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2014 ISSN Conference Review - Part IIa

Quick Hit Summary

In Part IIa of our ISSN conference review we shift our focus to the presentations of Day 2. Specific ones highlighted include those presented by Shawn Wells MPH, RD, CISSN & Gabriel Wilson PhD (Leucine, HMB, And Amino Acid Metabolites Support Muscle Growth and Athletic Performance), Mike Roberts, PhD (Molecular Updates on the Effects of Phosphatidic Acid: Muscle Physiology and Beyond), and Brad Schoenfeld PhD, FNSCA (MAX Muscle: A Periodized Approach to Hypertrophy Training).

Part I Recap

Figure 1 ISSN logo. Image uses with permission.

Thanks for clicking in for Part IIa of our ISSN report. Hopefully you enjoyed Part I of our conference review. In case you missed it, a lot of great content was shared in it including…

  • Juan Carlos Santana, FNSCA – Weight Cutting Strategies for Elite MMA Fighters
  • Krista Varady, PhD – Alternate Day Fasting: Effects on Health & Body Composition
  • Darryn Willoughby, PhD – Ursolic Acid Supplementation
  • Mark Tarnopolsky, PhD – Creatine: Not Just for Sport
  • Steven Orris MS CSCS USAW CISSN – Strength Training and Sports Nutrition for the College Athletes

Alright. Enough reviewing of where we’ve been. Time to put on your game face, pop some nootropics and get ready for Part IIa of our review!

Shawn Wells MPH, RD, CISSN & Gabriel Wilson PhD – Leucine, HMB, And Amino Acid Metabolites Support Muscle Growth and Athletic Performance

Figure 2 . A partial look at the leucine family tree leading to α-Ketoisocaproate (KIC), α-hydroxy-isocaproic acid (HICA) & Beta-hydroxy-beta-methyl-butyrate (HMB). As shown above, 5% of leucine will eventually get converted to HMB and 1% gets converted to HICA. Image created by Sean Casey

Dr. Gabriel Wilson and Shawn Wells kicked off Day 2 of the 2014 ISSN conference with a presentation on leucine and its amino acid metabolites. As noted, leucine is the only amino acid that independently stimulates muscle protein synthesis. In order to maximally stimulate muscle protein synthesis, it appears that ~2-3g of Leucine is needed per meal (older individuals at the higher end of range). Furthermore, at least in an older population, it works in an “on-off” switch like fashion. In an interesting study completed by Katsanos et al, researchers had both younger and older individuals (~28-30 vs. ~66 years old) consume two different amino acid drinks (6.7g of essential amino acids) that differed only in leucine content (1.7 vs. 2.8g).2 In the younger population, the 1.7 g of leucine maximally stimulated muscle protein synthesis (MPS) with no further increase at 2.8g. In contrast, in the older population, only the 2.8g leucine drink led to significant increases in MPS.

Table 1 Amount of leucine in various protein sources. Information for egg, chicken and beef obtained from USDA Nutrient Database, whey and soy isolate from Norton et al.3, rice isolate from Joy et al.4, NOW Foods for Pea protein. Keep in mind that along with leucine content of protein sources, speed of absorption and accompanying amino acids play a role as well with respect to muscle anabolism.

Source g leucine/100g Protein Amt of protein needed for 2 g Leu (from source) Amt of protein needed for 3 g Leu (from source)
Whey Protein Isolate 10.9g ~19g ~28g
Whole Egg 8.6g 24g (4 large eggs) 35g (~5.5 large eggs)
Chicken (breast, raw) 8.2g 25g (~4 oz meat) 37g (~6 oz meat)
Beef (flank steak, raw, fat trimmed) 7.9g 26g (~4.3oz meat) 39g (~6.5 oz)
Pea Protein Powder 8.4g 24g 36g
Soy Protein Isolate 8g 25g 38g
Rice Protein Isolate 8g 25g 38g

The results of Katsanos et al.4 appear to parallel that observed by researchers at McMaster University who assessed MPS in response to various protein doses following a lower body resistance training protocol. In the first of their two studies, Moore et al. had 6 ‘young’ males (~ 22 years) complete 5 resistance training sessions (see sidebox); each followed by a different whole egg protein supplement (0, 5, 10, 20 or 40 g of protein/serving). Similar to Katsanos et al., Moore found that MPS incrementally increased before peaking at 20 g of egg protein (1.7g leucine). In a follow-up study involving an older population (~71 years old) Yang et al found that 10 g of whey protein failed to stimulate MPS following a resistance training session vs. no protein. Additionally, although 20g of whey (2.18g Leu) did enhance anabolism, it was significantly greater following a 40 g dose (4.36g Leu). Interestingly enough, at rest (ie – no exercise) , MPS peaked at 20g of whey in this population.

Dr. Wilson’s & Mr. Wells discussion then shifted to leucine's metabolic kid, KIC, as well as its metabolic grandkids HMB and HICA. With respect to HMB, the conversation focused around the studies presented at last year’s ISSN conference which I covered in part II of last years review. You can refer to that for more discussion. One additional note, Dr. Wilson and Mr. Wells stressed that a progressive, high intensity program is required to see long term benefits with HMB. Moving on to the other members of Leucine's family tree…

α-Ketoisocaproate (KIC)

Figure 3. Volume load following 5 sets to failure on leg presses preceded by 10.2g GAKIC or Placebo. * indicates statistically significant vs. placebo. Data adapted from Wax et al.6 Image created by Sean Casey

α-Ketoisocaproate (KIC) has been studied under various acute conditions with the idea that it helps to fight fatigue (potentially by removing metabolic waste products such as ammonia, etc). Unfortunately, to the best of my knowledge, only acute studies have been done on this supplement. There is some evidence supporting it's use when combined with glycine and arginine (GAKIC), the latter of which also plays a role in ridding the body of ammonia as discussed in a previous CP article on arginine. For instance, in a randomized crossover designed trial, Wax et al had seven resistance trained Division 1 male football athletes (trying out for a school in the SEC), complete two different testing sessions (one week apart). Each trial involved a 1 rep max test (1RM) followed by 5 sets of leg presses to failure (75% 1RM; 3min rest b/w sets).6 The trials differed only by ingestion of 10.2g GAKIC or a placebo 40 minutes prior to testing. Total volume load (reps*load) was 23% greater when consuming GAKIC vs. placebo (see Figure 3); individual data showed that almost all individuals experienced these gains with the most significant changes occurring during the 2nd set. No changes were noted in 1RM. In a similarly designed study, also from Wax et al, analogous results were seen in "resistance trained" females – improvements in volume load (although responses varied… ~1/2 didn't see much of a change according to the graphical representation of individual data) without any improvement in 1RM.7

Wax's results somewhat parallels what Buford & Koch found when testing 'trained' participants (3+ days/wk… for unspecified duration) on repeated cycling sprints as well as what Stevens et al observed in untrained participants complete isokinetic knee extensions.89 Both of these trials used 11.2g of GAKIC. On the other hand, Beis et al. failed to find any benefit of 11.2g GAKIC on repeated bouts of cycling in trained men involving "10 sprints of 10 s separated by 50-s rest intervals" leading them to conclude, "little evidence to support the ergogenic effects of GAKIC during high-intensity exercise performance in well-trained subjects."10

I've only run across 1 study that used KIC in isolation. In their study, Yarrow et al had 13 resistance 'trained' men (3x/wk, >2 months) complete 4 trials – 1.5g KIC, 1.5g Placebo (sucrose), 9 g KIC, 9g Placebo – prior to a completing 50% 1RM to fatigue tests (chest and leg presses) along with a 30 second repeated vertical jump test.11 The research team failed to find any significant differences between trials, leading him to conclude that multiple sets (vs. a single set as done in their study) on an exercise may be needed to elicit the ergogenic benefits of KIC…. or KIC just doesn't have a significant effect on its own even with higher dosing. As with most things, more research needs to be done here.

Bottom line …. GAKIC may help to resist fatigue, allowing you to push longer and harder in your workout. However, unless your workouts involve repeated bouts of activity (ie – HIIT, etc) where metabolic fatigue becomes an issue, you probably won't see much of a benefit from either GAKIC or KIC. As for me, do the high cost on GAKIC supplements and mixed findings, I personally prefer the purported metabolic garbage collector, citrulline, as well as the acid buffer, sodium bicarbonate. (aka – baking soda).

α-hydroxy-isocaproic acid (HICA)

Well, at risk of being called lazy for not expounding on this myself, I'm going to refer you over to my buddy Adel Moussa's SuppVersity Post on HICA that he wrote over the summer. There's no point in me re-writing what Adel's already done!

Mike Roberts, PhD – Molecular Updates on the Effects of Phophatidic Acid

Figure 4. mTOR – Not a Simple Molecule. As shown, amino acids & growth factors attach to a different domain on the mTOR molecule then phosphatidic acid. Adapted from Mike Roberts.

One of the "darling" supplements of the 2013 ISSN Conference was Phophatidic Acid (PA). As discussed in last year’s conference write-up, PA is a molecule that gets released during muscular contractions, attaches to the mTOR molecule and stimulates protein synthesis. Data presented by Dr Jacob Wilson at last year’s convention showed that vs. a placebo, PA led to significant gains in lean body mass as well as tended to decrease fat mass. However, as I noted in the conference review

“…Although these results are quite impressive, there is one important detail to keep in mind – neither of these groups supplemented their training with whey protein. Since both work via the mTOR pathway, it will be interesting to see if there is a synergistic relationship present when "stacking" these supplements or if a "ceiling effect" is observed with respect to acute and long term changes in body composition and performance…”

Thus, I was very interested in Dr. Roberts presentation which examined his recent research on the effects of "stacking" whey protein concentrate (WPC) + PA on acute anabolic signaling in rats. In theory, whey protein and PA may make a perfect stack. As shown in Figure 4, rather than competing for the same domain on the mTOR molecule, it appears they bind to different sections on the molecule.

With this potential synergy in mind, Dr. Robert's research team conducted an interesting study in which rats were given A) PA -1500 mg human equivalent dose (HED) B) WPC -10g HED or C) PA + WPC. Three hours post feeding, the gastrocnemius (ie – calf muscle) of each rat was removed and analyzed. As was to be expected, in isolation, PA as well as WPC increased protein synthesis. Additionally, the combination increased anabolic markers (p70s6k, etc). Yet, when it came to actual muscle protein synthesis, NO synergy was found between WPC and PA when assessed three hours post.

Although these results are disappointing, as pointed out by Dr. Roberts, this does not mean that a potential synergy isn't present between these anabolic compounds – his team only assessed 1 time point (3 hrs post). More research is needed to examine what is happening at the tissue level 6, 9. 12+ hours after ingestion since WPC and PA have different time courses w/ respect to mTOR activation. Thus, the anabolic duo may exert their synergistic effects on muscle protein synthesis at these later time points and potentially lead to greater gains in performance vs. either in isolation.

Some other interesting tidbits from this study, with respect to WPC & PA on mRNA…

  • WPC + PA caused a 30% reduction in myostatin mRNA (vs. water) which was superior to both the PA and WPC in isolation (For reference, myostatin plays a role muscle breakdown)
  • WPC + PA significantly increased skeletal muscle Glut-4 mRNA by 60% (vs water) which was superior to WPC alone (Glut-4 is responsible for sucking glucose from your bloodstream into your muscles)

Hopefully research examining this potential synergistic effect will make the jump from rats to humans soon … both within the research lab as well as that being done in your neighborhood gym! Because let's be honest, mRNA & markers of protein synthesis are great, but it's what we feel in the gym/on the court and see in the mirror that truly matters!

Brad Schoenfeld, PhD – Max Muscle: A Periodized Approach to Hypertrophy Training

Dr. Brad Schoenfeld … In terms of formal human performance research and reviews, is there any individual putting out cooler, more frequent, stuff than this guy? A quick search of Brad Schoenfeld on PubMed indicates one thing – probably not. I asked Dr. Schoenfeld about this and he informed me that he's simply trying to answer the questions that bounced around in his mind while working as a personal trainer for 20+ years prior to becoming a PhD. I put emphasis on prior as Dr. Schoenfeld mentioned to me how beneficial this was for him to 'work in the field' for such an extended time period before actually studying it from a formal research perspective. In this presentation, Dr. Schoenfeld discussed his MAX Muscle™ approach to periodization for hypertrophy.

The Max Muscle program starts off with an 8 week strength mesocycle. As implied by the name, the goal of this phase is to simply become as strong as possible. In doing so, one is capable of lifting a heavier load once they start the hypertrophy cycle. It’s characterized by lower reps (1-5 reps) and longer rest periods (3 minutes). This is followed up by a highly dense, 4 week metabolic phase. The goals of the metabolic cycle are two-fold: 1) Improve one’s lactate threshold to resist fatigue during the subsequent hypertrophy phase and 2) Potentially elicit growth in Type 1 fibers via high reps (15-20 reps) with short rest intervals (<30 seconds). Upon completion of the metabolic training, one moves into a 10 week hypertrophy cycle which is broken down into two 4 week blocks before ending with a 2 week overreaching phase. Rep ranges during the hypertrophy blocks range from 6-12 with 60-90 seconds of rest between sets. During this phase, emphasis is placed on hitting the muscle from different angles and working in as many planes of movement as possible.

Bottom Line

More is still to come. Stay tuned as Part IIb focuses on …

  • Jacob M. Wilson PhD and Ryan Lowery BS CSCS (Fat Loss Strategies for Optimizing Body Composition)
  • Jeff Volek PhD RD (The Many Facets of Keto-Adaptation – Health, Performance, & Beyond)
  • Dr. Lonnie Lowery's labs investigation on the effects of acute caffeine ingestion on performance differences in males vs. females.


1 Photo by Sandstein. Accessed June 13, 2010 from: commons.wikimedia.org/wiki/File:Protein_shake.jpg

2 Katsanos CS1, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E381-7.

3 Norton LE1, Wilson GJ, Layman DK, Moulton CJ, Garlick PJ. Leucine content of dietary proteins is a determinant of postprandial skeletal muscle protein synthesis in adult rats. Nutr Metab (Lond). 2012 Jul 20;9(1):67.

4 Joy JM, Lowery RP, Wilson JM, Purpura M, De Souza EO, Wilson SM, Kalman DS, Dudeck JE, Jäger R.The effects of 8 weeks of whey or rice protein supplementation on body composition and exercise performance. Nutr J. 2013 Jun 20;12(1):86.

4 Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr. 2009.

5 Yang Y1, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr. 2012 Nov 28;108(10):1780-8.

6 Wax B1, Kavazis AN, Brown SP, Hilton L. Effects of supplemental GAKIC ingestion on resistance training performance in trained men. Res Q Exerc Sport. 2013 Jun;84(2):245-51.

7 Wax B1, Hilton L, Vickers B, Gilliland K, Conrad M. Effects of glycine-arginine-α-ketoisocaproic acid supplementation in college-age trained females during multi-bouts of resistance exercise. J Diet Suppl. 2013 Mar;10(1):6-16. doi: 10.3109/19390211.2012.758216. Epub 2013 Jan 29.

8 Buford BN1, Koch AJ. Glycine-arginine-alpha-ketoisocaproic acid improves performance of repeated cycling sprints. Med Sci Sports Exerc. 2004 Apr;36(4):583-7.

9 Stevens BR1, Godfrey MD, Kaminski TW, Braith RW. High-intensity dynamic human muscle performance enhanced by a metabolic intervention. Med Sci Sports Exerc. 2000 Dec;32(12):2102-8.

10 Beis L1, Mohammad Y, Easton C, Pitsiladis YP. Failure of glycine-arginine-α-ketoisocaproic acid to improve high-intensity exercise performance in trained cyclists. Int J Sport Nutr Exerc Metab. 2011 Feb;21(1):33-9.

11 Yarrow JF1, Parr JJ, White LJ, Borsa PA, Stevens BR. The effects of short-term alpha-ketoisocaproic acid supplementation on exercise performance: a randomized controlled trial. J Int Soc Sports Nutr. 2007 Jul 13;4:2.

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Written on October 26, 2014 by Sean Casey
Last Updated: October 27, 2014

This information is not intended to take the place of medical advice.Please check with your health care providers prior to starting any new dietary or exercise program. CasePerformance is not responsible for the outcome of any decision made based off the information presented in this article.

About the Author: Sean Casey is a graduate of the University of Wisconsin-Madison with degrees in both Nutritional Science-Dietetics and Kinesiology-Exercise Physiology. Sean graduated academically as one of the top students in both the Nutritional Science and Kinesiology departments.
Field Experience: During college, Sean was active with the UW-Badgers Strength and Conditioning Department. He has also spent time as an intern physical preparation coach at the International Performance Institute in Bradenton, FL. He also spent time as an intern and later worked at Athletes Performance in Tempe, AZ. While at these locations he had the opportunity to train football, soccer, baseball, golf and tennis athletes. Sean is also active in the field of sports nutrition where he has consulted with a wide variety of organizations including both elite (NFL’s Jacksonville Jaguars) and amateur athletic teams. His nutrition consultation services are avalable by clicking on the Nutrition Consultation tab.