Summary of Leucic Acid
Primary Information, Benefits, Effects, and Important Facts
Leucic acid (synonymous with the term α-hydroxyisocaproic acid and the latter's acronym HICA) is a metabolite of the branched chain amino acid known as leucine; leucine initially goes into one of two metabolic pathways (KIC or HMB) and then some of the KIC is further converted into HICA.
HICA is claimed to be an anti-catabolic and anabolic agent similar to HMB. The limited evidence that exists right now (literally one study in athletes and a mention of a pilot study conducted by the same researchers) suggests that there is benefit, but beyond needing replication this study is also confounded.
Although it would be imprudent to say that HICA is ineffective (which it does not appear to be) and similarly imprudent to say that it is worse than HMB or leucine, due to the lack of comparative data between HICA and HMB/leucine the question of 'which one to use' cannot be answered and we have no indication if HICA is better or worse than the other options.
HICA holds some promise for future research to tackle, but currently does not have enough evidence to support its usage as a supplement; it may simply be a more expensive and equally effective leucine.
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Also Known As
Alpha-Hydroxy-isocaproic acid, DL-alpha-Hydroxy-isocaproic acid, HICA
Do Not Confuse With
Leucine (parent amino acid), HMB (other metabolite)
How to Take
Recommended dosage, active amounts, other details
The only human evidence currently uses a daily dose of 1,500mg HICA, split into three divided doses of 500mg. There is not enough evidence to suggest if this is the optimal dose nor is there evidence to assess the comparative potency of HICA against leucine or HMB supplementation.
Editors' Thoughts on Leucic Acid
It is wholly possible that Leucic acid supplementation could be better than leucine supplementation (circumventing KIC might change the bioactivities around a bit) but this is currently not proven.
Future research will be more promising, but probably when investigating how leucic acid interacts with the BCKDH enzyme complex (KIC induces it to increase BCAA oxidation, and if this trait is not common to leucic acid then it would result in more anabolism)
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects leucic acid has on your body, and how strong these effects are.
||Level of Evidence
||Robust research conducted with repeated double-blind clinical trials
||Multiple studies where at least two are double-blind and placebo controlled
||Single double-blind study or multiple cohort studies
||Uncontrolled or observational studies only
Table of Contents:
Sources and Structure
Skeletal Muscle and Performance
Inflammation and Immunology
Leucic acid (synonyms of DL-α-hydroxy-isocaproic acid (HICA) and DL-2-hydroxy-4-methylvaleric acid), commonly referred to as its acronym HICA, is a leucine metabolite.
Parent leucine is known to be degraded into its primary metabolite which is the keto acid ketoisocaproic acid (called KIC or KICA) and the keto acid tends to exist in equilibrium with leucine. The same enzyme that mediates conversion of leucine to KIC is also required for conversion into HICA, as HICA is a reduction production of KIC via the Hydroxyisocaproic acid dehydrogenase enzyme. Anything that possesses the Hydroxyisocaproic acid dehydrogenase enzyme can produce HICA, and this seems to be humans (mostly in the liver) and select bacteria of the lactobacillus family.
HICA is thought to be relevant since it can exert anti-catabolic effects at physiological concentrations while KIC cannot, KIC requiring an infusion. This suggests that the hydroxy leucine metabolites may be more potent than the keto acid metabolites.
HICA is a minor leucine metabolite that possesses anticatabolic properties. It is produced from the major leucine metabolite (KIC) but in smaller amounts
HICA is found circulating in the blood naturally (at around 0.25+/-0.02mmol/L, which is approximately 1% that of KIC at 21.6+/-2.1mmol/L) and it is not bound to plasma proteins such as albumin. It is detectable in urine and other biological fluid as well.
The primary keto metabolite of leucine, KIC, is approximatley 100-fold more prominent in serum relative to the hydroxy metabolite HICA
Some foods appear to be naturally occurring sources of HICA, including:
Food sources are likely due to either fermentation (wine and sake) or bacterial incubation (cheeses) using lactic acid producing bacteria such as Lactobacillus plantarum or lactobacillus casei to promote conversion.
Some foods have a quite minor HICA content, which is likely related to fermentation or bacteria
2Skeletal Muscle and Performance
583mg of a sodium salt of HICA (500mg HICA equivalent) thrice daily (1,500mg total) for 4 weeks in trained soccer athletes undergoing routine exercise protocols noted that while there were no differences in fat mass the HICA group experienced an increase in lean mass (0.4kg in lower limbs; no change in upper body) while placebo experiencing a small decrease (0.15kg in lower limbs). This study had a dietary calorie and protein intake of 2,672+/-564kcal and 119+/-37g, respectively, and the authors made mention of a pilot study in wrestlers where 6 weeks of a similar dose failed to promote lean mass accrual.
A reduction in soreness (DOMS) has been reported with 1,500mg HICA daily in soccer players after 4 weeks by 23% (and stated to have occurred in a pilot study by the same authors when testing in wrestlers), and subjective training alertness appeared to be somewhat improved (significantly higher at week two, trending higher otherwise).
Appears to be somewhat effective at reducing muscular soreness and perhaps increasing lean mass, but overall has a low amount of evidence (possibly confounded as the researchers also hold patents) and there are no comparative studies of HICA against leucine or HMB
3Inflammation and Immunology
HICA appears to have anti-bacterial properties in vitro that are fairly broad, having an IC50 of less than 4.5mg/mL on 16 bacterial strains (excluding Lactobacillus rhamnosus at 9mg/mL).
Preliminary evidence that HICA could be antibacterial in the strains of bacteria that do not otherwise produce HICA (due to lacking the Hydroxyisocaproic acid dehydrogenase enzyme), although it is too preliminary to suggest what supplementation of HICA could do
Scientific Support & Reference Citations
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Regulation of valine metabolism in man: a stable isotope study.
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BLANCHARD M, GREEN DE, et al.
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Broadbent JR, et al.
Overexpression of Lactobacillus casei D-hydroxyisocaproic acid dehydrogenase in cheddar cheese.
Appl Environ Microbiol. (2004)
Sakko M, et al.
2-Hydroxyisocaproic acid (HICA): a new potential topical antibacterial agent.
Int J Antimicrob Agents. (2012)
Mortimore GE, et al.
Multiphasic control of hepatic protein degradation by regulatory amino acids. General features and hormonal modulation.
J Biol Chem. (1987)
Tischler ME, Desautels M, Goldberg AL.
Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle.
J Biol Chem. (1982)
Hoffer LJ, et al.
Alpha-keto and alpha-hydroxy branched-chain acid interrelationships in normal humans.
J Nutr. (1993)
Lancaster G, Mamer OA, Scriver CR.
Branched-chain alpha-keto acids isolated as oxime derivatives: relationship to the corresponding hydroxy acids and amino acids in maple syrup urine disease.
Jakobs C, Sweetman L, Nyhan WL.
Hydroxy acid metabolites of branched-chain amino acids in amniotic fluid.
Clin Chim Acta. (1984)
Mamer OA, Laschic NS, Scriver CR.
Stable isotope dilution assay for branched chain alpha-hydroxy-and alpha-ketoacids: serum concentrations for normal children.
Biomed Environ Mass Spectrom. (1986)
Some Volatile Components of Vitis Vinifera Variety White Riesling. 2. Organic Acids Extracted from Wine.
PROCESS FOR ENHANCING A FRESH CHEESE FLAVOR IN FOODS.
Lerch HP, et al.
Cloning, sequencing and expression in Escherichia coli of the D-2-hydroxyisocaproate dehydrogenase gene of Lactobacillus casei.
Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes.