Histamine Intolerance: The Hidden Cause of Your Mystery Symptoms

If you’ve ever felt like your body is playing a cruel game of ‘guess what’s wrong now,’ you’re not alone. One day, it’s a pounding headache; the next, your skin is breaking out in hives, or your stomach is in knots after a meal you’ve eaten a hundred times before. Maybe you’ve been told it’s stress, allergies, or even ‘just in your head.’ But what if there’s a deeper reason for these seemingly random symptoms? Histamine intolerance is often overlooked, yet it could be the missing link behind your body’s unexplained reactions. Let’s break it down and figure out what’s really going on.

What is Histamine Intolerance?

Histamine intolerance is a condition in which the body is unable to properly break down and regulate histamine, a compound involved in immune responses, digestion, and neurological function. Unlike a food allergy, which involves an immune system reaction, histamine intolerance occurs when histamine accumulates in the body due to an imbalance between its production and degradation. The enzyme diamine oxidase (DAO) is responsible for breaking down histamine in the gut, and when DAO activity is insufficient, histamine builds up, leading to symptoms that mimic allergic reactions.

Symptoms of Histamine Intolerance

Histamine intolerance presents a wide range of symptoms, making it difficult to diagnose. Common symptoms include:

●     Skin Reactions: Flushing, hives, itching, and eczema-like rashes

●     Digestive Issues: Bloating, diarrhea, nausea, and acid reflux

●     Neurological Symptoms: Headaches, migraines, dizziness, and anxiety

●     Cardiovascular Effects: Palpitations, low blood pressure, and irregular heartbeat

●     Respiratory Symptoms: Nasal congestion, sneezing, and difficulty breathing

●     Hormonal and Menstrual Irregularities: Worsened PMS, irregular cycles, and hot flashes

Because histamine affects multiple systems in the body, individuals with histamine intolerance often experience symptoms that fluctuate in severity and duration.

Why is Histamine Intolerance Often Misdiagnosed?

One of the biggest challenges with histamine intolerance is that it overlaps with many other conditions. It is frequently mistaken for allergies, irritable bowel syndrome (IBS), and even anxiety disorders. Conventional testing often does not identify histamine intolerance because there is no single definitive test to diagnose it. Blood tests can measure histamine levels or DAO activity, but results may not always correlate with symptoms. This leads to a frustrating cycle where individuals may undergo numerous tests and treatments without finding relief.

Triggers and Contributing Factors

Several factors can contribute to histamine intolerance, including:

●     Gut Health Imbalances: A healthy gut microbiome is essential for proper histamine metabolism. Dysbiosis, leaky gut, and small intestinal bacterial overgrowth (SIBO) can impair DAO production and lead to histamine buildup.

●     Nutrient Deficiencies: DAO enzyme function depends on certain nutrients, particularly vitamin B6, copper, and vitamin C. Deficiencies in these nutrients can exacerbate histamine intolerance.

●     Hormonal Fluctuations: Estrogen can promote histamine release, which is why some women notice worsening symptoms around ovulation or during PMS.

●     High-Histamine Foods: Aged cheeses, fermented foods, alcohol, processed meats, and certain vegetables like tomatoes and spinach are naturally high in histamine and can contribute to symptoms.

●     Medications: Some medications, including NSAIDs, antidepressants, and antihistamines, can interfere with DAO activity and histamine breakdown.

Testing for a Proper Diagnosis

Functional lab tests are used to measure histamine levels and diamine oxidase (DAO) activity. A high histamine to DAO ratio can indicate that a person is consuming too many histamine-rich foods and has insufficient enzymes to break down histamines.

Some practitioners may also use a histamine skin prick test to detect elevated levels.

While detecting high histamine levels is relatively straightforward, pinpointing the root cause of histamine intolerance is more complex. Practitioners may run additional tests, such as allergy tests, or investigate whether medication overuse is a contributing factor. It's also common to test for nutrient deficiencies or food intolerances. Conditions like leaky gut or small intestinal bacterial overgrowth (SIBO) are often examined as well.

A Whole-Body Approach to Managing Histamine Intolerance

Managing histamine intolerance involves more than simply avoiding high-histamine foods. A whole-body approach focuses on supporting gut health, optimizing nutrient levels, and reducing inflammation.

1. Supporting Gut Health

Since DAO is produced in the gut, improving gut health is a crucial step. Strategies include:

●     Healing the Gut Lining: Consuming bone broth, collagen, and glutamine can help repair intestinal permeability (leaky gut), which is often a contributor to histamine intolerance.

●     Balancing the Microbiome: Introducing probiotics that do not produce histamine, such as Lactobacillus rhamnosus and Bifidobacterium infantis, can support gut balance without exacerbating symptoms.

●     Addressing SIBO and Dysbiosis: If an overgrowth of bacteria is present, antimicrobial herbs, probiotics, and a temporary low-histamine diet may help rebalance the gut.

2. Optimizing DAO Activity and Nutrient Levels

Ensuring adequate levels of nutrients that support DAO function is essential. These include:

●     Vitamin B6: Found in poultry, bananas, and potatoes, B6 is crucial for DAO production.

●     Vitamin C: Acts as a natural antihistamine and supports immune function.

●     Copper: Helps activate DAO and is found in nuts, seeds, and organ meats.

●     Quercetin: A flavonoid with mast cell-stabilizing properties that can help reduce histamine release.

3. Adopting a Low-Histamine Diet Temporarily

While diet is not the root cause of histamine intolerance, temporarily reducing high-histamine foods can provide symptom relief while the body heals. Focus on fresh meats, non-citrus fruits, leafy greens, and freshly prepared meals rather than leftovers, which tend to accumulate histamine.

4. Reducing Stress and Supporting Detoxification

Chronic stress can contribute to histamine intolerance by increasing inflammation and impairing gut function. Practices such as deep breathing, gentle exercise, and sufficient sleep can help regulate histamine levels. Supporting liver detoxification through adequate hydration and cruciferous vegetables can also aid in breaking down histamine more efficiently.

 

Histamine intolerance is a complex condition that is often overlooked and misdiagnosed due to its wide-ranging symptoms. A whole-body approach that includes gut healing, nutrient optimization, stress management, and dietary adjustments can help restore balance and reduce symptoms. By addressing the root causes rather than just managing symptoms, individuals can achieve lasting relief and improve overall well-being.

References

https://www.rupahealth.com/post/a-functional-medicine-approach-to-histamine-intolerance

Jochum C. Histamine Intolerance: Symptoms, Diagnosis, and Beyond. Nutrients. 2024 Apr 19;16(8):1219. doi: 10.3390/nu16081219. PMID: 38674909; PMCID: PMC11054089.

Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-96. doi: 10.1093/ajcn/85.5.1185. PMID: 17490952.

Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020 Aug 14;10(8):1181. doi: 10.3390/biom10081181. PMID: 32824107; PMCID: PMC7463562.

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Strep Infection Affecting Behavior in Children (Copy)

What’s the big deal about Strep?

We’ve all heard of strep throat. Maybe even been diagnosed with it a time or two. Its a pretty common childhood infection that most of the time ends up resolving without sequelae after a short course of antibiotics. But we are learning that Group A Strep (GAS), the type of bacteria responsible for this infection has some extra ‘abilities,’ that can create complications in children following infection - especially in cases where the children are asymptomatic and go without treatment for an extended period of time.

While most individuals who experience a GAS infection develop symptoms such as sore throat, fever, chills, headache, possibly even abdominal pain, vomiting or rash, sometimes kiddos can be completely asymptomatic while harboring a strep infection. This actually happened to my son this past year. I had been getting messages from his kindergarten teacher several times a week regarding his ‘mischievious’ behaviors.  She confirmed that these were more than to be expected from the average active 5-6 year old boy. At home he was almost always in an awful mood, oppositional to the point of just toeing the line to see what he could get away with, and hyperfixated on curse words - like listening to music with profanity if he could get away with it and getting other kids to repeat those words at school - he was nearly obsessed with things he knew he wasn’t supposed to do, say or watch. We were in for a behavioral assessment per his teacher’s recommendation, and the pediatrician noticed his weight was down a few pounds. He denied any discomfort, but I mentioned he had seemed to be urinating more frequently (although not increasingly thirsty). She ordered a urinalysis and found there was moderate blood in his urine. Based on the blood, she ordered a rapid strep test (hematuria can follow a GAS infection). The rapid came back negative but culture popped positive for GAS.

Following the positive strep culture, we gave him a complete course of amoxicillin, which was challenging for me to agree to since he was asymptomatic…but strep is an infection that if we have confirmation of its existence, we really do need to address it. Left untreated, unpleasant things can happen. More to come on that.

This treatment took place over Christmas break. By the time the kids returned back to school, I was noticing gradual improvements in his behavior, but I thought it might be because of being home and having so much time together as a family and him receiving plenty of attention. His teacher remarked on the change in him as well. He was on a behavior check-in sheet daily that involved tallying behavior points to see if he could meet or exceed his points goal for each day. His goal was 46. Prior to treatment he was getting probably 30-40 points out of 56. Since eradicating the strep infection he has missed maybe 1-2 points almost every day, often getting a perfect score, and with the worst day being a substitute teacher when he earned only a 50 (less structure, off schedule, new person, etc). His teacher cannot get over his change in behavior. And he now asks us to quickly change the channel if he even hears an ‘almost’ curse word. He sits and builds legos for hours, asks to be a helper at school, and is patient and able to redirect himself when his brother is pushing his buttons. In the past, this would have been an emotional meltdown, often resulting in physical retaliation with a closed fist.

How does strep affect the brain if it lives in the throat?

You might have heard of a condition called rheumatic fever - very rare to see in the developed countries because we tend to (unfortunately) treat every kid with a sore throat with antibiotics even without testing or with a negative test. Rheumatic fever is an immune-mediated disease that occurs primarily as a complication of GAS infections. This is more common when strep infections aren’t treated immediately or completely. Complications with rheumatic fever occur because of what we refer to as a ‘virulence factor’ possessed by Group A Strep (GAS), which causes antibodies that the body creates toward a protein on the cell wall of the strep bacteria to also attack our own native tissue. This can affect the heart tissue and valves by chemicals called cytokines that are released by our immune system in an effort to destroy the invader. Because of this ‘molecular mimicry’ by the bacteria, the immune system reacts not only to the strep molecules but also to the human host molecules that were mimicked; an example of ‘cross-reactive’ antibodies. So basically, the body starts attacking itself (the innocent bystander) while trying to fight off the enemy. This is the foundational concept of most autoimmune diseases.

Studies at the National Institute of Mental Health (NIMH) and elsewhere have shown that some cross-reactive antibodies target the brain, accounting for the neuropsychiatric symptoms that can develop during/following infection. The basal ganglia has been suggested by MRI imaging in studies of children with neuropsychiatric symptoms following GAS infection to incur the greatest deal of inflammation. These conditions cause by GAS are referred to as PANDAS ( Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections)- however, Pediatric Acute-onset Neuropsychiatric Syndrome, or PANS, is an overlying group that has described the development of the same spectrum of symptoms following other infections like Lyme disease or Epstein Barr (mono), even Influenza A.

Severe cases of PANS/PANDAS cause symptoms such as dramatic behavioral changes, like the sudden onset of tics, OCD symptoms, bedwetting, and separation anxiety. More mild cases can be less obvious but cause increased trouble at school due to deterioration of learning abilities, developmental regression, aggression, irritability, emotional lability, oppositional behavior, urinary frequency, and sleep disturbances. I have heard of and worked with kids who have had the more severe and evident symptoms following a known infection with sore throat and fever, but it just wasn’t on my radar with my son being asymptomatic. Now I wonder what if he had never been tested and treated? Would it have worsened, or self-resolved? The results could be different for each kid depending on the how robust their immune system and what other factors might be taxing their immune reaction, such as other latent infections like Lyme or even environmental toxins (ie from processed foods, pesticides, personal care products, etc).

So do we just go around routinely testing kids for GAS? I don’t think so, but education and awareness are key. We (in the medical field) have previously assumed these autoimmune/inflammatory reactions to be relatively rare, and I’ve worked with several kiddos who were brushed off by their pediatricians because they didn’t believe in or understand the PANS/PANDAS existence. PANS and PANDAS are thankfully becoming increasingly recognized in the clinic and multiple parent interest groups are presently active in several European countries. A USA 2015 consensus paper for the diagnostic work-up recommended a broad assessment including psychiatric, immunological and infectious disease evaluation. However, some parts of these recommendations (i.e. the blood tests recommended) have been criticized for not being based on published patient data, The National Institute for Health and Care Excellence guidelines on OCD mention PANDAS, but do not provide a comprehensive description or any clinical guidelines.

A rapid strep test doesn’t always catch GAS infection if the child is asymptomatic. Some alternative tests that can be performed include an anti-strep antibody titer (i.e., the number of molecules in blood that indicate a previous infection), but this only tells us whether the child has ever had a previous strep infection. Sometimes based on the levels we can assume its been a recent infection, but its not always reliable because some children have 'positive' antibody titers for many months after a single infection.

A functional test that has been used fairly successfully in the functional medicine world is the Neural Zoomer, which measures immune reactivity to structures, tissues, cells, and chemicals in the brain and peripheral nervous system. This test can detect underlying inflammatory responses that may be causing symptoms related to mood, memory, aging, balance, nervous function, movement, pain, and more.

In addition, a thorough symptoms analysis and medical history may be enough to warrant a trial course of treatment. In addition to antibiotics (with good support of gut flora during treatment), a focus on nutritional support and management of other potential toxins contributing to inflammation can help mediate symptoms.

So what if you suspect your child is suffering from PANS/PANDAS but your pediatrician doesn’t understand or want to consider these conditions? You can look for a physician who specializes in the PANDAS Physicians Network (https://www.pandasppn.org/), or you can reach out to chat with me about working one-on-one to assess/manage the condition. Trust me, having been through it myself (albeit on a mild scale), I can’t tell enough people about this experience. Imagine your kiddo suffering from mental health and behavioral issues because of a sneaky little bacterial infection we have the tools to easily treat...

https://www.nimh.nih.gov/health/publications/pandas

https://pmc.ncbi.nlm.nih.gov/articles/PMC6401534/https://pmc.ncbi.nlm.nih.gov/articles/PMC6401534/

https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2020.00564/full

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When Your Hormones Are Telling You To Rest: A Comparison of Conventional and Functional Syndromes

What are the similarities between Overtraining Syndrome and HPA Axis Dysfunction?

As a functional medicine provider, I often find myself explaining that we aren’t inventing new diseases—we’re simply identifying and addressing root causes before they escalate into full-blown dysfunction. At a Sports Medicine (conventional medicine CME) conference this past week, one of the topics covered was something referred to as Overtraining Syndrome (OTS) in athletes. The similarities between OTS and what we in functional medicine refer to as HPA (hypothalamus-pituitary-adrenal) axis dysfunction are undeniable. Both conditions describe the body’s struggle to recover from chronic stress, yet one is widely recognized in conventional medicine, while the other is often dismissed.

Read on for side-by-side comparison.

The Three Stages of Overtraining Syndrome

OTS occurs when the body endures excessive training without adequate recovery, leading to a breakdown in performance and overall health. It progresses in three stages that affect the autonomic system and HPA axis:

1. Functional Overreaching: This is the “pushing through” phase many athletes experience. Mild fatigue, slight decreases in performance, and subtle mood changes appear but resolve with proper rest.

2. Non-Functional Overreaching: Recovery now takes longer, and symptoms intensify. Persistent fatigue, irritability, disrupted sleep, and decreased motivation start to interfere with training and daily life. The sympathetic nervous system is dominant and hypervigilant in this stage. Patients often overall just feel 'unwell.' 

3. Overtraining Syndrome: This is where things get serious. Chronic exhaustion, persistent muscle soreness, hormone imbalances, immune dysfunction, depression, and even increased injury risk become apparent. The body’s stress response is now completely dysregulated, and the parasympathetic nervous system dominates. This means excessive weight gain, brain fog - stuck in the 'rest and digest' mode.

The Connection to HPA Axis Dysfunction

In functional medicine, we recognize a nearly identical pattern in individuals exposed to prolonged stress, whether from overexercise, work, relationships, or other life demands. The hypothalamic-pituitary-adrenal (HPA) axis is responsible for regulating our stress response, primarily through cortisol production. Chronic stress—whether from overtraining or life stressors—leads to dysregulation, which progresses in much the same way as OTS.:

1. Acute Stress Response: Initially, the body responds with heightened cortisol production, keeping energy levels high and increasing alertness. (This is GOOD in the short term..not so good when we live in a prolonged acute stress response. In that case we progress to compensatory dysregulation in stage 2).

2. Compensatory Dysregulation: The system becomes overwhelmed, and cortisol patterns become erratic. Fatigue, disrupted sleep, and mood changes, like anxiety, emerge. Just as in non-functional overreaching, the sympathetic nervous system tends to be dominant and hypervigilant in this stage. 

3. Adrenal Exhaustion (or HPA Axis Dysfunction): The body can no longer mount an appropriate stress response. Cortisol levels may plummet, leading to extreme fatigue, burnout, brain fog, hormonal imbalances, and immune suppression. Once again, in stage 3, parasympathetic output dominates the body's everyday processes and causes a significant struggle to think clearly, function effectively, and lose weight. 

Functional Medicine Bridges the Gap

The medical world acknowledges Overtraining Syndrome as a real and debilitating condition, yet when similar symptoms arise in non-athletes due to chronic stress, conventional medicine often dismisses them. This is where functional medicine shines—we recognize that the body doesn’t differentiate between stress from excessive workouts and stress from an overbooked schedule.

By addressing HPA axis dysfunction early—through lifestyle adjustments, targeted nutrition, stress management, and adaptogenic herbs—we can prevent the downward spiral that leads to full-blown burnout.

The key message here is that the conventional medicine-defined Overtraining Syndrome and the functional medicine-recognized HPA axis dysfunction are just different names for the same physiological response to chronic stress. Functional medicine isn’t reinventing the wheel; we’re simply recognizing and treating these patterns before they become debilitating.

Overtraining Syndrome: A Practical Guide - PMC

A Review of Overtraining Syndrome—Recognizing the Signs and Symptoms - PMC

Introduction to the Hypothalamic-Pituitary-Adrenal Axis: Healthy and Dysregulated Stress Responses, Developmental Stress and Neurodegeneration - PMC

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