Oxaloacetate and Excitotoxicity

/, Supplements/Oxaloacetate and Excitotoxicity

Oxaloacetate and Excitotoxicity

Image by Comfreak from Pixabay 

The body produces energy from food and oxygen, in simplest terms. “Energy,” in this case, is ATP, or adenosine triphosphate. The vast majority of this is produced in the mitochondria via two processes: the Tricarboxylic acid cycle (TCA), and the Electron Transport Chain.

Oxaloacetate (OAA) is one of the intermediates in the TCA, so feeding it contributes to the cycle and thus to the production of the reduced forms of Vitamins B3 and B2 (NADH and FADH2, which then serve as electron donors to the electron transport chain where ultimately ATP gets produced). So like with every other intermediate in the process, it supports ATP production.

But OAA is special, relative to other TCA intermediates, because it also can contribute to formation of other amino acids (building blocks for proteins), or it can be used to manufacture more glucose, depending upon what the body needs (see the chart to the side).

The Excitotoxicity Connection

What might make OAA most interesting as a possible supplement is what happens as a byproduct of its conversion to other amino acids: it breaks down glutamate (see in red on the chart) and turns it into another intermediate of the TCA where it can enter and perpetuate the cycle.

Glutamate is an excitatory neurotransmitter, necessary in moderation, but excessive amounts are associated with excitotoxicity of all kinds, including multiple chemical sensitivity, traumatic brain injury or TBI, ischemic stroke, Alzheimer’s, and autism.

This makes OAA a glutamate scavenger, acting to potentially protect the brain from excessive and destructive levels.

Studies on how this might act clinically are scarce, though: what we have are primarily animal studies, and mostly OAA is delivered intravenously rather than orally. This study shows that IV OAA does provide neuroprotection after a TBI in rats. This study shows that OAA delivered directly to the abdominal cavity led to benefits for Alzheimer’s in rats, including decreased inflammation, new mitochondria production, and possibly the formation of new neurons.

Delivery Method Matters

I mention the delivery method because stability of OAA as a supplement is questionable. This study shows that test subjects took 200 mg daily, without a measurable increase of OAA in the blood. This might be because OAA breaks down quickly, or because it is not very bioavailable.

There are versions of it on the market that claim they have been stabilized, though, and other studies do suggest positive clinical outcomes from oral supplementation.

The Upshot

While there are other supplements that might also support energy production, I think the research into oxaloacetate’s ability to break down excess glutamate is most promising. Other supplements, such as L-Theanine can antagonize glutamate receptors, but the only other supplement I know of that can directly encourage glutamate breakdown is taurine. I’ve heard some anecdotal reports from patients that supplementary OAA has been effective, and will keep my ears open for further developments.

By |2020-11-06T08:52:58-07:00November 6th, 2020|Categories: Articles, Supplements|0 Comments

About the Author:

Dr. Lauren Deville is board-certified to practice medicine in the State of Arizona. She received her NMD from Southwest College of Naturopathic Medicine in Tempe, AZ, and she holds a BS in Biochemistry and Molecular Biophysics from the University of Arizona, with minors in Spanish and Creative Writing. She also writes fiction under a pen name in her spare time. Visit her author website at www.authorcagray.com.

Get Your “10 Supplements Everyone should have” guide FREE by signing up.