In today’s ultra-competitive world athletes and exercise enthusiasts’, both professional and non-professional, are looking to gain an edge in their performance. Many adults today turn to nutritional supplements to improve their athletic performance without ever doing any research to find out if supplements manufactures claims are true. Some of the most widely used nutritional supplements are branched-chain amino acids. Branchedchain amino acids are a subset of three of the nine essential amino acids, they are; Leucine, Isoleucine and Valine. They are marketed as recovery aids and are claimed by the manufactures’ to increase rates of muscle recovery from various types exercise and reduce levels of muscle soreness following exercise, which in-turn leads to increased training volume and improved athletic performance. With the very low level of governmental regulation in the nutritional supplement industry in the United States supplement companies can make product claims without having to show factual evidence that they do exactly what they say, as long as their product label contains the disclaimer; these statements have not been evaluated by the Food and Drug Administration. Not intended to diagnose, treat, prevent, mitigate or cure disease and the products have been deemed safe. Many consumers make their decision to purchase these products based on the manufactures claims without knowing if what they are purchasing will produce the advertised and desired results. This literature review focuses on if branch-chain amino acids do in-fact perform as the claims put forth by their manufactures would have consumers believe, i.e.; branched-chain amino acid supplementation results in increased rates of muscle recovery and lower levels of muscle soreness following various types of exercise and improved athletic performance, or are consumers simply wasting their money. This review will educate the reader in-detail on what branched-chain amino acids are, their roles in the body, their effects on muscle recovery and levels of muscle soreness following various types of exercise; aerobic, anaerobic and endurance, a conclusion on if the manufactures’ product claims are can be considered true and how, if appropriate, branched-chain amino acid supplementation can be applied to dietetic practice. All types of exercise result in stimulation of energy expenditure (ATP use) and protein catabolism (and synthesis) by the skeletal muscle, which results in a tired and/or weak feeling in the muscle(s) exercised and delayed-onset muscle soreness in the hours and days following exercise1,2. Branched-chain amino acids are marketed as nutritional supplements that act as muscle recovery aids which are claimed to help increase rates of muscle recovery (repair) by increasing protein synthesis in skeletal muscle as well as limiting muscle protein catabolism by acting as a minor fuel source for the muscle when available freely circulating in the blood via supplementation instead of the muscle protein itself being broken down for fuel during exercise2(337). Branched-chain amino acids like all amino acids are the building blocks of proteins and are found in protein rich foods. Branched-chain amino acids are part of the group of amino acids that are considered to be essential, meaning they can not be synthesized by the body in significant amounts so they must be obtained through the diet. Branched-chain amino acids are found throughout the body, but are found in their highest amounts in the skeletal muscle where they account for roughly 35% of the essential amino acids’ found in skeletal muscle1(236). The skeletal muscle is also the site where they are primarily catabolized, while most other essential amino acids are catabolized by the liver1(236). Branched-chain amino acids’ roles within the body are different than other amino acids as well, they primarily regulate protein metabolism, promote protein synthesis by stimulating mRNA translation, and suppress protein degradation by pathways involved in the phosphorylation of the mammalian target of rapamycin (mTOR), all of which mainly takes place in the skeletal muscle tissue2(236). Exercises’ effects on muscle protein synthesis are facilitated by branched-chain amino acids as evidenced by the study of the activation of intramuscular signalers involved in controlling protein synthesis, which include; mTOR, 70-kD S6 Protein Kinase, eukaryotic initiation factor 4E-binding protein, eukaryotic initiation factor 2B, glycogen synthase kinase-3, Creatine Kinase and Akt1(237)2,3,4. These intramuscular signalers are activated by exercise and also by administration of branched-chain amino acids in resting human muscle 1(237). Many of these intramuscular signalers will be seen later in this paper in the sections dedicated to the review of the studies on the effects of supplementation of branched-chain amino acids and their effects of muscle recovery and soreness. As previously stated, branched-chain amino acids play critical roles in protein metabolism in skeletal muscle. The physiological effects of branched-chain amino acids are thoroughly discussed in the research articles I reviewed. The articles I reviewed looked at aerobic, anaerobic and endurance exercise trials and the effects branched-chain amino acids had on rates of muscle recovery and levels of soreness when compared to a control group following these different types of exercise. The first two studies I reviewed involved the supplementation of branched-chain amino acids and their effects after aerobic exercise. The first study was performed by researchers affiliated with the Department of Exercise Health Science at the National Taiwan College of Physical Education and appeared in the Journal of the International Society of Sports Nutrition in November 2011. The study involved nine well-trained male wrestlers that participated in three trials, each of which were performed two weeks apart, that involved three exercise tests that were designed to mimic wrestling matches with a one hour rest period between match one and two and a 2 hour rest period between match two and three. Each match contained three exercise periods lasting two minutes each with a work to rest ratio of 10 seconds: 20 seconds. After each exercise period a two minute rest period was provided before the next exercise period. The exercises were performed on cycle ergometers, the subjects were asked to perform 10 second all out sprints where they were asked to pedal as fast as possible with a load on the cycle of 0.1 kp/kg of body weight. The 20 second rest period consisted of subjects pedaling at 60 RPM’s with no load. The peak and average power of each sprint was recorded. Prior to the tests, the subjects came in early in the morning after an overnight fast and blood samples were taken to in the fasted state to serve as a baseline measurement. All subjects then consumed the same “standardized” breakfast. After the second match three different supplementations were consumed: 1.2 g/kg glucose (CHO trial), 1 g/kg of glucose + BCAA’s (Leucine: Isoleucine: Valine = 2:1:1) (CHO+AA trial) and a Placebo trial. All supplementations were dissolved in 600ml of lemon flavored water to blind which group of three had which supplement. Blood samples were then taken immediately after the second and third trial and at 90 and 120 minutes after the third trial. Researchers were blinded to which groups consumed which supplement and looked at blood levels of; Hemoglobin concentration, plasma levels of Hematocrit, Nitric Oxide, Insulin, Glucose, Glycerol and Non-esterified Fatty Acids. The carbohydrate and amino acid trial group had higher levels of peak power and average power across all three matches in all three trials, and they also had lower reductions in peak and average power output across all three matches in all three trials, leading to the conclusion that the carbohydrate and amino acid group had improved rates of muscle recovery. Researchers concluded their studies had limitations because muscle biopsies’ had not been performed and the study did not look at neuromuscular or psychological fatigue and its relation to performance.5 The second Aerobic study I reviewed was performed by researchers affiliated with the School of Life Sciences, Northumbria University, Newcastle, UK, the School of Environmental Sciences and Development, Northwest University, Potchefsteroom, South Africa and the School of Sport Health and Applied Science, St Mary’s University College, Twickenham, UK. This study was published in the Journal of the International Society of Sports Nutrition May 2012. This study involved 12 well trained rugby and football players that were randomly assigned to two groups, a supplement group and a placebo group each with six members in a stratified, double-blind fashion. The study was based around a 12 day testing period where participants consumed a branched-chain amino acid supplement (Leucine: Isoleucine: Valine = 2:1:1) of 10g or a placebo in the morning and evening and a 20g bolus, one pre-exercise and immediately after exercise. Participants performed five sets of 20 drop-jumps for a total of 100 drop-jumps from a height of .6 meters followed by an immediate vertical jump with maximal force. Each jump had a 10 second interval and a two minute rest interval between sets. To measure levels of muscle soreness and rates of muscle recovery researchers looked at the following measurements; blood samples were taken to measure plasma Creatine Kinase activity, participants held a 90 degree knee-angle squat and qualitatively measured perceived pain on a visual scale, maximal voluntary contraction was measured in the knee extensors, vertical jump performance was measured and mid-thigh and calf circumference was measured. Creatine Kinase levels were significantly lower in the branched-chain amino acid group, levels of soreness in the 90 degree angle squat at 24 and 48 hours post exercise was significantly lower in the branched-chain amino acid group and maximal voluntary contraction decrease after exercise was significantly lower in the branched-chain amino acid group as well, when compared to the placebo group. Vertical jump performance and limb circumference of midthigh and calf did not show any significant difference between the two groups. The researchers concluded that that supplementation of branched-chain amino acids can reduce the negative effects of damaging exercise by attenuating Creatine Kinase efflux, reducing levels of soreness and improving rates of muscle recovery to a greater extent than a placebo control group.6 The second type of exercise I reviewed studies on was anaerobic exercise. The two studies I reviewed involved squats and lengthening muscle contractions (eccentric contractions). The first of the anaerobic studies I reviewed was performed by researchers affiliated with Nagoya University, Nagoya, Japan, the Nagoya Institute of Technology, Nagoya, Japan, Nagoya University Hospital, Nagoya, Japan, Chukyo Junior College, Mizunami, Japan and Aijnomoto Co. Kawasaki, Japan and was published in the International Journal of Sport Nutrition and Exercise Metabolism 2010. This study involved 12 untrained female participants randomly split into two groups of six, a branched-chain amino acid supplement group and a placebo group. Each group performed two trials of seven sets of 20 bodyweight squats with three minute rest intervals between sets separated by 11 weeks. The study was a double-blind crossover design with the supplement group receiving a branched-chain amino acid supplement with a mixture of Isoleucine: Leucine: Valine of 1:2.3:1.2 and the placebo group receiving 100mg of dextrin on the morning of the test. The researchers took fasting blood samples from each group as a baseline measurement and immediately after, one hour after and two hours after exercise. Researchers looked at blood and plasma levels of insulin, glucose, free branched-chain amino acid concentration, Creatine Kinase, Serum Myoglobin and Plasma Elastase concentration, and they took measurements of maximal voluntary isometric muscle contractions, as well as having participants perform slow bodyweight squats on days two to five after the test and qualitatively measure muscle soreness. After a thorough review of all of the findings in the two groups the researchers came to the conclusion that supplementation of branched chain amino acids has a positive effect on muscle recovery and a positive effect on lowering levels of delayed-onset muscle soreness.1(236-242) The second study I reviewed for anaerobic exercise was a cohort study that reviewed 57 different studies and looked at the results of branched-chain amino acid supplementation on eccentric muscle contractions and endurance exercise. I am only presenting the information on the review of the eccentric muscle contractions. This cohort study was performed by Dr. Kazunori Nosaka who is an associate professor at the School of Exercise, Biomedical and Health Sciences at Edith Cowan University in Joondalup, Western Australia, Australia and was published in the International Sports Medicine Journal 2007. After reviewing the studies he came to the conclusion that supplementation of Branchedchain amino acids does stimulate regeneration and/or remodeling of muscle and connective tissue following exercises involving eccentric muscle contractions. He also concluded that levels of delayed-onset muscle soreness and inflammation are reduced by supplementation. He did note that level of positive effects of supplementation are dependent on timing of supplementation, amount of supplementation, composition of supplement, amount of other food intake and magnitude of muscle damage from the exercise. In his conclusion he address that he would like to see more research done to further prove the beneficial effects of branched-chain amino acids on muscle recovery and attenuation of muscle damage.7 The final type of exercise I reviewed studies on was endurance exercise. The two studies I reviewed involved very different levels of endurance exercise. The first study I looked at studied nine untrained males and the effects of branched-chain amino acid supplementation had on attenuation of indicators of muscle damage during a series of three 90-minute cycling tests in comparison to three other groups; an iso-caloric group, a carbohydrate beverage group and a non-caloric beverage group. Subjects were blinded to the group in which they were in. Blood levels of Creatine Kinase and Lactate Dehydrogenase were measured along with isokinetic leg-extension and leg-flexion torque and muscle soreness, right before, immediately after, 4 hours, 24 hours and 48 hours post exercise. Participants performed a series of three 90-minute cycling tests each eight weeks apart. Each test consisted of cycling for 90 minutes at an intensity equivalent to 55% of each individuals VO2 max. After a review of all of the measurements, researchers came to the conclusion that supplementation of a branched-chain amino acid beverage results in attenuation of muscle damage leading to lower levels of muscle soreness significantly better than those that received an iso-caloric beverage, carbohydrate beverage and a noncaloric placebo beverage.4(595-605) The final study I reviewed looked at short-term amino acid supplementation’s effect on skeletal muscle damage in 100 km ultra-marathon runners. The study was performed by researchers affiliated with the Institute of General Practice and Health Services Research, at the University of Zurich, Zurich Switzerland and was published in the Journal of the International Society of Sports Nutrition April 2011. This study involved 28 experienced male ultra-marathon runners; they were broken into two groups of 14, one with amino acid supplementation and one with no supplementation. The amino acid group was administered 52.5g of an amino acid concentrate, which contained 14 different amino acids, of which branched-chain amino acids accounted for 20g of the 52.5g total. The supplement group consumed 12 amino acid tablets before the race, then 4 tablets at each of the 17 aid stations, for a total of 80 tablets or 52.5g of amino acids. Blood samples were taken from both groups before and after the race to measure levels of Urea, Creatine Kinase and Myoglobin. Participants also filled out subjective questionnaires about their levels of muscle soreness and their individual performances were compared to each participant’s personal best. After a review of all of the metrics researchers came to the conclusion that there was no significant difference in the anthropometric measurements, subjective levels of soreness or performance between the short-term amino acid supplement group or the control group. This was contradictory to what was hypothesized by researchers due to findings by previous studies. Researchers postulated that the duration of supplementation was possibly too short to have any kind of significant effect on the measurements reviewed in the two groups.8 As seen from the studies I reviewed, the supplementation of branched-chain amino acids overwhelmingly has positive effects on increasing rates of muscle recovery and reducing levels of muscle soreness in adults that participate in various types of exercise when compared to control groups. While this did not hold true for every research article I reviewed the postulated reason for lack of positive results in the ultra-marathon study seems to be legitimate. After thorough research one can conclude that the product claims put forth by the branched-chain amino acid supplement producing companies can be viewed as truthful and well substantiated. The claims made by the manufactures’ regarding improved athletic performance however have not been proven true and need to be further investigated. While the results of this research may not be as far reaching in the field of dietetics as some other topics, it is still significant. Dietitians working in private practice consulting individuals on how to live a healthier life through proper nutrition could apply this information when confronted with questions from clients/patients regarding how to reduce soreness or improve rates of muscle repair following their exercise routines. Exercise is as much as a part of healthy living as proper nutrition is and they are both recommended together as treatment plans for many co-morbidities and disease states. Because of this fact dietitians should be aware of this information in order to apply it to the treatment plans for their clients/patients, where applicable. The results of this review have wide reaching implications in the field of sports nutrition. Dietitians focusing on the field of sports nutrition have to provide their athletes with proper nutritional information in relation to the physical demands of the sport or activity in which they perform. Athletes trying to perform at the highest level they are capable of will benefit from this information when it comes to their ability to train with the frequency and magnitude which their sport requires, so those focusing in this field need to be aware of this information in order to provide the best nutritional guidance possible for their athletes and clients. It is in my opinion that these results will not result in any substantial changes in dietetic practice. This is due to the fact that the effect of protein on muscle repair has been well established for a long time, this information just provides more clarity on this issue of how to better alleviate muscle soreness and increase rates of muscle recovery following exercise with more than just protein supplementation alone. Journal article citations 1. Bajotto G, Inaguma A, Kobayashi H, et al. Branched-chain amino acid 2. 3. 4. 5. 6. 7. 8. supplementation before squat exercise and delayed-onset muscle soreness. Int J of Sp Nut and Ex Met. 2010; 20: 236-244. Gibala, M. Protein Metabolism and Endurance Exercise. J of Sp Med. 2007; 37: 337340. Blomstrand E, Eliasson J, Karlsson H, Konhnke R. Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. The J of Nut. 2006; 136: 269S-273S. Arguello E, Greer BK, Haymes E, et al. Branched-chain amino acid supplementation and indicators of muscle damage after endurance exercise. Int J of Sp Nut and Ex Met. 2007; 17: 595-607. Chang CK, Chang CM, Fang SH, et al. Effects of carbohydrate, branched-chain amino acids and arginine in recovery period on the subsequent performance in wrestlers. J of the Int Soc of Sp Nut. 2011; 8:20. Bell PG, French DN, Goodall S, et al. Exercise-induced muscle damage is reduced in resistance-trained males by branched-chain amino acids: a randomized, double blind, placebo controlled study. J of the Int Soc of Sp Nut. 2012; 9:20. Nosaka, K PhD. Muscle damage and amino acid supplementation: Does it aid recovery from muscle damage? Int Sp Med J. 2007; 8: 54-67. Ballmer P, Imoberdorf R, Knechtle B. et al. No effect of short-term amino acid supplementation on variables related to skeletal muscle damage in 100km ultrarunners – a randomized control trial. J of the Int So of Sp Nut. 2011: 8:6. Branched-Chain Amino Acids Literature Review Topic: Does supplementation of branched-chain amino acids increase rates of muscle recovery and reduce levels of muscle soreness from various types of exercise in adults? By: Andrew Winquist HUN3800 Section: 82263