Fibromyalgia Pain Linked with Glutamate and Histamine

October 16, 2017 | Linda J. Dobberstein, Chiropractor, Board Certified in Clinical Nutrition

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Fibromyalgia Pain Linked with Glutamate and Histamine
Chronic pain, exhaustion and the loss of health with fibromyalgia knows no boundaries. This was seen with Lady Gaga, who last month confirmed her struggles with fibromyalgia in a new documentary. It may be hard to imagine individuals who are in the spotlight and appear energetic and healthy to have fibromyalgia. The reality is there are millions of individuals who suffer from fibromyalgia (FM) and other similar illnesses (chronic fatigue syndrome, Lyme disease, multiple sclerosis, multiple chemical sensitivity, etc.) who look normal on the outside, but struggle with chronic illness. Many of them get through the day with a brave face only to go home and crash from pain and fatigue. No matter who it affects, the disorder is real. Knowledge about some key things can help those with fibromyalgia improve their quality of life.

Fibromyalgia: Multiple Abnormalities


Fibromyalgia often develops after situations of high acute or prolonged physical and psychosocial stress. Genetic vulnerabilities with other biological and environmental factors increase the risk. In response to various factors, chronic widespread pain, fatigue, sleep disturbances, and cognitive difficulties occurs. It affects women more than men.

The disorder was previously thought to be related to dysfunction with the muscle and surrounding tissues. However, medical research over recent years has shown that it is a central nervous system disorder. It is a disorder of abnormal pain processing within the brain which results in amplified pain known as “central sensitization”. Fibromyalgia is also related with other neurological changes or brain abnormalities, nerve fiber abnormalities/peripheral neuropathy, and neurochemical changes.

Central Sensitization


Central sensitization occurs as an exaggerated response to stimulus. The result is increased sensitivity to stimulus (such as light touch, massage, or clothing) that would not normally be expected to be painful. High persistent levels of stress cause changes in the autonomic nervous system in some individuals that leads to fibromyalgia.

An up-regulation of the sympathetic (fight-flight) autonomic nervous system and decreased parasympathetic (rest and digest) autonomic nervous system occurs. This neurological dysfunction ultimately leads to a locked-in pain pattern from increased oxidative stress and pro-inflammatory chemicals. Over time, alterations within the brain occur which affects pain processing, stress tolerance, sleep, and energy production.

Brain Fatigue


Fibromyalgia symptoms of brain fog, brain fatigue, and decreased cognitive functions can be difficult and debilitating. Recognition of brain changes with modern medical technology identifies and validates why these symptoms may occur. Most recently, new information published in July 2017 identified changes in brain waves and neurological activity via electroencephalograph activity (EEG).

Researchers found higher levels of “neural noise” in fibromyalgia patients. When higher levels of neural noise were present, fibromyalgia patients had greater problems with cognitive dysfunction. Neural noise was seen as reduced neurological power and loss of synchronicity between nerve cells. An analogy of neural noise would be like listening to your favorite radio station but the reception is poor due to high amounts of static and poor signal quality.

Other recent EEG studies in fibromyalgia patients demonstrate that parts of the brain that manage pain lack good connections between themselves, like a bridge broken in the road. This compromises the ability to inhibit pain. Other studies have shown loss of gray matter or brain shrinkage in fibromyalgia. These effects may be driven by chemical changes within the brain that provoke oxidative stress and tissue dysfunction.

Elevated Glutamate Levels


Two neurochemical compounds altered in fibromyalgia amongst others include the excitatory neurotransmitters glutamate and histamine. A significant study pertaining to fibromyalgia and the neurotransmitter glutamate was just released in the Clinical Journal of Pain in October 2017. In this systematic review, it was confirmed that elevated levels of glutamate are present in several regions in the brain (posterior cingulate gyrus, posterior insula, ventrolateral prefrontal cortex, and amygdala). High glutamate levels were also associated with amplified fibromyalgia symptoms. Those who follow fibromyalgia research may not find this completely new, but the review study confirms just how big of a concern it is. This makes management of elevated glutamate critical for fibromyalgia management.

Glutamate is a powerful excitatory neurotransmitter that is released in the brain by nerve cells and is necessary in small amounts for brain function with learning and memory. However, excess glutamate damages nerve cells. This occurs either because too much is produced or nerve cells are overly sensitized to “normal” amounts. Too much glutamate exposure leads to high levels of reactive oxygen species (ROS) and provokes oxidative, inflammatory stress to the brain. Symptoms of excess glutamate may lead to increased pain, anxiety, restlessness, sleep disturbance, depression, restless legs syndrome, increased itching, poor focus, and other decreased cognitive skills.

There are many reasons for too much glutamate in the brain. Elevated glutamate may result from neurodegenerative diseases, concussions/traumatic brain injuries, stroke, hypoglycemia, and noise stressChronic, sustained stress is another reason for elevated glutamate as the stress hormone cortisol triggers a release of glutamate in the brain. Stress refers to anything (physical, mental, or emotional) that upsets the body’s normal homeostatic balance.

Elevated thyroid hormone levels, like chronically elevated cortisol, may raise blood glutamate levels. Elevated blood glutamate levels may be problematic for the brain if the blood brain barrier is dysfunctional and leaky.

Elevated Histamine Levels


Histamine, like glutamate, is another excitatory neurotransmitter that is also released by stress and is elevated in fibromyalgia and chronic fatigue syndrome/myalgic encephalomyelitis patients. Histamine is involved with the immune system, skin, and digestive tract, but it plays a major role with wakefulness, blood pressure, satiety, and numerous other brain functions.

The brain and body contains histamine in immune cells called mast cells. Mast cells release histamine in response to various signals, like an allergen or other immune stressors. A major storage site of mast cells in the brain exists in the thalamus, which is located next to the hypothalamus. This region is the sleep-wake center of the brain.

When mast cells release high levels of histamine in the brain, it signals the hypothalamus which leads to wakefulness, disrupted sleep or insomnia. The release of histamine within the thalamus/hypothalamus is thought to lead to impaired sleep quality seen in fibromyalgia and chronic fatigue syndrome. Histamine release also perpetuates central sensitization or chronic widespread pain as histamine releases substance P and glutamate that causes oxidative stress, wind-up, and chronic inflammation.

Some individuals do not process histamine well because of the DAO gene variants. Others may have a diet high in histamine foods that the body cannot handle in significant amounts. Sources of histamine in the diet include fermented beverages and foods like wine, champagne, beer, kombucha, kefir, vinegar, yogurt, cured meats, and vinegar containing foods.

Mast cells are also highly abundant in the skin, which is why histamine release in the skin creates itching. Fibromyalgia patients have been found to have 5-14 times more histamine in their skin than others. Mast cells in the skin provide an immune defense in the skin against outside pathogens.

Nutrients to Manage Glutamate and Histamine


The relaxing neurotransmitter GABA is the opposite of glutamate. Medical treatment of fibromyalgia focuses on powerful medications like Lyrica and Neurontin which attempt to upregulate GABA production and dampen irritated nerves. However, these drugs have significant side effects.

Natural means of supporting GABA production in the brain involves vitamin B6, magnesium, glycine, taurine, theanine and other herbal compounds like lemon balm, noni, passion flower, and valerian root. These provide a gentler approach to helping the brain naturally make GABA.

Other nutrients play a key role in dampening glutamate. One of the most important nutrients at the forefront is magnesium. Magnesium blocks the receptor sites (NMDA) for glutamate and substance P in the brain. This results in decreased excitotoxic activity and oxidative stress to nerves, mitochondria, immune cells, and glial cells which helps calm down central sensitization and pain.

Together with magnesium, the brain needs adequate levels of the master antioxidant glutathione (made in the body by taking N-acetyl-cysteine), estrogen, and progesterone to buffer glutamate and oxidative stress. Coenzyme Q10 which is commonly low in fibromyalgia patients can buffer against glutamate neurotoxicity.

Insufficient vitamin B1 (thiamin) can also increase pain sensitivity and brain oxidative stress. Magnesium works in tandem with vitamin B1. If one is deficient, it impairs function of the other nutrient. The standard Western diet does not provide enough vitamin B1 or magnesium for most individuals.

Vitamin D deficiency is common in fibromyalgia patients and is considered a cause of widespread pain. Vitamin D provides a highly positive stabilizing, anti-inflammatory effect against glutamate and mast cells. Vitamin D deficiency worsens the negative impact of glutamate and histamine on the brain.

Women may find that vitamin D with progesterone is helpful for their fibromyalgia symptoms, as the combination helps protect the brain and buffer the release of glutamate. Progesterone is noted to work better with vitamin D for reducing glutamate than with just progesterone alone. Some women may also find natural estrogen helpful for neurological protection against the free radical damage caused by glutamate. Lab values can be helpful to know if estrogen or progesterone levels are out of balance.

Nutritional support can help reduce histamine levels and block mast cells from release of histamine. Nutrients include the tocotrienol forms of vitamin E, vitamin C, magnesium, and quercetin. These can be taken any time of the day or night to help with sleep, restlessness, and pain. Research shows that quercetin is noted to be a better mast cell stabilizer than the prescription drug cromoglucate/Cromolyn. This effect was especially seen in the skin.

Detoxification or breakdown of histamine uses methylation pathways in the body. Nutrients needed for this process included vitamin B1, B2, B3, B6, calcium, magnesium, copper, zinc, and sulfur.

Fibromyalgia is a complicated disorder. It knows no boundaries, but women are more likely to develop the disorder. Millions of individuals suffer from fibromyalgia or chronic widespread pain. Whether your fibromyalgia started after a motor vehicle accident, a severe illness or surgery, or after years of unrelenting output and stress, the accumulation of stressors leads to the result of disrupted health affecting the whole body.

This article focuses on some of the most important neurological concerns found with fibromyalgia. In order for the “wind-up” or central sensitization to be reduced, glutamate and histamine levels must be quenched along with the oxidative stress that occurs in its path. Focus on key nutrients like vitamin D, magnesium, coenzyme Q10, quercetin, B vitamins, tocotrienols, and others. It may not get you singing like Lady Gaga, but it may help you feel better and sing for joy.

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