Vagus Nerve infection hypothesis
This hypothesis is circulating and getting a readership in some CFS circles. I am a PubMed person, and I have been asked my opinion… so to PubMed I go.. There are just 13 articles
- Chronic fatigue syndrome from vagus nerve infection: a psychoneuroimmunological hypothesis.  ” The vagus nerve infection hypothesis offers testable hypotheses for researchers, animal models, and specific treatment strategies.” — so I expect published studies testing this to have been published on PubMed by now…. no luck.
- “Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.”  Wait a minute, no infection of the vagus nerve — rather the chemicals from gut bacteria impacting it instead!
- ” an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.”  – again no infection cited.
- “this action of cytokines (chemicals) can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve” 
- Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome[ 1995].
- Decreased vagal power during treadmill walking in patients with chronic fatigue syndrome.
In short, if there is an infection involved — it should have been identified by now by just sampling the tissue and papers published. Despite some sites promoting this, it appears to be a re-wrapping of old news in a new paper. For example, I see references to EBV on some of these websites — EBV re-activation has been known to be very high in the CFS population for generations (literally).
I would love to see the explanation of how an infection in the vagus nerve orchestrates different microbiome shifts. The theory of an infection is very easy to test with a mouse model, infect the vagus nerve of the mouse and see what their but bacteria is like in 6 weeks — there is no report confirming this (and not finding it would likely not result in a report being published). IMHO, it is a failed hypothesis.
Also, in connection to the Vagus Nerver, I was referred to a story on http://thelowhistaminechef.com/ involving Dr. Diana Driscoll, an optometrist (eye doctor) who has published a book, “The Driscoll Theory® Newly Revised: The Cause of POTS in Ehlers-Danlos Syndrome and How to Reverse the Process” as well as a custom supplement that she sells and has patented Parasym Plus(Thiamin(vitamin B1), ACP Choline AL-carnitine, Huperzia) (Patent, Patent).
I noticed that Dr. Driscoll ” is also a patient herself and mom to children also affected by, but now mostly recovered from these disorders and has now returned to work full time” In other words, what she advocates resulted in an improvement but not a full remission for her and her family. Her facts on symptoms are largely correct, one of her goals is to raise acetylcholine.
In reading the Patent, in her own words:
- “it was found by the present inventor that bowel disorders secondary to vascular nerve compression or damage to the preganglionic vagus nerve, eventually leads to organ dysfunction resulting in poor absorption of numerous other nutrients necessary to prevent signs and symptoms of dry eyes, dry mouth, delusions, motor dysfunctions, numbness and nystagmus.”
- ” majority of patients with these chronic syndromes resulting in such organ dysfunction are found to have numerous genetic defects“
- “”a bowel movement” was cited 7 times in each patent as an indicator as successful treatment.
The goal was a compound “comprising a choline compound; a cholinesterase inhibitor; and Acetyl-L-Carnitine,”
For CFS/IBS/FM, I have reservations about doing directly raising acetylcholine:
- “Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients.” 
- “We describe three cases who fulfill the criteria of CFS, in whom a defect of neuromuscular transmission and dysautonomia are present and who respond to acetylcholine-esterase inhibition… clinical CFS might be due to a combination of mild neuromuscular transmission defect combined with cholinergic dysautonomia.” 
- So the a cholinesterase inhibitor valid.
- “recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism….acetylcholine (ACh).. the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects.” 
- “Dysregulation of acetylcholine and adrenergic signalling could also explain various clinical symptoms of CFS.” 
Statement of two models
- Driscoll theory appears to be symptom mitigation. You needs to continue taking the supplements for symptom relief. She identifies that bowel disorder is a significant factor but does nothing about it (in what I have read). She admits that neither herself nor her family members being 100%, she is able to work again.
- Microbiome model is centered on the belief that most, if not all, symptoms are caused by the bowel disorder — including vagus nerve issues. I view that I have recovered to 100% multiple times: working as a software engineer at Microsoft, Amazon means 100% mental capacity and ability to work 60+ hr weeks under stress for long period of times.
There are studies supporting that this helps , but there have not been much followup for treatment. In reviewing this on PubMed, I found some interesting studies:
- A Further Investigation of the Effects of Extremely Low Frequency Magnetic Fields on Alkaline Phosphatase and Acetylcholinesterase. – some CFS/FM/IBS are sensitive to EMF (wifi, cell phones etc) — this may be the mechanism for this sensitivity
- “Comparison of Inhibition Kinetics of Several Organophosphates, including Some Nerve Agent Surrogates, using Human Erythrocyte and Rat and Mouse Brain Acetylcholinesterase . – Organophosphates have also been implicated in CFS
A common supplement that is such an inhibitor is Huperzine A. I have tried it (i.e. purchase a bottle and took it until it was empty, with no apparent effect). It is recommended by Dr.Lapp (based on other conditions). There are no studies on PubMed of Huperzine-A with Chronic Fatigue Syndrome. Another is Galantamine, this site mentions that synergy speculated that “Stacking an acetylcholinesterase inhibitor with a racetam/choline stack may have great benefits for cognition.” — I am a strong advocate of racetam (i.e. Piracetam etc) for brain fog relief. The site goes on to warn “Side effects can occur with higher levels of acetylcholinesterase inhibitors as well as racetam nootropics.”
A 2013 article review natural AChE inhibitors. It states “. Most of the drugs currently available for the treatment of AD are AChEi: tacrine (1), donezepil (2), rivastigmine (3) and galanthamine (4), all of which have limited effectiveness and some kind of side effect .” They have a very long list of plants tested, I have extracted a list of the ones with significant inhibition below. I was delighted to see Boswellia was one of them, a supplement that I already recommend strongly.
|Family and Botanical Name||Type of Extract (Solvent)||Plant’s Parts||AChE Inhibition (%)|
|Crinum jagus||MeOH||Leaf||74.25 (42 µg/ml)|
|Spondias mombin||MeOH||Root bark||64.77 (42 µg/ml)|
|Phoenix dactylifera||Hexane||Seed||52.96 (300 µg/ml)|
|Pulicaria stephanocarpa||CHCl3||Leaf||61.43 (0.2 mg/ml)|
|Onosma bracteata||MeOH||Leaf||59.73 (250 µg/ml)|
|Boswellia socotranao||CHCl3||Resin||71.21 (0.2 mg/ml)|
|Cistus laurifolius||EtOH||Leaf||80.07 (200 µg/ml)|
|Eureiandra balfourii||MeOH||Tuber||58.61 (0.2 mg/ml)|
|Juniperus phoenicea||EtOH||Leaf||53.44 (400 µg/ml)|
|Juniperus turbinata||Phenolic||Leaf||83.84 (400 µg/ml)|
|Alchornia laxiflora||MeOH||Stem bark||41.12 (42 µg/ml)|
|Cephalocroton socotranus||CHCl3||Bark||51.1 (0.2 mg/ml)|
|Genista tenera||EtOAc||Aerial||77.0 (70 µg/ml)|
|Peltophorum pterocarpum||MeOH||Leaf Stem bark||49.5 (42 µg/ml) 68.85 (42 µg/ml)|
|Callophyllum inophyllurn||MeOH||Root bark||56.52 (42 µg/ml)|
|Cyclotrichium niveum||EtOAc DCM||Whole plant||83.11 (250 µg/ml) 70.82 (250 µg/ml)|
|Hyssopus officinials||Hexane||Whole plant||55.0 (400 µg/ml)|
|Marrubium vulgare||Acetone||Aerial||62.70 (25 µg/ml)|
|Salvia chionantha||Essential oil||Aerial||56.7 (500 µg/ml)|
|Salvia fruticosa||DCM||Whole plant||51.07 (100 µg/ml)|
|Dorstenia gigas||CHCl3||Leaf||65.12 (0.2 mg/ml)|
|Orchis mascula||MeOH||Root||56.99 (250 µg/ml)|
|Corydalis intermedia||MeOH H2O||Whole plant Tuber Whole plant Tuber||84 (100 µg/ml) 97 (100 µg/ml) 57 (100 µg/ml) 78 (100 µg/ml)|
|Corydalis solidassp. laxa||MeOH H2O||Whole plant Tuber Whole plant Tuber||89 (100 µg/ml) 96 (100 µg/ml) 78 (100 µg/ml) 85 (100 µg/ml)|
|Corydalis solidassp. slivenensis||MeOH H2O||Whole plant Tuber Whole plant Tuber||82 (100 µg/ml) 97 (100 µg/ml) 48 (100 µg/ml) 87 (100 µg/ml)|
|Pinus halepensis||EtOH Essential oil||Needle Twig||60.15 (200 µg/ml) 83.91 (200 µg/ml)|
|Pinus pinaster||Pycnogenol||Bark||63.33 (200 µg/ml)|
|Cymbopogon jawarancusa||MeOH||Whole plant||72.36 (250 µg/ml)|
|Galium odoratum||Hexane||Whole plant||53.1 (400 µg/ml)|
|Morinda lucida||MeOH||Leaf||40.15 (42 µg/ml)|