α-KIC has been studied as a nutritional supplement to aid in the performance of strenuous physical activity. Studies have shown that taking ɑ-KIC and its derivatives before acute physical activity led to an increase in muscle work by 10%, as well as a decrease in muscle fatigue during the early phase of the physical activity.[8] When taken with other supplements over a two-week period, such as beta-hydroxy beta-methylbutyrate (HMB), participants reported delayed onset of muscle soreness, as well as other positive effects such as increased muscle girth.[9] It is important to note that studies have also suggested that ɑ-KIC taken alone did not have any significant positive impacts on physical performance, so it should be taken in conjunction with other ergogenic substances.[10] ɑ-KIC is not available as a supplement on its own, but its decarboxylated form HMB is available in calcium salt capsules or powder.[4]
The biochemical implications of α-KIC are largely connected to other biochemical pathways. Protein Synthesis, skeletal muscle regeneration, and skeletal muscle proteolysis have all been noted to change when ɑ-KIC is taken. There is not much research into the specific mechanisms taking part in these processes, but there is a noticeable correlation between ɑ-KIC ingestion and increased skeletal muscle protein synthesis, regeneration, and proteolysis.[4]
Multiple studies have demonstrated that there have been no adverse effects on humans nor animals that ingested α-KIC or HMB.[11][12]
In patients with maple syrup urine disease, who are unable to metabolize the branched chain alpha keto acids, α-KIC is believed to be one of the key mediators of neurotoxicity.[13]
Branched-chain alpha-keto acids such as α-KIC are found in high concentrations in the urine of people who suffer from Maple Syrup Urine Disease. This is disease is caused by a partial branched-chain alpha-keto acid dehydrogenase deficiency, which leads to a buildup of branched-chain alpha-keto acids, including α-KIC and HMB.[14] These keto-acids build up in the liver,[4][5][6] and since limited isovaleryl-CoA can be produced, these keto-acids must be excreted in the urine as α-KIC, HMB, and many other similar keto acids. Flare-ups in people who have this condition are caused due to poor diet.[7] Symptoms of Maple Syrup Urine Disease include sweet smelling urine, irritability, lethargy, and in serious cases edema of the brain, apnea, coma, or respiratory failure.[14][7] Treatment includes lowering leucine intake and a specialized diet to make up for the lack of leucine ingestion.[7]
^ abSomeren, Ken A. van; Edwards, Adam J.; Howatson, Glyn (1 August 2005). "Supplementation with β-Hydroxy- β-Methylbutyrate (HMB) and α-Ketoisocaproic Acid (KIC) Reduces Signs and Symptoms of Exercise-Induced Muscle Damage in Man". International Journal of Sport Nutrition and Exercise Metabolism. 15 (4): 413–424. doi:10.1123/ijsnem.15.4.413. PMID16286672.
^ abZanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH (April 2011). "HMB supplementation: clinical and athletic performance-related effects and mechanisms of action". Amino Acids. 40 (4): 1015–1025. doi:10.1007/s00726-010-0678-0. PMID20607321. S2CID11120110. HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).
^ abKohlmeier M (May 2015). "Leucine". Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.). Academic Press. pp. 385–388. ISBN978-0-12-387784-0. Retrieved 6 June 2016. Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds Figure 8.57: Metabolism of L-leucine
