New and Experimental Treatments for Mast Cell Disease and Allergy

Nanoparticles Targeting Mast Cells Prevent Allergic Reactions in Mice
Researchers at Northwestern University successfully used a new treatment to prevent anaphylaxis in allergic mice using nanoparticles that targeted the mice' mast cells.  These nanoparticles were coated with molecules meant to function as allergens, and another molecule- called Siglec-6 that- that signals mast cells not to react.  The result was that the targeted mast cells were deactivated, which protected the mice and kept them from experiencing anaphylaxis.  "In one final experiment, mice sensitized to an IgE allergen were given the nanoparticle infusions with the two antibodies, and exposed to their allergen. None experienced signs of an allergic reaction."

Mast Cells, MCAS, and Psychiatric Symptoms

Brain mast cells link the immune system to anxiety-like behavior
"Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior."

"Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links."

 

 

Dietary Fats and Oils

 (in progress)

Is Saturated Fat Bad For You?
Ketogenic diet therapy doesn't have to include any saturated fat; many people eat a vegan keto diet or one that is vegetarian without dairy, or some other specialized form of keto.  It's possible to make a keto diet that is compliant with almost any other restriction, such as vegan, vegetarian, Mediterranean, carnivore, and others.

Saturated fat, the estimated absolute risk and certainty of risk for mortality and major cancer and cardiometabolic outcomes: an overview of systematic reviews
Absolute risk is much more informative than relative risk- relative risk sounds more catchy but doesn't actually tell you as much.  When thinking about what a study means for you, whether its conclusion means you need to make changes, depends on the quality of evidence and not just the presence or absence of evidence.  This paper found that the evidence supporting a risk from consuming saturated fat was low or critically low quality.  When looking at the results of reducing or replacing saturated fat in terms of cancer mortality, the authors found that the evidence showed a range of 8 fewer deaths to 3 additional deaths per 1,000 people, and the certainty of evidence (quality) was low to very low.  So no clear-cut link between saturated fat consumption and risk of death from cancer.  When considering the impact of saturated fat in the diet and cardiac deaths, they found a rate of two deaths per 1,000 people with low to moderate certainty.  This does not support the strength of the message we get through doctors and public health to avoid saturated fat.

There are other factors to consider when seeing if the results of a study means anything for you individually.  To illustrate this point, consider one study that was included in this meta-analysis (with moderate quality evidence) that found 24 fewer deaths per 1,000 people from all-cause mortality in a treatment group that reduced saturated fat intake.  We need to look at the details to see what the implications are.  Most people being studied are eating the standard American diet, high in ultra-processed foods, and get their saturated fat from sandwiches, desserts and sweet snacks like cookies, cakes, ice cream, pastries; and rice and grain-based dishes like pasta and pizza, and milk and yogurt which is usually sweetened and flavored.  These foods are all high in sugars and simple starches.  Natural foods, including plain meats, cheeses, butter, etc are lower on the list.  The question then is how do you eat- if you eat lots of junk food, fast food, and processed food, then this study might apply to you.  If you already eat a diet primarily of whole foods and low processed foods then these results probably have no relevance for you.

"Nutrition science is full of low quality evidence that applies to a general population eating a low quality diet".  As a patient, we all deserve to have care providers who treat us as individuals.

A short history of saturated fat: the making and unmaking of a scientific consensus 

Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based?

Mast Cell Disease and Long COVID (aka PACS)

Long COVID and MCAS
Post-COVID Conditions: Information for Healthcare Providers
This is the CDC's current guidelines for treating Long COVID and they specifically mention MCAS as a possible cause of Long COVID symptoms that should be addressed.  They do not give information about diagnosing and treating MCAS however (here is the site they link to for more info about MCAS).

Missouri doctors make discovery about possible cause of long COVID
"Dr. Leonard Weinstock, a gastroenterologist at Missouri Baptist Medical Center, and others found that mast cell activation symptoms were increased in long COVID-19 patients.  Weinstock and his team hypothesized that the mast cell activation could cause long COVID-19 symptoms. They also believe that long COVID-19 symptoms could be mitigated by preventing mast cell activation."
The study referenced in this article can be found here.

Immunological dysfunction and mast cell activation syndrome in long COVID
"Long COVID-19 is the consequence of multiple immune system dysregulation, such as T-cell depletion, innate immune cell hyperactivity, lack of naive T and B cells, and elevated signature of pro-inflammatory cytokines, together with persistent severe acute respiratory syndrome-coronavirus 2 reservoir and other consequences of acute infection. There is an activated condition of mast cells in long COVID-19, with abnormal granulation and excessive inflammatory cytokine release. A study by Weinstock et al. indicates that patients with long COVID-19 suffer the same clinical syndrome as patients with mast cell activation syndrome (MCAS). Diagnosis and treatment of MCAS in patients with long COVID-19 will provide further symptomatic relief, and manage mast cell-mediated hyperinflammation states, which could be useful in the long-term control and recovery of such patients."

Mast cell activation symptoms are prevalent in Long-COVID
"In the present study, there was a high prevalence of MCA symptoms in LC patients prior to MCAS treatment. The symptom data and spider web plots illustrated that LC patients’ symptoms are virtually identical to those experienced by MCAS patients. These results support, but do not provide definitive proof of, our earlier hypothesis that LC might often arise out of a SARS-CoV-2-driven provocation of primary or secondary MCAS. Theories to explain promotion of MCA in LC include: 1) complex interactions of stressor-induced cytokine storms with epigenetic-variant-induced states of genomic fragility to induce additional somatic mutations in stem cells or other mast cell progenitors; 2) cytokine or SARS-CoV-2 coronavirus activation of mast cells and microglia; 3) dysregulation of genes by SARS-CoV-2 coronavirus leading to loss of genetic regulation of mast cells;  4) development of autoantibodies which react with immunoglobulin receptors on mast cells,  and 5) increase in Toll-like receptor activity by the coronavirus.  

In this study, MCA symptoms were significantly increased in LC. Uncontrolled, aberrant mast cells may in part underlie the pathophysiology of LC. Inflammation caused by COVID-19 is complicated, and other immune disturbances that have been seen in the acute infection such as excess dysfunction of the macrophage and serotonin release from platelets might or might not play roles in LC"

MCAS activated by Long COVID or PACS or by MIS-C or PIMS and MCAS activated by Vaccines or by Post Vaccine Syndrome: CRITERIA FOR CLINICAL DIAGNOSIS
"In Long COVID or Post-Acute COVID Syndrome (PACS), in Multisystem Inflammatory Syndrome in children (MIS-C or PIMS) and in Post Vaccine Syndrome, in addition to the symptoms of Hypoperfusion, Hyper-coagulability and Microclots (HHM), it is very important to identify the symptoms associated with Hypersensitivity (HS), Allergies, Histaminosis and Mast Cell Activation Syndrome (MCAS) which are also a frequent cause of persistent symptoms. But, several of the patients who present persistent symptoms after having COVID or MIS-C are not diagnosed in a timely manner for Histaminosis, Tryptasemia, , mast cell activation disorder (MCAD), MCAS, and several years may pass and they may even be admitted to a hospital or psychiatric center. with a treatment that does not correspond, so we have considered it convenient to disseminate for free the criteria that we have developed, which have taken as reference the current International Consensus Criteria for MCAS, which gives a high level of support for your application. The references of the scientific publications taken into account are available in the document at the following link: https://www.researchgate.net/publication/376047625 In a similar way to what occurs in Long COVID or PACS and in MIS-C or PIMS, vaccination against COVID can cause the activation of an MCAS in a patient who did not have it, or the enhancement of an already existing MCAS, therefore we have included the diagnosis of MCAS activated by COVID Vaccines or by Post-Vaccine COVID Syndrome, and we must mention that there is a significant number of these cases without, to date, having agreed upon and disseminated criteria for their adequate diagnosis and treatment."

 

How to Treat Long COVID

 Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study

Evaluation of nutrition risk and its association with mortality risk in severely and critically ill COVID-19 patients
"Most severely and critically ill patients infected with SARS CoV-2 are at nutrition risk.  The patients with higher nutrition risk have worse outcome and require nutrition therapy."

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey
"Recent evidence suggests that oxidative stress and endothelial dysfunction play critical roles in the pathophysiology of COVID-19 and Long-COVID. We hypothesized that a supplementation combining L-Arginine (to improve endothelial function) and Vitamin C (to reduce oxidation) could have favorable effects on Long-COVID symptoms.  Our survey indicates that the supplementation with L-Arginine + Vitamin C has beneficial effects in Long-COVID, in terms of attenuating its typical symptoms and improving effort perception."

Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial
"Long COVID, a condition characterized by symptom and/or sign persistence following an acute COVID-19 episode, is associated with reduced physical performance and endothelial dysfunction. Supplementation of l-arginine may improve endothelial and muscle function by stimulating nitric oxide synthesis.  l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population."

Alleviation of Post-COVID-19 Cognitive Deficits by Treatment with EGb 761®: A Case Series
"In many studies, EGb 761 has been demonstrated to protect endothelial cells, to have potent anti-inflammatory effects, and to enhance neuroplasticity. CASE REPORT Here, we report for the first time the application of EGb 761 in the therapy of post-COVID-19-related cognitive deficits. Three women and 2 men, aged 26 to 59 years (average age 34.6 years), presented with concentration and attention deficits, cognitive deficiencies, and/or fatigue 9-35 weeks after infection. A daily dose of 2×80 mg of EGb 761 did not cause any detectable adverse effects, and it substantially improved or completely restored cognitive deficits and, when initially present, also other symptoms, such as fatigue and hyposmia, within an observation period of up to 6 months."

NAD+ in COVID-19 and viral infections
"NAD+, as an emerging regulator of immune responses during viral infections, may be a promising therapeutic target for coronavirus disease 2019 (COVID-19). In this Opinion, we suggest that interventions that boost NAD+ levels might promote antiviral defense and suppress uncontrolled inflammation. We discuss the association between low NAD+ concentrations and risk factors for poor COVID-19 outcomes, including aging and common comorbidities. Mechanistically, we outline how viral infections can further deplete NAD+ and its roles in antiviral defense and inflammation. We also describe how coronaviruses can subvert NAD+-mediated actions via genes that remove NAD+ modifications and activate the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Finally, we explore ongoing approaches to boost NAD+ concentrations in the clinic to putatively increase antiviral responses while curtailing hyperinflammation."

Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study
"Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies.

Thiamine also works as a carbonic anhydrase isoenzyme inhibitor; thus, high doses of thiamine given to patients at the early stages of COVID-19 could limit hypoxia and decrease hospitalization [16]. Additionally, an in-vitro study found that high-dose thiamine lowers the T-helper cells (Th-17) cell pro-inflammatory response believed to be associated with the COVID-19 cytokine storm [17]"

Therapeutic Prospects for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-vitro Evidence and Pharmacokinetic Profile
"Three-week of 200 mg daily thiamine treatment significantly lowered the baseline IL-17 levels while increased IL-22 levels (anti-inflammatory response)."

"Somatization Disorders" are Rebranded Hysteria, Eugenics

The following is a comment I submitted as written testimony for a legislative hearing in Oregon regarding reclassifying various pain disorders with Somatoform Disorders in the state's medical code system:

I wish to address the proposal to group Fibromyalgia and chronic pain disorders with Somatoform Disorders.  When a patient presents to the doctor with physical symptoms, including pain, there is nothing scientific about assuming that the patient has a mental health condition rather than a physical one, and that mental health treatment is appropriate.  Cursory testing does not rule out the presence of a physical condition.  Many legitimate physical conditions aren't correctly diagnosed for many years, and may be misdiagnosed many times in the process.  For example, on average a person with celiac disease is properly diagnosed 8 years after first presenting to a doctor with symptoms.  During those 8 years, it can be said that no physical cause has been found for the patient's distress, but it makes no sense to say that they have a psychiatric condition that they are miraculously cured of when they are finally correctly diagnosed with celiac. 

The fact that there are simply so many physical conditions with a significant lag time between the time when a patient presents with complaints and accurate diagnosis should cast doubt on the usefulness and even the existence of actual somatoform disorders.  I lost count a long time ago of the number of cases I know of in which a person presented to the doctor with pain and other non-specific symptoms, was patronizingly dismissed and told to get counseling, eventually given pain meds, and then finally given testing only to be told that they have late stage cancer.  In a number of cases they were actually told "if only you'd come in sooner, we could have treated it".  Many of those people died.  It is also worth noting that new disorders are still being discovered, that medical testing is never 100% accurate, and there are over 7,000 rare diseases listed by the National Organization for Rare Diseases.

Somatoform Disorders are basically the updated name for "hysteria", an archaic concept based more on the misogynist ideas of it's time than any physical reality.  At that time, medicine was considered "scientific", but not exactly in the way we see it now- as a practice based on the sciences of biology and chemistry.  At that time, eugenics was considered science, and was deeply enmeshed in the theory and practice of medicine.  This historical reality has been swept under the rug, but the pseudoscience of eugenics still lingers in the medical practices of today- and I believe that the concept of "Somatoform Disorders" is one example.

The practice of medicine requires that patients be listened to and treated as the experts about life in their own bodies.  Treating them as misbehaving children, putting on a show for attention, has no place in a scientific practice.  I myself was subjected to this gaslighting and abuse for years while struggling to survive an illness which is life-threatening on a daily basis.  I was shamed and shunned until I myself arranged to have a tissue sample from a previous biopsy prepared by the lab that was storing it according to the instructions I got over the phone from the leading pathologist in the country for the disease that I knew I had, and then shipped to her hospital by Fed Ex.  Once she gave me the diagnosis, I was taken seriously and received more than 10 additional diagnoses. 

The delay in treating my medical condition, which I had been both laughed at and yelled at for daring to suggest I had, caused my condition to degenerate such that I have lived on life support since then.  At my lowest point, I was on oxygen, unable to eat and dependent on IV nutrition to survive, requiring continuous infusions of 2 medications, needed a central line which has resulted in 2 DVTs and 15 blood infections, was mostly bed bound, my back broken in 5 places, unable to take any pain meds and needed to undergo my surgeries without anesthesia, had skin cancer removed, had all of my teeth removed due to breakage, have had multiple heart attacks, and more.  There are many, many other people like me.  Most haven't survived.  You could say that "Somatoform Disorders" have a very high fatality rate- but not for the same reason that other deadly disorders do.  Please, it's the year 2024- isn't it time that our medical system reflected that?

This recent study shows examples of people with legitimate physical disease who were misdiagnosed with psychosomatic and psychiatric conditions, and the long-term harm it did them:

“I still can’t forget those words”: mixed methods study of the persisting impact on patients reporting psychosomatic and psychiatric misdiagnoses
"Patient-reported psychosomatic and psychiatric (mis)diagnoses are associated with persisting adverse impacts in multiple domains including mental health, medical relationships, self-worth, and some healthcare behaviours. Health services and clinicians should consider these potential adverse impacts on patients and offer support to reduce any persisting negative impacts."

The Martha Mitchell Effect
Martha Mitchell was married to the attorney general in the Nixon administration, John Mitchell.  She spoke up about the illegal activities that she was witnessing, but her claims were written off as delusional until the actual events of the Watergate scandal became public, when she was vindicated.  Sometimes a patient reports events to a doctor or other health care provider that the provider finds difficult to believe and considers to be delusions even when what the patient is reporting is actually true.  This is called the "Martha Mitchell effect" in reference to her experience of being wrongfully considered delusional.  This is particularly likely to happen when a patient's symptoms are the result of the malicious actions of another person, such as harm resulting from harassment or abuse.  This might include poisoning, stalking, gangstalking (group harassment), or gaslighting.  Abusers sometimes deliberately do things to their victims that make the victim sound crazy if they report it.  This is also more likely to occur if the patient reports harm from a medical procedure, treatment, or another medical provider, or from someone who is powerful or well known.

This effect was seen recently when some people presented to the hospital during the COVID 19 pandemic suffering adverse events from the COVID vaccines and were diagnosed as delusional when they were suffering actual side effects that were later acknowledged by the medical establishment and public health authorities.

Examples of medical gaslighting include:

Inappropriate Sinus Tachycardia
https://syncope.co.uk/inappropriate-sinus-tachycardia/
“Like Postural Tachycardia Syndrome IST is underappreciated by many in the medical profession and many doctors mistakenly consider it to be a psychological condition. People with IST can find themselves increasingly disabled and may experience high levels of anxiety.”

The Case of CIRS (Chronic Inflammatory Response Syndrome) and Mold Illness
There are many examples of medical conditions that were first described by patients and doctors, for which no physical cause was found for many years.  They were given "placeholder" names as syndromes until such time as their biological mechanism could be figured out, which they eventually were.  There is a list of conditions including Sick Building Syndrome, Chemical Sensitivities, Environmental Illness, Chronic Inflammatory Response Syndrome (CIRS), Toxicant Induced Loss of Tolerance (TILT), Mold Illness, Biotoxin Illness, that had been identified accurately based on patient reports, and in some cases treatments were even discovered based on patient reports of benefits.  These conditions are now understood to be manifestations of Mast Cell Disease, Mitochondrial Dysfunction, and genetic variants that limit detoxification of various compounds capable of inducing excessive inflammation, among other things.  The biological understanding came in time and validated the experiences that patients reported.