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Connecting the Dots: Histamine, PMDD, and Finding Lasting Relief through Functional Nutrition

If you’ve been exploring PMDD (Premenstrual Dysphoric Disorder) for a while, you’ve probably seen conversations about histamine intolerance being a potential root cause of PMDD or PME (Premenstrual Exacerbation). Understanding the connection between histamine and PMDD can help you make sense of the core issues driving your symptoms. From there, you can arrive at a targeted plan for relief. 

Of course, when you first learn about this connection, it can seem daunting. And because PMDD is such a complex condition, it’s natural to assume it requires a complex solution.

Yet I know firsthand it’s possible to get lasting relief from PMDD. In my case, I went from debilitating symptoms to welcoming my cycle each month.

But I didn’t find relief through one-size-fits-all solutions or super restrictive diets. Using a comprehensive functional medicine approach, I got clear on the unique root causes of my symptoms and restored balance in my body. 

Now my team and I are helping hundreds of people do the same. 

In this article, we’re exploring the link between PMDD and histamine so you can stop playing whack-a-mole with your symptoms and feel like yourself again. Using functional nutrition, cycle syncing, and other tools, we'll cover how you can reclaim your vitality while staying as flexible with your diet and lifestyle as possible. 

First, what is histamine?

To understand histamine, we first need to talk about mast cells. 

Mast cells are white blood cells that scan for issues in the body – inflammation, imbalances, triggers in the environment – and mount responses to them (1). Mast cells liberate and release histamine (among other inflammatory messengers) to trigger an immune response.

When you hear the word “histamine,” you might instantly think about allergies. Histamine is an important mediator of allergies, but it also plays a variety of roles in the body, regulating everything from stomach acid to ovulation to libido. It’s not all bad! 

However, because histamine influences so many bodily processes, symptoms occur when we’re overburdened by histamine or we can’t clear it out at the rate it’s being produced. This is histamine intolerance. 

 

Symptoms of Histamine Intolerance

If you’re experiencing any of the following symptoms, histamine intolerance may be a contributing root cause factor to your menstrual mood symptoms (2):

  • Mood disturbances such as feelings of anxiety, irritability, or even rage, especially around ovulation or the mid-luteal phase (about one week before your period)
  • Cyclical headaches (around ovulation and mid-luteal phase)
  • Breast tenderness or pain
  • Brain fog or confusion 
  • Itchy skin, hives, or rashes
  • Creepy crawly sensations
  • Irregular or fast heart rate
  • Low blood pressure
  • Dizziness
  • Throat tightness
  • Dermatographia (when you scratch your skin, it leaves raised, red marks)
  • Joint pain
  • Unexplained coughing or mucus formation after eating specific foods
  • Nasal congestion or allergies 
  • Digestive issues (indigestion or reflux)

 

 

The connections between PMDD and histamine intolerance

Histamine can be a contributing root cause of PMDD and PME because of the interplay between histamine and hormones. 

Cyclical hormonal shifts can cause histamine symptoms to intensify. At the same time, an overabundance of histamine (or the inability to clear it) contributes to PMS and PMDD symptoms like anxiety, brain fog, and irritability. 

Why does this happen?

Histamine symptoms often align with the menstrual cycle, typically increasing when estrogen rises during ovulation and the luteal phase (the week before the period). Estrogen stimulates our mast cells to release histamine and other immune-modulating messengers.

At the same time, estrogen also down-regulates the DAO enzyme, which is responsible for clearing histamine from the body. This can cause symptoms to stack upon each other and intensify (3). 

The issue is compounded: Not only is estrogen causing more histamine to be released, but it’s also downregulating the enzymes that help clear histamine out of the body. 

Pre-existing hormonal imbalances (like estrogen excess) can make this phenomenon worse. But this vicious cycle can occur with natural hormone fluctuations throughout the cycle, even without hormone imbalances. 

 

 

Another neurotransmitter important to the PMDD puzzle is GABA (Gamma-Aminobutyric Acid). GABA regulates mood, anxiety, and sleep. Some studies suggest that GABA function is altered in PMDD. For example, this study showed that those with PMDD had lower levels of GABA than those without PMDD (4), while another showed that GABA levels are different throughout the cycle among people with and without PMDD (5). 

Another study suggested that in PMDD, the GABA receptors are less able to adapt and respond to the changing levels, creating neurosteroid change sensitivity (6). All of this supports the possible role of GABA levels as a driving factor in PMDD.

Relatedly, the same cofactors that impact histamine metabolism (magnesium and B6) also play a role in GABA production. This suggests that deficiencies in magnesium and B6 could impact your body’s ability to produce GABA, leading to mood disturbances seen in PMDD and PME. 

Newer research suggests that GABA acts like a “brake,” reducing the intensity of histamine’s stimulating effects (7). 

You see, it’s all connected: hormones, histamine, and brain chemicals.  With a functional medicine approach, we identify the underlying imbalance to ensure “we’re barking up the right tree” to get you lasting relief. 

 

Underlying root causes of histamine intolerance

If you want to resolve your symptoms, it’s vital to understand the factors contributing to your histamine intolerance symptoms in the first place. Every person will have unique root causes, and in most cases, multiple root cause factors. In our work, we do a deep dive into your history and symptoms while bringing in functional lab testing to connect the dots and determine where to focus our efforts. 

Remember that mast cells are white blood cells that scavenge for triggers in the body. They’re looking for immune threats, so to speak. In response, they release immune-modulating messengers (histamine being one of them) to mount a response to whatever’s triggering the problem. 

When it comes to addressing histamine intolerance, we’re dealing with two issues at once. These triggers not only liberate lots of histamine, but they can also interfere with the body’s ability to produce enzymes that break histamine down, leading to a vicious cycle that feeds into itself. 

To understand why histamine triggers symptoms, visualize a bucket. 

Imagine the size of the bucket changes depending on a person’s individual tolerance to histamine (8). Their tolerance, or bucket size, is determined by factors like genetics (and how they produce certain enzymes that break histamine down) and their digestive health (because one of these enzymes, DAO, is also made in our intestinal lining). 

The histamine bucket is filled up by a variety of triggers such as stress, inflammation, certain gut pathogens and bacteria, hormone imbalances, and high histamine foods. Certain medications, nutrient insufficienies, and gut health issues can influence how well we produce the enzymes to clear out that bucket. 

 When the bucket gets filled (i.e. the body releases histamine) faster than we can empty it, it overflows. That tipping point is when we experience symptoms. 

 

Some of the most common root causes of histamine intolerance include: 

Genetics: Genetic predispositions can influence our ability to break down histamine. 

Studies have shown that variations in the DAO enzyme, the HNMT enzyme, and the MAOA enzyme can all affect histamine regulation and metabolism (9). Of course, it’s rarely just one gene on its own but the interplay between them that impacts your risk of histamine intolerance.

Inflammation: Histamine is one of the messengers the body liberates when it detects inflammation. Inflammation happens in everyone, and it’s a necessary part of the healing process. But chronic inflammation harms the body because it gradually damages cells, organs, and tissues (10), making it an underlying root cause factor of nearly every health condition, histamine intolerance included.

Gut microbiome imbalances: Studies suggest that people with histamine intolerance tend to have an overabundance of specific bacterial strains, as well as an overall lack of diversity in their microbiome (11). 

Nutrient insufficiency: Nutrients are cofactors for enzymes that produce histamine. Without these cofactors, the body can’t eliminate histamine, leading to an overload. Vitamin B2, B6, and copper are a few examples of nutrients required to effectively deal with histamine.

Medications: Specific medications can interfere with the production of enzymes that break histamine down. These include over-the-counter antihistamines, plus certain types of antidepressants and birth control.

 

How can I tell if histamine intolerance could be a root cause of my PMDD symptoms?

Along with the symptoms above, timing is a big factor to keep in mind. 

If your symptoms calm down after ovulation, then rear back up during your luteal phase (a week before your period), that may indicate a histamine intolerance is behind your PMDD symptoms. 

If you want to see whether histamine is a primary factor in your symptoms, do an experiment with over-the-counter antihistamines.

First, rate your symptoms before taking the medication and again two to four hours later. If your pain rating drops significantly, you’ll know histamine intolerance is contributing to your PMDD symptoms.  

If your symptoms do not reduce with over-the-counter antihistamines but your symptoms and cycle pattern strongly correlate, this experiment does NOT rule out that histamine is a factor.  It simply means the medications weren’t effective enough to tackle the issue. 

Even if the anti-histamines did work for you, you don’t want to do this regularly. Long-term antihistamine use can be counterproductive. As we mentioned above, these medications can actually block the enzymes we need to bail histamine out of the body, amplifying the underlying problem causing your symptoms in the first place. This is where a root-cause functional medicine approach comes in. 

 

A functional approach to PMDD: The principles of functional medicine

In conventional medicine, there’s a tendency to think in terms of single diagnoses with single cures. Yet this approach isn’t right for everyone, and it doesn’t always bring complete relief. 

Functional medicine takes a more holistic approach: It focuses on the interconnections between different organ systems and how they interact with each other and with our emotional and mental well-being.  Functional medicine also considers what factors are driving the underlying imbalance and how we can shift our nutrition, lifestyle, and environment to restore that balance.  

 

Using a personalized functional nutrition approach to leave behind the PMDD tsunami and enjoy peaceful periods

In my practice, I work on the principle that your wellness and nutritional needs are as unique as you are. Everything from your environment, your diet, your genetics, and even your core beliefs impact what will work best for you.

When I work with clients with PMDD or PME, we use a four-phase framework called Reset, Reveal, Rebalance, and Reclaim. This framework helps tease out the specific root factors behind PMDD and PME. From here, we’ll develop a personalized plan to move forward. 

The exact steps we take depend on your symptoms’ severity, your cyclical symptom pattern, and their underlying root causes.

Below is a glimpse into how we’ll approach each step of this process in our work together.

 

 

Phase 1: Reset

The first step is always to tame your acute symptoms. By finding relief, you’ll have a greater capacity to move forward. At the same time, simply taking action can be a form of relief in itself: knowing what to do to support yourself can remind you of how much agency you have over your symptoms. 

Next, we’ll focus on adding nutrient support. The body needs copper, Vitamin C, Vitamin B6, and other nutrients to create the enzymes needed to clear histamine out of the body.  When these essentials are absent or deficient, histamine intolerance can happen as a consequence. I often recommend starting with a high-quality multivitamin. From there, we use functional lab testing to determine your unique nutrient needs. This data allows us to create a customized plan using strategic supplements and food as medicine. 

Next, you’ll want to focus on eating an anti-inflammatory diet that supports blood sugar regulation. This means adding foods high in omega-3 fats, such as fish, nuts, and seeds. In our method, we make nutrition as simple as possible with cycle-aligned meal prep strategies.  

Some people benefit from reducing histamine-liberating foods such as leftovers or aged cheeses. But following a low-histamine diet forever isn’t the answer. 

We have to dig deeper to find the root causes, so you can find relief without being on a radically restrictive diet. Nobody wants to be on a low-histamine diet forever.

 

Phase 2: Reveal

 At our first appointment, we’ll decide which tests will be most valuable for you based on your symptoms and history. Since so many unique factors play into PMDD, functional lab testing, with the support of a functional practitioner, can help hone your focus.

Testing may include bloodwork to identify root causes of histamine intolerance like inflammation, nutrient insufficiencies, and hormone imbalances.  We often utilize comprehensive stool analysis as well to identify if you have an overgrowth of certain strains of bacteria that activate mast cells and promote histamine production. If that's the case, a low-histamine diet won't be enough to bring you symptom relief. 

We also have the option of testing to see whether you have specific genetic variants that set you up for PMDD-related challenges and histamine intolerance. For example, some genes impact histamine, hormones, brain chemicals, inflammation, and more. 

Keep in mind: Having genetic predispositions that influence the above areas doesn’t mean you’ll always have symptoms of histamine intolerance. It simply means the potential is there and that environmental factors can turn those genes on or off.  Having predispositions also in no way implies that PMDD will be a life sentence. Knowing your predispositions simply gives us more data, and it can make our approach even more targeted. 

During this part of our work together, we’ll also explore whether specific medications may be contributing to your symptoms. For example, certain types of birth control and antidepressants can block histamine breakdown because of synthetic estrogen. Since we’re not MDs, it’s never our job to prescribe medications or change your prescription. Instead, we help arm you with the right questions to discuss with your medical team. 

 

Phase 3: Rebalance

Solving your PMDD puzzle involves looking at the unique psychological and physiological factors behind your symptoms. As a result, what works for one person with PMDD might do nothing for another. For this reason, addressing the root causes of your symptoms can take so many different forms. 

A few essential pillars of my functional approach include: 

 

Cycle syncing

With my clients, I use a cyclical approach to diet changes and supplementation. 

Since your needs change throughout the month, it doesn’t make sense to eat and supplement the same way all cycle long. 

But it doesn’t have to be complicated. Cycle syncing can actually bring flexibility to your diet. Instead of avoiding foods with the potential to trigger symptoms, we’ll identify the specific times of the month when you’re most at risk for symptoms (typically your luteal phase). During that week, you might avoid alcohol, processed sugar, or other histamine triggers. 

This way, you can eliminate or reduce your acute symptoms without giving up the foods or drinks you enjoy altogether.

 

Creating a customized nutrition plan right for you

Since I know that following a restrictive, low-histamine diet isn’t sustainable or ideal for most people, I encourage my clients to focus on addition rather than subtracting. Focus on adding colorful, non-starchy vegetables, healthy, organic proteins, and fatty, omega-3-rich foods. 

Also, try adding more variety and color to your diet. The end goal should be to create a diet uniquely tailored to you and your body’s exact needs. 

Some people will benefit from being mindful of foods that trigger inflammation. In our process, we identify which foods are triggers and how much or how often you can tolerate those foods during different phases of your cycle. The goal is always the most flexible (and fun) diet possible while still keeping symptoms at bay.   

However, when you're dealing with multiple histamine triggers sometimes diet and lifestyle aren't enough.

There. I said it. Sometimes, we have to dig deeper to address the root cause so you're not fighting an uphill battle with diet alone. When we uncover and prioritize this root-cause factors with the functional lab testing (in the Reveal phase) diet and lifestyle get to be EASY.

 

Personalized supplementation 

Supplementation helps us fill in nutrient deficiencies we can’t get through food. The specifics will depend on your unique needs and what we uncover during the Reveal phase with functional lab testing. 

Yet magnesium and B6 deficiencies tend to be common among people with PMDD because they impact histamine metabolism. For this reason, they’re often a good place to start.

 

Nervous system support

Stress can play a major role in PMDD and histamine intolerance.

As a culture, we often believe we can create contentment and ease just by building a resilient, “tough it out” mindset. Yet the capacity (and the willingness) to step into a more empowering mindset and way of life depends on the state of your nervous system.

One of the essential parts of my work with clients is helping them build a toolkit to help them tune in and tend to their nervous system. Together, we create what I call a “NeuroMap” to help you have go-to, in-the-moment strategies, depending on the state of your nervous system. 

When you send your body a signal of safety, you build a greater capacity to respond to stress: This means you can address anything contributing to your pain or struggle without spiraling into overwhelm. 

 

Phase 4: Reclaim

Knowing the connection between PMDD and histamine intolerance allows you to create a strategy and approach that’s as unique as you are. Using functional medicine and functional nutrition, you can rest assured you’re not simply managing your symptoms: you’re meeting them head-on. We leave no stone unturned. 

In the final phase of our work together, after we’ve identified the cause of your symptoms and addressed them, we’ll explore how you can sustain results in the simplest possible way. 

And as fun as it can be to geek out on topics like the microbiome, nutrient deficiencies, and other aspects of functional medicine, I want to emphasize the goal isn’t to spend our lives optimizing everything. The goal is to focus on the foundational pillars of support, so you can reclaim your vitality and live your purpose… with ease and joy. 

When our bodies are inflamed or lacking essential nutrients, we’re incredibly sensitive to even the smallest things. But the more you stabilize your body, the more freedom you have to enjoy life. This way, you can keep your PMDD symptoms at bay without needing to obsess over your habits or put massive restrictions on your diet. 

If you’re ready to stop losing days to PMDD and reclaim your life, I’d love to invite you to join PMDD Revealed

This space allows you to apply this root-cause approach with deeply personalized 1-on-1 work, along with the support of a community doing the same.  he first step is scheduling a Strategy Session so we can decode your period problems and map out your path to peaceful periods. Click here to schedule

 

DISCLAIMER: All information is meant for education only and is not intended for the diagnosis or treatment of disease, nor does it serve as a substitute for medical treatment or advice. You should seek the advice of a physician with any questions or concerns regarding personal medical conditions.

 

References

 

  1. Weller, C. Mast cells. British Society for Immunology. https://www.immunology.org/public-information/bitesized-immunology/cells/mast-cells
  2. Hrubisko, M., Danis, R., Huorka, M., and Wawruch, M. (2021). Histamine intolerance–The more we know, the less we know. Nutrients. 13(7). https://www.mdpi.com/2072-6643/13/7/2228
  3. Briden, L. (October 11, 2020). The curious link between estrogen, mast cells, and histamine. Larabriden.com. https://www.larabriden.com/the-curious-link-between-estrogen-and-histamine-intolerance
  4. Liu, B., Wang, G., Gao, D. et al. (2015). Alterations of GABA and glutamate-glutamine levels in premenstrual dysphoric disorder: A 3T proton magnetic resonance spectroscopy study. Psychiatry Research: Neuroimaging. 231(1). https://www.sciencedirect.com/science/article/abs/pii/S0925492714002728
  5. Epperson, C.N., Haga, K., Mason, GF. (2002). Cortical y-Aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder. Arch Gen Psychiatry. 59(9): 851-858. https://jamanetwork.com/journals/jamapsychiatry/article-abstract/206680
  6. Turkmen, S., Backstrom, T., Wahlstrom, G., et al. (2011). Tolerance to allopregnanolone with a focus on the GABA-A receptor. British Journal of Pharmacology. 162(2): 311-327. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031054/
  7. Saras, A., Gisselmann, G., Vogt-Eisele, A. K. (2008). Histamine action on vertebrate GABA-A receptors: Direct channel gating and potentiation of GABA responses. Mechanisms of Signal Transduction. 283(16). P10470-10475. https://www.jbc.org/article/S0021-9258(20)62014-2/fulltext
  8. Burkhart. A. The low histamine diet: What foods can you eat? Does it help? The Celia MD. https://theceliacmd.com/the-low-histamine-diet-what-is-it-and-does-it-work/
  9. Campbell, B. Exploring the role of genetics in histamine intolerance and symptom expression. Dr. Becky Campbell. https://drbeckycampbell.com/exploring-the-role-of-genetics-in-histamine-intolerance/
  10. Spritzer, F. and Jones, J. (October 12, 2023). What is an anti-inflammatory diet and how to follow it. Healthline. https://www.healthline.com/nutrition/anti-inflammatory-diet-101#foods-to-eat
  11. Schink, M. Konturek, P.C., Tietz, E., et al. (2018). Microbial patterns in patients with histamine intolerance. Journal of Physiological Pharmacology. 69(4). https://pubmed.ncbi.nlm.nih.gov/30552302/.

 

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