Alpha Ketoglutaric Acid

What is Alpha Ketoglutaric Acid (AKG)?

One of the discoverers of Alpha-ketoglutarate (AKG), Hans Adolf Krebs, was awarded the Nobel Prize for Medicine in 1953. AKG was discovered in 1937 by Krebs and William Arthur Johnson as part of the overall identification of the citric acid cycle (Krebs cycle). 

Collectively, the Krebs cycle is a series of chemical reactions that our cells use to generate energy from the foods we eat (carbohydrates, fats, and proteins) into carbon dioxide.

What does it help with in the body? 

AKG is used by cells during growth and in healing from injuries and other wounds, and is especially important in the healing of muscle tissue. As an antioxidant, AKG interferes in nitrogen and ammonia balance, and affects epigenetic and immune regulation. 

The role of Alpha-ketoglutarate (AKG) is kind of complicated and a little challenging to describe in layman’s terms. It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. AKG not only extends lifespan, but also delays age-related disease. 

What have the studies shown?

A few studies published in the 1980s and 1990s in humans suggested the potential benefits of AKG in muscle growth, wound healing, and in promoting faster recovery after surgery.

AKG can modulate protein synthesis, help with bone development and with the loss of muscle mass. AKG increased muscle strength and endurance, in part by preventing muscle protein breakdown through a mechanism involving prolyl hydroxylase-3 and the β2 adrenergic receptor. 

AKG has been shown to have a protective effect against osteoporosis. One study in postmenopausal women with osteopenia showed that a daily dose of oral Ca-AKG (6 g AKG for 6 months) increased bone mass density by 1.6% from baseline. There was a significant decrease in the C-terminal crosslinking telopeptide of type-I collagen (a biomarker of bone reabsorption) in patients receiving Ca-AKG supplement compared to those only receiving calcium. 

AKG’s most notable benefit is its ability to modulate aging. AKG impacts protein metabolism, synthesis, and absorption from the alimentary canal. There is evidence that AKG can influence aging, and a number of studies suggest that this is the case. A 2014 study showed that AKG extends the lifespan of adult C. elegans by roughly 50% by inhibiting ATP synthase and the target of rapamycin (TOR).

AKG plays a role in the brain, in neurodegenerative disease, may be essential in long-term potentiation, memory, and neurotransmission. Intravenous AKG has been used to reduce vascular insufficiency during cardiovascular surgery. Several studies have shown the cardioprotective effects of AKG. During heart surgery, myocardial AKG concentration is critically low, hence cardiac cells are in a low energy state, leading to myocardial ischemic injury. One clinical trial showed that the addition of 28 g of AKG to cardioplegic blood reduces the appearance of ischemic biomarkers.

So far there are a few studies that investigate the role of AKG in the treatment of liver disease in humans. However, results from these studies and those in animals indicate that AKG may be useful in treating non-alcoholic fatty liver disease and reducing brain ammonia and glutamate level in patients with hepatic encephalopathy. 

Ca-AKG has been shown to improve kidney function and nutrition in patients with chronic renal failure. AKG also regulates acid–base balance in renal tubules and increases renal function 

AKG regulates signaling pathways linked to oncogenesis (cancer), making it one of the potential anticancer agents. The anticancer effect of AKG has been attributed to its ability to reverse the metabolic response to hypoxia and restore oxidative phosphorylation in cancer cells. 

Finally AKG has shown promise in its ability to stabilize the homeostasis of the immune system. 

What are some contraindications?

No significant side effects caused by alpha-ketoglutarate (AKG) have been reported in humans.

Source: https://www.sciencedirect.com/science/article/abs/pii/S1043276021002666 

For more information about AKG:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703346/

https://www.lifespan.io/topic/alpha-ketoglutarate-akg/ 

https://healthmatters.io/understand-blood-test-results/a-ketoglutaric-acid-akg 

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