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KIC

Also known as: KIC, alpha-ketoisocaproate, Alpha-ketoisocaproic acid

Overview

Alpha-ketoisocaproic acid (KIC) is a keto acid and a natural metabolite of the branched-chain amino acid leucine, produced during its catabolism in the body. It is also available as an exogenous nutritional supplement ingredient. KIC is primarily investigated for its potential role in enhancing exercise performance, reducing muscle damage, and promoting recovery, particularly in athletes and bodybuilders. As a metabolic intermediate, KIC may influence protein synthesis and energy metabolism during physical activity. While it is related to muscle metabolism, the research supporting its efficacy is considered moderate, with some randomized controlled trials available, but a scarcity of comprehensive systematic reviews or meta-analyses specifically on KIC. The quality of current evidence is limited, with few high-quality studies and no robust findings demonstrating significant benefits.

Benefits

Current scientific evidence does not strongly support significant benefits of Alpha-ketoisocaproic acid (KIC) supplementation for exercise performance or muscle recovery. A 2007 randomized, double-blind, placebo-controlled crossover study found no significant ergogenic benefit of short-term KIC supplementation on moderate- or high-intensity exercise performance. Unlike its metabolite HMB (beta-hydroxy-beta-methylbutyrate), which has more robust evidence for reducing muscle damage and inflammation, KIC itself lacks strong evidence for significant performance or recovery benefits. No clear evidence supports benefits in specific populations such as athletes or the elderly, and effect sizes or clinical significance have not been established due to the lack of significant findings. Acute supplementation has been studied, but no long-term benefits have been demonstrated.

How it works

Alpha-ketoisocaproic acid (KIC) functions as an intermediate in the catabolism of the branched-chain amino acid leucine. Its proposed mechanism of action involves influencing muscle protein metabolism and energy pathways. While KIC may modulate muscle energy metabolism and protein turnover, its direct effects and specific molecular targets are not well characterized, with its influence likely being indirect via its role in leucine metabolism. When taken orally, KIC is readily absorbed, with serum concentrations increasing by 150-300% within 45 minutes, indicating good bioavailability. However, the precise biological pathways through which KIC exerts any beneficial effects, if any, remain largely undefined.

Side effects

Alpha-ketoisocaproic acid (KIC) is generally considered safe at studied oral doses ranging from 1.5 g to 9 g. Controlled trials have reported no significant adverse effects, and there is no data indicating uncommon or rare serious adverse events. No specific drug interactions have been well studied, and there are no established contraindications for KIC supplementation. Information regarding its safety in special populations, such as pregnant or breastfeeding individuals, children, or those with pre-existing medical conditions, is insufficient. While acute doses up to 9 g have not shown toxicity, comprehensive long-term safety data is limited, and caution is advised until more extensive research is available.

Dosage

Due to the lack of demonstrated efficacy, a minimum effective dose for Alpha-ketoisocaproic acid (KIC) has not been established. Studied oral doses have ranged from 1.5 g to 9 g, typically administered prior to exercise. The maximum safe dose observed in studies is 9 g acutely, with no reported toxicity at this level. For optimal absorption and to achieve peak serum levels, KIC supplementation is generally recommended 25 to 45 minutes before exercise. Studies have primarily utilized KIC in oral capsule form. While peak serum levels are reached within 45 minutes, the impact of co-ingestion with other nutrients on KIC absorption has not been well studied, and no specific cofactors are identified as required for its action.

FAQs

Is KIC effective for muscle building or performance?

Current evidence does not support significant benefits from KIC supplementation alone for muscle building or exercise performance.

Is KIC safer than other leucine metabolites like HMB?

KIC's safety profile appears comparable to HMB, but HMB has more robust evidence supporting its efficacy for muscle benefits.

Can KIC be combined with other supplements?

There is no specific data on combining KIC with other supplements; caution is advised due to limited research.

How quickly does KIC work?

Oral KIC reaches peak serum levels within approximately 45 minutes after ingestion.

Research Sources

https://pmc.ncbi.nlm.nih.gov/articles/PMC2042499/ – This randomized, double-blind, placebo-controlled crossover trial investigated acute KIC supplementation (1.5 g and 9 g) in resistance-trained subjects. The study found no significant improvement in moderate or high-intensity exercise performance, indicating a lack of ergogenic benefit from KIC.
https://pmc.ncbi.nlm.nih.gov/articles/PMC6210682/ – This review on leucine metabolites highlighted that HMB, a related compound, possesses more consistent evidence for its role in muscle recovery and anti-inflammatory effects. It implicitly contrasts HMB's robust evidence with the less clear role of KIC in these areas.
https://onlinelibrary.wiley.com/doi/10.1002/fsn3.2887 – This source, likely a systematic review or meta-analysis on HMB, demonstrates significant benefits of HMB on hormonal responses and muscle recovery. It serves to underscore the difference in the quality and strength of evidence between HMB and KIC, with HMB having clearer clinical support.