Unraveling the Allergy-Gut Connection: A Journey to Histamine Balance

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Adapted from episode 105 of The Perfect Stool podcast hosted by Lindsey Parsons, EdD, Gut Health Coach, and edited for readability.

What are allergies, and what causes allergic reactions in the body?

Allergies are immune system reactions to substances that are typically harmless to most people but trigger an exaggerated response in those who are allergic. The immune system plays a crucial role in protecting the body from harmful invaders, such as viruses and bacteria. However, in the case of allergies, it can mistakenly identify allergens, like pollen, dust mites, pet dander or certain foods, as threats. When someone with allergies encounters these allergens, their immune system releases chemicals like histamines and cytokines from their mast cells, which are cells found in the skin and mucous-lined surfaces of the body, including the digestive tract, which are intended to ward off the perceived threat. These chemicals cause common allergy symptoms such as sneezing, itching, swelling, and congestion. Essentially, allergies are a result of the immune system’s overzealous response to substances it incorrectly perceives as dangerous. 

I’m sure you’re familiar with over-the-counter cures for allergies: antihistamines like Claritin, Zyrtec and Benadryl, which help quell the histamine response. These antihistamines are like putting a band-aid on the issue by blocking histamine receptors, but they don’t actually do anything about the histamine levels themselves. So, they’re great for comfort, but they’re not a long-term fix, and have unwanted side effects like drowsiness and lower stomach acid levels, which will impact your protein digestion and can lead to a higher stomach and intestinal pH, which as I’ll explain later, is counterproductive. 

So let’s dig a bit more into histamine. First of all, it’s not just the chemical our bodies produce when our immune system goes into battle mode, but it’s also involved in a lot of other biochemical processes, including regulating our digestion, helping us to build stomach acid, and serving as a neurotransmitter that regulates other neurotransmitters like serotonin. Histamine is also involved in helping wake us up as part of our sleep cycle. It’s also involved in our circulatory system, menstrual cycle and in regulating inflammation (meaning not just creating inflammation but also regulating it). So it’s really an incredibly important chemical that our body produces, and we can’t just try to block all of it because of that. 

In a typical scenario, our body both produces and breaks down histamine. This is crucial to maintain balance. However, sometimes this balance can go awry. This breakdown process relies on two major enzymes: diamine oxidase (DAO) and Histamine N-methyltransferase (HNMT). When we lack these enzymes, histamine accumulates, and we end up with more histamine than our body can handle. This excess histamine can lead to a range of problems.

This may look like skin rashes, eczema, hives, sensitivity to cold or heat, pounding headaches, fatigue, brain fog, constant nasal drip, asthma, heightened anxiety, disrupted sleep patterns, digestive issues like heartburn, bloating, or diarrhea and food intolerances. Essentially, when there’s an abundance of histamine circulating in our body, it binds to histamine receptors all around our body, causing disturbances and intensifying these symptoms everywhere.

There are two terms that describe this allergic situation. One is histamine dysregulation, where we produce too much histamine, and suffer the consequences of excess histamine wreaking havoc in our system.

The other term is histamine intolerance. This latter term relates to the body’s ability to break down histamine from ingested foods. And I imagine many of you may not be aware that histamine is also present in many of the foods we eat. Histamines are found particularly in aged or fermented foods like sauerkraut, wine, or aged meats or cheeses, and foods that have gone bad or have been stored for a long time. And even some seemingly innocent foods like avocado, spinach or tomatoes have natural levels of histamine. Then there are foods that cause the release of histamine, like citrus, bananas, dairy products, chocolate, pineapple, nuts, strawberries, food additives, shellfish, and artificial dyes and preservatives. 

When you consume foods that naturally contain histamine or histamine-releasing foods, your gut usually deploys the enzyme DAO to break down the histamine. However, in histamine intolerance, there’s often a deficiency of DAO, or it doesn’t function optimally, resulting in an inability to effectively break down histamine from these foods.

As a result, histamine from the ingested foods gets absorbed into the bloodstream, leading to increased systemic histamine levels. This can cause symptoms like headaches, hives, digestive problems, and more, specifically triggered by the histamine-containing foods you eat.

In essence, the main distinction lies in the source of the excess histamine. Histamine dysregulation originates from the body’s overproduction of histamine, while histamine intolerance is primarily linked to the inability to process histamine from foods due to DAO deficiencies or dysfunction. Both can lead to a variety of symptoms, but they have different underlying mechanisms.

Now what you may not realize is the way that SIBO, or small intestine bacterial overgrowth, can lead to histamine-related issues. First, when we have an over-abundance of bacteria in our digestive tract, it tends to generate inflammation. Certain bacteria, the gram-negative ones, produce substances known as lipopolysaccharides, which can trigger the mast cells to release histamine within the digestive system. So, when there’s substantial inflammation due to bacterial overgrowth, it results in increased utilization of DAO. As a result, we might deplete our DAO reserves, making it insufficient to handle the histamine from our diet. That’s one way bacterial overgrowth can contribute.

Secondly, recent research points to certain types of bacteria commonly associated with SIBO being histamine producers. In a study in which stool was examined to find the connection between urinary histamines and bacteria in IBS patients, it was found first that IBS patients with high urine histamine had a gut microbiome that produced significantly more histamine, and second, that Klebsiella aerogenes was the primary histamine producer, producing 100 times more histamine than other bacteria. Other previous research has also suggested Morganella morganii as another potential high gut histamine producer. Klebsiella is known as one of the primary overgrown bacteria in SIBO, which is why many SIBO sufferers also have histamine intolerance, because an overgrowth of these histamine-producing bacteria in our gut depletes our DAO reserves and interferes with our histamine tolerance. So, it’s a double whammy effect from both inflammation from gram negative Klebsiella and excess histamine-produced by bacteria in the context of bacterial overgrowth.

So some people dealing with terrible allergies are not just getting them from environmental triggers, but may also be experiencing histamine intolerance related to diet and not realize it. 

How can gut bacteria help reduce histamine?

In addition to SIBO in particular, research has revealed a compelling link between gut health and allergies, with multiple studies showing that individuals with allergies often exhibit alterations in their gut microbiome composition, characterized by a reduced diversity of beneficial bacteria. This imbalance, referred to as dysbiosis, can lead to a weakened gut barrier, allowing allergens and toxins to pass through more easily.

Furthermore, research has suggested that certain gut bacteria, such as specific strains of Bifidobacterium and Lactobacillus, may play a protective role against allergies by regulating the immune system and promoting tolerance to allergens. Conversely, disruptions in the gut microbiome’s balance have been associated with an increased risk of developing allergies, including food allergies, hay fever, and asthma. 

Now let’s talk about how to modulate the gut in order to reduce histamines. As noted above, an abundance of Klebsiella aerogenes, which produces histamines, can be part of the problem. Researchers discovered that K. aerogenes is most prolific in producing histamine when the pH of the gut is around 7.0. But, histamine production nearly ceases when the pH drops below 6.0 or rises above 8.0. This finding is significant because the colon’s pH typically ranges from 5.5 to 7.5, with lower pH values associated with better colon health. So modifying the colon’s pH to increase its acidity (meaning lowering the pH) could be a strategy to reduce histamine production by K. aerogenes. I should thank Lucy Mailing for these insights into histamine intolerance and colon pH and many of the suggested interventions before I go on. 

So how do we do lower colon pH? Specific bacterial strains like Bifidobacteria and lactobacilli increase lactic acid levels, playing a role in colon pH. Researchers have observed that in “humanized” mice with a microbiota from IBS patients displaying high urine histamine levels, lactic acid levels were notably lower. Not surprisingly, they also found reduced levels of lactic-acid-producing bacteria, including lactobacilli. Further investigation revealed that certain lactobacilli could modulate histamine production by K. aerogenes, likely through the production of lactic acid. This suggests that specific lactobacilli strains may contribute to regulating histamine production by K. aerogenes.

While much of the discussion has centered on the colon, it’s essential to consider the presence of Klebsiella species in the small intestine. Studies have indicated that Klebsiella species may be more prevalent in the duodenum, the upper portion of the small intestine, in individuals with gastrointestinal symptoms. This presence in the small intestine can potentially disrupt the overall microbial community. Furthermore, it’s suggested that some Klebsiella species found in the gut may originate from the oral cavity, indicating that saliva could act as a reservoir for transmitting Klebsiella to the gut, where they may flourish if the gut environment is conducive. In portions of the small intestine with lower acidity, such as the ileum, which can have pH levels as high as 7.4-7.8, histamine production by K. aerogenes may be supported. In summary, K. aerogenes produces histamine, and its production is influenced by pH levels, while lactic acid and specific lactobacilli and bifidobacteria strains can impact this process. Additionally, Klebsiella’s presence in the small intestine may also contribute to histamine production, particularly in less acidic regions.

What can I do with my gut to impact my allergies?

If your allergy symptoms are worse after eating certain foods, or you have lots of gut symptoms in addition to allergic symptoms or at the same time as them, you may have a histamine intolerance problem. So how can you bring down your gut pH and try to reduce your populations of inflammatory bacteria? Here are some potential interventions. The trick is that you may not be able to tolerate these interventions while populations of Klebsiella or other histamine producing bacteria are high. So it may be necessary to use antimicrobial herbs first to bring down the bacteria. But after that, you can start interventions for changing the environment in your gut and bringing down your gut pH.  

One first easy step is by eating lots of lacto-fermented foods that have high amounts of lactobacilli, which will produce lactic acid and reduce the pH in your gut. And my next episode will be about fermenting foods so stay tuned for that. Second you can take probiotics with lactobacilli. One strain in particular, Lactobacillus plantarum 299v, has been shown in clinical trials for IBS to be better tolerated by histamine-sensitive individuals. You can find it in the Jarrow Formulas, Ideal Bowel Support probiotic*, and Metagenics UltraFlora® Intensive Care* or Hyperbiotics’ PRO-IBS Support* all of which are available in my Fullscript Dispensary.

And there are also a number of probiotics that are designed for breaking down histamine, and have no histamine producing strains, which many do. These include Seeking Health’s ProBiota HistaminX* and Vitanica’s Flora Symmetry*: 

Third, you can include vinegar with or before your meals, which has been shown in animal models to reduce colonic pH. 

Other potentially beneficial interventions for people with histamine intolerance include butyrate or its preferred supplement form, tributyrin, which may help to promote colon acidity and suppress mast cell activation. And of course I have to plug my own supplement Tributyrin-Max here. But keep in mind that tributyrin will slow colon motility so if you’re constipated, I’d pick a lower dose butyrate supplement than mine and only use one every few days. But if your stool is loose, a higher dose one like Tributyrin-Max is a good choice. I’d start with 1 with a meal and titrate up to as many as 1-2 per meal until your stool is solid with a clean wipe, decreasing it when and if you get constipated. 

If you have any signs or possible contributing factors to low stomach acid, like low pancreatic enzymes, H pylori overgrowth, low chloride levels on a blood test, specifically under 100 mmol/L, abnormally high or low serum protein and serum globulin levels, especially in the presence of relatively normal liver enzymes, which are the ALT and AST, low phosphorous levels, high BUN levels of 20 mg/dL or more or B12 or iron deficiencies or acid reflux, supplementation with Betaine HCl, which is just supplementary stomach acid, will reduce the pH of the stomach and small intestine. 

And then doing things to reduce colon transit time and increase colon motility, especially if you’re constipated will also help with a lower colon pH. My go to’s for that are vitamin C and magnesium citrate. For vitamin C, I usually recommend the Perque C Guard powder, ¼ tsp. three times a day, and increase from there as needed. And then the Natural Vitality Calm Magnesium*, which comes in plain or a variety of flavors, which is magnesium carbonate and turns into citrate when you mix it in water. That helps with motility. You can find all the flavors and the plain in my Fullscript dispensary at a discount.

I recommend starting with ½ tsp. before bed and increasing by ½ a tsp. every 2 days until you hit 2 tsp. or more as needed to get the colon moving. If this isn’t enough to get things moving, you may have a bad case of IMO or intestinal methogen overgrowth and may need some antimicrobial interventions too. 

Then of course there’s eating a low histamine diet, following for example Dr. Jocker’s Low Histamine Food Plan, but ideally that’s a temporary fix until you get the gut issues under control. 

And then finally, time restricted eating will help, meaning only eating when it’s light out, because Klebsiella aerogenes proliferates more rapidly in the presence of melatonin, which comes out at night. And I actually have a former client whose symptoms pointed very strongly towards histamine intolerance who had terrible night time itching, and she reached out to me to tell me that when she implemented a 17-hour nightly fast, stopping eating after 4 or 5 p.m., her itching went away. 

Then of course there are other supplements that help stabilize or modulate mast cells and may decrease symptoms. Quercetin (found in Megagenetics Quercetin 500*) is one of the best known. Taking 500 mg. a half hour before you eat may be helpful if your symptoms point to histamine intolerance. 

Or taking 1 500 mg. capsule a day on an ongoing basis if your allergies do not seem food-related. 

Curcumin and silymarin are also mast cell stabilizers and curcumin is a great general anti-inflammatory. You can find them in Biomatrix’s Support Mucosa* (quercetin, turmeric root extract and silymarin), Progressive Professional’s Milk Thistle Complex* (curcumin and silymarin) and NFH’s Liver SAP*.

These types of products with silymarin tend to be geared towards liver support, so if you are concerned you have liver issues, like fatty liver, have high fasting glucose or hemoglobin A1C or skin issues, or drink a lot or alcohol, then then these types of supplements might do good double duty in helping support your liver. 

And then there are actual DAO supplements, and although I’ve heard mixed results about their efficacy from other practitioners, I do have clients who swear by them. Two are Designs for Health’s HistaGest DAO*, and Seeking Health’s Histamine Digest*.

What lifestyle interventions can I do to maintain a healthy gut microbiome and decrease allergies?

Now beyond the advice for people with gut-related histamine issues, I want to highlight the lifestyle interventions that will help people with allergies that do not seem to be related to the gut, but keeping in mind that with 70% of our immune system found in our gut, decreasing systemic inflammation via the gut is still relevant. 

First, try to increase your dietary diversity by consuming a diverse range of fiber-rich foods such as fruits, vegetables, whole grains, and legumes, and I’ll especially highlight the importance of legumes, meaning beans, lentils, split peas, hummus, etc. in providing adequate dietary fiber and supporting a diverse microbiome of beneficial gut bacteria. I recommend getting ¼ to ½ cup of these high fiber foods a day. And on top of that, I’d particularly recommend the following foods for their immune balancing and histamine managing properties: parsley, coriander, raw red onion, broccoli, nettle* and tulsi teas* and fresh ginger and turmeric. These natural options can help balance your immune response and manage histamine.

Second, incorporate probiotic-rich foods like yogurt, kefir, sauerkraut, and kimchi into your diet. These foods contain live probiotic cultures that can support a balanced microbiome.

Third, include healthy prebiotics in your diet, from foods like garlic, onions, leeks and asparagus, which also serve as nourishment for beneficial gut bacteria.

Four, limit processed foods and sugary foods, which often contain additives and preservatives that can negatively affect gut health and which will feed pathogenic organisms in the gut. 

Fifth, make sure you stay hydrated. This is important to keep your system moving and not have stagnation and constipation, not to mention supporting overall digestion and ensuring a suitable environment for gut bacteria to thrive. Half of your body weight in ounces if you measure your weight in pounds is recommended as a minimum. 

Sixth, try to manage your stress. I’ve seen so many clients whose health declined in response to a major stressful period in their life. You can do this by first trying to change the way that you perceive stress. Sometimes work can be fast-paced and challenging and if you perceive it that way, then your body will not necessarily ramp up the cortisol commensurate with a stress response. But if you perceive it as stressful and negative, it will. Or if you set up unreasonable expectations of the people around you, and I’m speaking from experience here, thinking things like “my children should never say ‘no’ to me or talk back to me”, then you will no doubt have a higher stress response than if you have more reasonable expectations like “sometimes kids disobey their parents and my job is to guide them gently”. And then pick out a stress-reduction technique you like, such as meditation, yoga, prayer, breathwork or Epsom salt baths, which have the added benefit of giving you magnesium. Try to get in at least 10-15 minutes of a relaxation technique a day. And finally, if you’re in a toxic relationship or have toxic people in your life, start the process of considering whether and how to remove yourself from toxic people, enlisting the help of a therapist or friends as necessary. 

Seventh, avoid the overuse of antibiotics, especially for upper respiratory infections that are usually viral in nature. If your doctor has given you antibiotics in the past, you’re more likely to request and expect them, but if anything, the best stance is challenging a doctor who wants to prescribe you antibiotics unless it’s confirmed that you have a bacterial infection, and then making sure you get the most narrow spectrum antibiotic you can, and for the shortest duration recommended. 

Eight, engage in regular exercise, which has been linked to a more diverse and balanced gut microbiome.

And last, prioritize getting adequate (meaning 7-9 hours) and quality sleep, which supports immune function and contributes to overall well-being.

Are there supplements that will help with my allergies? 

Certain supplements may support gut health, which, in turn, can have a positive impact on allergies. Here are some supplements that have been associated with potential benefits for allergies through their influence on gut health:

I mentioned probiotics earlier for people with histamine intolerance, but let me add that if you have seasonal type allergies, you may want to look at a spore-based probiotic. One of the most researched ones is called Enterogermina*, which comes out of Italy but is very reasonably priced for a 20-vial course on Amazon. In studies, it was shown to reduce nasal congestion and the need for antihistamines. Spore-based probiotics have also been shown to reduce post-prandial, meaning after a meal, lipopolysaccride levels, which is one cause of inflammation.

Research also suggests that the most common probiotic strains, Lactobacillus and Bifidobacterium, may reduce allergy symptoms by modulating the immune response. A very researched combo probiotic is Seed Synbiotic*, which has some strains in it that were particularly researched for helping with allergies. 

If you can’t get enough prebiotic fiber in your diet from fruits and vegetables, ideally from 5 servings a day, you may want to try a prebiotic supplement to provide the fiber and nutrients that beneficial gut bacteria need to thrive. One good one is Pure Encapsulations’ Poly-prebiotic powder*: 

Then if you’re not eating two servings of fatty fish like salmon, sardines or anchovies a week, then I’d recommend an Omega-3 fatty acid supplement. Either fish oil or algae oil if you are vegan, have anti-inflammatory properties, may help reduce allergic inflammation and support overall gut and immune system health. My favorites are Nordic Naturals’ ProOmega 2000* which I like because you get 1000 mg of EPA and DHA in one, which is a sufficient dose for most people. If you have high cholesterol issues too, you may want to take two of those. And of course pick grassfed or pasture raised eggs, beef, lamb and dairy, if you eat it, for the higher Omega 3 content. 

Or if you’re a vegan or vegetarian, you can use one like Nordic Naturals Algae Omega*, but you may need to take more of them to get to 1000 mg of EPA and DHA and may need even more than that because you aren’t getting it from your diet. 

And then one of the most important substances for immune health is vitamin D. Adequate vitamin D levels are important for a balanced immune response and may help reduce the risk of allergies. I have yet to see a single client who achieved optimal vitamin D status without supplementing. I suggest you get your vitamin D tested and shoot for an optimal range of 60-80 ng/mL. If you aren’t there, most people I find need 3000-5000 IU a day to get there and stay there, which I always recommend to combine with vitamin K2, preferably in the mk4 form. I like the drops because you can adjust your dose as you test and retest. I only know of one D3/K2 drop with K2 in the mk4 form, which is the Adapt Naturals one*.

Then you may have specific other vitamin and mineral deficiencies that are necessary for creating the DAO enzyme. The most common ones are vitamin B6, best gotten in a complete methylated B complex, and one good one is from Priority One* that’s got a reasonable amount of all the B vitamins in it, although if you’ve had any identified B vitamin deficiencies or have issues like anxiety or depression, you may want to select a B complex with higher levels of related B vitamins. I should also note that I don’t think I’ve ever seen a test from a client who had sufficient levels of all the B vitamins. I’m not sure if this is a poor diet issue or a gut health issue, or a soil depletion issue, but I recommend a B complex to almost everyone I work with. 

Then the other vitamins and minerals for making DAO are Vitamin D as previously mentioned, Vitamin C and Magnesium. These are all essential for breaking down histamine and managing histamine levels via DAO.

And finally, black seed oil, derived from cumin seeds, has also been found in research on rats and humans to be effective in decreasing markers of allergic inflammation, nasal mucosal congestion, nasal itching, runny nose and sneezing attacks. It also has antifungal properties, so if you’re dealing with candida as well as allergies, it’s a good choice. I prefer the liquid as you can get a lot more in 1 tsp. of liquid than you can put in a capsule. Here are a couple good ones:

Heritage Organic Black Seed Oil*

ZHOU Nutrition Organic Black Seed Oil

And if none of this helps you, I should also note that if you have mold or a history of mold in your home or workplace, that and Lyme disease, or Bartonella, can also cause these types of heavy allergy symptoms and what’s called Mast Cell Activation Syndrome, and Bartonella will also give a sense of buzzing or vibrations in body, so you may want to do further testing to see if those things are issues. 

If you’re struggling with  bloating, constipation, diarrhea, soft stool, acid reflux, IBS, IBD or any type of chronic disease, etc. and want to get to the bottom of it, that’s what I help my clients with. You’re welcome to set up a free, 30-minute breakthrough session with me (Lindsey). We’ll talk about what you’ve been going through and I’ll tell you about my 3- and 5- appointment health coaching programs in which I recommend lab tests, educate you on what the results mean and the protocols used by doctors to fix the problems revealed. Or if you’re ready to jump in right away or can just afford one appointment at a time, you can set up an 1-hour consultation with me. 

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