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The Vagus Nerve: New Understandings, Emerging Research and Implications for Overall Wellness.

In recent years, the vagus nerve has become a topic of great interest, especially as it relates to stress, anxiety, depression, mood and sleep. Social media and popular blogs propose a slew of hacks and home remedies aimed at toning the vagus nerve. And with such product offerings as essential oils, pillow mists, vibrating bracelets and vagus nerve stimulation devices, an entire industry around the vagus nerve is emerging.

The fascination with all things vagal is not unwarranted. Problems with the vagus nerve are implicated in a diverse variety of ailments, and conditions ranging from cortisol issues, immune dysfunction and hormonal dysregulation to migraines and sleep disturbances may share a common contributing mechanism of action: the vagus nerve.

“Therapeutically, our goal is to assist patients and to regulate and balance the autonomic system—taking down the sympathetic fight-or-flight response and upregulating the rest-and-digest parasympathetic tone,” says Mark J. Tager, M.D., co-founder of the non-profit Vagus Nerve Society. “It is this imbalance that is the primary contributor, or at least an exacerbating factor, in many disease states.”

 

The wandering cranial nerve X.

The longest and most complex of the 12 cranial nerves, the vagus nerve—also known as cranial nerve X—impacts and interacts with myriad organs and systems. Its name derives from the Latin word for “straying” or ‘”wandering”—an appropriate designation, since the vagus nerve follows an extensive pathway, traveling from the medulla to the gut and touching nearly every organ in the body.  This bidirectional superhighway is made up of thousands of motor and sensory fibers—about 80 percent afferent (sensory) fibers and 20 percent efferent (motor) fibers. As the main component of the parasympathetic nervous system, it’s intimately involved in a vast array of physiological functions, including digestion, immune response, heart rate, respiratory rate and mood.

Of particular interest is the role of the vagus nerve in regulating systemic inflammation, and its association with the gut-brain axis. “Only recently have we come to understand the role of the vagus nerve in the detection and regulation of systemic inflammation through a mechanism known as the cholinergic anti-inflammatory pathway, discovered by Kevin J. Tracey, M.D.,” says Tager. Subsequent research suggests additional mechanisms by which the vagus nerve influences inflammation. As a result of these findings,  the vagus nerve is an emerging therapeutic target for addressing multiple chronic inflammatory disorders, including ulcerative colitis, Crohn’s disease, irritable bowel syndrome and rheumatoid arthritis.[1], [2], [3] 

Furthermore, the vagus nerve plays a vital role in the gut-brain axis. Afferent fibers in the nerve relay data from the gut to the brain, transmitting information about pain, inflammation, satiety, motility, the presence of toxins or irritants, intestinal barrier integrity, the microbiome and more. Efferent fibers carry signals from the brain back to the gastrointestinal tract, modulating digestion, gut motility, the release of hormones and neurotransmitters and other functions. And given the link between gut, brain and mood, vagus nerve interventions may prove to be a valuable approach for treating anxiety, depression and other mood disorders.

Even in the absence of clinical conditions, addressing what’s known as “vagus insufficiency” has profound implications for overall health and well-being. The term— coined by Peter S. Staats, M.D., co-founder of the Vagus Nerve Society—is intended to describe patients who have multiple functional symptoms that, on the surface, seem unrelated. “These so-called multiple morbidity syndromes all have a link to the vagus nerve in some way,” Staats says. “We now recognize that the mechanism underlying this presentation is one of latent causation.” The traditional approach, he says, has been to refer patients to a specialist for each presentation—a psychiatrist for anxiety, a gastroenterologist for gastrointestinal issues, a cardiologist for heart palpitations, and so forth. “As it turns out,” says Staats, “stimulating the vagus nerve in people with these constellations of symptoms will resolve many of these problems.”

A comprehensive protocol aimed at correcting vagus insufficiency not only addresses clinical conditions but may also enhance overall health and wellness. From life hacks to evidence-based interventions, here’s what we know.

 

Cold water immersion, home remedies, life hacks.

Vagus-nerve life hacks and pop cures abound. Some of the most popular: cold water therapies—submerging the face in freezing water, placing an ice pack wrapped in cloth on the chest or completely immersing the body in icy water—are said to lower heart rate, calm anxiety, encourage sleep and strengthen immunity. A rationale for these claims exists: sudden exposure to cold induces a stress response and a subsequent activation of the parasympathetic nervous system via the vagus nerve. Additionally, holding the breath and submerging in water induces the so-called “diving reflex,” triggering an immediate decrease in heart rate.

Specific, targeted massages around the neck and shoulder area also appear to improve vagal tone. Vagus nerve massage involves stroking and twisting the trapezius muscle by gripping between the trapezius and sternocleidomastoid muscle, below which the main strand of the vagus nerve runs, as well as stroking the muscles at the base of the skull. In one small study, vagus nerve massage increased heart rate variability, considered a measure of vagal tone, while promoting subjective relaxation and significantly reducing stress. Carotid sinus massage—pressing gently and lightly with the fingers on the side of the neck along the carotid artery—is thought to enhance vagal tone and slow heart rate, and case reports hint at using the technique to abort seizure activity in epilepsy.[4], [5]

 

Diaphragmatic breathing.

Controlled breathing has been used for centuries to calm, balance and reset the nervous system. Also called “belly breathing” or “abdominal breathing,” diaphragmatic breathing involves taking deep, slow breaths and allowing the abdomen to expand on the inhale. As the abdomen moves outward, the diaphragm drops. On the exhale, the belly draws in and the diaphragm moves upward.

Research suggests such regulated, intentional breathing directly and indirectly impacts the central nervous system, working in part by stimulating the vagus nerve  via the phrenic nerve that controls the movement of the diaphragm. Decreasing respiratory rate through targeted breathing practices also promotes parasympathetic nervous activity while suppressing sympathetic nervous activity.[6], [7], [8]

In a systematic review and meta-analysis, voluntary slow breathing increased heart rate variability, a measure of vagal tone, during and immediately after sessions. Other research shows benefits on vagal tone from even a single session of slow, deep breathing, as well as a marked reduction in anxiety. Along with pace and fullness of breath, the pattern of inhale and exhale are important. Some research reports that eight breaths per minute makes parasympathetic nervous activity dominant. Additional studies suggest a pace of 5.5 breaths per minute results in greater heart rate variability than other patterns. Interestingly, regulated breathing seems to be even more effective in older adults, and since vagal response decreases with age, breathing exercises could be a valuable tool in a healthy aging protocol.[9], [10], [11]

 

Meditation and movement.

Like diaphragmatic breathing, meditation and movement practices like yoga and tai chi appear to modulate the central nervous system and support vagal tone. Contemplative practices have been linked to vagus nerve activation and increased heart rate variability. In one review, mindfulness meditation and loving-kindness meditation were among the effective interventions shown to improve heart rate variability and vagal tone. In another study, four weeks of meditation enhanced vagal nerve activity, as well as mood and measures of mental health in caregivers.[12], [13], [14]

One meta-analysis found tai chi and yoga modulated sympathetic-vagal balance, with significantly favorable effects on heart rate variability and stress reduction. Other research validates the impact of various yoga practices on activating the vagus nerve and increasing heart rate variability. The regulated, intentional breathing that’s central to yoga and similar contemplative movement approaches is primarily responsible for these benefits, and stretching may also play a role in increasing heart rate variability.[15], [16], [17]

 

Aerobic workouts and resistance training.

Regular exercise supports all aspects of health, including vagal tone—but certain types of workouts yield greater results. Research demonstrates higher heart rate variability in athletes, compared to sedentary controls, and some studies show improved vagal tone is especially evident after vigorous exercise. In one trial, a moderate-to-vigorous-intensity exercise program increased heart rate variability within 12 weeks in previously sedentary men. High intensity interval training (HIIT) in particular is linked with notable improvements in heart rate variability and vagal tone, as is resistance training.[18], [19], [20]

 

Diet and nutrition.

While little evidence exists on the precise mechanisms of action, overall nutrition has direct and indirect benefits on the vagus nerve. In one literature review, high intakes of saturated or trans-fat and high-glycemic carbohydrates were associated with reduced heart rate variability. High-fat meals  and greater intake of carbohydrates are also related to diminished vagal tone, and in one study, trans-fat consumption predicted lower heart rate variability five years later. Interestingly, a small trial linked high-sodium intake with increased heart rate variability, while a low-sodium diet appeared to decrease vagal tone.[21], [22], [23]

Specific dietary components shown to improve heart rate variability both immediately and in the longer term include the Mediterranean diet, omega-3 fatty acids, B-vitamins, probiotics and polyphenols. In one study, subjects who conformed to the Mediterranean diet had higher heart rate variability across a range of indices, with an increased intake of omega-3 fats from fish thought to be a contributing factor.[24], [25]

In another study, yogurt enriched with alpha-lactalbumin, bioactive peptides and B vitamins improved heart rate variability, and a diet that includes pistachios was linked with higher heart rate variability. Intake of polyphenol-rich red wine, but not of spirits or beer, is likewise associated with increased heart rate variability. And given the intimate relationship between the two, gut-supportive regimens and diets like Paleo or low-FODMAP also impact the vagus nerve. Nutrient testing and gut health tests can identify issues with absorption or metabolism, and nutrigenomics provides valuable insights into how an individual patient absorbs, transports and metabolizes key nutrients.[26], [27]

 

Herbs and supplements.

Along with dietary nutrients, certain herbs and botanicals benefit the nervous system and influence the vagus nerve. Recent research suggests withanolide components in ashwagandha—some as yet unidentified—alleviate stress, anxiety, depression and insomnia by modulating the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary axes, as well as through GABAergic and serotonergic pathways.[28], [29], [30]

“Dr. Tracey’s work paved the way for a better understanding of how nutraceuticals contribute to downregulating inflammation,” Tager says. Herbs like turmeric/curcumin, ginger and ashwagandha send signals to the brain via the afferent vagal fibers in the gut. These signals go to a portion of the brain known as the nucleus tractus solitarius, and then through other brain connections, efferent signals are sent through the vagus to multiple organs, including the spleen. “This results in the release of anti-inflammatory norepinephrine and acetylcholine, which then act upon the mast cells to reduce inflammatory cytokine production,” says Tager. “We also have evidence showing a positive association between omega-3 polyunsaturated fatty acid supplementation and improvements of heart rate variability, which can decrease the risk of cardiac arrhythmias.”

The close relationship connection between the vagus nerve, the gastrointestinal tract and gut microbiota should be considered. “The gut microbiome produces the major quantity of neurotransmitters in the body, an estimated 70 to 80 percent,” says Tager. “Lactobacillus and Bifidobacterium, for example, produce GABA. Other strains produce norepinephrine, acetylcholine or serotonin. These neurotransmitters don’t cross the brain barrier—they work instead by stimulating the afferent vagus nerve fibers from the gut to the brain. The gut bacteria also produce short-chain fatty acids such as butyrate which is mainly utilized to maintain the health of the gut lining.”

Studies point to the specific impact of various probiotics on vagal afferent activity and the enteric nervous system. But probiotics are only one part of a comprehensive gut-brain therapeutic approach that must incorporate dietary adjustments, including increasing intake of plant-based fiber and fermented foods, decreasing simple carbohydrates and sugar, and moderating saturated fat and fried food consumption, Tager says. Other supplements that enhance gastrointestinal health include serum-derived bovine colostrum, zinc carnosine, glutamine, deglycyrrhizinated licorice, ginger, turmeric and peppermint teas, as well as oral enzymes to support digestion.

 

Vagus nerve stimulation implants and devices.

Compelling evidence demonstrates the effectiveness of vagus nerve stimulation for a variety of conditions. In 2005, the FDA approved implantable devices for use in treatment-resistant depression, and similar devices have been approved for treating obesity and epilepsy. Ongoing research continues to show stimulating the vagus nerve can help people with diabetes, post-traumatic stress disorder, autoimmune issues like rheumatoid arthritis, inflammatory bowel disease, gastroparesis and other disorders.[31], [32], [33], [34]

Because implantable devices require invasive surgical procedures that generally aren’t covered by insurance, they’re not readily available for most patients. New, non-invasive devices offer an attractive and affordable alternative. Transcutaneous auricular vagus nerve stimulators show promise  in treating epilepsy, depression, and cardiovascular and digestive system diseases. Other possible applications include addiction, cranial neuropathies, behavioral and cognitive problems, sleep disorders and pain management.  Cervical transcutaneous devices yield similar benefits. FDA-approved handheld stimulators like gammaCore and TruVaga are inexpensive and easy to incorporate into your practice. Both show potential for improving focus, concentration, cognitive performance, sleep and stress, with enormous opportunities for enhancing long-term health and overall wellness.[35], [36]

Check out this webinar:

 

Harnessing the Power of the Vagus Nerve: A Synergistic Approach with Lifestyle, Supplementation, & Non-Invasive Stimulation* with  Mark J. Tager, MD

 

 

References:

[1] Falvey A. Vagus nerve stimulation and inflammation: expanding the scope beyond cytokines. Bioelectron Med. 2022; 8, 19.

[2] Breit S et al. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018 Mar 13;9:44.

[3] Bonaz B et al. The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Front Immunol. 2017 Nov 2;8:1452.

[4] Meier M et al. Standardized massage interventions as protocols for the induction of psychophysiological relaxation in the laboratory: a block randomized, controlled trial. Sci Rep. 2020 Sep 8;10(1):14774.

[5] Laine Green A, Weaver DF. Vagal stimulation by manual carotid sinus massage to acutely suppress seizures. J Clin Neurosci. 2014 Jan;21(1):179-80.

[6] Gerritsen RJS, Band GPH. Breath of Life: The Respiratory Vagal Stimulation Model of Contemplative Activity. Front Hum Neurosci. 2018 Oct 9;12:397.

[7] Kocjan J et al. Network of breathing. Multifunctional role of the diaphragm: A review. Adv. Respir. Med. 2017;85:224–232.

[8] Hamasaki H. Effects of Diaphragmatic Breathing on Health: A Narrative Review. Medicines (Basel). 2020 Oct 15;7(10):65.

[9] Chang Q et al. Effects of slow breathing rate on blood pressure and heart rate variabilities. Int. J. Cardiol. 2013;169:e6–e8.

[10] Lin IM et al. Breathing at a rate of 5.5 breaths per minute with equal inhalation-to-exhalation ratio increases heart rate variability. Int J Psychophysiol. 2014 Mar;91(3):206-11.

[11] Magnon V et al. Benefits from one session of deep and slow breathing on vagal tone and anxiety in young and older adults. Sci Rep. 2021 Sep 29;11(1):19267.

[12] Poli A et al. A Systematic Review of a Polyvagal Perspective on Embodied Contemplative Practices as Promoters of Cardiorespiratory Coupling and Traumatic Stress Recovery for PTSD and OCD: Research Methodologies and State of the Art. Int J Environ Res Public Health. 2021 Nov 10;18(22):11778.

[13] Yuen AW, Sander JW. Can natural ways to stimulate the vagus nerve improve seizure control? Epilepsy Behav. 2017 Feb;67:105-110.

[14] Díaz-Rodríguez L et al. Effects of Meditation on Mental Health and Cardiovascular Balance in Caregivers. Int J Environ Res Public Health. 2021 Jan 13;18(2):617.

[15] Zou L et al. Effects of Mind⁻Body Exercises (Tai Chi/Yoga) on Heart Rate Variability Parameters and Perceived Stress: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. J. Clin. Med. 2018;7:404

[16] Vinay AV et al. Impact of short-term practice of yoga on heart rate variability. Int J Yoga. 2016;9:62-6.

[17] Logan JG, Yeo S. Effects of Stretching Exercise on Heart Rate Variability During Pregnancy. J Cardiovasc Nurs. 2017 Mar/Apr;32(2):107-111.

[18] Melanson EL, Freedson PS. The effect of endurance training on resting heart rate variability in sedentary adult males. Eur J Appl Physiol. 2001;85:442-9.

[19] Guiraud T et al. High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure. Med Sci Sports Exerc. 2013 Oct;45(10):1861-7.

[20] Lin LL et al. Effects of Resistance Training Intensity on Heart Rate Variability at Rest and in Response to Orthostasis in Middle-Aged and Older Adults. Int J Environ Res Public Health. 2022 Aug 25;19(17):10579.

[21] Nagai N et al. Metabolic responses to high-fat or low-fat meals and association with sympathetic nervous system activity in healthy young men. J Nutr Sci Vitaminol. 2005; 51:355–360.

[22] Soares-Miranda L et al. Trans-fatty acid consumption and heart rate variability in 2 separate cohorts of older and younger adults. Circ Arrhythm Electrophysiol. 2012; 5:728–738.

[23] McNeely JD et al. Dietary sodium effects on heart rate variability in salt sensitivity of blood pressure. Psychophysiology. 2008 May;45(3):405-11.

[24] Young HA, Benton D. Heart-rate variability: a biomarker to study the influence of nutrition on physiological and psychological health? Behav Pharmacol. 2018 Apr;29(2 and 3-Spec Issue):140-151.

[25] Dai J et al. Mediterranean dietary pattern is associated with improved cardiac autonomic function among middle-aged men: a twin study. Circ Cardiovasc Qual Outcomes. 2010; 3:366–373.

[26] Sauder KA et al. Pistachio nut consumption modifies systemic hemodynamics, increases heart rate variability, and reduces ambulatory blood pressure in well-controlled type 2 diabetes: a randomized trial. J Am Heart Assoc. 2014; 3:pii: e00087.

[27] Janszky I et al. Wine drinking is associated with increased heart rate variability in women with coronary heart disease. Heart. 2005; 91:314–318.

[28] Dou Y et al. Curcumin attenuates collagen-induced inflammatory response through the “gut-brain axis”. J Neuroinflammation. 2018 Jan 6;15(1):6.

[29] Huang Y et al. Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers. Neurogastroenterol Motil. 2019 Jun;31(6):e13585.

[30] Speers AB et al. Effects of Withania somnifera (Ashwagandha) on Stress and the Stress- Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021;19(9):1468-1495.

[31] Breit, 2018.

[32] Lamb DG et al. Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence. Front Med (Lausanne). 2017 Jul 31;4:124.

[33] Aaronson ST et al. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry. 2017 Jul 1;174(7):640-648

[34] Marsal S et al. Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study. The Lancet Rheumatology. 2021; 3:4, e262-e269.

[35] Wang Y et al. Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application. Neurosci Bull. 2021 Jun;37(6):853-862.

[36] McIntire LK et al. Cervical transcutaneous vagal nerve stimulation (ctVNS) improves human cognitive performance under sleep deprivation stress. Commun Biol. 2021 Jun 10;4(1):634.

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