Emergence of Oxaloacetate as a Supplement for CFS/ME/SEID Treatment

Oxaloacetate (OAA), a key component in the Krebs cycle of cellular energy production, has recently come under the spotlight as a potential supplement for the treatment of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). This interest was primarily fueled by the findings of Dr. David Kaufman and related studies indicating a significant depletion of oxaloacetate in CFS/ME patients.

Moreover, the supposed ability of oxaloacetate to enhance mitochondrial function, reduce inflammation, and improve energy production presents a promising avenue for CFS/ME management. Evidence suggesting improvements in fatigue levels among patients, albeit preliminary, has further contributed to its appeal. With studies indicating potential benefits, including enhancing mitochondrial biogenesis and regulating key metabolic pathways, oxaloacetate supplementation has emerged as a beacon of hope for many grappling with the debilitating effects of CFS/ME. Nonetheless, the journey towards fully understanding and establishing oxaloacetate’s efficacy in CFS/ME treatment remains ongoing, underscoring the need for continued research and patient-centric explorations.

Oxaloacetate: What is It and How Does It Work?

Oxaloacetate (OAA) is turning heads in the arena of potential treatments for chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME/CFS), and even for those grappling with long-haul COVID symptoms. As a compound that plays a crucial role in the body’s energy production processes, particularly in the mitochondrial function, OAA’s effects on energy metabolism and fatigue have drawn attention from researchers and doctors alike.

Definition and Role in the Mitochondrial Function

Oxaloacetate is a key intermediate in the Krebs cycle (also known as the citric acid cycle or TCA cycle), which is a pivotal pathway in cellular respiration within mitochondria, the powerhouse of the cell. This process generates ATP, the primary energy currency of the cell, essential for various cellular functions. OAA effectively helps convert nutrients into usable energy, hinting at its potential impact on addressing energy deficits observed in ME/CFS and related conditions.

Previous Studies on Oxaloacetate for Energy Production

Research has revealed that ME/CFS patients might exhibit mitochondrial dysfunction, leading to impaired energy production. Given oxaloacetate’s integral role in mitochondrial energy processes, supplementation with OAA has emerged as a novel approach to potentially enhance mitochondrial function and, consequently, energy production. Animal studies and preliminary human trials indicate that OAA supplementation may activate pathways that increase mitochondrial biogenesis, boost antioxidant protection, and enhance brain insulin signaling—factors contributing to its energizing effects.

Potential Mechanisms for Treating Chronic Fatigue Syndrome

The depletion of oxaloacetate in ME/CFS patients, as indicated by metabolomics studies, underlines the potential of OAA supplementation to replenish this crucial compound, normalizing energy metabolism. By enhancing NAD+ production, reducing inflammation, and possibly reversing the Warburg effect (a condition where cells produce energy through glycolysis even in the presence of oxygen), OAA could tackle the energy deficit and fatigue pervasive in ME/CFS sufferers.

Examination of Recent Studies and Trials

The exploratory nature of oxaloacetate supplementation in treating ME/CFS and long COVID symptoms has led to several clinical investigations, notably the in-house study led by Dr. David Kaufman and a non-randomized controlled trial. These studies aim to untangle the effects of OAA on chronic fatigue syndrome and related conditions.

Findings from Dr. David Kaufman’s In-House Study

Dr. Kaufman’s in-house study tracked the effects of oxaloacetate supplementation in a small group of ME/CFS patients. Although lacking a control group, the results were described as “extraordinary.” Patients receiving OAA reported significant improvements in fatigue levels measured by established fatigue scales. With many participants eager to continue the supplementation, the findings, although preliminary, suggest a promising impact of OAA on mitigating ME/CFS symptoms.

Insights from the Non-Randomized Controlled Clinical Trial

A broader non-randomized controlled trial involving ME/CFS and long-COVID patients evaluated the efficacy of oxaloacetate in alleviating fatigue. Compared to historical placebo data, the study revealed considerable reductions in both physical and mental fatigue, with the effects becoming notably pronounced at higher doses. These outcomes underpin the potential of OAA as a supplementary intervention for chronic fatigue conditions, advocating for more extensive, placebo-controlled trials to conclusively establish its benefits.

The exploration into oxaloacetate as a supplemental treatment offers a glimmer of hope for chronic fatigue syndrome and long-COVID sufferers. While the current evidence points towards promising outcomes, rigorous clinical trials are paramount to validate oxaloacetate’s efficacy and safety fully. As we await more comprehensive studies, oxaloacetate stands as a compelling candidate in the quest for effective treatment options for these debilitating conditions.

Pros of Oxaloacetate Supplementation

Reported Improvements in Fatigue Levels

Oxaloacetate supplementation has shown promising results for individuals suffering from chronic fatigue syndrome (CFS) and long-term fatigue associated with conditions like Long COVID. Various studies and patient reports indicate a significant reduction in fatigue levels among users. For instance, a study conducted by Dr. David Kaufman observed remarkable improvements in CFS patients’ energy levels after incorporating oxaloacetate into their regimen. Many participants reported a substantial decrease in fatigue, with some patients experiencing reductions as high as 35% in fatigue severity scores. These findings suggest oxaloacetate’s potential in addressing one of the most debilitating symptoms of CFS and related conditions, offering hope for those who have found little relief from other treatments.

Additional Benefits Beyond Energy Production

Beyond merely reducing fatigue, oxaloacetate supplementation appears to offer several additional health benefits. Its role in enhancing mitochondrial function and promoting better energy production at the cellular level is crucial, as mitochondrial dysfunction is often noted in CFS patients. Furthermore, oxaloacetate has been reported to possess antioxidant properties, potentially aiding in the reduction of oxidative stress, which is another contributing factor to CFS symptoms. Some studies also suggest that oxaloacetate might help improve cognitive function, providing a mental clarity boost to individuals dealing with “brain fog,” a common complaint among CFS sufferers. These ancillary benefits, combined with the main effect of reducing fatigue, make oxaloacetate a compound of interest in the ongoing search for effective CFS treatments.

Cons and Considerations

Adverse Effects and User Experiences

Like any supplement, oxaloacetate is not without its potential drawbacks. While many users report positive outcomes, others have encountered adverse effects that have led to discontinuation of the supplement. Some reported side effects include gastrointestinal distress, such as indigestion and gastritis, especially at higher doses. Insomnia was another reported side effect, although less common. These adverse reactions underscore the importance of approaching oxaloacetate supplementation cautiously, recognizing that individuals may respond differently, and what works well for one person may not be suitable for another.

Cost and Accessibility Issues

One significant barrier to oxaloacetate supplementation for chronic fatigue syndrome treatment is the cost. The high price tag associated with effective dosages can make it inaccessible to many who might benefit from it. In a study outlining the usage of oxaloacetate in treating fatigue, patients required doses of up to 1,000 mg multiple times a day to see improvements. These doses can cost upwards of $500 a month, a prohibitive amount for many individuals suffering from CFS, who may already be dealing with financial constraints due to their condition.

Nevertheless, some CFS/ME/SEID patients shared on online forums that they experienced improvement with just 200mg per day. It is recommended to begin with a low dosage and expect to notice some progress within a few weeks. 

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BenaGene with thermally stabilized oxaloacetate or 3-carboxy-3oxopropanoic acid, a key intermediate in the Kreb’s Cycle which is involved in cellular energy production.


In exploring the potential of oxaloacetate supplement for chronic fatigue syndrome (CFS) and the related condition, long COVID fatigue, a clear picture emerges: this supplement offers a promising avenue for treatment with several desirable benefits, yet also raises questions regarding cost, methodology, and the need for further research.


  • Significant Reduction in Fatigue: Clinical and anecdotal evidence point towards oxaloacetate’s ability to make a “striking and surprising” difference in reducing fatigue for those suffering from CFS and long COVID. The supplement appears to improve mitochondrial function, reduce inflammation, and possibly aid in correcting metabolic imbalances thought to contribute to these conditions.
  • Dosage Flexibility and Response: The supplement’s effectiveness was observed at various doses, indicating a dose-response relationship where higher doses could yield better outcomes. This suggests that individual responses to the supplement can be managed through dose adjustments.
  • Potential for Long-term Relief: Some individuals have reported sustained improvements in fatigue levels, suggesting that oxaloacetate could offer long-term benefits for managing symptoms of CFS and long COVID—not just temporary relief.


  • Cost Concerns: The high cost of oxaloacetate, especially at higher doses needed for optimal results, places it out of reach for many. This financial barrier could significantly limit access to what may be a beneficial treatment.
  • Insufficient Research and Verification: The excitement around oxaloacetate is tempered by the need for rigorous, large-scale, placebo-controlled trials to verify its effectiveness. Concerns have been raised about the methodology of existing studies, potential conflicts of interest, and the reliability of reported results.
  • Side Effects and Individual Variability: Like any supplement, oxaloacetate may not work for everyone, and there may be side effects in certain individuals. Personal experiences with the supplement are varied, and what works for one person may not work for another.

In conclusion, oxaloacetate presents a compelling, yet not fully validated, treatment option for those battling the debilitating effects of chronic fatigue syndrome and long COVID. While the reported benefits are encouraging, we must advocate for more extensive, unbiased research to confirm its efficacy, understand its action, and ensure its accessibility. For now, individuals interested in trying oxaloacetate should do so under the guidance of a healthcare provider, weighing the potential benefits against the cost and current uncertainties surrounding its use.


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Information on this blog is intended solely for informational purposes and may not be used as a substitute for professional advice and/or information.

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