Metabolic Modulator

Alpha-Ketoglutarate

Alpha-ketoglutaric acid

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

1000–3000 mg/day

watchEffect Window

Days to weeks in trial settings

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Alpha-ketoglutarate is a Krebs-cycle intermediate investigated for metabolic and healthy-aging support, but human nootropic/performance evidence remains limited.

Evidence varies widely by compound. Some have controlled human data for specific outcomes such as lipid markers, glycemic response, or symptom relief, while others are supported mainly by mechanistic studies. Minority uses include inflammation modulation and antioxidant effects. Dose, formulation, and safety constraints often determine whether measurable benefits occur.

Krebs-cycle-related intermediate with theoretical energy and nitrogen handling relevance. Direct human benefit claims remain low-certainty.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • No validated standalone cognition/performance benefit
  • Plausible metabolic context support

Secondary Outcomes

  • GI tolerability outcomes
  • Formulation-dependent recovery signals

Safety

Contraindications and Interactions

Contraindications

  • CKD
  • Metabolic acidosis
  • Unstable electrolyte conditions

Side effects

  • GI discomfort
  • Bloating
  • Fatigue in sensitive users

Interactions

  • Renally active agents
  • Multiple metabolic intermediates
  • High-dose electrolyte formulas

Avoid if

  • Severe renal disease
  • Acid-base instability
  • Polypharmacy without clinician review

Evidence

Study-level References

alpha-ketoglutarate-SRC-001Controlled supplementation and mechanistic crossover studies.

Human and translational summaries of alpha-ketoglutarate-containing supplementation paradigms.

Population: Adults in performance/nutrition experiments with variable co-formulations.

Dose protocol: 1-3 g/day AKG with mixed nutrients.

Key findings: Weak directional support for metabolic context outcomes. No established nootropic effect.

Notes: Product formulation heterogeneity and small scale.

Paper content

Weak directional support for metabolic context outcomes; no established nootropic effect.

alpha-ketoglutarate-SRC-002Safety synthesis and translational review.

Preclinical and human safety-focused literature around dicarboxylic metabolic intermediates.

Population: Healthy and stressed adult participants.

Dose protocol: Variable AKG doses.

Key findings: Mixed tolerability profile, generally acceptable at modest doses.

Notes: Limited high-quality replication.

Paper content

Mixed tolerability profile, generally acceptable at modest doses.

alpha-ketoglutarate-SRC-003Retrospective open-label study with DNA methylation testing at baseline and endpoint.
Sourceopen_in_new

Demidenko O, Barardo D, Budovskii V, Finnemore R, Palmer FR, Kennedy BK, Budovskaya YV. Rejuvant, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging. Aging (Albany NY). 2021;13:24485-24499. doi:10.18632/aging.203736. PMID:34847066.

Population: Generally healthy adults taking Rejuvant (calcium alpha-ketoglutarate formulation with vitamins).

Dose protocol: Rejuvant formulation (calcium alpha-ketoglutarate with vitamins) daily for an average of 7 months.

Key findings: Average 8-year reduction in biological age as measured by TruAge DNA methylation clock (p=6.538e-12). Greater benefits in older participants.

Notes: Retrospective, open-label, no placebo control. The formulation includes vitamins alongside AKG, so the effect cannot be attributed to AKG alone. DNA methylation age is a surrogate marker. Interesting signal requiring confirmation in placebo-controlled trials.

Paper content

This retrospective study examined 42 individuals who took Rejuvant (a calcium alpha-ketoglutarate formulation with vitamins) for an average of 7 months and measured biological age using the TruAge DNA methylation clock. Participants showed a mean 8-year reduction in biological age (p=6.538e-12). Greater benefits were observed in older individuals, and effects were maintained across both sexes. While highly statistically significant, the study lacked a placebo control and used a retrospective design, meaning confounding cannot be excluded.

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