Excitotoxicity occurs when a stimulant triggers neurons to fire excessively. The signal comes from the NMDA receptor, which can be triggered by several neurotransmitters, which causes release of calcium within the cell. Because the body always wants to seek balance, excess of any electrolytes draws water from the extracellular space, to balance electrolyte concentreations. So as a result of this sudden high calcium concentration inside the neuron, the cell swells and dies.
Any substance that can cause this process to occur is considered an excitotoxin.
Excitotoxicity has been associated with neurological conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis (ALS). I also wrote here on the association with Multiple Chemical Sensitivity.
The substances that can affect the NMDA (N-methyl-D-aspartate) receptors, as either primary stimulants or antagonists, include glutamate, aspartate, and magnesium.
Glutamate, Glutamic Acid, and MSG
The primary agonist, or stimulant, to the NMDA receptors is glutamate. Glutamate is produced from the amino acid glutamic acid. Glutamate isn’t bad, as stimulation of the NMDA receptors is involved in learning and memory—but everything in the body is about balance. Too much of a good thing becomes a bad thing. For example, excessive glutamate receptor stimulation can lead to:
- Free radical generation, leading to oxidative damage. The prevailing theory of aging, and of many chronic diseases, has to do with oxidative damage, so this is a big one.
- Mitochondrial damage. The mitochondria are in every cell of the body except for red blood cells, and are responsible for generating your body’s energy currency. Unfortunately this process also becomes a vicious cycle: the mitochondrial damage leads to increased NMDA activity, producing more oxidative damage and even more mitochondrial damage.
- Destruction of neurons in the hypothalamus. The hypothalamus is the body’s master endocrine gland, and it uses glutamate as its neurotransmitter; destruction can lead to obesity, short stature, hypogonadism or infertility and low sex hormones, as well as disruption of sleep-wake cycles, temperature regulation, hypothyroidism, headaches, and more.
- Excessive release of insulin, leading to a drop in blood sugar and potentially overeating.
Excitotoxicity due to glutamate can result from excessive amounts of glutamate, either from overeating foods containing MSG or free glutamic acid, or from inability to break down normal amounts of glutamic acid (see GAD receptor support below).
You’re not going to get an excess of glutamate crossing the blood brain barrier just from eating lots of protein, though: in that case, amino acid concentrations will be in relative balance, and the body will use them as building blocks as needed. But unfortunately, glutamic acid is a very common additive as a flavor enhancer in processed foods, and it’s not usually on the label.
MSG is Monosodium glutamate, or a glutamate with one sodium atom attached to it. The FDA requires manufacturers to list this on the food label, if it’s pure. But free glutamic acid poses the same health risks as MSG, and the FDA does not require a label for it. According to Dr Russell Blaylock’s book, Excitotoxins: The Taste That Kills, we should also be wary of the following labels:
- natural flavors, natural flavorings, seasonings, or spices. These labels can hide anything–including, usually, free glutamic acid.
- Anything with the words hydrolysates, hydrolyzed, or autolyzed, such as protein hydrolysates, hydrolyzed protein or hydrolyzed vegetable protein, or hydrolyzed plant protein, autolyzed yeast, hydrolyzed soy protein, hydrolyzed oat flour, etc. Really, avoid any sort of modification of protein, like plant protein extract or textured protein, protein concentrate or protein isolate.
- Anything with caseinate in it: sodium caseinate or calcium caseinate.
- Anything listing soy in a processed food is a possible culprit. (For recipes that call for soy sauce, I’m a fan of coconut aminos as an alternative—they taste the same, without the potential GMO issues, gluten issues, or glutamic acid issues.)
- Anything enzyme-modified, as enzymes can release excitotoxic amino acids.
- Anything with the word malt in it, such as malt flavoring, barley malt, or malt extract.
- Anything suggesting broth if it’s not pure organic broth, including boullion or stock.
Support for GAD (Glutamic Acid Decarboxylase)
Avoiding free glutamic acids in processed foods is more than half the battle. But once the levels of glutamate are high, or for those who have a genetic mutation leading to a slow GAD (Glutamic Acid Decarboxylase) enzyme, some additional support may be needed.
GAD converts glutamic acid into GABA, the calming neurotransmitter associated with decreased anxiety, so that it doesn’t funnel into glutamate instead. Every enzyme has cofactors, or vitamins and minerals that are necessary for them to function. GAD’s cofactors are vitamins B1 (thiamine) and B6 (pyridoxine). Thiamine is a rare deficiency for most, so B6 is probably most relevant for supplementation, if supplementation is needed.
Taurine also fits in here, as it helps to increase GAD activity as well as stimulate GABA receptors.
Aspartate and Aspartame
Another excitotoxic food additive is aspartame, a derivative of the amino acid aspartate or aspartic acid. While aspartate doesn’t bind as strongly to the NMDA receptors as glutamate, it is usually consumed in beverages rather than in foods, which means it hits the bloodstream that much quicker (in the same way that sugar spikes blood glucose levels faster in beverages than when combined with protein or fat). So aspartame-induced excitotoxicity can be responsible for the same problems listed above, including oxidative stress, mitochondrial damage, hypothalamic damage, and an insulin surge. This last point may be in part why many artificial sweeteners paradoxically have been associated with weight gain.
The most common source of aspartate excitotoxicity is of course NutraSweet (aspartame), used as a sugar alternative most commonly in coffee and tea. For better sugar alternatives, click here.
Magnesium actually blocks the NMDA receptors; in order for calcium channels to open, the magnesium has to be dislodged. Because of this, it can protect against excitotoxicity and has been proposed as part of disease management for neurological diseases such as ALS, Alzheimer’s, Parkinson’s, and Huntington’s Disease.
Magnesium threonate crosses the blood brain barrier better than other forms, so it seems a natural choice here. Magnesium glutamate and aspartate should be avoided, since those may potentially work at cross purposes, for obvious reasons.
As I wrote here, sometimes the problem with excitotoxicity isn’t necessarily an excess of the NMDA receptor stimulants or a deficiency of magnesium, but damage to the receptor itself. This has been shown to occur with various chemicals, including the insecticide DDT, formaldehyde, organophosphates, toluene, and carbon monoxide.
While magnesium supplementation would still make sense here, the focus in cases of excitotoxicity secondary to chemical damage should be on antioxidant support.
Other NMDA Modulators
Additional NMDA modulators which can help to calm down excitotoxicity include:
Dietary considerations are probably most relevant to this discussion for the widest number of people. You can memorize the list of labels that strongly imply the presence of free glutamic acid, and specifically avoid NutraSweet—but it’s better to avoid processed foods altogether as much as possible, and eat real foods.
Also, I’d suggest checking magnesium RBC on bloodwork to determine whether your levels are in optimal ranges, and supplement if they are not. If you suffer from symptoms of excitotoxicity, I’d choose magnesium threonate and steer clear of magnesium aspartate or glutamate.