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Untangling Histamine Intolerance: Strategies for Finding Interstitial Cystitis Relief

Updated: Nov 25, 2023

Histamines play a critical role in our bodies in combatting potential attacks. When the body detects an external force that could cause problems, one of the immediate responses is to send out “the immune system troops” as a defense. However, this isn’t the only way that histamines participate in bodily functions; they are also involved in hormonal balance, digestion, our central nervous system, and our perception of pain. Due to this integrated process, things can go very wrong when an individual develops histamine intolerance. An imbalance in histamines can potentially contribute to autoimmune diseases and the development of interstitial cystitis. Understanding how histamine functions can assist in pinpointing and altering behaviors, items, foods, and environmental triggers that play a role in histamine intolerance and similar long-lasting health issues.


Histamine 101 Explained Histamines are stored in the body's mast or “immune” cells, as well as a type of white blood cell called “basophils.” They are an integral part of our local immune systems and are designed to immediately react to an injury or attack. Examples of an “attack” might be a bee sting, pollen or food allergy, or an injury that breaks the skin. For allergies, an attack can be anything that you breathe in or eat that you are allergic to. The immediate symptom is puffiness, swelling, itching, sneezing, and/or your sinuses filling up. When the cells are notified of any form of attack, they release histamines, and these cause blood vessels in the area of the attack to leak out the contents to get the immune cells to the necessary area(s).

Other Histamine Jobs Histamines are neurotransmitters that act as communicators to send priority messages from the brain to your body. Science has found that histamines are part of the components of stomach acids that assist in breaking down food. This means that histamine levels can affect digestion, food breakdown, and absorption.

Histamines and Ovulation Another important interaction involves the connection between female hormones and histamines. Estrogen, a hormone, can boost the creation of histamines in certain cells while also inhibiting the performance of the DAO enzyme in the gut (Diamine oxidase is a vital enzyme in the body, mainly in the gut lining, responsible for breaking down histamine). On the contrary, progesterone, another hormone, works in the opposite way by increasing the regulation of DAO, which helps manage histamine levels. This intricate relationship between hormones and histamines highlights the complex nature of histamine intolerance and its ties to hormonal changes. This is important to note for those who may suffer from histamine intolerance because IC symptoms may vary during different times of the ovulation cycle. You may notice that symptoms are the worst in the first two weeks of ovulation, but the symptoms will lessen as estrogen decreases and progesterone increases.


Histamine Intolerance The job of histamines is to cause the blood vessels in the body to dilate or swell so that the all-important white blood cells can locate and attack a problem or infection. When all is balanced, the body’s natural immune response helps fight off the intrusion or problem and bring about healing. Once the job of the histamine is done, the body’s enzymes break down histamines so that they don’t build up. However, when something goes wrong, and enzymes don’t break down the histamines properly, you can develop what is known as “histamine intolerance.” Since histamines travel through the bloodstream, the buildup can affect all portions of your body, including the gut, lungs, bladder, skin, brain, and cardiovascular system. Histamine intolerance can create a condition where the body's responses are over-exaggerated.


Histamine intolerance can be problematic for individuals with interstitial cystitis due to the presence of histamine receptors in the bladder. In some people with interstitial cystitis, the bladder wall becomes inflamed and irritated, leading to various symptoms like pain, urgency, and frequency of urination. Histamine, as a signaling molecule, can exacerbate this inflammation by binding to its receptors in the bladder, triggering a heightened immune response and worsening symptoms. For individuals with interstitial cystitis, who might already have a sensitive and inflamed bladder, increased histamine levels from either dietary sources or internal factors can contribute to increased discomfort and exacerbation of their condition.

Most Common Causes of Histamine Intolerance If the body's natural mechanisms are sluggish or somewhat inactive in clearing out accumulated histamines, it can lead to an exaggerated response when situations arise that demand histamine release. This results in an excessive discharge of histamines, leading to an overwhelming surplus that triggers severe symptoms.


Certain causes of histamine intolerance are rooted in genetics, often concerning enzymes that have lower activity levels, which can become overwhelmed when faced with excessive environmental or dietary histamine, leading to an accumulation that can't be effectively processed. The primary enzyme responsible for breaking down histamine is called diamine oxidase (DAO). Histamine intolerance can also stem from factors like leaky gut, small intestinal bacterial overgrowth (SIBO), and an inadequate diet.


The DAO enzyme mentioned earlier can also be affected by foods that act to block the enzyme. These can include: alcohol, black tea, green tea, mate tea, and energy drinks. Other causes for low DAO can include Gluten intolerance, leaky gut, SIBO, inflammation from Crohn’s, ulcerative colitis, and inflammatory bowel disease. Medications also affect DOA, specifically the histamine blockers that many people take, which deplete the body of DOA.

Medications that affect DOA include:

  • Non-steroidal anti-inflammatory drugs (ibuprofen, aspirin)

  • Antidepressants (Cymbalta, Effexor, Prozac, Zoloft)

  • Immune modulators (Humira, Enbrel, Plaquenil)

  • Antiarrhythmics (propranolol, metoprolol, Cardizem, Norvasc)

  • Antihistamines (Allegra, Zyrtec, Benadryl)

  • Histamine (H2) blockers (Tagamet, Pepcid, Zantac)

Specific dietary problems for histamine intolerance include foods already high in histamines such as spinach, tomatoes, proteins, fermented foods, avocado, eggplant, bananas, fermented alcohol products such as wine, vinegar, nuts, aged cheeses, cured meats, soured foods such as buttermilk and sour cream, smoked fish, chocolate, dried fruit, most citrus fruits, cow’s milk, papaya, pineapple, shellfish, strawberries, wheat germ, many of the artificial dyes and preservative additives. There are also dietary deficiencies that can cause histamine intolerance. These include low vitamin B12, B6, B2, and B1 intake, and folate. Low mineral deficiencies can include zinc, copper, magnesium, and methionine.


Environmentally caused histamine intolerance can include living or working in a location with a high pollen count, mildew, mold, dust mites, and natural gas leaks. It’s also understood that some estrogen-based medications such as birth control pills or hormone replacement therapy, can contribute to histamine intolerance. Hormonal imbalances create a condition where the body can’t metabolize estrogen well in the liver and this can lead to a situation known as “estrogen dominance,” which increases histamines as well as affects PMS, and creates heavier menstrual cycles and interstitial cystitis symptoms.

Genetic Variants Explained The most prevalent genetic variations involve SNPs (single nucleotide polymorphisms), where a DNA building block is substituted with another that functions less effectively, reducing enzyme efficiency. These variations arise from diverse DNA building blocks, also known as single nucleotide bases, each governing various functions. Some rely on specific vitamins like B2, iron, and B5, while others produced due to gut infections necessitate B6 and copper. Each of these components crucially contributes to achieving a balance between stable mast cell production and effective histamine reduction. The genes that are susceptible to these issues encode enzymes responsible for clearing out or metabolizing histamines. Various factors, including an inadequate diet and lifestyle, can contribute to these challenges.


Most Common Histamine Intolerance Symptoms: While many of us may have some of these symptoms, you may fall prey to histamine intolerance if you experience more than just a few. The symptoms can include:

  • Headaches, including migraines

  • Problems sleeping, including falling and staying asleep

  • High blood pressure or hypertension

  • Dizziness or vertigo

  • Accelerated heart rate, aka arrhythmia

  • Problems regulating body temperature

  • Anxiety

  • Nausea and/or vomiting

  • Cramping in the abdominal area

  • Hives

  • The swelling of tissue

  • Flushing

  • Nasal congestion and sneezing

  • Runny nose

  • Seasonal allergies

  • Difficulty breathing

  • Asthma, including when exercising

  • Abnormal menstrual cycle

  • Exhaustion or fatigue

  • Itching

  • Irritability

  • Motion sickness

  • Interstitial cystitis symptoms, including urgency and pain

Best Diet to Overcome Histamine Intolerance If you find that you are experiencing a lot of the histamine intolerance symptoms, adjusting your diet to include the following can assist you. A low-histamine diet should include:

  • Freshly cooked meat or poultry

  • Freshly caught fish

  • Cooked eggs

  • Gluten-free grains: rice, quinoa, corn, millet, amaranth, teff

  • Pure peanut butter

  • Fresh fruits: mango, pear, watermelon, apple, kiwi, cantaloupe, grapes

  • Fresh vegetables (except tomatoes, spinach, avocado, and eggplant)

  • Dairy substitutes: coconut milk, rice milk, hemp milk, almond milk

  • Cooking oils: olive oil, coconut oil

  • Leafy herbs

  • Herbal teas

Supplements that might help alleviate histamine intolerance include:

  • Buffered Vitamin C: Known for its antioxidant properties, vitamin C can help support the breakdown of histamine.

  • Quercetin: This flavonoid has anti-inflammatory and antihistamine properties, potentially aiding histamine regulation.

  • Vitamin B6: Important for DAO enzyme function, vitamin B6 can contribute to efficient histamine breakdown (if you are sensitive, it's best to consume foods high in vitamin B6).

  • Methylated Vitamin B12: Supports overall immune and nervous system health, potentially assisting in histamine management.

  • Copper: Essential for DAO enzyme activity, copper can help modulate histamine levels.

  • Zinc: Plays a role in DAO enzyme production and function, which could aid in histamine metabolism.

  • Probiotics: Beneficial bacteria in the gut can enhance gut health, potentially reducing histamine-producing gut infections.

  • Omega-3 Fatty Acids: Possessing anti-inflammatory properties, omega-3s might help manage histamine-related inflammation.

  • Magnesium: Can potentially improve DAO enzyme function and mitigate histamine buildup.

  • Nettle Leaf: A natural antihistamine, nettle leaf may help counter histamine effects.

  • Berberine: This can potentially enhance the effectiveness of quercetin and other antihistamines.

  • Seeking Health Histamine Digest: A DAO enzyme supplement to support histamine food intolerance and digestive health. Take it before eating.


Mast Cell Activation and Mastocytosis and Interstitial Cystitis While histamine intolerance is considered to be less severe, mast cell activation and mastocytosis is associated with conditions such as interstitial cystitis and inflammatory bowel disease (IBD). Specialists don’t have a complete handle on these conditions. However, they do know that in many inflammatory conditions, there is an overabundance of mast cells (mastocytosis) or overactive mast cells (MCAS or mast cell activation syndrome). These conditions may be helped by reducing histamine intake, but they are more severe and can interfere with daily life, requiring treatments from specialists.

The bladder contains mast cells with numerous granules that release essential molecules. Factors such as medications, extreme cold, stress, trauma, toxins, and neuropeptides can trigger these mast cells to release their contents, leading to sensitization of sensory neurons, which perpetuates mast cell activation. This sets off a chain reaction, potentially resulting in blood vessel dilation, inflammation of the bladder mucosa, and attraction of inflammatory cells. Mast cell activation has been linked to various interstitial cystitis issues. This condition is considered a syndrome arising from multiple factors, and researchers studying it have identified mast cell activation and bladder mastocytosis as contributing elements.

Actions That You Can Take If you have been living with some or all of these symptoms, there are some actions that you can take to get your “normal” life back.

  • Alter your diet to include low histamine food intake.

  • Address and heal a leaky gut through diet, lifestyle, and treating any infections.

  • Stress reduction: Adrenaline and cortisol are created when stressed and place a significant demand on your overall health, including increased histamine problems.

  • Think about getting a genetic test: Your genetic predisposition can play a major part in your health, and there are some choices that you may have. To learn more and find a healthcare professional: http://gettoknowyourdna.com/

  • Clean up your environment: Reduce dust in your home, use an air purifier, avoid scented candles, fragrances, perfumes, regular detergents, fabric softeners, and cleaning products, and replace them with clean, non-toxic products.

  • Take Supplements to help.

Histamine intolerance can play a significant role in exacerbating interstitial cystitis (IC) symptoms. Understanding the complex connections between histamines, mast cells, and the bladder's sensitivity provides insights into potential approaches for relief. To address this issue and alleviate discomfort, a holistic strategy is important. This involves modifying your diet to avoid histamine-rich foods, incorporating natural antihistamines, and considering DAO enzyme supplements. Managing stress, promoting gut health, and seeking guidance from healthcare professionals tailored to your needs are crucial steps in lessening the impact of histamine intolerance on IC symptoms. By combining lifestyle changes and well-informed techniques, individuals dealing with histamine intolerance can aim for an improved quality of life and diminished IC-related challenges.




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