An Explanation of How These Two Seemingly Unrelated Conditions Are Intertwined.

• What is SIBO?|
• What is Histamine Intolerance?|
• The Gut-Histamine Connection|
• Can SIBO Cause Histamine Intolerance?|
• Where to Go From Here|

Did you know that there’s a connection between your digestive system and your immune system? That’s right, there are many points of contact between your gut and your immunity. Not only does a large part of your immune system rely on having a healthy gut microbiome, but there’s a connection between histamine (an immune response) and gut health as well [1].

If you’ve ever experienced an allergy attack—whether something minor like seasonal allergies or a rash, or something scary like a severe peanut allergy—you have experienced a histamine response. But what you may not realize is that certain gut conditions are associated with a greater histamine response, and sometimes even a histamine intolerance. There is increasing evidence that histamine intolerance is a gastrointestinal condition and originates in the gut [2]. 

One of the gut conditions associated with histamine intolerance is SIBO (small intestinal bacterial overgrowth). We don’t know for sure whether SIBO causes a histamine response, but both cause similar symptoms, and it seems to be the case that treating SIBO can help relieve symptoms of histamine intolerance.Let’s take a closer look at SIBO, histamine intolerance, and the potential for a single intervention protocol to provide relief for both.

What is SIBO?

SIBO is an overgrowth of bacteria in the small intestine. Normally, the upper part of the small intestine has 1,000–100,000 colony-forming units (CFU) per mL, and the large intestine has 10 trillion to 100 trillion CFU/mL [3]. When the bacteria in the upper intestine get more numerous, it’s usually safe to call it SIBO [3].

Symptoms of SIBO include:

• Gastrointestinal symptoms [4, 5]:
  • IBS (irritable bowel syndrome)
    • SIBO occurs in 38% of people with IBS, which has very similar symptoms, including:
      • Bloating/distension
      • Flatulence
      • Cramps
      • Diarrhea
      • Constipation
• Systemic symptoms, specifically affecting the nervous system:
  • Chronic fatigue: a 2013 study found that 80% of people with chronic fatigue syndrome had SIBO [6]. 
  • Poor mood: a 2022 study found that SIBO patients reported higher stress, anxiety, and neuroticism than non-SIBO patients [7].
  • Brain fog: a 2018 study found that SIBO was 40% more common in those with brain fog [8]. 
• Other conditions that often co-occur with SIBO [4]:
  • Celiac disease
  • IBD (inflammatory bowel disease—Crohn’s disease and ulcerative colitis)
  • Rosacea and psoriasis
  • Restless legs syndrome 
  • Joint pain 
  • Hypothyroidism 
  • Increased TPO (thyroid peroxidase) antibodies—above 35 typically indicates a Hashimoto’s diagnosis [9] 
  • NAFLD (non-alcoholic fatty liver disease) and diabetes 

Digestive conditions that may lead to SIBO include:

• Low stomach acid
  • When stomach acid is too low for efficient digestion, nutrient absorption, and defense against pathogens, SIBO can take hold [11]. 
• Post-infectious IBS
  • SIBO can also arise from IBS that develops after an infection [12].
• Low digestive enzymes or bile, which are stimulated by stomach acid and inhibit pathogens, can make room for SIBO [11].
• When motility, or the rate at which contents move through the gut, is too slow, parts of the small intestine can become stagnant like a pond with no water circulation, allowing bacteria to overgrow [11].
• Leaky gut
  • Leaky gut (intestinal permeability) can arise from various insults, including SIBO. SIBO creates toxins in the gut, leading to inflammation that can damage the gut lining. Leaky gut can also contribute to SIBO (a two-way street) [13].

Medical conditions that may lead to SIBO include:

• Altered small intestine anatomy can create pockets that catch foodstuffs, which sit and invite bacteria to procreate [11]. Such alterations include:
  • Ileocecal valve dysfunction
  • Short bowel syndrome
  • Adhesions from abdominal surgery
• Medications can disrupt normal digestive function in ways that make it easy for bacteria to overgrow in the small intestine. Examples include:
  • Antacids (Long-term use of acid blockers can lead to low stomach acid) [4]
  • Opioids [14]
  • NSAIDs [15]

We don’t have enough research yet to know whether any specific diet is linked to SIBO. However, smoking can raise the risk of SIBO—one study found it raised the odds by six [16]! And stress and anxiety are risk factors for SIBO [7]. 

We know that stress can lead to nutrient malabsorption, lower stomach acid production, delay stomach emptying, dysregulate mast cell and histamine production, and negatively impact your microbiome [17]. So finding ways to reduce stress would, at least to some degree, help reduce your risk of SIBO and a histamine response.

What is Histamine Intolerance?

Histamine intolerance occurs when the body can’t break down histamine. As histamine builds up in the body, it may cause upset stomach, headache, or allergy-like symptoms. When those with histamine intolerance eat foods high in histamine, their levels of histamine continue to rise, making symptoms more likely.

Histamine is found in all body tissues. It plays a vital role in the immune system, particularly in allergy, inflammation, and autoimmunity [1]. It also helps the stomach secrete acid and aids blood cell development [1].

This condition is far less common than SIBO, likely affecting only 1% of the US population, but there may be more undiagnosed cases [18]. 

Common histamine intolerance symptoms include:

• Bloating [25]
• Diarrhea [19]
• GERD
• Heart rate changes or palpitations [19]
• Low blood pressure [26] 
• Headaches/migraines [27]

Other symptoms may include:

• Seasonal allergy symptoms (itchy eyes, sneezing, runny nose)
• Rash
• Hives
• Depression
• Irritability
• Brain fog
• Headaches
• Insomnia
• Fatigue
• Joint Pain

After comparing these lists of symptoms with the ones above for SIBO, you might be beginning to draw a connection between the two conditions. Again, we don’t know that there’s a causal relationship in one direction or the other, but the two seem pretty clearly connected.

Interestingly, some foods that increase histamine load overlap with food triggers for SIBO, but not all of them.

Foods High in Histamine and DAO

Foods high in histamine are harder for those with histamine intolerance to break down, leaving histamine to build up in the body and leading to the symptoms I just laid out.

High-histamine foods include:

• Tofu and soy sauce
• Cheese
• Mushrooms
• Chocolate
• Yeast products

• Smoked fish
• Processed meats
• Nuts and seeds
• Foods with vinegar
• Sweetened beverages
• Fermented foods and drinks
• Over-ripe fruit
• Leftovers from the fridge

Diagnosing Histamine Intolerance

A histamine intolerance diagnosis is one of exclusion. The most accurate test for histamine intolerance so far has been a positive response to a low-histamine diet. However, there may be a potential psychological component too [31]. A 2023 study investigating this diagnosis found that nearly 63% of those studied displayed histamine symptoms in reaction to a placebo instead of real histamine.

Testing for serum DAO may also help diagnose the condition [19, 28, 29].

In the clinic, if we suspect someone has histamine intolerance, we start by trying a low-histamine diet. Diet is the first step in a three-step process we often use for histamine intolerance, including tailored supplements and lifestyle modifications. 

The Gut-Histamine Connection

Increasing evidence suggests that histamine intolerance is a gastrointestinal condition that originates in the gut [2]. Recent studies looking at the potential connection between the two conditions show that those with histamine intolerance are more likely to have gut dysbiosis, imbalances, or leaky gut than those without and that low DAO levels are associated with IBD [24, 32, 33].

Other studies have found that over half of IBS patients react to histamine-releasing foods and tend to have higher histamine levels and more histamine-producing bacteria in their gut [34].

This research seems to show that digestive issues like gut dysbiosis may cause histamine to build up in the digestive tract when:

• Bacteria in the gut produce excess histamine.
• A damaged intestinal lining (leaky gut) cannot process histamine into other compounds.
• Damage to the intestinal lining leads to immune system activation and reactivity, producing more histamine.

This body of research suggests that addressing gut issues may also address histamine issues.

Can SIBO Cause Histamine Intolerance?

We can’t prove a causal relationship between SIBO and histamine intolerance, but I hope that I’ve presented enough compelling evidence to convince you that there is, at the very least, a clear connection between the two conditions.

Treating SIBO and Histamine Intolerance

In our clinic, we’ve found that clients dealing with histamine issues and food sensitivities benefit from some of the same interventions that help our SIBO clients. The dietary treatment for SIBO is a low-FODMAP diet, and we also recommend probiotics like our Triple Therapy Probiotic Powder Sticks to our clients [35, 36]. These two interventions seem to help both SIBO and histamine intolerance [37, 38, 39].

Some practitioners recommend taking a low-histamine probiotic product. However, this recommendation overlooks the net beneficial effect of probiotics on the gut ecosystem. 

A few lifestyle changes are also key in addressing both conditions—both enhancing progress and leading to quicker recovery:

• Aim for 7–8 hours of restful sleep every night.
• Manage or mitigate your stress.
• Nurture supportive relationships and healthy social connections.
• Spend time in the sun and in nature.
• Walk as much and as often as you can.
• Engage in a healthy amount of exercise.
• Talk to your medical provider about smoking cessation programs.

These lifestyle shifts not only support your physical health, but your mental health as well. The mind-body connection should be a big priority when dealing with any health conditions related to gut health and immune health. I outlined the effects of stress, but it can’t be overstated that stress management and mental health are intricately connected to so many other systems of the body, especially the digestive system.

SIBO-Specific Interventions

The elemental diet is a more aggressive diet intervention than low-FODMAP, which can be employed if you’re experiencing particularly severe digestive symptoms or if the low-FODMAP diet doesn’t seem to be moving the needle quickly enough on your symptoms. 

The best research we have for the elemental diet is a two-week trial that showed an 80% success rate for SIBO patients, which was actually more successful than the standard antibiotic treatment [40].

That being said, in some SIBO cases, your doctor or healthcare practitioner may also recommend or prescribe an antibiotic called rifaxamin, or antimicrobials like oil of oregano to do similar work. You may also consider prokinetics, which are supplements that support healthy motility [41]. These don’t have the same success rate as antibiotics, antimicrobials, or the elemental diet, but they may be helpful for reducing the risk of SIBO in people who take proton pump inhibitors for acid reflux or GERD [42].

Histamine-Specific Interventions

A low-histamine diet overlaps, to a large degree with the low-FODMAP diet; however, it is a bit more restrictive. When it comes to dietary interventions, I always recommend starting with the least restrictive option first and then continuing down the line with more restrictive ones until you experience some relief. This approach allows you to more clearly identify which specific food intolerances or issues you might have in the least restrictive way possible.

That being said, if you find that a low-FODMAP diet isn’t doing the trick for you, you might consider beginning to restrict further. A low-histamine diet restricts three categories of foods:

• Foods high in histamine
• Foods that may trigger a release of histamine in the body (called histamine liberators)
• Foods that block or inhibit the DAO enzyme

For a more comprehensive explanation of this diet, take a look here. You may also be interested in our Low Histamine Diet ebook.

Quercetin is a plant flavonoid with antihistamine and anti-inflammatory effects that have the potential to help reduce histamine intolerance symptoms and inflammation [43, 46, 47, 48, 49]. It also seems to be more effective for women in reducing biomarkers of inflammation, especially when given in high doses (>500 mg/day) [49].

Research on DAO enzyme supplementation has shown that it may be helpful in reducing histamine intolerance symptoms. For example, DAO supplements can:

• Reduce migraine patients’ need for migraine medication [27].
• Improve fatigue, anxiety, and depression in fibromyalgia patients [44].
• Reduce the severity of hives and the need for antihistamines in hives patients [50].

Vitamin C has known antihistamine properties [51]. One recent study found that intravenous ascorbic acid (vitamin C) helped reduce serum histamine in patients with infectious or allergic diseases [52].

Low vitamin B6 seems to correlate with lower levels of DAO enzyme. We need more research in this area, but the correlation suggests that taking supplemental vitamin B6 may help support DAO production and reduce intolerance [53].

Where to Go From Here

Since there seems to be overwhelming clinical data supporting the connection between gut health and histamine response, the most practical steps should probably involve caring for your gut. SIBO may or may not be the root cause of histamine intolerance, but a SIBO protocol does seem to help with symptoms of histamine intolerance.

I always advocate for starting with the least intrusive plan, least restrictive diet, and lowest level of difficulty. In this case, that would mean opting for a low-FODMAP diet and starting a probiotic. Always talk to your medical provider, as I don’t give direct advice to individuals who aren’t my clients. If you’d like to be a client, reach out to our clinic. We’d love to get you set up with an appointment.

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Dr. Michael Ruscio is a DC, Naturopathic Practitioner, researcher, and clinician. He serves as an Adjunct Professor at the University of Bridgeport and has published numerous papers in scientific journals as well as the book Healthy Gut, Healthy You. He also founded the Ruscio Institute of Functional Health, where he helps patients with a wide range of GI conditions and serves as the Head of Research.