Oxaloacetate Feeds and GROWS Brain Cells - Alzheimers Cure?
Companies / BioTech Aug 23, 2014 - 12:24 PM GMTBy: John_Mauldin
By Patrick Cox
Oxford Paper Shows Oxaloacetate Feeds and Grows Brain Cells
The headline above is good news for those of us who want to proactively protect our health and extend our lives. I remain pretty cynical about the vast majority of supplements that claim life-extension benefits, but this compound is one of the rare exceptions. Before describing this important paper, published by in the Oxford journal Human Molecular Genetics, let me explain a bit about oxaloacetate, which John Mauldin and I both take several times a day.
Oxaloacetate, also called oxaloacetic acid and abbreviated as OAA, plays a central and critical role in metabolic processes shared by all animals, including humans. Probably the best known of these processes is the citric acid cycle, which is part of a greater process by which your cells make the only kind of energy that your body can actually use. This greater process, which takes place entirely inside the tiny mitochondria in every cell of your body, is called cellular respiration.
Included below is the Wikipedia graphic of the citric acid cycles. You’ll notice that oxaloacetate is at the juncture of two critical subsystems. If you would like to know more about cellular respiration, I recommend that you go to the Khan Academy website and search for the series of videos on cellular respiration. You should, in fact, have a basic understanding of cellular respiration because we are experiencing a scientific revolution right now concerning mitochondria that is going to change everything from life spans to our electrical power grid.
Source: “Citric acid cycle with aconitate 2” by Narayanese, WikiUserPedia, YassineMrabet, TotoBaggins
Mitochondria convert the food we eat, which is useless at the level of molecular biology, into the only form of energy that our cells can use. Simplistically, we might say that this energy is adenosine triphosphate (ATP), but that isn’t the real story.
Adenosine triphospate starts with adenine, one of the four nucleobase letters that our DNA is written in. To this adenine three phosphate groups are attached. The third of these phosphate groups has an unstable but extremely useful molecular bond. Under the right circumstances, it can break free, releasing the electrochemical bonding energy that held it to the adenine and two phosphate groups.
This electrochemical energy can be transferred to other molecules, so they can do what they need to do. The separate pieces can then be recycled by the mitochondria to make more ATP. The mitochondria do this by attaching another phosphate group to the two phosphates left on the adenine handle.
This molecular bonding energy, derived from ATP, runs the biological world. It powers your muscles, your genome, and your very consciousness. When we are young, our mitochondria are literally dynamos. Hundreds to thousands of mitochondria in each cell provide all the power we need to function optimally. In the average human body, there is only about eight ounces or a cup of ATP at any one time. Its energy is utilized and the molecule recycled so rapidly, however, we process our body weight in ATP every day.
Mitochondria are enormously interesting. Functionally, they are remarkably like bacteria and even have their own independent DNA, very similar to bacterial DNA, arranged in a circular plasmid. This, along with the double layer of membrane surrounding the mitochondria, is evidence of the theory that they were once independent bacteria that early eukaryotic cells engulfed. While there are 70 thousand or so coding genes in our genomes, located in our cells’ nuclei, human mitochondria have only 37 genes. Lacking the complex repair mechanisms of the genome, they are unfortunately subject to deterioration as we age.
Though we have traditionally thought of all these trillions of mitochondria in our cells as tiny separate organ-like structures, called organelles, it is more useful to think of them as parts of a network or system. When we, and our mitochondria, were healthy and young, the entire energy grid constantly communicated, via messenger proteins, with its various parts as well as the master genome.
When they function optimally, mitochondria respond to situations, merging and dividing. When we need more energy, they can increase through a process called mitochondrial biogenesis—which is the subject of the paper that spurred this article.
The biological revolution I was referring to earlier is a more complete understanding of the mitochondrial power grid. A critical part of that revolution is the dawning realization that mitochondrial function, degraded due to age or injury, may be repaired if the components needed to produce ATP are abundant.
One of those components is a naturally occurring substance, oxaloacetate, which has been used by significant numbers of people for some time now. A lot of supporting scholarship and research on OAA has already been done by important scientists and I’ll include links to a few papers at the bottom of this piece. The new paper just published in the Journal of Human Molecular Genetics is particularly interesting.
Frankly, the title alone was enough to command my attention. It is, “Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.” In other words, OAA increases energy production in the brain, improves processing of insulin for greater energy and resistance to type 2 diabetes, lowers autoimmune inflammatory disorders associated with a variety of diseases, and helps grow new neurons in mice.
Yes, there have been drugs that worked in mice but not in people, but the mitochondrial processes are so similar across mammalian species, I don’t think this is a particularly relevant concern. Moreover, this study explains a great deal that we have seen in other studies and, anecdotally, in people. Even if you only read the abstract here, it’s worth your time.
If, in fact, you are going to research oxaloacetate, you’re probably going to have to rely on the studies. This is not simply because this is new science, it’s extremely hazardous legally for companies that own rights to such natural products to make statements that might be interpreted by the FDA as medical claims—even if they’re true.
We have just seen, in fact, one of the most important nutraceuticals ever discovered, anatabine citrate, withdrawn from the market due to an FDA request. What provoked the regulators was not an exaggeration or false claim but a link on the company’s website to an accurate statement by one of the world’s leading neurologists at an important international conference. Here is a link to that story published elsewhere.
This is by no means, by the way, the only astonishing research regarding the naturally occurring alkaloid anatabine citrate. Here are stories about just a few.
The company that owns rights to the nutraceutical anatabine citrate is also involved in the process of taking the molecule through the regulatory process to drug status. To get that done, it had little choice but to comply with the FDA’s requests to stop marketing the nutraceutical version of its biotechnology.
If this strikes you as infringing free speech, you’re not the only one. My wife, a nutritional biologist, has long complained to me of what her profession calls regulatory information hoarding. I’ve written previously about the negative impact of this policy on public health.
A prime example is the regulatory attitude about vitamin D. Despite the emergence of a true consensus among top researchers that current government-recommended doses are causing, through vitamin D deficiency, considerable unnecessary suffering and death, manufacturers of vitamin D dare not reference this research.
Fortunately, UC San Diego’s School of Medicine is spearheading an attempt to educate the public about vitamin D. It is cooperating with many other major universities in an effort called Grassroots Health to get the word out about epidemic vitamin D deficiencies. UCSD TV has compiled a really useful series of videos on the subject here. By the way, here is more recent and compelling evidence that vitamin D deficiency plays a role in Alzheimer’s disease (AD).
Oxaloacetate in Clinical Trials for Alzheimer’s and Parkinson’s Disease
The University of Kansas Medical Center Research Institute has already completed the safety and pharmacokinetics phase of Alzheimer’s disease trials. UK is also engaged in trials of oxaloacetate for Parkinson’s disease.
You’ll notice if you dig deeper that all three of the substances I’ve mentioned so far seem to significantly ameliorate Alzheimer’s. This is because AD is an inordinately complicated disease that is brought on by the aging of a number of critical biological systems. Anatabine citrate acts on the immune system. Vitamin D is an essential hormonal regulator of other nutrients. Oxaloacetate works by improving efficiency of the mitochondrial energy grid.
The growing burden of AD is the single biggest medical threat to our aging society. So all three of these therapies should be understood and adopted, but even they are probably not the end of the story. It will probably require other solutions to completely cure Alzheimer’s. The upside, however, is that all of the factors that lead to AD are general conditions of aging. If we can slow or reverse these factors, the pace of aging itself will also be changed.
Moreover, I’ve experienced many of those changes personally, as have quite a few others. I should be quite clear, by the way, that neither I nor anyone else at Mauldin Economics have any financial arrangement with the company that owns rights to oxaloacetate, trade named benaGene. The same is true of anatabine citrate, which was until recently sold as Anatabloc, or any producer of vitamin D, including the sun, which is the primary source of ultraviolet B (UVB), which is converted in the skin to vitamin D.
The company that owns the rights to a heat-stabilized version of oxaloacetate, benaGene, is also involved in clinical studies. This is why you will find almost none of the scientific research about the molecule on the company’s website. Heat stabilization, incidentally, is the breakthrough that makes it possible to store OAA for easy clinical as well as over-the-counter uses.
For those who would like to study independently, here are a few links. This study shows that OAA prevents organophosphate pesticide brain damage.
This study shows that mice with brain cancer that were treated with OAA had dramatically improved recovery and survival rates.
This study showed OAA assisting in liver repair by promoting DNA synthesis.
Similarly, this PDF of a Japanese study discusses OAA-induced pancreatic repair.
Though this study took place using worms, it showed that OAA increases life span through a pathway similar to calorie restriction. At the very least, it is promising given everything else we know about oxaloacetate.
Do we need more research? Of course we do. Fortunately, it’s happening. Perhaps I should be quiet and let that research go forward without the risk of attracting regulatory attention. Perhaps, but—for good or ill—it’s not my nature.
Patrick Cox
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