Inflammation and mast cell activation syndrome
(My notes for an interview by Dr John Campbell with Dr Tina Peers)
She learned about MCAS because her daughter suffered terribly with eczema and other symptoms that a doctor identified as Histamine Intolerance and MCAS, and treatment made a huge difference for her. Dr Peers then began recognizing the syndrome in many of her own patients and providing them with answers, many of whom had given up on ever understanding their various chronic health issues. Her basic level guidance is for patients to take anti-histamines (blocking both H1 and H2 receptors), supplements including vitamin C (for its anti-histamine property), and following a low histamine diet.
The world leader in mast cell disease research is Dr Molderings at Bonn University. Mast cell diseases aren't taught in medical school so it's up to patients to tell their doctors about it if they have it. There are 2 conditions- Histamine Intolerance, which occurs when a patient doesn't produce enough diamine oxidase (an enzyme in our stomachs that reduces the amount of histamine in our food), and MCAS, which is when a person's mast cells release too much histamine too easily. Most of her MCAS patients are also diamine oxidase deficient (leading to increased absorption of histamine from food) so they get a "double whammy". In the medical literature, the incidence of Histamine Intolerance is approx 3-5%, but the incidence of MCAS is between 17-20% (According to Dr Molderings).
She also does genetic testing with her patients to look at their methylation markers and their histamine metabolism- she finds that her MCAS patients rarely have normal diamine oxidase production (the enzyme that breaks down histamine in the gut) and tend to have KIT gene mutations (the genes involved in coding for mast cells). There are 50 known variations of KIT genes. Symptoms and syndromes she ties to MCAS include eczema, rosacea, Chronic Fatigue Syndrome (ME/CFS), migraine and other headaches, rash,
urticaria, psoriasis, IBS, diarrhea, fibromyalgia, other joint problems, bloating, nausea and vomiting, interstitial
cystitis, POTS, and are hypermobile. She says 80% of MCAS patients are hypermobile (may have EDS) and 80% are female, and 30% have interstitial cystitis.
Dr Campbell gives a simple overview of mast cells- they are a type of white blood cell that resides in tissue rather than circulating. They trigger an inflammatory process when we want them to, including heat, pain, redness and swelling, which brings increased blood supply and nutrients to a damaged or infected area to help the healing process. Mast cells store histamine to release when needed, but they also store another 1,000 cytokines. They are concentrated in areas where our bodies are in contact with the outside world including our skin, lining the nasal passages, sinus passages, and respiratory system, they line the entire GI tract, they line the urogenital tract; she compares them to bouncers at a club who are just inside the door to stop "undesirables" from coming in.
In MCAS they become overzealous and pick a fight with all sorts of things, sometimes almost anything, that they come in contact with. When they react (degranulate), they release one or some or many of these different cytokines (often called mediators) and in various combinations, and they can release 350 chemokines which pass messages to other mast cells to join the reaction (this is how you get systemic reactions aka anaphylaxis). Mast cells also line our nerves, and histamine is also a neurotransmitter. Mast cells in the stomach (chromogranin cells) release stomach acid. Histamine plays essential roles in the body, but we need it to be carefully regulated so that we have only what we need, where we need it, and for how long we need it.
MCAS patients have excessive histamine lingering, as well as other chemicals that can cause bruising (heparin), elastase 2 causes membranes to break down, clotting factors contributing to clot formation. There is always inflammation and there may or may not be allergic-type reactions, including anaphylaxis, and dystrophisms which are formations of new tissue (abnormal tissue growth). Examples include cysts, often in the breast and pancreas (can also include skin tags, scar tissue, and fibroids). MCAS patients can also have poor wound healing. The symptoms a person experiences will correspond with where the over-reactive mast cells are concentrated, such as asthma occurring in people with abnormal mast cells in the lungs (in these cases inhalers may not work because the mechanism is different). For people with concentrations of mast cells in their skin, things as simple as their clothes rubbing on their skin or pressure from waistbands can cause itching and rashes or bruising.
Dr Campbell asks, given the enormous variation in presentation, how do you suspect and diagnose MCAS? Dr Peer responds that you recognize patterns of inflammatory symptoms, they often have sensitivities including to things touching skin such as tags, as well as a very heightened sense of smell and aversion to bright lights and loud noises. You also have to consider what other conditions might also produce the pattern of symptoms the patient is presenting with. Testing for cytokines can help but need to be developed more. The more the mast cells are triggered, the more sensitive the person can become over time. Infections can make MCAS worse. She says there is "consensus 1" criteria, which requires a positive blood test for specific markers and rules out many people, and "consesnsus 2" criteria that don't require the blood test. Instead, consensus 2 says that if the provider has a reasonable suspicion of MCAS that they can try some of the basic treatments and lifestyle changes, including some basic medications, and if the patient improves significantly, it can be inferred that they do have MCAS.
There is a website called "what the bleep can I eat .com" that has a good list of histamine levels in foods. It's worth noting that there is a lot of innacurate information online about histamine levels in foods. The site lists about 200 foods that have no, or very low histamine levels. Some of the very high histamine foods include tomatoes, bananas, avocados, spinach, gluten, tea and coffee, green tea, alcohol, chocolate (the last 3 also block diamine oxidase production). Processed foods tend to be high in histamine, as well as leftovers (anything being re-heated or left around for awhile) because bacteria present on foods converts the amino acid histidine to histamine. You can think of a "histamine bucket" in the sense that it takes a certain amount of exposure to add up to the level that triggers a reaction, so a person may get away with a food one day but not another day.
A person can take diamine oxidase supplements when eating to help reduce the histamine load (DAO supplements)- as an aside, these often contain ingredients that are problematic for MCAS people so be careful with them. Pea shoots have a high level of diamine oxidase and eating some of them before a meal can also help. In the big picture MCAS people do best on a ketogenic or paleo diet, with fewer carbohydrates, because these diets are so anti-inflammatory. In addition to dietary changes, some supplements help, including vitamin C which has anti-histamine and antibiotic properties, and is anti-inflammatory. Vitamin D with K2 is also important, as is magnesium, CoQ10, l-carnitine (acetyl), and iodine, things to support the mitochondria.
MCAS people get mitochondrial dysfunction which then limits energy production. Our cells have thousands of mitochondria in each one- our mitochondria produce 70-80kg of ATP every day (this is because as soon as we make it, it's gone, so it's made at a high frequency). Our mitochondria are 32% of our body weight. Our heart has the highest density of them, and then the liver. The post-exertional malaise, the hallmark symptom of ME, is due to mitochondrial dysfunction such that they can't produce ATP at the rate the person's body needs it. Most of us (in the UK and America?) have low iodine levels in our bodies. Iodine is important for the glands, including breast, thyroid, thymus, and prostate. She instructs her patients to take 2 to 3 drops of Lugol's 15% before bed, in water. It supports mitochondria but it also keep the upper gut sterile, which it should be. Seaweed is a good food source, surprisingly, fish does not.
So much inflammation comes from the gut, there are so many mast cells in the gut. Getting the inflammation in the gut under control is a really important part of getting MCAS under control and managed because the inflammation in the gut spreads to other parts of the body. As an aside, Dr Campbell mentions that an oncologist he knows has told him that a lot of cancer seems to come from chronic inflammation, including the gut, and that iodine supplementation can reduce the chances of developing cancer. Mitochondrial dysfunction also seems to be critical in getting cancer, because it's the mitochondria that signal cell death when a cell has mutated and is growing out of control. Inflammation in the gut leads to leaky gut, which means that whole proteins can get into the bloodstream instead of their breakdown products, amino acids. Inappropriate proteins in the bloodstream wreak havoc, including triggering allergies.
The lining of the gut is only one cell thick, and their are mast cells directly behind those cells. If the mast cells swell, they can cause cracks to form between the cells lining the gut (leaky gut). The first 20 feet of our guts are supposed to be sterile, but since our modern diets include sugar, dairy, and some other things, bacteria that should be killed are instead being fed and multiplying, and causing inflammation. Eliminating all sugars and refined carbohydrates would be best for most people, but people with MCAS should be low-histamine ketogenic. Sugars and carbs are addictive- instant gratification. We want a microbiome, but it should be in the colon. Taking iodine won't affect that part of the gut. Eating in season when possible. You can break the addiction to sugar in 2 weeks- there is a gene that switches off. Good probiotics help.
Figuring out a medication regime for each person is a slow process of trial and error. She suggests starting with the over-the-counter anti-histamines, one at a time, in higher doses than on the box. Once you've found one that works, add in famotidine, which is an anti-histamine for H2 receptors (mostly in the gut, but also in the heart and brain). After that, mast cell stabilizers are added. Quercetin at 500mg 3x a day is easy because it's available OTC. Prescription meds in this category include Ketotifen (in America this has to be compounded because there is no commercial version for oral use), working up to 1mg at night. If that doesn't help, there is Rupatidine- people take one or the other. The third medication is Gastrocrom (cromolyn sodium), that stays in the gut. MCAS with IBS symptoms tend to do well on Gastrocrom. Each patient takes their own cocktail of medications and treatments. LDN (Low Dose Naltrexone) is very helpful for many people with MCAS.
Dr Peet is also using medicinal mushrooms for their immunomodulatory capabilities, to help calm the mast cells. She emphasizes that the mushrooms must be very high quality. Mushrooms themselves are high in histamine, but extracts can be made that leave the histamine behind. The sunshine mushroom is a mast cell stabilizer, reducing histamine and cytokine release from mast cells. She recommends the company Hefasta Terra, a Spanish company- their products are organic and tested, no fillers, and they grow the mushrooms themselves. They also do clinical research. She recommends Myco Sol (sunshine mushroom) and Myco 5, which contains sunshine mushroom, reishi (balances hormones, lowers anxiety, improves sleep, anti-inflammatory, analgesic), chaga (kills cancer cells), shiitake and mistake (treats mycotoxins). Lion's Mane mushroom crosses the blood-brain-barrier and can stimulate growth of neurons.
Mast cells can live for 2 to 4 years- some are replaced sooner, but it can take patience to heal from severe MCAS for this reason. New mast cells can become over-reactive when they enter tissues where the existing mast cells are already edgy, this can perpetuate the problem. Dr Peet says that CIRS (Chronic Inflammatory Response Syndrome) from mold can co-occur with mast cells and can look nearly identical to MCAS but she implies that it needs to be considered separately. Lyme Disease and Epstein-Barr (HHV-5) can also be very similar. She says you don't want to miss any of those if they are comorbid with the MCAS.
Tryptase is an enzyme that is released by mast cells when they degranulate under certain circumstances, and is the source of a great deal of controversy in the MCAS world. In 2012, a consensus statement (consensus statement 1) was put out by some of the doctors and researchers who had been working on mast cells stating that there needed to be an elevation in serum tryptase for MCAS to be diagnosed. The year before that, another statement (consensus statement 2) had been put out by about 40 of the doctors and researchers working in the field who made a broader definition of MCAS that was based on the patients they were seeing which was more flexible in its diagnostic criteria. The authors of consensus statement 2 argued that in many parts of the world, it's not always possible to get a serum tryptase level measured, and they noted that many patients who they were treating with success didn't have elevated serum tryptase levels anyway. Statement 1 excludes many people with the profile of MCAS and denies them treatment. Many people feel that if the treatment works, that is good evidence that MCAS is present.
