Last Updated: January 16, 2023

Alpha-ketoglutarate (AKG) is an important biological compound that plays a central role in regulating energy production through the Krebs cycle, which is the main way cells create energy. AKG has been used to increase muscle protein synthesis, but may also be useful as a supplement for longevity and healthy aging.

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Alpha-Ketoglutarate is most often used for

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?
Note that Alpha-Ketoglutarate is also known as:
  • 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]

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Update History
  1. ^Gyanwali B, Lim ZX, Soh J, Lim C, Guan SP, Goh J, Maier AB, Kennedy BKAlpha-Ketoglutarate dietary supplementation to improve health in humans.Trends Endocrinol Metab.(2022-Feb)
  2. ^Naeini SH, Mavaddatiyan L, Kalkhoran ZR, Taherkhani S, Talkhabi MAlpha-ketoglutarate as a potent regulator for lifespan and healthspan: Evidences and perspectives.Exp Gerontol.(2023-May)
  3. ^Liu, S and Yao, KThe Antioxidative Function of Alpha-Ketoglutarate and Its ApplicationsBiomed Res. Int..(2018-01)
  4. ^Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H, Lucia ASupplements with purported effects on muscle mass and strength.Eur J Nutr.(2019-Dec)
  5. ^ The role of glutamine and α-ketoglutarate in gut metabolism and the potential application in medicine and nutritionJ Pre Clin Clin Res.(2007-01)
  6. ^Bill Campbell, Mike Roberts, Chad Kerksick, Colin Wilborn, Brandon Marcello, Lem Taylor, Erika Nassar, Brian Leutholtz, Rodney Bowden, Chris Rasmussen, Mike Greenwood, Richard KreiderPharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult menNutrition.(2006 Sep)
  7. ^Wu N, Yang M, Gaur U, Xu H, Yao Y, Li DAlpha-Ketoglutarate: Physiological Functions and Applications.Biomol Ther (Seoul).(2016-Jan)
  8. ^Bayliak MM, Lushchak VIPleiotropic effects of alpha-ketoglutarate as a potential anti-ageing agent.Ageing Res Rev.(2021-Mar)
  9. ^Azar Asadi Shahmirzadi, Daniel Edgar, Chen-Yu Liao, Yueh-Mei Hsu, Mark Lucanic, Arash Asadi Shahmirzadi, Christopher D Wiley, Garbo Gan, Dong Eun Kim, Herbert G Kasler, Chisaka Kuehnemann, Brian Kaplowitz, Dipa Bhaumik, Rebeccah R Riley, Brian K Kennedy, Gordon J LithgowAlpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging MiceCell Metab.(2020 Sep 1)
  10. ^Chin RM, Fu X, Pai MY, Vergnes L, Hwang H, Deng G, Diep S, Lomenick B, Meli VS, Monsalve GC, Hu E, Whelan SA, Wang JX, Jung G, Solis GM, Fazlollahi F, Kaweeteerawat C, Quach A, Nili M, Krall AS, Godwin HA, Chang HR, Faull KF, Guo F, Jiang M, Trauger SA, Saghatelian A, Braas D, Christofk HR, Clarke CF, Teitell MA, Petrascheck M, Reue K, Jung ME, Frand AR, Huang JThe metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR.Nature.(2014-Jun-19)
  11. ^Guo L, Chen S, Ou L, Li S, Ye ZN, Liu HFDisrupted Alpha-Ketoglutarate Homeostasis: Understanding Kidney Diseases from the View of Metabolism and Beyond.Diabetes Metab Syndr Obes.(2022)
  12. ^Riedel E, Hampl H, Steudle V, Nündel MCalcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations.Miner Electrolyte Metab.(1996)
  13. ^Xue H, Tu Y, Zhang G, Xin X, Hu H, Qiu W, Ruan D, Zhao YMechanism of ultrasound and tea polyphenol assisted ultrasound modification of egg white protein gel.Ultrason Sonochem.(2021-Dec)
  14. ^Son ED, Choi GH, Kim H, Lee B, Chang IS, Hwang JSAlpha-ketoglutarate stimulates procollagen production in cultured human dermal fibroblasts, and decreases UVB-induced wrinkle formation following topical application on the dorsal skin of hairless mice.Biol Pharm Bull.(2007-Aug)
  15. ^Bhattacharya R, Gujar N, Singh P, Rao P, Vijayaraghavan RToxicity of alpha-ketoglutarate following 14-days repeated oral administration in Wistar rats.Cell Mol Biol (Noisy-le-grand).(2011-Jul-27)
  16. ^Prosser JM, Majlesi N, Chan GM, Olsen D, Hoffman RS, Nelson LSAdverse effects associated with arginine alpha-ketoglutarate containing supplements.Hum Exp Toxicol.(2009-May)
  17. ^ Wax B et alAcute Ingestion of L-Arginine Alpha-Ketoglutarate Fails to Improve Muscular Strength and Endurance in ROTC CadetsInt J Exerc Sci.(2013)
  18. ^J Krajícková, V Pesáková, M Adam, K E SeniusEffect of tolfenamic acid on the metabolism of the main connective tissue components in ratsArzneimittelforschung.(1987 Feb)
  19. ^Oleksandr Demidenko, Diogo Barardo, Valery Budovskii, Robb Finnemore, Francis R Palmer, Brian K Kennedy, Yelena V BudovskayaRejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation testAging (Albany NY).(2021 Nov 30)
  20. ^Yuan Wang, Peng Deng, Yuting Liu, Yunshu Wu, Yaqian Chen, Yuchen Guo, Shiwen Zhang, Xiaofei Zheng, Liyan Zhou, Weiqing Liu, Qiwen Li, Weimin Lin, Xingying Qi, Guomin Ou, Cunyu Wang, Quan YuanAlpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylationsNat Commun.(2020 Nov 5)
  21. ^Morita M, Kudo K, Shima H, Tanuma NDietary intervention as a therapeutic for cancer.Cancer Sci.(2021-Feb)
  22. ^Yuan Su, Tao Wang, Nan Wu, Diyan Li, Xiaolan Fan, Zhongxian Xu, Shailendra Kumar Mishra, Mingyao YangAlpha-ketoglutarate extends Drosophila lifespan by inhibiting mTOR and activating AMPKAging (Albany NY).(2019 Jun 26)