True or False: α-Hydroxy-Isocaproic Acid aka HICA is a Potent Anti-Catabolic, Just Like the Shiny Ads Say

Even Arnold benefited from α-hydroxy-isocaproic acid aka HICA - the HICA his body produced and the HICA he got from his diet, whenever he ate cheese and other fermented foods.

You know that I am not the kind of person who likes to tell others what to do. After reading my summary of the contemporary research on α-hydroxy-isocaproic acid aka HICA, you should yet be able to decide whether it's worth a try or not.

If you take a look at the pertinent databases you will realize that there are more patents than papers on α-hydroxy-isocaproic acid - usually, this is a good indicator we are dealing with another industry scam, but in contrast to the many funky forms of creatine, α-hydroxy-isocaproic acid does actually have a handful of studies to back up that it does... or I should say "that it could" help you getting big and buffed.

If I had to chose between HMB and HICA, I would choose HMB... or better stick to whey!

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That being said, it may be worth taking a look at what α-hydroxy-isocaproic acid actually is. Just like HMB which is about to make a comeback in liquid form, these days, HICA is a metabolite of the mTOR and thus protein synthesis triggering branch-chained amino acid leucine. It is also known as "leucic acid" or "DL-2-hydroxy-4-methylvaleric acid" and is formed by α-hydroxylaction from leucine. It's one of the end-products of leucine metabolism in muscle and connective tissue (Walser. 1978). It's usual concentration in our blood is about 0.2560.02 mmol/L - that's ~100x less than the amount of α-keto-isocaproic acid (KIC), the corresponding keto acid of leucine of which you'll find more than 21 mmol per liter in your blood.

Figure 1: Relative changes in lean mass (%) during 4 weeks of intense soccer training on 1.5g/day HICA (Mero. 2010)

Cheese, wine, soy sauce, etc. - the recently celebrated fermented foods, they all contain HICA, which appears to be the anti-catabolic counterpart to leucine. While the latter is a potent promoter of protein synthesis, the former appears to make sure that the work of its predecessor leucine is not lost.

It is thus no wonder that the promising results of a 2010 study by Mero et al. were recorded during an intensive and thus potentially catabolic training period in soccer athletes. In contrast to the placebo group, where only one individual gained a significant amount of lean mass, while 4 lost muscle, the subjects who had been consuming 1.5g/day of α-hydroxy-isocaproic acid gained 300g of lean mass, on average, in the course of the 4-week study.

That's not much and it was not fat free (ca. 150g of fat), but the data in Figure 1 shows that this is a difference between minimal muscle loss and gain... and I guess most athletes would prefer a marginal muscle gain over a marginal loss of lean mass.

HICA, a potent anti-catabolic? I don't think so!

The notion that HICA is, above all, a muscle loss inhibitor appears questionable, if we take a look at the results Charles H. Lang, Hugues Magne, Elizabeth Offord and Denis Breuille presented at a 2013 FASEB meeting. In the abstract to their presentation they cite the results of a rodent study in the course of which the rodents were immobilized for two full weeks. The consequence, an increase in the expression of catabolic hormones and a profound loss of muscle mass was identical in both the HICA and placebo supplemented groups, but in spite of the fact that "αHICA did not alter the immobilization-induced increase in proteasome activity and atrogene expression", the muscle mass had returned to control values only in αHICA-fed rats after 14 days.

No performance enhancing effects: In spite of the increase in muscle size (or should I say absence of a decrease?) Mero et al. didn't record any performance enhancing effects of HICA in their study w/ professional soccer players. Minimal muscle gain, yes. Reduced DOMS, yes, even that. Increased performance? No. As the authors point out, the study period (4 weeks) may have been to short. That's correct, but if you take another look at the data in Figure 1 you would still expect to see marginal differences, at least, right?

The fast recovery in the HICA group was associated with increased muscle protein synthesis and higher levels of the "protein synthesis pump initiator proteins" S6K1 and 4EBP1 in the previously immobilized muscle. The results Lang et. al. have not yet published in a full paper (at least I couldn't find it) put a huge questionmark behind the long-heralded hypothesis that HICA supplementation would slow muscle loss and puts it in line with its cousin HMB and its precursor leucine as a purported pro-anabolic muscle builder.

Figure 2: Gastrocnemius weight (rel. to control) immediately before and 14-days after the immobilization (Lang. 2013).

The data from the corresponding full paper the authors published a couple of month later in the American Journal of Physiology - Endocrinology and Metabolism you see in Figure 2 are even more impressive, though. According to this rodent data HICA is a more potent muscle (re-)builder than leucine; and, importantly, neither of the two does what the industry keeps promising: prevent muscle catabolism in response to disuse.

Bottom line: A confirmation of Lang's results in humans and/or a resistance training scenario like the one Wilson et al. did for the free acid form of HMB recently ("Breakthrough HMB Research: Additional(!) 10% Reduction in Body Fat, 5% Higher Lean Mass + 2x Higher Strength Gains After 12W of Heavy Lifting in Trained Individuals" | read more) are yet still missing. Aside from the previously cited soccer player study by Mero et al. we do have...

• a paper by Chow & Walser (1975) who report that leucine and its α-hydroxy analog (HICA) promote muscle growth equally effective, although replacement of leucine with HICA reduced food intake and increased the volume of urine and its nitrogen concentration
• a study by Woods & Goldman (1979) who report that HICA can be used as a leucine replacement in the diet without reducing food intake or growth of the animals

...and thus not enough arguments for me to spend money on currently hilariously overpriced α-hydroxy-isocaproic acid, but I am running a non-profit blog, so if you are making big money with a website or whatever else and want to give it a try - there is no evidence that HICA may harm anything but your purse.

Reference:

• Chow K., and Walser M. "Effects of substitution of methionine, leucine, phenylalanine, or valine by their alpha-hydroxy analogs in the diet of rats." J Nutr 1975;105(3):372 8
• Lang, Charles H., et al. "Chronic α-hydroxyisocaproic acid treatment improves muscle recovery after immobilization-induced atrophy." American Journal of Physiology-Endocrinology and Metabolism 305.3 (2013): E416-E428.
• Mero, Antti A., et al. "Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance in athletes." Journal of the International Society of Sports Nutrition 7.1 (2010): 1.
• Walser, Mackenzie. "Therapeutic compositions comprising alpha-hydroxy analogs of essential amino acids and their administration to humans for promotion of protein synthesis and suppression of urea formation." U.S. Patent No. 4,100,160. 11 Jul. 1978.
• Woods M., and Goldman P. "Replacement of L-Phenylalanine and Leucine by a-Hydroxy analogues in the diets of germ-free rats." J Nutr 1979;709:738 43.