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)

Herpes Viruses in the Brain and Nervous System

Cognitive and psychiatric impairment in herpes simplex virus encephalitis suggest involvement of the amygdalo-frontal pathways
"The long-term neuropsychological and psychiatric sequelae of herpes simplex virus encephalitis (HSVE) and their relationship to the volume of temporal lesions and to amygdala and hippocampus damage remain undefined. We have conducted a prospective study of long-term sequelae in 11 patients with clinically presumed HSVE and detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction.  Long-term memory disorders were seen in 6 patients, associated with the larger lesions and damage of at least two structures. Long-term behavioural changes with emotionalism, irritability, anxiety or depression were prominent in 7. Left prefrontal hypoperfusion appeared in 8 patients, associated with psychiatric disorders in 7 and left amygdala damage in 6. The reduction of amygdala and hippocampus volume was correlated with the overall volume of lesions. Different patterns of mesial temporal lobe damage occurred, involving either amygdala alone, or amygdala and hippocampus, but never hippocampus alone. MRI volumetric measurements in HSVE could be a good indicator of long-term prognosis. Persistant behavioural changes could be related to an amygdala and frontal dysfunction."

Kluver-Bucy Syndrome is a brain disorder that can occur following a case of Herpes Simplex Virus Encephalitis (HSVE). "The syndrome in humans is due to bilateral destruction of the amygdaloid body and inferior temporal cortex, most commonly due to herpes simplex encephalitis (HSE). It shares visual agnosia and loss of normal fear and anger responses in common with the monkey model but one also sees loss of memory with dementia, distractability and seizures. The hypersexuality tends to be less overt than in the monkeys but may be public and unacceptable."  While the full disorder is rare in humans, apparently partial forms are much more common.  This becomes more relevant when you keep in mind that many human syndromes occur on a very wide scale, so some individuals can have only shadows of the symptoms that are subclinical or only have a few symptoms rather than all of them. 

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.

Infections Alter Our Genetic Expression

Research published in the Dec 15th issue of the journal Immunity has found that infections alter the expression of host genes.  The changes that result from infection are different for viruses and bacteria and may be used in the future as a way to distinguish viral infections from bacterial ones.  Additionally, they found that the expression of a group of 11 genes were altered by the influenza virus and this could serve as a useful way to distinguish influenza from other viral infections.  They found that the influenza vaccine led to the same changes in gene behavior.  There is hope that this could be a way reduce the overuse of antibiotics by identifying more accurately which infections are viral and therefore not appropriate for antibiotic treatment.  

From this article in Science News about this research and what it means:

"To find the viral fingerprints, computational immunologist Purvesh Khatri of Stanford University and colleagues combed through a wide variety of publicly available datasets that included information about how human genes behaved after an infection of influenza, human rhinovirus and respiratory syncytial virus, or RSV. The researchers churned these diverse datasets through a series of sophisticated mathematical analyses, a process that ultimately pinpointed a consistent viral calling card — a list of nearly 400 genes, each of which grew either more or less active during a viral attack. Many of those genes make proteins known to be involved in virus responses and inflammation."

This is the abstract for the journal article itself:

Integrated, Multi-cohort Analysis Identifies Conserved Transcriptional Signatures across Multiple Respiratory Viruses

 While this research looked at the effects on human genes for three viruses, it seems likely that at least some other viruses have this effect as well.  This is particularly interesting since ME/CFS and Fibromyalgia often begin with a viral infection that seems to act as a trigger, maybe this is how?  Maybe some people have some problem with the mechanism that corrects these changes after infection, if that happens, or maybe the way the gene expression is altered is not the same in some people, or maybe there are mutations in these genes that do not become apparent until their expression is changed in this way?  I also can't help but wonder if the flu vaccine alters DNA expression, maybe other vaccines do as well, and again maybe this plays a role in the onset of some adverse reactions and disorders that can follow vaccination?

Infections can Trigger Mast Cells and Histamine Release

It has recently been discovered that Influenza infection can trigger mast cell activity and that this may be a major factor in the morbidity associated with influenza infection.  It is thought that the severity of some influenza strains is due to an overreaction of mast cells (and other immune cells such as dendritic cells) that causes damage to the lungs that then allows bacterial infections to take hold.  You can read more about this idea here:

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond
A post on the blog MastAttack has great information about the role of infections in triggering mast cells and releasing histamine (as well as other mediators).  From the post:

"TLR2 is one of the most well studied and understood of toll-like receptors found on mast cell surfaces. TLR2 is also known as CD282. Substances that bind to TLR2 include many molecules released by bacteria and fungi. Several types of peptidoglycans and found in bacterial cell membranes bind TLR2. In particular, lipoteichoic acid is a potent activator of TLR2. This molecule is found on the surfaces of gram-positive bacteria, like Staphylococcus spp. (Staph, MRSA) and Streptococcus spp. (Strep). Other bacteria that are known to activate TLR2 include Neisseria meningitides, Haemophilus influenzae, and Borrelia burgdorferi, among others. Mycobacteria are also activating to TLR2. Zymosan is found in cell membranes of yeast and binds TLR2. Aspergillus fumigatus (fungi) and several viruses, including Herpes simplex, Varicella zoster,Cytomegalovirus and measles, activate TLR2 responses. Heat shock protein 70 (HSP 70) is released by cells in the body when they are under certain types of stress, and this can activate TLR2.

Multiple studies reported that stimulation of TLR2 with peptidoglycan (a constituent of gram positive bacterial cell membranes) induced degranulation. Stimulation with peptidoglycan induced histamine release as well as cytokine release in a 2003 study (Varadaradjalou 2003). Another study found that peptidoglycan did not cause statistically significant degranulation, but zymosan (a fungal product) and Pam3Cys (a synthetic molecule that acts like LPS, another component of bacterial membranes) did induce significant degranulation (McCurdy 2003). Other studies have not been able to replicate these results."
Here are a few other relevant studies:

Enhancement of IgE-mediated histamine release from human basophils by immune-specific lymphokines.
In this study, it was found that basophils that have been exposed to certain viruses release more histamine in the presence of ragweed IgE than basophils that were not previously exposed to the virus.

Chronic urticaria and blastocystis hominis infection. A case report
In this case study it is found that a parasitic infection is the cause of a woman's chronic hives.

Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release

Infection with Borrelia burgdorferi, the pathogenic agent in Lyme Disease, can activate mast cells and cause the release of tumor necrosis factor alpha.

Autoimmune Encephalitis (including PANDAS/PANS)

Recorded presentation by Dr Melanie Alarcio MD from the 2014 FACES Encephalitis Conference.

When it comes to autoimmune encephalitis, misdiagnosis is the norm rather than the exception.  Many doctors have never heard of Hashimoto's Encephalitis (HE) or other autoimmune forms of encephalitis (called AEs).  AEs are just not something in the awareness of most mainstream doctors.

What is the difference between encephalitis and encephalopathy?

Encephalitis is irritation and inflammation of the brain, usually occurring in an acute manner.  Encephalopathy is a diffuse disease of the brain that alters brain function or structure (these definitions came from the NINDS fact sheets and here).  Encephalitis is more likely to present with abnormal test results, such as an MRI or spinal tap whereas encephalopathy tends to not show up on tests well, or to show up in subtle ways.  Clinical features of encephalitis include a flu-like prodromal state, followed a few days later with headache, fever, vomiting, altered mental status, often seizures, hallucinations, visual disturbances, and may include rigidity of the neck of there is also meningitis.   With encephalopathy the hallmark is an altered mental state.  Clinical features include confusion, progressive loss of memory and cognitive ability, personality changes, inability to concentrate, lethargy or other progressive loss of consciousness, involuntary movements like myoclonus, tics or tremors, and sometimes seizures.  Causes of encephalitis are usually infectious, such as bacteria, viruses, parasites or fungi.  They are rarely autoimmune or triggered by medication.  Encephalopathy can also be caused by infectious agents, but it is more often the result of metabolic or mitochondrial problems, exposure to toxic substances, trauma, stroke, or brain tumor.

Diagnosis is based on a good clinical history and exam.  She says this is a learned and sadly rare skill.  Then testing can include CSF analysis, imaging studies like MRI or EEG, antibody testing, serologic testing, and brain biopsy.  Encephalitis is first classified as infectious vs non-infectious, if infectious as viral or non-viral.  Non-infectious is classified as ADEM, antibody mediated paraneoplastic or non-paraneoplastic, seronegative autoimmune or non-vasculitic autoimmune inflammatory encephalitis.  Viruses that can cause encephalitis include herpes simplex, other herpes viruses including varicella zoster, CMV, EBV, HHV6, adenoviruses, influenza A, enteroviruses, poliovirus, measles, mumps, rubella, rabies, arboviruses (including West Nile virus, Japanese B encephalitis, tick-borne encephalitis viruses), bunyaviruses (such as La Crosse strain of California virus), and reoviruses (such as Colorado tick fever).

Non-viral causes include tuberculosis, mycoplasma, listeria, Lyme and coinfections, aspergillis, candida, toxoplasma gondii, and Schistosomiasis, among others (list is at 10:03).  Non-infectious causes are more rare, but are becoming less rare recently.  ADEM is Acute Demyelinating Encephalomyelitis, it's thought to be a later response to an infection.  It is often post-vaccination, which is why it's seen a lot in children.

What is the function of the immune system?

It protects us from infectious micro organisms, and it maintains the "uniqueness" of the individual (for example, rejecting transplants).  Because of this second job, one of the fundamental abilities of the immune system is to distinguish "foreign" from "self".  Disorders of the immune system include hypersensitivity, autoimmunity, and immune deficiency.  It wasn't until the 1950s and 60s that it was widely accepted in mainstream medicine that autoimmunity could be the cause of illness.  Autoimmunity can result from genetic predisposition triggered by environmental factors.  Autoimmune disease affects between 3 and 8 percent of the general population, with some forms such as adult-onset RA being much more common than other forms such as Systemic Sclerosis.

Autoimmune disorders are not rare, but autoimmune brain disorders ARE rare.  The brain was thought to be separated from the immune system for many years, because there are no lymphocytes in the CSF (cerebrospinal fluid), no lymphatic drainage from the brain, and there is a low level of immune-derived molecules in the brain.  Also the blood-brain-barrier limits the movement of immune molecules into the brain.  There are links between the brain and the immune system, however.  The autonomic nervous system modulates the immune system in two ways:

"Sympathetic nervous system (SNS) innervates all lymphoid organs and that catecholamines, the end products of the SNS, modulate several immune parameters.  (Lymphoid organs are where immune molecules come from).

And "immune system is tuned by norepinephrine released locally or circulating epinephrine from the adrenal medulla."

Another connection between the brain and the immune system is the neuroendocrine humoral outflow via the pituitary.

At 26:35 is a drawing of how the immune system gets activated by a systemic immune insult, but she says you can substitute stress at that point as well.  Stress (or any other insult) triggers monocytes to release interleukin 1 and TNF-alpha.  The BBB in the hypothalamus is only a single cell layer, and these pro-inflammatory cytokines can disrupt that thin membrane and enter the hypothalamus.  It then triggers the PVN (periventricular nuclei) to release CRF (corticotropin releasing factor) which then acts on the pituitary gland which then releases ACTH to trigger the adrenal gland to release cortisol.  This is how stress triggers your immune system and then the immune system affects the brain.

Autoimmune or immune-mediated encephalopathy comprises many different syndromes.  Symptoms include inattention, hyperactivity, delusions, paranoia, and hallucinations.  They often mimic psychiatric disorders such as schizophrenia and bipolar.  These are things that generally onset over days or weeks, not years.  At 30:45 is a table showing the similarities between PANDAS, NMDA encephalitis, limbic/paraneoplastic encephalitis, and Hashimoto's Encephalitis.  These also share an aspect of movement disorders, which is about dopamine.  Dopamine is also involved in the hallucinations and delusions and the emotional component of speech (connection to stuttering?).  Treatment for these disorders is all immune based.

She says that in medical school, they are taught that if it is medical, it cannot also be psychiatric, and if it is psychiatric, it cannot also be medical.  She says we only have one brain and that one brain gives us both the psychiatric and neurological manifestations.  She sees a lot of PANDAS/PANS cases and believes that they are part of a wider group of autoimmune or immune-mediated encephalopathy or encephalitis.  She also sees a lot of concussion patients, and they present much the same way.

There is no standard practice guidelines for physicians for these disorders, so each may treat differently.  All therapies are immunomodulatory, such as IVIG, plasmapheresis, methotrexate, etc.  There are also not standard doses of these medications and treatments.  For IVIG, she gives 1 to 1.5 grams per kg per day for 2 days.  An immunologist will often give more like 0.5 grams.  Recovery occurs over months, not immediately.  There can be remission and there can be recurrences.  Antibiotics are used in some cases.  In addition to treating an underlying infection, they also have non-antimicrobial action.  They can also decrease the antigenic load from undetected or asymptomatic infections (in particular Group A Strep. She says strep has been with us for a long time  and has evolved ways of avoiding detection in the human body to come back later to get us), they can change inflammatory cell metabolism by altering the cytokines, can allow normalization of tryptophan levels which then affects serotonin levels, and offers neuroprotection by increasing expression of glutamate transporter GLT1.

In concussion, there is something called a glutaminergic surge, which can lead to neurodegeneration and the neuropsychiatric symptoms of concussion.  Antibiotics can actually help with that.  Ibuprofen can also help by suppressing the production of prostaglandins, and because it can have an anti-inflammatory effect on the blood-brain-barrier, which also helps to limit anti-neuronal antibodies from crossing into the brain.

Her call to action for medical colleagues....listen to the parents, listen to the patient.  Don't assume that they are making this up. There is a need to establish a standard of care across medical disciplines.

Vertical Viral Transmission as Pathogenesis in Autism?

A study published in 2010 out of Rome, Italy has found evidence of vertical viral transmission in postmortem evaluations of the brains of people with autism.  The study was undertaken because there is evidence of heritability of autism, that is of it being passed along in families, that is stronger than the evidence that is being found for a genetic cause for this heritability.  So the question was asked, in what other ways could a disorder such as autism be passed from one generation to the next?  Infections are certainly one way that this can occur.  To quote from the study "Autism is a highly heritable behavioral disorder. Yet, two decades of genetic investigation have unveiled extremely few cases that can be solely explained on the basis of de novo mutations or cytogenetic abnormalities. Vertical viral transmission represents a non-genetic mechanism of disease compatible with high parent-to-offspring transmission and with low rates of disease-specific genetic abnormalities."

This study, Association of autism with polyomavirus infection in postmortem brains,
found that three viruses were significantly more prevalent in the brains of people with autism than in the controls "BKV, JCV, and SV40 combined are significantly more frequent among autistic patients compared to controls (67% versus 23%, respectively; P < .05). "  SV40 is Simian Virus 40, a monkey virus that was a contaminant in polio vaccines used between 1955 and 1963.  BK and JC viruses are closely related to each other, and are part of the family of polyomaviruses (which is a subgroup of papovaviruses). SV40 is also a papovavirus.

SV40 has long been suspected of causing cancer in humans, but evidence has been mixed and inconclusive.   The Immunization Safety Review Committee of the Institute of Medicine put out a report on this question that can be viewed here, which essentially says that the epidemiological evidence that has been used to deny a connection between SV40 and cancer is too flawed to rule out a possible connection, that the idea that SV40 could contribute to human cancers is plausible, and that ongoing investigation is required.

The paper "BK Virus: A Clinical Review" provides more information about BK virus:

-the etiologic agent of progressive multifocal leukoencephalopathy (PML).
-The kidney, lung, eye, liver, and brain are sites of BK virus-associated disease, both primary and reactivated.

-BK virus has also been detected in the tissue samples of a variety of neoplasms, which have predominantly been brain tumors of glial and neural origin, although there is controversy regrading associations between these neoplasms and BK virus.

-A few investigators have proposed various mechanisms whereby BK virus can induce neoplasia (cancer).

-There may even be an association between BK virus and autoimmune disease.

-Although rarely recognized, BK virus might cause both primary CNS disease and reactivation CNS disease as well.

-Additional disorders of the CNS associated with BK virus include encephalitis, Guillain-Barre Syndrome, and Meningoencephalitis.

-Many authors have reported that BK virus can exist in a latent phase in various organs [12–27]. Much of the data are based on PCR experiments; exceptions are mentioned below. Similar in concept to the latent state of the herpesvirus [101], these authors propose that BK virus can remain within a cell in a nonreplicating or minimally replicating form. Within the cell, the latent viral genome may either remain episomal or it may be integrated in the host cell genome. In either state, few if any viral genes are transcribed, thereby keeping the virus out of reach of the immune system. Implicit in the definition of latency is the concept of virus reactivation in certain settings.

-Reactivation disease is observed in patients with relative or absolute immunodeficiency (generally cellular immunodeficiency rather than humoral immunodeficiency).

-researchers reported an increased prevalence and persistence of BK viruria in patients with systemic lupus erythematosus. In their study, the prevalence of BK viruria was 16% in patients with systemic lupus erythematosus and 0% in controls. Of the 20 patients who were tested, persistent or recurrent viruria was found in 60% of patients with systemic lupus erythematosus [90]. This same relationship is seen between BK virus and other autoimmune diseases, including rheumatoid arthritis and polymyositis [117]. Although whether there is causality has not been determined.

-Although it is not proof of causality, the strongest data, including demonstration of viral DNA integration into tumor cell genomes, and even the findings of some in situ studies, support a correlation between BK virus and many brain and urinary tract tumors [66, 70, 87].

-Other researchers that have observed the same phenomenon from a different perspective have examined the association of BK viral infection with an increased number of chromosomal aberrations. The induction of chromosomal aberrations via BK virus T antigen is observed in vitro in human fibroblast cell lines [85]. Also, one study reported that a group of patients with polyomavirus infection who were exposed to radiation experienced a greater number of chromosomal aberrations than did a similar group of persons without infection [86].

-Moens et al. [88, 89] demonstrated indirect interaction between the large T antigen of BK virus and native cell estrogen receptors that, via trans activation, enhances the promoter of BK virus. The researchers postulated that there was a hormone-mediated association with BK virus reactivation and even neoplasia.

More on JC Virus:

From Understanding the JC VIrus and the Risks for MS Patients:
-The JC Virus is the cause of Progressive Multifocal Leukoencephalopathy (PML), in which "it infects the white matter of the brain and attacks the cells responsible for making myelin, the protective coating that covers and protects nerve cells.".  

-This virus can be triggered to reactivate either because the immune system of the person with MS is compromised, or because the person is taking immune-suppressing medications.  

More information on JC infection can be found here:

-Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the central nervous system (CNS), caused by the polyoma virus JC virus (JCV) and characterized by focal demyelination.
-PML manifests as focal neurological deficits, usually with insidious onset and steady progression. Because the demyelinating lesions can involve different brain regions, specific deficits vary from patient to patient. Any region of the CNS can be involved, although some areas seem to be more favored, including the occipital lobes (with hemianopsia), frontal and parietal lobes (aphasia, hemiparesis, and hemisensory deficits), and cerebellar peduncles and deep white matter (dysmetria and ataxia).
-Spinal cord involvement is rare.
-Although lesions can be multiple, one often is clinically predominant.
-Initial symptoms and signs often begin as partial deficits (e.g., weakness in one leg) that worsen over time and involve a larger territory (e.g., evolution to hemiparesis) as individual lesions expand concentrically or along white matter tracts. The focal or multifocal nature of the pathology is responsible for the consistency of clinical presentations with distinct focal symptoms and signs, rather than as a more diffuse encephalopathy, or isolated dementia or behavioral syndrome, all of which are uncommon without concomitant focal findings.

The article JC Virus Infection of the Brain has some more updated information:

-Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE (JCV encephalopathy), JCVGCN (JCV Granular Cell Neuronopathy), and JCM (JCV Meningitis).
-Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency.
-It has become evident that PML has outgrown its name. JCV infection is no longer a 1-dimensional opportunistic infection, limited to HIV and lymphoproliferative disorders. Although HIV accounts for approximately 80% of the PML cases, there is increasing incidence of the disease in non-HIV settings.
-JCV is a ubiquitous human pathogen, and both inhalation and ingestion of contaminated water have been suggested as major modes of transmission of the virus.
-Usually, severe deficiency of T-cell immunity (cellular immunity) is necessary for reactivation of JCV.
-Calabrese et al18 recently reviewed 37 cases of PML in the setting of rheumatic diseases. All patients in this series were treated with some form of immunosuppressant before PML manifestation. Of all the rheumatologic conditions SLE was most commonly associated (65%) with PML. Other associated rheumatic diseases were rheumatoid arthritis, Wegener granulomatosis, dermatomyositis, polymyositis, and scleroderma. There are also reports of PML in patients with Sjogren syndrome19 and sarcoidosis20 with no prior immunomodulator therapy. In both of these cases, there was associated lymphocytopenia. It is unclear whether the rheumatologic condition or the lymphocytopenia was responsible for PML.
-PML has also been described in patients with primary immunodeficiency disorders, ICL being the most common condition to be associated with PML.28–30 PML has also been described in patients with common variable immune deficiency.
-Until recently, severe depletion of cellular immunity was considered an absolute requirement for the development of PML. However, there are now case reports of PML with less overt immunodeficiency, such as cirrhosis, renal failure, psoriasis, dermatomyositis, and even pregnancy.6 Furthermore, there are multiple reports in the literature of PML without any documented immunodeficiency.6 It is very important that neuroradiologists be aware of this expanding demography of PML, JCE, JCVGCN, and JCM.
-The pathogenesis of PML is divided into 3 phases. The first phase is a primary clinically unapparent infection. In the second phase, the virus maintains a persistent latent peripheral infection in the urinary tract, bone marrow, and probably the spleen.35 The presence of JCV in the bone marrow and shedding of the virus in urine are well documented in asymptomatic immunocompetent carriers.36,37 The CNS has also been suggested as a potential site for JCV persistence. The third or final phase is that of reactivation and dissemination of the virus with presumed hematogenous spread to the CNS.
-The authors concluded that tests for BK virus and JCV should be included in the investigative program for patients with meningitis or encephalitis.
-PML may involve gray matter as well. The thalamus is the most common area, followed by the basal ganglia.49,88 Usually gray matter lesions are associated with white matter involvement in almost all cases. Vary rarely, PML lesions can be isolated to the gray matter.
-As briefly mentioned previously, PML can occur in MS patients treated with natalizumab. It is very difficult to differentiate a new PML lesion from an MS plaque in patients treated with natalizumab.

More interesting finds about BK virus, JC virus, and SV 40:

Hypothesis- "Rogue cell"-type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus and has implications for oncopenesis

Abstract- "The hemagglutination inhibition antibody titers against the JC and BK polyoma viruses (JCV and BKV, respectively) are significantly elevated in individuals exhibiting "rogue" cells among their cultured lymphocytes. However, the elevation is so much greater with respect to JCV that the BKV elevation could readily be explained by cross reactivity to the capsid protein of these two closely related viruses. The JCV exhibits high sequence homology with the simian papovavirus, simian virus 40 (SV40), and inoculation of human fetal brain cells with JCV produces polyploidy and chromosomal damage very similar to that produced by SV40. We suggest, by analogy with the effects of SV40, that these changes are due to the action of the viral large tumor antigen, a pluripotent DNA binding protein that acts in both transcription and replication. The implications of these findings for oncogenesis are briefly discussed."

The Basics of the Methylation Pathway

These are my notes for a presentation given by Dr Ben Lynch about identifying and supporting methylation issues in patients with MTHFR (which you can watch here).  It is a great place to start to learn about methylation.  This post covers the first 30 minutes of the presentation, which focus on methylation chemistry.  The last 60 minutes is specifically about MTHFR and can be seen in this post.

What is methylation?

Methylation is basically the biochemistry surrounding the giving of a methyl group from one substance to another to alter it (a methyl group is one carbon atom with 3 hydrogen atoms attached, CH3).  The recipient of the methyl group can include DNA, RNA, chemicals from our environment that have made it into our bodies, neurotransmitters and hormones, our immune system, and our nerves.  For example, thymine is what you get when a methyl group is added to uracil.  Without adequate methylation, there will not be adequate thymine for DNA synthesis. 

The Functions of Methylation Include:

-Gene regulation (turning genes off and on)
-Transforming harmful chemicals in our bodies into less harmful and water soluble forms so that they can be excreted in the urine, or in some cases making it fat soluble and storing it in our bodies (our bodies sometimes use fat cells to store harmful chemicals until our bodies are able to detoxify them safely.)
-Making neurotransmitters and regulating their level in the blood.
-Breaking down excess estrogen.
-Building some immune cells, especially T-cells and NK cells.
-DNA and RNA synthesis
-Producing energy (CoQ10, carnitine, ATP).
-Production of myelin coating on nerves.

How Is Methylation Regulated?

It is regulated by how much substrate is available (the end product of methylation), and the amount of enzymes available.  Too much of a substrate can "turn off" methylation as a feedback mechanism.  Methylation is "done" by enzymes.  Enzyme function may be inhibited by a lack of needed cofactors (vitamins and/or minerals needed to make the enzyme work), or because the DNA that codes for the enzyme is mutated such that the enzyme is misshapen and not able to function adequately (such as in the case of an MTHFR variance).

How is Methylation Disturbed?

-Deficiency of the vitamins and minerals that function as cofactors, such as zinc, magnesium, and vitamin B6.  (This is how Pyroluria leads to under-methylation)
-Certain medications, such as antacids can disrupt methylation.  Antacids casue B12 deficiency, and without adequate B12 methylation is limited.
-Some nutrients, such as niacin, use up methyl groups and thus suppress methylation.
-Environmental toxicity from chemicals such as aldehydes (common in perfumes), chemicals used in building and remodeling, heavy metals such as mercury and arsenic, alcohol, all require methylaiton to be processed so they place a strain on the methylation system.  Candida (yeast) also produces acetylaldehyde and this page discusses how it interrupts methylation in more detail.
-Too much substrate limits methylation, such as too much SAM-e, or glutathione, or cysteine.  All of these "shut down" methylation.  This is mostly an issue from over supplementation.  (People with high plasma cyteine who are mercury poisoned are often sensitive to foods containing a form of sulfur called thiols, I wonder if this is why?)
-Genetic mutations.  There are many possible ones.  (Yasko testing seems to me to be the best way to find out about these).

Disorders That Are Related to Under-Functioning of the Methylation System

Autism, MS, Fibromyalgia, Diabetes, Parkinson's, Chronic Fatigue Syndrome, Alcoholism and other addictive problems, ADHD, Insomnia, Alzheimer's, Cancer, Allergies, Bipolar, Schizophrenia, Depression, Anxiety, Neural Tube Defects including Spina Bifida, Cleft Palate, frequent miscarriages, Infertility, Tongue Tie, Tethered Spinal Cord, Chiari Malformation, Pulmonary Embolisms, Atherosclerosis, Immune Deficiency, Chronic Viral Infection, Congenital Heart Defects, Chemical Sensitivity, Thyroid Dysfunction, Neuropathy, Down's Syndrome, and mercury poisoning.

Why Are Disorders of Under-methylation Increasing?

-Changes in food supply resulting in less nutrition in foods and more chemical contaminants such as pesticides.
-Increased stress from fast pace of modern living (I think this is quesitonable, I think human life has always had its stresses, but I do think the modern ones are different and perhaps we are less resilient to them as we are not adapted yet).
-Our environment is saturated with chemicals- in our water, food, air, clothing, toys, electronics, cookware, etc.
-Exposures from pharmaceuticals (drugs and vaccines).

How Can Under-methylation Be addressed and Reversed?

-A multifaceted approach is needed, that looks at lifestyle, diet, environment, mental outlook, and nutrition.  This is a lot, but still not enough for many people.  For these people it is necessary to take genetics into account as well.  He believes that MTHFR is the most common genetic cause.  There are many others as well.
-The list of mutations that he has in his presentation is long, but the ones that jump out at me as likely relevant to Roo and I are GAD (which transforms glutamate to GABA), HNMT (secondary enzyme for processing histamine, after DAO), MTR/MTRR (recycling of B12), CBS (processes homocysteine), and for Roo NOS which processes ammonia, and for both of us GSTM1 which produces glutathione.  This list is really worth looking at.
-As an interesting aside, he says that DAO, which is the primary enzyme that breaks down histamine, if more often damaged or down regulated by environmental factors than be inherited genetics.  Alcohol in particular suppresses it's function.

The Amino Acids Lysine and Arginine and Herpes Reactivation

Once you have a herpes virus in your body, it is with you for life.  After an initial infection, which can be mild or severe, it will go dormant in the body.  If the immune system becomes weakened, from another illness or from stress for example, the virus can reactivate and cause a flare up.  One example is shingles which happens when the varicella zoster virus, which is herpes virus 3, reactivates and causes a painful rash.  The body uses the amino acid lysine to keep herpes viruses dormant.  Several factors can influence the amount of lysine that is available in the body for this purpose.  Yeast produces a metabolite that deprives the body of lysine.

Also, our diet can matter.  Lysine competes in the body with arginine, another amino acid.  Depending on which sources of protein we eat, we may be taking in more lysine or more arginine.  Eating a lot of arginine can actually cause a flare up of a herpes virus.  To keep the viruses dormant, ideally we should consume a ration of 2:1 lysine to arginine or better.

This is a list of how much lysine and arginine various foods contain

Notice that generally sources of animal protein, dairy and meat, have more lysine to arginine, and plant sources of protein (grains, nuts, beans, etc) tend to have lower amounts of lysine to arginine or even more arginine than lysine (and PLEASE don't eat margarine!!).  The ratio isn't the only significant number here though, the total number of mgs matters.  For example, 246 grams of Ricotta cheese has 3290 mg of lysine to 1550 mg of arginine, the difference is large and it is an excellent source of lysine despite the large amount of arginine that it also contains.  3 grams of garlic contains 8 mgs of lysine and 19 mgs of arginine, for a ratio that favors arginine, but the actual amount of arginine above the lysine is so low that it won't cause problems.  I hope that makes sense. 

You can also use supplements to increase your intake of lysine relative to arginine.  Many sites and groups recommend around 1000 mg 3 x a day of lysine during an outbreak, but differ on how much to take to prevent outbreaks.  That would probably depend somewhat on your dietary intake of lysine and arginine, the amount of yeast you have in your body, as well as your own individual needs. Some people take high doses of arginine for mitochondrial support or when detoxing oxalates, so these may be times when a supplement is particularly helpful.  

Lysine for treating herpes simplex virus
"HSV cells synthesize higher levels of arginine and lower levels of lysine than human host cells. Increasing cellular lysine concentrations disrupts HSV’s balance between lysine and arginine and inhibits viral replication. "  This article discusses a number of clinical trials testing the efficacy of lysine at treating and preventing HSV- results were mixed, with some studies showing modest efficacy in reducing the number of outbreaks.  Sources are listed at the end of the article.

"In addition to its role in the Krebs cycle, lysine has many other functions within human metabolism, including aiding in the conversion of fats into energy, improving calcium absorption by bone, forming a matrix for collagen, and helping maintain the serotonergic pathway in the brain."  They then elaborate further "It is thought that lysine deficiency results in a pathological increase in serotonin in the amygdala, which is responsible for emotional regulation and stress response.5 When serotonin increases unchecked, the amygdala becomes overstimulated, resulting in a low-level serotonin syndrome with anxiety, diarrhea, and other symptoms of excess serotonin."  They then report a small study that found a small but significant improvement in mood from increased dietary intake of lysine-rich foods.

About.com lists some of the common herbal supplements used to fight herpes as well.

Nora Gedgaudas on Adrenal Function, Hypoglycemia, and Chronic Infection

These notes are for one section of a talk given by Nora Gedgaudas during the Paleo Summit.  She was refuting the idea of safe starches, put forward by Paul Jaminet (author of The Perfect Health Diet), and discussing hypoglycemia.  She explains that hypoglycemia only occurs in people who are (unnaturally) temporarily adapted to getting glucose from dietary sugars and starches, and that for people who are fat burners- which is what the human body is adapted for- mood and cognitive functioning are not dependent on blood sugar levels.  The human body can make all of the glucose it needs in the liver from amino acids, there is no need to get it from the diet.  

The exception to this, she explains, is when people have chronically depressed cortisol levels.  What really caught my attention is that she says that this low cortisol production is not because the adrenals themselves have been "exhausted" by stress, which she says is an outdated idea.  She says that cortisol output is not controlled by the glad itself, but by the brain.  It is mitigated by the HPA (Hypothalamus Pituitary Axis), specifically by a group of cells inside the hypothalamus called the Paraventricular Nuclear cells (PVN).  The level of cortisol that we produce depends on how these cells are stimulated- whether the balance of neurochemicals leans towards excitatory or inhibitory, but in particular by the presence of inflammatory cytokines.  To rephrase that, low cortisol levels are caused by inflammation in the brain.  Various stressors on the body result in the release of these cytokines, including chronic infection.  This process can also impact our balance of neurotransmitters.

Levels of cortisol that are either suppressed or too high can have a negative effect on immune activity in our guts.  Adequate cortisol levels are necessary to regulate our glucose needs.  Without adequate cortisol, we feel chronically fatigued and inflamed.  She says that hypoglycemia isn't a glucose deficiency, but rather it's an infection or some other source of inflammation that needs to be addressed.  Blood sugar surges suppress our immune function, which she sees as further evidence that low carb diets are not to blame for the rampant immune suppression going on currently- rather low fat diets, which tend to be high in sugar and starches, are a more likely culprit.  She says that the cultivation of a fat-burning metabolism is a life-saver for people with auto-immune conditions.  (This is very validating for me to hear, as I have noticed that my body does so much better when in ketosis.)

The Healing Power of Camel's Milk

Camel's milk is reported to have healing properties, including healing allergies, reducing inflammation, regulating the immune system to decrease auto-immune problems, and increasing the immune system's ability to fight pathogens.  Camel's milk does not contain casein, the protein that most people who are allergic to milk react to, so it is often tolerated fine by people with dairy allergy.  What really got my attention is that it is said to support the immune system much the way IV/IG (intravenous immunoglobulin) treatment does, something I've been interested in for a long time as a treatment for PANDAS but am not able to afford.

We began by drinking several ounces per day and then slowly increased to 6 oz each per day.  We noticed benefits immediately, but the benefits were also dose-dependent so increased as our intake increased.  We seemed to keep the improvements when we stopped taking it.  It tastes a little salty but has a mild flavor so has been one of the easiest interventions to do as well as one of the most effective.  My kids were happy to drink it as "hot chocolate"- I would warm it slightly (not too much to keep it raw), and mix in some carob powder and honey.  It is expensive, however, because we get ours shipped frozen from a farmer halfway across the country, otherwise this would be a daily treatment for us.

This is the intervention that put Roo over the line to recovery.  We started the camel milk during a several weeks break from an educational program that the kids were doing, and when we came back people were surprised and impressed at the rapid improvements Roo experienced.  His language and speech improved dramatically, he was more calm and at ease and socially outgoing, and generally less anxious.  People also commented on how healthy I looked, and now that I know how sick I actually was, it makes sense.  I think the immune balancing properties are what made such a difference for us.

Here are several general sources of information about camel's milk that I have found helpful:

Camel Milk: Healing or Hype? From Julie Matthews' site Nourishing Hope

Got (Camel) Milk?  Is an article that appeared in The Autism File magazine

Camel Milk for Health

Handbook of Research on Health and Environmental Benefits of Camel Products
I don't have this book yet but it looks like essential reading for someone who truly wants to understand this subject. 

Information about the nutritional and therapeutic composition of camel's milk:
  Bioactive natural products in donkey and camel milk: a perspective review
"Human milk guarantees a healthy development and improves immunity. It is hypoallergenic. Sometimes, it is necessary to substitute this food with other milk for different reasons. Cow, sheep, goat, camel and donkey milk are natural alternatives. We evaluated the different compounds within donkey and camel milk analyzing their biomolecular characteristics and potential benefits for human health. Camel and donkey milk bioactive products could be good candidates for controlling several diseases and excellent substitutes in the case of milk protein allergies in infants."

The nutritional composition of camel's milk (this page contains a lot of information about the exact amount of various nutrients that occur in camel's milk).  A published paper also outlines the nutritional content of camel milk

Evaluation of camel milk: gross composition-a scientific overview
"This extraordinary and unique composition of camel milk makes it an excellent food for populations who live in regions (arid and semi-arid) where plants (fruits and vegetable) are uncommon. This scientific insight into the gross composition of camel milk could encourage consumers to incorporate this food into their diet and encourages dairy industry operators to consider the possible transformation of camel milk and its use as an ingredient in food. "

Nutritional significance and promising therapeutic/medicinal application of camel milk as a functional food in human and animals: a comprehensive review
"CM possess unique composition as compare to the cow milk with abundant amount of medium chain fatty acids in fat low lactose and higher concentration of whey protein and vitamin C. Besides the nutritional significance of CM, it also contains higher concentration of bioactive compounds including bioactive peptides, lactic acid bacteria (LAB), lactoferrin (LF), lactoperoxidase, lysozyme casein and immunoglobulin... Consumption of fresh or fermented CM and its products presumed exceptional nutraceutical and medicinal properties, including antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, hepatoprotective, nephroprotective, anticancer and immunomodulatory activities. Moreover, CM isolated LAB exhibit antioxidant and probiotic effects leading to enhance the innate and adaptive immune response against both gram-negative and gram-positive pathogenic bacteria. The main objective of this review is to highlight the nutritional significance, pharmaceutical potential, medicinal value and salient beneficial health aspect of CM for human and animals."

A comprehensive review on health benefits, nutritional composition and processed products of camel milk
"Consumption of camel milk and its products are presumed to be associated with antidiabetic, anti-cancerous, anti-hypertensive and many other health benefiting properties. Different in vitro and in vivo studies on camel milk have revealed various underlying mechanisms such as presence of bioactive proteins (lactoferrin, immunoglobulins, lactoperoxidases, etc.) as well as generation of various bioactive peptides upon digestion as possible scientific rationale for its health benefiting properties...  Therapeutic values of camel milk offer an extra advantage for its utilization in production of different functional food products. As such this review aims to present detailed compositional analysis, status of various feasible products from camel milk and the comprehensive discussion on the various health beneficial properties associated with camel milk and its components."

Medicinal value of camel milk and meat
"Camel milk and meat are unique from other ruminant’s milk and meat in terms of composition as well as claimed health effects. Camel milk has low cholesterol, high minerals (sodium, potassium, iron, copper, zinc and magnesium) and high vitamin C when compared with other ruminant milk. Camel milk contains various fatty acids, enzymes and protective proteins. Camel milk has potential therapeutic effects, such as antibacterial, antiviral, antidiabetic, anti-ageing and anticarcinogenic. The medicinal properties of camel milk can be attributed to the presence of protective proteins, which may possibly play a pivotal role for the enhancement of immune defense mechanism."

There has even been a TED talk about camel milk.  I was actually not very impressed with it overall;, but it did have some interesting information, so it was still worth watching.

Studies Regarding the Therapeutic Use of Camel Milk in Medical Treatment:
 Chapter 36 - Nutraceutical Properties of Camel Milk
"Camel milk is known for its medicinal properties, which have been widely exploited for human health since ancient times. Many studies have reported that camel milk has potential therapeutic properties such as antidiabetic, wound healing in diabetic patients, hepatitis C infection curing, treatment of autism, hypoallergenic effect, and antihypertensive. It has also been proven as a good alternative for people with cow milk allergy and as a therapeutic agent to reduce the harmful effects of exposure to toxins. Most of these properties are attributed to the unique characteristics of camel milk proteins, especially whey protein. Therefore in this chapter, the health-promoting activities of camel milk and their protein hydrolysates as well as their potential as an alternative for people with cow milk allergy was discussed."

A state-of-art review on camel milk proteins as an emerging source of bioactive peptides with diverse nutraceutical properties
"The generation of camel milk derived bioactive peptides (CM-BAPs) have started to grab keen interest of many researchers during the past decade. CM-BAPs have shown more significant bioactive properties in comparison to camel milk intact proteins. CM-BAPs can be obtained using enzyme hydrolysis to form hydrolysates, or by the fermentation process. In this systematic review, 46 research articles exploring the health-related bioactive properties of CM-BAPs through in-vitro and in-vivo studies have been included. CM-BAPs have been reported for their antioxidant, anti-diabetic, anti-obesity, antihypertensive, antibacterial, antibiofilm, anticancer, anti-inflammatory, anti-haemolytic, and anti-hyperpigmentation activities. The effects of factors such as molecular weight of peptides, type of enzyme, enzyme to substrate ratio, hydrolysis temperature and duration have been analyzed. The in-vitro studies have provided enough evidence on certain aspects of the pharmacological actives of camel milk bioactive peptides."

Camels’ biological fluids contained nanobodies: promising avenue in cancer therapy
"Recently, there has been an evolving interest in utilizing nanobodies of camel origin as therapeutic tools against cancer...  The current review highlights the potential use of nanobodies that are naturally secreted in camels’ biological fluids, both milk and urine, in the development of nanotechnology-based therapy for treating different types of cancers and other diseases."

The Antioxidant, Anti-Inflammatory and Immunomodulatory Effects of Camel Milk
"Camel milk (CM) has been found to have several health benefits, including antiviral, antibacterial, anti-tumor, anti-fungal, antioxidant, hypoglycaemic and anti-cancer activities. In addition, CM can counter signs of aging and may be a useful naturopathic treatment for autoimmune diseases...  The anti-inflammatory mechanism of CM in various inflammatory disorders was consistently reported to be through modulating inflammatory cells and mediators. The common anti-inflammatory bioactive components of CM seem to be lactoferrin. The antioxidant effects of α-lactalbumin, β-caseins and vitamin C of CM work by reducing or inhibiting the production of reactive oxygen species (ROS), hydroxyl radicals, nitric oxide (NO), superoxide anions and peroxyl radicals, likely alleviating oxidative stress. Higher levels of protective proteins such as lysozyme, IgG and secretory IgA compared to cow's milk, and insulin-like protein activity of CM on ß cells appear to be responsible for the immunomodulatory properties of CM. The evidence indicates that CM and its bioactive components has the potential to be a therapeutic value for diseases that are caused by inflammation, oxidative stress and/or immune-dysregulation."

Invited review: Camel milk and gut health—Understanding digestibility and the effect on gut microbiota
"Furthermore, antibodies help the digestive system by destroying the antigens, which are then overwhelmed and digested by macrophages. The connection between the gut microbiota and human health has gained substantial research attention, as it offers potential benefits and supports disease treatment. The gut microbiota has a vital role in regulating the host's health because it helps in several biological functions, such as protection against pathogens, immune function regulation, energy harvesting from digested foods, and reinforcement of digestive tract biochemical barriers. These functions could be affected by the changes in the gut microbiota profile, and gut microbiota differences are associated with several diseases, such as inflammatory bowel disease, colon cancer, irritable bowel disorder, mental illness, allergy, and obesity. This review focuses on the digestibility of CM components, particularly protein and fat, and their influence on gut microbiota modulation. Notably, the hypoallergenic properties and small fat globules of CM contribute to its enhanced digestibility. Considering the rapid digestion of its proteins under conditions simulating infant gastrointestinal digestion, CM exhibits promise as a potential alternative for infant formula preparation due to the high β-/α_s-casein ratio and protective proteins, in addition to the absence of β-lactoglobulin."

Consumption of camel's milk by patients intolerant to lactose. A preliminary study.
"Except for two patients, who had mild reactions to the maximum dosage of camel's milk (250 mL), the acceptance was excellent. Pasteurization of camel's milk did not affect tolerance. Also, most of the patients showed significant clinical reactions when drinking very low amounts of cow's milk. Camel's milk can be considered an option for the individuals intolerant to lactose who present symptoms when ingesting cow's milk."

Release of angiotensin converting enzyme-inhibitory peptides during in vitro gastro-intestinal digestion of camel milk
"Angiotensin-converting enzyme (ACE)-inhibitory peptides released from camel milk after simulated gastro-intestinal digestion were identified. The hydrolysis degree increased during digestion. The highest ACE-inhibitory activity was found in the post-pancreatic <3 kDa fraction. Peptides responsible for the biological activity were isolated by reversed-phase high-performance liquid chromatography and identified by mass spectrometry. Among the identified sequences, 17 were identical to known bioactive peptides with ACE-inhibitory activity."

Camel Milk for Food Allergies in Children
(A small scale study with impressive results)

Behavioral Benefits of Camel Milk in Subjects with Autism Spectrum Disorder
" Significant differences were detected on Autism Spectrum Disorder (ASD) by CARS, SRS and ATEC scales, following 2 weeks of camel milk consumption, but not in the placebo group."

Camel Milk as a Potential Therapy as an Antioxidant in Autism Spectrum Disorder (ASD)
"All measured parameters exhibited significant increase after camel milk consumption (P < 0.5). These findings suggest that camel milk could play an important role in decreasing oxidative stress by alteration of antioxidant enzymes and nonenzymatic antioxidant molecules levels, as well as the improvement of autistic behaviour as demonstrated by the improved Childhood Autism Rating Scale (CARS)."

Leptin and camel milk abate oxidative stress status, genotoxicity induced in valproic acid rat model of autism
"Leptin or CAM treatment of autistic animals showed a significant improvement of all measured parameters and genetic expression values. The improvement was pronounced in animals treated with CAM. These results suggest that CAM is a potential therapeutic candidate for autism via regulation of inflammatory and apoptotic pathways. Leptin plays an essential role in alleviation of autistic behaviour through antioxidant effects."  (CAM = camel milk)

Patient report: autism spectrum disorder treated with camel milk
"This patient report is about my son, who was diagnosed with autism spectrum disorder (ASD) at 3 years of age, and the effects I observed when he began drinking camel milk daily. Beginning at age 9, he drank one half cup of raw camel milk a day and experienced overnight an improvement in his symptoms. His continued regular consumption of camel milk was associated with sustained symptom improvements for 6 consecutive years (2007-2013)."

Nutritional and Therapeutic Characteristics of Camel Milk in Children: A Systematic Review
"Camel milk as a supplemental treatment seems less invasive and costly than specialist care, medications, alternative treatments, and behavioral interventions. Based on our findings, camel milk is safer for children, effective in the treatment of autism, improves general well-being, promotes body natural defenses, is a good nutritional source, and can helps the daily nutritional needs of humans."

Mast cell stabilizing potential of Camel milk (Camelus dromedaries) in the management of asthma
"These findings suggest that camel milk (Camelus dromedaries) possesses mast cell stabilizing properties and therefore can be a candidate for the antiasthmatic treatment and thus, it may be used in the management of asthma."

Research Development on Anti-Microbial and Antioxidant Properties of Camel Milk and Its Role as an Anti-Cancer and Anti-Hepatitis Agent
"Camel milk is a rich source of vitamin C, lactic acid bacteria (LAB), beta-caseins and milk whey proteins, including lactoferrin, lysozyme, lactoperoxidase, alpha-lactalbumin and immunoglobulin. The lactoferrin plays a key role in several physiological functions, such as conferring antioxidant, anti-microbial and anti-inflammatory functions in cells. Similarly, the camel milk alpha-lactalbumin has shown greater antioxidative activity because of its higher antioxidant amino acid residues. The antioxidant properties of camel milk have also been ascribed to the structural conformation of its beta-caseins. Upon hydrolysis, the beta-caseins lead to some bioactive peptides having antioxidant activities. Consequently, the vitamin C in camel milk has a significant antioxidant effect and can be used as a source of vitamin C when the climate is harsh. Furthermore, the lysozyme and immunoglobulins in camel milk have anti-microbial and immune regulatory properties. The LAB isolated from camel milk have a protective role against both Gram-positive and -negative bacteria. Moreover, the LAB can be used as a probiotic and may restore the oxidative status caused by various pathogenic bacterial infections. Various diseases such as cancer and hepatitis have been associated with oxidative stress. Camel milk could increase antiproliferative effects and regulate antioxidant genes during cancer and hepatitis, hence ameliorating oxidative stress. In the current review, we have illustrated the anti-microbial and antioxidant properties of camel milk in detail. In addition, the anti-cancer and anti-hepatitis properties of camel milk have also been discussed."

In vitro investigation of anticancer and ACE-inhibiting activity, α-amylase and α-glucosidase inhibition, and antioxidant activity of camel milk fermented with camel milk probiotic: A comparative study with fermented bovine milk
"The proteolytic and antioxidant activity of water soluble extracts (WSEs) from all fermented camel milks were higher than those of fermented bovine milk. α-Amylase inhibition of WSEs were >34% in both milk types fermented with all strains during storage periods, except the WSE of camel milk fermented by Lp.K772. The highest ACE-inhibition of the WSE from camel milk fermented by Lr.K777 was >80%. The proliferations of Caco-2, MCF-7 and HELA cells were more inhibited when treated with the WSE of fermented camel milk."

The molecular basis of the anti-diabetic properties of camel milk
"Over the years, strong evidence have been accumulated in favor of the beneficial effects of camel milk on glucose homeostasis with significant anti-diabetic properties in both human and animal diabetic models...  In this review, we speculated about the potential mechanisms and summarized few mechanistic-based studies that investigated the biological activity of camel milk and its protein components on the different aspects that may be involved in the anti-diabetic effects. A special emphasis is given to the molecular events engaged by camel milk proteins/peptides on two key aspects: insulin secretion and insulin receptor activity. Thus, the review gives a molecular rationale to the anti-diabetic effects of camel milk. This will help to identify the anti-diabetic agent(s) contained in camel milk and to understand better its mechanism of action in order to use it for the management of diabetes mellitus."

Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a traditional ethnomedical practice.
"These results suggest that, as an adjunct to standard management, daily ingestion of camel milk can aid metabolic control in young type 1 diabetics, at least in part by boosting endogenous insulin secretion."

Camel milk modulates the gut microbiota and has anti-inflammatory effects in a mouse model of colitis
"Our results showed that camel milk can prevent body weight loss and colon shortening, reduce the disease activity index, and attenuate colon tissue damage. Additionally, camel milk could reduce the over expression of inflammatory factors, inhibit the apoptosis of intestinal epithelial cells, and promote the expression of claudin-1, occludin, and zonula occludens-1 proteins. Moreover, camel milk effectively regulated intestinal microbiota in mice with colitis by increasing the gut microbiota diversity, increasing the abundance of beneficial bacteria (such as g_norank_f_Muribaculaceae, and Lachnospiraceae_NK4A136_group), and reducing the number of harmful bacteria (Bacteroides, Escherichia-Shigella). In addition, camel milk increased the levels of intestinal short-chain fatty acids. The results of the present study demonstrated that via regulating the intestinal microbiota, maintaining intestinal barrier function, and inhibiting proinflammatory cytokines, camel milk can ameliorate dextran sodium sulfate–induced colitis."

Camel milk regulates T-cell proliferation to alleviate dextran sodium sulphate-induced colitis in mice
"In the present study, the effects of camel milk (CM) on dextran sodium sulphate (DSS)-induced acute and chronic colitis in a mouse model were investigated. The results showed CM effectively alleviated the injury induced by DSS to the colon mucosa and imbalance of immune cells in mice. However, treatment with CM significantly increased the body weight of mice and decreased the disease activity index (DAI), histopathological score, proliferation of Th17 cells and concentration of inflammatory cytokine IL-17. The results from the present study indicate CM possesses intestinal protective effects."

Assessment of Broad-Spectrum Antimicrobial, Antibiofilm, and Anticancer Potential of Lactoferrin Extracted from Camel Milk
"Lactoferrin is a multifunctional glycoprotein present in mammalian milk. It possesses antimicrobial, antioxidant, immunomodulatory, and several biological functions...  The highest inhibitory effect of whole lactoferrin at the concentration (4 mg/ml) was observed against methicillin-resistant S. aureus (MRSA) and S. aureus, while 10 mg/ml concentration was effective against K. pneumonia, and 27 mg/ml was potent against multidrug-resistant (MDR) bacteria, P. aeruginosa. Likewise, MRSA was more sensitive toward iron-free lactoferrin (2 mg/ml) and hydrolyzed lactoferrin (6 mg/ml). The tested lactoferrin forms showed variability in minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) among tested bacteria. The scanning electron microscopy (SEM) analysis images revealed distortions of the bacterial cells exposed to lactoferrin. The antibiofilm effect differed depending on the concentration and the type of the bacteria; biofilm inhibition ranged from 12.5 to 91.3% in the tested pathogenic bacteria. Moreover, the anticancer activity of lactoferrin forms exhibited a dose-dependent cytotoxicity against human lung cancer cell line (A549)."

This page from Camel Milk For Health has a list of relevant studies regarding the nutrient content of camel milk, it's effectiveness at treating diabetes and autism, and more.  There is a lot of information on this site so I encourage you to look around.  It includes recordings of several doctors who presented findings at a symposium to study camel milk.

This page from Camel Milk USA also lists a number of studies, mostly about diabetes, but some other ones as well. 

Where to Get Camel Milk:

Dessert Farms

Camel Milk USA Discount Club

Camel Milk America

Camel Milk Association

OASIS Camel Dairy (they sell soaps, lotions, and other personal care products made of camel milk)

Camilk USA

This page from Camel Milk for Health lists a number of sources, including some outside the US.