Oxaloacetate (or Oxaloacetic Acid) is an organic compound that is involved in many neurophysiological processes within your body. It plays a key role in functions such as: amino acid synthesis, citric acid cycle, fatty acid synthesis, gluconeogenesis, glyoxylate cycle, and the urea cycle. For example, oxaloacetate is considered an intermediate in the Kreb’s cycle prior to following NAD+ conversion from L-malate and before Pyruvate formation.
There is compelling evidence to suggest that oxaloacetate may act as a neuroprotective agent within the brain. It appears to protect neurons from glutamatergic excitotoxicity (i.e. neurotoxicity) and simultaneously decrease neuroinflammation. Moreover, it has been shown to decrease brain damage stemming from ischemic attacks.
In addition to oxaloacetate’s neuroprotective properties, there is preclinical evidence to suggest that it may significantly extend lifespan. It is theorized to extend lifespan as a result of increasing cellular energy and mimicking various biological benefits associated with caloric restriction (e.g. minimizing blood-glucose levels). As a result of its neurobiological mechanisms, oxaloacetate may be a neutraceutical supplement to consider for optimization and preservation of long-term brain health.
5 Oxaloacetate Benefits: List of Possibilities (Scientific Research)
There are many documented benefits associated with administration of oxaloacetate, and many other preclinical [speculative] benefits based on rodent studies. The most prominent benefits derived from oxaloacetate administration are related to its ability to preserve neuronal health and inhibit damage as a result of glutamatergic excitotoxicity. In addition, it appears as though oxaloacetate expedites recovery from brain injuries and promotes mitochondrial biogenesis (growth of new mitochondria).
1. Neuroprotective Agent
Oxaloacetate acts as a neuroprotective agent, primarily as a result of its ability to scavenge glutamate within the blood. It also can enhance recovery from a traumatic brain injury and/or ischemic attack by decreasing the size of damage and elicit neurorestorative effects, particularly of long-term potentiation (LTP). Below is a brief synopsis of potential therapeutic applications associated with oxaloacetate followed by a summarization of the research.
- Prevents glutamatergic excitotoxicity (neurotoxicity)
- Offers neuroprotection against insecticides
- Protects brain from damage following injury or stroke
- Expedites neurological recovery following injury or stroke
- Protects mitochondria within the brain
- Elicits a neurorestorative effect of long-term potentiation (LTP)
- Inhibits mitochondrial DNA damage
- May prevent ischemic attacks
2014: It is known that brain damage from pesticide exposure is irreversible, permanently killing brain cells and impairing many aspects of neurological functioning. Currently there are no known pharmaceutical options that can be administered to mitigate and/or prevent brain damage following exposure to pesticides. It appears as though when the brain is exposed to pesticides, an increase in glutamate exacerbates the brain damage.
However, by using glutamate scavengers to decrease glutamate in the blood, the amount of glutamate in the brain decreases, which inhibits the significance of pesticide-induced brain damage. In animal models of paraoxon intoxication, the combination of oxaloacetic acid (OAA) and glutamate-oxaloacetate transaminase (GOT) were tested for efficacy of preventing brain damage. Researchers noted that the combination of OAA and GOT reduced neuronal damage in the animals exposed to paraoxon, an insecticide-based neurotoxin.
Upon simultaneous administration of oxaloacetic acid and glutamate-oxaloacetate transaminase, levels of blood glutamate rapidly plummet. This results in a decrease of glutamate that enters the brain, ultimately warding off secondary neurotoxicity as a result of the paraoxon. Specifically, researchers documented that blood-glutamate scavengers (oxaloacetic acid and glutamate-oxaloacetate transaminase) provided neuroprotection against the paraoxon.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24149933
2012: It is known that reducing glutamate concentrations in the blood following traumatic brain injuries leads to improved neurological prognoses. This is due to the fact that reducing glutamate prevents glutamatergic excitotoxicity, which commonly occurs following traumatic brain injuries. Researchers speculate that administration of glutamatergic scavengers to reduce blood glutamate concentrations should inhibit brain cell death (via excitotoxicity).
On the other hand, they believe that administration of glutamate would likely exacerbate damage as a result of a traumatic brain injury. Researchers conducted studies in rats and administered glutamatergic scavenging agents following a traumatic brain injury. Groups of rats were assigned to receive: saline (control group), pyruvate, oxaloacetate, and glutamate.
To assess responses to these agents, they recorded brain cell survival rates in the hippocampus and administered a Neurological Severity Score (NSS) assessment. The NSS was administered after the traumatic brain injury at intervals of: 1 hour, 1 day, 2 days, 7 days, 14 days, 21 days, and 28 days. The biomarker of glutamate concentration within the blood was measured prior to the brain injury and 90 minutes following the injury.
Results indicated that administration of oxaloacetate and pyruvate experienced significantly greater rates of neuronal survival within the hippocampus compared to the control. Administration of the glutamate resulted in an increase in hippocampal apoptosis. This study supports the idea that oxaloacetate scavenges excess glutamate within the bloodstream and promotes the survival of brain cells.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22129535
2012: Glutamate is responsible for promoting neurodegeneration as a result of ischemic attacks. Various glutamate antagonists have been administered in attempt to inhibit the neurotoxicity associated with glutamate. In many cases, these antagonists have appeared to be effective in the early stages of development, but ultimately fail to survive later stages of clinical trials.
In a 2012 report, researchers note that oxaloacetate acts as a neuroprotective agent and is capable of attenuating the toxic effects of glutamate following ischemic attacks. Researchers note that oxaloacetate is effective as a result of its ability to activate the enzyme GOT (glutamate-oxaloacetate transaminase). Authors suggest that oxaloacetate is a potent neuroprotective substance that may provide clinical benefit for those that have experienced a stroke.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22085530
2012: The scavenging of glutamate from the bloodstream is an effective way to minimize glutamatergic concentrations within the brain. Reducing glutamatergic concentrations within the brain is known to facilitate superior neurological recovery following traumatic brain injuries and strokes in rodents. A study published in 2012 aimed to determine the efficacy of oxaloacetate and pyruvate (blood-glutamate scavengers) for treating a subarachnoid hemorrhage in a group of rats.
The rats were administered one of the following within 60 minutes of the subarachnoid hemorrhage: saline (control), oxaloacetate, or pyruvate. Baseline blood samples were attained from the rats, as well as 90 minutes post-subarachnoid hemorrhage to determine glutamate concentrations. Researchers recorded the neurological functioning of the rats approximately 24 hours following the subarachnoid hemorrhage.
Results indicated that blood glutamate levels were significantly lower among those administered oxaloacetate or pyruvate following the subarachnoid hemorrhage. In addition, glutamate concentrations in cerebrospinal fluid were significantly reduced among those administered pyruvate. Both oxaloacetate and pyruvate administration resulted in significantly superior performance on neurological assessments.
Further evidence indicated that the blood-brain barrier (BBB) was significantly protected by pyruvate, whereas both oxaloacetate and pyruvate provided neuroprotective effects for the parieto-occipital regions of the brain. Results indicate that oxaloacetate (and pyruvate) protect the brain from damage by scavenging glutamate.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22711471
2011: An ischemic stroke occurs as a result of blood circulation loss to a certain region of the brain. Symptoms often include numbness of the face, paralysis, difficulty speaking, and abnormal gait. Ischemic strokes often are caused by excessive build-up of glutamate within the brain, leading to glutamatergic excitotoxicity.
Researchers published a study in 2011 analyzing the efficacy of two enzymes for improving recovery following ischemic strokes. Specifically, they assessed levels of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transminase (GPT) – both of which are thought to scavenge blood glutamate. The scavenging of blood glutamate is thought to reduce likelihood of glutamatergic excitotoxicity within the brain.
They assessed a total of 365 individuals that had undergone ischemic strokes within 12 hours. Blood samples were collected to determine levels of the two biomarkers: GOT and GPT. Of these 365 ischemic stroke patients, they measured neurological outcomes. It was discovered that greater blood concentrations of GOT and GPT resulted in lower blood glutamate levels.
Furthermore, neurological outcomes were best among those with greater levels of GOT and GPT as evidenced by the modified Rankin Scale. This suggests that these enzymes likely scavenge blood glutamate and ultimately reduce glutamatergic excitotoxicity within the brain. Computerized Tomography (CT) neuroimaging revealed that greater levels of GOT and GPT resulted in reduced stroke volume.
Authors noted that associations between good outcomes were stronger between high GOT (oxaloacetate) than GPT (pyruvate), but both were beneficial. This suggests that oxaloacetate can reduce damage from strokes and enhance post-stroke neurological recovery efforts.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21265738
2011: Researchers noted that GOT (glutamate-oxaloacetate transaminase) is able to scavenge blood-glutamate and convert it into various “tricarboxylic acid cycle intermediates.” The conversion to these intermediates ultimately means that the neurotoxicity potential of glutamate can be significantly reduced as a result of oxaloacetate. Since acute ischemic strokes are associated with glutamatergic neurotoxicity, researchers discussed how GOT (glutamate-oxaloacetate transaminase) expression may offset some of the glutamatergic damage.
In rodents that have endured acute ischemic strokes, administration of pure oxygen during the ischemic attack resulted in an upregulation of GOT. The upregulation of GOT resulted in reductions in glutamate levels and mitigated ATP losses. The greater the expression of GOT, the less the brain damage from the stroke.
This was evidenced by mice without GOT who experienced the greatest damage and worst post-stroke recovery outcomes. It is clear that oxaloacetate (GOT) offsets the neurotoxic potential of glutamate. Moreover, it appears as though GOT converts glutamate to energy, using it as fuel to promote recovery and survival.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21361730
2011: When a person experiences an ischemic stroke, their brain accumulates excess extracellular glutamate, which often exacerbates the damage. Decreasing blood-glutamate concentrations has been thought to reduce brain-glutamate concentrations, thereby mitigating glutamatergic neurotoxicity following a stroke. Researchers note that the blood enzyme glutamate-oxaloacetate transaminase (GOT) may metabolize glutamate and provide neuroprotection from glutamatergic neurotoxicity.
A study published in 2011 assessed the efficacy of the GOT enzyme in providing neuroprotective following a middle cerebral arterial occlusion (MCAO). Administration of oxaloacetate activated GOT, which decreased concentrations of blood-glutamate and brain-glutamate following the MCAO. Ultimately, increased GOT meant less MCAO-induced damage and improved neurological outcomes compared to a control group (which didn’t receive oxaloacetate).
Results highlight the neuroprotective advantages of oxaloacetate administration for preventing MCAO-induced brain damage and improving neurological outcomes following MCAO. It should be speculated that these results may indicate therapeutic efficacy of oxaloacetate among humans that are susceptible to a stroke and/or have experienced a stroke.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21266983
2011: Yet another study from 2011 suggested that the GOT (glutamate-oxaloacetate transaminase) enzyme is able to facilitate the removal of glutamate from the blood, ultimately reducing glutamate within the brain. In various studies, increased levels of GOT are associated with neuroprotection against ischemic strokes. This study reviewed levels of GOT within the blood of patients that had endured ischemic strokes.
The goal was to determine whether levels of GOT were associated with therapeutic benefits. Researchers noted that in multiple independent studies, there was an association between poor prognostic outcomes and low GOT with high blood glutamate. Individuals with the lowest levels of GOT and highest blood glutamate had the worst recovery after 90 days and greater brain damage as a result of the stroke.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21266984
2011: Studies suggest that both oxaloacetate and pyruvate are capable of decreasing transmission of glutamate from the blood to the brain. They accomplish this by scavenging and metabolizing glutamate within the blood, reducing the amount that enters the brain. It is known that epileptic seizures often cause excitotoxicity, leading to the death of neurons.
The excitotoxicity associated with neuronal death is often a result of excess glutamate. In rat models of status epilepticus (non-stop seizures), researchers tested oxaloacetate, pyruvate, and a combination of both. These were administered 30 minutes after the onset of seizures, and were dosed according to the bodyweight of the rats.
Using an optical fractionator method, researchers were able to count neurons in the hippocampus. They specifically assessed the CA1 and hilus regions approximately 5 hours after the seizure onset. Results indicated that co-administration of oxaloacetate and pyruvate protected all neurons in the CA1 region of the hippocampus; none were lost.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21185899
2009: A study published in 2009 discussed the fact that oxaloacetate administration following a traumatic brain injury protects the brain from glutamatergic neurotoxicity. It accomplishes this protective effect by decreasing levels of blood-glutamate. This study investigated the mechanisms by which oxaloacetate protects the brain from neurotoxic glutamate activity.
They investigated oxaloacetate’s effect in a group of rats that had experienced closed head injuries. A neurological severity score (NSS) was collected 1-hour post-injury for a baseline measure. Rats treated with oxaloacetate experienced significant improvements as noted by NSS assessments given at 24 hours and 48 hours post-injury.
Researchers determined that oxaloacetate provides neuroprotective effects as a result of its ability to scavenge blood glutamate. The rats administered oxaloacetate had significantly lower blood glutamate levels compared to control groups and greater improvement in neurological severity scores.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19543002
2009: Neurological pathologies are often associated with heightened levels of glutamate in brain fluids. It is known that when blood-glutamate concentrations are reduced, brain-glutamate is simultaneously reduced. The fact that blood-glutamate reduction can prevent brain-glutamate excitotoxicity is promising for those that have endured ischemic strokes.
Ischemic strokes are associated with elevations in brain-glutamate, which often increase stroke-related brain damage. The enzyme GOT (glutamate-oxaloacetate trasaminase) is known to scavenge blood-glutamate, which in turn decreases the likelihood of glutamatergic neurotoxicity. A study from 2009 sought to assess the efficacy of the GOT enzyme on long-term potentiation (LTP) impairment in rats that had endured ischemic strokes.
A forebrain ischemic stroke in rats resulted in LTP impairment in a region of the hippocampus. Administration of intravenous oxaloacetate immediately after the stroke was able to scavenge glutamate, and more impressively restore long-term potentiation (LTP) after stroke-induced impairment. This suggests that oxaloacetate can have a neurorestorative effect among those with brain injuries.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19135048
2009: In nearly every case of traumatic brain injuries or lesions, glutamate levels immediately increase, resulting in excitotoxicity. This excitotoxicity can exacerbate damage inflicted as a result of the traumatic brain injury, and is problematic in that it may inhibit various aspects of neurological recovery. That said, it is known that the glutamatergic excitotoxicity can be offset via administration of oxaloacetate.
Oxaloacetate essentially metabolizes glutamate within the blood, which reduces glutamate levels within the brain. A study published in 2009 involved a group of rats that had endured photothrombotic lesions. Oxaloacetate was administered for 30 minutes following the lesions and provided significant neuroprotective benefit as a result of reducing blood-glutamate concentrations.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19259807
2007: Individuals with high levels of glutamate within brain fluids have often endured a traumatic brain injury or a stroke. It is thought that excess glutamate can be deleterious to the long-term health of the brain, resulting in excitotoxicity and brain damage. This brain damage leads to potentially irreversible neurological impairments.
One intervention to inhibit excess glutamate levels within brain fluids is to reduce glutamate levels within the bloodstream. Administration of scavenging agents such as oxaloacetate are thought to reduce blood-glutamate concentrations, ultimately minimizing the likelihood of glutamatergic excitotoxicity within the brain. Researchers tested this hypothesis in rats that had endured a “closed head injury.”
They administered oxaloacetate based on the rats’ bodyweights and determined that following a closed head injury, oxaloacetate was able to reduce blood glutamate concentrations by approximately 40%. When rats were co-administered oxaloacetate and glutamate following the closed head injury, no therapeutic effects were observed; the two substances likely canceled each other out. Researchers determined that the neuroprotective effects of oxaloacetate were strongest when used prior to the closed head injury or within 60 minutes post-injury.
No significant benefits were observed when rats were administered oxaloacetate 2 hours post-injury. Recovery from the closed head injury (CHI) was strongest among those receiving oxaloacetate. Authors concluded that it was specifically due to its ability to scavenge blood glutamate, thereby mitigating glutamatergic neurotoxicity.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17014847
2003: Researchers sought to determine the effect of alpha-ketoglutarate and oxaloacetate on mitochondrial DNA damage and seizures. The mitochondrial DNA and seizures were induced deliberately by kainic acid as a result of 45 mg/kg injections in mice. It was discovered that seizures abated when mice were injected with either alpha-ketoglutarate (2 g/kg) or oxaloacetate (1 g/kg) prior to the injection of kainic acid (a neurotoxin).
Normally kainic acid damages mitochondrial DNA in various regions of the brain of mice, including the frontal lobe and middle cortex. When the mice were given injections of alpha-ketoglutarate or oxaloacetate prior to the kainic acid, these substances completely inhibited all damage to the mitochondrial DNA in the frontal and middle corticies. Kainic acid is also known to increase lipid peroxidation, or the process by which free radicals damage cells.
Co-administration of oxaloacetate (or alpha-ketoglutarate) with kainic acid mitigated any lipid peroxidation. Authors of this study concluded that oxaloacetate (and alpha-ketoglutarate) prevent seizures and completely protect against kainic acid-induced mitochondrial DNA damage. While this research was conducted in mice, many speculate similar effects in humans.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12749815
2. Mitochondrial Biogenesis
Another prominent benefit associated with administration of oxaloacetate is increased mitochondrial biogenesis. Mitochondrial biogenesis refers to the formation of new mitochondria within cells. When brains atrophy and/or experience neurodegeneration, the bioenergetic function within the brain declines and the mitochondria often become damaged and/or dysfunctional.
Growth of new mitochondria may reverse and/or inhibit certain aspects of neurodegeneration as a result of biogenesis. Mitochondrial biogenesis may restore our neurons with increased cellular energy. When mitochondria are healthy and working properly, they help facilitate communication among neurons via manufacturing of ATP (adenosine triphosphate).
The ATP provides neurons (and all cells) with energy to maintain cellular health and literally power your brain. Preliminary evidence from mice studies suggests that administration of oxaloacetate enhances brain bioenergetics, insulin signaling pathways, promotes neurogenesis, reduces neuroinflammation, and aids in mitochondrial biogenesis.
- Aids in mitochondrial biogenesis
- Promotes neurogenesis
- Reduces neuroinflammation
- Enhances insulin signaling pathways
- Optimizes brain bioenergetics
2014: It is noted that bioenergetic function within the brain often declines as a result of neurodegenerative diseases. A 2014 study suggested that administration of oxaloacetate (OAA) may offer therapeutic effect due to the fact that it is a bioenergetic intermediate. The goal of researchers was to test various biomarkers following administration of oxaloacetate including: brain bioenergetics, insulin signaling, inflammation, and neurogenesis.
A group of mice were administered 1-2 g/kg of oxaloacetate once per day for up to 2 weeks. Results indicated that oxaloacetate altered mRNA and proteins in a way that signified mitochondrial biogenesis. Measures of post-administration biomarkers revealed that oxaloacetate also decreased neuroinflammation, promoted neurogenesis in the hippocampus, and activated pathways responsible for insulin signaling.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25027327
3. Anti-Aging & Longevity
It is well-established that caloric restriction can increase lifespan in animals, and a similar response is thought to occur in humans. The lifespan increase derived from caloric restriction is not the only associated benefit. Many other health-related biomarkers improve among individuals who restrict calories compared to individuals who indulge in copious amounts of food.
Oxaloacetate appears to offset certain biomarkers associated with aging in C. elegans. In addition, some claims suggest that it is also effective at extending the lifespan of rodents. Whether an increase in lifespan would be evident among humans is currently unknown, but many scientific researchers hypothesize a similar response.
2009: A study published in 2009 sought to determine whether supplementation of citric acid metabolites may mimic the longevity increase associated with caloric restriction. Researches administered oxaloacetate to the nematode Caenorhabditis elegans. They discovered that oxaloacetate supplementation increased longevity.
The longevity increase was a result of FOXO/DAF-16 transcription factor and AMP-activated protein kinase. It is unclear as to whether increased longevity would be evidenced in humans administered oxaloacetate and/or other animals. Some anecdotal claims suggest increases in the lifespan of mice as a result of oxaloacetate supplementation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19793063
4. Blood Sugar Regulation (Diabetes)
Some of the first research ever conducted with Oxaloacetate was in Japan, whereby researchers tested it among individuals with diabetes. They realized that the plant “Euonymus alatus” (also referenced as “winged spindle” or “burning bush”) was able to reduce blood sugar levels in mice. Researchers isolated the blood-sugar lowering constituent from the plant and documented that it was “oxaloacetic acid” (OAA).
It was tested in humans and determined to be effective in a majority of participants with both Type 1 and Type 2 diabetes. It appears as though no major follow-up studies were conducted oxaloacetic acid for the treatment of diabetes. Some potential long-term effects were noted in rodent research including enlargement of the pancreas; whether there is significant danger associated with this effect is unknown.
1968: In the late 1960s, researchers investigated the Euonymus alatus plant for its ability to lower blood sugar. They were specifically looking to come up with an innovative treatment for diabetes mellitus due to the ineffectiveness of various oral drugs. By studying the Euonymus alatus plant, they were able to isolate the specific constituent responsible for lowering blood sugar.
That specific component was discovered via infrared spectral analysis, and happened to be none other than oxaloacetic acid (OAA) a.k.a. a form of oxaloacetate. The researchers then created a sodium-based form of oxaloacetic acid known as OAA-sodium, and tested it on animals. They discovered that it significantly lowered blood sugar levels in both normal and diabetic animals.
Researchers proceeded to administer OAA-sodium to 10 humans with Type I diabetes and 11 with Type II diabetes. Results indicated that it effectively reduced blood sugar in all individuals with Type I diabetes and in over half of those tested with Type II diabetes (6 out of 11). It was concluded that there were minimal adverse effects and that insulin was secreted via an “unknown mechanism” as a result of OAA-sodium administration.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/4884771
5. Anticancer & Antitumor Properties
One study conducted with oxaloacetate discovered that it may be an antitumor and possibly anticancer agent. Researchers implanted gliomas within the brains of mice and rats, discovering that administration of oxaloacetate reduced the invasiveness of the tumors, as well as the tumor size. When used as an adjunct along with an antitumor drug (Temozolomide), synergistic effects were observed with increased survival rates of over 200%.
2012: Glutamate in the brain is known to aid in the growth of malignant tumors. Researchers speculated that reducing glutamate levels in the blood would reduce glutamate in the brain, ultimately inhibiting growth of malignant tumors. Administration of oxaloacetate is one such way by which excess blood-glutamate concentrations are metabolized and reduced.
It was suggested that oxaloacetate may have anticancer properties in that it protects the brain from glioma-induced damage. Researchers tested their hypothesis in a group of rats and mice that had been administered glioma brain implants. The implanted glioma were derived from either rat cells (C6) or human cells (U87).
Following the implantation of the malignant brain tumors, animals were given: saline (control group), oxaloacetate either with human GOT (glutamate-oxaloacetate transaminase) injections or without them. A group of mice was also given a treatment combining oxaloacetate, GOT, and Temozolomide. Results indicated that drinking oxaloacetate had smaller tumor size, regardless of whether they received GOT (glutamate-oxaloacetate transaminase).
It was also discovered that the tumors were less invasive and the animals survived longer than those given a saline solution. The group of mice that had received the oxaloacetate with Temozolomide as an experienced survival rate increases by an estimated 237%. Researchers noted that oxaloacetate scavenges glutamate needed for the growth of cancerous tumors, and may prove therapeutic for treatment of human gliomas.
Moreover, it appears as though administration of the drug Temozolomide (approved to treat brain tumors) with oxaloacetate provides synergistic benefit. Due to the favorable preclinical safety profile of oxaloacetate, human trials are warranted.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22392507
Oxaloacetate investigated for treatment of Parkinson’s disease
Another speculative benefit is that oxaloacetate may prove therapeutic upon administration for the treatment of neurodegenerative diseases, specifically Parkinson’s. A double-blind, placebo-controlled, parallel-group, pilot study is currently underway to assess the preliminary safety, tolerability, and efficacy of oxaloacetate for Parkinson’s. The testing will compare 100 mg oxaloacetate (OAA) with a placebo (100 mg ascorbate) administered once per day.
The study is being conducted by the University of Kansas in collaboration with Terra Biological LLC, manufacturers of benaGene™ (a brand name formulation of oxaloacetate). All participants in the study are required to be at least 30 years of age and have a diagnosis of idiopathic Parkinson’s disease within 7 years. Participants will be taking stabile doses of levodopa that aren’t subject to adjustment during the trials.
It appears as though researchers are currently in Phase 2 of the clinical trials. The testing will involve a total of 3 visits by each participant and 2 follow-up phone calls to determine any safety issues over a period of 4 months. As a side note, several anecdotal reports have surfaced among users of oxaloacetate with diagnoses of Parkinson’s, suggesting that oxaloacetate may provide substantial benefit.
Theoretically, it makes sense that oxaloacetate would provide benefit to patients with Parkinson’s due to the fact that excess glutamate is often a culprit for worsening of symptoms. Since oxaloacetate scavenges glutamate, there’s less of a chance of excitotoxicity, ultimately protecting neurons from death and preserving brain matter.
- Source: https://clinicaltrials.gov/show/NCT01741701
What are the most prominent benefits of Oxaloacetate?
There appear to be many notable benefits that can be derived from oxaloacetate supplementation. It is clear that supplementation of oxaloacetate reduces glutamate concentrations within the bloodstream. The less glutamate in the blood, the lower the glutamate levels within the brain.
Maintaining low levels of glutamate within the brain prevents neuronal damage as a result of excitotoxicity. Should you experience a traumatic brain injury, ischemic attack, or neurotoxicity as a result of pesticide exposure – administration of oxaloacetate may mitigate a significant portion of the damage. Therefore, many studies highlight its potent capabilities as a neuroprotective agent.
In addition, oxaloacetate appears to help the brain recover quicker as a result of damage, and restore long-term potentiation following a stroke. Administration of oxaloacetate after an ischemic attack appears to shrink the volume of the ischemia, indicating that it facilitates recovery as a neurorestorative agent. Another prominent benefit associated with oxaloacetate is its ability to facilitate the production of new mitochondria via mitochondrial biogenesis.
Studies indicate that it also protects mitochondrial DNA and is able to inhibit neuroinflammation. An array of other possible benefits to be attained from oxaloacetate include: blood sugar reduction (among those with diabetes), antitumor and anticancer properties (especially when used as an adjunct), treatment of Parkinson’s disease, prevention of neurodegeneration (as a result of scavenging glutamate), and life extension. Preclinical evidence suggests that administration of oxaloacetate mimics biological processes associated with caloric restriction, ultimately extending lifespan.
Are there any potential risks associated with taking Oxaloacetate?
There aren’t any major risks associated with oxaloacetate supplementation based on the research. Due to the fact that it isn’t well-tested in humans, there may be significant risks that remain undocumented. Oxaloacetate is a natural substance that is present in low amounts within a variety of foods.
However, the natural amount in these foods is too low to derive significant therapeutic benefit. Since humans that supplement oxaloacetate are ingesting quantities that are substantially greater than what were evolutionarily ingested, it is unknown as to whether mega-doses of oxaloacetate carry biological consequences. Thus far it appears as though supplementation is likely benign, and more therapeutic than deleterious.
Assuming you are taking a thermally stabilized formulation of oxaloacetate, the risks should be considered relatively low. Despite oxaloacetate’s minimal preclinical risk profile, the long-term effects are not well documented and dosing guidelines aren’t well understood. Perhaps the biggest drawback associated with oxaloacetate supplementation is its cost per dosing.
Cost of oxaloacetate is over $1 per dose due to the fact that there are few sellers. Those that are selling oxaloacetate have carved out a nice little niche in the supplement industry. Assuming more human trials are published with favorable results, you can expect other supplement manufacturers to hop on the oxaloacetate bandwagon – which will help drive down its [arguably exorbitant] pricing.
Limitations associated with Oxaloacetate research
There remain several limitations associated with oxaloacetate research. Perhaps the biggest limitation is the lack of human trials. In addition, there need to be more long-term studies with double-blind, placebo-controlled, randomized designs. It is also unclear as to whether certain dosages provide more substantial benefit and/or risks than others.
- Dosage optimization: The optimal dosage of oxaloacetate for maximum therapeutic benefit isn’t well-known. Current-market formulations of oxaloacetate are manufactured in doses of 100 mg to be taken once daily. It is unclear as to whether more and/or less is needed based on a person’s bodyweight and whether 100 mg is enough to provide significant benefit.
- Lack of human trials: The lack of human trials analyzing the efficacy of oxaloacetate makes it difficult to fully endorse as a supplement. While supplementation may provide significant benefit, there may be some concerns with safety when administered over a long-term. Further, it is unclear as to whether its benefits among rodents also apply to humans.
- Long-term: The long-term effects associated with oxaloacetate aren’t well-documented in rodents. Some suggest that there are no noticeable adverse long-term effects and that most long-term effects may be conducive to optimal health and longevity. Still, long-term human trials will help us better understand oxaloacetate’s safety.
- Study designs: For optimal accuracy of results, oxaloacetate studies should be placebo-controlled, double-blinded, and randomized. Not all published studies incorporate this type of design, which could compromise the accuracy of results.
Further Research of Oxaloacetate is Warranted
Although consistent administration of oxaloacetate appears to provide a cornucopia of health benefits, further research is necessary to confirm beneficial claims in humans. Just because a substance is well-tolerated and promotes health in rodents does not mean that results are always similar in humans. Since there is significant promise associated with oxaloacetate, and possibly oxaloacetate-analogues in medicine, expect actual human studies to surface in future years.
There are a multitude of potential avenues to explore when researching oxaloacetate. A study should be conducted to determine the dosage and efficacy of oxaloacetate to significantly lower blood-glutamate concentrations. After this is determined in humans, oxaloacetate can be tested as an intervention among those that experienced an ischemic attack, brain injury, stroke, etc. – to determine whether it improves neurological outcomes.
It is already being tested as an adjunct for Parkinson’s disease. Though oxaloacetate may provide significant benefit to the brain, another idea for a study would be to test its ability to lower blood glucose. One study from the late 1960s showed significant benefit for lowering blood sugar among diabetics, but no follow-up study was ever conducted.
Trials of oxaloacetate for the treatment of gliomas would be beneficial due to the fact that it may have antitumor and anticancer properties in humans. Moreover, many are hoping that various biomarkers associated with life extension can be tested to determine whether oxaloacetate activates anti-aging physiological processes. Oxaloacetate could be tested head-to-head with caloric restriction as well as combined with caloric restriction to determine whether it provides synergistic benefit.
Have you tried Oxaloacetate as a nutraceutical supplement?
If you’ve taken oxaloacetate as a nutraceutical supplement, feel free to share your experience in the comments section below. Did you notice any objective or subjective benefits as a result of taking it? It’s difficult to determine whether oxaloacetate provides significant benefit to humans, despite an abundance of therapeutic outcomes when administered to rodents.
Share the specific source of oxaloacetate you took and whether it was thermally stabilized with Vitamin C. Some individuals involved in quantified-self have attempted to assess objective measures associated with oxaloacetate administration such as blood glucose levels. Even among these individuals it remains unclear as to whether it provides significant benefit.
Anecdotal reports have documented oxaloacetate as improving cognitive function and working memory. That said, it is difficult to determine whether these are legitimate outcomes or merely a byproduct of a placebo effect or inaccurate subjective reporting. While the jury is still out on oxaloacetate’s therapeutic value in humans, preliminary evidence suggests that it may emerge as a highly-popular health-preserving supplement in forthcoming years.