Vitamin B12 and histamine intolerance can have a lot to do with gut health and are worth exploring regarding the root cause of gut imbalances.

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Vitamin B12 and histamine intolerance can have a lot to do with gut health and are worth exploring regarding the root cause of gut imbalances. As discussed in this article, histamine intolerance can cause chronic digestive issues and other unwanted inflammation-related symptoms. 

Histamine intolerance is often confused for allergies or other digestive health conditions such as Small Intestinal Bacterial Overgrowth (SIBO). If you suspect you might be struggling with histamine intolerance, here is what you need to know about how to manage your symptoms naturally and achieve healing from the inside out. 

Hint: It all starts with your gut health! 

WHAT IS HISTAMINE?

Histamine is a naturally occurring chemical in the body that is involved in the immune response. It works closely with the digestive and nervous systems. Therefore, histamine is essential in immune reactions, digestion, and neurological function. For this reason, histamine is a topic to explore when looking to improve gut health. 

It is also a biogenic amine, which are a group of compounds that are produced from amino acids. Biogenic amines are naturally found in foods, especially those that are aged, fermented, or spoiled. 

The many functions of histamine include:

• Responding to allergic reactions
• Triggering inflammation 
• Stimulating stomach acid secretion in the gut
• Regulating many neurological responses, such as appetite and wakefulness

HOW IS HISTAMINE PRODUCED IN THE BODY? 

Histamine is produced through the decarboxylation of the amino acid histidine. This reaction is catalyzed by an enzyme called histidine decarboxylase, which removes a carboxyl group from histidine, converting it into histamine.

Various cells in the body, certain strains of bacteria found in the intestines, and fermented, aged, or improperly stored foods can convert histamine. It is estimated that 5% of total histamine comes from food and gut bacteria, while the remaining 95% is produced by specialized cells in the body. 

Once conversion occurs, histamine is primarily stored within mast cells and basophils. Specific enzymes, like diamine oxidase (DAO) and Histamine N-methyltransferase (HNMT), break down histamine within the body to help regulate its levels. 

DAO is the primary enzyme breaking down histamine from food and the gut microbiota. It is produced and stored in the epithelial lining of the intestines. Histamine N-methyltransferase (HNMT) is the enzyme responsible for metabolizing histamine that is released by immune cells. It is found within cells throughout the body.

It’s important to note while both DAO and HNMT help manage histamine within the body, DAO is the main enzyme that affects histamine intolerance due to its critical role in processing dietary histamine.

WHAT IS HISTAMINE INTOLERANCE?

Histamine intolerance is a condition that occurs when histamine breakdown is impaired, causing histamine to build up in the body and trigger symptoms similar to an allergic reaction. Specifically, it is thought that people with histamine intolerance don’t produce enough diamine oxidase (DAO), the enzyme responsible for breaking down histamine in the intestines.

It was first mentioned in scientific studies around 20 years ago and has steadily gained attention since then, with nearly 80% of research on the topic being published in the last decade. Some experts have estimated that 1-3% of the population has histamine intolerance, with a higher prevalence in middle-aged females. 

Histamine intolerance begins when the body cannot break down or metabolize histamine. This quickly leads to excess histamine levels in the bloodstream and causes unwanted symptoms. There are many root causes of histamine intolerance, and the key to finding and addressing them.

CONDITIONS ASSOCIATED WITH HISTAMINE INTOLERANCE

Conditions associated with histamine intolerance may include: 

Gastrointestinal Disorders

Histamine intolerance is commonly associated with various gastrointestinal conditions, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease.

Conditions that damage or inflame the intestinal lining can impair the production of DAO, the enzyme responsible for breaking down histamine in the gut. Additionally, gut dysbiosis, in which histamine-producing bacteria overgrow, can further increase histamine levels in the gastrointestinal tract.

Headaches And Migraine

Histamine intolerance has been associated with headaches and migraine, potentially due to histamine’s ability to dilate blood vessels and trigger inflammation.

Studies have found that up to 87% of people with migraine have low DAO levels, and supplementing with DAO or following a low-histamine diet may reduce symptoms.

Additionally, many of the foods that have been identified as common migraine triggers, such as alcohol, aged cheese, and processed meats, are high in histamine. 

Eczema And Other Skin Conditions

Due to histamine’s role in promoting inflammation, histamine intolerance may contribute to certain skin conditions, including atopic dermatitis (eczema) and urticaria (hives). 

In people with eczema, consumption of histamine-rich foods can sometimes worsen symptoms, with some experiencing improvements while following a low-histamine diet. A 2006 study found that 19% of participants with eczema had low serum DAO activity, compared to 20% in those with suspected histamine intolerance and 0% of healthy controls. 

Insomnia And Other Sleep Disorders

Histamine is a key player in regulating the sleep-wake cycle. When released in the body, histamine promotes wakefulness through interactions with brain receptors. 

When histamine levels are elevated, it can keep the brain in a heightened state of alertness, making sleep more difficult and potentially contributing to insomnia symptoms.

In a recent study, 83% of participants with symptoms of insomnia carried genetic SNPs that decrease DAO production. Individuals with a greater number of DAO-related SNPs were the most likely to experience insomnia symptoms, especially difficulty staying asleep and early morning awakenings.

Fibromyalgia

Recent studies suggest a potential link between histamine intolerance and fibromyalgia, a chronic disorder that causes widespread musculoskeletal pain, fatigue, and many other symptoms. One study found that women with fibromyalgia who carried specific gene variants exhibited more severe symptoms, including dry skin and digestive issues. 

Additionally, supplementation with DAO has been shown to reduce fatigue, anxiety, and depression for some individuals with fibromyalgia. 

SIGNS & SYMPTOMS OF HISTAMINE INTOLERANCE 

Histamine intolerance can cause a variety of symptoms. Interestingly, they often mimic an allergic reaction without an actual allergen present. It’s important to note the difference between histamine intolerance and food allergies, though, as they are often used interchangeably. 

Histamine intolerance results from a deficiency in one of the enzymes that breaks down histamine, while food allergies occur when the immune system mistakenly identifies a food as a threat.

Unlike food allergies, where even a tiny amount of the allergen can trigger symptoms, histamine intolerance depends on the total amount of histamine consumed over time. 

Gastrointestinal Related Symptoms of Histamine Intolerance May Include: 

• Abdominal pain
• Bloating 
• Constipation
• Diarrhea 
• Gas
• Nausea 

Other Related Symptoms of Histamine Intolerance May Include: 

• Difficulty breathing
• Nasal congestion or runny nose 
• Tachycardia (rapid heart rate) 
• Fainting 
• Muscle weakness 
• Fainting 
• Menstrual cramps 
• Dizziness 
• Dermatitis 
• Urticaria 
• Frequent headaches 
• Flushing and redness
• Sneezing

In a 2019 survey of 62 people with histamine intolerance, bloating was reported as the most common (and severe) symptom, occurring in 92% of respondents. 

Therefore, properly managing histamine levels in the body is essential in improving gut health! 

ROOT CAUSES OF HISTAMINE INTOLERANCE 

Many conventional doctors do not acknowledge histamine intolerance. Those who are familiar with the condition might recommend a low-histamine diet, DAO supplements, and antihistamines. 

In my practice as a Functional Medicine Registered Dietitian, understanding what causes histamine intolerance in the clients I work with is the key to addressing it. Correcting the root cause of why histamine is building up in the body is superior to a low-histamine diet, antihistamines, and even natural supplements. 

There are many common causes of histamine intolerance to consider, including:

Genetic Predisposition

Certain single-nucleotide polymorphisms (SNPs) in the DAO gene (AOC1) can reduce enzyme activity and increase the risk of histamine intolerance symptoms.

Over 50 SNPs have been identified and are particularly relevant in Caucasian individuals. Genetic testing can identify these SNPs, but having them does not guarantee that a person will experience symptoms of histamine intolerance.

Low Enzyme Production 

Low levels of digestive enzymes, such as DAO, are known to break down histamine within the body. Lower levels of DAO can contribute to high histamine levels, leading to histamine intolerance. Low enzyme production is typically due to gut dysbiosis, H. Pylori, or nutritional deficiencies. 

Histamine-Rich Foods

Consuming too many high-histamine foods triggers or worsens histamine intolerance. High histamine foods include aged cheese, fermented foods, alcohol, cured meats, tomatoes, leftover foods, and more.

In addition, alcohol competes with histamine for aldehyde dehydrogenase, an enzyme essential for breaking down both compounds. Alcoholic beverages, especially red wine, are also naturally high in histamine.

Histamine Overproduction

Certain conditions, like mast cell activation syndrome or chronic allergies, can cause the body to release too much histamine into the body.

Leaky Gut 

Gut dysfunction, like Leaky Gut, hinders the body’s ability to break down histamine properly. 

Studies show individuals having higher levels of zonulin, a marker of intestinal permeability (or Leaky Gut), suggests that Leaky Gut may play a role in the development of histamine intolerance. 

Additionally, some experts have theorized that infection with Helicobacter pylori could be an underlying cause of histamine intolerance in some patients, but more research is needed. 

Medications 

Certain medications can reduce DAO levels in the body, increasing histamine buildup. Medications that may contribute to increased histamine include antibiotics, NSAIDs, diuretics, muscle relaxants, antihypertensives, analgesics, and antidepressants. Talk with your healthcare practitioner about any concerns regarding your medications. 

Nutrient Deficiencies 

Nutritional deficiencies and/or imbalances may contribute to histamine intolerance by reducing DAO activity. For example, vitamin B6 and copper act as cofactors for DAO, and deficiency in these nutrients is linked with lower serum DAO levels. 

When nutritional deficiencies are ongoing, they can impact hormones. Hormone fluctuations impact DAO production, particularly in women. DAO activity tends to be higher during the luteal phase than the follicular phase of the menstrual cycle. 

Understanding histamine intolerance is the first step in naturally managing any symptoms. Working with a trusted practitioner who can help you identify the root cause is essential. By visiting this link, you can check out how my 1:1 gut health coaching program can help you get to the root causes. 

HISTAMINE BUCKET THEORY

I always share the bucket theory about toxin buildup and how it relates to gut health.  Histamine intolerance works very similarly! It’s not an immediate response; instead, it’s more about how much histamine builds up in your system over time.

Think of your body’s ability to break down histamine like a bucket. Some people have a big bucket that can handle more histamine without issues, while others have a smaller one that fills up quickly. This depends on genetics, enzyme function, gut health, nutrient status, and overall health.

Your bucket fills up with histamine from different sources—foods like aged cheese and fermented veggies, lifestyle factors like stress and alcohol, and other factors we mentioned in this article that slow down histamine breakdown.

When the bucket overflows, symptoms like headaches, itching, or digestive issues appear. The key to managing histamine intolerance isn’t avoiding histamine altogether. Managing histamine intolerance is about keeping your bucket from spilling over by balancing your intake and supporting your body’s ability to break it down.

The problem I often see when someone tries to improve histamine intolerance is that they aren’t addressing root-cause factors filling their histamine bucket, and causing it to overflow. 

HOW VITAMIN B12 AFFECTS HISTAMINE INTOLERANCE

Vitamin B12 (also called cobalamin) is a water-soluble vitamin that has an impressive influence on histamine response. It plays important roles in DNA synthesis, red blood cell production, and neurological function. 

Vitamin B12 is a cofactor for enzymes involved in the methionine cycle, improving methylation. Methylation is a bodily process that affects the metabolism of histamine. So, adequate levels of vitamin B12 support the breakdown of histamine. 

Vitamin B12 can help improve DAO levels to support histamine breakdown further in the case of a DAO deficiency. As previously discussed, the DAO enzyme is key in regulating histamine levels, so increasing it can benefit those with histamine intolerance. 

Additionally, studies show that a vitamin B12 deficiency increases the risk of developing histamine intolerance, likely due to its effects on the DAO enzyme.

VITAMIN B-12, HISTAMINE INTOLERANCE, AND THE GUT HEALTH CONNECTION

The gut aids in the production and breakdown of histamine, so the two are closely connected. Gastrointestinal diseases that damage enterocytes (the cells lining the intestines) may result in decreased DAO activity because this is where DAO is produced.

For example, Crohn’s disease, carbohydrate malabsorption, celiac disease, irritable bowel syndrome, and ulcerative colitis have been linked with impaired DAO activity.

In these cases, restoring gut health and repairing the intestinal lining may be key to improving DAO production and managing histamine intolerance symptoms.

In fact, any dysfunctions of the gut can contribute to histamine intolerance, including: 

• Leaky Gut– When the gut lining is damaged, more histamine can be absorbed into the bloodstream, impacting the DAO enzyme’s production. 

• Dysbiosis– Imbalances in the gut microbiome can increase histamine production, leading to excess levels in the body.

• Inflammatory Bowel Disease– IBD and other inflammatory bowel conditions can decrease DAO levels and trigger mast cell activation, causing histamine to increase.

• SIBO– Similar to other microbiome imbalances, Small Intestinal Bacterial Overgrowth can cause elevated levels of histamine in the gut.

• H. Pylori– Some experts have theorized that infection with Helicobacter pylori could be an underlying cause of histamine intolerance in some patients. 

Since the gut plays a primary role in histamine regulation, gut dysfunction can quickly trigger or worsen histamine intolerance.  

Unfortunately, gut conditions can also affect the absorption and utilization of vitamins and minerals. When gut dysfunction goes unnoticed and unaddressed, vitamin B12 deficiency is common. 

Since we know that vitamin B12 is so helpful in supporting histamine intolerance, this can worsen symptoms. Other common issues that can contribute to B12 malabsorption include:

• Frequent use of antacids or acid-blocking medication 
• Surgical removal of the digestive organs 
• Chronic alcohol use
• A diet lacking in B12-rich foods

ADDRESSING HISTAMINE INTOLERANCE WITH VITAMIN B12 

There are many ways to naturally manage and address the symptoms of histamine intolerance, including functional testing, dietary changes, and supplementation.

Functional Testing 

When addressing histamine intolerance, it’s important to test, not guess. Consider working with a functional practitioner to test your levels of histamine, B12, and other factors. Functional testing is an effective approach to identifying and addressing possible histamine intolerance. 

Dietary Approach 

Many whole foods are loaded with vitamin B12. Prioritizing a whole-food diet, especially foods high in vitamin B12, is a helpful way to increase B12 levels. Foods that are rich in B12 include:

• Beef liver
• Shellfish
• Fish 
• Beef 
• Chicken 
• Egg yolks
• Dairy products 

Adopting a low-histamine diet might be beneficial while working on improving the root cause of histamine intolerance. A low-histamine diet is often the first-line treatment for histamine intolerance. It can be used as an elimination diet to identify food triggers and help reduce histamine levels in the body.

Research on this diet is very limited, but a recent trial found that it significantly reduced gastrointestinal and skin-related symptoms in participants with histamine intolerance.

It’s important to note this diet should be a temporary tool for symptom management rather than a permanent dietary change. After an elimination phase, foods can be gradually reintroduced to assess individual tolerance.

Limiting foods that are high in histamine include: 

• Aged cheese
• Cured meats
• Fermented foods
• Citrus fruits
• Leftovers

Making these simple dietary changes can go a long way in managing histamine intolerance.

Supplement Approach

Vitamin B12 supplementation is an effective way to address histamine intolerance. After testing, always work with a practitioner to determine the appropriate dosage for you. 

Methylcobalamin is an active form of B12, consisting of a cobalamin molecule attached to a methyl group. This form is used by methionine synthase in the cytosol of cells to convert homocysteine to methionine. It is also the primary form found in milk and eggs. 

If supplementing with B12, opt for high-quality B12 supplements, like the ones in my online dispensary through Fullscript. 

A popular choice among health practitioners and dietitians is Pure Encapsulations Methylcobalamin (also available on the Fullscript supplement dispensary), which contains 1,000 mcg of vitamin B12 (as methylcobalamin) per capsule. 

As always, consult your doctor or licensed healthcare provider to determine the appropriate supplements for you and your health goals. 

USING A FUNCTIONAL MEDICINE APPROACH TO VITAMIN B12 AND HISTAMINE INTOLERANCE 

Functional lab tests can provide deeper insight into potential underlying imbalances or dysfunction that could contribute to histamine intolerance and make mast cells more sensitive to triggers.

Here are some of the lab tests I order for my clients as a functional practitioner as part of a root-cause approach to treating histamine intolerance:

GI Map

Comprehensive stool testing evaluates the gut microbiota, which plays a role in histamine intolerance. GI-MAP by Diagnostic Solutions Laboratory is the gold standard and popular among dietitians and other functional medicine practitioners.

Micronutrient Analysis

Micronutrient testing assesses the levels of vitamins and minerals, such as vitamin B12, vitamin B6, and copper, needed to support DAO production. 

I use the micronutrient panels from Vibrant Wellness because the panels show intracellular and extracellular nutritional status. Identifying the difference in vitamin, mineral, and essential fatty acid deficiencies is key! 

Food Sensitivity Testing 

An accurate food sensitivity test, such as the Leap MRT, is an effective tool for identifying foods that cause an immune response. In my clinical practice, I find that identifying unique food sensitivities for a period of time and calming down the immune response improves gut dysfunction and speeds up the healing process. 

Removing food sensitivities can improve leaky gut in combination with other therapeutic diets, lifestyle, and supplement modifications, and it can also support histamine intolerance. 

Mycotoxin Testing

Mycotoxin testing can help detect the presence of harmful mold or fungi metabolites in the body. Mold exposure can trigger mast cells to release high amounts of histamine. I love the Mycotoxin test from Vibrant Wellness, which helps detect possible mold exposure. 

WRAPPING IT ALL UP 

Histamine plays an essential role in the body. However, too much of a good thing, even histamine, can cause problems. Fortunately, there are ways to manage histamine intolerance naturally. 

The first step is understanding what is causing histamine intolerance. Any deficiencies, dysbiosis, or other issues identified via functional lab testing should be addressed, along with associated conditions that may contribute to histamine intolerance. 

Treating underlying imbalances may reduce histamine load, increase DAO production, improve B12 nutrient status, and improve symptom management over the long term.

Check out my signature 1:1 program, The Microbiome Makeover, to understand and address your histamine intolerance and take a root-cause approach to healing your gut for good! 

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