Mast Cell Activation Syndrome - MCAS, and Histamine

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Genetics may be a factor in who is more at risk for having excess histamine. There is an enzyme needed to break down the excess histamine from foods, within the intestinal tract, which some people may not be able to make. It can be purchased as a supplement and taken with meals. Other people may have overactive mast cells which are the type of immune cell that produces histamine throughout the body. (10 , 11)

     If the mast cells are overactive, MCAS - Mast Cell Activation Syndrome, symptoms may be more severe than a seasonal allergy type of histamine reaction and may include: "rashes, hives, itching, flushing, fainting, headache, abdominal pain, nausea, vomiting, gastroesophageal reflux disease (GERD), fatigue, chronic pain, trouble breathing and many more." (11) To complicate trying to figure out if this is a problem for oneself or a patient the overactivity of mast cells may also be associated with other complex conditions that have varied symptoms too, including: "allergies, autism, autoimmune disorders, cancer, diabetes, Ehler-Danlos syndrome, postural orthostatic tachycardia syndrome (POTS), fibromyalgia, Lyme disease, mastocytosis, migraines and obesity." (11) Add the various symptoms together and a person might have a confusing mixture of "twenty to thirty symptoms" and feel "extremely ill." (11)

    Lab tests frequently are not helpful for diagnosing many of the conditions or MCAS and it may also be unclear whether a person is having histamine symptoms because of intestinal digestion or microbiome problems or due to overactive mast cells throughout the body. Severity of symptoms may be worse if the problem is related to mast cell activation throughout the body. Treatment approach would also be different. Some people might be helped by use of the digestive histamine enzyme while others wouldn't need it. Both types, digestive histamine excess and mast cell over activity, would be helped by decreasing histamine containing foods or ones that increase release of histamine from mast cells. 

     Eliminating all histamine from the diet would be impractical if not impossible. Reducing the amount might make a significant difference though in reducing the negative symptoms. More details about identifying the type of problem with lab tests or other clinical indicators and an elimination diet description are available here: westonaprice.org. (11)

Overactive mast cells may involve cannabinoid deficiency. Mast cells have both Cannabinoid Receptor Type 1 and Type 2 on the cell surface and when activated they cause an inhibition of the mast cell.

• "Mast cells contain CB1 and CB2 receptors, which when activated inhibit mast cell release (R). Research shows that cannabinoids can suppress mast cell degranulation. ... Our results show that CB1 and CB2 mediate diametrically opposed effects on cAMP levels in mast cells. " (12, 13)
• "We have previously shown that exposure of mast cells to cannabinoids that bind to both CB1 and CB2 cause a net suppression in the proinflammatory responses." [...] "At short time points, ligation of either CB1 or CB2 leads to a suppression of cAMP levels. However, over a longer exposure time course, the cAMP responses that follow ligation of the two receptors are diametrically opposed. These results allow us to draw two conclusions. First, the results imply that CB1 and CB2 receptors are not redundant when co-expressed in mast cells. Secondly, the results suggest that the two receptors couple to distinct signalling pathways that diverge downstream of the Gαi/o proteins to which they are both coupled." (13) 
• "CBD alone without THC maybe ineffective at treating dysfunctional mast cells because THC has a strong binding affinity for both CB1 and CB2 receptors, cannabidiol (CBD) has no particular binding affinity. Instead, many of the therapeutic benefits of CBD are created through indirect actions." (12)

That may suggest that a short time, small amount of THC & CBD used may not help suppress the mast cells, by increasing cAMP sufficiently, while a longer exposure, larger dose might be needed for the inhibition - and that both the CB1 and CB2 receptor types need to be activated for the suppression of mast cell. CBD activates CB2 receptors and THC activates CB1 receptors

Edibles or smoke? "However, when it comes to MCAS patients who are more severe, they tend to not tolerate ingesting the Medical Cannabis oil or edibles but may can inhale the actual Organic Medical Cannabis Flower and find great relief from MCAS symptoms." (12). Vaporizers are available that can be used with good quality medical cannabis.

Mast cells are a type of immune cell that can release all of its stored chemicals or only particular ones. Some triggers might cause release of histamine while others might not. Mast cells tend to be located within specific tissue areas of the body or along epithelial layers (skin and membrane linings of blood vessels or other tissue), rather than be free moving like some other types of immune white blood cells. (10) Some people may have overactivity in some areas of the body rather than throughout the entire body. Mast cell activation may also be involved in autoimmune diseases including Multiple sclerosis, Type 1 Diabetes, and Rheumatoid arthritis. (10) The excessive release of cytokines and inflammatory chemicals can lead to cell damage in surrounding tissue. 

• More information about mast cells and what they do is included in Mast Cells: MCAS, genetics and solutions. geneticlifehacks.com (10). 

Viruses can activate mast cells, which then release histamine and other inflammatory cytokines and chemicals. The immune mast cells are also called granulocytes because when activated they release little packets, granules, full of the inflammatory chemicals. 

     Flu virus has been found to activate mast cells and mast cell inhibitors helped reduce lung damage and mortality in severe cases of influenza where an over-reaction of the immune response had occurred. Too much inhibition during an active infection might not be helpful though, because the goal is to kill the virus infected cells or other pathogens that can activate mast cells. (10) 

     Regarding COVID19 illness, the cytokine interleukin 6 (IL-6) tends to be present in excess, (17), and it is a mast cell activator. (10) Vitamin C can help inhibit IL-6. (16) 

Mast cell stabilizer medications and a COX2 inhibitor has been found helpful for MCAS.

Medications that may help reduce mast cell activation in Irritable Bowel Syndrome, a condition similar to Inflammatory bowel disease but less severe, include mast cell stabilizers and "a medication to reduce prostaglandin E2 synthesis (e.g. a COX2 inhibitor) stopped the hypersensitivity in the animal model of IBS. [ref]" (10) Pomegranate peel extract and other antioxidants may act in part through COX2 inhibition.(post) Prep tips for pomegranate & the peel, see: G13. Pomegranate.

Histamine promotes wakefulness, so an excess may lead to insomnia problems, and it affects a lot of varied behaviors and balance of functions throughout the body, disparate - a wide range of behaviors, which suggests why there can be such a wide range of symptoms, and homeostatic - balance of body functions - no longer as able to stay at an even center, too tired, or too excited, too cold or too flushed, numbness or pain - roughly. 

• "Brain histamine promotes wakefulness and orchestrates disparate behaviors and homeostatic functions." [...] "Dysfunctions of the histaminergic system may also contribute to the pathogenesis of multiple sclerosis and its murine model of experimental autoimmune encephalomyelitis," [...] "Histamine neurons send broad projections within the CNS that are organized in functionally distinct circuits impinging on different brain regions." (14)

Histamine may also lead to feeling too itchy too often.

• "Histamine itch and non-histamine itch are mainly mediated by TrpV1 and TrpA1 respectively. In addition, Trp channels can be coupled to cytokine receptors, toll like receptors or may even be directly activated by pruritogens." (15)

Inflammatory bowel disease (IBD) can involve overactive mast cells and excess histamine activating Trp channels in the intestines, (10), leading to sudden diarrhea and/or pain. "Pruritigens" refers to other chemicals that directly activate Trp channels such as horseradish or Latex that cause itching, (pruritus). Others may cause the bowel symptoms of IBD including cinnamaldehyde from cinnamon, capsaicin from hot pepper, curcumin in turmeric, and other chemicals in spices or herbs like ginger, cloves, and mint. Previous post 1, post 2/ webpage G3.5-3.6.2, G5.

Yes, it is not easy to figure out what you can eat if you have Mast Cell Activation Syndrome, or to safely use as skin care products or medications as some of the ingredients might be Trp channel activators.

Tips to worry less  - Think about whether you can do anything about the issue? If no, try to let the worry go. If the only thing you can control about a problem is your own attitude about it, then work on acceptance - attitude adjustment. Reframing problems as a blessing may be a stretch, but it might help to look at things as learning experiences, or a message to work on priorities. Pain and stress may be sending a message that delegating some tasks, or streamlining how you do something might be needed.

    Writing worries on notes and putting them in a worry jar is another idea - you did something about it. You can look through your worries later. If yes, plan your time - 1. write down your goals, long term - 5-10 years, mid length, this year, and short term, this day/week/month, and 2. make an action plan, what steps to take today, write a list. 3. Do your plan, cross off your list items. It can feel more organized and good to check off your short term goals, and more peaceful to have a plan. (18) 

Regarding the complexity of Mast Cell Activation Syndrome, or histamine from food - writing down your symptoms and daily food, beverages, and other lifestyle issues that standout from your routine can help to start seeing a pattern of which foods or habits might be adding to the problem. 

     Elimination diets are quite simple to start with only a few of the least allergy prone foods, and gradually more are added back later. It needs to be followed for a couple weeks to get the body cleared out of the potential problem foods and hopefully start feeling better, whether itchy, headaches, fatigue, brain-fog, or pain, numbness, or other symptoms. Then add only one thing back and see if symptoms return. Symptoms may be fairly immediate, or the next day or two so gradual reintroduction will be easiest to track whether it seems to cause symptoms.

     Lab tests and other help and medication may be nice too, if available, but an elimination diet can be done fairly easily and safely. Stick to a variety of foods from the different food groups and read bottles on any supplements or medications to check for ingredients that might also be trigger substances 'starch' is usually wheat or corn based unless specifically labeled like tapioca or arrowroot starch. See the resource links earlier on the page for food lists, a food diary and information about elimination diets for histamine issues. 

     Not all people have exactly the same sensitivities and there can be an additive effect, many problem foods on the same day as stress - may become a flare up. Some of the lists vary and some are more restricted than others, but most have similarities in the worst risk foods. Starting with eliminating some of those and seeing if you start feeling better can also be a way to work towards learning what are problem foods for you personally. 

The terminology and diagnostic criteria for mast cell over activity is still new. Some problems may include stimulation of mast cells without complete degranulation - release of histamine and other cytokines (IL-6 is a cytokine - a cell signal chemical) contained within the mast cell. The name ‘Mast Cell Mediator Disorders (MCMD)’ has been established for symptoms involving less severe mast cell activity than full degranulation. (25)

     The excess Interleukin-6 that is commonly seen in COVID-19 illness may lead to over active mast cells in people who did not have seasonal allergy or Mast Cell Activation Syndrome symptoms for most of their lives (it can be genetic based). "Constant IL-6 exposure can cause the body to form more reactive mast cells." (23)

     How mast cell activation relates to Long Covid survivors may also vary based on personal genetic and other unknown factors in their environment or body burden of toxins (yes, we tend to contain a large mixture of modern toxins and heavy metals, (26)). Histamine containing or promoting foods could be a factor that varies based on a person's diet and food sensitivities, in addition to mast cell activity throughout the body.

     Mast cell activation may vary based on what each individual is more sensitive to, as well as including some more typical problem foods or chemicals that everyone with overactive mast cells might find problematic. Symptoms can include a broad range and include mental health and behavior changes so diagnostic approaches might miss an inflammatory chronic immune response as the cause.

     In Long Covid there may be residual virus but it is possible, maybe probable, that there is simply an overactivation of the mast cell system continuing to react to any food or toxin or even stress.

Mast cells can be activated by viruses and are involved in defense against a viral infection. (20) People suffering with over activity of mast cells tend to not have very many colds or flu symptoms, even though they may have many other symptoms associated with the excessive inflammation and elevated histamine levels, or they may have lingering cases.

• "Colds and flu often last longer for people with Mast Cell Activation Syndrome or Histamine Intolerance. This is because these viral infections can set off a cascade of mast cell reactions lasting weeks or a few months." (24)

Suppressing a mast cell response while trying to actively fight a viral infection would be limiting the body's natural defense against a virus. Polyphenolic flavonoids are known to reduce mast cell inflammation and some have antiviral benefits such as luteolin.(20)

• "A recent report correlated coronaviruses infection with activation of mast cells and subsequent cytokine storms in the lungs.7 Mast cells are known to be triggered by viruses. 8" Inhibition of mast cell‐associated inflammation could be accomplished with natural molecules, especially the polyphenolic flavonoids.23 The flavone luteolin (not lutein, which is a carotenoid) has been shown to have broad antiviral properties.24, 25, 26" (20)

Luteolin is found in celery, thyme, green peppers, and chamomile tea. (21) Some with over activity of mast cells might do better with the celery and thyme. Green peppers may be a mast cell/histamine problem food (22) and chamomile tea is a flower which some people with seasonal allergies (mast cell activation) may react to. See reference G10.12, Nrf2 Promoting Foods, chamomile tea is discussed and may be beneficial for people who are not sensitized to its pollen. 

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.