Autonomic nervous system problems of one type or another appear to be ubiquitous in chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), postural orthostatic tachycardia syndrome (POTS), and long COVID. One place they show up in is something called low heart rate variability (HRV) scores that are indicative of an overactive sympathetic nervous system (SNS) or fight/flight response.
Low HRV has been found in many diseases including ME/CFS/FM and its cousins (Gulf War Illness), irritable bowel syndrome (IBS), postural orthostatic tachycardia syndrome (POTS), as well as cardiovascular diseases, anxiety, depression, Parkinson’s disease, epilepsy, and others.
Because the vagus nerve controls the activity of the sympathetic nervous system, the SNS dominance seen in ME/CFS, FM, POTS, and similar diseases may be less a function of an overwrought SNS and more a function of an underactive vagus nerve.
Because the vagus nerve is such a ubiquitous nerve that does so many things (relays sensory signals to the brain, affects motor functioning, reduces inflammation, alters neurotransmitter levels, reduces gut permeability (leaky gut), promotes neuroplasticity), stimulating the nerve could potentially have profound effects.
Andrea Parker Gives Vagus Nerve Stimulation a Try
All that led Andrea Parker, an Australian occupational therapist with a severe case of ME/CFS, to give vagus nerve stimulation a try. She found that it helped, shared her story with others, and then presented her findings at a 2019 ME/CFS South Australia Inc. seminar.
Andrea’s bout with glandular fever/infectious mononucleosis several years prior may have set things up. Thirteen years later, a stomach bug combined with stress left her with a case of “post-viral fatigue” and a three-month layoff from work.
It wasn’t until three years later, though, when too much exercise combined with stress left her with severe ME/CFS and knocked her out of the workforce for 15 months, that she said she really “got” what ME/CFS was. On her worst days she said she felt like she was dying – and noted that was a descriptive term – she actually had the feeling that her body was dying.
She’s much better now – is working again – and was at the seminar to share what helped her get better. She made it clear that she is not a doctor, is not claiming any new treatments or cures for ME/CFS, and requested that everyone check with their doctor before trying any new treatments.
The general timeline of her partial recovery was:
- May 2012 – severely ill, 15 months off work.
- Nov. 2012 – supplements began to improve her health
- Sept 2013 – She began a graded return to work and was able to slowly build up her hours up over time.
- 2019 – at the time she trialed tVNS she described her ME/CFS as moderate. The tVNS got her into a mild/moderate category.
She believes the problems with the autonomic nervous system (ANS) play a major role in ME/CFS/FM and similar diseases.
Two Theories of Illness
Two theories of illness undergird her understanding of what happened.
Bob Naviaux’s cell danger response (CDR) theory asserts that low levels of ATP production in the mitochondria are associated with an autonomic nervous system in a fight/flight threat response.
As classically understood, the ANS is composed of two circuits: (1) the sympathetic nervous system (SNS) or fight/flight circuit that arouses the body for action; and (2) the parasympathetic nervous system (PNS) or rest and digest circuit that calms the SNS down – allowing the body to rest and restore itself.
Stephen Porges’ Polyvagal Theory of illness, on the other hand, posits that the ANS has three circuits, not two. Besides the two circuits noted above, Porges believes a freeze/faint immobilization circuit is present.
Parker showed a fascinating chart from Babette Rothschild, a trauma specialist who has embraced Porges’ system, which depicts how symptoms change as the fight/flight system becomes more dominant.
- Active Alert Phase (SNS 1) – the moderate levels of arousal at this stage leave the muscles toned, breathing, heart rates and blood pressure increased. Feet feel cool, digestion slows, emotions like anger, shame, excitement, anxiety show up, and contact with others is “probable”.
- Fight or Flight (SNS II) – high levels of arousal result in tense muscles, faster heart rate, elevated blood pressure, cold hands and feet, and a complete stoppage of digestion. Emotions like rage and fear show up, and contact with others is limited.
- Hyper-freeze (SNS III) – muscles are rigid, tachycardia and hyperventilation occur, blood pressure is very high, extremes of cold/heat are felt, emotions like terror show up, and contact with others is “unlikely”.
Does What Happens in Vagus Stay in Vagus?
Parker’s goal was to take her system out of fight/flight, and in so doing, reduce inflammation, improve her ability to exercise, help her gut, improve her sleep and cognitive functioning, and so on.
Her question was whether she could use a vagus nerve stimulation device and other treatments to communicate messages of safety to the cells (e.g. the cell danger response) and potentially improve their energy production.
The Parasym Stimulator
Two forms of vagus nerve stimulation are available. An implanted version has been approved for use in the U.S. for epilepsy and treatment-resistant depression, and non-invasive stimulators which latch onto the ears are available in some countries.
In Australia in 2019, Andrea had her choice of three VNS stimulating devices that were available (Parasym, Nemos, Gammacore). She chose Parasym. Parasym had the advantage of not requiring a prescription, was at $1,200 actually cheaper, and simpler to use than the others. Parsym also provided a frequency and recommended duration (30 minutes AM/PM) for people with ME/CFS and was considered a relatively low-risk device.
(Parasym devices are available in the UK and European Union and Australia but not in the U.S. or Canada.)
Andrea Parker and Vagus Nerve Stimulation – the Short Version
During her self-trial, she assessed her response using the Modified Fatigue Impact Scale. Overall, her score dropped from 40/84 to 20/84 – a 50% improvement in 8 weeks – something she described as “kind of mind-blowing”.
She experienced improvements in almost every area, and in some that were surprising. Besides improvements in thinking, malaise, exercise without PEM, pain in her hands, anxiety, and feeling stronger, she reported that her vision improved, that she could better handle noisy, highly stimulating environments, and that – she said with a big smile – her agility and ability to play the piano greatly improved.
She still has IBS, but her symptoms have improved and using the VNS device has started her gut moving. Neither her insomnia nor her tinnitus improved. (Parasym has, however, a tinnitus protocol which she has not yet tried.)
The only noticeable side-effects were weird bleeding episodes (nose, butt) and some bruising after about a month.
The Friends Trial
The results, she said, kind of fairly well “blew her brain” and she started communicating about them. After she found five friends willing to try the stimulator, she used Dan Neuffer’s ANS Rewire Questionnaire as the MFISM to assess the results. She noted that this was not a clinical trial and no conclusions can be drawn from it.
Of the five, none had the dramatic results that Andrea did. Looking at all three scores, one person had about a 15% improvement, another a 25% (ANSRO), and another a 25% improvement (MFIS). The other two had negligible improvements.
Those who did improve tended to experience reduced cognitive fatigue, reduced pain, light, sound, smell hypersensitivity, improved bowel symptoms, less IBS, and increased activity levels.
One person improved quickly, then ramped up her activity levels and crashed. She ended up being a non-responder who might have ended up as a responder had she taken it easier.
Andrea Parker and Vagus Nerve Stimulation – the Long Version
Improving Heart Rate Variability (HRV)
Andrea’s attempt to improve her heart rate variability level, and thus calm down her sympathetic nervous system or fight/flight response, led her to try a number of options that ended up helping. Her supplements began her partial recovery process. They included:
Fish oil – has been shown to enhance parasympathetic nervous system activity and it started her recovery. (SelfDecode recently reported that for some people with CRP gene variant, omega-3 fatty acids are effective for reducing anxiety. This is because high CRP levels produce inflammation and anxiety and omega 3 fatty acids can bring them down.)
Healthy diet and probiotics – L rhamnosus (Bioceuticals Ultrabiotic 45) – a probiotic – that is also believed able to affect HRV – produced a massive improvement in mood/cognitive functioning. She noted that it was very expensive and did not work when she was severely ill, but afterward it was very helpful.
Stress management – slow breathing and meditation with longer out-breaths helped. Since inhalation actually stops vagus nerve activity, holding your breath (as I know that I’m prone to do) jacks up the fight/flight response. The rest and digest response, on the other hand, is activated during the out-breath. (Andrea suggested trying breathing in for four counts and breathing out for six). CBT and acceptance commitment therapy helped to calm her system down as well.
Exercise – if safe and done within the energy envelope (tai chi, yoga, others), exercise can improve vagus nerve functioning.
Improving Her Low Energy State
To treat her low energy state, Andrea reported that she took lots of supplements, Vitamin D3 drops taken through the tongue, did cognitive rehab (brain HQ) – only if you have the energy to do it, as well as setraline (Zoloft) for anxiety, zolpidem tartrate and zoplicone (Imovane) for insomnia.
Improvements Using the HRV and Energy Enhancing Treatments
Andrea went from severe to mild/moderate ME/CFS. Besides the other improvements she noted with the vagus nerve stimulation, her severe and frequent migraines virtually disappeared, her anxiety and mood problems improved significantly, her sensitivities were reduced, her mild autistic traits (which she didn’t know she had) improved, and her hair stopped falling out.
She still has ME/CFS but is obviously much improved.
Vagus Nerve Stimulation Survey
Andrea didn’t stop with her five friends. She teamed up with Dawn Wiley, the founder of the Facebook Group “A Vagus Adventure AVA” and Physio for ME’s Dr Nicola Clague-Baker at the University of Liverpool to develop a survey of TNS effectiveness in ME/CFS.
If you have ME and have experimented with vagus nerve stimulation, please take the international survey.
Vagus Nerve Stimulation – the Future
Suffice it to say that many disease groups are interested in using vagus nerve stimulation to calm the sympathetic nervous stimulation down and reduce inflammation, improve gut functioning, reduce anxiety, improve neuroplasticity, and so on.
One person with extreme fibromyalgia benefited greatly from invasive vagus nerve stimulation. Several fibromyalgia studies that are, or have gotten, underway include Norwegian, a Turkish one, a U.S, and a large Spanish/German one. Several POTS vagus nerve studies are underway at the University of Oklahoma. One long-term study reportedly found that while “progressive global improvement” had occurred, significant symptom burdens remained. A shorter trial found increased HRV and improved norepinephrine levels.
No ME/CFS studies were found, but Sjogren’s Syndrome study did find that non-invasive VNS markedly reduced fatigue, improved immune functioning, and reduced pro-inflammatory cytokines.
- Andrea Parker was battling ME/CFS as an occupational therapist when she decided to try vagus nerve stimulation and tame the fight/flight response she believed was depleting her energy, causing her cognitive, gut, sleep and anxiety issues, and other symptoms.
- The vagus nerve regulates the functioning of the fight/flight response which heart rate variability studies in ME/CFS, fibromyalgia, POTS, and many other diseases indicate is hyperactivated. Given the many systems of the body (immune, cardiovascular, central nervous system, gastrointestinal) the vagus nerve effects, trying to plump it up a bit in order to knock the fight/flight response down makes perfect sense.
- Andrea’s bouts with glandular fever/infectious mononucleosis, a stomach infection, and overwork/overexercise had landed her out of the workforce for an extensive period of time. She used other treatments to turn her severe ME/CFS into moderate ME/CFS and was back at work when she decided to try the vagus nerve stimulator
- She used a fatigue questionnaire to assess how effective the Parsym device (available in Australia/the UK) was. Her score reflected how she felt – a 50% drop in most of her many symptoms – a result she called “mind-blowing”. The only symptoms that didn’t dramatically improve were her insomnia and her gut symptoms.
- Of the five friends who replicated the trial three produced significant benefits (@25% improvements) and two did not.
- Andrea and others have created an International ME/CFS Vagus Nerve Stimulation Survey to see how others are doing.
- Vagus nerve stimulation trials are currently underway in fibromyalgia and postural orthostatic tachycardia syndrome (POTS) but not to my knowledge in ME/CFS.
- Andrea also listed other treatment approaches she used to tamp down the fight/flight response and improve her energy. She is now well but has vastly improved.
- With the National Institutes of Health (NIH) and private industry pouring money into mapping the peripheral nervous system and devising devices to manipulate it for better health, the future of this kind of stimulatory technology – whenever it shows up – appears to be bright, indeed.
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A recent review of the field suggested that the vagus nerve stimulation field is rapidly evolving, and that different forms and techniques are being developed. The review noted that the idea of using non-invasive approaches to stimulate the vagus nerve only first emerged in the early 2000s.
Newer, non-invasive ear-based vagus nerve stimulating devices called “closed-loop” devices, which adapt rapidly to changing conditions, could offer a more personalized approach. These devices would employ biofeedback to adjust the amount and frequency of stimulation present to keep the vagus nerve functioning at an optimal level.
SPARCING Vagus Nerve Stimulation Breakthroughs?
These awards have the potential to catalyze next-generation neuromodulation therapies that could bring improved specificity for patients over both drug therapies and previous-generation devices.” SPARC Program Manager Gene Civillico, Ph.D
The NIH’s Stimulating Peripheral Activity to Relieve Conditions (SPARC) could go a long way to improving vagus nerve stimulation. The $250 million 10-year initiative is largely engaged in funding basic research that will illuminate how the peripheral nervous system – of which the vagus nerve plays a large part – works and devise better ways to treat it.
The VNS technology available now simply stimulates a big nerve that engages in a multitude of activities. Fully harnessing the power of this complex nerve (the neck area of the vagus nerve contains over 100,000 fibers) is going to take some work, though, and significant resources are going to map in, fine detail, where the vagus nerve goes and what it connects to. Besides placing the stimulation more precisely, researchers hope to be able to determine which patterns and frequencies of stimulation work better.
Once researchers know which fibers stimulate which organs, more powerful and precise devices can be developed. One study, for instance, is mapping the vagus nerve projections to the brainstem – a possibly key area in ME/CFS. A Colorado team is developing an optical or light probe that will not only be able to report on the activity in the different branches of the vagus nerve but determine which stimuli can activate them.
Gut problems can be amongst the most difficult to fix in ME/CFS/FM and almost half of the SPARC-funded studies will focus on the “second nervous system” — the gut.
One will map the vagus nerve innervation in the small intestine to learn how it affects gut motility and functioning in hopes of finding new ways to treat the pain associated with irritable bowel syndrome and other “sensory” gastrointestinal disorders. A New York team is developing a wireless tool to monitor the activity of vagus nerve endings that innervate the gut.
Another study right up the ME/CFS/IBS alley found that epithelial cells lining the gut are – in response to the release of ATP – turning on the sensory nerves. Those activated sensory nerves, in turn, may be causing the mysterious gut pain that’s present even when no signs of inflammation are found. Another study with obvious IBS/ME/CFS connection attempts to determine how secretions from cells in the bowel are able to turn on pain pathways in the brain in IBS.
In “A Spark in the Periphery” Emily Walz reported that GlaxoSmithKline and Verily Life Sciences (formerly Google Life Sciences) are pumping more than $700 million into a company, Galvani Bioelectronics, that will develop miniaturized electronic devices for peripheral nerve stimulation. DARPA, the Defense Advanced Research Projects Agency, is getting into the act as well, devoting $90 million into the hunt for better electroceuticals.
Theoretically, attempts to boost parasympathetic nervous system activity in ME/CFS and FM make sense and anecdotal reports suggest that it may be helpful for some. Vagus nerve stimulation research is in its infancy in ME/CFS and fibromyalgia, but with the international survey and fibromyalgia clinical trials underway, we should have some idea of its effectiveness in these diseases in the relatively near future.
As Andrea Parker demonstrated, other means of boosting vagus nerve activity and taming the fight/flight response can be helpful. A blog on using breathwork and other approaches to try and get the vagus nerve back on track is coming up.
With hundreds of millions of dollars being pumped into bio-electroceutical research by the NIH and private industry, future devices – whenever they come – should be more precise and more powerful.
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