The Ergogenic Effects of Glutamine: Counterpoint. Erin Williams, Alison McKay, Krystiana Corrado March 28, 2017

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1 The Ergogenic Effects of Glutamine: Counterpoint Erin Williams, Alison McKay, Krystiana Corrado March 28, 2017

2 Hypothesis Our Approach: Glutamine supplementation does not indluence anticatabolic activity and glycogen synthesis so as to improve responses to resistance training. Opposition: Glutamine supplementation does indluence anti-catabolic activity and glycogen synthesis so as to improve responses to resistance training.

3 Roadmap Slide Our counterpoint argument is focused on... Glutamine is not involved in the muscle repair process Glutamine supplementation does not change lean tissue mass. Glutamine supplementation does not signidicantly increase intramuscular glycogen levels Critique the opposing point argument

4 Non Clinical Uses Glutamine supplements can be used for rehydration, which will increase time to fatigue during exhaustive exercise (Hoffman et al, 2010) Clinical Uses Oral glutamine supplementation is used to: Minimize side effects of chemoradiotherapy including weight loss and esophagitis (Gul et al, 2010) Compensate for ischemia-reperfusion injuries when renal arginine is reduced by producing citrulline and arginine (Brinkmann et al, 2016)

5 Proposed Mechanism Glutamine (Gln) is glycogenic can be converted to glucose by gluconeogenesis to fuel metabolic reactions: Gln is converted to glutamate by gln synthase. Transamination reaction with pyruvate produces alanine (also glycogenic). Glucose production initiates insulin release, activates glycogen synthase. Increases hepatic glycogen stores, reduces Fig. 1: Net change in glycogen storage in μmol g -1 wet wt following Saline, Alanine (Ala) + Glycine (Gly), and Glutamine infusions. * = SigniDicant differences at 5% by repeated measures ANOVA. catabolic amino acid release. (Varnier et al, 1995)

6 Proposed Mechanism Exogenous glutamine supplements allegedly maintain muscle mass by fuelling gluconeogenesis in place of stored glutamine. Fig. 2: Increases plasma [glutamine] and [insulin] in μmol l -1 during glutamine ( ) infusion. * = signidicant difference 5% repeated measures ANOVA vs. preinfusion concentrations. (Varnier et al, 1995)

7 Proposed Mechanism Ingestion of glutamine can initiate growth hormone (GH) release, therefore has an anabolic effect. Glutamine converts to citrulline in the small intestine, which supports renal arginine synthesis. Heightened plasma arginine stimulates the release of GH. Supplements increase glutamine delivery to small intestine and increase downstream GH release. (Welbourne, 1995) Growth Hormone (mol/l) Control Glutamine (Min) Fig. 3: [GH] in mol/l before and after supplement. * = SigniDicant at 5% by repeat measures ANOVA. Average for all subjects ( ).

8 Recommended Daily Allowance (RDA) Con1licting data on glutamine supplementation exists therefore a Dietary Reference Intake cannot be DRI-ved (Rathmacher et al, 2004) performed a double blind study which concluded an observed safe limit of 14g/day (Candow et al, 2001) reported supplementing as high as 45g/day without subjects reporting negative effects

9 Safe use Observed toxicity: plasma glutamine = 1.3 mmol/l Case Study: A woman overdosed on acetaminophen, causing high plasma glutamine. This Resulted in: Osmotic stress and Cerebral edema Short term effects: Confusion Agitation Plasma Glutamine (mmol/l) Hrs. after Acetaminophen Ingestion Fig. 4: Recorded plasma [glutamine] against hrs after acetaminophen ingestion. Toxic levels at 120 hrs. (Brusilow et al, 2011)

10 Research Outcome #1 Refuting Ergogenic Effects Methods: (n=89) Rats on 2 week weight training program. Rats received: 1. High dose of Sustamine (alanine + glutamine supplement) 2. Low dose of Sustamine 3. Whey Protein supplement 4. Placebo supplement (control) 5. Sedentary without supplement (control) Post exercise muscle samples were taken to evaluate the activation of the m-tor muscle regeneration pathway and associated proteins such as p70s6k. (Wang et al, 2015)

11 #1 Continued Results: Flexor hallucis longus muscle (FHL) samples showed little phosphorylation of P70S6K in both Sustamine groups, therefore there was less activation of protein synthesis. FHL phosphorylated P706SK (% of Standard) Supplementation of glutamine induced less protein synthesis, therefore had a poor anabolic response. * * Fig. 5: ModiPied from Wang et al, 2015 Fig. 5: Amount of P70S6K activation as a % of standard levels across experimental conditions. * = signidicant at P < 0.05 vs Whey. Low sustamine (LSUS) and high sustamine (HSUS) groups show signidicantly less activation than whey condition.

12 Research Outcome #2 Refuting Ergogenic Effects Methods: (n=31) Previously active subjects participated in a 6 week resistance training program with various supplementations. Double blind, repeated measures. Subjects were supplemented: 1. Glutamine 2. Placebo Because glutamine is typically consumed through oral supplementation, this study best represents the population. DXA imaging was used pre and post program to quantify changes to lean tissue mass. (Candow et al, 2001)

13 #2 Continued Results: Both glutamine and placebo groups increased lean tissue mass to the same degree between weeks 1-6. Equal slope between groups shows improvement to the same extent. Therefore glutamine supplementation provided no anabolic advantage to resistance training. (Candow et al, 2001) Fig. 6: Mean lean tissue mass (kg) for glutamine ( ) and placebo ( ) groups between weeks 0-6. Error bars show SEM while * = signidicance at P < 0.05 compared to week 0.

14 Research Outcome #3 Refuting Ergogenic Effects Methods: (n=8) Trained subjects performed glycogen depleting exercise with supplement ingestion 15 minutes following completion. Repeated measures study. Subjects received: 1. Glucose (control) 2. Glucose + glutamine 3. Glucose + wheat protein (hi glutamine dose) 4. Glucose + whey protein (normal glutamine dose) A muscle biopsy was taken before and after supplementation to measure muscle glycogen resynthesis. (Van Hall et al, 2000)

15 #3 Continued Results: No signidicant difference in rate of glycogen resynthesis between control and glutamine conditions. Even after glycogen depleting exercise, there was no restorative benedit to glutamine Muscle glycogen resynthesis (mmol / (kg dry muscle. hour)) Glucose Gln Wheat Whey supplementation. Fig. 7: Rate of muscle glycogen resynthesis in mmol/ (kg dry muscle.hour) during recovery from intense exercise after glucose, or glucose + glutamine (Gln), wheat protein, or whey protein supplementation. Values are means +/- SEM. (Van Hall et al, 2000)

16 Evidence to Refute Effect #1 Methods: (n=18) Subjects performed glycogen depleting exercise for 90 minutes with intermittent sprint periods, followed by supplement infusion 30 minutes after completion of exercise. Subjects received: 1. Glutamine infusion 2. Alanine + Glycine infusion 3. Control: saline infusion Muscle tissue samples were collected before and after infusion to measure muscle glycogen stores. (Varnier et al, 1995)

#1 Continued Results: Glutamine infusion group had 2-fold increase in overall Glycogen (Gly) storage after infusion. Supports that glutamine infusion promoted skeletal muscle glycogen storage.

17 #1 Continued Results: Glutamine infusion group had 2-fold increase in overall Glycogen (Gly) storage after infusion. Supports that glutamine infusion promoted skeletal muscle glycogen storage. = 1 hour infusion = 2 hours infusion Refute: Glycogen depleting training causes greater stress, and muscle Fig. 8: Net Glycogen accumulation glycogen depletion than resistance μmol g -1 wet wt during three training. Physiological response is infusions. * = signidicant differences different. Similar studies also show at 5% by repeat measures ANOVA converse results (see G. van Hall et al.) (Varnier et al, 1995)

18 Evidence to Refute Effect #2 Methods: (n=9) Subjects ingested supplement. Subjects received: -Control: Vehicle- Carbonated soft drink (ph 3.8, 20g glucose) -Vehicle + 2g L-glutamine Blood samples taken prior, then 30, 60 and 90 minutes after supplementation. Samples were measured for plasma glutamine, and growth hormone (pgh). (Welbourne, 1995)

19 #2 Continued Results: Recorded 4-fold increase in plasma growth hormone (90 min) following increase in plasma glutamine, promotes protein synthesis. Refute: 1hr of moderate exercise causes 20-fold increase in plasma growth hormone, 4-fold increase is minor in comparison (Candow et. al) Fig. 9: Plasma growth hormone concentrations (mol/l) before and after supplement was given. Average for all subjects ( ) (Welbourne, 1995)

20 In Conclusion Glutamine supplementation does not indluence anti-catabolic activity and glycogen synthesis so as to improve responses to resistance training.

21 References 1. Brinkmann S, Bujs N, van Leeuwen P, et al. Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial. Am J Of Physiol. 311(3): F567-F Brusilow S, Cooper A, Brusilow S, Cooper A. Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy. Crit Care Med. 39(11): Candow D, Chilibeck P, Burke D, Davison K, Smith-Palmer T. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol. 86(2): Gul K, Mehmet K, Meryem A. The effects of oral glutamine on clinical and survival outcomes of non-small cell lung cancer patients treated with chemoradiotherapy. Clin Nutr

22 5. Hoffman J, Ratamess N, Maresh C, et al. Examination of the ef]icacy of acute L-alanyl-L-glutamine ingestion during hydration stress in endurance exercise. J Int Soc Sports Nutr. 7: 8, Rathmacher J, Nissen S, Abumrad N, et al. Supplementation with a combination of beta-hydroxyl-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. J Parenter Enteral Nutr. 28(2): Van Hall G, Saris W, van de Schoor P, Wagenmakers A. The effect of free glutamine and peptide ingestion on the rate of muscle glycogen resynthesis in man. Int J Sports Med. 21: Varnier M, Leese G, Thompson J. Stimulatory effect of glutamine on glycogen accumulation in human skeletal muscle. Am J Of Physiol. 296: E

23 9. Wang W, Choi R, Ivy J, et al. L-Alanylglutamine inhibits signaling proteins that activate protein degradation, but does not affect proteins that activate protein synthesis after acutre resistance exercise. Amino Acids. 47(7): Welbourne T. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr. 61(5):

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