Oxaloacetate Information

1. Conditions Studied

Oxaloacetate has been studied for a variety of conditions, including:

• Neurodegenerative diseases such as Alzheimer's and Parkinson's.
• Diabetes and glucose regulation disorders.
• Brain injuries and stroke.
• Aging and longevity.
• Metabolic disorders.

2. Efficacy in Treating Conditions

The efficacy of oxaloacetate in treating these conditions varies:

• Some animal studies suggest neuroprotective effects, but human data is limited.
• There is some evidence that it may help in regulating glucose, but more research is needed.
• Its effectiveness for brain injuries, stroke, and metabolic disorders requires more robust clinical trials.

3. Health Benefits

Oxaloacetate may have several health benefits, including:

• Potential to protect neurons and support brain health.
• May assist in blood sugar regulation and potentially benefit diabetic patients.
• Could contribute to cellular energy production and metabolism.
• May have anti-aging effects by mimicking caloric restriction.

4. Downsides

While generally considered safe, there are potential downsides to oxaloacetate supplementation:

• Limited human studies mean potential long-term effects are not well understood.
• Possible side effects are not fully characterized.
• May interact with other medications or health conditions.

5. Genetic Variations

Oxaloacetate's effects may be influenced by genetic variations:

• Individuals with variations in genes related to the citric acid cycle may experience different effects.
• Genetic differences in glucose metabolism could modify the efficacy of oxaloacetate in blood sugar regulation.
• Further research is needed to understand the relationship between genetic variations and oxaloacetate's effects.

Oxaloacetate Research Summary

Lifespan and Health Impact Studies

A study by the National Institute on Aging Interventions Testing Program (ITP) investigated the effects of compounds including oxaloacetic acid on mouse lifespan, with no significant lifespan extension observed at the tested dosages.

Neuroprotective Effects and Brain Metabolism

Research has demonstrated the neuroprotective effects of oxaloacetate in rats with traumatic brain injury by reducing blood glutamate levels and activating glutamate-oxaloacetate transaminase. This resulted in improved neurological outcomes.

Metabolic Transport and Shuttle Systems

The malate/oxaloacetate shuttle was successfully reconstructed in non-synaptosomal rat brain mitochondria, relying on a carrier-mediated transport system for oxaloacetate with a Km value of 60 micromolar. Similar systems were identified in rat kidney mitochondria, essential for gluconeogenesis and energy transport.

Oxaloacetate in Caloric Restriction Mimetics

Oxaloacetate supplementation in nematodes (Caenorhabditis elegans) has shown to increase lifespan by activating the FOXO/DAF-16 transcription factor and AMP-activated protein kinase (AMPK), which are also involved in the benefits of dietary restriction.

Oxaloacetate's Influence on Mitochondrial Biogenesis

In a mouse study, oxaloacetate administration promoted mitochondrial biogenesis, improved insulin signaling, reduced inflammation, and stimulated neurogenesis in the brain.

AMPK Activation and Cellular Energy Balance

AMP-activated protein kinase (AMPK) can be activated by beta-NAD, which is influenced by the cellular redox state (NAD/NADH ratio), suggesting that oxaloacetate could play a role in cellular energy regulation through its effects on NAD/NADH.

References:

1. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice
2. Oxaloacetate uptake into rat brain mitochondria and reconstruction of the malate/oxaloacetate shuttle
3. Oxaloacetate permeation in rat kidney mitochondria: pyruvate/oxaloacetate and malate/oxaloacetate translocators
4. The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate
5. The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury
6. Blood-mediated scavenging of cerebrospinal fluid glutamate
7. Effect of glutamate and blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome and pathohistology of the hippocampus after traumatic brain injury in rats
8. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis
9. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae
10. Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation
11. Tissue-specific regulation of SIRT1 by calorie restriction
12. Intermediary metabolism
13. Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway
14. Malate and fumarate extend lifespan in Caenorhabditis elegans
15. Biochemical regulation of mammalian AMP-activated protein kinase activity by NAD and NADH

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