Histamine Intolerance, Autoimmunity, and Multiple Sclerosis

Posted March 24, 2021

Enjoy this guest post from my friend and colleague Dr. Becky Campbell. She will be presenting more on histamine intolerance, autoimmunity and multiple sclerosis on April 6 on the Wahls Protocol® Virtual Seminar Bonus Call. Learn more and register at terrywahls.com/seminar

Did you know that multiple sclerosis (MS) affects about 1 million people in the United States? Multiple sclerosis is an autoimmune disease that affects your brain and spinal cord. It involves an immune-mediated process that involves an abnormal immune response that attacks your central nervous system (CNS) which is made up of your spinal cord, brain, and optic nerves. Symptoms of multiple sclerosis can affect your motor function, eye health, neurological function, and other areas of your health.

You may wonder why am I talking about multiple sclerosis as a functional medicine doctor who specializes in histamine intolerance. My interest is not surprising considering that research suggests that there is a connection between histamine intolerance and autoimmune diseases, such as multiple sclerosis. I regularly see patients who visit my practice because they have done all the steps to address their autoimmune disease yet are still dealing with a variety of chronic symptoms. The answer usually lies in histamine intolerance. Once we address that, they usually see a decrease in symptoms and improved health. If you are still dealing with symptoms despite your effort to recover, histamine intolerance may just be your answer too.

In this article, you will learn what histamine intolerance is. You will understand its main root causes and the most common symptoms. You will learn about autoimmune disorders. I will discuss what autoimmune disorders are, what are the underlying causes and most common symptoms of autoimmune disorders, and how they are diagnosed. You will learn about the connection between autoimmune disorders and histamine intolerance. You will learn about multiple sclerosis. I will discuss what multiple sclerosis is, what are the main causes and most common symptoms of MS, and how it’s diagnosed. I will share my top recommendations to address histamine intolerance naturally if you have any multiple sclerosis or any other autoimmune disease.

What Is Histamine Intolerance

You’ve probably heard about histamine from anti-histamine medications prescribed for allergies. Because of the ‘anti’ part of the word ‘anti-histamine’, histamine gets a bad rap, when in fact, it’s actually incredibly important for your health and well-being.

Histamine is an important part of your immune system. It is a critical chemical that is responsible for a variety of functions in your body, including getting rid of allergens as part of your immune response, communicating with your brain, and triggering stomach acid release to aid digestion. Under normal circumstances, your body releases DAO enzymes to take care of and breakdown any build-up of any excess histamine, however, if you don’t have enough DAO enzymes or if you have more histamine that these enzymes can handle, it will result in excess histamine.

Histamine intolerance means that your body has too much histamine, more than it can handle, which can lead to various health issues. Histamine intolerance can affect your entire body, including your gut, brain, lungs, cardiovascular system, and hormonal health. It can lead to inflammation, immune health issues, autoimmune reactions, and symptoms all over your body. Histamine intolerance can manifest in a variety of ways, including hormonal issues, migraines, headaches, skin problems, digestive issues, sleep disturbances, bladder problems, anxiety, fast heart rate, blood sugar issues, seasonal allergies, and more (1).

Symptoms of Histamine Intolerance

Symptoms of histamine intolerance may differ from person to person. They may affect your entire body. Symptoms of histamine intolerance may include:

Fatigue
Sleep disturbances or insomnia
Headaches or migraines
Diarrhea
Nausea or vomiting
Acid reflux
Other digestive issues
Congestion or runny nose
Eczema, psoriasis, and other skin issues
Hives
Flushing
Facial swelling or other tissues swelling
Red eyes
Tightness in the throat
Asthma attacks
Seasonal allergies and hay fever
Crawling sensation on the skin or scalp
Low blood pressure
Hypertension
Tachycardia or fast heart rate
Heart palpitations
Drop in blood pressure when standing up
Vertigo or dizziness
Anxiety
Panic attacks
Confusion
Irritability
Mood fluctuations
Abnormal menstrual cycle
Premenstrual syndrome (PMS)
Abnormal menstrual cycle
Bad morning sickness or hyperemesis gravidarum

Causes of Histamine Intolerance

Histamine intolerance doesn’t just happen out of nowhere. There are a variety of factors that may set you up for histamine intolerance. During your treatment plan, we can uncover potential root causes of your histamine intolerance and address them to achieve a full recovery and optimal health.

The main root cause of histamine intolerance include:

Mast cell activation syndrome (MCAS)
Gluten intolerance
Leaky gut syndrome
Gut infections
Inflammatory digestive disease
Nutrient deficiencies
Genetic mutations
Certain medications

What Are Autoimmune Disorders

Your immune system’s job is to defend against foreign pathogens, like viruses, bacteria, yeast, and toxins, and even cancer cells. Under normal circumstances, a healthy immune system is able to protect your body from disease and infection through an immune response. It produces antibodies that help to destroy pathogens. It basically releases an army of fighting cells to attack and destroy any foreign invaders that may harm you.

If you have an autoimmune disease, your body is no longer able to distinguish between its own healthy cells, unhealthy cells, and foreign invaders. It means that your immune system is malfunctioning and mistakenly attacks its own healthy cells, tissues, and organs.

Having an autoimmune disorder may result in the destruction of body tissue, changes in organ function, and the abnormal growth or function of an organ. Depending on the autoimmune disorder you are dealing with, it may affect only one or multiple organs and tissues. Autoimmune disorders may affect your joints, connective tissues, muscles, skin, endocrine glands, such as your thyroid or pancreas, blood vessels, red blood cells, and brain. Autoimmune disorders come with an array of symptoms for fatigue, pain, skin issues, digestive problems, to practically any other chronic symptoms. Autoimmune diseases can seriously weaken your bodily functions. They can be debilitating and in some cases even life-threatening when left untreated (2, 3).

Causes of Autoimmune Disorders

While the exact cause of autoimmune disorders is not yet completely understood, there are multiple factors that may play a role (2, 3, 4, 5, 6):

Being female over being male
Genetics and family history
Eating an inflammatory diet
Pesticides, mercury, and other toxic exposure
Poor gut microbiome imbalance
Infections, including gut infections and chronic infections
Chronic stress
Ultraviolet radiation

Common Autoimmune Disorders

While there are hundreds of autoimmune disorders out there, the most common autoimmune disorders include (7):

Hashimoto’s thyroiditis
Graves’ disease
Celiac disease
Multiple sclerosis
Systemic lupus erythematosus (SLE)
Rheumatoid arthritis (RA)
Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis
Psoriasis and psoriatic arthritis
Addison’s disease
Sjögren’s syndrome
Type 1 diabetes
Pernicious anemia
Myasthenia gravis
Autoimmune vasculitis

Symptoms of Autoimmune Disease

Symptoms of an autoimmune disease can vastly differ depending on which autoimmune condition you are dealing with. However, early symptoms of many autoimmune conditions may be similar. Early symptoms of autoimmune disease may include:

Fatigue
Muscle aches
Various pains
Swelling and redness
Skin rashes
Numbness or tingling in your hands or feet
Hair loss
Brain fog or trouble concentrating
Weight changes
Digestive symptoms
Low-grade fever

Again, your symptoms may vary depending on your autoimmune disease. Symptoms often go in periods of flare and remission. Many of these symptoms may also mimic other chronic health issues, including fibromyalgia, Lyme’s disease, chronic fatigue syndrome, non-autoimmune thyroid disease, non-autoimmune digestive issues, or non-autoimmune skin issues, or other health issues, including histamine intolerance, mast cell activation syndrome, or food sensitivities. Working with a healthcare practitioner, getting the appropriate testing, and receiving the right diagnosis is critical for an appropriate treatment protocol and recovery.

Diagnosis of an Autoimmune Disease

After going through your health history, symptoms, and a physical exam, your doctor will likely order a variety of tests. An antinuclear antibody test (ANA) is commonly used as a first step to determine if you have an autoimmune disorder. Other blood tests may also be used to look for specific antibodies or inflammation. Depending on the type of autoimmune disease you have, other tests, including imaging, may be used for a proper diagnosis and appropriate treatment.

What Is Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease and a nervous system disease that affects your brain and spinal cord. It affects about 1 million people in the United States alone. It is the most common, non-traumatic cause of neurological disability among young people in both North-America and Western-Europe. MS involves an immune-mediated process that involves an abnormal immune response that attacks your central nervous system (CNS) which is made up of your spinal cord, brain, and optic nerves. This results in inflammation within your CNS that also damages the myelin sheath, a fatty material that surrounds, insulates and protects your nerve fibers and nerve cells.

MS can result in a variety of issues. When the myelin sheath or nerve fibers are harmed or destroyed, it can negatively affect or even stop important messages within your CNS. Multiple sclerosis refers to multiple areas of scarring because of the scar tissue that develops in the damaged areas of your CNS. Any damage that occurs within your CNS can result in a variety of neurological symptoms. Symptoms and the severity of symptoms may differ from person to person, the progress of the disease, and the success of their treatment (8, 9, 10, 11).

Causes of Multiple Sclerosis

The causes of MS are not completely understood yet, but the combination of genetic, environmental, immunological, dietary, and lifestyle factors may all play a role. Causes of multiple sclerosis may include (12, 13, 14, 15):

Genetics and family history
Abnormal immune response
Vitamin D deficiency
Smoking
Obesity
Chronic infections, including the Epstein-Barr Virus (EBV), human herpes virus, Chlamydia pneumonia, and measles
Environmental allergies
Heavy metals and other toxins
Gut dysbiosis
Mitochondrial dysfunction
Eating an inflammatory diet
Chronic stress
Geographic and socioeconomic factors
Lyme disese

Symptoms of Multiple Sclerosis

Symptoms of multiple sclerosis may affect your motor functions, vision, and other areas of your health. Symptoms of MS may include:

Numbness or weakness in one or more limbs, usually one on the side or your legs and trunk
Electric-shock sensations that happen with certain neck movements, such as moving your neck forward, which is also referred to as the Lhermitte sign
Tremors
Unsteady gait
Lack of coordination or balance
Muscle weakness
Dizziness
Tingling in parts of your body
Pain in parts of your body
Fatigue
Blurry vision
Partial or complete vision loss typically affecting one eye at a time
Prolonged double vision
Thinking and memory problems
Trouble organizing thoughts
Slurred speech
Mood swings and irritability
Problems with bladder, bowel, and sexual functions

Diagnosis of Multiple Sclerosis

The timely diagnosis of multiple sclerosis is critical to prevent permanent neurological damage and start appropriate treatment as soon as possible. Diagnosis of multiple sclerosis involves a variety of tests. After going through your medical history and symptoms, your doctor may order a neurological exam, eyes exam, various imaging, and sometimes a spinal tap. Various blood tests may be used to rule out other autoimmune and chronic health conditions (16).

Histamine Intolerance and Autoimmunity

You might’ve noticed that the symptoms of histamine intolerance and common symptoms of autoimmunity overlap. Certain possible causes of histamine intolerance and autoimmune diseases, including gut microbiome balance, chronic infections, an inflammatory diet, and toxin exposure, also overlap.

Can some of your autoimmune symptoms be contributed to or enhanced by histamine intolerance? Is there a connection between histamine intolerance and autoimmunity? Can histamine intolerance be the missing link in the understanding and treatment of autoimmune conditions?

Research suggests that both histamine and your mast cells that release histamine play an active role in the development and symptoms of autoimmune diseases. Many autoimmune conditions, including multiple sclerosis, rheumatoid arthritis, and Hashimoto’s thyroiditis are all characterized by increased mast cell activity, histamine release, and inflammatory agent activity.

According to a 1994 study published in Clinical Immunotherapy, histamine may play a role in autoimmune diseases. The study explains that “histamine participates in the regulation of the immune response via binding to specific histamine receptors expressed on cells of immune origin. Histamine may be involved in the development of autoimmune disease via a pathological change in its regulation of the expression of MHC class II restriction antigens by action on histamine H2 receptors.” Researchers suggest that mast cell stabilizing drugs or specific histamine H2 receptor antagonists may be beneficial to reduce autoimmune activity (17).

A 2015 review published in Mediators of Inflammation explains that autoimmune diseases and allergic diseases share similarities, including a hypersensitive immune response that ends up destroying your own body. Mast cells can counteract T regulatory (Treg) cell function. Mast cells and histamine release has also been shown to promote inflammation in both multiple sclerosis and rheumatoid arthritis. The review suggests that targeting mast cells may be a new treatment option for certain autoimmune diseases (18).

A 2012 study published in Biochimica et Biophysica Acta (BBA) has also connected mast cell activity to autoimmunity. The study explains that your mast cells are innate immune cells that also contribute to pathogenic responses that contribute to autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. Mast cell histamine response is necessary during an encounter with an allergen or an infection. Similar to this role, they also play a role when inflammation occurs. Mast cells are necessary for the recruitment of neutrophils, which make up 40 to 70 percent of your blood cells, around the area of inflammation. While the role of mast cells in recruiting neutrophils is necessary and beneficial in infections, when it comes to inflammation related to autoimmune settings, it can become highly problematic. Neutrophils can promote local vascular permeability which allows inflammatory cells to enter and contribute to the destruction of tissues (19).

Histamine Intolerance and Multiple Sclerosis

Much of the research on the relationship between histamine intolerance and autoimmune diseases has been done on multiple sclerosis. To understand the connection, you have to understand that there are four types of histamine categorized based on their ability to bind to protein: H1, H2, H3, and H4.

Types of Histamine Receptors

H1 Histamine Receptor: The H1 histamine receptor plays a role in your allergic response. It is allocated throughout your peripheral nervous system, especially in smooth muscles. It plays a role in causing blood vessel dilation promoting blood vessel permeability, stimulating sensory nerves. H1 receptor activation can also cause sneezing, nasal congestion, and runny nose. It can also prevent potassium channels in neuronal cell membranes which leads to the depolarization of neurons and higher neural excitation, which increases the number of neurotransmitters being released by a neuron (20).
H2 Histamine Receptor: The H2 histamine receptor is located on the parietal cells in your heart, stomach, vascular smooth muscle, and immune cells. H2 receptor activation causes gastric acid release, neutrophil, and basophil activation, T cell stimulation, and increases the activity of the natural killer cells. Together with H1 histamine receptors, H2 activity can cause a runny nose and sinus swelling (20).
H3 Histamine Receptor: The H3 histamine receptor is found on nerve cells that contain histamine. H3 receptors spread out across your central nervous system, especially in your hippocampus, hypothalamus, thalamus, cortex, caudate nucleus, and olfactory tubercle. This may help the regulation of dopamine, norepinephrine, GABA, and other neurotransmitters in both the peripheral and central nervous systems (20).
H4 Histamine Receptor: The H4 histamine receptor is located on your immune cells and tissues, including the bone marrow, peripheral blood leukocytes, and the spleen, as well as the colon, liver, and lungs. It may help the movement of disease-fighting white blood cells, eosinophils, and may upregulate adhesion molecules (20).

Histamine, Histamine Receptors, and Multiple Sclerosis

A 2010 study published in Neuropharmacology has discussed that histamine may play a critical role in the pathophysiology of MS. Histamine can change the blood-brain barrier permeability which can increase infiltrated cells in the central nervous system and cause neuroinflammation. The paper also states that histamine may also play a protective role in MS. It seems that while H1 and H4 histamine receptors may make MS worse, H2 and H3 receptors may help (21).

A 2013 study published in Fluids and Barriers in CNS has looked at the cerebrospinal fluid (CFS) histamine analysis of 36 19-year-old MS patients. They found that the CSF histamine levels were significantly higher in participants with MS than in participants of the control group. These results suggest that histamine may play a factor in multiple sclerosis and chronic inflammatory diseases that affect the central nervous system (22).

A 2018 study published in the American Journal of Clinical and Experimental Immunology, on the other hand, has found lower than healthy histamine and diamine oxidase (DAO) enzyme levels in participants with relapsing-remitting MS. The study enrolled 50 relapsing-remitting MS patients of 41 years of age and used an enzyme-linked immunosorbent assay (ELISA) test to determine serum levels of both histamine and DAO enzyme levels. Results suggest that while too much histamine can be a problem, too low histamine levels may not be ideal for MS patients. Since both studies were relatively small, further studies are needed for more insight (23).

A 2012 review published in Frontiers in Systems Neuroscience has also looked at the connection between histamine and neuroinflammation. Many studies that aim to understand MS use the murine model of experimental autoimmune encephalomyelitis (EAE), an animal model for brain inflammation. Models have found that histamine may play an important regulatory role in MS and EAE (24).

A deficiency in mast cells has also been linked to lower severity of MS. Since fewer mast cells mean lower histamine production, this may mean that less histamine may lead to less severity of symptoms. Looking at EAE models, histamine participates in both the development and the progression of EAE by modulating T lymphocytes, chemotaxis, adhesion molecule expressions, and cytokine behavior. All of these factors play a key role in autoimmune disease and MS. Different histamine receptors may also play a different role (24).

H1 and H2 receptors modulate cytokine and chemokine production, while H4 modulates chemotaxis. While H2 can downregulate both Th1 and Th2 immune responses, H1 can promote a Th1 response. H3 receptors are mostly confined to the CNS where they restrict the release and synthesis of histamine and control neurotransmitter release. It seems that H3 plays a role as central control of cerebrovascular tone and may reduce the susceptibility to neuroinflammatory diseases. The removal of H3 seems to actually may cause more severe symptoms of EAE (24).

The H4 receptor is a common target for both asthma and autoimmune disease treatment strategies. H4 can increase inflammation and cause the progression of pathological responses. Introducing H4 antagonists can reduce inflammation in both allergies and autoimmune conditions. However, it seems that H4 may act differently depending on its activation on different hematopoietic cells. We need further research to completely understand the role of the H4 histamine receptor, other histamine receptors, and mast cells in autoimmunity and multiple sclerosis (24).

Natural Solutions for Histamine Intolerance

Do you have multiple sclerosis or other autoimmune health issues and also experiencing symptoms of histamine intolerance? Here is what I recommend to improve your health naturally:

Eat a Low-Histamine Diet

To improve histamine intolerance, I recommend that you start with your diet. Follow a low-histamine nutrition plan. Start by eliminating all high-histamine foods for one month, then slowly re-introduce them one by one following The 4-Phase Histamine Reset Plan.

I developed the 4-Phase Histamine Reset Plan to help people like you who are dealing with histamine intolerance and related health issues. This reset plan is a simple, easy-to-follow yet refined system. You have to follow each step carefully to see results so it is critical that you understand and follow each step properly.

To understand each step and guide your recovery, I recommend that you read my book, The 4-Phase Histamine Reset Plan: Getting to the Root of Migraines, Eczema, Vertigo, Allergies, and More. In this book, I explain everything about histamine intolerance and each phase of the plan in detail. I will also share my favorite delicious low-histamine recipes to nourish your body and support your health. Don’t worry, eating a low-histamine diet doesn’t have to be boring. I trust that you will love these recipes as much as my patients and my family does. Pick up a copy, today to learn more about The 4-Phase Histamine Reset Plan and my recommendations.

Reduce Stress and Improve Your Lifestyle

Chronic stress and poor lifestyle choices are silently damaging our health every day. They can trigger histamine intolerance and autoimmunity and amplify your histamine intolerance, autoimmune, and multiple sclerosis symptoms. While following a low-histamine diet, I recommend that you also improve your lifestyle.

Make sure to get 7 to 9 hours of quality sleep. Move your body throughout the day and exercise regularly. Spend time in nature. Reduce your stress levels through meditation, guided visualizations, breathwork, progressive relaxation, journaling, and yoga. Seek out uplifting activities and try new hobbies. Find a supportive community and spend time with supportive friends and family. Make sure that you also have some quality ‘me-time’ every day. No matter how busy you are, even if it’s just 5 – 10 minutes a day, it’s important to have some time just for yourself.

Beyond chronic stress, poor sleep, and a lack of movement, bringing toxic products in our lives is another poor lifestyle choice that can contribute to histamine intolerance and autoimmunity. To reduce your toxic load, eliminate toxic personal care and cleaning products as well and instead use organic, natural, or homemade products. Avoid the use of plastics and opt for paper, cloth, glass, wood, bamboo, and stainless steel appliances, tools, and products instead whenever you can.

Final Thoughts

Multiple sclerosis (MS) affects about 1 million people in the United States and the most common, non-traumatic cause of neurological disability in young adults. Multiple sclerosis is an autoimmune disease that affects your brain and spinal cord and can lead to symptoms affecting your motor function, eye health, neurological function, and other areas of your health. Research suggests that mast cells, histamine, and histamine intolerance may play a role in the development, progression, and severity of the symptoms of multiple sclerosis and other autoimmune disorders. Addressing histamine intolerance may support your recovery and help to reduce or eliminate symptoms that you may experience despite following MS or autoimmune protocols diligently. Follow my recommendations to recover from histamine intolerance to reduce your symptoms and improve your health.

If you are dealing with histamine intolerance and autoimmune disease or multiple sclerosis, I invite you to schedule a consultation with us. We can help to identify the root cause of your condition and recommend a personalized treatment plan to repair your body and regain your health and well-being. Schedule your consultation here.

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