COVID and Histamine

COVID and Histamine

The link between long-COVID and Histamine

The link between long-COVID and Histamine is already apparent. Long-COVID is also referred to as ‘post-COVID syndrome.’ It is defined as symptoms that develop during or following an infection consistent with COVID-19 and persist for more than 12 weeks and cannot be explained by an alternative diagnosis.

 

 

 

Studies show that COVID-19 has similar symptoms to the symptoms of Mast Cell Activation Syndrome (MCAS) and Histamine Intolerance. Therefore treatment of MCAS or HIT can be a possible treatment also for COVID.

There is a growing number of people with long-covid, and their symptoms present in some ways similar to patients with mast-cell-driven inflammation.

Symptoms of long-COVID

Breathlessness, cough, chest pain, palpitations, tachycardia, brain fog, loss of memory, loss of concentration, sleep disturbance, headache, numbness, dizziness, abdominal pain, nausea, diarrhea, reduced appetite, fatigue, fever, joint pain, loss of taste and smell, muscle pain, symptoms of depression, anxiety, tinnitus, sore throat, skin rashes

Prevalence of Long-COVID

“37.7% of the participants reported one or more symptoms lasting 12 weeks or more” (1) and one-third of the participants reported that their Long COVID symptoms significantly affected their daily lives.

Covid and Histamine

There is limited guidance on managing Long COVID, but some doctors have started suggesting a low histamine diet. This recommendation is because COVID-19 symptoms have similarities to the symptoms of MCAS (Mast cell activation syndrome) and Histamine Intolerance.

Mast cell activation syndrome is a complex condition whereby mast cell releases mediators (such as histamine) in response to some kind of triggers, which causes a wide range of symptoms affecting multiple body systems. According to the theory, MCAS could trigger long-COVID symptoms, where mast cells release excess histamine in response to viral infection.

One study suggests that hyperinflammation in COVID-19 can lead to dysfunctional mast cells or mast cell degranulation when mast cells release inflammatory mediators.

Low Histamine Diet

The low histamine diet can help in managing Long COVID; however, if mast cells release too much histamine, the diet won’t be enough. If someone is eating a low-histamine food, their symptoms will improve but won’t disappear for long, and there is not enough evidence to suggest this will be helpful for everyone. There are studies on the effect of the natural antihistamine Quercetin, which is a good antihistamine in the case of long Covid.

Covid and antihistamines

Early treatment of symptomatic COVID-19 patients with antihistamines and azithromycin, had excellent outcomes.

COVID and QUERCETIN

In the covid patient group receiving Quercetin, laboratory markers and results showed improvement after the administration of Quercetin. Quercetin, as a common flavonoid of many fruits and vegetables such as high capers, lovage, and tea (Camellia sinensis), is proven to inhibit SARS-CoV-2 binding to the human cell via virus-specific protease and viral S-protein S-human ACE-2 interface (Nair et al., 2002; Uchida et al., 2011; Gormaz et al., 2015).

Histamine intolerance symptoms

Histamine intolerance symptoms

 

 

Histamine intolerance literally does not exist. Intolerance does exist to other externally administered substances, e.g. fructose, lactose. Histamine is constantly produced and broken down in the body, histamine taken from the outside is not normally a problem, on the contrary, it has many benefits.

Histamine intolerance symptoms and causes

Histamine intolerance symptoms are extremely varied. First, before diving into this topic, you need to understand what histamine intolerance is.

Although histamine intolerance does not exist in this context, we will use this term to describe this complex phenomenon because it is prevalent in the public consciousness in this name.
Understanding the role of histamine in our body can help us understand the processes behind histamine intolerance. Histamine is a tissue hormone produced by the enzyme histidine decarboxylase and vitamin B6 from the amino acid histidine. This process takes place in many plant and animal organisms. Histamine, an amazingly versatile and vital hormone widely used in the living world, has an effect on life or cells from the first moment of our lives. Histamine plays a neurotransmitter role in our body, both in the central and peripheral nervous systems.

In our body, histamine acts on cells mainly at 4 receptor types [1].

H1 receptors:

It causes contraction of the intestinal, bronchial and uterine smooth muscle tissues
It constricts the wall of small veins, dilates the wall of the arteries
Nerve cells: Pain, itching
Central nervous system: Increased alertness
Ovaries: Estrogen release
Uterus: Supports ovarian implantation

H2 receptors:

Stimulation of gastric secretion
Increasing heart rate, heart rate
Increasing muscle tension
Increased immune defense

H3 receptors:

Like H1 receptors, causes alertness and increased concentration
Inhibition of serotonin, GABA, and acetylcholine release in the peripheral nervous system,
Regulation of hunger and thirst in the central nervous system

H4 receptors:

Enhancement of cellular immune defense
Increasing the inflammatory readiness of skin cells

The condition called histamine intolerance

The condition called histamine intolerance (also known as histaminosis) involves complex, different organ systems with colorful, very different individual conditions. Symptoms, despite their color, show characteristic patterns. Symptoms can be triggered by certain foods, medications, chemicals, and the intensification of symptoms that later affect psychological stress.

Histamine intolerance is not a diagnosis but a concept/description to summarize symptoms. Stakeholders often respond to certain foods that either contain histamine, block certain histamine-degrading pathways, or even bloat (FODMAP fibers).

The Background

The background of the symptom formation called histamine intolerance is, in many cases, the excessive activity of mast cells, in particular mast cells. There is often an inflamed intestinal wall and a lack of micronutrients. Symptoms may also be caused by deficiencies in the two enzymatic pathways that degrade histamine, such as a lack of the enzyme diamine oxidase (DAO) and the lack of micronutrients required for the production of the DAO enzyme (vitamin C, vitamin B6, copper, manganese) and also the lack of micronutrients required for the enzyme (HNMT) (B12, folic acid, magnesium, zinc). Decreased enzyme activity can also be caused by genetic factors, which can predispose some people to symptoms. In the case of a proper supply of nutrients, they do not appear because the body usually maintains several pathways to perform a given function, so there are 2 enzyme systems available for the breakdown of histamine.

The Whithrawal

Withdrawal of symptomatic foods from the diet is, at most short-term relief. A true, lasting solution to histamine intolerance is achieved through a complex, personalized approach. This includes the regeneration of the digestive system, the targeted support of biochemical pathways for the breakdown of histamine, and to the regulation of the hormonal effects of overactivity of histamine-producing immune cells and, if necessary, to detect and counteract underlying chronic infections.

The list of Histamine intolerance symptoms

Individual sensitivity is very different. Some patients do not tolerate any amount of histamine in their food, while others are sensitive only to foods with the highest histamine content [2]. Some people only respond to certain foods containing histamine, not others, or they may only respond to foods that cause specific bloating. In the most severe cases, patients do not tolerate the smallest amount of histamine.

Gastrointestinal symptoms:

Stomach cramps, IBS
Nausea, vomiting
Puffiness
Reflux, feeling acidified
Diarrhea, less often constipation
Mucus production
Crohn’s disease is also common in patients

Dermatological problems:

Hives, eczema [3], neurodermis
Local edema (e.g., around the mouth)

Cardiovascular symptoms:

Fast heartbeat, extrasystoles
Blood pressure drop, sometimes high or fluctuating pressure
Dizziness, fainting
Edema

Psychiatric symptoms:

Flushing, anxiety, panic attack
Strange feelings, feeling of emptiness, depersonalization, derealization

Allergological and immunological symptoms:

Sore throat, cough, frequent sore throat
Clogged nose, runny nose, nasal polyps, chronic sinusitis
Asthma bronchiale (exogenous, ie. caused by pollen, animal hair, mold, or endogenous, ie. without known cause, but after consumption of wine, cheese, or tuna)
Some cases of drug allergy
Histamine entering the bloodstream can also cause anaphylactic shock

Gynecological symptoms:

Menstrual cramps, cramps

Other:

Headache, migraine
Swelling of the lower eyelid

 

What is in the background?

The following partly mutually reinforcing problems may play a role in the development of histamine intolerance:

1.

Poor gastric function, low gastric acid, and digestive enzyme deficiencies: Due to reduced efficiency of protein digestion, undigested proteins are broken down in the gut by pathogenic bacteria, some of which produce histamine directly.

2.

The entire digestive system, stomach, pancreas, etc., innervation of the parasympathetic nervous system, so it occurs by the Vagus nerve, weak gastric function, and digestive enzyme deficiency may be due to weaker gastrointestinal innervation due to chronic stress.

3.

The pathogens of Lyme disease, Borrelia, can also damage the Vagus nerve, which is why Lyme disease often appears with gastrointestinal symptoms, enzyme deficiencies, and histamine intolerance.

4.

Strong symptom formation often occurs after antibiotic treatments. The destruction of beneficial bacteria and the overthrow of the intestinal flora allow room for the growth of histamine-producing bacteria. In addition, repeated or higher doses of antibiotics may impair mitochondrial function, leading to a reduction in the production of steroid hormones, mast cell activation, and histamine intolerance in addition to general tissue energy deprivation.

5.

Inadequate diet, micronutrient deficiency: The enzymatic degradation pathways of histamine are highly demanding of micronutrients and vitamins.

6.

Immunological problems: Chronic infections are often present in the background of increased activity of histamine-producing mast cells, e.g., Lyme disease, but dental foci can also occur.

7.

Endocrine problems: Higher levels of estrogen and progesterone resp. Lack of cortisol triggers increased activity of histamine-releasing mast cells.

8.

In the case of vitamin B12, folic acid, and magnesium deficiencies, the breakdown of histamine is inadequate;

9.

In vitamin D deficiency, mast cells release more histamine.

10.

Mitochondrial dysfunction: Chronic infections, micronutrients, and vitamin deficiencies are also common, and toxic metal loads, sometimes the toxic effects of drugs or other intoxications may play a role.

How to help histamine intolerance?

When solving histamine intolerance, it is worth distinguishing between short and long-term solutions. Avoid foods that contain or release histamine and cause common symptoms in the short term for about 3-4 weeks. Complicated lists and tables of differently classified foods in terms of histamine can be found here: SIGHI list.

In the longer term, a strategy is needed that includes micronutrient replenishment and, thus, the gradual return of foods that contain or release histamine. Foods that cause individual sensitivity should be reloaded only slowly, in parallel with the regeneration of the body, always taking into account the current individual sensitivity.

Foods containing histamine have many positive effects, some of which are high in micronutrients. Dietary histamine also increases gastric acid levels, which improves protein digestion, kills pathogen-producing bacteria that also produce histamine, and helps utilize vitamin B12.

The problem and the biological background of histamine intolerance are often confused in practice with mast cell activation syndrome (MCAS), so the solutions are similar. For more information on specific protocols and adjuvants, see the MCAS article.

Histamine intolerance can be made asymptomatic and stable even under severe physical or mental strain: Targeted dietary, lifestyle, and nutritional supplementation protocols, partly based on laboratory results, and digestive regeneration improve the body’s vitamin and micronutrient levels. Although the regulation of the functions of the digestive system and the intestinal flora, in most cases, a stable, drug-free state can be achieved.

Other contexts

The symptoms associated with histamine metabolism are not always clearly distinguishable; in some cases, histamine intolerance, mast cell activation disease (MCAD), or mast cell activation syndrome (MCAS). In practice, it is rare to see cases of “pure” histamine intolerance; in most patients, mixed symptoms are reported.

Mastocytosis is not mast cell activation syndrome; the two concepts are often confused. During mastocytosis, more significant amounts of mast cells accumulate in the skin or some organs. The cause is unknown to science. Correlations with IgE-mediated allergies, mental and psychiatric illness, and low vitamin D levels have also been found [5].

Butyric acid

Butyric acid

Butyric acid is a short-chain fatty acid believed in providing optimal benefit to the gastrointestinal tract. It is highly produced in the gut by bacterial fermentation of undigested carbohydrates such as dietary fiber.Butyric acid has been scientifically shown to support and promote the health of the GI tract and microbiome.

 

 

Butyrate is an essential source of energy for the intestinal epithelium. It plays a crucial role in regulating the proliferation and differentiation of epithelial cells, protecting immune function and mucous membranes. Butyrate has antitumor activity and antimicrobial effect against the most enteric pathogens, thereby significantly improving the composition of gut microflora.

Indigestible carbohydrates (prebiotics) increase colonic butyrate concentration, which is thought to be responsible for its beneficial effects. In inflammation caused by oxidative stress, damage to the integrity of cell-cell connections and an increase in cell permeability may occur, depending on the extent and duration of the oxidative effect.
The therapeutic value of the protective n-butyrate improves the intestinal epithelium’s barrier function, maintains a healthy intestinal flora, and promotes the regeneration of intestinal epithelial cells.

Butyric acid treatment

Decrease in cell layer resistance induced by acute oxidative stress after low-dose butyrate treatment decreased, indicating that the role of a mechanical barrier is strengthened. Based on experimental results, the composition of the intestinal flora has become favorable.
The number of beneficial lactic acid bacteria and the amount of L-lactic acid they produce in the small intestine also increased. Butyrate affects the coliform bacteria; it can also be used effectively to prevent and overcome the development of infectious conditions in the intestinal tract.

Butyrate controls pathogenic bacteria through regulating intestinal oxygen availability. Several studies have reported another important mechanism where butyrate can indirectly control pathogenic bacterial overgrowth, i.e. contributing to intestinal oxygen availability 

Specific benefits of Butyrate for the gut:

Maintenance of normal intestinal bacteria
Increased absorption of macronutrients
It is an essential element of intestinal homeostasis
Improves tight junctions in leaky gut
Improves the mucus layers of the gut
Helps gut cells to kill pathogens
Keeps the oxygen levels in the colon low
Regeneration of the intestinal mucosa
Reduces the incidence of IBS symptoms
Intestinal pain after antibiotic treatment

But Butyrate has shown benefits for the whole body

Supports mast cells and modulates histamine
Supports the immune system by lowering inflammation and helping reduce autoimmunity
May improve skin issues
May help with allergies and asthma
Can protect against alcohol-induced leaky gut and inflammation
It is considered cancer protective has shown anticancer effect
In mice, studies showed improvement in insulin sensitivity, mitochondrial density, and satiety after eating
In mice, research showed it helped the brain recover from strokes
Support weight loss with increasing Bacteroidetes in the gut. – Firmicutes and Bacteroidetes are two major groups in the gut. Having more Firmicutes than Bacteroidetes is associated with weight gain and obesity.

How it works:

4 levels of leaky gut:

Loosening of the tight junctions in the gut lining – allows food and other things to pass through to the bloodstream
Loss of mucus layer in the gut
Low good bacteria species
Loss of ability to kill pathogens in the gut

Butyrate’s effect on leaky gut:

Improves the tight junctions in the gut lining
Supports healing mucus layers in the gut
Increases good bacteria in the gut
Supports cells to kill pathogens in the gut
Butyrate supports the gut at the cellular level.

Studies have shown that people who have the following conditions tend to be low in butyrate:

Inflammatory Bowel Disease
Crohn’s Disease
Ulcerative Colitis
Irritable Bowel Syndrome (IBS)
IBS-C (constipation-dominant)
IBS-D (diarrhea-dominant)
Type 1 diabetes
Obesity
Rheumatoid Arthritis
Parkinson’s DiseaseHo
Children with allergies

How do you know whether or not you have healthy butyrate levels?

Find out the signs of low butyrate!
To have good butyrate levels, you need to know if you have the suitable microbiome species in your gut and if you need to eat enough fibers or to be fermented, and during this process, butyrate will be produced. Your butyrate levels wcorrectecrease if you don’t have the right species of bacteria or enough prebiotics in your diet.

How do you fix your butyrate levels?

You need to have butyrate-producing bacteria, but unfortunately, only one of these bacteria is available commercially – Lactobacillus rhamnosus.
So, unfortunately, there is no good recommendation to increase your butyrate levels, so you need to focus on fiber and prebiotics.

What to do, then?

You have to eat a variety of vegetables.
Increase your intake of resistant starch, but if you don’t tolerate fiber and starch, it can be a problem and leads to a vicious circle.

The only thing you can do is choose the correct type of butyrate supplement.

When choosing, you need to consider the…:

  • type of butyrate is very fragile; butyrate needs to bond with salt that stabilizes it. But research shows that tributyrin is more potent and doesn’t require digestion to break apart the chemical bonds.
    Plus, some research suggests tributyrin is safer for human consumption than butyrate salts.
  • the butyrate delivery: Butyrate will be broken down in the stomach and won’t reach the gut. To avoid this, you need to choose liposomal or so-called enteric delivery. Unfortunately, the liposomal butyrate is very smelly
  • purity (without additives)
  • easy to use

L-Glutamine

L-Glutamine

L-glutamine

L-glutamine, the universal amino acid.

 

 

L-glutamine is the most common amino acid in the bloodstream, accounting for 30-35% of the amino acid content of the blood.

This is a well-known and popular dietary supplement not only for athletes but it is an effective amino acid for gut regeneration in SIBO.

What is glutamine?

L-glutamine is the most common amino acid in the bloodstream, accounting for 30-35% of the amino acid content of the blood. It is a conditionally essential amino acid because it is used in large amounts by our body.

It is found in animal and plant proteins, in the form of supplements, and is widely popular in the fitness community and among those who lead a healthy lifestyle. It is also found in large amounts of casein and whey protein.It is essential to know that most people do not get enough this amino acid from food.

Therefore, dietary supplementation is an excellent way to strengthen the immune system and improve the ability to fight infections and diseases.

Benefit of L-glutamine

Glutamine has several physiological effects that research has confirmed in turn that even a person living an average life should have enough reason to pay more attention to this amino acid.

1. Improves gastrointestinal health

This amino acid is good for health if you have gastrointestinal problems, such as irritable bowel syndrome (IBS), inflammatory bowel diseases such as Crohn’s disease, ulcerative colitis, diverticulitis, diverticulitis, permeable bowel, or any problem related to leaking bowel. (e.g., joint pain, rosacea, or autoimmune response).

We regularly need a certain amount of this mino acid because it is an essential nutrient for the gut to rebuild and regenerate. It is worth noting that a man famous for discovering the Krebs cycle (also known as the “citric acid cycle”) was the first to suggest L-glutamine treats intestinal problems.

Sir Hans Adolf Krebs – a German-born British biochemist who won the Nobel Prize in 1953 – found that it helped improve a healthy gut immune response.

A study published in the journal Clinical Immunology found that L-glutamine normalizes the effects of the TH2 immune response that stimulates inflammatory cytokines. The result of L-glutamine in these studies shows that it reduces intestinal inflammation and may help recover food sensitivity.

2. Helps with leaky gut and ulcers

Millions of people struggle with leaky gut syndrome, which is today the leading cause of autoimmune disease. Leaky gut can cause thyroid problems such as Hashimoto’s disease; contributes to arthritis, skin problems such as psoriasis, and other serious health problems.

Because glutamine is the primary fuel source for small intestinal cells, it has been shown in clinical trials to cure the pain of a leaking gut. A study published in a medical journal examined 20 hospitalized patients and found that supplementation with L-glutamine reduced intestinal permeability.

Animal experiments published in the British Journal of Surgery have found that L-glutamine promotes the cure for ulcerative colitis and inflammatory bowel disease. It can also help heal ulcers by protecting them from further damage and is a healthier, natural alternative to antibiotics for treating stomach ulcers.

If we do seem to suffer from Leaky Gut Syndrome, L-glutamine is the number one amino acid we need to heal and repair.

3. Effect on the brain – enhances brain health

It is a precursor of the neurotransmitter glutamate in the brain. Glutamine is key to improving brain health. Why?

Interrupting the glutamine-glutamate cycle can result in brain problems, including Reye’s syndrome, epilepsy, bipolar disorder, schizophrenia, anxiety, depression, and alcohol dependence. Glutamine can also prevent the brain from aging.

Mitochondrial dysfunction causes abnormal growth of the neurotransmitter glutamate; again, the brain is at risk for developing the above problems. A study at the University of Medicine in New York found that even mild traumatic brain injury caused cerebral atrophy. Much of this damage is due to an interrupted glutamine-glutamate cycle and an abnormal increase in glutamate levels.

4. Improves IBS and diarrhea

Glutamine improves IBS and diarrhea by balancing mucus production, resulting in healthy bowel movements. If you have Hashimoto’s disease or an abnormal thyroid problem, it should be part of the diet for hypothyroidism. If you also have symptoms of IBS, such as persistent diarrhea or ulcers, this should be part of your IBS diet.

5. Glutamine is essential for the immune system

One of the most critical functions of glutamine is its role in the immune system. It is a vital fuel source for immune cells, including white blood cells and specific intestinal cells. However, your blood levels may drop due to severe injuries, burns, or surgery.

If the body’s need for glutamine is more significant than its ability to produce it, it can break down protein stores, such as muscle, to release more amino acids. In addition, the immune system may be compromised if there is low glutamine available. For these reasons, high-protein, high-glutamine, or glutamine supplements are often prescribed after severe injuries such as burns.

Studies have shown that glutamine supplements can improve health, reduce infections and result in shorter hospital stays after surgery. Moreover, they have been shown to improve survival and reduce medical costs in critically ill patients.

Other studies have shown that glutamine supplements can improve the immune system in animals infected with bacteria or viruses. However, the benefits for healthy adults are not strongly supported, and the needs of these individuals can be met through diet and natural production of the body.

6. Promotes muscle growth and reduces muscle breakdown

L-glutamine can provide significant support if you aim to increase athletic performance, boost metabolism, improve recovery, or build muscle. During intense exercise, the body gets stressed, and the muscles and tendons require more glutamine than the amount provided by a regular diet.

So after an intense workout, your cellular glutamine levels can drop by 50% and your plasma levels by 30%! This state of muscle breakdown is a gateway for the body when it uses its muscles to gain energy, not carbohydrates. But glutamine supplementation can prevent this from happening. Supplementation with L-glutamine allows the forces to fight and endure a little longer, which increases strength and helps restore skeletal muscle.

One study found that glutamine supplements allow faster regeneration of intense weight training because it improves muscle hydration. This facilitates muscle recovery and reduces the recovery time for wounds and burns.

Therefore, glutamine supplementation is not only helpful and widespread for bodybuilders, but in almost every sport. It can take up to six days to replenish your glutamine levels after an intense workout, so it’s essential to take it regularly if you do intense exercise.

Some athletes say glutamine works best when combined with branched-chain amino acids (BCAAs), especially leucine. Others consume creatine after a workout to improve muscle recovery and restore the body’s energy stores.

7. Improves athletic performance and recovery from endurance practice

One of the primary roles of L-glutamine in the body is to support detoxification by cleansing the body of high ammonia. It acts as a buffer and converts excess ammonia to other amino acids, amino sugars, and urea.

Exercising for about an hour can reduce the amount of glutamine in your body by 40%. It can also cause suppressed immune function. This hurts your endurance training and can lead to overtraining syndrome. L-glutamine is also beneficial for long-term athletes as it boosts the immune system (T-helper cells).

Animal experiments have shown that increasing T-helper cells can reduce the “stress” associated with overtraining syndrome.

8. Glutamine and overtraining

During intense exercise, our body uses glutamine from storage sites faster than it can replenish. When this happens, the body breaks down the muscles, and thus the catabolic state begins. It is proven that oral glutamine supplementation supports glycogen storage, aids in synthesizing other amino acids, and reduces the catabolic state during overtraining.

With low glutamine levels, both performance and regeneration are compromised. After strenuous exercise, glutamine levels drop significantly, so we are more exposed to infections in the so-called “open window” period after workouts.

This amino acid consumed after exercise can help us in this as well. A study of marathon runners showed that runners consuming glutamine had a 35% reduction in the risk of developing infections. Consuming enough glutamine after workouts will also help with regeneration and strengthen your immune system.

The most potent antioxidant for the body plays a crucial role in synthesizing glutathione. It is well known for its ability to increase GH (growth hormone) levels, which can be effectively increased by consuming as much as 4 g. During a rigorous and strenuous training process, such as training camps, preparation periods for regeneration time are not always sufficient.

Athletes may experience what is known as Over Training Syndrome (OTS). The researchers linked this OTS to an amino acid imbalance. This disruption of the amino acid balance can lead to poor performance, loss of mood, and the risk of developing infections that can lead to upper respiratory disease.

9. Stimulates fat burning and improves diabetes

Research has shown that HGH (growth hormone) levels increase by nearly 400 percent after glutamine supplementation. This hormonal response increases resting metabolism and enhances the post-burning effect or EPOC training.

Post-burn is essential for fat burning, weight loss, and fibrous muscle building. L-glutamine also burns fat and increases lean muscle mass by suppressing insulin levels and stabilizing blood sugar levels; therefore allows the body to use less muscle mass to maintain the blood sugar levels and insulin sensitivity of the cells.

Thirty grams of glutamine supplementation per day for six weeks “significantly improved cardiovascular risk factors and body composition in patients with type 2 diabetes. Therefore, L-glutamine benefits diabetics and those with high cravings for sugar and carbohydrates.

Resources
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Samuni Y, Goldstein S, Dean OM, Berk M. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta. 2013 Aug;1830(8):4117-29.

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Fulghesu AM, Ciampelli M, Muzj G, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002 Jun;77(6):1128-35.

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Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol. 2009 Feb;181(2):741-51.

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Badawy A, State O, Abdelgawad S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand. 2007;86(2):218-22.

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Porpora MG, Brunelli R, Costa G, Imperiale L, Krasnowska EK, Lundeberg T, Nofroni I, Piccioni MG, Pittaluga E, Ticino A, Parasassi T. A promise in the treatment of endometriosis: an observational cohort study on ovarian endometrioma reduction by N-acetylcysteine. Evid Based Complement Alternat Med. 2013;2013:240702.

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Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000 Aug;16(2):253-62.

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Sandhir R, Sood A, Mehrotra A, Kamboj SS. N-Acetylcysteine reverses mitochondrial dysfunctions and behavioral abnormalities in 3-nitropropionic acid-induced Huntington’s disease. Neurodegener Dis. 2012;9(3):145-57.

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Quercetin

Quercetin

Quercetin is certainly one of the most exciting dietary flavonoids. It’s been linked to improved exercise performance and reduced inflammation, blood pressure, and blood sugar levels. Plus, it may have brain-protective, anti-allergy, and anticancer properties, and it is a natural antihistamine. 

Numerous studies support the existence of a natural antihistamine because it regulates the release of histamine from basophils and mast cells (1). This regulatory mechanism can be used for various unwanted symptoms, allergies, asthma, and histamine intolerance symptoms.

QUERCETIN suppresses the release of histamine from basophils and mast cells, so reduces the symptoms of histamine intolerance or mast cell activation syndrome (2)

Other benefits

  • Reduces cellular inflammation
  • Prevention of allergies, in the alleviation of existing allergic symptoms
  • Protects the heart and nervous system
  • Prevention of osteoporosis, in the reduction of symptoms during menopause
  • May help in weight loss

Allergies, Histamine intolerance

The enzyme diamine oxidase (DAO) is responsible for the proper breakdown of histamine. Histamine plays an important role in the dynamic functioning of our body, but if the activity of the DAO enzyme decreases, we can experience various unpleasant symptoms due to high histamine levels: hives, eczema, swollen mouth, cough, runny nose, digestive problems, bloating, flatulence or abdominal pain. In these cases, the regulatory function of quercetin may be helpful.

In addition to quercetin, DAO enzyme activity can be supported by supplementing other micronutrients. Among other things, zinc, copper, manganese, magnesium minerals, B vitamins (including choline and inositol), and vitamin C help proper production.

Quercetin displays high antioxidant and anti-inflammatory properties that have been proven by many in vivo and in vitro studies. Its anti-allergic mechanism of action through the inhibition of enzymes and inflammatory mediators has also been extensively studied. It is well known that quercetin is an inhibitor of human mast cell activation through the inhibition of Ca2+ influx, histamine, leukotrienes, and prostaglandins release. The results of the studies prove the unique position of this supplement in the treatment of allergic disorders and the possibility of using phytochemicals such as quercetin for an efficient cure. (3)

 

Antibacterial and antiviral activity

This excellent flavonoid is known to exhibit antibacterial effects against almost all strains of bacteria, particularly affecting the gastrointestinal, respiratory, urinary, and dermal systems. (4)

Cardiovascular health

In 2008, a randomized, placebo-controlled crossover trial in 12 healthy men showed biochemical evidence of improved endothelial function (such as augmentation of nitric oxide status) with as little as 200 mg/day of quercetin. (5)

Obesity

This flavonoid actually blocks the uptake of glucose from the blood, depriving fat cells of the raw material they need to manufacture and accumulate fat molecules. (6)

In another study, genistein, quercetin, and resveratrol together decreased lipid accumulation in fat cells by 17%, 20%, and 17%, respectively, the combination of all three agents decreased lipid accumulation by an impressive 80%. (7)

Treatment of histamine intolerance

Treatment of histamine intolerance

Treatment of Histamine intolerance

Histamine intolerance occurs when histamines, chemicals released by the body in response to allergens, build up in the body and have a negative impact on health and well-being.

People with Histamine intolerance may experience symptoms such as headaches, nausea, digestive issues, rashes and more if they consume foods with high histamine content or aren’t able to break down histamines efficiently.

However, there are treatment options that can help alleviate symptoms and even heal Histamine intolerance over time. 

First steps in the treatment of histamine intolerance

There are very effective natural solutions for histamine Intolerance and Mast cell activation syndrome that can be added to the medical treatment or can be used alone. In the treatment of histamine intolerance and mast cell activation syndrome, if we think of natural substances, the same can be said, i.e. the goal is to reduce the amount of histamine in the body, so it is worth controlling the process of histamine breakdown and stabilizing mast cells. 

I did not take the natural treatment of histamine intolerance and MCAS separately because, like the symptoms, the proper natural active ingredients are similar too. However, the treatment of MCAS is a very complex thing. In many cases, when the immune system has calmed down, the asymptomatic stage can be maintained only by taking natural remedies. In histamine intolerance, with the help of natural supplements, you can become asymptomatic in the long run if the root cause is treated.

First of all, the cause of both histamine intolerance and mast cell activation syndrome should be explored. In the case of histamine intolerance, the first thing to think about is the inflammatory condition of the intestinal tract. I have described the causes in previous articles. Read them here: HIT  , MCAS

There is often a problem that the therapy used to eliminate the root causes is not tolerated by the individual. This is a major challenge for all diseases, especially MCAS. If you have severe histamine intolerance or MCAS, you may have severe symptoms of the medication you are taking for the root cause (such as parasites, lyme, SIBO, retroviruses, or molds).

The reaction is individual for everyone. It is also advisable to consult a specialist regarding natural active substances, who are experts in the natural treatment of these health conditions. However, it is a fact that certain substances can be used safely. It is worth switching the substances if possible and observing which is the most suitable active ingredient for you.

Based on the above, both Histamine intolerance and mast cell activation syndrome should be treated along the following 4 pillars*

1. Low histamine diet: Minimize your intake of histamine through food

2. Helping to breakdown histamine

3. Stabilization of mast cells

4. Stabilising the immune system and reducing inflammation

Here are the natural options that are best suited for treating histamine or mast cell activation problems.

1. Low histamine diet

To reduce histamine levels in your body, you should adopt a low histamine diet. Avoid the following:

Alcohol
Smoked and cured meat
Seafood
Pickled foods
Fermented foods
Leftovers
Canned sh or meat
Berries, especially strawberries (except blueberry)
Preservatives
Vinegar
Try to eat foods as fresh as possible, and stick to anti-inflammatory professional foods. See Low histamine food list

2. Helping to breakdown histamine

Diamine oxidase (DAO) stabilizes mast cells, but more importantly, it is the predominant enzyme besides HNMT enzyme that breaks down histamine. To increase your DAO levels, you can take DAO enzymes. You can also increase your DAO levels with high doses of vitamin C.
You should also avoid anything that blocks the release of DAO. Alcohol is in the first place in blocking the DAO. The worst thing happens when you drink alcohol, histamine is released from your mast cells, and DAO is simultaneously inhibited.

3. Stabilization of mast cells

If you would try any kind of natural supplement, I recommend the following:
Only pure and well-trusted formulations should be chosen. I have tried many kinds of natural supplements. It happened once that I had such intense diarrhea after taking that supplement that I needed to rebuild my gut flora from the beginning again.

I recommend a 3-day trial period with a lower dose of the new supplement before increasing the daily dose or the next supplement. My favorite supplement for stabilizing histamine release is Quercetin. If you want to know everything about the possible treatment, you will have the chance to get all the information on our membership site soon. Check back later.

Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/
What is Hitamine intolerance

What is Hitamine intolerance

What is histamine intolerance

Histamine intolerance is associated with impaired histamine breakdown in the body.
Histamine is a chemical that plays a key role in the functioning of the immune, digestive, and nervous systems.

As a neurotransmitter in the nervous system, it communicates important messages from your body to your brain. In the digestive system, histamine is an essential component of stomach acid, which helps to break down food in the stomach. However, histamine’s most well-known role is its part in the immune system.

Let’s dive deeper into what histamine intolerance is.

One of the main roles of histamine is to cause an immediate inflammatory response, which functions as a red flag of the immune system to notify the body of potential attackers. So, histamine causes blood vessels to dilate so that white blood cells, the immune system’s defender cells, can quickly find and attack the invader. This process is part of the natural and healthy immune response, and ideally, diamine oxidase (DAO) enzymes, also known as “histamine enzymes” will break down the histamine.

However, if this histamine is not broken down and eliminated properly, it begins to build up in the body, causing histamine intolerance. This increased histamine can affect many different parts of the body, contributing to the wide range of symptoms that make histamine intolerance challenging to diagnose.
Although histamine has critical physiological functions in the body, the accumulation of large amounts of histamine can pose a health risk. The proper functioning of histamine degradation systems is key to preventing the accumulation of histamine. Consumption of food with an unusually high histamine content (usually above 500 mg/kg) that exceeds the degradation mechanisms may lead to histamine poisoning, a type of food poisoning.

DAO, the first step to histamine breakdown

Poisoning is based primarily on the determination of elevated plasma histamine levels and/or and/or the identification of consumed foods with unusually high histamine levels. However, for the diagnosis of histamine intolerance, it is also important to look at the DAO level because if it is present in a reduced amount, the breakdown of histamine does not take place to such an extent that it can eliminate the excess accumulated histamine.

The amount of DAO in the blood fluctuates enormously, so histamine intolerance can be diagnosed by histamine levels and a 4-week elimination diet. The drastic so-called zero diets mustn’t last longer than 4 weeks as it further reduces the level of DAO. Replacing the DAO will make it possible to avoid having to follow a zero diet all the time, but we can only expect an improvement in the condition once the causes have been identified and eliminated.

Histamine degradation process

There are two main histamine metabolic pathways, i.e., the enzymes diamine oxidase (DAO) and histamine N-methyltransferase (HNMT), responsible for the breakdown of excess histamine.
The DAO enzyme contains copper, found mainly in the small intestine, liver, and white blood cells, and is produced in large quantities by the placenta.

Its cofactors are 6-hydroxydopa, pyridoxal phosphate (vitamin B6), and vitamin C.DAO degrades extracellular histamine. DAO is produced primarily by the small intestine, ascending colon, placenta, and kidney. In the intestine, DAO activity gradually increases from the duodenum to the ileum, and the enzyme itself is found mainly in the intestinal wall.

Most of the histamine, primarily in the central nervous system, is broken down by the enzyme methyltransferase. HNMT can be synthesized intracellularly but can also enter the cell from the extracellular space and is responsible for inactivating intracellular histamine. Insufficient amounts of S-adenosyl methionine (SAM) are available in case of undermethylation, which can also cause histamine to build up in the blood.

Undermethylation may also be due to micronutrient deficiencies, such as the lack of magnesium, and the digestive system e.g., vitamin B12 deficiency due to stress.

Positive effects of histamine

Some foods containing histamine have an exceptionally high micronutrient content, and dietary intake also increases gastric acid levels, which are important for protein digestion, killing of otherwise histamine-producing pathogenic bacteria, and absorbing vitamin B12 and micronutrients in food.

It is no coincidence that foods containing histamine are among the most popular delicacies, cf. e.g., Mediterranean food (Ripe cheeses, tomatoes, matured ham, red wine).

Other positive effects

– helps the production of stomach acid, thus the functioning of the stomach and digestion
– dilates blood vessels, lowers blood pressure
– regulates the sleep-wake cycle, makes you alert
– controls appetite, reduces weight
– improves learning skills and memory, increases intelligence
– regulates cell differentiation and growth
– regulates the neuroendocrine and immune systems
– accelerates wound healing

Negative effects of histamine

Other adverse effects are that it increases the tendency of smooth muscle tissue (gastrointestinal tract, lungs, uterus), dilates blood vessels (redness, itching, edema, drop in blood pressure), and increases the permeability of blood vessel walls.

The forms of symptom formation associated with histamine metabolism are not always clearly distinguishable and, in some cases, are referred to as histamine intolerance or mast cell activation syndrome (MCAS).

There is a significant overlap between the three problems in terms of both symptoms and causes, and thus the path to living without symptoms is similar.

Sources of histamine

  • The downsides of histamine appear when the total intake and production of histamine significantly exceeds the histamine-degrading capacity of DAO and methyltransferase enzymes.

    • Histamine can be formed by the breakdown processes carried out by bacteria, e.g., during fermentation.
    • The histamine content of fresh food and meat increases rapidly during storage.
    • The intestinal flora also produces histamine in large quantities when certain bacteria settle in the intestinal tract.
    • Histamine is released in the body under stress, most notably at high cortisol levels, by mast cells, basophilic white blood cells, lymphocytes, neurons, and gastric mucosal cells. It also plays a significant role in the functioning of the digestive, nervous, and immune systems.

So how does excess histamine develop in the body?

  • Foods containing histamine
  • In case of dysregulation of mast cells
  • From mental/emotional stress
  • From physical stress – overtraining is also included
  • By taking certain medications
  • As a result of inflammatory processes: inflammation of the intestinal tract (e.g. SIBO) and damage to the intestinal mucosa are among the primary causes, as the intestinal wall is unable to produce DAO.

Histamine ingested with food

Histamine from the diet first encounters the intestinal epithelium in the body where its breakdown begins. Therefore, although HNMT is also present in the gastrointestinal tract, the higher presence of DAO plays a major role in protecting the body against externally occurring histamine, whether from ingested food or histamine produced by the intestinal microbiota.

Histamine is present in a wide range of foods in highly variable concentrations. The main cause of histamine formation in foods is the type of histidine produced by enzymes of bacterial origin. Many bacteria are responsible for microbial spoilage of food or fermentation processes that can produce histamine.

What foods cause symptoms?

Histamine is heat stable and cannot be neutralized during baking or cooking. Foods containing histamine:

Cheeses, sour milk products (cheeses made from raw milk and long-aged cheeses contain the most)

Red wine, sparkling wine, white wine, beer (Alcohol also blocks the action of the enzyme that breaks down histamine so that it can cause increased symptoms)

Dried, matured, smoked, canned fish and fish sauces, tuna (rich in histidine, from which a lot of histamines is quickly formed due to the large body during slow cooling), e.g., mackerel, sardines, herring, and salmon

Seafood only after long transport and storage (not fresh)

Dried, smoked, and processed meat products (e.g., salami), ham, sausages, bacon

Sauerkraut, pickles, and other pickles

Wine vinegar, balsamic vinegar

Emmental, camembert, Roquefort, gouda, cheddar, moldy and smoked cheeses

Mustard, ketchup, soy sauce

Chocolate, cocoa (tyramine, phenylethylamine), coffee, black tea

Bread and cakes made with yeast

Nuts, hazelnuts, sunflower seeds

Foods high in histamine in bulk

Foods high in histamine in bulk
Alcohol, mainly wine, champagne and beer, pickled or canned food – sauerkraut. pickles, mayonnaise, olives, matured cheeses, including goat cheese, cured / smoked meat products – salami, ham, sausages, bacon, salami, pepperoni, lunch meats and sausages, mussels, various types of fish: mackerel, mahi-mahi, tuna , sardines, Beans and legumes – chickpeas, soybeans, peanuts, walnuts – walnuts, cashews, cashews and peanuts, chocolate and other cocoa-based products, avocado, eggplant, spinach and tomatoes, most lemons, apricots, dried plums figs, raisins, wheat-based products, vinegar, processed and ready meals, savory snacks, sweets with preservatives and artificial colors.sour foods: sour cream, sour milk, buttermilk, sourdough bread

Histamine releasing foods

Most lemon fruits – kiwi, lemon, lime, pineapple, plum…, cocoa and chocolate, nuts, papaya, beans and legumes, tomatoes, wheat germ, additives – benzoate, sulfites, nitrites, glutamate, food colors

Beverages that are diamine oxidase (DAO) blockers
Alcohol, black tea, energy drinks, green tea, mate tea

Histamine emissions are caused by the following:

Certain vegetables: Tomatoes, spinach, eggplant, avocado, peas, lentils, beans
Certain fruits: Strawberry, raspberry, banana, papaya, kiwi, pineapple, mango, grapefruit, tangerine, pear
Acetaldehyde, a decomposition product of alcohol, can also cause the release from mast cells. For those with less genetically available acetaldehyde dehydrogenase enzymes (e.g. most Asians or women in general), this also causes redness.

Pollen-connected food allergies: Apples, nuts, carrots, soy, kiwi, figs (birch pollen allergy), celery, white wormwood, chamomile, sunflower and sunflower honey, anise, dill, fennel, coriander, cumin and parsley
A comprehensive summary of the problem of histamine is available in German: R. Jarisch, Histaminintoleranz und Seekrankheit [4].

Low histamine foods

Freshly cooked meat, poultry (frozen or fresh),
Freshly caught fish
Boiled eggs
Gluten-free grains: rice, quinoa, corn, millet, amaranth
Fresh fruits: mango, pear, watermelon, apple, kiwi, melon, grapes
Fresh vegetables (excluding tomatoes, spinach, avocados, and aubergines)
Milk substitutes: coconut milk, rice milk, hemp milk, almond milk
Edible oils: olive oil, coconut oil
Leafy herbs
Herbal teas

For a full list of official groceries, see the SIGHI grocery list

How does nutrition affect histamine intolerance?

The list of foods that do not contain histamine is very short, such as entirely pure water, refined fats, sugar, and salt. Nevertheless, it is a known phenomenon that a glass of water can occasionally cause symptoms in some very sensitive people.

Eliminating symptomatic foods from the diet is only a short-term solution. Long-term avoidance of histamine does not provide permanent asymptomatic relief without eliminating the true causes of histamine intolerance. Some foods rich in histamine are by far the richest in nutrients.

Exclusion of these leads to an exacerbation of the body’s micronutrient deficiency and a slow deterioration of the condition. In the longer term, in addition to measures to regenerate the digestive system, the intake of quality foods rich in particular nutrients is essential for asymptomatic relief.

These nutrients allow the proper biochemical processes in the body to take place, such as the enzymatic processes that break down histamine.

Foods that cause symptoms to act through different mechanisms:

Allergies
Intolerances (IgG or IgE antibodies)
Through bloating-causing foods (FODMAP fibers)
Through direct histamine content
Occasionally by blocking certain enzymes or interfering with the biochemical process in the body (eg, alcohol inhibits the DAO enzyme)

In some pre-existing chronic infections, bactericidal agents have also induced histamine reactions (Jarisch-Herxheimer reaction).
Micronutrient deficiencies due to an inadequate quality effect are exacerbated by the fact that gastrointestinal function is usually poor in these conditions (e.g., low gastric acid levels, which may be due to stress).

They also lead to the growth of pathogenic, histamine-producing intestinal bacteria caused by stomach acid and digestive enzyme deficiencies. Microbial deficiency initially occurs as a hidden process, and the body’s resilience slowly declines.

Worsening histamine intolerance due to micronutrient deficiency is a vicious circle. As a result of the increase in micronutrient deficiencies and the slow deterioration of the biochemical functions of the injured organism, the body will become increasingly sensitive to food. Thus, the diet becomes narrower, the micronutrient deficiency increases, and the body becomes more and more susceptible to histamine-containing foods.

The organization of those affected by histamine intolerance is affected by intestinal or immunological problems; even several foods independent of histamine are typically not tolerated. In the end, many people get to the point where they only eat rice and fries.

If you have symptoms besides eating low histamine diet you probably have MCAS mast cell activation syndrome. Then READ THIS article

Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/

Histamine intolerance or MCAS

Histamine intolerance or MCAS

Histamine intolerance or MCAS?

Histamine intolerance or MCAS (Mast Cell Activation Syndrome.) There is not much difference between the symptoms of these two health issues. In this article, we discuss the details related to the difference.

 

Difference between Histamine Intolerance and Mast Cell Activation Syndrome

The main difference between MCAS and histamine intolerance is that in MCAS, mast cells are not working correctly and release excessive chemical mediators. In contrast, histamine intolerance is a condition in which dietary histamine accumulates in the body because the body cannot break it down. (1)

Histamine intolerance is a so-called subset of MCAS. If you have discovered you have histamine intolerance, you need to test MCAS. (2)

What are mast cells?

Mast cells are particularly found in tissues that are in close contact with the environment such as skin, airways, and gastrointestinal tract but are found in most tissues throughout the body.

Mast cells are types of white blood cells that release up to 200 signaling chemicals, ie. mast cell mediators into the body as part of an immune system as a defense response against foreign invaders (parasites, fungi, bacteria, or viruses), allergens and environmental toxins.

Mast cell mediators include histamine, proteases, leukotrienes, prostaglandins, chemokines, and cytokines, and their job is to signal and guide other cells, tissues, and organs to respond to the hostile invaders, therefore mast cells are protecting us from infection, heal wounds, create new blood cells, and develop immune tolerance.

However, if these cells are dysfunctional or overactive, they can cause serious issues. (3) In case of MCAS the mast cells secrete too much mediators, not just histamine, though, histamine is still a major component.

What is Mast Cell Activation Syndrome?

Mast cell activation syndrome (MCAS) is an immunological condition where mast cells inappropriately release excessive chemical mediators. (4) In most cases, this condition is mild, however, it can exacerbate due to stressful life events.

MCAS symptoms

The symptoms of MCAS are the same as those of histamine intolerance. The difference between these two health problems may be that while histamine intolerance is caused by some kind of inflammation and methylation disorder or/or DAO enzyme deficiency, which may improve after the cause is removed, in the case of MCAS, the mast cells are too sensitive to triggers and often inexplicably the patient produces symptoms for no reason, and this state of health can hardly be reversed, it can only be maintained.

The most common symptoms of MCAS include:

  • The trouble with allergies and asthma
  • Overreaction to insect bites, bee stings, and chemical intolerances
  • Facial and chest flushing skin rashes including hives and angioedema
  • Itchiness and a burning feeling
  • Brain fog and headaches
  • Poor wound healing and easy bruising

Symptoms in bulk:

Red eyes, irritated eyes, dry eyes, burning eyes, vision problems and conjunctivitis, nasal congestion, sinusitis, runny nose, laryngitis and intranasal wounds, tinnitus, clogged, acne, acne wounds, itchy throat, itchy throat difficulty swallowing, hives, skin flushing, itching, skin rashes, flushing, bruising easily , angioedemareddish or pale complexion, cherry angiomata (skin growths), patchy red rashes, red face in the morning, cuts that won’t heal, fungal skin infections, fainting, fainting upon standing, increased pulse rate (tachycardia), palpitations, spikes and drops in blood pressure, high pulse or temperature, high triglycerides, lightheadedness, dizziness, hot flashes, wheezing, asthma, shortness of breath, difficulty breathing deep, abdominal pain, epigastric tenderness, nausea, vomiting, diarrhea and/or constipation, abdominal cramping, bloating,

GERD/acid reflux, high colesterol, high bilirubin, elevated liver enzymes, numbness and tingling in the hands and feet, headaches, migraines tics, tremors, brain fog, memory loss, poor concentration, difficulty finding words, muscle pain, fibromyalgia, muscle weakness, blood clots, deep vein thrombosis, increased bruising, heavy menstrual bleeding, bleeding nose, anemia, increased white blood cell count, platelets, decreased white blood cell counts, decreased neutrophils, decreased lymphocytes, decreased platelets, excesses of IgA, IgG, IgM, IgE, increased MCV, anxiety, panic, depression, decreased attention span, attention deficit/hyperactivity disorder (ADHD), forgetfulness, and insomnia, anaphylaxis.

Possible causes

The exact cause of mast cell activation syndrome is unknown. It is sometimes called an idiopathic condition because it is hard to determine the exact thing that triggers mast cell overactivation.  (6)

This condition can be present if the mast cells are abnormal but in secondary MCAS, the mast cells themselves are normal, but they become abnormally activated by an external stimulus. People with secondary MCAS have triggers that provoke an exaggerated immune response. MCAS actually is a multisystem condition and the main suspected cause in most cases is some form of inflammation. If you have been diagnosed with any of the following conditions, probably MCAS can also be detected. Health issues may include, but are not limited to the following (7):

Chronic Inflammatory Response Syndrome (CIRS)
Irritable bowel syndrome
Intestinal dysbiosis
SIBO
Obesity, Diabetes
Toxins
Asthma and allergies
Autoimmune diseases (lupus, rheumatoid arthritis and Hashimoto’s disease)
Candida overgrowth
Celiac disease
Parasitic infections
Skin diseases such as eczema and psoriasis
Food intolerance and allergies
Gastroesophageal Reflux (GERD)
Infertility and endometriosis

Health conditions that can aggravate MCAS:

Chronic inflammatory response syndrome (CIRS),
Poor methylation due to genetic MTHFR defects (leading to low SAMe levels that degrade histamine intracellularly),
Histamine N-methyltransferase HNMT enzyme deficiency.
Lack of an enzyme based on intestinal diamine oxidase (DAO) that breaks down histamine of food. (8,9)

Diagnosis of mast cell activation syndrome (11)

First of all the proper diagnosis of MCAS requires the presence of several symptoms from the list above. In addition, other disorders should be ruled out by a functional medicine professional.
When symptoms listed above affecting at least 2 organs are present and they are chronic and are found not to be caused by another health condition, the presence of MCAS is suspected.

The second necessary criteria is the examination of  serum tryptase levels, i.e., if the tryptase level rises above a threshold within a narrow (usually one to two hours) time interval after a symptomatic episode. According to the consensus serum tryptase levels that are at least 20% above baseline serum tryptase levels, plus 2 ng / ml, after the onset of symptoms, meets the second criterion of mast cell activation syndrome.

For example, if a patient had a basal (baseline level, at least 24 hours after a reaction) serum tryptase level of 8 ng/ml, a 20% rise, plus 2 ng/ml, would be 11.6 ng/ml. To meet the above criterion for serum tryptase, the patient would need a post-reaction serum tryptase level above 11.6 ng/ml. The calculation would be conducted as follows:

(8 ng/ml x 1.2) + 2 ng/ml = 11.6 ng/ml
If tryptase level does not rise sufficiently to meet the growth required for the co-criterion, other mediator tests may be sufficient. Examples include elevated urinary n-methylhistamine, prostaglandin D 2 or its metabolite, 11β-prostaglandin F 2α (24-hour urine test for any of the three).

Finally, the third co-criterion requires a response to drugs that inhibit the action of histamine and to drugs that inhibit other mediators produced by mast cells or inhibit the release of mast cell mediators. You can read about this in moredetails in the “Balance your histamine release protocol”.

Resources
  • m B-R, SeoH-S, Ku J-M, et al. Silibinininhibits the production of pro-inflammatory cytokines through inhibition of NF-κB signaling pathway in HMC-1 human mast-cells. Inflammation. Research. 2013;62(11):941-950. doi:10.1007/s00011-013-0640-1.
  • ChapowalA. PetasitesStudy Group. Randomisedcontrolled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ 2002;324:144-6.
  • Hayes, N. A. and Foreman, J. C. The activity of compounds extracted from feverfew on histamine release from rat mast-cells. J Pharm Pharmacol1987;39(6):466-470
  • Hsieh et al. Baicalein inhibits IL-1ß- and TNF-a-induced inflammatory cytokine production from human mast-cells via regulation of the NF-?B pathway. ClinMolAllergy. 5: 5. 2007.
  • TheoharidesTC, Patra P, Boucher W, et al. Chondroitin sulphateinhibits connective tissue mast-cells. British Journal of Pharmacology. 2000;131(6):1039-1049. doi:10.1038/ sj.bjp.0703672.
  • Ro JY, Lee BC, Kim JY, et al. Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast-cells activated with specific antigenantibodyreactions. J PharmacolExpTher. 2000;292:114–121. 73.
  • https://www.ncbi.nlm.nih.gov/pubmed/24477254
  • https://www.ncbi.nlm.nih.gov/pubmed/28458279
  • https://www.ncbi.nlm.nih.gov/pubmed/9421440
  • https://www.ncbi.nlm.nih.gov/pubmed/10344773
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/