Leucic Acid

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. ^[1] The same enzyme that mediates conversion of leucine to KIC ^[2] is also required for conversion into HICA, as HICA is a reduction production of KIC via the Hydroxyisocaproic acid dehydrogenase enzyme. ^[3] 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. ^[4]

HICA is thought to be relevant since it can exert anti-catabolic effects at physiological concentrations while KIC cannot, ^[5] KIC requiring an infusion. ^[6] 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 ^[7] ) and it is not bound to plasma proteins such as albumin. ^[7] It is detectable in urine ^[8] and other biological fluid as well. ^{[9] [10]}

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:

• Wine and Sake^[11]

• Cheese^[12]

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. ^{[3] [13]}

Some foods have a quite minor HICA content, which is likely related to fermentation or bacteria

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).^[14] 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.^[14]

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).^[14]

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

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). ^[4]

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