AKG Supplements (Alpha-Ketoglutarate)

DALL·E 2023 04 07 18.45.39 The letters A K and G used only one time into cyber art

AKG (alpha-ketoglutarate) supplements. Are they safe and effective? What are the risks?


AKG is a messenger molecule which acts as a metabolic enhancer for many chemical reactions. It is a compound within the Krebs cycle of aerobic respiration that produces energy for the body. It contributes to the formation of glutamine and glutamate. Glutamine is the primary source of energy for cell division and also enhances protein and muscle development. Glutamate is a brain neurotransmitter and also contributes to bone formation.

Why Supplement?

Ponce de Leon Health claims Rejuvant brand CA-AKG can prevent age-related bone loss and osteoporosis while also reducing biological aging by 8 years after only 7 months of supplementation. They claim it can also reverse the graying of hair in mammals. In mouse trials, AKG extended lifespan between 10-20% and healthspan by 50%.

Positive Impact

AKG helps to build muscle and heal muscle injuries. It is used by some healthcare providers to reduce blood supply problems during heart surgeries and for preventing muscle breakdown after surgery or trauma, even though evidence of benefit is limited.

In a 2020 study, AKG supplements protected mice against age-related osteoporosis and rejuvenated aged Mesenchymal stem cells.

AKG improves the effectiveness of hemodialysis for those with chronic kidney disease (CKD).

There is insufficient evidence that AKG supplements improves athletic performance, reducing pain and improving function in tendinopathy and helps with bacteria infections.

According to RenuebyScience, AKG restores DNA integrity, manages oxidative stress and age-related inflammation.

According to Brian Kennedy, AKG increases red blood cell production, improves adult stem cell function and demethylates DNA.

November 2021 results from Ponce de Leon and the Buck Institute of Aging’s study (called Aging Well) of 42 participants declared they had reduced biological age by an average of 8 years in men after only 7 months of supplementation using TruMe’s biological aging testing. However, see concerns below.

Which Vendor?

Ponce de Leon Health claims Rejuvant ($120-$150 / month) CA-AKG can dramatically reduce biological age. They use TruAge testing to measure chronological age to biological age on their website showing unrealistic changes of 13, 19 and 34 years among their family members. Rejuvant provides a sustained release delivery system to avoid breakdown of AKG in the gut.

RenuebyScience ($48.50) offers a sustained release liposomal delivery system.

ProHealth Longevity ($18)

Klaire Labs ($21.24)


Optimal dosage levels are not scientifically determined at this time. Each vendor has different recommendations. 6 grams per day was proven safe in a human osteoporosis study according to Ponce de Leon scientist Brian Kennedy.

Rejuvant LifeTabs, taken once daily contain two tablets, making up one serving of 900mcg Vitamin A, 190mg Calcium and 1000mg Calcium Alpha-Ketoglutarate – LifeAKG (™).

Clinical Trials?

There are two clinical trials for AKG with Rejuvant. 

The Aging Well study was supposed to recruit 100 participants and have a placebo arm. TruMe’s testing methodology is neither rigorous nor transparent. The integrity of the results is questionable, especially since there was no placebo group. Much more rigorous, transparent and longer-term human trial testing is needed.

Side Effects

No significant side-effects for AKG have been reported in humans, however, there is a lack of clinical trial data. 

Studies in rats with 14 day usage did find some toxicity, resulting in diarrhea and weight loss.

There is a variation of AKG called Arginine AKG (AAKG) which is popular with weight lifters. Side effects can include abdominal pain, diarrhea and gout. AAKG can also interfere with blood pressure lowering medications and make asthma conditions worse.

Potential Interactions

AAKG is not to be used by those who have previously suffered a heart attack.

According to Ponce de Leon, berberine cancels out the effect of AKG. Individually, each performed great in mice, although AKG was 3x better.

AKG is not recommended for those who are pregnant or breast-feeding as there is insufficient research.

Data Sources


DALL-E-2 (image generation)


Longevity Technology

Modern Healthspan




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