In today’s hectic, hyper-scheduled world, most of us are busier than ever — so it’s no wonder so many of us are tired.

But what happens when tired becomes exhausted? And what happens when that exhaustion starts interfering with every aspect of your life and nothing you do seems to improve your symptoms?

This is the reality for millions of people suffering from chronic fatigue syndrome. And if you’re currently struggling with the effects of this disorder, you know that finding answers can sometimes feel like an uphill battle.

And while modern medicine still has more questions than answers when it comes to this disorder, research has uncovered some promising findings that can help some patients address the underlying causes of their chronic fatigue syndrome.

What is Chronic Fatigue Syndrome

The name chronic fatigue syndrome is fairly self-explanatory. It is a devastating and often “invisible” illness, that can leave sufferers struggling to complete even simple day to day activities.

Chronic fatigue syndrome is characterized by extreme fatigue, even after a restful sleep. Chronic fatigue syndrome, or CFS, is also known as myalgic encephalomytis (ME), or systemic exertion intolerance disease (SEID)[1].

While the primary symptom of CFS is typically severe fatigue that interferes with your ability to carry out normal activities, there are a number of additional symptoms that sufferers may experience including:

• Brain fog
• Poor concentration
• Headaches
• Insomnia and other sleep disorders
• Anxiety
• Depression
• Joint and muscle pain
• Digestive disturbances
• Feeling exhausted after exercise
• Enlarged lymph nodes
• Sore throat

What Causes Chronic Fatigue Syndrome

Chronic fatigue syndrome is still not entirely understood, and researchers have not identified a specific cause. It is speculated that CFS could stem from a number of contributing factors including[2,3]:

• Hormonal imbalances
• Poor immune system response
• Viral infections
• Food allergies/sensitivities
• Oxidative stress
• Increased activity in histamine-producing mast cells [4].

The Role of Histamine in the Body

Histamine is a type of chemical known as a biogenic amine that is naturally produced by the body. Histamine is vital to properly regulate many bodily functions including sleep, blood pressure, digestion, sexual function, mucus secretion, and smooth muscle contraction. It also functions as a neurotransmitter in the brain, carrying chemical messages between neurons [5]. [Click here for a diagram outlining the impacts of histamine on different tissues and organ systems].

Under normal circumstances, the body produces small amounts of histamine to maintain balance among body systems. But when the body responds to stressors such as allergies, wounds, or foreign pathogens our white blood cells — specifically mast cells and basophils — secrete large quantities of histamine as part of the immune response.

Once released, histamine causes capillaries to become more permeable to allow white blood cells to move into the capillaries so they can target and attack the irritants or foreign invaders. This increased capillary permeability also causes fluid to move out of the tissues to rid the body of infectious agents and irritants [6].

What is Histamine Intolerance

The term histamine intolerance is misleading because it is not an issue of intolerance, but an issue of overload.

Histamine intolerance occurs when there is an accumulation of histamine in the body. Either due to increased histamine availability or impaired histamine degradation [7].

Think of histamine levels as a cup. Our body is designed to manage and maintain histamine levels up to a point — but when histamine levels are too high, the cup overflows.

It is this overflowing of the cup that creates the negative symptoms associated with histamine intolerance.

Signs You May Have Histamine Intolerance

The signs of histamine intolerance can be quite broad and include [8,9]:

• Fatigue
• Brain fog and poor concentration
• Headaches or migraines
• Difficulty falling asleep and/or insomnia
• Anxiety
• Joint pain
• Digestive disturbances
• Unexplained weakness
• Abnormal menstrual cycle
• Tissue swelling/inflammation
• Temperature dysregulation
• Dizziness or vertigo
• Breathing problems
• Tachycardia
• Itching
• Hives
• Severe allergies
• Flushing
• Acid reflux
• Nausea/vomiting

Factors That Contribute to Histamine Intolerance

Histamine intolerance is an overload of histamine. So this can be caused by either increased histamine availability or impaired histamine degradation. It is usually a combination of the two that results in excessive amounts of histamine floating around in the body.

Reduced DAO Activity

DAO is an enzyme responsible for breaking down histamine. If DAO levels are impaired or insufficient to cope with the amount of histamine being synthesized or ingested, histamine levels will rise [10]. A number of factors can influence DAO production and availability including:

• Genetics
• Medications
• Long-term NSAID use
• Alcohol consumption
• Diet
• Vitamin deficiencies

Inflammation Causing Foods

Some level of histamine is present in most foods, but some contain higher levels than others. Foods containing high levels of histamine contribute to histamine load and if consumed in excess can overwhelm the bodies ability to keep up with breaking it down [11,12].

There are also certain foods that promote inflammation in the body which indirectly lead to increased levels of histamine. Some pro inflammation foods include:

• Excess sugar
• Sugar alcohols
• Trans fats and refined oils
• Alcohol
• Gluten
• MSG
• Food additives like preservatives and dyes
• Corn
• Soy
• Dairy

Digestive Imbalances

A number of gastrointestinal imbalances can contribute to histamine intolerance[13]:

• Leaky gut syndrome
• Gluten sensitivity
• Small intestinal bacterial overgrowth (SIBO)
• Ulcerative colitis
• Crohn’s disease
• Inflammatory bowel disease (IBS)

Since inflammation and increased histamine levels can also aggravate these conditions, it can create a vicious cycle.

Bacterial Overgrowth

Some researchers have speculated that histamine intolerance can result from an overgrowth of bacteria from undigested food. The undigested food results in an influx of histamine that DAO is unable to degrade properly.

High-Stress Lifestyle

When the body is under stress it releases a hormone called cortisol which stimulates the nervous system to put the body in “fight or flight” mode.

This signals to the body that it is under attack — so it pours all of its resources into energy conservation in order to direct all energy at managing this perceived threat.

This results in a cascade of hormonal responses that activate the immune system and trigger the release of more histamine[14, 15].

This is great when we are actually facing a threat. But the problem arises when chronic stress habitually triggers this response and significantly contributes to overall histamine load.

There are also a number of other hormones impacted by chronic stress that directly and indirectly impact histamine levels including estrogen, progesterone, cortisone, and thyroid hormones [16, 17].

How is Histamine Intolerance Treated?

The focus of healing histamine intolerance is lowering overall histamine load. By addressing both sides of the equation by limiting the amount of histamine synthesized and ingested, as well as increasing the body’s capacity to degrade histamine, histamine levels can be brought to healthy levels and decrease or eliminate symptoms.

Low Histamine Diet

It is impossible to entirely avoid histamine-containing foods, but making dietary choices that minimize histamine intake can reduce your overall histamine load. High histamine foods to avoid include:

• Alcohol
• Fermented food or drinks (like kombucha, pickles, or sauerkraut)
• Tomatoes
• Foods containing artificial dyes or preservatives
• Yeast
• Chocolate and cocoa
• Dairy
• Processed, cured, smoked, or fermented meats
• Leftover meat

It is unrealistic to avoid high histamine foods forever. But implementing a low histamine diet for a few months while working on other lifestyle changes to reduce your histamine load can go a long way in reducing your symptoms.

DAO Supplement

Reducing your intake and synthesis of histamine is a big part of the equation. The other aspect of reducing histamine load is to improve the bodies ability to break it down.

This can be accomplished by adding a supplement to increase DAO levels. DAO supplements can drastically improve symptoms. Finding DAO supplements in a brick and mortar store can be tricky, but a quick online search can yield several selections that can go a long way in healing histamine intolerance.

Heal Your Gut

Impaired gut health creates a vicious cycle of not only creating more histamine but also inhibiting the body’s ability to break down histamine. Taking steps to heal your gut will reduce your overall histamine load and help maintain healthy levels.

Some simple steps to begin healing your gut include:

• Eliminate inflammatory foods such as gluten, corn, soy, sugar, refined oils, and dairy
• Add in lots of healing foods such as nutrient dense vegetables, bone broths, healthy fats, and omega 3-s
• Take supplements such as glutamine and a high-quality probiotic
• Drink plenty of water
• Establish and maintain a healthy elimination pattern

Lifestyle Changes

Systemic inflammation is one of the primary causes of increased histamine production. Making lifestyle changes that reduce inflammation and promote healing can reduce the body’s production of histamine.

The most powerful ways to reduce chronic inflammation are to heal your gut and to consume whole, healing foods. But there are a few other lifestyle changes that can yield big results such as:

• Prioritizing restful sleep
• Partaking in regular light exercise (intense exercise like running or Crossfit can actually worsen symptoms)
• Minimizing stress
• Scheduling in time to just relax
• Meditation, yoga, and/or deep breathing

The Link Between Histamine Intolerance and Chronic Fatigue Syndrome

It’s no surprise that there is a significant overlap of symptoms between chronic fatigue syndrome and histamine intolerance.

Nearly all of the proposed underlying factors thought to contribute to and cause chronic fatigue syndrome increase histamine levels in the body.

An overactive or overstimulated immune system, increased mast cell activity, viral infections, oxidative stress, hormonal imbalances, and food allergies/sensitivities can all trigger the body to launch an immune response — causing an increase in histamine circulating in the body.

While diet, supplements, and lifestyle changes are imperative to treating the root cause of any diagnosis, it is important to do so under the guidance of a healthcare professional. If you suspect that you may be struggling with chronic fatigue syndrome or histamine intolerance, it is essential to contact a doctor experienced in treating patients with chronic fatigue syndrome.

It can also be useful to keep a symptoms diary to track the patterns of your symptoms in relation to other factors such as diet, exercise, environment, stress, etc. This can help your healthcare provider get a clearer picture of your diagnosis and treatment options.

None of the above is intended to be taken as medical advice. If you suspect you are dealing with chronic fatigue syndrome, histamine intolerance, or any other disorder, seek the consultation and guidance of a qualified healthcare provider.