Alpha Ketoglutarate: What You Need to Know Before Starting

What Is Alpha Ketoglutarate (AKG)?

Alpha ketoglutarate (AKG) is a naturally occurring compound that plays a critical role in cellular energy production. Unfortunately, this vital metabolic intermediate steadily declines as we age, making AKG supplementation an increasingly popular longevity strategy.

There are 3 main formulations of alpha ketoglutarate (AKG):

• Calcium-AKG (Ca-AKG) for oral supplements
• Ornithine-AKG (OKG) for clinical nutrition support
• Esterified AKG for topical, anti-aging skincare products

How Does Alpha Ketoglutarate Work in Your Body?

Alpha ketoglutarate functions through multiple pathways that may support healthy aging:

• ‍Mitochondrial Energy Production: AKG is necessary fuel for your mitochondria's TCA cycle (also called the Krebs cycle) and supports NAD+ regeneration—critical for energy metabolism.
• ‍Epigenetic Regulation: As a substrate for TET and Jumonji enzymes, alpha ketoglutarate helps demethylate DNA and histones, potentially reversing age-related gene expression changes.
• ‍Metabolic Signaling: AKG mildly inhibits mTORC1 while activating AMPK, mimicking the beneficial effects of caloric restriction without the dietary limitations.
• ‍Collagen Synthesis: The compound provides essential building blocks for bone and connective tissue formation, supporting structural health.
• ‍Antioxidant Support: Alpha ketoglutarate chelates reactive iron and supports glutamine recycling, indirectly reducing oxidative stress.

The Evidence for Alpha Ketoglutarate: What Human Studies Show

• Biological Age Reversal: an impressive study involved 42 mid-life adults taking approximately 1g of calcium alpha ketoglutarate daily for 7 months. Results showed DNA methylation age decreased by 8 years with no serious adverse effects. While the accuracy of DNA methylation tests is far from certain, these results nonetheless show an interesting trend.
• Bone Health Benefits: a study of post-menopausal women demonstrated that 6g of Ca-AKG daily for 24 weeks reduced bone breakdown markers by 18% and improved lumbar bone mineral density by 1.6%. These were small differences that were similar to the control group, but a noteworthy trend for a difficult-to-treat condition (osteoporosis).
• Faster Wound Healing: 20g of ornithine alpha ketoglutarate (OKG) daily reduced wound closure time by approximately 35% and halved nitrogen losses in burn patients.
  
  • Additionally, elderly patients with heel pressure ulcers given 10g of OKG daily for 6 weeks experienced accelerated healing in ulcers ≤ 8 cm².
• Skin Anti-Aging Effects: topical alpha ketoglutarate applications in skincare showed improved hydration and reduced fine-line depth after 28 days.
• Heart Health: alpha ketoglutarate given to patients undergoing cardiac surgery improves outcomes.

Who Should Consider Alpha Ketoglutarate Supplementation?

Patients seeking the following benefits should discuss alpha-ketoglutarate supplementation with doctors at Clarus Health:

• Longevity: potential epigenetic age reduction and metabolic resilience.
• Osteopenia reversal: potential improvements in bone density.
• Injury Recovery: accelerated wound healing and tissue repair.
• Aesthetics and skin health: improvements hydration and fine lines.

Is Alpha Ketoglutarate Safe?

Alpha ketoglutarate supplementation appears safe with few side effects. As always, you should discuss any supplement with your doctor before starting.

Current Research and Future Directions

Two major clinical trials are currently investigating alpha ketoglutarate's potential:

• ABLE Study: Testing 1g daily Ca-AKG versus placebo for DNA methylation age effects
• AEGIS Trial: Examining 1g AKG for enhanced surgical recovery

The Bottom Line: is Alpha Ketoglutarate Worth it?

Alpha ketoglutarate has a lot of science supporting its safety and benefits in bone health, wound healing, skin quality, and biological age markers. While we still need more human studies to confirm these observations, alpha ketoglutarate may play a role in your wellness stack. Speak with a doctor at Clarus Health today to learn more about AKG's role in precision medicine for health and longevity.