Should I take alpha-ketoglutarate (AKG)?

Our read is that alpha-ketoglutarate (AKG) is a promising longevity compound that has been successfully reproduced in experiments and is a central metabolite in the TCA and Krebs cycles that declines with age.

Experts suggest that supplementing with AKG may be beneficial, with some reporting it can reduce hair greying, frailty, extend median lifespan, and reverse epigenetic age.

While a controlled clinical trial is underway, preliminary findings and expert use indicate a positive impact in people.

Peter Attia has used a rejuvenant product containing alpha-ketoglutarate (AKG) for years, and some experts mention supplementing 18-month-old female mice with alpha-ketoglutarate and administering it at 1% in drinking water.

• 01Peter Attia and Rhonda Patrick state that alpha-ketoglutarate is a promising longevity compound that has been successfully reproduced in experiments.
• 02Peter Attia notes that funding translational research for aging interventions, such as the AKG trial costing $1-1.5 million, is a high-leverage investment for potentially adding a decade to lifespan.
• 03David Sinclair claims that molecules including alpha-ketoglutarate, acetate, lysine, S-adenosylmethionine, and NAD+ influence modifications to DNA and its packaging proteins.
• 04David Sinclair states that alpha-ketoglutarate can convert white fat into beige fat when administered at 1% in drinking water.
• 05Peter Attia and David Sinclair highlight that alpha-ketoglutarate is a central metabolite in the TCA and Krebs cycles that declines with age and may be beneficial when supplemented.
• 06Peter Attia, Bryan Johnson, and David Sinclair report that supplementing 18-month-old female mice with alpha-ketoglutarate reduced hair greying, frailty, and extended median lifespan by 10-16%.
• 07David Sinclair mentions that a combination of alpha-ketoglutarate and vitamins reversed biological age by an average of eight years in seven months in a study.
• 08David Sinclair associates the antihypertensive drug doxazosin and the metabolite AKG with reduction or reversal of biological age.
• 09Peter Attia has used a rejuvenant product containing alpha-ketoglutarate (AKG) for years, adding and removing other substances like astaxanthin, fucoidan, and rapamycin to assess their individual effects, and measures outcomes.
• 10Peter Attia and David Sinclair indicate that supplementing with time-release alpha-ketoglutarate (AKG) has shown in rudimentary methylation clock analyses to reverse epigenetic age by a few years.
• 11Peter Attia states that taking sublingual NAD with epigenine and rejuvenant (AKG + vitamin A + B complex) acutely improves exercise performance, characterized by a higher heart rate relative to respiratory rate and perceived exertion.
• 12Peter Attia notes that time-release AKG can reverse aging by a few years according to rudimentary methylation clocks.
• 13Peter Attia expects time-release alpha-ketoglutarate (AKG) to have a positive impact in people.
• 14Rhonda Patrick reports that worms fed alpha-ketoglutarate extended their lifespan by 70% through TOR inhibition.

Peter Attia notes that a controlled placebo double-blinded clinical trial is being conducted to test time-release AKG for mechanistic information, excluding vitamins. Peter Attia and David Sinclair mention that alpha-ketoglutarate has reports of lifespan extension in yeast, worms, flies, and mice, but has not been tested as extensively as rapamycin. David Sinclair states that alpha-ketoglutarate is a cellular chemical used for amino acid synthesis, energy production, and reversing DNA methylation age. David Sinclair suggests that alpha-ketoglutarate may reprogram biological age.

A controlled placebo double-blinded clinical trial providing definitive mechanistic information on time-release AKG in humans would change the verdict.