As we age, everything slows down – including our brains. Specifically, it’s the metabolism of our brain cells that slows down appreciably… and that’s a process that occurs in the ‘energy furnaces’ of the cells, the mitochondria.
What goes on in the mitochondria is critically important to the continued proper function of the neurological system, including your brain’s ability to protect itself from the ravages of oxidative stress and neurotoxicity. Nowhere is this more evident than in the growing understanding of Alzheimer’s disease and other neurodegenerative diseases like Parkinson’s disease: the slower the baseline metabolism, the greater the risk of the disease.
That brings me to the Mitochondrial Cascade Hypothesis, which suggests that Alzheimer’s begins with genetic control of baseline mitochondrial function. It turns out that preventing and even reversing degenerative illness such as Alzheimer’s may rely on strategies affecting the mitochondria, as found in a relatively new breakthrough practice that’s being called ‘Mitochondrial Medicine’.
And this is where something called oxaloacetate (and oxaloacetic acid, or OAA) enters the story. Because this metabolic acid has shown the potential to protect your brain not only from trauma, but also from stroke, neurodegenerative disease, and even cancer.
And all of those protections can keep you blowing out more and more birthday candles every year.
You can alter the course of your future
According to this hypothesis, which was developed by Dr. Russell Swerdlow and others, there are epigenetic factors – including environmental toxins and dietary issues – that affect the rate at which mitochondria create energy.
Likewise, the more rapidly the rate of metabolism diminishes due to epigenetics and gene expression, the more the risk of Alzheimer’s and other neurodegenerative diseases increases. The theory is that the more your metabolism slows down… the more beta amyloid accumulates in the brain. And that build-up of beta amyloid is what’s been implicated in the development of Alzheimer’s.
On the flip side, theoretically, anything that improves energy production in the mitochondria (and the cytoplasm) of the cells could alter the course of neurodegenerative diseases like Alzheimer’s… or even reverse them altogether.
And that’s exactly how OAA works.
If you studied biochemistry in high school, you might remember the Krebs Cycle, the mitochondrial mechanism by which food is metabolised and mixed with oxygen to create energy (in biochemical terms, called ATP).
Amino acids, vitamins and minerals, and other nutritional factors are involved, but basically the Krebs Cycle involves organic acids converting into each other, a process that frees electrons to subsequently promote the creation of ATP.
The organic acids are usually called by their ‘salt’ names: citrate, isocitrate, alphaketoglucarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate. Although researchers have tried ALL of these Krebs Cycle acids to see whether they might enhance cellular energy production, oxaloacetate is the one that, to me, has the most exciting possibilities.
And here are the four main reasons why:
1. As with other intermediates in the cycle, inadequate levels of OAA lead to a diminishing in cellular energy.
2. OAA is the critical first step in how the brain and the heart (amongst other organs) continue to produce energy during a period of fasting (a process called ‘gluconeogenesis’.
3. OAA breaks down into aspartic acid, which is used in the clearing of waste products by the kidney (the ‘urea cycle’). It’s long been known that reduced levels of OAA in the body at birth usually lead to progressive neurological deterioration. This critical need for OAA carries on into adulthood.
4. Numerous studies have identified OAA as one of the main ‘glutamate scavengers’ in the neurological system – and we now know that excess glutamate, a toxic brain chemical, is elevated during times of stresses, like closed-skull traumatic brain injuries (CTBI) and stroke. It turns out that administering OAA enhances the movement of glutamate from the brain to the bloodstream, where it can be altered or eliminated.
And, as we know with contact sports like rugby, CTBI and its long-term relative, chronic traumatic encephalopathy (CTE), are becoming a major concern. But it’s not just professional athletes who are at risk. Any older adult who’s ever had a head injury – even decades ago – has good reason to be concerned, as do parents of active children who get a hard knock on the head now and then.
Like a safety helmet for your brain cells
To test the ability of OAA to lessen the effects of CTBI – and perhaps prevent the development of CTE – by lowering glutamate levels, researchers have administered OAA to rats in laboratory settings and then exposed them to CTBI.
In one study, the authors confirmed ‘the neuroprotective effect’ of OAA against brain injury – which, they explained, ‘strengthens the likelihood of its future applicability as a novel neuroprotective agent for the treatment of ischaemic stroke patients’.1
This is supported by an article from 2012 that outlines the experimental and clinical evidence for using OAA in the prevention and treatment of ALL brain injuries – whether ischaemic (vascular, as from a stroke) or traumatic (as in CTBI).2
Also, in 2014, researchers working with laboratory mice discovered that OAA actually stimulates the regrowth of nerve cells in the brain by improving the activity and intactness of messenger RNA and protein factors in the brain that encourage the regrowth of nerve cells.
What’s more, OAA appears to be involved in the utilization of insulin in the neurological system… and it may be the key to controlling Alzheimer’s and other neurodegenerative diseases,3 since there seems to be a relationship between Alzheimer’s and brain insulin and how your brain utilizes sugar. (And, as I shared with you previously, many researchers now think of Alzheimer’s disease as ‘Type-3 diabetes’!)
In addition, OAA has been shown to raise the production levels of the critical antioxidant glutathione… and even improve the levels of GABA, a neurotransmitter that helps to control anxiety and mood disorders, as well as enhance the quality of sleep.
All this – in addition to its ability to scavenge the dangerous glutamate molecules in the brain!
No wonder it’s being studied more and more for its uses in brain diseases.
I’ve even added it to my own regimen for my Parkinson’s disease (more on dosing later).
Time to gobble up what’s fuelling your tumour
There’s also a possible and VERY exciting role that OAA can play in the treatment of devastating and potentially lethal brain cancers, called gliomas.
As I mentioned earlier, OAA is a glutamate scavenger – and that means that it can, at least in theory, ameliorate any condition that arises as a result of too much glutamate.
Well, it seems that the presence of glutamate is critical for a malignant glioma to grow… to destroy the brain tissue it comes in contact with… and even to stimulate the seizure activity that is associated with brain cancer.
In fact, studies of glioma cells in the laboratory show that glutamate is released from the cells until the surrounding fluid has excess of 1,000 times the normal level! Your body then metabolizes the elevated glutamate into substances that actually protect the tumour cells from damage from chemotherapy and radiation, as well as from your own immune system.
Since glutamate-lowering drugs have intolerable side effects (if they work at all), this is a job that’s made for a scavenger of glutamate. And OAA fits the bill perfectly.
There are now a number of animal studies demonstrating the effectiveness of OAA in the treatment of gliomas, including a 2012 study that demonstrated the positive effects of OAA on glioma cells implanted in mice,4 as well as separate rat studies.
A metabolic hack without the hunger
There is one more major use of OAA that’s just as exciting… one that stems from the knowledge that decreasing the calories in someone’s diet by 25 to 40 per cent of their baseline will extend their lifespan, lessen their risk of kidney disease, Alzheimer’s disease, type-2 diabetes, cancer, and heart disease.5
That’s right, calorie restriction can make you live longer!
It happens by turning on some metabolic pathways that are associated with anti-ageing – and OAA, by virtue of turning on the gluconeogenesis pathway that I mentioned earlier, turns on the same metabolic pathways that lead to longer life, at least in animals.6
Studies in humans have also been positive. In one study, giving OAA to diabetic patients lowered fasting blood-sugar without side effects.7
Researchers have since repeated the anti-diabetic effect of OAA… and have hypothesized that lower blood-sugars will have the same effect metabolically as calorie restriction.
Keep your brain young… and extend your life!
Clinical studies have validated that OAA is extremely safe in therapeutic doses (usually 100mg twice daily, at least to start). I use a well-researched, nutraceutical OAA supplement by Terra Biological called benaGene, which is labelled as an ‘anti-ageing’ formula.
Its claim to fight ageing is true, of course – but its wonders don’t stop there!
And not the least of them is improving your glucose metabolism… something that’s been shown to have LIFEEXTENDING benefits.
As described on the website for the product, benaGene stimulates ‘the same molecular pathways as calorie restriction with natural human metabolites found in the Krebs Cycle, without the need for reducingn calorie intake’.
You should be able to find it pretty much anywhere online. But, as always, check with a doctor (ideally, one who’s wellversed in integrative medicine) before starting any new supplementation programme to make sure it’s safe for you.
Wishing you the best of health,
Dr. Glenn S. Rothfeld
Nutrition & Healing
Full references and citations for this article are available in the downloadable PDF version of the monthly Nutrition and Healing issue in which this article appears.