Vagus Nerve Stimulation for ME/CFS, POTS, & Long-Haul COVID
Basic Vagus Nerve Anatomy
The vagus nerve is one of the longest nerves in your body, stretching from your brainstem down through your neck and chest to your abdomen. It acts like a superhighway for signals traveling between your brain and many of your organs. This nerve is involved in many important tasks, such as controlling your heart rate, digestion, and even your immune system. Treatments geared toward this nerve may have system-wide effects and are under study for fibromyalgia, long-haul COVID, and postural orthostatic tachycardia (POTS), among other conditions.
How Viruses Can Infect the Vagus Nerve
Usually during an acute infection, like a respiratory virus, the vagus nerve stimulates the body to rest and relax so healing can take place. This brings on the feeling of fatigue that makes us rest during an acute infection. However, when a virus is strong enough to infect the vagus nerve itself, the message of rest is amplified to an exaggerated degree. Severe fatigue. A red alarm to rest.
The vagus nerve, like other parts of the nervous system, can be vulnerable to viral infections. Certain viruses tend to infect nerve tissues, and the vagus nerve is no exception. These are called neurotropic viruses and you are familiar with many of them already: HHV6, SARs-COV-2, enterovirus, coxsackie, cytomegalovirus, and Epstein-Barr virus.
Infections of the vagus nerve can lead to a variety of symptoms and are thought to be strongly associated with postviral fatigue conditions. Dysfunction of the vagus nerve is impaired in ME/CFS patients, likely due to the initial infection that triggered the illness and/or reactivation of the old virus in vagus nerve tissue (1-3).
This is also a reason why antiviral drugs are generally not very effective for ME/CFS symptoms. They are helpful in only a small fraction of patients. If the infection is lingering in the vagus nerve and nearby nervous tissue, the antiviral drug has no chance of reaching that site to have an effect. It is the ultimate form of defensive cover (1, 3).
There is perhaps another way…
How External Vagus Nerve Stimulators Work
Vagal nerve stimulators are not new. Implanted devices have been approved and used for the treatment of refractory epilepsy since 1997, treatment-resistant depression since 2005, and cluster headaches since 2016. Less invasive, transcutaneous electrical stimulators have also been developed and approved. In the EU, these are recently approved for the treatment of refractory epilepsy and pain.
The external transcutaneous vagus nerve stimulators (tVNS) are devices that send mild electrical pulses to the vagus nerve via an accessible body area. Unlike implanted devices, which are often housed in the chest cavity, external VNS devices are placed on the tragus of the ear—that little button of the ear that we press on when we don’t want to hear something.
Vagus Nerve Stimulation Reduces Inflammation
Inflammation is a key factor in ME/CFS, long-haul COVID, and fibromyalgia. It also stands to reason that any reduction in the inflammatory burden will improve symptoms and the overall condition. Reducing inflammation is my #1 priority, be it through diet, nutrition, or supplements. We also now have a tool to reduce it with technology. External vagus nerve stimulation has shown promise in reducing inflammation through the following mechanisms:
Anti-Inflammatory Pathways: The vagus nerve is part of the inflammatory reflex, a mechanism by which the nervous system regulates the immune response. When stimulated, the vagus nerve can activate anti-inflammatory pathways, helping to reduce the production of inflammatory molecules like cytokines, IL-8 and TNF-alpha (2).
Modulating the Hypothalamic–Pituitary–Adrenal (HPA) Axis: studies show that these devices stimulate the adrenal glands to release glucocorticoids, a potent anti-inflammatory hormone (1).
Modulating the Immune System: By influencing the immune system and giving it a bit of a reset, tVNS can help maintain a balance between pro-inflammatory and anti-inflammatory signals (2).
Reducing Systemic Inflammation: Regular use of tVNS has been associated with lower levels of systemic inflammation and improved blood flow and oxygen delivery. Low oxygen levels and low blood flow to the brain are characteristic features of ME/CFS and long-haul COVID.
Better Sensing of the Gut Environment: Sensory fibers of the vagus nerve can detect microbial stimuli and dysbiosis in the gut and other areas, potentially contributing to chronic inflammation in ME/CFS.
Key Research Findings on External Vagus Nerve Stimulation
So far, clinical trials are short on participants. We need a lot more study with larger cohorts. However, the results are thus far very promising! The use of these devices in postviral conditions has long been underway. I hope more groups design studies in ME/CFS using appropriate diagnostic criteria. Let’s look at a few recent studies.
Vagal Nerve Stimulation in Chronic Fatigue
Research has shown that external vagus nerve stimulation can significantly reduce fatigue, especially in individuals with chronic fatigue syndrome. Studies suggest that tVNS helps by modulating the autonomic nervous system, reducing inflammation, and improving sleep quality.
A study of 40 individuals with the autoimmune disease Sjogren’s used an external vagus nerve stimulator device for 56 days. Levels of fatigue improved when compared to a placebo. There were improvements found in neurocognitive tests and positive changes in the brain as measured by electroencephalography, EEG (4).
A 2023 study of 31 patients with moderate-to-severe ME/CFS received 20 min of INMEST (a type of electrical stim that hits the vagus nerve up the nose) twice a week for 1 month. Plasma cytokines IL-17A, IL-12B and CCL28 were reduced after the treatment. Participants didn’t report improvements in fatigue, perhaps attributed to the taxing effort to get to the testing center (5).
Vagal Nerve Stimulation in Postural Orthostatic Tachycardia Syndrome (POTS):
Studies have indicated that tVNS can help manage POTS symptoms by improving autonomic regulation and reducing the heart rate response upon standing. This can lead to better blood flow and reduced symptoms of dizziness and fatigue.
One study found that 2-months of VNS use resulted in lower levels of autoantibodies to key autonomic nervous system receptors: alpha-1 and beta-1-adrenergic receptors (6).
Vagal Nerve Stimulation in Long-Haul COVID:
Many long-haul COVID patients experience symptoms such as fatigue, brain fog, and heart palpitations, which may be related to vagus nerve dysfunction. Early research suggests that tVNS may help alleviate these symptoms by improving autonomic balance and reducing inflammation. Some studies have reported improvements in energy levels, cognitive function, and overall well-being in long-haul COVID patients using tVNS.
A small 2022 study by ME/CFS veteran Ben Natelson underwent 35 min a day of transcutaneous vagal nerve stimulation for 6 weeks. All participants showed benefits in some subjective parameters, like the SF-36 scale. No changes were found in perceived brain fog, however (7).
Cautious Optimism
Of all possible treatments for postviral conditions, vagal nerve stimulation seems the most promising. Clinical trials show little to no adverse effects. This treatment is contraindicated for some, including pregnant women, those with pacemakers, implants, or other implanted electrical devices.
There also needs to be a lot more study of these devices. Each device functions a bit differently, has varying electrical frequencies, and may not precisely target vagus nerve branches in the ear. There are also no standardized treatment protocols (e.g. treatment time, duration, frequency).
In general, the vagus nerve is a crucial part of your nervous system, and external vagus nerve stimulators are devices that can potentially help manage fatigue, reduce inflammatory load, modulate the HPA axis, and affect the gut environment. I’ll keep following the research on these with great interest. Dr. Craig has been trialing the Nurosym device. Stay tuned for updates on social media.
References
1. Linnhoff S, Koehler L, Haghikia A, Zaehle T. The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue. Front Immunol. 2023 Jan 9;13:935614. doi: 10.3389/fimmu.2022.935614. PMID: 36700201; PMCID: PMC9869163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869163/
2. Sant'Anna FM, Resende RCL, Sant'Anna LB, et al. Auricular vagus nerve stimulation: a new option to treat inflammation in COVID-19?. Rev Assoc Med Bras (1992). 2023;69(6):e20230345. Published 2023 Jun 2. doi:10.1590/1806-9282.20230345
3. VanElzakker MB. Chronic fatigue syndrome from vagus nerve infection: A psychoneuroimmunological hypothesis. Med. Hypotheses (2013), http://dx.doi.org/10.1016/j.mehy.2013.05.034
4. Tarn J, Evans E, Traianos E, et al. The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome. Neuromodulation. 2023;26(3):681-689. doi:10.1016/j.neurom.2022.08.461
5. Rodriguez L, Pou C, Lakshmikanth T, Zhang J, Mugabo CH, Wang J, Mikes J, Olin A, Chen Y, Rorbach J, Juto JE, Li TQ, Julin P, Brodin P. Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance. Oxf Open Immunol. 2023 Apr 17;4(1):iqad003. doi: 10.1093/oxfimm/iqad003. PMID: 37255930; PMCID: PMC10148714.
6. Stavrakis S, Chakraborty P, Farhat K, et al. Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. JACC Clin Electrophysiol. 2024;10(2):346-355. doi:10.1016/j.jacep.2023.10.015 https://pubmed.ncbi.nlm.nih.gov/37999672/
7. Natelson, B., Blate, M. & Soto, T. Transcutaneous Vagus Nerve Stimulation in the Treatment of Long COVID-Chronic Fatigue Syndrome. Preprint at https://doi.org/10.1101/2022.11.08.22281807.
