Cardiac Manifestations of MCAS, with an Emphasis on POTS/Dysautonomia, Long COVID, and COVID Vaccine Injury

Cardiac Manifestations of MCAS with Dr. Andrew Maxwell
(interviewed by Tanya Dempsey, transcript here.  Dr. Maxwell is a board-certified pediatric cardiologist and pediatrician. He received his medical degree from Johns Hopkins Medical School and a residency in pediatrics at the University of California at San Francisco, followed by clinical and research fellowships in pediatric cardiology at Lucille Salter Packard in Stanford Hospitals and Children's Hospital of Philadelphia)

"Dr. Maxwell walks us through his thinking and how MCAS is linked to POTS and Long COVID. This episode is a must-listen for patients and practitioners alike."  He says this connection is more important than ever because " in the age of COVID where we're seeing more POTS, Kounis syndrome, myocarditis and even inappropriate sinus tachycardia, which I see a lot of, which is probably a localized version of myocarditis."

Mast cells can cause dysautonomia and POTS, and this is often connected with Ehlers-Danlos Syndrome (EDS).  He says the major issue underlying MCAS is an environmental exposure which can be a pathogen (like a virus) or a toxic substance.  In the case of Long COVID and COVID vaccine injury, he says it's probably the spike protein that is the toxic element activating mast cells because that's what the virus and the vaccine have in common.  He says that "mast cells are doing a lot of the things that we are seeing in these patients causing post COVID long haul syndrome leading to POTS with or without the post COVID long haul. I mean, it could be very specifically POTS, it could be very specifically Kounis syndrome. It could be very specifically myocarditis, could be very specifically inappropriate sinus tachycardia. But I believe mast cells are very frequently the underlying mediator of that inflammation. Now, it could be where it’s partly a mediator and something more direct or some other thing as being a mediator as well. But I see time and time again a pretty good response to full mast cell suppression. So that, that again informs us that very commonly it’s mast cells doing the mediation."

"Kounis syndrome is basically an allergic spasm of the coronary arteries. And so when you have a spasm of the coronary arteries, you have essentially all the signs and symptoms of the angina that might lead one to believe they’re having problems with coronary perfusion. And you are. But it is reversible with, with mast cell medications."  He says he doesn't think his colleagues are making the connection that this chest pain is related to mast cell activation and therefore can be treated with mast cell meds effectively.  He also believes that Kounis Syndrome is much more common than previously thought, so it's important to get the word out and inform more doctors about it.

He says he identifies MCAS patients by taking a close look at their clinical picture, really looking at their symptoms across body systems, and taking a thorough medical history.  This shows if a viral infection seems to have been the trigger.  He points out that some patients have never had a positive test for COVID but were known to have been exposed and developed "long haul" symptoms following the exposure at the right time, so they were just asymptomatic.  "What I kind of look, try to look for is the food sensitivities, the GI distresses that are a little bit different with mast cell activation. And then the one particular feature, what I call rushes of flushes, which is sure there’s tachycardia and palpitations, burst of racing heart palpitations, but you can find that in both the straightforward dysautonomia and mast cell activation. So how do you tell the difference between the two? You get the flushing and the rashiness with rushes of flushes. And that’s kind of how I say, okay, this is definitely a mast cell phenomenon going on."

In diagnosing and treating mast cell disease, he doesn't rely much on lab testing.  He feels it doesn't add much to his understanding of the patient or how he will treat them, which is driven by their symptom presentation "we might start with that type of therapy including fludrocortisone, midodrine, corlanor, beta blockers, pyridostigmine, that type of medication directed toward dysautonomia slash POTS."  After that, he will employ what he calls his "bicycle tire management strategy" which means:

"What I mean by the bicycle tire management strategy is you gotta consider mast cell activation like a bicycle tire with about seven holes in it. And those holes are you know, excessive histamine consumption in the diet. The GI tract as being a source of additional mast cell activation, so having the GI tract in order, and then mast cell action itself, both systemically and within the GI tract. And then those particular receptors of histamine, H1 and H2. So therapy would be an H1 blocker, an H2 blocker, mast cell suppression systemically with usually a lukast. Zafirlukast is what I prefer. I usually avoid montelukast and with a cromolyn substance in the gut. So Gastrocrom here in the US. Finally, quercetin is a natural version of the systemic mast cell stabilizer. So I usually have patients on quercetin. I consider it kind of a freebie that not really being exposed to a med is very safe, so why not? And then making sure the GI motility is working well, making sure that there’s no evidence of what we call SIBO, small intestinal bacterial overgrowth, doesn’t necessarily mean I work them up for that in any way. I just mean I put ’em on probiotics. Make sure if they have any evidence of slow GI motility, put ’em on a burra, gass or ginger root extract (not sure what "burra" or "gass" refer to). Rarely have to go something more extensive medication-wise with that. And then of course, put them on a low histamine diet, make sure they’re not adding histamine to their system. That’s usually the, the, in my view, patching all seven holes of that bicycle tire. And when you have all seven holes patched, You can expect a change."

When asked why he prefers Zafirlukast over Monteleukast, he says it is primarily because he sees Monteleukast cause a lot of depression in his patients.  He attributes this to mast cells releasing elastases, that breakdown the blood-brain-barrier (and also the gut barrier and the endothelial layer in capillaries) by breaking down small proteins called cadherins that hold these things together, making them "leaky".  He says he sees similar results with a lot of the dopamine agonist antagonists like Reglan.  He speculates that this scenario may be more common in children.  Dr Dempsey points out that she sees better responses to Monteleukast (and other meds) when they are compounded, so the excipients used in the standard formulations may be the problem.  

(This is his complete quote from above, included because it may be of particular interest to some readers "Mast cells not only secrete histamine, but they secrete elastases and elastases breakdown the little proteins that hold things together, what are called cadherins and maybe other proteins too. But I really focus on the cadherins. Cadherins hold together, the GI epithelium, that’s the E-cadherin. So that’s where your leaky gut comes from and it holds together what are called VE-cadherins hold together, the capillaries, the endothelium within capillaries. And so if they break down, you get increased leaky capillary in general, but blood-brain barrier. And we see that with not only montelukast, we see it with a lot of the dopamine agonist antagonists like Reglan where patients will much more commonly have extra pyraminal effects being put on Reglan and other types of dopamine modifying agents.")

They go on to discuss the idea of grouping together conditions like MCAS, POTS, and other commonly comorbid conditions because it's clear that these conditions frequently occur together.  At first, doctors referred to "the triad" which included MCAS, EDS, and dysautonomia.  It then expanded to "the pentad" when GI dysmotility (GI involvement in general) and autoimmunity were added.  The direction of causality is unclear- which condition came first?  Did the leaky gut become an "auto-antibody generator over time"?  Did the autoimmunity start this whole progression?  The idea of identifying the 5 main pieces is that a patient would then need to set up a team of 5 doctors to manage these conditions, although in reality that is often not possible to do.  Then the next two conditions were added, bringing it to "the septad"- many patients had underlying infections, such as Lyme Disease, and they also had what is often called "ME/CFS" which is now generally recognized to be mitochondrial dysfunction.  Dr Dempsey than added 3 more things to bring it up to a "decad" including small fiber neuropathy, cervical instability and tethered cord, and autoimmune encephalopathy (such as PANDAS/PANS).  This last component acknowledges the brain fog and cognitive issues, the neuropsychiatric issues, and endocrine issues especially thyroid, adrenal, and sex hormone issues.  Dr Maxwell adds that he sees many of these additional pathologies that are being added to the list as sub-forms of things already on the list, so it may not make much difference how much you expand the list or keep it short in terms of making sure that you recognize and treat the patient's whole picture.  

It's worth noting that in the above discussion, Dr Maxwell puts forth the idea that there can be localized expressions of some of these conditions that may not meet full criteria, that were caused by a localized environmental exposure.  For example, a person who was exposed to "something that’s aerosolized and breathed in, and what happens is you have a localized nasal pharyngeal mast cell activation that then causes havoc in the nasal pharyngeal region, specifically CCI, TMJ issues, and then loss of airway. So the airway becomes floppy for different reasons. And so you see these particular patients and they’re kind of a setup for this phenomenon I see and call "spiky leaky syndrome." (CCI is cranial cervical instability, meaning the vertebrae in the neck are unstable).

Dr Maxwell is then asked if how he sees the patient picture changes how he treats the mast cells and he says generally, no, that he pretty much starts everyone on his usual mast cell protocol.  If a patient seems to need more than that, he says "another strategy I have are IV infusions of mast cell meds... getting saline along with Benadryl, Toradol, Ativan, and famotidine and IV form, and oftentimes on ondansetron as well. And so that often works much more effectively than the oral forms."  He may also increase the dose of LDN (Low Dose Naltrexone).  He also adds that if a patient is really "POTSie" and has "angina type symptoms and you’re thinking the mast cell meds aren’t gonna work fast enough for that, you might try some antianginal type strategy, something like a nitric oxide releaser to open up their coronaries as quick as possible."  

They then go on to discuss how mast cells are related to and can cause Dysautonomia and POTS, and specifically how the COVID virus and the COVID vaccines have both been shown in research to contribute to the onset of both Dysautonomia and POTS specifically.  This discussion begins at [00:26:26] in the interview- if this is very interesting to you, I suggest going to the interview and reading the entire very long quote.  This is my summary of what Dr Maxwell is saying:

POTS is basically what happens when the person's venous system becomes "saggy" and "stretchy" rather than as rigid as it needs to be to appropriately control blood flow throughout the body as the body moves around and changes position.  When the person stands up, the venous system is too "saggy" to bring the full amount of blood up to the heart to fill it when ti pumps so it pumps partially empty, resulting in low cardiac output.  This causes the heart to beat faster, as tachycardia, in an attempt to increase cardiac output.  One of the reasons that MCAS more broadly and COVID or COVID vaccine injury more specifically can cause this situation is that the spike protein activates mast cells, which then release mediators that break down the connective tissue of the venous system itself, causing it to become too "saggy" to function properly. 

He says there are also several ways that mast cell activity can affect the functioning of the autonomic nervous system directly, which is the branch of the nervous system that regulates things like circulation, heart rate, and blood pressure.  "(M)ast cells activated in the gut can then cause inflammation of the sensory portion of the Vagus nerve. It’s the information heading back to the brain. And so if it’s irritating and inflaming the sensory portion of the Vagus nerve, it’s as I consider it like almost like a CPU u you know, computer system with information going into the CPU, if it’s garbage in, it’s gonna be garbage back out. And so, it affects how the motor portion of the Vagus nerve works. And so you have a dysautonomia of the motor portion of the Vagus nerve that results from a inflammation of the sensory portion of the Vagus."

He outlines another way that mast cell activation can lead directly to dysfunction of the Vagus nerve as well as several other cranial nerves, which could also be leading to POTS and Dysautonomia in patients following a COVID infection or vaccine injury.  Mast cells in the neck becoming activated could be releasing the mediators mentioned above that can "tenderize" connective tissues, in this case ligaments in the neck that hold the cervical vertebrae in place.  This could in theory result in a situation very similar to what is called CCI (Cranial Cervical Instability) and is often seen in EDS patients (Ehlers-Danlos Syndrome, which is often comorbid with MCAS). He sees this as essentially "carpal tunnel syndrome" of the neck but says that because it acquired by mast cell activation, it is more of a clinical diagnosis and may not show up on the radiology and other types of testing used to identify CCI in EDS patients, that is more structural.  In this scenario, the C1 vertebra (aka the atlas) becomes loose and unstable, and gets pushed forward, which compresses the cranial nerves 9, 10 (the Vagus nerve), and 11 that are exiting the spine at that spot.  Those nerves are then compressed against the jugular vein, which is then compressed against the stylo hyoid ligament.  If this situation becomes chronic, these nerves can become damaged, which can then lead to dysfunction of the parasympathetic nervous system by way of a little bit of CCI.  

More evidence that this happening is that you’re also seeing cranial nerve 9 and cranial nerve 11 dysfunction, which can present as tinnitus, phonophobia (sensitivity to and/or fear of certain sounds) and hyperacusis (an abnormally strong reaction to sound, occurring within the auditory pathways), vertigo, and what’s called globus feeling of a mass in the back of the throat.  Dr Maxwell says he also sometimes sees "what’s called eagle syndrome type symptoms with turning the head and having pain upon turning your head. From side to side, sharp stabbing pains in the neck or pain at the base of the tongue. Those are all glossopharyngeal nerve findings. And then the cranial nerve 11 is a motor nerve to the trapezius and it innervates the trapezius. So when it’s injured, oftentimes will cause a knottiness something beyond coat hanger pain in the trapezius, but rather a knottiness in the trapezius. So when you hear these patients complaining of all these symptoms, that it sounds almost crazy that they’re related. No, there’s one place in the body where these three nerves are together and they happen to run right in front of the lateral process of c1. So when that slips forward and chronically does so, I think it causes this, this list of symptoms together."

When Dr Maxwell is asked how he manages and treats this situation with the slipped C1 vertebra if he suspects it, he responds "I will get the physical therapist involved. And I’ll often assess their airway as well, because if they have that going on, they may have a floppy airway as well, and they may be losing it at night and showing what we call upper airway resistance syndrome, which is a subtle form of sleep apnea. So we oftentimes, I get sleep studies to look at that. Oftentimes I’ll get ENT and the oral airway doctors including oral surgeons involved to make sure that they’re not losing their airway, myofunctional therapists to help strengthen the musculature of the airway. And then there’s a class of physical therapists that are geared entirely toward CCI. So I will get them and get them involved. One of the things that I’ve found useful as a test of concept in these patients is what happens if they were to get some what’s called NUCCA therapy, NUCCA. And that’s a particular form of chiropractic therapy that focuses on the Atlas. And so these NUCCA chiropractors have been very, very helpful in putting C1 back in place. And these patients can respond right away to their POTS like symptoms. Their dysautonomia improves right away."  He says this is a test of concept because while the NUCCA therapy is very effective, the improvements don't last long. He discusses prolotherapy as an option and says that he encourages the therapist to inject platelet-rich plasma (from the patient in order to avoid MCAS being triggered by something foreign).  

He sees this therapy, like he does the POTS therapies, as "band-aid" therapies to help as the longer-term stabilization of the mast cells and treatment of any residual COVID is taking effect.  This may include the body clearing residual spike protein, treating a lingering COVID infection, or treating another infection that was latent and reactivated from the immune suppression of the COVID or vaccine (such as HHV6, EBV, or Lyme).  He says he will treat with anti-virals if "the PCRs are positive or if the IGMs for those viruses are positive".  

They discuss this paper Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection, which found a significantly higher risk of developing certain conditions associated with POTS after both COVID infection and COVID vaccines, including Dysautonomia, POTS, and MCAS, as well as some other conditions including UTIs, lower back pain, and symptoms like dizziness, fatigue, and anxiety.  They go on to talk about how complicated it is to weigh the costs and benefits of vaccination for the population of people who already have any of these conditions or who are at higher risk for developing them, especially given that the nature of COVID infection has changed. 

Dr Maxwell's last message for patients "for the patients seeking help, you know, find the right provider that works with you. Don’t let someone dismiss you. I hear again and again being told, you know, there’s no point in managing anything. You’re gonna get better with your long COVID. And you know, we’ve seen long COVID patients two years out who were just struggling, not everybody. And it’s great to see some patients getting better even on their own. But you never know who thoses are gonna be, and so you’re gonna want to try to modify what could be a very long road. And so you know, make sure you’re finding someone who’s addressing your issues that has a a pretty good handle on the underlying causes that can do it in a systematic way. And I think you’ll have some success."

Further information on the topics discussed in this interview:

Mast cells in the autonomic nervous system and potential role in disorders with dysautonomia and neuroinflammation
"Mast cells... having potential involvement in the pathophysiology of dysautonomias and neuroinflammatory disorders. MC are located perivascularly close to nerve endings and sites such as the carotid bodies, heart, hypothalamus, the pineal gland, and the adrenal gland that would allow them not only to regulate but also to be affected by the autonomic nervous system (ANS). MC are stimulated not only by allergens but also many other triggers including some from the ANS that can affect MC release of neurosensitizing, proinflammatory, and vasoactive mediators. Hence, MC may be able to regulate homeostatic functions that seem to be dysfunctional in many conditions, such as postural orthostatic tachycardia syndrome, autism spectrum disorder, myalgic encephalomyelitis/chronic fatigue syndrome, and Long-COVID syndrome."

Phonophobia and Hyperacusis: Practical Points from a Case Report

NUCCA

Prolotherapy

POTS association with COVID-19 vaccination and COVID-19 infection
"Although any comparison of post-exposure rates should be interpreted cautiously, given the baseline differences in POTS incidence in the two mutually exclusive populations, these results indicate that POTS might be occurring at a higher-than-expected frequency following COVID-19 vaccination, although at an overall rate lower than the frequency of POTS occurring following SARS-CoV-2 infection."

Apparent risks of postural orthostatic tachycardia syndrome diagnoses after COVID-19 vaccination and SARS-Cov-2 Infection
 "POTS-related diagnoses appear to be acquired with increased frequency after, compared to before, COVID-19 vaccination, particularly when compared to more commonly diagnosed conditions"

"For new diagnoses made after vaccination, we found that the five conditions with the highest post-vaccination odds of new diagnoses were myocarditis, dysautonomia, POTS, mast cell activation syndrome and urinary tract infection (UTI). Two POTS-associated conditions had lower odds, with fatigue demonstrating a moderate ratio and Ehlers–Danlos syndrome (EDS) having the second from the lowest ratio."

"There is biological plausibility for the association between POTS and COVID-19 vaccination in particular. Before the pandemic, mRNA vaccination had been administered in small trials predominantly involving cancer therapy, demonstrating rare off-target neurological effects such as Bell’s palsy, which has also been seen with COVID-19 vaccination^25,26. In SARS-CoV-2 infection, multiple reports of post-infection POTS invoke the possibility of an immune-mediated mechanism triggered by an antigenic component of the spike protein shared with vaccination^13,24,27. Given the broad expression of ACE2 preceptors, inflammasome activation by synthetic spike protein could result in multi-systemic effects, including neurocardiogenic targets and potential induction of variable types of autoimmunity^28,29,30. Additionally, the lipid nanoparticle coating in mRNA vaccine formulations is known to be highly inflammatory, although effects related to the lipid coating appear less likely contributors than spike-protein-mediated effects³¹. Further research is needed to clarify potential mechanisms related to either vaccine formulation or vaccine target."

Postural orthostatic tachycardia syndrome after COVID-19 vaccination
"Ten patients (3.9%) at a quaternary-care POTS clinic reported new or worse POTS symptoms after the mRNA COVID-19 vaccine. All patients had pre-existing comorbidities, suggesting a potential group of patients to monitor for post-vaccine POTS. Symptoms responded to guideline-directed POTS therapy."  (Pre-existing conditions included previous COVID-19 infection, Hypermobile EDS, MCAS, and auto-immune cardiac, neurological, and gastrointestinal symptoms)

Mast Cell Activation Syndrome and the Vagus Nerve

These are my notes from the article "Mast cell activation syndrome and the vagus nerve"
written by Ross Hauser, MD of Caring Medical on February 4, 2023 

Many patients diagnosed with MCAS (Mast Cell Activation Syndrome) also have neck pain that is diagnosed as (or can be described as) upper cervical instability or cervical spine instability.  It is generally assumed that this pain is part of the existing illness, but in this article Dr Hauser explains that the causality could be going the other way.  Many of these patients are also diagnosed with  Chronic Fatigue Syndrome, Myalgic Encephalomyelitis (ME/CFS), POTS, or some other form of Dysautonomia.  When these patients see specialists to see if the neck pain and problems could be causing some of their symptoms, some are then diagnosed with "degenerative disc disease in their cervical spine and a loss of the cervical curve contributing to kyphosis".Dr Hauser explains that:

"Which brings us to an important question, which came first? Autonomic nervous dysfunction or immune-mediated allergy?  At a minimum, we know they are interconnected. A lot of antigen-antibody immune complexes and a host of histamine releases are going to excite the autonomic nervous system throughout and likewise, autonomic nervous system dysfunction makes antigen-antibody reactions more likely. The patient has the symptoms, is it the neck causing them? Is it the allergies?"

He explains that the way cervical instability could lead to symptoms of MCAS, etc, is because it may be causing the vagus nerve to be pinched or compressed in the neck or: "damaged cervical ligaments’ inability to hold the “wandering” vertebrae in place."  The vagus nerve is how signals from the brain reach the viscera (the organs in your torso) in order to control them, so anything that impedes its function can have major consequences:

"When the vagal nerve sensory afferents are dysfunctional, the important body sensors for homeostasis are switched off. Cervicovagopthy or vagus nerve disorder brought on by cervical spine instability, has wide-ranging negative effects on mucosal barriers in the intestines and lungs, producing a large number of inflammatory mediators, including histamine."

Dr Hauser explains that many patients who fit this profile- having MCAS along with many of the following additional diagnoses- EDS (Ehlers-Danlos Syndrome, POTS (Postural Orthostatic Tachycardia Syndrome), Gastroparesis, Fibromyalgia, sleep disturbances, low blood pressure, serious gastrointestinal pain and dysfunction, "When someone has a myriad of symptoms like this, it is of course difficult to believe they all start spontaneously without a common thread linking them together. In a person like this, when all is a mystery, we follow the neurology, we look for short-circuiting messages between brain and body being caused by compression of the arteries, veins, and the nerves that travel through the cervical spine."

Dr Hauser notes that many of the different disorders and symptoms experienced by these patients Do have established connections and that these connections are further evidence of vagus nerve involvement.  A key example of this is the interconnection between the immune system and the gut, mediated by the vagus nerve, in which modulating signals are sent both ways.  Also, regulating signals and neurotransmitters in this system are part of the mechanism that the body uses to turn inflammation on and off.  To explain this he quotes a may 2021 study in the journal Frontiers in Pharmacology:

“Inflammatory bowel disease, irritable bowel syndrome, and severe central nervous system injury (of which the vagus nerve plays a dominant role) can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation (movement, or better thought of as escaping to other parts of the body) to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases.”

"The researchers add that repairing the intestinal barrier represents a potential therapeutic target for many diseases. Repair means addressing the dysfunction of enteral afferent nerves, efferent nerves, and the intrinsic enteric nervous system that play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors."

"Histamine is synthesized by mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells, where it is stored intracellularly and released upon stimulation. It can be found basically everywhere in the body, including the spinal cord and brain. Histamine causes smooth muscle cell contraction, vasodilation, increased vascular permeability and mucus secretion, tachycardia, alterations of blood pressure, and arrhythmias, while it stimulates gastric secretion and nociceptive nerve fibers. Histamine increases secretions such as hydrochloric acid in the stomach and is vital to protecting the lungs and gastrointestinal tract from infections. When histamine levels are high, increased secretions in the lungs, therefore, cause coughing, phlegm production, sneezing, and diarrhea occur in the digestive tract in an attempt by the body to rid itself of an infectious agent or toxin."

When the transmission of nerve impulses along the vagus nerve from the brain are interrupted or stopped, this can limit the body's ability to regulate and maintain homeostasis (balance of systems), which can keep the body from appropriately limiting the inflammatory response.  It also results in higher histamine content of mast cells, mast cells being more responsive to nerve signals to react, which ultimately means a higher level of histamine in the organs systems.  

"The GI tract harbors the largest population of mast cells in the body and is thus the main reservoir of the body’s histamine. The mast cells’ job is to maintain intestinal permeability and make sure that no microorganisms or antigens enter the body. (A dysfunction of this system can lead to Leaky Gut Syndrome and inflammation of the intestines.) The neurological control over mast cells and their various digestive functions is via the vagal influences on the enteric nervous system.  Elevated histamine levels in the body occur when there is an increase in intestinal permeability (regardless of the cause), including that from synthetic foods (industrial food additives, chemicals in food, genetically modified foods), Ehlers-Danlos syndrome (EDS), and cervical spine instability induced cervicovagopathy."

The effects of histamine on gut function, and how this impacts other disease processes especially autoimmune, has been well-studied.  Some common industrial food additives are known to trigger mast cells to make the gut more permeable (increase the amount of space between cells that line the gut and regulate what gets into the bloodstream and what doesn't), allowing larger proteins than usual into the bloodstream.  Once there, these proteins can trigger allergic and other inflammatory responses and are especially associated with autoimmune disease.  

"Histamine intolerance results from excessive histamine and a decreased ability to absorb or neutralize it.  Elevated levels of histamine give symptoms that mimic allergic reactions, and these include diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritis, flushing, and skin lesions. A true allergy is tied to IgE-mediated histamine release, which is to be differentiated from histamine intolerance. The latter is associated with some forms of urticaria, eczema, asthma, food sensitivity, migraines, and chronic GI and neurological ailments, including inflammatory and irritable bowel syndromes."

"The reservoir of histamine in the body originates in the gut and comes from the breakdown of food that is ingested or the microbiota-generated histamine. Histamine intolerance is akin to lactose intolerance in that the body is missing a key enzyme to digest a food substance. In histamine intolerance, it is DAO in the digestive tract, a deficiency of which leads to elevated histamine levels in the body. DAO is synthesized by the intestinal villi (enterocytes) and is constantly released from the intestinal mucosa into the gut, as well as the blood circulation, during eating and digestion."

Mast cell dysfunction is also being increasingly recognized as a major part of many neurological and psychiatric disorders, especially neurodegenerative disease.  "What is being suggested is that the Mast cells are causing runaway neurological inflammation by excerpting a disruptive influence (bad messages) on the central nervous system and brain and this is leading to neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease for example." 

"vagal activity, partially driven by gastric mast cells, induces long-lasting changes in corticotrophin-releasing factor signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors."

"What they found was vagus nerve stimulation resulted in a significant reduction of the different inflammatory parameters assessed. They said their results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine.  In other words, if the vagus nerve is working correctly, anti-inflammatory and mast cell activation could be suppressed."

Further Information from Dr Hauser:
Can Chronic fatigue syndrome and Myalgic encephalomyelitis be caused by cervical stenosis and cervical spine instability? 

Postural Orthostatic Tachycardia Syndrome (POTS), the Vagus Nerve and Cervical Spine instability

Treatments for Neck Pain and Cervical Instability: A review of upper cervical instability and symptom treatment with Ross Hauser, MD

Cervical Curve Correction – Caring Cervical Realignment Therapy

Research Articles Cited in this Article (not all):
How to evaluate the patient with a suspected mast cell disorder and how/when to manage symptoms

Diagnosis of mast cell activation syndrome: a global "consensus-2"

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium

Evaluation and Classification of Mast Cell Disorders: A Difficult to Manage Pathology in Clinical Practice

Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay

The Gut's Little Brain in Control of Intestinal Immunity

Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy

Myocarditis and Pericarditis

WHAT IS MYOCARDITIS?
Myocarditis is an inflammation of the heart muscle (myocardium).  Infection with a virus usually causes myocarditis. Sometimes myocarditis can result from a reaction to a drug (including some antibiotics) or be part of a more general inflammatory condition such as Lupus.  Severe myocarditis can cause cardiac arrhythmias and can lead to heart failure if it weakens your heart so that the rest of your body doesn't get enough blood. Clots can form in your heart, leading to a stroke or heart attack.

Symptoms of myocarditis include fatigue, shortness of breath, chest pain, edema (fluid buildup) in the legs and feet, and cardiac symptoms such as tachycardia (rapid heartbeat) and arrhythmia (abnormal heart rhythm).  Because myocarditis is often caused by a virus, the person may also have typical viral symptoms such as fever and joint pain.  Myocarditis can be caused by a wide variety of pathogens including bacteria, viruses, parasites, and fungi.  Herpes viruses such as Epstein-Barr (HHV-5) and Herpes Simplex (aka cold sores, also know as HHV-1) are common viral causes, as are cold viruses and echoviruses (GI infections often called "stomach flu").  The most common bacterial causes are streptococcus, staphylococcus, and the bacteria associated with Lyme Disease.  Other infections that can be responsible include toxoplasma gondii (the parasite associated with cat feces), histoplasma (a fungus associated with bird and bat droppings), yeast (candida) and mold such as aspergillus.  

WHAT IS PERICARDITIS?

Pericarditis is swelling and irritation of the pericardium, which is a thin layer of tissue surrounding your heart. Pericarditis often causes sharp chest pain that occurs when the irritated layers of the pericardium rub against each other, but can also cause dull aching pain.  The pain usually occurs on the left side of your chest and can radiate down your left arm and up along your neck into your jaw.  Other symptoms can include shortness of breath (especially when lying down), palpitations, fever, edema in the legs, feelings of weakness and fatigue, and cough.  Pericarditis can have a fast onset and only last a short time, or it can come on slowly and become chronic. 

New MMWR CDC study compares covid myocarditis to vax myocarditis | Is it good science?
This study by the CDC claims that the rate of myocarditis is much higher after a SARS CoV2 infection than it is after vaccination.  Dr Prasad says that this is not the real question, the real question is how many doses of vaccine are best for someone who has already had COVID 19 vs someone who has not.  There has been a claim that is circulating that says that myocarditis after infection is always worse than it is after vaccination, but is this true?  This paper significantly underestimates the number of people who've had COVID 19 infection but not a vaccine.  It is capturing only those people whose infections were serious enough for them to be tested in a hospital but not those who tested at home or simply didn't test.  It's known that many Americans didn't get testing from a hospital, probably the milder cases, so this paper seems to be biased by only counting the COVID 19 infections that were worse and more dangerous.  Also, the rate of Myocarditis after vaccination is consistent with findings in other countries, but the rate after COVID 19 is 50 times higher than the rate found in the UK in a high quality study.  The study uses billing claims coding as an indicator of myocarditis but this is also problematic.  People sick enough with SARS CoV2 to be hospitalized are more likely to be tested for myocarditis, and be coded that way, so it is likely to pick up on other things that could have received a billing code of myocarditis. 

Myocarditis and Pericarditis After Vaccination for COVID-19

Stress (Cortisol and Adrenaline)

The inside of the adrenal glands is neurological tissue, which is where adrenaline is made.  The outer part is glandular tissue and is where cortisol is made.  Cortisol is a hormone and adrenaline is a neurotransmitter.  The adrenals release these chemicals in order to help the body to function in situations of short-term stress, but can remain active for a long time.  They are part of the sympathetic nervous system, which is also known as the "fight or flight" system.  The opposing branch of the autonomic nervous system is the parasympathetic response, which is a state of relaxation.  The adrenal glands are not part of the parasympathetic system so that system is unable to "turn them off".  Fear, worry, and anxiety are part of the sympathetic response.  

The Effects of Stress

Stress causes problems with sleeping, often resulting in waking during the night (often around 2 AM) and can mean that a person sleeps best in the morning rather than at night.  Cardiovascular effects include changes in blood pressure and heart rate, and inflammation of the arteries.  Cortisol is an anti-inflammatory hormone. The synthetic version is called prednisone.  Long term cortisol exposure leads to loss of sensitivity by the cortisol receptors on cells, similar to how insulin resistance happens in diabetes.  With cortisol resistance, more cortisol may actually increase inflammatory symptoms in a seemingly paradoxical way.  Diseases that can develop in this situation include arthritis, auto-immune diseases, and joint inflammation.

The Effects of Cortisol on the Immune System

Cortisol affects the white blood cells of the immune system because part of what it does is to "turn off" the immune system.  Cortisol inactivates Natural Killer T-cells, which kills viruses and cancer cells.  It also suppresses the ability of the immune system to fight pathogens in general.  There are even certain bacteria that activate your hypothalamus to activate cortisol so that your body can't defend itself as well.  

Cortisol and Memory

In the short term, cortisol helps in the formation of emotional memories because these memories may help you to survive in the future, but in the long term the hippocampus is damaged, leading to memory loss and brain fog.  This can also result in becoming per-occupied with a few specific problems, which can lead to keeping you awake at night because you can't turn off the worries.  You can get stuck in a problem-solving mindset but it doesn't result in actual helpful solutions.  

Mineral Loss

Long-term exposure to cortisol leads to the loss of potassium, which is a mineral that supports calmness and relaxation.  Loss of potassium leads to more stress and this can create a cycle.  Sugar also depletes potassium.  Thiamine (vitamin B1) is an important anti-stress vitamin that causes relaxation and comfort. Thiamine also increases levels of GABA, which is a neurotransmitter of relaxation and calmness.  It also causes a loss of hydrogen ions, which are acidic, which puts your body into a more alkaline state.  People under a lot of chronic stress become too alkaline, not too acidic.  This leads to tight muscles, twitches, tetany. muscle cramps, can't absorb electrolytes well, and breathing problems can result.  As the acid levels decrease this can cause low levels of stomach acid and poor digestion.  

Catabolic Effect

Catabolism is the process in which muscles are broken down in order to turn the amino acids, the components that muscle proteins are made of, into glucose to fuel the "fight or flight".  Connective tissues including collagen and elastin are also broken down in this process (this is why stress can make a person wrinkly).  Cortisol also demineralizes bone, causing osteopenia and osteoporosis.  

Effect on Kidney Function

Chronically high cortisol levels cause the kidneys to filter less (meaning hold on to less and instead allow more to be lost in the urine), including minerals such as potassium.  Sodium is filtered and saved and this is why kidney problems can lead to water retention.  Addison's Disease is a rare and more serious form of adrenal disease in which potassium is filtered but sodium is lost in the urine.  Cushing Syndrome is related.  

Cortisol and Blood Sugar

Cortisol is also called a "glucocorticoid" because it helps to regulate glucose levels.  It can help make glucose out of non-carbohydrate sources including fats, proteins, and even ketones. It also plays a role in storing and releasing glucose.  Cortisol can activate insulin leading to a "flat tire" around the gut, and this also leads to all the issues associated with high insulin.  

Cortisol and Digestion

The process of digestion is under the control of the parasympathetic system, and becomes compromised when cortisol levels remain elevated.  The digestive system becomes sluggish resulting in bloating, indigestion, poor absorption of nutrients, and even ulcers.  The fact that cortisol also increases insulin levels this can also affect digestion and cause excess belly fat.  

Excess cortisol can lead to low levels of vitamin D which is ironic as vitamin D does many of the same things that cortisol does, but without the negative side effects.  It is an anti-inflammatory and can influence the immune system to lower inflammation rates, in particular it tamps down the cytokine storm.  

How to Lower Stress and Reduce Cortisol

It can lower mental stress to find activities that increase physical stress such as jobs around the house, yard work, etc.  These activities result in a kind of physical tiredness that can improve sleep.  Exercise and other types of physical activity can also be helpful.  Worry and stress are associated with inaction, feeling almost paralyzed, and keeping busy with activities helps keep you moving and keeps your mind from getting stuck on certain topics.  Taking vitamin B1 is very helpful at cutting stress down.  It can have an almost immediate effect if taken when you feel very stressed.  Making sure that you get enough potassium and magnesium is important and both are easily gotten from the diet, especially vegetables.  Reducing carbohydrate intake helps because carbs keep the body stuck in a "fight or flight" response.  Taking vitamin D lowers stress and improves mood.  Implementing a ketogenic diet and intermittent fasting helps to address a lot of the physical symptoms and mood symptoms from high cortisol.  Including adaptogens in your daily routine, as a supplement or tea or other ways, supports healthy adrenal function.  

Learning to breathe so that the inbreath and the outbreath are the same duration helps balance the sympathetic and parasympathetic arms of the autonomic nervous system.  If you practice this when you lay down to go to bed it will help you sleep.  Below is the link to a video made by Dr Berg showing a technique to reduce stress at the end of the day, using a thing that puts pressure on the base of the skull.

Dr.Berg's Webinar On Stress Relieving: Easily Get Rid of Stress & Sleep Like a Baby

This is an adaptogen supplement recommended by Dr Berg

Growth Hormone

Growth hormone is sort-of opposite of cortisol, it protects proteins.  It’s anti-aging whereas cortisol is pro aging.  GH is triggered by sleep,  intense but intermittent exercise, eating enough protein, and intermittent fasting. 

Takotsubo Cardiomyopathy

Takotsubo syndrome

"Takotsubo syndrome is a reversible acute heart failure frequently precipitated by an emotional or physical stress. The clinical presentation resembles acute coronary syndrome. Pathogenesis is complex and may involve brain-heart axis and neuro-hormonal stunning of the myocardium. Coronary angiography reveals normal epicardial arteries with no obstruction or spasm. NT-ProBNP maybe remarkably elevated. Regional wall motion akinesia (RWMA) of left ventricle extends beyond the territory of one coronary artery. Reduced left ventricle ejection fraction (LVEF) and RWMA recover in 6–12 weeks. Prognosis is generally good. Recent meta-analysis shows in-hospital mortality of 1–4.5% and recurrence rate of 5–10% during five year follow-up."

Takotsubo Cardiomyopathy, or Broken-Heart Syndrome

"Takotsubo cardiomyopathy mimics acute coronary syndrome and is accompanied by reversible left ventricular apical ballooning in the absence of angiographically significant coronary artery stenosis. In Japanese, “tako-tsubo” means “fishing pot for trapping octopus,” and the left ventricle of a patient diagnosed with this condition resembles that shape. Takotsubo cardiomyopathy, which is transient and typically precipitated by acute emotional stress, is also known as “stress cardiomyopathy” or “broken-heart syndrome.”

The clinical features of takotsubo cardiomyopathy.

"The cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments, together with hyperThe cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments, together with hyperkinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology. The cardiac events did not recur over a 1-4 year follow-up.kinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology. The cardiac events did not recur over a 1-4 year follow-up."

" Coronary vasospasm, myocarditis and other substantial diseases previously described were ruled out as the cause of takotsubo cardiomyopathy in our subjects. Prognosis was good without any form of treatment, provided that the patients survived the severe heart failure state. Catecholaminergic or adrenoceptor-hyperactive cardiomyopathy may be the cause of this cardiomyopathy."

Plasma brain natriuretic peptide in takotsubo cardiomyopathy.

" Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition."

The Cardiovascular System (and Blood)- Relevant Symptoms, Conditions, and Disorders

About the Cardiovascular System in General:
Human Circulatory System

This short video is a good introduction to how the circulatory system works, with very good graphics to demonstrate what is happening.
Human heart anatomy
Cardiovascular System 1, Heart, Structure and Function (Dr John Campbell)
Heart Structure and Function Basics video from Anatomy Zone
What Happens During a Heart Attack | Anatomy of a Heart Attack

About Blood:
Blood types matter (YouTube video)

How to Know if You Have a Blood Clot
How blood pressure works - Wilfred Manzano

Hypertension - An Introduction to High Blood Pressure
Understanding Blood Pressure Readings

Accurate Blood Pressure Measurement Robert B. Baron, MD MS, UCSF School of Medicine
It's very rare for this procedure to be done thoroughly.
The recommendations are:

(If not followed correctly, each of these points will make the BP to be higher than it otherwise is).
-the patient should be seated in a chair for 5 minutes.
-the arms should be bare and supported.
-no cigarettes or coffee, and no talking during procedure.
-properly fitting cuff (the cuff is often too small, more than half of patients need an intermediate cuff).  Home kits for taking BP often include cuffs that are too small, and when having BP taken at a health fare or supermarket the machine will also likely feature a cuff that is too small for many people.
-multiple readings should be taken during a single appointment, several minutes apart at least, and then averaged together.
-hypertension (having high BP) can only be diagnosed after a pattern of high BP readings, not just after a single visit.  If a health care provider tells you that your BP is high after taking it during one visit, they mean that the numbers were high in the moment but this is NOT the same as diagnosing
Hypertension. 

 

Key minerals to help control blood pressure
This page on the Harvard Medical School's website details the important role that calcium, magnesium, and potassium play in regulating blood pressure.  People who take diuretic medication can lose these minerals in their urine and become deficient.
Calcium - "Calcium is important for healthy blood pressure because it helps blood vessels tighten and relax when they need to".  There is disagreement among medical experts regarding the optimal level of calcium in the body.  There are some studies that seem to show a higher incidence of heart disease in people consuming the RDA or higher of calcium, so many doctors recommend getting all of your calcium from your diet and avoiding supplements.  (Note- many foods that are high in calcium, such as spinach, some other leafy greens, and cow dairy are high in anti-nutrients that block the absorption of calcium so are actually low in bioavailable calcium.  Also, some doctors have encouraged patients to take Tums or other antacids because they contain calcium, however the form they contain is calcium carbonate which is not bioavailable, and they actually interfere with the absorption of calcium from any source because adequate stomach acid is required to break food down enough for your body to get access to the calcium it contains.) 
Magnesium - "We need magnesium to help blood vessels relax."  Many foods are high in magnesium, but as with calcium, anti-nutrients can block its absorption.  Magnesium is often taken "to bowel tolerance", meaning that to much magnesium supplementation can trigger a laxative effect and diarrhea.
Potassium -  "Normal body levels of potassium are important for muscle function, including relaxing the walls of the blood vessels. This lowers blood pressure".  Potassium levels in the blood have a strong effect on the heart so it is important to be careful to get an amount within the proper range.  A doctor can help you with this.  Potassium is in many foods so most people can get plenty in their diet if they are conscientious.  

The ratio potassium-to-magnesium intake and high blood pressure
" Our results suggest that, in healthy individuals with magnesium and potassium intake below recommended dietary allowance, the high potassium-to-magnesium ratio is inversely associated with incident high blood pressure."

 

Electrolyte minerals intake and cardiovascular health
"Appropriate intake of micronutrient, such as electrolyte minerals is critical for the well-being of the cardiovascular health system. However, there are some debates regarding the impacts of dietary and/or supplemental intake of these minerals, on the risk of cardiovascular events and associated risk factors. High sodium intake is adversely associated with the risk of hypertension. Although many reports refered to the positive association of Na intake and cardiovascular events and all-cause mortality, however, other studies indicated that low Na intake is related to higher risk of all-cause mortality and HF-related events. By contrast, dietary potassium, magnesium and calcium have an inverse correlation with cardiovascular events and risk factors, especially with blood pressure. There are some controversies about cardiovascular effects and all-cause mortality of high Ca intake, including no effect, preventive or adverse effect with or without vitamin D. Calcium supplementation might be beneficial for prevention of cardiovascular events and all-cause mortality only in individuals with low intake. Moreover, calcium intake showed a J- or U-shaped association with the risk of cardiovascular diseases."

 

Associations of Dietary Zinc-Vitamin B6 Ratio with All-Cause Mortality and Cardiovascular Disease Mortality Based on National Health and Nutrition Examination Survey 1999-2016
"a high dietary zinc−vitamin B6 ratio increasing the risk of CVD mortality (HR = 1.27, 95% CI: 1.19−1.35), whereas a moderate dietary zinc−vitamin B6 ratio appeared to be beneficial for CVD mortality. These results suggest that increasing the appropriate proportion of dietary zinc and vitamin B6 intake is associated with a lower risk of CVD mortality."

The neurotransmitter norepinephrine is a vasoconstrictor, meaning that it raises blood pressure.

 

Specific Symptoms, Conditions, and Disorders:
Acute Coronary Syndrome  "ACS is a manifestation of CHD (coronary heart disease) and usually a result of plaque disruption in coronary arteries (atherosclerosis)."  This page from Mayo Clinic provides information about the testing that will be done at a hospital to determine if you are having a heart attack or unstable angina.  Kounis Syndrome (see this post) is a form of ACS in which mast cells and eosinophils are involved.
Acute Intermittent Porphyria
Aneurysms (brain, aortic, abdominal) - "An aneurysm is an abnormal bulge or ballooning in the wall of a blood vessel. An aneurysm can burst (rupture), causing internal bleeding and often leading to death. Aneurysms usually don't cause symptoms, so you might not know you have an aneurysm even if it's large."

Bradycardia is "an abnormally low heart rate of less than 60 beats per minute."

Carcinoid heart disease occurs when high levels of vasoactive substances released from liver neuroendocrine metastases flow to the right heart and cause endocardial damage.  
Carcinoid Heart Disease: Review of Current Knowledge (2019)
Carcinoid Heart Disease Guidelines (from American College of Cardiology)

Catecholaminergic Tachycardia

Coronary Artery Syndrome 

Disseminated Intravascular Coagulation (DIC)

Heart Failure (Compensated and De-compensated)  "Heart failure — sometimes known as congestive heart failure — occurs when the heart muscle doesn't pump blood as well as it should. When this happens, blood often backs up and fluid can build up in the lungs, causing shortness of breath."

Hemochromatosis comprises a group of inherited disorders that can cause iron overload, which primarily affects the liver and joints and results from a failure in the regulation of the key liver-derived iron regulatory hormone hepcidin to respond to increasing iron stores.
Kounis Syndrome (Allergic heart attack)

Kyphoscoliotic Heart Disease
Kyphoscoliotic heart disease; report of five cases. 

Myocarditis and Pericarditis
Platelet Storage Pool Deficiencies - "Platelet storage pool deficiencies are bleeding disorders caused by problems with platelet granules.  Granules are little sacs inside the platelet where proteins and other chemicals are stored."
Pulmonary Arterial Hypertension "PAH is a specific type of high blood pressure that affects your heart and lungs. When you have PAH, the blood vessels in your lungs become narrower. This means your heart has to work harder to pump blood to your lungs."

Polycythemia Vera
Polycythemia Vera: Signs and SymptomsIs a myeloproliferative neoplasm, technically a chronic blood cancer.  Almost all patients have a JAK2 mutation.  Primary finding is a high red blood cell count and may also include high white cell count and high platelet count.  Patients are usually a bit older, may be prone to clots.  Often found on routine blood testing.  Some have an enlarged spleen.  Other symptoms can include itching, fatigue, and blood clotting.  Bone Marrow can become scarred/fibrotic.  Sweating and fevers for no reason.  Later in disease may have anemia or underproduction of some blood cells.
How I Treat Polycythemia Vera - Alessandro Vannucchi, MD
Tachycardia "is an abnormally fast heartbeat, causing the heart to beat more than 100 times per minute at rest. There are three types of tachycardia: sinus, supraventricular, and ventricular. Changes from the normal sequence of the heart’s electrical impulses cause all three types of this heart rhythm problem."
Takotsubo Cardiomyopathy

Understanding Testing and Test Results:
How Heart Failure is Diagnosed
BNP can help differentiate if shortness of breath is coming from heart or lungs.
Hematology – Elevated Hemoglobin: By Karima Khamisa M.D.