High glutamate: symptoms and causes

10What does high glutamate mean?

When doctors speak of high glutamate, they mean that a large amount of it stays in the synapses or that its receptors are activated more than necessary, so nerve cells stay in a state of overexcitation. This is completely different from a raised level of a substance in the blood, such as sugar or cholesterol.

This usually happens for one of three reasons: excess release from cells, the inability of astrocytes to clear it quickly, or increased receptor sensitivity after long adaptation to a suppressing substance such as alcohol. All three can combine in one case.

11What is glutamate excitotoxicity?

Excitotoxicity is the condition in which glutamate turns from a useful messenger into an agent of destruction. When nerve cells are exposed to a large amount of it for a long time, NMDA receptors open too much and calcium floods into the cell in amounts it cannot tolerate.

1. Stage 1
   Glutamate buildup

   Because of lack of oxygen, injury or seizure, glutamate is released in large amounts and its clearance fails.

2. Stage 2
   Receptor overactivation

   NMDA and other receptors stay open and calcium enters the cell.

3. Stage 3
   Disruption inside the cell

   Excess calcium exhausts the cell’s energy centers and harmful compounds form that attack cell components.

4. Stage 4
   Cell death

   The cell begins a programmed death cascade, and may in turn release more glutamate, widening the circle.

Scientific reviews regard excitotoxicity as one of the most important mechanisms of secondary injury after head injury and stroke, meaning the damage that continues in the hours and days after the first injury. That is why emergency and intensive care doctors work to protect the brain early by controlling oxygen, blood pressure, sugar and temperature.

12What symptoms may be linked to glutamate overactivity?

There is no set of symptoms specific to glutamate alone, but conditions in which its activity rises share signs of nervous system overexcitation. Their severity varies with the cause:

• Seizures or epileptic attacks, the clearest form of nerve overexcitation
• Confusion and disorientation, with difficulty knowing place and time
• Agitation and severe tension, tremor and inability to settle
• Hallucinations, auditory or visual, especially in alcohol withdrawal
• Severe insomnia and inability to sleep with excessive alertness
• Increased sensitivity to pain, so that what was not painful before now hurts
• Severe headache and sudden neurological changes in stroke and head injury

Some research points to a role for glutamate imbalance in anxiety, obsessive-compulsive disorder (OCD), migraine and chronic pain, but these are research links that have not yet become a test or diagnosis a doctor uses for a particular person.

13What causes high glutamate in the brain?

Note that food is not among these causes; eating foods rich in glutamate does not raise its level in the brain in healthy people, as we explain in our glutamate guide.

14Why does high glutamate cause seizures on suddenly stopping alcohol?

Alcohol enhances calming GABA and suppresses glutamate’s NMDA receptors. With chronic drinking the brain adapts by increasing glutamate receptors and reducing GABA sensitivity so that it stays balanced despite the alcohol. When the person suddenly stops, the strengthened glutamate system is left without brakes, and the nervous system enters a state of overexcitation.

Medical references note that withdrawal seizures usually appear within about two days of the last drink, and that the more dangerous delirium tremens may appear after several days. Repeated withdrawal episodes also make the next ones more severe, a phenomenon doctors call “kindling.” That is why stopping alcohol or sedatives after dependence must be done under medical supervision. Details of the symptoms and timeline are on the alcohol withdrawal symptoms page.

15Which diseases are linked to increased glutamate activity?

These diseases have multiple causes, and glutamate is one link in their chain, not the only cause. That is why no treatment of glutamate alone is enough to treat them.

16How does the doctor diagnose conditions linked to high glutamate?

Because glutamate cannot be usefully measured in the blood, the doctor works in reverse: looking for the condition that causes the overexcitation and measuring its effects.

1. Medical history: When did the symptoms begin? Did the person stop alcohol or a sedative medication? Was there a head injury?
2. Neurological examination: Assessing consciousness, speech, movement and reflexes.
3. CT or MRI of the brain to look for a stroke, bleeding or injury.
4. Electroencephalogram (EEG) to detect seizure activity.
5. Blood tests for sugar, salts, and liver and kidney function, because they affect brain excitability.
6. Magnetic resonance spectroscopy is used in research to measure glutamate and is rarely requested for individual diagnosis.

17How are conditions linked to high glutamate treated?

Treatment is always directed at the cause, while protecting the brain from continued overexcitation. We mention only the general categories here, since the choice and doses are the doctor’s decision alone:

Do not try to lower “glutamate” with supplements or harsh diets; they have not been shown to change its level in the brain, and they may interfere with epilepsy or psychiatric medications.

18When should you go to the emergency room for symptoms linked to high glutamate?

Some cases of glutamate overactivity cannot wait, because every minute of continued seizure or interrupted blood flow to the brain means nerve cells being lost. Go to the emergency room or call the ambulance on 123 if any of the following signs appear:

• A seizure lasting several minutes, or back-to-back seizures without the person recovering in between.
• Signs of stroke: a drooping face, weakness in an arm or leg, or sudden slurred speech.
• Confusion, hallucinations, tremor, sweating and fever days after stopping alcohol.
• Repeated vomiting or unusual drowsiness after a head injury.