What is alpha-ketoglutarate?
AKG is a compound called a carboxylated keto acid. It is produced in the body naturally and is used in the Krebs cycle, a sequence of intracellular reactions that creates energy in the form of ATP. AKG is also important for several other metabolic and cellular processes. AKG helps maintain nitrogen balance within the body, is a precursor to several amino acids, is a source of energy for cells, and functions as an antioxidant. It is used to produce glutamine. Glutamine is an amino acid that is useful for muscle protein synthesis and for several important functions within the immune system.[1][3]
What are alpha-ketoglutarate’s main benefits?
In sports nutrition, AKG has been used as a supplement to improve muscle protein synthesis and to decrease muscle breakdown, and is therefore used by athletes to improve body composition.[4][5] AKG supplementation might also improve athletic performance. One study found that an arginine plus alpha-ketoglutarate (AAKG) supplement improved bench press strength, but not aerobic capacity. More research is needed here to support claims of AKG as an ergogenic aid.[4][6][4]
AKG is also used in recovery from surgery or trauma, because it is a precursor to the amino acid glutamine. Although glutamine is a nonessential amino acid, it is sometimes called “conditionally essential” because the amount of glutamine the body needs for recovery after a significant trauma may exceed the amount the body is able to produce. In this instance, an AKG supplement can help the recovery process.[7][8]
AKG has been suggested as a longevity supplement; some research in roundworms, rats, and mice suggests that it could increase lifespan and delay the onset of age-related diseases, although clinical trials will need to confirm these findings.[9][7][10][8]
In people with chronic kidney disease, particularly those receiving dialysis as treatment, administering AKG in combination with calcium improved biomarkers of kidney function.[11][12]
AKG was found in one study to increase the expression of involucrin, filaggrin, and serine palmitoyl transferase. These molecules are all important for the structure of the outer layer of the skin and for hydration of the outer skin layer, so using AKG topically could improve the appearance of the skin.[13][14]
What are alpha-ketoglutarate’s main drawbacks?
AKG supplementation alone doesn’t appear to carry significant side effects. One study found the no observed adverse effect level (NOAEL) to be at 1g/kg body weight in rats.[15]
Adverse effects, including heart palpitations and dizziness, have been reported by those using AAKG, which is a combination of arginine with AKG. This combination is commonly used by athletes.[16][4]
While AAKG is considered to be ergogenic, the evidence to support this is actually not conclusive. Improvements in strength have been reported in some studies,[6] but other studies report no improvement in performance, strength, and endurance.[4][17] Given the potential for adverse effects, the risk might not be worth the small potential benefits.
How does alpha-ketoglutarate work?
AKG is helpful as a precursor to amino acids. It reacts with ammonia in the body to form glutamine and other amino acids. Glutamine in turn is an important source of energy for lymphocytes and enterocytes (a type of white blood cell and intestinal cells, respectively), and can be used by the body to recover from trauma. This reaction with ammonia also forms glutamate, which helps increase proline production, which is important for collagen production.[8][7]
AKG is also a regulator of gene expression, and works on cell signaling pathways that are involved in the aging process. It might extend lifespan by limiting the activity of ATP synthase, an energy carrier for cellular energy metabolism. AKG also inhibits target of rapamycin (TOR) and its mammalian equivalent, mammalian/mechanistic target of rapamycin (mTOR), which are protein kinases that regulate cell growth and metabolism across several kingdoms of life. Inhibiting ATP synthase and TOR/mTOR seems to prolong life as demonstrated in worms, mice, and flies.[7][10][8] AKG also shows some antioxidant activity, both in eliminating reactive oxygen species (ROS) and by improving the activity of other enzymes that do so, such as superoxide dismutase (SOD).[18][3]
What are other names for Alpha-Ketoglutarate
- Oxoglutaric acid
- 2-Oxopentanedioic acid
- 2-Keto-glutaric acid
Dosage information
In research, the dosages used range from 3.6 g to 6 g, with higher dosing in people who have suffered burns, but a recommended daily dose has not yet been established.[1] Since the effects are dose-dependent, finding an accurate dosing recommendation will be an important part of ongoing research.[2]
Frequently asked questions
AKG is a compound called a carboxylated keto acid. It is produced in the body naturally and is used in the Krebs cycle, a sequence of intracellular reactions that creates energy in the form of ATP. AKG is also important for several other metabolic and cellular processes. AKG helps maintain nitrogen balance within the body, is a precursor to several amino acids, is a source of energy for cells, and functions as an antioxidant. It is used to produce glutamine. Glutamine is an amino acid that is useful for muscle protein synthesis and for several important functions within the immune system.[1][3]
In sports nutrition, AKG has been used as a supplement to improve muscle protein synthesis and to decrease muscle breakdown, and is therefore used by athletes to improve body composition.[4][5] AKG supplementation might also improve athletic performance. One study found that an arginine plus alpha-ketoglutarate (AAKG) supplement improved bench press strength, but not aerobic capacity. More research is needed here to support claims of AKG as an ergogenic aid.[4][6][4]
AKG is also used in recovery from surgery or trauma, because it is a precursor to the amino acid glutamine. Although glutamine is a nonessential amino acid, it is sometimes called “conditionally essential” because the amount of glutamine the body needs for recovery after a significant trauma may exceed the amount the body is able to produce. In this instance, an AKG supplement can help the recovery process.[7][8]
AKG has been suggested as a longevity supplement; some research in roundworms, rats, and mice suggests that it could increase lifespan and delay the onset of age-related diseases, although clinical trials will need to confirm these findings.[9][7][10][8]
In people with chronic kidney disease, particularly those receiving dialysis as treatment, administering AKG in combination with calcium improved biomarkers of kidney function.[11][12]
AKG was found in one study to increase the expression of involucrin, filaggrin, and serine palmitoyl transferase. These molecules are all important for the structure of the outer layer of the skin and for hydration of the outer skin layer, so using AKG topically could improve the appearance of the skin.[13][14]
The first studies showing that AKG might be able to both extend lifespan and delay the onset of age-related diseases were done on roundworms.[10] More recent studies in mice also showed an increase in both lifespan and healthspan with AKG supplementation.[9][19] AKG also slows down muscle loss, both as an amino acid precursor and through its interaction with protein receptors that can reduce muscle atrophy. Through epigenetic regulation, AKG decreased signs of age-related bone loss in mice. One study showed that AKG supplementation increased bone mass and accelerated bone regeneration in mice.[20] Its anti-inflammatory effects, antioxidant effects, and its role in the production of glutamate could lower the risk of neurodegenerative diseases.[1][2][21] Interestingly, in some studies done in fruit flies and mice, AKG only had an impact on the lifespan of females, although healthspan did seem to improve in both males and females.[8][9][22] These all point to a promising role in anti-aging for AKG in the future, but more clinical trials will need to be done before AKG can be recommended as an anti-aging supplement for humans.
AKG supplementation alone doesn’t appear to carry significant side effects. One study found the no observed adverse effect level (NOAEL) to be at 1g/kg body weight in rats.[15]
Adverse effects, including heart palpitations and dizziness, have been reported by those using AAKG, which is a combination of arginine with AKG. This combination is commonly used by athletes.[16][4]
While AAKG is considered to be ergogenic, the evidence to support this is actually not conclusive. Improvements in strength have been reported in some studies,[6] but other studies report no improvement in performance, strength, and endurance.[4][17] Given the potential for adverse effects, the risk might not be worth the small potential benefits.
AKG is helpful as a precursor to amino acids. It reacts with ammonia in the body to form glutamine and other amino acids. Glutamine in turn is an important source of energy for lymphocytes and enterocytes (a type of white blood cell and intestinal cells, respectively), and can be used by the body to recover from trauma. This reaction with ammonia also forms glutamate, which helps increase proline production, which is important for collagen production.[8][7]
AKG is also a regulator of gene expression, and works on cell signaling pathways that are involved in the aging process. It might extend lifespan by limiting the activity of ATP synthase, an energy carrier for cellular energy metabolism. AKG also inhibits target of rapamycin (TOR) and its mammalian equivalent, mammalian/mechanistic target of rapamycin (mTOR), which are protein kinases that regulate cell growth and metabolism across several kingdoms of life. Inhibiting ATP synthase and TOR/mTOR seems to prolong life as demonstrated in worms, mice, and flies.[7][10][8] AKG also shows some antioxidant activity, both in eliminating reactive oxygen species (ROS) and by improving the activity of other enzymes that do so, such as superoxide dismutase (SOD).[18][3]
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