Oxaloacetate
Summary
Oxaloacetate is a cellular energy intermediate sold in a stabilized form. Human data are limited: an open-label study in 76 people with ME/CFS and 43 with long COVID reported 22–28% less fatigue against a historical placebo, and a 30-person Alzheimer's dose study found it safe with brain-imaging changes but no cognitive benefit.
Key facts
- A Krebs (citric acid) cycle intermediate; supplements use anhydrous enol-oxaloacetate (AEO) for stability[1]
- ME/CFS: Chalder fatigue scores fell 22.5–27.9% from baseline at 6 weeks, compared with a 5.9% historical placebo response; no concurrent placebo group[1]
- 500 or 1,000 mg twice daily for 1 month was safe; the higher dose raised brain glucose uptake on PET, but cognitive scores did not improve[2]
- The Alzheimer's study did not find consistent changes in blood oxaloacetate levels[2]
- 2 graded human outcomes on this page
- October 13, 2026
How it works
ProposedOxaloacetate feeds the Krebs cycle and is proposed to support cellular energy production and the NAD+/NADH balance. In the Alzheimer's study, 1,000 mg twice daily increased brain glucose uptake and parietal glutathione on imaging, suggesting target engagement; links to symptom outcomes are unproven.[2]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Fatigue | Grade D | Improved | Open-label · n = 119 · 2022 | 1 row |
| Cognition | Grade D | Mixed | Pilot RCT · n = 30 · 2021 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Physical and mental fatigue in ME/CFS and long COVID | Improved | Grade D | Open-label trial · n = 119 · 2022 Adults with ME/CFS (76; 74% women) or long COVID fatigue for ≥6 months (43) Form: Anhydrous enol-oxaloacetate capsules · Dose: 500 mg twice daily to 1,000 mg three times daily · Duration: 6 weeks ME/CFS fatigue scores fell 22.5–27.9% from baseline (p<0.005), above a 5.9% historical placebo response; long COVID fatigue also fell. | 35764955 (opens PubMed)Source [1] |
| Brain metabolism and cognition in Alzheimer's disease | Mixed | Grade D | Pilot RCT · n = 30 · 2021 Adults with Alzheimer's disease Form: Oxaloacetate capsules · Dose: 500 or 1,000 mg twice daily · Duration: 1 month Both doses were safe. The higher dose increased brain glucose uptake (FDG PET) and glutathione vs the lower dose; cognitive scores did not improve. | 32715609 (opens PubMed)Source [2] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Anhydrous enol-oxaloacetate (AEO) capsules | Varies[1][2] | No consistent rise in blood levels was found after 1 month of dosing in Alzheimer's patients; no head-to-head form comparisons.[2] | 500–1,000 mg twice daily for 1 month was safe and tolerated; doses up to 1,000 mg three times daily were used for 6 weeks.[2][1] | ME/CFS, long COVID and Alzheimer's studies |
Studied doses
Doses studied in human trials ranged from 1,000 mg/day (500 mg twice daily) to 3,000 mg/day (1,000 mg three times daily) for 4 to 6 weeks. Retail longevity products often contain 100 mg, far below these amounts.[1][2]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
None found in our sources.
Who should be careful
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
How to read the label
Cost per studied dose, without the sales pitch
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Frequently asked questions
Does oxaloacetate help chronic fatigue or long COVID?
An open-label study reported 22–28% less fatigue in ME/CFS after 6 weeks, but it had no placebo group of its own.[1]
Does oxaloacetate help Alzheimer's or memory?
In a 30-person safety study, 1,000 mg twice daily changed brain energy measures on imaging but did not improve cognitive scores.[2]
Is oxaloacetate an anti-aging supplement?
It is marketed that way, but no human study has measured aging or lifespan outcomes.[1][2]
Is oxaloacetate safe?
Up to 1,000 mg twice daily for a month was safe in Alzheimer's patients; long-term data are lacking.[2]
Sources
- [1]Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.. J Transl Med, 2022. open-label
- [2]Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients.. Alzheimers Dement, 2021. pilot-RCT
What changed
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.
- Self-review pass (strict second read): fatigue study labelled non-randomized with historical control; Alzheimer's study labelled as a two-dose comparison without placebo. Drug interactions checked explicitly for anticoagulants, diabetes and blood-pressure drugs, levodopa, antibiotics and chemotherapy: no published data, stated as such in Who should avoid.