GABA & Glutamate in Chronic Fatigue Syndrome

What Jobs They Do, What Problems They Can Cause

The insula, in red, is involved in memory, learning, and emotional response. Dorling Kindersley/Getty Images

GABA and glutamate are neurotransmitters—chemical messengers in your brain. One is calming, one is stimulating, and they're supposed to stay in balance with each other. So what happens if this balance is thrown off?

Some research suggests an imbalance of these two substances may play a role in fibromyalgia (FMS). Research is less solid on their involvement in chronic fatigue syndrome (ME/CFS), with some studies turning up evidence of dysregulation and others finding nothing.

In Your Brain

The human brain is incredibly complex. Each neurotransmitter performs a variety of functions, and they interact with each other and your neurons (brain cells) in an intricate manner that we don't fully understand.

Still, we're constantly learning more about the brain and researchers have been able to link certain neurotransmitter abnormalities to certain illnesses or symptoms. They've also found ways to change neurotransmitter function and can see the very real effects it has on research subjects.

The brain is an efficient recycler, often using one neurotransmitter to create another. This function makes a lot of sense when you're talking about neurotransmitters with opposite functions, such as GABA and glutamate. The better-known serotonin and melatonin pair is another example, as are norepinephrine and dopamine. All of those neurotransmitters are believed to be dysregulated in these conditions.

When one neurotransmitter in a pair is out of balance, it may throw the other one out of balance, as well.

Glutamate

Glutamate is kind of the cheerleader of your brain. One of its primary functions is to get other brain cells fired up. It stimulates them so they can do important things like learning new information or forming memories—other things in which glutamate is involved.

However, a cheerleader who never stops making you spell things gets annoying after a while. Too much of a stimulant isn't a good thing, as anyone who's drunk way too much coffee can tell you. In certain situations, glutamate can become what's called an "excitotoxin," meaning that it sometimes appears to over-excite neurons until they commit suicide.

The ability to cause the death of brain cells is why glutamate is believed to be involved in some degenerative brain diseases such as Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease.) (Note: FMS and ME/CFS are NOT believed to be degenerative.)

In FMS, research shows abnormally high levels of glutamate in a part of the brain called the insula or insular cortex. Researchers went looking there because that area is highly involved in pain and emotion, which are key components of the condition. The insula is also involved in sensory perception, motor skills, anxiety, eating disorders, and addiction.

Research also has linked high glutamate levels with depression and low cognitive function in people with type 1 diabetes. (Glutamate can be derived from glucose, which is often high in diabetics.) At least one FMS study has suggested that lowering glutamate levels can reduce pain.

Excess brain glutamate is believed to cause numerous symptoms, including:

  • hyperalgesia (pain amplification, a key feature of FMS)
  • anxiety
  • restlessness
  • ADHD-like symptoms, such as inability to focus

In ME/CFS, some researchers hypothesize that glutamate function is low, which means the brain isn't getting enough stimulation. However, this belief is not yet supported by evidence.

A glutamate deficiency in the brain is believed to cause symptoms including:

  • insomnia
  • concentration problems
  • mental exhaustion
  • low energy

GABA

GABA stands for gamma-amino-n-butyric acid. Your brain uses glutamate to produce GABA.

A primary function of GABA is to calm your brain.

It's also involved in sleep, relaxation, anxiety regulation and muscle function.

GABA is believed to be either low or inefficiently used in FMS. Thus far, research does not suggest GABA dysregulation in ME/CFS.

Because of GABA and glutamate's close relationship, symptoms of brain GABA deficiency may resemble, or overlap with, those of brain glutamate excess.

Finding a Balance

If you suspect GABA/glutamate dysregulation is causing some of your symptoms, talk to your doctor about it. There are drugs, supplements, and dietary changes that may help you find the right balance. You can explore those options here:

Sources:

Hannestad U, Theodorsson E, Evengård B. International journal of clinical chemisty. 2007 Feb;376(1-2):23-9. Epub 2006 Jul 14. 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.

Harris RE, et. al. Arthritis and rheumatism. 2008 Mar;58(3):903-7. Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia.

Lyoo IK, et. al. Archives of general psychiatry. 2009 Aug;66(8):878-87. Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus.

Murrough JW, et. al. NMR in biomedicine. 2010 Jul;23(6):643-50. Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder.

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