The Relationships of Glutamine, Glutamate, and Glutathione

ALS Diet Pages

You've heard the term "no man is an island" or "the knee bone is connected to the shin bone"? The fact that nothing works alone is absolutely true in biochemistry. The bottom line problem with ALS, Parkinson's, Multiple Sclerosis and many other brain or neurological problems is damage by oxidation. Of that fact, we must remain acutely aware (and also that there are extraordinary factors, like heavy metal toxicity, that cause oxidation to be such a horrific problem in sufferers of neurological diseases). Why one neurological disease is different in symptoms from another would be due to degree of oxidation, location of oxidation, degree of body toxicity, body defense systems in place (or missing), etc.

In the field of Personalized Regenerative Medicine we look to remove offending toxins and supply everything the body needs for repair in as natural a way as possible. This is often diametrically opposed to pharmaceutical-medical folks who spend millions seeking that one magic pill to counteract any one of many aspects of a disease. Often, the underlying cause of a disease isn't even known when a drug is taken; neither are all the possible side-effects of a drug. Hence, we have historically witnessed many disastrous outcomes such as those with Fen-Phen® or Vioxx®.

That said, we can't simply remove, nor excessively supply, any one compound, especially not by using an extreme diet or toxic drug to do so. Amino acids and molecules are related, have a purpose, and of themselves are not the problem. Below is one example of three related molecules that are involved in neurological disease, but not "the problem", in and of themselves, as you'll see as you read on.

Glutamine is an amino acid synthesized by the astroglia from another amino acid, called glutamic acid or glutamate. Glutamine is referred to as a conditionally essential amino acid because under certain circumstances the body is unable to produce enough glutamine to meet its needs, so it becomes "essential" during these times to obtain glutamine from the diet. Someone with a neurological disorder would never want to supplement glutamine. And in fact, we would want to remain vigilant to avoid supplements that contain multiple ingredients. Glutamine can be hidden in the list of ingredients or be a component of an ingredient and is the precursor to the excitotoxin glutamate. In a whole foods organic diet, we will be supplying all the building blocks needed for the body to produce its own needed glutamine.

Glutamate (also glutamic acid or L-glutamate, which simply refers to the orientation of the glutamate molecule) is an amino acid (protein building block) neurotransmitter in the brain responsible for the ability of neurons to synapse (connect) and thus do their job. In Snyaptic Self, 2002, Joseph LeDoux said "You are your synapses. They are who you are." So true. It is when something goes awry (like heavy metal toxicity) in neurons' ability to connect and do their job that we present with all the "neurological symptoms" of the various neurological diseases: Tingling, numbness, cramping, inability to think, depression, eyesight fluctuations, fatigue, muscle wasting, and more. You need glutamate. You consume glutamate present in natural foods in your diet, some "bound" some "free" (only the "free" glutamate behaves as an excitotoxin in excess). You consume from less than .3 gram (300 mg) to 1 gram of "free" glutamate daily in a whole foods organic diet. You do not need to add it to your diet in "supplemental" or "seasoning" form (MSG). In fact, be very cautious about accidental supplementation by taking any supplement that contains any soy or fermented products which, by nature, generate free glutamates. When you take them, you are taking free glutamates.

Glutathione is a "good guy" generally. The problem is when it breaks down into its component parts and releases free glutamate (see below). The average diet will take in approximately 100 milligrams of glutathione daily, but studies have shown that much of the oral intake is not even absorbed from the intestines into the blood. Glutathione deficiency has been seen in those who take Tylenol® (acetaminophen) above the recommended amount (either large amounts all at once, or smaller amounts over a longer period of time) - and, in fact, acetaminophen's toxicity to liver and kidneys has been shown to be due to a lack of protective glutathione (acetaminophen toxicity in emergency rooms is handled by administration of high doses of N-aceytlycysteine (NAC), a precursor to glutathione.

Glutathione is made from the amino acids L-cysteine + L-glutamate + glycine. The glutathione the body needs is manufactured in the liver. Much ado is made about supplementing glutathione to counteract the oxidative reactions in the brain occurring in ALS, MS and more. But there are problems with supplementation of glutathione or its precursors. Consider these factors:

  • When the body has excess nitric oxide it converts to peroxynitrite and this reacts with glutathione to make s-nitrosglutathione (a molecule involved in inflammation and vasodilatation).
  • Since glutathione is poorly absorbed from the intestines into the blood (and this may be worse in people who have physiological problems, preventing it from doing so), taking the precursors glutamine or N-acetylcysteine in an attempt to manufacture glutathione can backfire. In fact, people working with autistic children have found that the children do not do well on supplemental NAC or glutamine. Migraneurs (known nitric oxide excess leading to excessive vasodilatation and inflammation) will find that intravenous glutathione will cause a migraine of the worst sort (see #1).
  • Gamma-Glutamyltransferase (GGT) is a glycoprotein that catalyzes the hydrolysis of glutathione to glutamate - and thus sufferers of neurological diseases like migraines and ALS are just as likely, because of all the factors wrong in their bodies, to break glutathione down into it's components, releasing glutamate (excitotoxin). [Characteristics of Alcohol Dependent Subjects with Very Elevated Levels of Gamma-Glutamyltransferase (GGT) Jean-Bernard Daeppen et al. Journal of Studies on Alcohol, Vol. 60, 1999.]
  • Such factors commonly present in ill and hurting people (and the population in general) are higher-than-normal insulin levels (alcohol or sugar consumption, diabetics, etc.) or when the liver has been damaged (as from heavy metals or acetaminophen) and cause the liver's "hepatocytes" to release the enzyme GGT (see #3)

All attempts with amino acids (and other nutrients) should be aimed at balancing, not depleting the body nor supplying an excess unnaturally of any one amino acid (with a few exceptions, like using a single amino acid to exert a safe pharmaceutical effect as opposed to resorting to a dangerous drug). Our list of foods to emphasize for ALS (low-arginine) are based upon balance and using human milk as the "standard" of balance of arginine to lysine (see arginine section).

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