Alpha-Ketoglutarate (a-KG) is an intermediate of the Krebs cycle and is the precursor for the synthesis of glutamine, glutamate, proline, and arginine. Few data exist on the use of a-KG as an ergogenic aid. Like glutamine, however, there are some clinical data that suggest a possible anti-catabolic role.
Wernerman et al. state that the “addition of a-ketoglutarate to postoperative total parenteral nutrition prevented the decrease in muscle protein synthesis and free glutamine that usually occurs after surgery.” a-KG was infused into anesthetized postoperative dogs, resulting in a net uptake by skeletal muscle predominantly, and the kidneys, liver, and gut secondarily.
However, a-KG infusion did not change intramuscular glutamine or glutamate concentrations. In a study from the Karolinska Institute in Stockholm, researchers found that a-KG had similar effects as glutamine. In this investigation, biopsies of skeletal muscle were taken before surgery (removal of the gall bladder) and 3 days after surgery.
On each day following the operation, the control group was in negative nitrogen balance but not in the a-KG-supplemented group. Blomqvist et al. compared the effects of a-KG, glutamine, and glucose on protein metabolism in postoperative patients. Healthy patients that underwent total hip replacement surgery received either 2 g/kg of glucose, 0.28 g/kg of glutamine, or 0.28 g/kg of a-KG during surgery and the first 24 hours.
Protein synthesis decreased in the glucose group but not in the glutamine or a-KG groups. Intramuscular glutamine concentration did not change in the a-KG or glutamine group but decreased in the control.Based on the little evidence that exists, a-KG may exert an anticatabolic effect similar to glutamine under conditions of stress such as postsurgery. This is hardly surprising inasmuch as a-KG can be converted to glutamine.
No studies have specifically examined the safety of highdose a-KG use. However, because much of the work done on a-KG is on patients postsurgery, it would seem plausible that the use of a-KG for those who are healthy should not pose an undue health risk. Doses as high as 0.28 g/kg have been used in clinical studies (comparable to 21 g for a 75-kg individual).