Oxaloacetate is a stabilized energy-cycle supplement promoted for longevity. Its longevity case rests only on a worm study, never shown in mammals or people. The strongest human evidence is for easing chronic fatigue and long COVID, though nearly all comes from the maker. It appears well tolerated, with mostly mild digestive or sleep effects. (Full Review)

Protocol

Fatigue Dose

2,000 mg/day

As used in trials; commonly split 1,000 mg twice daily

Longevity Dose

100–200 mg/day

Marketed benaGene dose; extrapolated from mechanism, not outcome trials

Timing

Morning / early afternoon

Split dosing across the day given the short half-life; avoids sleep disruption

Time to effect

Fatigue Reduction

~6 weeks

Dose-dependent improvement; allow several weeks before judging response

Reassessment Point

6–12 weeks

Set a defined trial with a planned stop-if-no-benefit decision

Benefits

Medium: Reduction of fatigue in chronic fatigue syndrome and long COVID

Low: Mimicry of caloric restriction / longevity signaling; improved glucose regulation and insulin sensitivity; support of brain energy metabolism and neuroprotection

Speculative: Adjunctive anti-tumor / anti-glioma activity; emotional premenstrual symptom relief

Contraindications

Parkinson's disease

Pregnancy, breastfeeding, children

Key Interactions

Glucose-lowering drugs and supplements (metformin, sulfonylureas, insulin, berberine, alpha-lipoic acid, chromium)

Levodopa / Parkinson's medications (levodopa-carbidopa, dopamine agonists)

Other mitochondrial / energy supplements (NMN, NR, CoQ10, creatine, ribose)

Iron supplements (via co-formulated vitamin C)

Risk & Side Effects

Low: Gastrointestinal upset; insomnia and activation

Speculative: Possible worsening of Parkinson's disease symptoms; unknown long-term and reproductive safety; theoretical metabolic acidosis or substrate loading at high doses

Monitoring

Marker	Target	Why
Fasting glucose	70–90 mg/dL	Detects the additive glucose-lowering effect, especially with antidiabetic agents
HbA1c	< 5.4%	Tracks longer-term glucose impact of any insulin-sensitizing effect
Fasting insulin	2–5 µIU/mL	Assesses whether insulin sensitivity improves over time
Comprehensive metabolic panel (liver and kidney markers)	ALT/AST < 25 U/L; eGFR > 90 mL/min/1.73m²	General safety surveillance for an organic-acid metabolite, particularly at higher doses
hs-CRP	< 1.0 mg/L	Tracks any anti-inflammatory effect claimed mechanistically

Cadence: Baseline before starting; again at ~6–12 weeks, then every 6–12 months for long-term use

Qualitative Assessment

Physical fatigue and exertion tolerance
Mental fatigue, focus, and cognitive clarity
Sleep quality and whether dosing time affects it
Day-to-day energy and post-exertional recovery
Mood and stress resilience

Oxaloacetate for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment