscarinic cholinergic receptor (anticholinergics) such as atropine and scopolamine are called vagolytic because they inhibit the action of the vagus nerve on the heart, gastrointestinal tract and other organs. Anticholinergic drugs increase heart rate and are used to treat bradycardia (slow heart rate) and asystole, which is when the heart has no electrical activity.¹¹⁵ 

Ways to Increase Your Vagus Nerve and Promote Optimal Wellness

Vagus nerve stimulation may be achieved by one of the vagal maneuvers: holding the breath for a few seconds, dipping the face in cold water, coughing, or tensing the stomach muscles as if to bear down to have a bowel movement (Valsalva maneuver).

1) Prayer and Meditation – Faith, Hope, Compassion, Love, and Connection to God

“[If] you do not listen to Theology, that will not mean that you have no ideas about God. It will mean that you have a lot of wrong ones – bad, muddled, out of date ideas.” —C.S. Lewis¹¹⁶ 

Loving kindness meditation promotes feelings of goodwill towards yourself and others.¹¹⁷ How positive emotions build physical health: perceived positive social connections account for the upward spiral between positive emotions and vagal tone.¹¹⁸ 

The mechanisms underlying the association between positive emotions and physical health remain a mystery. We hypothesize that an upward-spiral dynamic continually reinforces the tie between positive emotions and physical health and that this spiral is mediated by people’s perceptions of their positive social connections. We tested this overarching hypothesis in a longitudinal field experiment in which participants were randomly assigned to an intervention group that self-generated positive emotions via loving-kindness meditation or to a waiting-list control group. Participants in the intervention group increased in positive emotions relative to those in the control group, an effect moderated by baseline vagal tone, a proxy index of physical health. Increased positive emotions, in turn, produced increases in vagal tone, an effect mediated by increased perceptions of social connections. This experimental evidence identifies one mechanism-perceptions of social connections-through which positive emotions build physical health, indexed as vagal tone. Results suggest that positive emotions, positive social connections, and physical health influence one another in a self-sustaining upward-spiral dynamic.

There is no greater joy than to be working in loving kindness in serving God above all else. But how do we find out what God’s will is for us? Before we can know God’s will, we must desire it above everything else. We must pray to God with “simple intentions,” asking that our desires be pleasing to Him. We should feel a longing for God’s presence to be with us always throughout our entire life in every moment, and in any situation we are in. “Loving kindness” implies a deep desire to make others happy even when it requires self-sacrifice, suffering and in extreme cases even death. “Watch the movie “Pay It Forward.” ¹¹⁹ 

Studies tell us that patients who are given spiritual support have a significantly better quality of life and longer life.

Research conducted by Dacher Ketlner, director of the Social Interaction Laboratory at the University of California, Berkeley showed that stimulating that vagus nerve is not only good for you – it’s good for the planet! “Our research and that of other scientists suggest that activation of the vagus nerve is associated with feelings of caretaking and the ethical intuition that humans from different social groups (even adversarial ones) share a common humanity. People who have high vagus nerve activation in a resting state, we have found, are prone to feeling emotions that promote altruism – compassion, gratitude, love and happiness.”¹²⁰ 

Compassion is an effective response to another’s suffering and a catalyst of prosocial behavior. Compassion, which is associated with activation in the PAN system, is associated with heightened parasympathetic activity through the vagus nerve and is a core affective component of empathy and prosociality.

A new science of happiness is finding that these emotions can be readily cultivated in familiar ways, bringing out the good in others and in oneself. Here are some recent empirical examples:

• Experiences of reverence in nature or of being around those who are morally inspiring improves people’s sense of connection to one another and their sense of purpose.
• Meditating on a compassionate approach to others shifts resting brain activation to the left hemisphere, a region associated with happiness, and boosts immune functions.
• Talking about what we are thankful for – in classrooms, at the dinner table or in a diary – boosts happiness, social well-being and health.
• Devoting resources to others, rather than indulging a materialist desire, brings about lasting well-being.¹²¹ 

Meditation Improves Gene Expression

After eight hours of mindfulness practice, meditators showed a range of genetic and molecular differences, including altered levels of gene-regulating machinery and reduced levels of pro-inflammatory genes, which correlated with faster recovery from a stressful situation.¹²² 

Become a Poustinik

Prayer and meditation offer opportunities for enhanced emotions throughout the day, not simply during meditation. Most importantly, you can use the insights and psychological skills developed during meditation practice in many situations and life domains.¹²³ 

Meditation and mindfulness, which are perhaps best known as elements of Eastern religious-spiritual practice, have also proven to be fruitful topics within empirical research on well-being.

For instance, for more than two decades, Kabat-Zinn and colleagues have reported evidence that meditation helps people self-regulate stress, anxiety, chronic pain, and various illnesses.¹²⁴ 

A recent meta-analysis of nearly 300 findings concluded that positive emotions produce success and health as much as they reflect these good outcomes.¹²⁵ 

Our entire life should be a meditation. We should strive to be each, a ‘Poustinick.’ The Poustinik is also seeking and living the external “doing” life in harmony with the internal “being” which sees life above all else as an eternal pilgrimage where we explore the vast spaces of God. This is a deep journey within that is far more beautiful and satisfies more than anything we could imagine. Within this journey you become poor in spirit and you realize, “the need to have becomes the need not to have not.”

Practice Quietness and Stillness to Enter the Great Mystery of God

In the age of reason and rationale-thinking how do we explain the phenomena of God? We can’t just simply think of God, or enter numbers and know Him. In the true sense of the God (for Christians Christ) experience, there is an understanding, and the need for “contemplation,” followed by a response, which is only experienced within a place of “hesychia.” Hesychia, is the Greek word for “quit,” and it is a spiritual practice of being totally still used by the Eastern Christian Mystics.

There are four characteristics:

• A state by which you strive to be in a place of total rest, stillness and quit, which excludes reading and even mediation.
• Repetitive prayer often with beads or knotted ropes – Eastern Christians say the “Jesus Prayer” Western Catholics say the “Rosary” Prayer beads are also used in Buddhism, Islam, Sikhism and the Bahá’í Faith to mark the repetitions of prayers and/or chants.
• Physically position your body in a way to enable yourself to do deep breathing so you can let go and bring the mind into the heart.
• The feeling of inner warmth and perspiration, a true experience of “Total Divine Light.” The Buddhist would call this experience “interconnectedness.”

“Prayer of the heart” occurs when the Prayer moves from merely mental repetition, forced along by your own effort, to an effortless and spontaneous self-repetition of the Prayer that emanates from the core of your being, your heart.

Theology and Religion Linked to Better Life for Everyone

Regular attendance at religious services is linked to healthy, stable family life, strong marriages, and well-behaved children.¹²⁶ The practice of Religion also leads to a reduction in the incidence of domestic abuse, crime, substance abuse, and addiction. In addition, religious practice leads to an increase in physical and mental health, longevity, and education attainment. Moreover, these effects are intergenerational, as grandparents and parents pass on the benefits to the next generations. Many research studies now indicate that religious practice serves the common good.¹²⁷ 

2) Chanting, Humming and Relaxing/Uplifting Music

Since the vagus nerve is connected to the vocal cords, chanting and humming mechanically stimulates it. You can hum a song, or even better chant a repetitive spiritual meditative piece of music, transport yourself to a monastery and imagine yourself singing with the monks.

Singing in general seems to promote more well-being. Choir singing is known to promote wellbeing. One reason for this may be that singing demands a slower than normal respiration, which may in turn affect heart activity. Song structure, respiration, and HR are connected. Unison singing of regular song structures makes the hearts of the singers accelerate and decelerate simultaneously.¹²⁸ 

A meta analytical study has shown that relaxing music affects blood pressure and heart rate in coronary heart patients and cancer patients. Relaxing music provides great benefits to both patient and clinician. There is a close relationship between relaxing music and health procedures, can use every area of the health noninvasive, safe, cheap and is a method that doesn’t have side effects.¹²⁹ 

3) Deep Breathing

Deep breathing is a great way to stimulate the vagus nerve. We can extend the inhalation and the exhalation. So, by those practices we can activate the parasympathetic nervous system. That means expanding your diaphragm, a muscle located horizontally between the chest cavity and stomach cavity. Also known as “belly breathing,” diaphragmatic breathing is characterized by an expansion of the abdomen instead of the chest. Other ways to stimulate your vagus nerve include cold-water facial immersion after exercise and submerging the tongue.

When breathing remember the following:

• Breathe slowly.
• Breathe deeply, from the belly.
• Exhale longer than you inhale.

You can proceed as follows: take a deep inhalation into your belly (i.e. expanding your diaphragm) to the count of five, pause, and then exhale slowly through a small hole in your mouth. While at rest most people take about 10 to 14 breaths per minute. To get into parasympathetic/relaxation/healing mode it is ideal to reduce your breath to 5 to 7 times per minute. Exhaling through your mouth instead of nose makes your breathing more of a conscious process, and helps you to observe your breath more easily.¹³⁰ 

4) Washing Your Face with Cold Water or Putting Your Tongue in Cold Water

Cold water exposure activates the vagus nerve through the mammalian dive reflex. This ancient survival mechanism slows the heart rate and redirects blood flow to vital organs, promoting parasympathetic dominance.¹³¹ 

5) Vagus Nerve Stimulation Devices: Pulsetto and VeRelief Mini

After extensive clinical experience with various vagus nerve stimulation devices, I find the Pulsetto to work the best for most people. This advanced device delivers precise, comfortable transcutaneous auricular vagus nerve stimulation (taVNS) that consistently produces measurable improvements in heart rate variability and subjective well-being.¹³² 

Why Pulsetto Excels:

Precision Engineering: The Pulsetto uses carefully calibrated electrical parameters that target the auricular branch of the vagus nerve with optimal frequency and intensity ranges (typically 10-25 Hz) that research shows to be most effective for vagal activation.¹³³ 

User Compliance: Unlike bulkier devices or those requiring complex setup procedures, the Pulsetto’s ergonomic design and simple operation encourage consistent daily use, which is essential for building vagal tone over time.¹³⁴ 

Measurable Results: Clinical studies with similar taVNS devices show significant improvements in heart rate variability, stress hormone levels, and inflammatory markers within 2-4 weeks of regular use.¹³⁵ 

Safety Profile: The device operates well within established safety parameters for transcutaneous electrical stimulation, making it suitable for most individuals without the risks associated with invasive VNS procedures.

Clinical Protocol for Pulsetto Use:

Frequency: Use 4-5 times per day, ideally before meals to maximize parasympathetic activation during digestive periods.

Duration: 10-20 minute sessions are typically optimal, allowing sufficient stimulation without causing habituation or discomfort.¹³⁶ 

Timing: Pre-meal use enhances the natural parasympathetic activation that occurs during digestion, creating a synergistic effect that supports both vagal tone and digestive function.¹³⁷ 

Combination Therapy: Pulsetto use can be combined with breathing exercises, meditation, or botanical protocols for enhanced benefits.¹³⁸ 

The VeRelief Mini offers another option for transcutaneous auricular VNS, though in my clinical experience, it shows less consistent results across diverse patient populations compared to the Pulsetto.¹³⁹ Also consider the home therapeutic model as well for more intensive intervention.¹⁴⁰ 

6) Laughter

Laughter is more than just an expression of joy, it’s a powerful force for health, longevity, and human connection.¹⁴¹ From ancient wisdom to modern scientific research, the evidence overwhelmingly supports the idea that humor and laughter contribute to physical, mental, and even spiritual well-being.¹⁴² 

A groundbreaking study in Psychosomatic Medicine reveals that humor may be key to longevity. Research following 53,556 Norwegians over 15 years found that women with strong cognitive humor skills had 48% lower mortality risk overall, with even more dramatic reductions in deaths from heart disease (73%) and infection (83%). Men with high humor scores showed a 74% lower risk of death from infection only.

The study focused on cognitive, social, and affective components of humor, with only the cognitive aspect showing significant health benefits. According to study co-author Sven Svebak of the Norwegian University of Science and Technology, this cognitive component, a stable personality trait, may help people process daily experiences more positively, reducing stress hormone levels that can compromise immunity.¹⁴³ 

7) Improving the Gut Flora

Balancing the gut microbiome. The presence of healthy bacteria in the gut creates a positive feedback loop through the vagus nerve, increasing its tone.¹⁴⁴ Gut microbiome appears to determine immunotherapy response. In examining patients’ microbiome, researchers looked at both its diversity and its composition. The results showed a significantly greater diversity of types of bacteria in the microbiome of patients who responded to immunotherapy.¹⁴⁵ 

Responders had a significantly greater abundance of bacterial taxa of the order Clostridiales, specifically, Ruminococcus spp, compared to nonresponders, whereas nonresponders had a greater abundance of bacteria of the order Bacteroidales. Ruminococcus spp is significant in the fermentation of complex carbohydrates in the large bowel. A diet rich in complete carbohydrates has been shown to increase Ruminococcus spp.¹⁴⁶ 

Botanical Compounds for the Brain-Gut Connection

A large number of medicinal plants and their secondary metabolites with potential antiulcer (nervine and immune modulating as well) activities have been used both traditionally and have been recently verified from scientific studies. Treatment with botanicals and botanical compounds, such as alkaloids, terpenes, phenolics and flavonoids, produce effective therapeutic results, with no or few side effects and no toxicity.¹⁴⁷ 

The Mederi Care Approach to Herbal Nervines

In my practice, I’ve found that combining herbs and nutrients enables me to create formulas that are far more effective than relying on a single herb. This is the traditional manner of practicing herbalism, and it is as much an art as it is a science.¹⁴⁸ Stress, anxiety, and depression are common afflictions for those of us living in modern society, and the consequences of these emotional states affect not only our emotions, but also our bodies.¹⁴⁹ 

Emotional distress causes a cascade of hormonal events that negatively influence the cardiovascular, immune, digestive, and reproductive systems, as well as the brain and nervous system.¹⁵⁰ For this reason, I always begin with lifestyle recommendations to provide a foundation for stabilizing and strengthening the nervous system.¹⁵¹ 

In addition, I prescribe botanical formulas that provide a broad spectrum of support for the nervous system. In traditional herbal medicine we call these herbs “nervines.” Nervines support and relax the nervous system while nourishing and strengthening it. They fortify the “Vital Spirit” and gently support the Kidney and Liver Networks as well.¹⁵² 

One of the great benefits of botanical medicine is that plants have pleiotropic effects – which means that they have multiple benefits. So, for example, when we’re treating anxiety and stress, we can at the same time be enhancing immunity, or bolstering cardiovascular health, or strengthening the body’s defenses against cancer. Herbs are complex in that they bathe cells with hundreds of compounds, some of which may have very specific and direct ways in which they work, while others are non-specific and play a supportive role.¹⁵³ 

Herbal nervines are unique in that they quiet down the sympathetic nervous system while enhancing the parasympathetic nervous system. Not only does this help us to feel more relaxed, but it also may prevent illness and enable us to live a healthier and longer life.¹⁵⁴ 

Rauwolfia (Rauwolfia serpentina/vomitera): The Premier Sympatholytic

Rauwolfia is very specific for Type A sympathetic types as it tones down the sympathetic nervous system and can act as a mild tranquilizing agent. Rauwolfia serpentina root has been used for centuries in India, and Rauwolfia vomitera in Africa, for the treatment of a variety of disorders including snake bites, insect bites and stings, insomnia, and insanity.¹⁵⁵ In India and Nepal, it is a common treatment for hypertension and insomnia. Gandhi took it frequently at night for its calming actions.

Rustom Jal Vakil was a famous Indian cardiologist who, in 1949, “published a watershed paper on the antihypertensive properties of Rauwolfia serpentina and affected a paradigm shift in the management of hypertension.” “Rauwolfia was the world’s 1st successful blood-pressure-lowering agent.¹⁵⁶ 

Some of these alkaloids act similar to beta blockers. Reserpine inhibits the re-uptake of norepinephrine, causing its depletion by enzymes. Another alkaloid, ajmaline, has anti-arrhythmic action and inhibits ventricular arrhythmias. Rauwolfia has tranquilizing effects because, like beta-blockers, it reduces the effects of the stress hormone norepinephrine.¹⁵⁷ 

Although reserpine remains very useful in the treatment of hypertension, whole rauwolfia extract standardized to 1% reserpine is far more effective and has fewer side effects. In low dose, reserpine acts synergistically with other cardiovascular tonic herbs and nutrients in formulations.¹⁵⁸ 

Clinical Research on Rauwolfia

Rauwolfia serpentina significantly decreased blood pressure in test groups as compared to controls. Significant impact was reported on serum lipid profile and serum proteins as well as hepatoprotective and renoprotective potential in animal groups given herbal extract as compared to control groups.¹⁵⁹ 

A recent review of all compiled studies done on reserpine found it to be as effective as other first-line antihypertensive drugs. Reserpine is effective in reducing systolic blood pressure roughly to the same degree as other first-line antihypertensive drugs.¹⁶⁰ 

Anti-Cancer Properties

Anti-prostate cancer activity of a beta-carboline alkaloid enriched extract from Rauwolfia vomitoria has been demonstrated. Rauwolfia vomitoria extract standardized for beta-carboline alkaloids was tested for ability to influence the growth and survival of human prostate cancer cell lines. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed various doses of Rauwolfia extract.¹⁶¹ 

Reserpine induces apoptosis and cell cycle arrest in hormone independent prostate cancer cells through mitochondrial membrane potential failure. Results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis.¹⁶² 

Antitumor activities of Rauwolfia extract and potentiation of gemcitabine effects against pancreatic cancer have been demonstrated. Rauwolfia induced apoptosis in pancreatic cancer cells in a concentration-dependent manner, and completely inhibited colony formation. The combination of Rauwolfia and gemcitabine had a synergistic effect in inhibiting cell growth.¹⁶³ 

Constitutional Applications

Rauwolfia is a “sympatholytic” agent. As a result, it increases the level of calm and decreases stress responses. This can be associated with an emotional-cognitive feeling of tranquility. Some people find this a little disturbing and experience it as “depression” or “emptiness,” others find it a positive and beneficial experience conducive to meditation – Gandhi used to drink Rauwolfia tea daily for its calming and pro-meditative influence.¹⁶⁴ 

Traditional Nervine Botanicals

Chamomile (Matricaria recutita)

Chamomile has been used as a traditional herbal remedy for its digestive, relaxation and calming effect. It was one of the important medicinal herbs native to southern and eastern Europe, known in ancient Egypt, Greece, and Rome. The pharmacological properties include antiinflammatory, antiseptic, carminative, healing, sedative, and spasmolytic activity.¹⁶⁵ 

Active compounds include the terpenoids α-bisabolol and its oxide azulenes including chamazulene and acetylene derivatives. Among flavonoids, apigenin is the most promising compound. Apigenin decreases cortisol plasma concentrations and has sedative, analgesic, anxiolytic, anti-inflammatory and immunomodulatory effects.¹⁶⁶ 

One clinical trial suggests that chamomile extract reduces stress and these effects may be a consequence of its inhibiting cortisol production and its calming and anxiolytic effects. Results from an 8-week, randomized, double-blind, placebo-controlled trial showed that chamomile extract therapy had superior anxiolytic efficacy versus placebo in mild to moderate generalized anxiety disorders.¹⁶⁷ 

Chamomile treatment significantly improves generalized anxiety disorder. Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms.¹⁶⁸ 

GI Protective Effects

Studies in preclinical models suggest that chamomile inhibits Helicobacter pylori, the bacteria that can contribute to stomach ulcers.¹⁶⁹ Chamomile is believed to be helpful in reducing smooth muscle spasms associated with various gastrointestinal inflammatory disorders.¹⁷⁰ Oral administration of the aqueous extract of Chamomile flowers at a dose of 400 mg/kg prevented gastric ulceration in mice.¹⁷¹ 

Passionflower (Passiflora incarnata)

Passionflower is one of the herbal extracts I most frequently use in combination herbal nervine tonic formulas that naturally promote tranquility.¹⁷² Clinical studies demonstrate that passionflower extract can significantly reduce anxiety levels in patients undergoing medical procedures and in those with generalized anxiety disorder. The herb works primarily through its interaction with GABA receptors, increasing the availability of this calming neurotransmitter in the brain.¹⁷³ 

Kava (Piper methysticum)

Kava is one of my favorite herbs – not only for its beneficial effects on the nervous system, but also because it appears to have unique anti-cancer properties.¹⁷⁴ However, as with any herb, I recommend using it in combination with other herbs and nutrients.

Research into psychoactive plants that affect the central nervous system (CNS) has flourished, with an abundance of pre-clinical in vitro and in vivo studies validating many herbal extracts as having an array of biopsychological effects.¹⁷⁵ I always use a combination of herb formulas and not just single herbs – I think of the herbs harmonizing and working together like a great jazz band.

The Core Nervine Formula

The herbal extracts I most frequently use include passionflower (Passiflora), ziziphus (Ziziphus spinosa) seed, kava kava (Piper methysticum) root, lemon balm (Melissa officinalis), oat seed (Avena sativa), saffron (Crocus sativa), skullcap (Scutellaria lateriflora), and lavender flower (Lavandula spp.).¹⁷⁶ 

Skullcap (Scutellaria lateriflora) was used by both Native American Indians and the Eclectic physicians to ease anxiety and stress. Skullcap has a soothing influence upon the nervous system that encourages quiet relaxation and restful sleep, without sedation. Combined with Avena sativa, it is the classic nervine duo for calming, tonifying, and regenerating the entire nervous system.¹⁷⁷ 

I also find L-theanine, glycine and/or GABA to be extremely effective when combined with botanicals. In choosing herbs and nutrients that are beneficial for stress, anxiety, and depression, I select those that have synergistic and tonic-like effects on the neurotransmitter, nervous and endocrine systems.¹⁷⁸ This includes acting as GABA receptor agonists and/or boosting GABA levels. GABA (γ-aminobutyric acid) is an inhibitory neurotransmitter that reduces nerve impulse transmission between neurons; low levels of GABA in the central nervous system are associated with anxiety, depression and insomnia.¹⁷⁹ 

Additional Digestive-Supportive Botanicals

Aloe Vera (Aloe barbadensis Miller)

Aloe vera is a well-known medicinal herb used for commercial and therapeutic properties in many parts of the world. AV gel contains compounds with proven antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory, anti-diabetic, immunomodulatory, and wound healing properties.¹⁸⁰ AV gel contains acemannan, which has been identified as the primary polysaccharide responsible for enhancing humoral immune response and cellular immunity.¹⁸¹ 

Celery Seed (Apium graveolens)

The purified component, termed (CAH), isolated from the crude alcohol extract of celery seeds, had potent bactericidal effects against H. pylori; the MIC and MBC were 3.15 lg/ml and 6.25–12.5 lg/ml, respectively.¹⁸² 

Ginger (Zingiber officinale)

Gingerols are the major pungent compounds present in the rhizomes of ginger and are renowned for their contribution to human health and nutrition. Both gingerols and shogaols exhibit a host of biological activities, ranging from anticancer, anti-oxidant, antimicrobial, anti-inflammatory and anti-allergic to various central nervous system activities.¹⁸³ 

The potential role of ginger extract was evaluated in modulating the extent and severity of ulcerative colitis. Results showed a valuable effect of ginger extract against acetic acid-induced ulcerative colitis possibly by its antioxidant and anti-inflammatory properties.¹⁸⁴ 

Holy Basil (Ocimum sanctum)

Holy basil has potent stress-protective and antiulcer effects. The mechanism of action was studied using aspirin, indomethacin and alcohol induced ulcer models and it was possibly due to the inhibition of 5-lipooxygenase.¹⁸⁵ 

Licorice (Glycyrrhiza glabra)

Licorice is well documented in written form starting with the ancient Greeks. Glycyrrhizin is the major active constituent obtained from licorice roots, one of the most widely used in herbal preparations for the treatment of liver complaints. The plant is used as anti-inflammatory, spasmolytic, laxative, anti-depressive, anti-ulcer and anti-diabetic.¹⁸⁶ 

Proton Pump Inhibitors and Gut Health

Today, millions of us spend billions of dollars each year on medications, mostly PPIs (Proton pump inhibitors), designed to lessen or get rid of stomach acid. Yet, suppressing a natural process like stomach acid secretion for long periods can have serious unintended consequences; and these drugs are very difficult to get off of because of rebound effects.¹⁸⁷ 

Modern medicine and the pharmaceutical industry together has given stomach acid a bad name, but it’s really kind of a bum rap. Stomach acid serves several constructive purposes. Pepsin, an enzyme that is essential to the preliminary digestion of protein, needs an acidic environment in the stomach to be effective.¹⁸⁸ 

PPI usage is associated with an increased risk of several diseases and conditions including pneumonia, c. difficile infections, bone loss and osteoporosis (you need stomach acid to absorb nutrients such as calcium into the bone), and vitamin B12 deficiency, to name a few.¹⁸⁹ 

Clinical Integration and Safety Protocols

Personalized Constitutional Approaches

Understanding constitutional types and individual response patterns is essential for optimizing vagus nerve support protocols. The Mederi Care approach recognizes that each person has unique physiological, psychological, and energetic patterns that influence their response to therapeutic interventions.

The Type A Sympathetic Constitution

Characteristics: High baseline sympathetic activity, tendency toward anxiety and hypertension, rapid pulse, difficulty relaxing, driven personality, prone to cardiovascular disease and stress-related disorders.

Primary Intervention: Rauwolfia-based formulations provide the most targeted support for this constitutional type.

Supporting Protocol:

• Rauwolfia serpentina (standardized whole plant extract): 100-200mg daily
• Passionflower and lemon balm for additional GABA support
• Magnesium glycinate: 400-600mg daily
• Daily Pulsetto sessions, particularly evening use
• Cold water therapy and breath work
• Meditation focusing on surrender and letting go

Safety Considerations

While botanical medicines offer significant advantages over pharmaceutical interventions, proper safety protocols remain essential:

Rauwolfia Considerations:

• Avoid in severe depression or suicidal ideation
• Monitor blood pressure in hypotensive individuals
• Potential interactions with MAO inhibitors and certain psychiatric medications
• Use lower doses in elderly or debilitated individuals¹⁹⁰

VNS Device Safety:

• Contraindications include implanted electronic devices, active seizure disorders, pregnancy
• Monitor for blood pressure changes and heart rate variations
• Watch for skin irritation at stimulation sites¹⁹¹ 

Unitive Medicine Applications

Current research is exploring genetic factors that influence vagus nerve function and response to interventions. Polymorphisms in genes affecting neurotransmitter metabolism, inflammatory responses, and autonomic function may predict individual responses to specific botanical medicines and VNS protocols.¹⁹² 

Digital Health Integration

Emerging technologies are combining HRV monitoring, smartphone applications, and AI-driven protocols to create personalized vagus nerve optimization programs that adapt in real-time to individual physiological patterns.¹⁹³ 

Conclusion: The Future of Unitive Medicine

The convergence of ancient wisdom and modern science in vagus nerve optimization represents a paradigm shift in healthcare. By integrating spiritual practices, lifestyle modifications, evidence-based botanical medicines like Rauwolfia and traditional nervines, and carefully selected technologies like the Pulsetto device, we can create personalized protocols that address the root causes of autonomic dysfunction.

The Mederi Care approach recognizes that true healing involves not just the suppression of symptoms, but the restoration of optimal physiological function through support of the body’s innate healing mechanisms. The vagus nerve, as the primary pathway connecting mind, body, and spirit, offers a unique opportunity to facilitate this restoration.

Laughter is more than just an expression of joy, it’s a powerful force for health, longevity, and human connection. From ancient wisdom to modern scientific research, the evidence overwhelmingly supports the idea that humor and laughter contribute to physical, mental, and even spiritual well-being. Whether through improving circulation, reducing stress hormones, enhancing immunity, or fostering deeper social bonds, laughter acts as a natural medicine that benefits every aspect of our lives.

As we continue to deepen our understanding of the vagus nerve’s role in health and disease, the integration of traditional healing wisdom with cutting-edge research will undoubtedly yield new insights and therapeutic approaches. The future of medicine lies not in choosing between ancient and modern approaches, but in their thoughtful integration under the guidance of experienced practitioners who understand both the art and science of healing.

May this comprehensive approach serve as a roadmap for those seeking to optimize their autonomic nervous system function and discover the profound connection between physical health, emotional well-being, and spiritual vitality.

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