"Research is what I'm doing when I don't know what I'm doing." —Wernher Von Braun

(1912-1977)

Victor Martinez’s awesome physique is a product of excellent genetics, long-term

training, sound nutrition and a committed attitude. Clearly, these factors can’t be replaced by the

use of sports supplements. However, scientific study has identified a number of products offering

true benefits to performance (e.g., creatine) or the achievement of nutritional goals (e.g., meal

replacement products). Nevertheless, I must emphasize the point that supplements should be

used as an adjunct to an otherwise balanced nutritional plan, not as a substitute.

Even when a supplement doesn’t produce a true physiological effect, a person may attain

some benefit because of a psychological boost or placebo effect. The placebo effect describes a

favorable outcome arising simply from an individual’s belief that he/she has received a beneficial

treatment. That’s why MD´s "Supplement Performance" column provides only scientific

information on dietary supplements based on placebo-controlled studies published in the leading

peer-reviewed scientific journals. I’m not interested in anecdotal stories or opinions of selfproclaimed

supplement "gurus."

With that said, this article examines some science behind alpha-ketoisocaproic acid

(KIC), an anti-catabolic agent targeted to serious athletes. MD Publisher and Editor-in-Chief

Steve Blechman launched the first commercial KIC-containing product (Twinlab KIC Fuel) a long

time ago. However, it never became a very popular item. I think the reason was the high

production cost and thus, relatively high retail price. It’s also likely that most consumers using KIC

didn’t take in a sufficient daily dose to achieve optimal results. Recently, some supplement

companies have launched their own KIC-containing formulations and it seems to me that these

days, the production cost is much more reasonable.

KIC is a keto acid of leucine (an important branched-chain amino acid controlling muscle

protein metabolism). Branched-chain keto acids (BCKAs) are very similar to branched-chain

amino acids (BCAAs). In fact, the only difference is the presence of a keto group instead of an

amino group. Thus, BCKAs can be viewed as ammonia-free sources of BCAAs. KIC is clearly the

most important BCKA and some feel there’s every reason to believe that KIC will prove to be of

value to serious athletes, including bodybuilders.

Although leucine can be converted to KIC (transamination) and both tend to increase

parallel in the blood when leucine is used, there’s evidence that it has anti-catabolic (proteinsparing)

properties separate from leucine. A 1984 rat study, published in Biochemical Journal,

reported that leucine stimulated protein synthesis, but didn’t reduce protein degradation when

leucine transamination was inhibited. So, the anti-catabolic effects of leucine, in contrast to its

anabolic effects, required its transamination.

This study appears to confirm the results obtained from an earlier study that concluded

KIC has anti-catabolic, but not anabolic, effects. That is, KIC reduced muscle protein degradation,

but didn’t stimulate protein synthesis. Also, supplements containing KIC in relatively high doses

have been shown to decrease the rate of 3-methylhistidine excretion by patients with Duchenne´s

muscular dystrophy. Scientists use 3-methylhistidine as an indicator of contractile muscle

degradation.

A recent study at Kingston University (UK) examined the effects of KIC and betahydroxyl-

beta-methylbutyrate (HMB) supplementation on signs and symptoms of exerciseinduced

muscle damage following a single bout of eccentrically biased resistance exercise. Six

non-resistance trained male subjects performed an exercise protocol designed to induce muscle

damage on two separate occasions. The investigators gave them 3 grams of KIC and 3 grams of

HMB or placebo (fake supplement) for 14 days prior to exercise. The results indicated that HMB

KIC supplementation reduced signs and symptoms of exercise-induced muscle damage. Whether

HMB KIC has similar effects in experienced weight trainers remains to be determined.

KIC is essential for energy production in muscle and for the detoxification (removal) of

ammonia. During high-intensity exercise, such as resistance training, ammonia is produced in

large quantities, which may play a role in muscle fatigue. However, there are no published studies

examining the effects of KIC supplementation on athletic performance. On the other hand, there’s

recent evidence suggesting that glycine-arginine-alpha-ketoisocaproic acid (GAKIC) has antifatigue

properties.

Also, KIC may increase "anabolic drive" via stimulation of insulin secretion. Both leucine

and KIC have been shown to stimulate insulin secretion. Insulin increases transport of amino

acids into the cells and thus, has both anabolic and anti-catabolic effects.

There’s convincing evidence that KIC has anti-catabolic (protein-sparing) properties, but

doesn’t appear to have direct anabolic effects. Nevertheless, KIC may increase anabolic drive via

insulin. On the other hand, it’s now well established that leucine stimulates muscle protein

synthesis. Thus, it might be a good idea to combine KIC with leucine: KIC (anti-catabolic)

leucine (anabolic) = dynamic duo? Only time will tell.

The author of this article has no financial relationship with supplement companies selling

KIC and/or leucine.