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Article summary:

• Histamine is a vital part of the body’s immune defense system.
• When a person has allergies, their immune system views specific allergens as threats. It responds by releasing histamine to remove them.
• Only certain cells in the body can make histamine.
• Anaphylaxis is a quite serious and life-threatening allergic reaction.
• Mast cells are a type of white blood cell found in human tissues that detect and respond to foreign substances, like allergens.
• When triggered, mast cells become activated and explode (degranulate), releasing a variety of chemicals called “mediators.” One of these mediators is histamine. 
• Mast cells and their mediators are essential for normal bodily functions. Problems arise when these cells become overactive. 
• Histamine intolerance comes from histamine building up to a level that exceeds the amount the body needs. 
• Symptoms of histamine intolerance appear to worsen by eating foods and beverages that are naturally high in histamine or participating in activities that stimulate histamine release.
• Mast cell activation syndrome (MCAS) is a condition where there is mast cell dysfunction. It results in symptoms that span a wide range of bodily and organ systems.
• People with MCAS may experience repeated episodes of acute anaphylaxis (severe allergic reaction).
• Low histamine diets, supplements, opening drainage pathways, and addressing root causes are natural options to address histamine levels in the body. 

You’re probably familiar with the word “histamine,” although most likely in the context of “antihistamine.” When faced with typical allergy symptoms or a runny nose from a cold, many people reach for antihistamine medications. But the vast majority never considers how or why antihistamine works, or knows anything about histamine.

Histamine is part of the body’s natural defense system. The immune system produces these organic compounds in response to allergens (substances that trigger an allergic reaction). Histamine initiates the process of removing allergens from the body or skin. 

However, as histamine performs its job of ridding you of allergens, they can trigger typical allergy symptoms. You itch, sneeze, or tear up in the process. While histamine performs a useful and necessary role, they can also cause way more problems than most people realize.

Allergens—such as dust, mold, pet dander, or pollen—may not affect some people. But if you have allergies, your immune system views specific allergens as threats. It responds by releasing histamine to remove them. Your body’s immune system is only trying to keep you safe by releasing histamine. However, it overreacts, giving you those all-too-familiar allergy symptoms… or sometimes, much worse.

A Deeper Look at allergic reactions

When the body encounters an allergy trigger, the immune system initiates a chain reaction of events to defend against the threat.

1. The immune system “sees,” or recognizes, an allergen. →
2. The immune system sends a chemical signal to specialized cells (mast cells) in the blood, gut, lungs, mouth, nose, and skin. →
3. The mast cells receive the signal and release histamine, which is stored within them. →
4. As the histamine exits the mast cells, it increases blood flow to the allergen-affected area. →
5. This results in inflammation, which signals other substances from the immune system to step in and carry out repairs. →
6. Histamine travels and then attaches itself to specific receptors in the body. →
7. Once at the receptor site, histamine acts to rid the body of the allergen.

Histamine can cause membranes to make more mucus, resulting in a stuffy or runny nose. They also may create hives, itchy eyes and skin, skin rashes, and sneezing. Histamine-induced irritation might also affect the throat, prompting a cough.¹

Along with these symptoms, a more serious reaction could result in anaphylaxis, which can be life-threatening. 

Anaphylaxis

Anaphylaxis is a severe allergic reaction that leads to anaphylactic shock. If not treated immediately, anaphylactic shock can be fatal—a critical difference from other allergic reactions. Anaphylaxis also usually involves more than one system of the body. With anaphylaxis, you may experience:

• Cardiovascular-related symptoms, such as fainting, low blood pressure, and rapid pulse
• Gastrointestinal tract symptoms, such as abdominal cramps, diarrhea, nausea, and vomiting
• Lung-related symptoms, such as difficulty breathing, shortness of breath, throat swelling, and wheezing
• Skin-related symptoms, such as flushing, hives, itching, and swelling

Mast Cells

Mast cells play a vital part in your immunity, and stem cells in the bone marrow produce them. They’re found in most tissues throughout the body, especially those in close proximity to the outside environment. This includes the GI tract, lung, nose, and skin. They also interact closely with neurons (nerve cells).²

As a primary immune function, mast cells detect and respond to foreign substances. When triggered by foreign substances, these little cells become activated and explode (or degranulate). This process releases a variety of chemicals called “mediators.”³

Mediators manage other reactions and play many other yet to be discovered roles. There are over 200 mediators stored within the granules of mast cells, including histamine. While the nervous and digestive systems also have cells that can produce histamine, mast cells are the primary source of histamine in the body. ^4 5 

Though best known for their role in allergies, mast cells are also involved in the following:⁶ 

• Defense against pathogens
• Development of immune tolerance
• Formation of new blood cells
• Inflammatory processes
• Maintenance of blood-brain barrier function 
• Wound healing
  

Mast cells and their mediators are essential for normal body function. However, problems arise when these cells become overactive, as they do in individuals with Mast Cell Activation Syndrome (MCAS). Alongside MCAS, histamine intolerance is another potential problem from excess inflammatory responses.

Histamine Intolerance

Histamine intolerance or sensitivity comes from a buildup of histamine that exceeds the standard amount required for normal functioning. Under routine conditions, certain enzymes break down excess histamine. More specifically, diamine oxidase (DAO) is the main enzyme tapped to break down excess histamine. 

The substances produced from histamine breakdown are then sent to the kidneys and excreted in the urine. Under normal conditions, this ensures that histamine levels do not exceed the level above where symptoms start to appear, or the “limit of tolerance.” However, without enough diamine oxidase to deal with an overabundance of histamine, histamine levels increase. The excess histamine causes symptoms that resemble allergies.⁷

Histamine intolerance vs allergies: What’s the difference?

At this point, it’s easy to feel confused. When you hear “histamine,” your first thought is probably typical seasonal allergies. So how does histamine intolerance differ from allergies? 

With typical allergies, your body encounters allergens and produces histamine. This can contribute to increased levels of histamine in your body. However, not everyone who has allergies also has histamine intolerance. You may have allergic reactions to pollen, but still have enough DAO to ultimately deal with the histamine in your system. 

On the other hand, histamine intolerance may actually be behind your symptoms. Indeed, some people who believe they have allergies could instead have histamine intolerance. Since the symptoms of allergies and histamine intolerance overlap, it can be difficult to differentiate. 

One way to tell the difference is immediate vs delayed reactions. If you react immediately to a specific allergen—such as a type of food—then it’s easy to recognize your reaction as a specific allergy. But if you experience symptoms outside a trigger, it’s possible you have built up excess histamine overtime, leading to histamine intolerance.

Along with this, histamine intolerance tends to produce more comprehensive symptoms that affect a wide range of systems in the body. 

Histamine intolerance symptoms

Histamine intolerance can lead to a multitude of symptoms, including the following:⁸

• Abdominal cramps
• Abnormal menstrual cycle
• Anxiety
• Asthma trigger
• Diarrhea 
• Difficulty breathing
• Difficulty falling asleep
• Difficulty regulating body temperature
• Dizziness or vertigo
• Fatigue
• Flushing
• Headaches
• Hives
• Itching of the nose or eyes
• Itchy skin
• Low blood pressure (hypotension)
• Migraines
• Nasal congestion
• Nausea and vomiting
• Red eyes (conjunctivitis)
• Runny nose
• Slow, quick, or irregular heart beats (cardiac arrhythmia)
• Sneezing
• Tissues swelling

Histamine intolerance causes

Histamine intolerance has multifaceted symptoms, so you could easily misinterpret it as something else. Currently, there are no proven histamine intolerance tests, apart from elimination diets. Because of this, histamine intolerance is often overlooked and rarely diagnosed. But when presented with multiple corresponding symptoms, you should consider histamine intolerance.

Numerous factors can cause or contribute to histamine intolerance, including:⁹ 

• Deficiency of DAO enzyme 
• Mast Cell Activation Syndrome (MCAS)
• Mutation of Histamine N-Methyltransferase (HMNT), a gene that plays a crucial role in breaking down histamine into another compound
• Overproduction of histamine
• Poor drainage from the liver and bile duct
• Poor methylation in the liver

Mast Cell Activation Syndrome (MCAS)

Mast cell activation syndrome (MCAS) is commonly referred to as a type of mast cell activation disorder (MCAD). MCAS occurs when your mast cells release too many mediators at once, often at wrong times. MCAS spans a wide range of systems, including the cardiovascular system, gastrointestinal tract, neurological system, respiratory system, and skin. This condition is also associated with repeated episodes of anaphylaxis, often for unknown reasons. ¹⁰ 

As already mentioned, MCAS is behind a significant number of histamine intolerance cases because histamine is a type of mediator released from mast cells. So if your mast cells release too much histamine, it can lead to histamine intolerance. 

So, what triggers mast cell activation? Both internal and external sources can trigger MCAS. Abnormal internal signals can cause your mast cells to continually activate. External sources can also trigger your mast cells. For example, infections, mold, chemical exposure, insect and reptile venom, and medications can all activate mast cells. If your mast cells are functioning properly, you would most likely have an immediate allergic reaction to one of these external sources. But with MCAS, you would experience a more severe reaction because your mast cells are overproducing. 

MCAS symptoms

MCAS symptoms may vary significantly per individual. Because it can manifest in entirely different ways, MCAS can also be hard to pinpoint. But the most obvious indication of MCAS is recurring anaphylactic episodes, without a clear cause. 

MCAS symptoms often resemble those of an allergy, a cold, food poisoning, or another infectious disease. They can also persist chronically or in episodes. While there is a wide range of possible symptoms, the most common symptoms include:¹¹

• Acute or chronic inflammation, pain, and swelling
• Chronic inflammatory diseases
• Dizziness and vertigo
• Edema (swelling)
• Gut issues: abdominal pain, diarrhea, constipation, heartburn, indigestion, IBS, and nausea
• Headaches and migraines 
• Heart palpitations
• Hot flashes and excessive sweating
• Itchy and irritated skin
• Low blood pressure
• Menstrual cramps and painful periods
• Nervous system issues: anxiety, concentration disorders, depression, fatigue, memory disorders, and sleep disorders
• Skin rashes and redness
• Vomiting

Measuring mast cell mediators

Mast cells can produce many substances that cause inflammation. But only the elevation of a few mediators or their metabolites, during episodes of MCAS, are reliable and measurable in specific laboratory tests. In particular, these test for increased levels of mast cell tryptase in the blood. Along with this, you can test for 11B-Prostaglandin F2α, Leukotriene E4, and N-methylhistamine in the urine.¹²

Mast cell tryptase levels in the blood should be evaluated between 30 minutes and 2 hours after the start of an episode. This is then compared with a baseline level taken many days later, when you are no longer experiencing a reaction. As for urine tests, a 24-hour collection of urine is started at the onset of a reaction.

These are not standard laboratory tests. You will need to work with an allergist or medical provider who can assure they are ordered and completed in a timely fashion. 

Diagnostic criteria

As previously mentioned, MCAS symptoms can overlap with many other conditions. This explains why to receive a diagnostic, these criteria are typically required:¹³

• The presence of anaphylactic symptoms
• The elevation of mast cell mediators during symptoms 
• The resolution of symptoms with appropriate treatment(s)

In some cases, when you exhibit the right symptoms, a medical practitioner may try putting you on a treatment regimen instead of testing. And if treatment using inhibitors and blockers of mast cell mediators manages the symptoms, the diagnosis is then confirmed.

Solutions for Histamine Intolerance and MCAS

Anaphylaxis and MCAS 

For acute episodes of MCAS, conventional solutions are similar to treating anaphylaxis. When experiencing severe and life-threatening reactions, treatment starts with epinephrine. Besides this, you may take any of the following to handle symptoms: ^{14 15}

• Antihistamines may help, including the first and second-generation histamine type 1 receptor blockers. Treatment with histamine type 2 receptor blockers could be useful for some symptoms, such as abdominal pain and nausea.
  
• Aspirin can reduce flushing by blocking the production of prostaglandin D2.
• Corticosteroids are helpful for hives, swelling, and wheezing, but are only recommended as a last resort.
• Leukotriene inhibitors can block the effects of leukotriene production, reducing abdominal cramping and wheezing.
• Omalizumab can reduce mast cell reactivity and sensitivity to allergens, accomplished by blocking the binding of IgE to its receptors. This makes it especially effective for anaphylaxis.

When immediate treatment for anaphylaxis isn’t necessary, several non-pharmaceutical options can help with histamine intolerance and MCAS.

Diamine Oxidase

Diamine oxidase (DAO) is the main enzyme that breaks down histamine in the gut. When DAO enzymatic activity is low, histamine food sensitivities or intolerances can occur.^{16 17} 

DAO is a sensitive enzyme. Certain chemical influences can inhibit its activity. Specific DAO-inhibiting substances can block the ability of DAO to break down. Some of these include:^{18 19 20}

• Alcohol (ethanol) and acetaldehyde (a product of alcohol breakdown)
• Certain biogenic amines (compounds found in varying concentrations in food and beverages, such as beer, cheese, fish, meat, vegetables, and wine)
• Certain medications (including some commonly used antibiotics, antidepressants, antihistamines, antihyperglycemics, antihypertensives, and muscle relaxers) 
• Mate tea
• Theobromine (a compound found in green tea)
  

Fortunately, diamine oxidase is available in supplement form, and it has shown the ability to reduce symptoms of histamine intolerance and mast cell activation disorders.^{21 22}

Low-Histamine Diet

People with an intolerance to histamine may experience a wide array of symptoms involving different organs and systems. Histamine-rich foods can cause diarrhea, headaches, or skin irritation in people with poor histamine tolerance.

Quantifying histamine levels in food can prove challenging. Histamine levels may vary significantly even in the same food product. In general, fermented foods have high levels of histamine. Fresh foods tend to have the lowest levels. It is also suggested that some foods that are not histamine-rich can instead trigger histamine release. These foods are considered histamine liberators. 

It’s helpful to know which foods are high in histamine. These foods contain high levels of histamine: ²³

• Alcohol, beer, champagne, and wine
• Canned, frozen, or salted fish, including sardines and tuna
• Cured and fermented meats, such as fermented ham, salami, and sausages
• Eggplant
• Fermented dairy products, including buttermilk, cheese (especially aged), kefir, sour cream, and yogurt
• Fermented grains, such as sourdough bread
• Fermented soy products, including miso, natto, soy sauce, and tempeh
• Fermented vegetables, including kimchi and sauerkraut 
• Kombucha
• Pickles or pickled vegetables
• Spinach
• Tomatoes and tomato ketchup
• Vinegar
• Worcestershire sauce
• Yeast extract

These foods are suspected histamine liberators:²⁴

• Alcohol
• Bananas
• Citrus fruits, including grapefruits, lemons, limes, and oranges
• Cocoa
• Egg whites
• Food additives, including colorants, flavorings, preservatives, and stabilizers 
• Legumes
• Nuts
• Papaya
• Pineapple
• Seafood
• Spices
• Strawberries
• Tomatoes

For more ideas on low-histamine diets, the Low Histamine Chef may be a good resource. 

Quercetin 

Quercetin is a flavonol, one of a group of phytochemical compounds found in high concentrations in many plant-based foods and beverages. Quercetin has significant antioxidant activity. It also scavenges free radicals and has anti-allergic properties, which provide:

• Antiviral activity
• Immune system stimulation
• Inhibition of histamine release
• Reduction of pro-inflammatory cytokines, interleukin IL-4, and leukotrienes 

Overall, quercetin contains many anti-inflammatory and immune-supportive properties. Quercetin is available in supplement form, or you can add more quercetin-rich foods to your diet. Natural sources high in quercetin include:^{25 26}

• Apples
• Berries
• Black tea
• Broccoli
• Buckwheat
• Capers
• Cherries
• Citrus fruits
• Kale
• Grapes
• Honey
• Onions
• Shallots
• Some botanicals, including elderberry, ginkgo, and St. John’s wort 

Getting to the Root Cause

The above can all offer support when dealing with histamine intolerance and/or MCAS. But these only help lessen reactions; they don’t reach the root cause of the problem. 

As you went through learning about histamine intolerance and MCAS, you may have asked yourself this: “Why would my mast cells overactivate when others don’t?” and “Why can some people handle histamine better than others?”

At the end of the day, there’s a why behind histamine intolerance and MCAS. Beyond the different reasons you may be susceptible, or the possible triggers, there’s an underlying cause: your body is overburdened with toxins. 

Your mast cells are designed to clear away harmful substances, including allergens, and overall protect your body. But in the toxic environment we live in today, your immune system can easily get overwhelmed. Excess toxins and other pathogens can dismantle your immune system and pile on inflammation. As a result, it disrupts your immune function—including your mast cells.

Drainage 

A healthy detox system runs like good plumbing. You should be able to drain toxins out of your body. But if toxins and pathogens clog your system, these toxins can get stuck. And then more piles on, until your body is overflowing. It’s this overflow that prevents your immune system from tolerating normal allergens. Your body needs clear drainage pathways to detox and handle common immune threats. 

To boost drainage, you will want to support your detox organs. Look for supplements that contain bowel-moving herbs, support the kidney and liver, and help reduce inflammation. 

parasites

Drainage issues and parasites go hand-in-hand. Parasites like to hang out in your detox organs, including your kidney and liver. To stay in your body, these critters purposefully clog up your system to prevent proper digestion and cleansing. Along with this, parasites can disrupt other essential areas of the body, increase inflammation, and store toxins within them. They also like to steal nutrients from you. All of this can affect your immune system, mast cells, and your ability to handle histamine.^{27 28 29 30}  

There’s a number of parasite-killing herbs you can tap into to clear these critters out. But Mimosa pudica seed is a particularly potent parasite killer and gut scrubber. Mimosa pudica seed grabs onto parasites and removes them via your stools. It can also paralyze and inactivate different parasites, making it easier to clear them out.^{31 32}

Mold, Heavy Metals, and Chemicals

Parasites are not the only potential instigator. Mold, heavy metals, and chemicals can also build up in the body. These toxins can damage your immune system and organ function, not to mention increase inflammation. Mold can suppress your ability to withstand allergens and chemicals. Heavy metals may disrupt your immune system and raise your IgE levels, which allows for more allergic reactions. And chemicals like glyphosate break down your detox organs and mitochondria, all of which are essential for healthy immune function and detox. Even more telling, glyphosate can increase putrescine and cadaverine intake, which affect the body’s ability to manage histamine.^{33 34 35 36}   

All of these toxins can significantly burden your immune and mast cell function. To help reduce their impact on your body, try taking binders designed to pull out these damaging toxins. You can also use mitochondrial-supporting supplements to boost your immune function. 

If you or a loved one has a chronic illness, histamine intolerance or MCAS may be contributing to or exacerbating the condition. Take a closer look and see if your allergies may actually be connected to mast cell dysfunction. And remember to get to the root cause and address drainage, inflammation, immune function, and possible toxins and pathogens. Each piece of the puzzle helps you come closer and closer to the vibrant health you want and deserve.

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