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The Science of Stress: Exploring HPA Activation and Diamine Oxidase

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How Stress Response and Histamine Levels Interact

Think of your body as an intricate system, with various components cooperating to maintain your well-being. One important part is the HPA axis, which helps us handle stress. Another part is an enzyme called Diamine Oxidase (DAO), which helps us manage a chemical in our food called histamine.

These two parts can affect each other in interesting ways, which can be important if you’ve heard of something called ‘histamine intolerance’. Let’s dive in to understand more about how the HPA axis and DAO work together in our body.

The Role of the HPA Axis in the Body

Ever wondered what happens in your body when you’re stressed? Let’s take a walk through the Hypothalamic-Pituitary-Adrenal (HPA) axis, which is just a fancy name for our body’s stress response team.

The HPA axis is like a three-part team in our body: the hypothalamus and pituitary gland in our brain, and the adrenal glands near our kidneys. When we face a stressful event, this trio springs into action, making sure our body is ready to deal with whatever challenge it is facing.

How Does the HPA Axis Respond to Stress?

Think of stress as the signal to start a race.

As soon as our brain activates the HPA axis due to stress, which initiates a hormonal response, the hypothalamus sends out Corticotropin-Releasing Hormone (CRH), a hormone that kicks everything into gear.

This hormone tells the pituitary gland (like our body’s relay runner) to send out another hormone called Adrenocorticotropic Hormone (ACTH).

Now, ACTH does a crucial job. It tells our adrenal glands to release a hormone called cortisol, which is like the body’s superhero in times of stress. It does two main things: it helps our heart pump blood faster and it gives us an energy boost by increasing sugar in our bloodstream.

In a perfect scenario, once the stress is over, cortisol should decrease quickly, letting our body know that it can relax. This is like the cooldown period after a race, allowing our body to get back to its usual state.

What Happens If Our Stress Response Doesn’t Turn Off?

But what happens if we’re constantly stressed, and this race never ends? If our HPA axis is always active, our body is always in stress mode. Over time, this can affect parts of our brain that control the HPA axis, just like how a relay team might get tired if the race never ends.

Constantly being in stress mode can also make it harder for our bodies to fight off infections. That’s because too much cortisol can weaken our immune system.

Moreover, our body’s persistent stress mode has been linked to several health issues like

  • Diabetes
  • Obesity
  • Heart disease
  • Mood disorders like depression.

The Role of Diamine Oxidase (DAO) and Histamine Release

Histamine, a compound found in many foods, is perfectly harmless in small amounts. However, a sudden histamine release from mast cells – immune cells stored in connective tissues, can cause symptoms similar to allergies.

That’s where an enzyme encoded by the DAO gene, enters the scene. Diamine Oxidase’s primary job is to break down histamine in our small intestine, regulating the histamine levels in our bodies.

DAO operates like our body’s clean-up crew. When histamine is released into our body from the foods we eat or from mast cell activation, DAO swoops in and removes it, ensuring a balance in our histamine levels.

This histamine degradation is essential as it stops the continuous stimulation of histaminergic neurons, which play a role in our body’s inflammatory and immune responses.

The Effects of DAO Deficiency

But what happens if our body doesn’t have enough DAO? This situation can lead to an excess of histamine because it’s not being broken down properly.

When mast cell degranulation, or the process by which mast cells release histamine, exceeds DAO’s capacity to neutralize it, we experience what’s known as ‘histamine intolerance’.

Histamine affects various parts of our body, binding to receptors on cells in our skin, the endothelial cells lining our blood vessels, and even on certain brain cells, including dopaminergic neurons which play a vital role in our mood and reward system.

Symptoms of histamine intolerance can include things like:

  • Headaches
  • Allergic rhinitis
  • Skin flushing
  • Itchiness
  • Diarrhea
  • Heart issues

Thankfully, there are ways to measure and manage DAO activity. Blood tests can reveal DAO deficiency, and if this is the case, there are practical ways to address it. Research has shown that adhering to a diet that limits histamine-rich foods or taking DAO supplements can be beneficial.

The Connection Between the HPA Axis and Histamine Intolerance

Histamine intolerance might sound like a mouthful, but it’s actually a condition that can cause common symptoms like headaches, allergic rhinitis, upset stomach, or skin issues.

This happens when we don’t have enough of an enzyme called Diamine Oxidase (DAO) in our bodies. DAO’s job is to break down the excess release of histamine, a compound found in many foods.

Now, you might be wondering, “What’s the HPA axis got to do with all this?” Well, it plays a crucial part. The HPA axis is a vital part of our body’s stress response team, and it’s been identified as a possible player in the development of histamine intolerance.

How Does the HPA Axis Connect with Histamine Intolerance?

When our body faces stress, the HPA axis jumps into action. However, when this happens a lot—like when we’re under chronic stress—it can lead to an imbalance in our body’s histamine levels.

Why is this? It’s because the HPA activation can influence the production and activity of our gatekeeper enzyme, DAO. So, when the HPA axis is always “on,” it can lead to less DAO in our body.

This means histamine isn’t broken down as it should be, leading to an accumulation of histamine, which can make the symptoms of histamine intolerance worse.

So, What Does This Mean for Histamine Intolerance Management?

In short, the activation of the HPA axis can play a role in histamine intolerance by affecting the production and activity of DAO. This results in reduced breakdown of histamine and a build-up of histamine in our body.

This information is key in managing histamine intolerance. By understanding the relationship between the HPA axis activation and DAO activity, we can explore ways to balance the HPA axis and support DAO function.

By doing so, it may be possible to alleviate the discomforts that come with histamine intolerance. It’s all about keeping our body’s histamine levels in check and helping the gatekeeper enzyme, DAO, do its job effectively.

Maintaining Balance: Simple Steps to Regulate HPA Axis and DAO Levels

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Living with histamine intolerance can be challenging. However, the good news is that a few lifestyle changes can help manage this condition by balancing the HPA axis and DAO levels in the body.

Here’s how:

  • An HPA axis tailored diet: A specific diet rich in nutrient-dense carbohydrates, healthy fats, clean, whole foods, and free from artificial ingredients can help improve the HPA axis’s function.
  • DAO-friendly foods: Foods like kidney beans, lentils, peas, and chickpeas can help increase DAO levels. Protein from grass-fed, organic sources and fresh seafood can also boost DAO activity.
  • Proper nutrition: Certain nutrients like phosphorus, calcium, zinc, magnesium, iron, and vitamin B12 can support DAO activity. Including foods rich in these nutrients in your diet can help maintain good DAO levels.
  • Regular exercise and sleep: Exercising regularly and getting enough high-quality sleep can support overall health and digestion, which in turn, can help DAO levels.
  • DAO supplements: Available in capsule form, these supplements can help break down histamine when consumed. However, they don’t increase internal DAO levels.


The connection between the HPA axis and DAO is a critical aspect of understanding our body’s ability to manage stress and dietary histamine.

Chronic activation of the HPA axis can influence the effectiveness of DAO, leading to a potential buildup of histamine in our body. This can manifest as histamine intolerance.

By recognizing this relationship, we can explore ways to balance HPA axis activity and enhance DAO function to manage and potentially alleviate the symptoms of histamine intolerance.

As we continue to learn and understand these complex biological interactions, we enhance our ability to optimize our health and manage conditions like histamine intolerance effectively.

Boost Your Body’s Balance with DAO Supplements from SeeBeyond Shop

In the complex orchestra of our body’s functions, Diamine Oxidase (DAO) plays a key role in maintaining the harmony of histamine levels. If you’re seeking a solution to help your body manage histamine more efficiently, consider our DAO supplements at SeeBeyond Shop.

Our supplements are carefully formulated to assist your body in histamine breakdown. Made with high-quality ingredients, our DAO supplements could be just what you need to keep your histamine levels in check. While these supplements don’t directly increase your body’s internal DAO levels, they aid in the process of histamine degradation when consumed.

Don’t let histamine intolerance disrupt your rhythm of life. Give your body the support it needs to keep the music playing smoothly. Check out our DAO supplements at SeeBeyond Shop today and step towards a more balanced lifestyle.

We are offering 30 minutes for free to talk to one of SeeBeyond's Functional Medicine Practitioners to create a personalized regimen.

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