alpha-Ketoisocaproic acid (KIC) is an intermediate (the keto acid) in the metabolism of leucine (amino acid). Alpha-Ketoisocaproic acid is considered a branched-chain keto acid (BCKA) . Branched-chain keto acids play a role in normal amino acid metabolism  and are viewed as an ammonia-free source of branched chain amino acids.
Can Ketoisocaproate Improve Exercise?
Alpha-Ketoisocaproic acid has been previously shown to enhance high-intensity exercise performance in combination with glycine and L-arginine (glycine-arginine-alpha-ketoisocaproic acid or GAKIC) [2,3]. However, a more recent study failed to find ergogenic effect of glycine-arginine-alpha-ketoisocaproic acid on repeated bouts of high-intensity exercise in trained individuals . KIC has also been shown to reduce exercise-induced muscle damage and preserve skeletal muscle force production when ingested with beta-hydroxy-beta-methylbutyrate (HMB) . In 2010 Nunan and colleagues  noted that exercise-induced muscle damage is not attenuated by HMB and KIC supplementation but may provide limited benefit in the recovery of muscle function after exercise-induced muscle damage in untrained subjects.
Joshua and associates  examined the efficacy of short-term KIC supplementation in a well-controlled study. They wanted to see if alpha-ketoisocaproic acid by itself provides any ergogenic value in moderate and high-intensity single bout exercise performance. They used two doses (1,5 grams and 9 grams) and reported that KIC did not improve exercise performance, at either dose.
In theory, KIC supplementation may enhance exercise performance through a variety of mechanisms. Ketoisocaproate may reduce endogenous ammonia that hinders muscle function  and attenuates exercise-induced muscle damage .
Interaction With Cortisol
One study  in lambs reported that addition of KIC to feed reduces plasma cortisol levels. This effect was not observed in cows .
Ketoisocaproic Acid Side Effects
Studies are not reporting any adverse effects.
(Other common names: 4-Methyl-2-oxopentanoic acid, α-ketoisocaproic acid, 2-Oxoisocaproic acid, Ketoleucine, α-keto-isocaproic acid, KIC, Ketoisocaproate, Potassium Ketoisocaproate)
Walser, Mackenzie. “Role of branched-chain ketoacids in protein metabolism.” Kidney Int 38.4 (1990): 595-604.
- Buford, Britni N., and Alexander J. Koch. “Glycine-arginine-alpha-ketoisocaproic acid improves performance of repeated cycling sprints.” Med Sci Sports Exerc 36 (2004): 583-587.
Stevens, Bruce R., et al. “High-intensity dynamic human muscle performance enhanced by a metabolic intervention.” Medicine and science in sports and exercise 32.12 (2000): 2102-2108.
Beis, Lukas, et al. “Failure of Glycine-arginine-α-ketoisocaproic acid to improve high intensity exercise performance in trained cyclists.” International journal of sport nutrition and exercise metabolism 21.1 (2011): 33-39.
Van Someren, Ken A., Adam J. Edwards, and Glyn Howatson. “Supplementation with [beta]-hydroxy-[beta]-methylbutyrate (HMB) and (KIC) reduces signs and symptoms of exercise-induced muscle damage in man.” International Journal of Sport Nutrition & Exercise Metabolism 15.4 (2005): 413-424.
Nunan, David, Glyn Howatson, and Ken A. van Someren. “Exercise-induced muscle damage is not attenuated by [beta]-hydroxy-[beta]-methylbutyrate and [alpha]-ketoisocaproic acid supplementation.” The Journal of Strength & Conditioning Research 24.2 (2010): 531-537.
Yarrow, Joshua F., et al. “The effects of short-term KIC supplementation on exercise performance: a randomized controlled trial.” Journal of the International Society of Sports Nutrition 4.1 (2007): 1-6.