Glutamate in Fibromyalgia & Chronic Fatigue Syndrome

What is Glutamate?

Illustration shows a glutamate molecule.
Glutamate. MediaForMedical/UIG/Getty Images


Glutamate is a neurotransmitter normally involved in learning and memory. It is considered an excitatory neurotransmitter, which means it stimulates areas in the brain or other parts of the nervous system. That's an essential part of the learning process, so in that way, glutamate is a good thing.

But lots of glutamate isn't necessarily something you want. In some cases, it can become an excitotoxin, which means that it overstimulates your brain cells.

Unchecked, it can get them to the point of committing cellular suicide. These are neurons we're talking about, and your brain can't make new ones to replace those that are lost.

Glutamate's role as an excitotoxin is believed to be involved in a variety of neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis (known as ALS or Lou Gherig's disease).

Glutamate & Fibromyalgia

Research shows that people with fibromyalgia have abnormally high levels of glutamate in the area of the brain called the insula (pictured above). The insula is highly involved in processing both pain and emotion. The high glutamate levels are an indicator that this region of the brain may be chronically overstimulated in fibromyalgia.

The insula also is involved in:

  • the senses
  • anxiety
  • motor skills
  • cravings
  • eating disorders
  • addiction

Many of those problems are symptoms of this condition, overlapping conditions, or share similar pathology.

Glutamate is present in areas of the body outside of the nervous system, where it functions as a hormone. In this role, a 2016 study suggests that exercise may decrease glutamate-related pain in people with fibromyalgia, which may help explain the poorly understood connection between the condition and exertion.

Glutamate in Chronic Fatigue Syndrome

Studies are divided as to whether glutamate dysregulation plays a role in chronic fatigue syndrome, which also involves many of the symptoms listed above. In contrast to fibromyalgia, studies suggest that glutamate levels may be low in some regions of the brain.

We also have some evidence to suggest that this disease may involve genes that are related to glutamate dysregulation.

As an amino acid, glutamate is a component of monosodium glutamate (MSG), which is used in pharmaceuticals and as a food additive. Some health-care practitioners believe MSG can be harmful to people with fibromyalgia, while others believe it is not. Some people say that eliminating MSG from their diets has helped alleviate symptoms of fibromyalgia and chronic fatigue syndrome, but these claims are not substantiated by medical science.

Glutamate & Other Neurotransmitters

In the brain, glutamate is balanced by a calming neurotransmitter called GABA.

Other neurotransmitters involved in these conditions include:

Pronunciation: GLOO-ta-mate

Also Known As: L-glutamic acid, glutamic acid, L-glutamate

Hannestad U, Theodorsson E, Evengård B. International journal of clinical chemisty. 2007 Feb;376(1-2):23-9. beta-Alanine and gamma-aminobutyric acid in chronic fatigue syndrome.

Harris RE, et. al. Arthritis and rheumatism. 2009 Oct;60(10):3146-52. Elevated insular glutamate in fibromyalgia is associated with experimental pain.

Kuratsune H, Yamaguti K, Lindh G, et al. NeuroImage. 2002 Nov;17(3):1256-65. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain.

Martins DF, Siteneski A, Ludtke DD, et al. Molecular neurobiology. 2016 Sep 13. [Epub ahead of print] High-intensity swimming exercise decreases glutamate-induced nociception by activation of g-protein-coupled receptors inhibiting phosphorylated protein kinase a.

Smith AK, Fang H, Whistler T, et al. Neuropsychobiology. 2011;64(4):183-94.Convergent genomic studies identify association of GRIK2 and NPAS2 with chronic fatigue syndrome.

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