As we age brain function can slow down, anxiety, depression, and fatigue can set in.  There are ways to improve brain function and energize your system that don’t require the side effects of stimulants.  One capsule of Bulletproof® Upgraded™ aging formula contains 100mg of oxaloacetate (OAA) and 150 mg of vitamin C to help boost brain function, reduce aging symptoms while energizing you.  Vitamin C is added to protect OAA from oxidizing and becoming pyruvate.  This is a safe and effective way to Bulletproof® your brain.  OAA has been reported to protect neurons from toxins allowing your metabolic processes to run smoothly.  The nice thing is that this is a supplement and not a pharmaceutical.  You’ll be pleased to know that Upgraded™ aging formula is 100 percent soy-free, gluten-free, and sugar-free.  No colorants, flow agents, or preservatives have been added.  This product is water soluble, easily absorbed, and has been demonstrated to enter the bloodstream within 30 minutes after ingestion.     

OAA is an intermediate product in the tricarboxylic acid cycle (TCA).  It comes from the dehydrogenation of malic acid.  This is a molecule that is produced by all cells and is involved in the production of ATP in the mitochondria.

OAA is found in oranges and apples.  OAA is an unstable molecule such that it doesn’t survive more than one day at room temperature.  Fortunately, more recently a new procedure has come out that has the ability to thermally stabilize OAA making it now available in supplement form.

OAA experiments have demonstrated that it has the ability to increase lifespan, improve endurance levels, increase antioxidant activity, maintain healthy blood sugar levels, protect mitochondrial DNA as well as protect retinal, neural, and pancreatic tissues.  OAA has the ability to mimic a calorie restricted diet while activating longevity genes.

OAA and Longevity

Calorie restricted diets have been demonstrated to increase lifespan by up to fifty percent in animal studies.  However, this may be a problem for humans in that low calorie diets can bring about decreases in body temperature, muscle loss, and brain dysfunction.  That’s where OAA comes to the rescue.  OAA takes the place of a low caloric diet without restricting the calories and avoiding any side effects.  This simple molecule has been demonstrated to activate longevity genes.

Animal models show that oxaloacetate tells genes to keep you alive longer than would normally be possible.  The body has to respond to a wide range of conditions such as changes in the kind of foods you eat and how much you eat.  When you take in few calories such as being on a restricted calorie diet, this activates the AMPK-FOXO pathways.  AMP-activated protein kinase (AMPK) is an enzyme that is activated by low energy levels.  Recall that ATP is the energy currency of the cell.  ATP gets broken down to ADP and AMP during metabolism.  If you have a lot of AMP around, that means you’re low in ATP.  In other words, you are running out of energy to run your metabolic pathways.  When energy is low AMPK is activated and in turn activates the FOXO pathways.  FOXO stands for Forkhead transcription factors that bind to a particular DNA sequences.  AMPK activates FOXO transcription factor DAF-16.  As a transcription factor, it binds to certain genes allowing for those genes to be transcribed.  DAF-16 regulates hundreds of genes that are involved in stress response, antimicrobial genes, and metabolic genes.  So, DAF-16 is at the center of activating longevity genes as initiated by a restricted calorie diet or supplementation with OAA.  In vitro studies have demonstrated that OAA increases NAD+ (nicotinamide adenine dinucleotide) levels by fifty percent which in turn activates the AMPK-FOXO pathways.

OAA and Brain Activity

OAA is important to brain activity.  OAA keeps your neurons protected from toxic levels of the excitatory neurotransmitter glutamate.  Excess amounts of glutamate tends to over stimulate certain neurons causing excitotoxicity which destroys them.  Excess glutamate is also known to attack oligodendrocytes  which are the cells that form myelin around axons.  Myelin is a fat wrapping that increases conduction velocity of action potentials.  Under normal conditions, glutamate is kept in check however, during chronic stress, glutamate metabolism is impaired letting glutamate build up.  This will eventually lead to glutamate toxicity.  OAA  has been demonstrated to lower blood glutamate levels by 40 percent in animals.  There is an enzyme that can convert glutamate into tricarboxylic acid cycle intermediates which is known as glutamate oxaloacetate transaminase (GOT).  This pathway may be sufficient in harnessing excess neurotoxic extracellular glutamate protecting neurons from excitotoxicity.  Glutamate is actually converted into fuel for neurons.  Given that OAA has the ability to lower glutamate levels, it is being considered for use in patients who have experienced ischemic stroke. 

OAA and Mitochondria

Mitochondria take a lot of abuse over time and damage to this organelle is reported to be a major contributor to the aging process.  Inside mitochondria is where oxidative phosphorylation occurs responsible for the generation of ATP.  OAA protects mitochondrial DNA by increasing the production of NAD+ levels which protects DNA from free radical damage.  Maintaining healthy mitochondria increases life-span.

Suggested Reading:

Omodei D, et al. Calorie restriction and prevention of age-associated chronic disease. FEBS Letters. 2011 Jun 6;585(11):1537-42.

Colman RJ. Nonhuman primate calorie restriction. Antioxidant & Redox Signaling. 2011 Jan 15;14(2):229-39.

Fontana L. Calorie restriction and cardiometabolic health. Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):3-9.

Weiss EP, et al. Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1205-19.

Speakman JR, et al. Caloric restriction. Mol Aspects Med. 2011 Jun;32(3):159-221.

Ingram DK. Calorie restriction mimetics: an emerging research field. Aging Cell. 2006 Apr;5(2):97-108.

Chiba T, et al. Development of Calorie Restriction Mimetics as Therapeutics for Obesity, Diabetes, Inflammatory and Neurodegenerative Diseases. Curr Genomics. 2010 December; 11(8): 562–567.

Williams DS, et al. Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway. Aging Cell. 2009 Dec;8(6):765-8.

Cash A. Oxaloacetic Acid Supplementation as a Mimic of Calorie Restriction. Open Longevity Science, 2009, 3, 22-27.

Haslam JM. The permeability of mitochondria to oxaloacetate and malate. Biochem J. 1968 May; 107(5): 659–667.

Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000 Apr;130(4S Suppl):1007S-15S.

McEntee WJ. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl). 1993;111(4):391-401.

Zlotnik A, et al. Brain neuroprotection by scavenging blood glutamate. Exp Neurol. 2007 Jan;203(1):213-20.

Rink C. Oxygen-inducible glutamate oxaloacetate transaminase as protective switch transforming neurotoxic glutamate to metabolic fuel during acute ischemic stroke. Antioxid Redox Signal. 2011 May 15;14(10):1777-85.