Undermethylation leads to elevated histamine; elevated histamine causes undermethylation. In either case, simple changes to diet and addition of supplements can make a difference on the mood and other consequences of elevated histamine.
Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79±4 to 114±6 bpm), increased systolic blood pressure on standing (from 117±5 to 126±7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157±12 versus 117±9 in normal controls and 119±7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50±10 versus 17±3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but β-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
Do you have trouble with histamine? Research shows that mast cell activation syndrome induces a hyperactive immune system, causing the release of histamine.
Mast cell activation syndrome is a complex condition but one that is becoming more well-known. Mast cell disorder can also be classified as either being
Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS) are inter-related diseases.
What is Mast Cell Activation Syndrome? “Traditionally, Mast Cell Activation Syndrome (MCAS) was considered a rare disease generally focusing on the mast cell mediators tryptase and histamine and the blatant symptoms of flushing and anaphylaxis. New research indicates that it plays a large role in many chronic health conditions. Mast cells are coordinators of our […]
Mast Cell Activation Syndrome (MCAS) is a disorder where components of the blood stream, namely mast cells, secrete various substances
When to Suspect MCAD- while there are no two identical people with MCAD (like fingerprints) there are common themes that run through this community. At this time there is no "official" list but these symptoms appear common to those suffering with MCAD.
When I began my food elimination journey, before I even started to tackle the eczema I was experiencing, I was trying to get rid of hives. After being cleared of allergies, and doing some research, I found that in some cases hives can be a result of a histamine overflow.
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Everyone has heard of allergies, histamine, and especially antihistamines, but less people have heard of mast cells. Our doctors are able to differentiate between Mast Cell Activation Syndrome, Histamine Intolerance, and Mastocytosis that share many of the same symptoms but different root causes. At the Biologix Center, we conduct sensitive testing of your body using direct resonance testing. Learn more about Biologix Advanced Testing Techniques today!
Do you experience this, too?
Do you have trouble with histamine? Research shows that mast cell activation syndrome induces a hyperactive immune system, causing the release of histamine.
Do you experience this, too?
Can diamine oxidase help your histamine levels? Here's what you need to know to find a clean formula that works.
When Infection Triggers an Auto-Inflammatory Reaction Lyme disease is the fastest growing vector-borne disease in the U.S. today with an estimated 329,000 Americans affected annually. Studies have shown that anywhere from 10-60% of patients who are treated with a standard course of antibiotics for Lyme Disease, will have continuing, sometimes debilitating symptoms. The CDC calls this chronic condition "Post Treatment Lyme Disease Syndrome" (PTLDS). There is a growing body of evidence that demonstrates the reason for this condition may be due to an undiagnosed co-infection (like babesia bartonella, ehrlichia or anaplasma)[1] and/or treatment resistant Lyme bacteria, also known as persistent infection. (see my prior post on Lyme Persisters) The other possibility is that the infection triggers a dysfunction within the immune system. This can lead to an autoimmune or auto-inflammatory disease separate from or in addition to the infection. In this post I will be exploring how Lyme Disease can trigger an auto-inflammatory reaction through Mast Cell Activation. How The Immune System Reacts to Infection Some people with impaired immune systems may not immediately detect an infection, allowing for a delay in the immune response. Other invaders, especially those that are slow growers like HIV, Leprosy, TB and Lyme may have a sub-clinical phase during which the immune system fails to recognize the stealth infection allowing it to disseminate throughout the body. The immune system is divided into two categories called Innate Immunity and Adaptive Immunity. The innate immune system is the early defense mechanisms that activate when a foreign invader enters the body. The adaptive (or acquired) system is more complex in that it is able to recognize antigens on the outside of foreign agents and create an immune response that is specific to that infection. The adaptive system also forms memory cells capable of responding to future attacks. Early in the onset of an infection, the causative agent (virus, bacteria, protozoa, etc...) will provoke changes in a healthy immune system. This is called an immune response. Whenever cells or tissues of the body are injured or infected there is a resulting inflammatory response. Inflammation causes a vascular reaction with the purpose of delivering blood and healing nutrients to the area of injury. How Lyme Disease Hides in Connective Tissue Lyme Disease is caused by Borrelia burgdorferi a corkscrew shaped bacterium with an affinity for connective tissue[2]. Connective tissue is the most widely distributed, varied type of tissue found in the human body. It includes: loose connective tissue (epithelia, fascia, pleura, pericardial sac, esophagus, and the outer covering of blood vessels, nerves, and brain.); fat (adipose tissue); dense irregular connective tissue (skin, capsules around organs and fibrous sheath around bones); dense regular connective tissue (tendons and ligaments); cartilage (ear, larynx, joints, between ribs, intervertebral discs); bone (skeleton); and blood (erythrocytes, leukocytes, and platelets). Borrelia is known to spread to the Lymphatic system within the first 24 hours after infection.[3] During inflammation the lymphatic channels will maintain in an open position not only increasing flow of protein and lymphatics but also inadvertently spreading infectious agents. From the lymphatic system Borrelia will move to collagen rich areas of the body. Collagen is a type of connective tissue found in skin, bone, tendon, cartilage, synovium, the walls of blood vessels and the outer covering of nerves. (see my prior post on Decorin and Collagen) What Are Mast Cells The mast cell is an immune sentinel or "guard" that originates from stem cells in the bone marrow. It is found abundantly in the skin, respiratory tract, gastrointestinal and genitourinary tracts, but can also be found in clusters next to small blood vessels, the nervous system, and in loose connective tissue where Lyme likes to hide (see above). The purpose of a mast cell is to alert the immune system to outside invaders (wounds, bacteria, viruses, bee stings, allergens, etc). The surface of the mast cell is covered with IgE receptors which are very sensitive to allergens and parasites. When a foreign antigen comes into contact with the mast cell it will trigger the release of the contents of the mast cell. One of the contents is histamine, a powerful vasodilator which affects vascular permeability, smooth-muscle contraction, and secretion of certain mucosal cells. The histamine alerts the immune system which then helps to defend and clear the body of pathogens and allergens. If too many mast cells are activated at once the patient will undergo a life-threatening inflammatory reaction called anaphylaxis.[4] Watch This Short (2min) Video on Mast Cell and Histamine. What Is Histamine Histamine is a vasoactive mediator, chemically known as a biogenic amine. There are five biogenic amine neurotransmitters: dopamine, norepinephrine, epinephrine, serotonin and histamine. Histamine acts to mediate arousal and attention, as well as producing pro-inflammatory signals from mast cells to various cells within the immune system. These cells include macrophages, dendrites, T-lymphocytes, B-lymphocytes, endothelia, and antigen specific Th1 and Th2 T-helper cells. Histamine is responsible for stimulating stomach acid (HCL) and contributes to vasodilation and increased vascular permeability. Large amounts of Histamine are stored within the mast cells that are present in the granules of connective tissues. There are four basic histamine receptors in the body: H1, H2, H3 and H4 which I have highlighted below: click to enlarge Histamine is broken down by methyl compounds therefore high histamine levels may cause depleted methyl groups. Methylation defects (MTHFR) may lead to inability to clear histamine which may lead to histamine intolerance and a host of other disorders. In the central nervous system histamine is metabolized by Histamine N-methyltransferase (HNMT), and in the digestive tract it is broken down by Diamine oxidase (DAO) enzymes. Patients with low DAO levels are at increased risk for histamine intolerance (DAO SNP's can be seen on 23andME or diagnosed if plasma levels are below 10kU/L). Low DAO can be a result of genetics, or caused by gluten intolerance, leaky gut, SIBO, Crohn's, ulcerative colitis, and inflammatory bowel disease. [5] In addition to histamine, mast cells release a number of inflammatory mediators. I have included a partial list below: click to enlarge How Does Infection Trigger Mast Cell Activation While mast cells are primarily known for detecting allergens, recent studies suggest that they can be directly activated by bacterial infections. In fact, in a 1999 study, scientists were able to detect mast cell activation by Borrelia burgdorferi, the spirochete that causes Lyme Disease, although they were not, at that time, able to identify the surface molecule that triggered the activation.[6] Humans do not form an adaptive immunity to bacteria, and because all bacteria can form biofilm, there is a constant low level immune battle going on with all chronic infections. As the Mast Cells react to the bacteria they will release their contents (see table above) resulting in a continuous histamine reaction. Known Triggers for MCAD/MCAS If you suspect you have acquired Mast Cell Activation Syndrome (not a genetic defect) the question should be why. In addition to addressing the histamine, I believe you should also look to the root cause and treat that accordingly. The following is a partial list of known triggers for MCAD/MCAS. 1. Heavy Metals (The effects of Heavy Metal ions on histamine release) 2. Influenza Virus (Mast Cells and Influenza A Virus) 3. Parasitic Infections (Generations of Mucosal Mast Cells is Stimulated by Helminth) 4. Tuberculosis (Mycoplasma pneumonia - induced activation and cytokine production in Mast Cells) 5. Candida (Opportunistic Candida albicans elicits a temporal response in Mast Cells) 6. Fungal Infections (Role and Relevance of Mast Cells in Fungal Infections) 7. Epstein-Barr Virus (Computational discovery of Epstein-Barr Virus Targeted Genes and Pathways) 8. Lyme Disease (referenced #6 below) What is Mastocytosis Mastocytosis is caused by an over production of Mast Cells. These Mast Cells are also over active, in which they too easily release their contents. There are two basic types of Mastocytosis: Cutaneous (limited to skin), and Systemic (spread throughout the body), with several subtypes of each. (See AAAA&I Definition) With Mastocytosis excess mast cells build up in your skin, around blood vessels, within the respiratory system, gastrointestinal and urinary tracts or within the reproductive organs. Conditions Associated with Mastocytosis *Rheumatoid Arthritis *Lupus *Crohns Disease *Ehlers-Danlos Syndrome *Urticaria Pigments (cutaneous) What Is Mast Cell Activation Syndrome (MCAS) Mast Cell Activation Syndrome (MCAS) is caused by over active Mast Cells without an abnormal increase in the numbers of mast cells as seen in Mastocytosis. MCAS can be a result of genetics, or triggered by stress, sunlight, bacteria, mold, viruses, allergens, drugs, and chemicals. MCAS is often found in patients with Ehlers-Dalos syndrome (EDS) and postural othrostatic tachycardia syndrome (POTS)[7]. It is also found in a subset of patients with common variable immunodeficiency (CVID) and Lyme Disease. [8] To quote Dr. Theoharides (AKA- "The Mast Cell Master") "Mast cells are the 'universal alarm cell" that starts the inflammatory cascade. They can be triggered by infection, allergens, environmental factors like pollution, or even emotional stress. Once that happens, mast cells set into motion a series of inflammatory reactions, including the activation of immune cells and the release of tumor necrosis factor-alpha (TNF-a), a pro inflammatory protein or cytokine." Common Symptoms Associated with Mast Cell Activation Syndrome *Abdominal Pain *Anaphylaxis *Bloating *Bone Pain *Brain Fog (difficulty concentrating) *Fatigue *Flushing *Food Intolerance *Headaches *Insomnia *Mood swings *Lightheadedness *Nausea/vomiting *Panic attacks *Sensitivity to Multiple medications *Shortness of Breath *Skeletal lesions *Skin Rashes *Rapid Heart Rate Common Conditions Associated with Mast Cell Activation Syndrome *Acne *Allergies *Angioedema *Anxiety *Asthma *Chronic Fatigue Syndrome *Chronic pelvic Pain *Dermatitis *Depression *Dysautonomia *Eosinophil esophagitis *Fibromyalgia *Gastroesophageal reflux disorder (GERD) *Gluten Intolerance *Interstitial cystitis (bladder pain syndrome) *Irritable bowel syndrome *Migraines *Multiple chemical sensitivity syndrome *Osteopenia *Postural orthostatic tachycardia syndrome (POTS) What is Histamine Intolerance Histamine intolerance is suspected when a person has numerous adverse allergy-like reactions to foods, beverages, medications and other substances; yet shows negative results with allergy testing. The histamine intolerance is caused by histamine overload and/or diamine oxidase (DAO) deficiency. Diamine oxidase is the main histamine degrading enzyme with predominant activity in the gut. The clinical evidence for histamine intolerance is based on chronic headache, diarrhea, vomiting, heat flush, rhinitis and asthma-like symptoms.[9] What To Do If You Suspect A Mast Cell Activation Disorder I corresponded with Lawrence Afrin, MD a Professor of Medicine, Division of Hematology, Oncology and Transplantation at The University of Minnesota. Since the mid 2000's Dr. Afrin's clinical work has focused on hematology and mast cell disorders (See About Dr. Afrin Here). He says prior to beginning treatment for MCAD or MCAS it is important to have "at least a couple of points of laboratory evidence to meet current published criteria." Treated properly patients can live a normal healthy life, but like any complex illness improper treatment can exacerbate the condition. Dr. Afrin has just recently published a book entitled Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity. To Quote Dr. Afrin, "MCAS is a chameleon, difficult to identify for many reasons. It presents with different symptoms --which are often inflammatory or allergic in nature--to varying degrees in different places in the body." Recommended Diagnostic Tests For MCAD/MCAS Mastocytosis >Skin Biopsy >Bone Marrow Biopsy >Blood Work: (look for anemia, elevated histamine, low platelets (thrombocytopenia), high white count (leukocytosis), low albumin levels, or high tryptase levels, D-Dimer, Complement C3a, C4a. >Genetic Testing (see link) Mast Cell Activation Syndrome >Based primarily on clinical findings >Blood Work: Serum Tryptase (above 15g/ml), elevated Cytokines, C-Reactive Protein (CRP), Fibrinogen, Cytokine-panel + Tumor Necrotic Factor (TNF), Total IgE, Serum Diamine Oxidase (below 10K/ul), 24 hour urine for Methylhistamine (PGD2), Corticotropin (CRH), Platelet Activating Factor (PAF), Vascular Endothelia Growth Factor (VEGF), 5-HIAA. (add Catecholamines for POTS) >Other: Stool Test* (mast cells & eosinophils), Food Allergy Testing, Allergy Skin Testing *(GI Effects gdx.net has a very comprehensive stool test, micro biome, parasites, bacteria, etc.) Treatment: *Antihistamines H1, H2, H3, H4 (see Histamine Blockers in Table Above) *Alpha lipoid acid *Avoid Stress *Bisphosponates *Digestive Enzymes *Flavonoid *Hypolipidemics *Immunomodulation (allergy desensitization, stem cell transplantation) *Low Histamine Diet *Mast Cell Stabilizers (Cromolyn, Ketotifen, Luteolin, Quercetin, Interferon) *NSAIDS *N-Acetylcysteine *Probiotics *Proton pump inhibitors *Vitamin C *Tricyclic Antidepressants (antihistaminic) References: 1. About Lyme Disease Co-Infections 2. Dynamics of Connective-tissue Localization During Chronic Borrelia burgdorferi infection. Mast Cells 3. Lymphadenopathy During Lyme Borreliosis is Caused by Spirochete Migration-Induced Specific B Cell Activation. 4. Mast Cells 5. Sociedad Internacional Del Deficit De DAO 6. Borrelia burgdorferi Spirochetes Induce Mast Cell Activation and Cytokine Release. 7. Hyperadrenergic Postural Tachycardia Syndrome in Mast Cell Activation Disorders 8. Mast Cell Activation Syndromes. 9. Pseudo-Allergies Are Due to Histamine Intolerance Other: Basic Definitions (highlighted) from Wikipedia All Other References: Pathophysiology Clinical Concepts of Disease Process 3rd Edition Informative Links: -Understanding Auto-Inflammatory Disease -Mast Cell Activation Disease: A Concise Practical Guide for Diagnostic Workup and Therapeutic -Mast Cell Research -Video: Dr. Lawrence Afrin - Mast Cell Activation Syndrome -Dr. Theo Theoharides - Mast Cell Master -American Academy of Allergy Asthma and Immunology -National Institutes of Health Genetic and Rare Disease Information Center -Mast Cell Proliferative Disorders: Current View on Variants Recognized by the World Health Organization Other Helpful Links: -Jennifer Story: Mast Cell Activation Syndrome, Misdiagnosed as Lyme Disease -The Many Faces of Histamine Intolerance -Yasmin Ykelenstam - Healing Histamine: Natural Mast Cell Stabilizers for Histamine -Mast Cell Aware I will leave you with this final Quote from Dr. Afrin: You will not find another disease besides systemic mast cell disease that better illustrates the old “four blind men and an elephant” problem. There are lots of factors that go into every specialist looking at a patient with mast cell disease from a different perspective, seeing only the problems that they’ve been taught to see in their own domain. And in the first 13 years of my career post-fellowship, I practiced that way, too. As just one example, I can’t begin to count the numbers of patients I’ve seen in that time who’ve had “anemia of chronic inflammation.” Mysterious anemia, nobody knows why, no clear source of the chronic inflammation, and we just leave it at that. And it’s acceptable in the medical community to just leave it at that. For lots of reasons (many relating to our healthcare financing systems), the physician can’t spend nearly as much time with each patient as would be needed or desirable to get to the root of every mystery. So the hematologist sees the anemia, the gastroenterologist sees the irritable bowel syndrome, the rheumatologist sees the fibromyalgia, the cardiologist sees the palpitations, the neurologist sees the migraine headaches and neuropathy, and so on and so forth. We all just constantly miss the elephant.
My knees, fingers, and toes were constantly swollen, and my joints felt like they were on fire. Have you felt like this, too?
High histamine is the hallmark of MCAS, so many jump to a low histamine diet as the solution. But is it the right mast cell activation syndrome diet for you?
Do you experience this, too?
Yoga for Mast Cell Disease Patients Find some peace in stressful times with these 30 […]
When a diagnosis turned the things I loved most into the things that could kill me
What is Mast Cell Activation Syndrome? “Traditionally, Mast Cell Activation Syndrome (MCAS) was considered a rare disease generally focusing on the mast cell mediators tryptase and histamine …
Mast Cell Activation Syndrome (MCAS) MCAS is also commonly referred to as a type of Mast Cell Activation Disorder (MCAD). Let’s start with “what’s a mast cell?” Unless you’re a medical professional you’ve probably never heard of them. I certainly hadn’t. Mast cells are best known for releasing histamine and being a key player in
Try some mast cell stabilizing foods to improve symptoms of mast cell activation syndrome and histamine intolerance.
Mast cells are regulators & protectors of the human immune system. Mast Cell Activation Syndrome (MCAS) may occur if mast cells no longer function properly.
Systemic mastocytosis is a rare disorder characterized by accumulation of mast cells in organs such as the skin, liver, spleen, intestine, or bone marrow.
Do you experience this, too?
Low magnesium is often a problem with Mast Cell Activation Syndrome and Histamine Intolerance? Without enough magnesium, it can be hard ...
Systemic mastocytosis is a blood disorder characterized by infiltration of clonally derived mast cells in different tissues, including bone marrow, the gastrointestinal (GI) tract, the liver, and the spleen. What is the Pathology of Systemic Mastocytosis? The pathology of systemic mastocytosis is: -Etiology: The cause of systemic mastocytosis is a random change (somatic mutation) in
Discover hope and practical strategies for living with MCAS. Learn how a low histamine diet, natural antihistamines, reducing toxicity, and gut healing can offer relief.
And what you should know if you have a chronic illness.
