By: Anssi Manninen

Reprinted with permission from Muscular Development.

We sense fatigue when we have exercised to the point when we feel the task requires greater effort than it should. Fortunately, certain sports supplements have anti-fatigue properties. For example, it's as clear as a bottle of Finlandia Vodka® that muscle creatine phosphate depletion leads to fatigue ^1,2 and creatine supplementation can increase creatine phosphate concentration.³

Consequently, creatine supplementation improves maximal power/strength, work performed during sets of maximal effort muscle contractions, single-effort sprint performance, and work performed during repetitive sprint performance.³

The latest anti-fatigue supplement appears to be a glycine-arginine-alpha-ketoisocaproic acid (GAKIC). Actually, the first study examining the effects of GAKIC supplementation on exercise performance was published in 2000. Although this study was extremely well-controlled and published in the prestigious Medicine & Science in Sports & Exercise, ⁴ it never made any headlines.

I do remember reading this article back in 2000 and found it very interesting, but I didn´t recall it until yesterday when Boss Blechman called and mentioned that there is a another GAKIC study in the latest issue of that same journal.

What The Heck Is GAKIC, Anyway?

GAKIC is a glycine and arginine monohydrochloride salt of alpha ketoisocaproic acid calcium.

Alpha-ketoisocaproate (KIC):

Alpha-ketoisocaproate (KIC) is a keto acid of leucine (branched chain amino acid). Branched-chain keto acids (BCKAs) are very similar to branched-chain amino acids (BCAAs), the only difference being the presence of a keto group instead of an amino group. Thus, BCKAs can be viewed as ammonia-free sources of BCAAs.

KIC is anti-catabolic, particularly during catabolic states. ⁶ Since any intense, strenuous activity is also catabolic, some feel there is every reason to believe the KIC will prove to be of value to bodybuilders, powerlifters and aerobic athletes. ⁶ Further, BCKAs are essential for energy production in muscle and for the detoxification (removal) of ammonia. During an intense exercise of high intensity, such as resistance exercise, ammonia is produced in large quantities and it has been suggested to play a role in fatigue. ⁶ Finally, KIC stimulates insulin secretion.

KIC is metabolised further to alpha-amino-n-butyrate and beta-hydroxy-beta-methylbutyrate (HMB), a compound popularized by Bill Philips. Although HMB certainly does not feel like Deca, a recent meta-analysis (quantitative statistical analysis that's applied to separate, but similar, experiments) found that HMB supplementation led to a net increase in lean body mass (0.28 percent per week) and strength gains (1.4 percent per week), but the effect of these changes was less than 0.2; such a change is considered small. ⁹ To my knowledge, alpha-amino-n-butyrate has not as yet been investigated in humans for its anabolic and anti-catabolic properties, but it may have some anabolic and/or anti-catabolic effects.

Glycine:

Glycine is a non-essential amino acid. It has been shown to increase growth hormone secretion in a dose-dependent manner. For example, Dr. Kasai and co-workers reported that oral administration of 6.75 grams of glycine to 19 human subjects increased growth hormone levels significantly for three hours, peaking at three to four times baseline at two hours. ⁷

Further, glycine plays a role as an excitatory neurotransmitter. A neurotransmitter is a chemical contained in synaptic vesicles in nerve endings that is released into the synaptic cleft, where it causes the production of either excitatory or inhibitory postsynaptic potentials.

Finally, glycine used with arginine has been shown to increase endogenous (SEL) creatine levels by increasing creatine synthesis. ⁶ A number of studies using glycine for the alleviation of fatigue were done in the 1930s and 1940s, but the results were minimal. ⁸

Arginine:

Arginine, normally a nonessential amino acid in humans, is considered essential under certain conditions. Arginine has a significant role in nitrogen detoxification and has been shown to be beneficial in various diseases including liver and other diseases in which ammonia levels are extremely high. ⁶ As noted above, ammonia has been suggested to play a role in fatigue.

Learn more about Arginine, click here.

GAKIC Patent

According to the U.S. Patent Number 6,100,287 ("Materials and methods for enhancing muscle performance and recovery from fatigue),

1. GAKIC treatment increases the ability to sustain athletic muscle force during intense anaerobic muscle exercise;

2. GAKIC treatment increases the ability to sustain athletic muscle work during intense anaerobic muscle exercise; and

3. GAKIC increases the overall muscle performance by decreasing muscle absolute fatigue while retarding the rate of muscle fatigue.

Learn about the background of the invention and view the patent here.

GAKIC Studies

The purpose of the first GAKIC study by Dr. Bruce Stevens and colleagues at the University of Florida was to quantify the effects of GAKIC supplementation on human muscle dynamic performance (strength, work, fatigue) measured under conditions of acute, exhaustive, high-intensity, anaerobic isokinetic exercise. ⁴

Subjects (13 healthy men) were orally administered 355-mL low calorie cranberry juice containing either 11.20 grams of freshly dissolved powdered GAKIC, or 9.46 grams of sugar isocaloric control. This was consumed in three equal aliquots (parts of a whole) over 45 minutes.

The results demonstrated that GAKIC supplementation significantly improved performance compared to control isocaloric sugar treatment. The authors summarized the salient findings as follows:

1. GAKIC increased the ability to sustain muscle force (concentric torque) up to at least 28 percent during intense acute anaerobic muscle exercise;

2. GAKIC increased the ability to sustain muscle total work by up to at least 12 percent during intense anaerobic muscle exercise; and

3. GAKIC increased the overall muscle performance by delaying muscle fatigue during the early phases of anaerobic exercise through at least 15 minutes.

The purpose of the second GAKIC study by Drs. Britni Buford and Alexander Koch at Truman State University was to determine the effects of GAKIC supplementation on repeated bouts of anaerobic cycling performance. ⁵

Again, subjects (10 healthy men) consumed the treatment beverage (GAKIC or sugar) in three equal aliquots over a 45-minute period (The dosing regimen employed was identical to the first study by Dr. Stevens and co-workers). The results of this second study indicated that GAKIC supplementation significantly attenuates the drop in mean power output associated with repeated sprints of anaerobic cycling.

Bottom Line

According to Drs. Buford and Koch, "These findings reinforce the notion that GAKIC supplementation may be a useful aid for strength-power athletes, similar to creatine supplementation.

Unlike creatine, which requires approximately five days of loading to produce improvements in high-intensity work, GAKIC appears to impart an ergogenic effect within minutes of consumption." However, more research is needed before firm conclusions can be drawn.

About The Author

Anssi Manninen, M.H.S., is a well-published research scientist in the sports nutrition field. He holds an M.H.S. in sports medicine from the University of Kuopio Medical School. His current position is Senior Science Editor at Advanced Research Press, a publisher of Muscular Development, FitnessRx for Men, and FitnessRx for Women. Anssi is also an Associate Editor for Nutrition & Metabolism, a BioMed Central publication.

References

1. Brook GA, Fahey TD, White TP, Baldwin KM (2000) Fatigue during muscular exercise. In: Human Bioenergetics and Its Applications. New York: McGraw-Hill, pp. 800-822.
2. Greenhaff PL, Casey A, Constantin-Teodosiu D, Tzintzas K (1999) Energy metabolism of skeletal muscle fiber types and the metabolic basis of fatigue in humans. In: Hargreaves M, Thompson M, eds. Biochemistry of Exercise X. Champaign, IL: Human Kinetics, pp. 275-287.
3. Kreider RB (2003) Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem, 244:89-94.
4. Stevens BR, Godfrey MD, Kaminski TW, Braith RW (2000) High-intensity dynamic human muscle performance enhanced by a metabolic intervention. Med Sci Sports Exerc, 32:2102-2108.
5. Buford BN, Koch AJ (2004) Glycine-arginine- -ketoisocaproic acid improves performance of repeated cycling sprints. Med Sci Sports Exerc, 36:583-587.
6. Di Pasquale MG (1997) Amino Acids and Proteins for the Athlete: The Anabolic Edge. Boca Raton, FL: CRC Press.
7. Kasai K, Kobayashi M, Shimoda S (1978) Stimulatory effect of glycine on human growth hormone secretion. Metabolism, 27:201-204.
8. Bucci LR (1993) Nutrients as Ergogenic Aids in Sports and Exercise. Boca Raton, FL: CRC Press.
9. Nissen SL, Sharp RL (2003) Effect of dietary supplements on lean mass and strength gains with resistance exercise: a meta-analysis. J Appl Physiol, 94:651-659.

anssi.manninen@gmail.com

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