More Endurance, Greater Strength Gains, Less Exhaustion: Alpha-Keto Acids (KIC, AKG...) - Overlooked Ergogenics?

This is a scenario, where the results of the study at hand would apply - if that's you, go ahead get yourself some BCKAs; if it's not read at least the bottomline before you spend your money on the "latest", but not necessarily "greatest" ergogenic
As a seasoned SuppVersity veteran, you will be aware that the number of supplements that work is pretty small. The number of supplements that will actually make a difference that's not just statistically significant can probably even be counted on the fingers of one hand and arginine-alpha-ketoglutarate, aka AAKG, the purported nitric oxide booster is certainly not one of them and that despite the fact that there are one or two studies, which showed minuscule performance improvement from large doses of this combination of arginine and the alpha-keto acid to glutamine alpha-ketoglutarate. Against that background it is however even more intriguing that a group of scientists from the Section of Sports and Rehabilitation Medicine, Department of Internal Medicine II at the University of Ulm in Germany and a colleague from China report in a soon to be published paper in the Journal of the International Society of Sport Nutrition (JISSSN)that AKG, as in "AAKG minus arginine", and even more so its cousins KIC, KIV and KMV, the alpha-keto acids to the BCAA (thus BCKAs) are pretty potent ergogenics.

From sick people to sedentary people

Based on physiological considerations, as well as previous research that has unfortunately mostly been conducted with sick participants, Liu et al. hypothesizes that the provision of spplemental keta-acids (KAS) would be able to improve exercise tolerance, training effect, and stress-recovery in healthy subjects, as well. In order to validate this hypotheses, the researchers recruited 36 untrained male volunteers and assigned them randomly to one of the three study arms. Depending on which of the arms the subjects belonged to, they had to ingest one of the following visually identical supplement mixes
  • AKG - 0.2 g/kg body weight AKG in the form of Na-AKG and Ca-AKG
  • BCKA - 0.2 g/kg b.w. α-ketoisocaproate, KIC, 47.4%; α-ketoisovalerate, KIV, 30.0% and α-ketomethylvalerate, KMV, 22.6% from Na-KIC, Ca-KIV and Ca-KMV
  • Placebo - energy and sodium, as well as calcium equivalent with glucose, CaCO3, NaHCO3 
twice a day; either within two hours before and two hours after their 5 training session or between 4PM and 8PM on non-training days (note: the supplementation was not discontinued in the 5th recovery week either

Endurance + HIIT-like sprinting = temporary overtraining aka overreaching

Though the protocol was specifically designed to induce a state of temporary overtraining aka overreaching, I know people who are training like this for years - allegedly no beginners, although some of them look like that... and that's not 'cause they don't supplement with AKG or KIC ;-) That aside, I am still asking myself how you can possibly sprint "all out" for 3 minutes and would discourage you copy this "HIIT-esque" exercise protocol and stick to shorter (~30s) real all out sprints /w 90-120s rest in-between
The actual training intervention lasted for 4 weeks and consisted of a standardized workout program, of which Yuefei Liu and his colleagues write that it was specifically designed to "challenge energy metabolism by achieving an 'overreaching' [aka temporary overtraining] training level" (Liu. 2012). To make that possible, the 33 untrained subjects (BMI~24kg/m²; age 25-26y) who made it through the four week protocol (three dropped out) performed the two-part exercise regimen consisting of 
  • 30 minute treadmill running at the anaerobic threshold run followed by,
  • 3 x 3 minute sprints (all out; HR  ≥ 95% max)
five times a week under professional supervision. The training was carefully documented, training times recorded and rest-stress-questionnaire-sport (RESTQ; cf. Kellmann. 2001) questionnaires had to be filled at the end of every training week.

The diet was comparable among the different groups and did not change throughout the study period (total caloric intake: 2509 ± 115 kcal/day; 49.2% carbs, 30.3% fats; 17.1% protein and alcohol 3.4% *wtf!*) and no other supplements were allowed to make sure that the results would not be skewed by copious amounts of sodium bicarbonate ;-)
Note: Since KAS are meant to buffer ammonia build-up while sodium bicarbonate, aka baking soda will buffer blood pH (and inhibit the formation of lactic acid), they would stack well (click here to read more about baking soda and the latest study about the beneficial effects of baking soda on high volume leg days)!
Surprising results: Longer, harder, ...

Just as the researchers had assumed, the relatively small amounts supplemental α-keto acid  (KAS), of which the scientists expected that they would reduce the exercise induced hyperammonemia (=accumulation of ammonia, a breakdown product from the oxidation of amino acids in the blood) Banister and Wilkinson held (at least partly) responsible for the fatiguing effect of longer lasting high intensity exercise (Banister. 1990; Wilkinson. 2010).

Unfortunately, the scientists don't make it 100% clear what the "training time" they measured was, but I hope that you would agree that it is sensible to assume that this refers to the timespan during each workout at which the subjects actually reached the prescribed target heart rates, i.e. the anaerobic threshold for the endurance part and 95%+ of their individual HRmax for the sprints.
Figure 1: Effect of AKG and BCKA (KIC+KIV+KMV) supplementation on exercise performance (expressed relative to target time at the given HR) in the course of the 4-week overreaching phase (data based on Liu. 2012)
In order to make the data more legible and thus easier to understand I did therefore express the figures the scientists measured relative to the maximal time the participants could have been performing at the target heart rates, i.e. 5 x 30min (150min running)  and 5 x 3 x 3min (45 min sprinting) per week, in the endurance and sprint part of their five weekly sessions, respectively. Based on the plot of these calculations (figure 1), you can easily see that the provision of the keto acids of the BCAAs, i.e. KIC, KMV & KIV, the BCKAs, were more effective than the keto acid of glutamine (AKG) in buffering the cumulative performance decrements that occurred from week 1-4.

... less exhausting and more productive

Figure 2: Somatic and emotional RESTQ-sport scores (top, middle), as well as isokinetic peak force development (Liu. 2012)
These findings are corroborated by both, the results of the weekly RESTQ questionnaires, i.e.
  • the general stress levels were markedly increased in the control group during the third week, but did not change in BCKA group; a significantly higher baseline stress level in the AKG group make the data difficult to interpret, but it can still be assumed that the "stress-buffer effect" was similar to the BCKA group, as the levels remained constant over the whole 4 +1 week study period
  • the somatic complaints showed a slight increase in the control group, but were overall not statistically different between the groups (see figure 2, top)
  • the emotional exhaustion did increase significantly in both, the control and the AKG group, but it does not appear certain that the slight disadvantage the AKG group appears to have compared to the control group is more than statistically significant; after all, thebaseline general stress levels were also higher and could be a confounding factor here (see figure 2, middle)
as well as the performance increases in the isometric maximum torque and isokinetic maximum performance tests for the quadriceps femoris of the dominant leg, which yielded statistically significant...
  • increases in torque & isokinetic strength only in the AKG and BCKA groups and
The gains in endurance capacity, on the other hand, did not differ between the groups.

Remember: Ergogenics allow you to work harder - in other words, you got to do more, not less!

Overall the data does still support something people tend to overlook and supplement manufacturers and vendors like to disguise: Ergogenics don't build muscle, strength or make you run faster over night. Regardless of the exact mechanism by which those compounds work, it in the end always the increase in training intensity and/or volume (or your ability to increase the latter faster without running the risk of overtraining), which will eventually help you to make greater or faster progress - or as the subheading says: You got to work harder / more - not less!

That said, despite the fact that AKG, did perform astonishingly well (so well indeed that the occasional beneficial study result from arginine-alpha-ketoglutarate =AAKG studies could actually be a result of the AKG part of the purported NO booster), the alpha-keto acids of the three BCAAs appear to be the better supplement choice for beginners in overreaching phases... but wait! Let's be honest, is it really advisable for a beginner to employ an advanced training technique like overreaching? And wouldn't you advice him or her to strength train if strength (remember, the only exercise parameter with significant improvements, in the study at hand) was his / her goal? I would think so...
Bottom line: The study is nice, the results are impressive, but the study population (untrained individuals) and their diets (low protein, low fat variety of SAD diet + a beer every evening *hello?*) don't really allow for conclusions to be drawn as far as the effects of keto acids, i.e. the effects of both AKG, as well as the BCKAs, on trained athletes / seasoned gymrats with adequate protein intakes on reasonable training regimen is concerned. To cut a long story short, I would not go and buy any of those keto acids before we don't have at least a single independent, peer-reviewed study that would confirm their efficiacy in a group of trainees who are at least experienced recreational athletes. It would obviously be even better to see those trainees supplement with KAS on top of a protein shake, creatine and maybe BCAAs while they eat a protein rich, nutritionally balanced whole-foods diet (like you?), but let's be honest, I don't think we will see a study like that anytime soon, ... but in case we do, you know where you are going to read about the results first, right?

References
  • Banister EW, Cameron BJ:  Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med 1990, 11(Suppl 2):S129–S142. 
  • Kellmann M, Kallus KW. Recovery-Stress Questionnaire for Athletes. Human Kinetics. 2001 ISBN-13: 9780736037761  
  • Liu Y, Lange R, Langanky J, Hamma T, Yang B, Steinacker JM. Improved training tolerance by supplementation with alpha-Keto acids in untrained young adults: a randomized, double blind, placebo-controlled trial. J Int Soc Sports Nutr. 2012 Aug 2;9(1):37. 
  • Wilkinson DJ, Smeeton NJ, Watt PW: Ammonia metabolism, the brain and fatigue;
    revisiting the link. Prog Neurobiol 2010, 91:200–219. 
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