Branched Chain Amino Acids (BCAAs) – All you need to know

hr-line

What are Branched Chain Amino Acids?

i

  • Branched Chain Amino Acids (BCAA) are three essential amino acids, namely valine, leucine and isoleucine, among the nine essential amino acids. They have branched aliphatic side chains attached to a central carbon atom.1
  • They account for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals.2
  • They are naturally found in many foods, such as meat, eggs, chicken and fish, accounting for 15% to 25% of the total protein intake; thus, supplementation is not necessary. However, supplementation has benefits in certain situations.3

Who should take BCAA?

i

  • High endurance athletes competing in long races as BCAAs are metabolized in muscles to generate energy, delay central fatigue and maintain mental performance.
  • Some people use BCAAs to prevent fatigue and improve concentration.
  • BCAAs are also used to help slow muscle wasting in people who are confined to bed.
  • Used also in stress-associated conditions, such as burns, trauma and surgery, as an important source of calories. They can also be used in intravenous solutions pre- and postoperatively for malnourished patients.
  • Patients with advanced chronic liver disease can benefit from BCAAs supplementation in decreasing hepatic encephalopathy occurrence, stimulating more albumin synthesis and decreasing the incidence of hepatocellular carcinoma.

Contraindications

i

  • Amyotrophic Lateral Sclerosis patients should avoid Branched Chain Amino Acids because of their susceptibility to cause pulmonary failure and mortality.
  • Hepatic encephalopathy patients should be closely monitored due to BCAAs susceptibility to increase plasma ammonia levels.

Branched Chain Amino Acids Product Comparison

Optimum Nutrition BCAA
popular
  • Branched Chain Amino Acids Optimum Nutrition 200 Servings
BulkSupplements BCAA
lowest price, most popular
  • BulkSupplements Branched-Chain Amino Acids Powder
Cellucor BCAA Supplement
popular
  • 150g Branched Chain Amino Acids + 48g Beta Alanine Cellucor
Natura Formulas BCAA
popular
  • 48g BCAA Natura Formulas

Benefits of BCAAs based on scientific research

Branched Chain Amino Acids supplementation increases muscle protein synthesis and muscle growth in people with limited protein intake increasing muscle power.

A study was done in 2012 on 63 years old subjects. The supplemented group were given 51 g of amino acids during 2 days of trail walking in mountains. Effort indicators, such as heart rate, active energy expenditure, fatigue sensation and food and water intake, were measured. The study found that trail walking in mountains required higher effort in the placebo group compared to the supplemented group.4

BCAAs supplementation enhances fatigue resistance in endurance exercises (in untrained individuals only).

Branched Chain Amino Acids supplementation increases fatigue resistance as shown by a 2011 study on volunteers supplemented by 300 mg/kg/day for three days. On the third day, they performed exhaustive exercises. The supplemented group showed more fatigue resistance than the placebo group.5

 

A study was performed in 1997 on male endurance-trained cyclists. They performed severe exercises on a cycle ergometer for 60 minutes at 70% of their capacity and for 100% for another 20 minutes. During exercise the subjects were given either a solution of BCAAs or flavoured water (placebo). They rated their perceived exertion and mental fatigue. BCAAs group’s perceived exertion was 7% lower and their mental fatigue was 15% lower than the placebo group. The plasma concentration ratio of free tryptophan/BCAAs in the placebo group showed 45% increase during exercise and 150% increase five minutes after exercise, while the supplemented group showed no increase, or even decreased.6

 

A study was done in 1995 on trained male athletes. They were tested during cycle exercises at 70-75% maximal power output. Exercise time to exhaustion was not found to differ between the supplemented group and the placebo group.7

Branched Chain Amino Acids supplementation improves both mental and physical performance.

A study was done in 2008 to evaluate the role of BCAA rich diet on exertion and mental and physical performance during an offshore sailing race. Sailors were divided into 2 groups: one group consumed BCAAs rich diet, and the placebo group consumed another diet. The testing race lasted 32 hours. A vertical jump and a handgrip test were performed, and mental performance was evaluated with a standardized battery of tests. Fatigue feeling decreased significantly in the supplemented group compared to the placebo group. The placebo group showed a significant decrease in short-term memory.8

BCAAs supplementation enhances psychomotor performance and rapid responses to external stimuli in sport activities that change in intensity, such as soccer and other team games.

A 2011 study was designed to discover the effects of BCAAs supplementation on rapid response to external stimuli and on psychomotor performance during treadmill-exercise simulating soccer game. Male soccer players were divided into 2 groups. The supplemented group took 7 g of BCAAs 1 hour before the exercise. Their multiple choice reaction time was recorded. This time was shorter in the supplemented group compared to the placebo group.9

Branched Chain Amino Acids supplementation suppresses exercise-induced muscle damage.

A study was made in 2010 on young untrained females. The participants were divided into 2 groups, one ingested BCAAs and the other ingested the placebo, before squat exercises. They performed 7 sets of 20 squats/set with 3 min rest between sets. Delayed onset muscle soreness was significantly lower in the supplemented group than the placebo group. Leg-muscle force during maximal voluntary isometric contractions was measured 2 days after exercise which was found to be higher in the supplemented group. Serum myoglobin concentration was increased by exercise in the placebo but not in the supplemented group. Plasma elastase, an index of neutrophil activation, was significantly higher in the placebo group. This study demonstrated that BCAAs supplementation suppresses muscle damage.10

Branched Chain Amino Acids supplementation helps patients with advanced chronic liver disease.

BCAAs have been shown to affect gene expression, protein metabolism, albumin synthesis, apoptosis and regeneration of hepatocytes. In liver diseases, BCAAs levels are low and aromatic levels are high which predisposes to hepatic encephalopathy. To reverse that, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.11

How to use Branched Chain Amino Acids 1

i

  • There is not a standardized protocol for BCAAs supplementation. Many factors affect the needed amount, such as your goals, body mass, age, gender and exercises.
  • Recommended isoleucine dose is 48-72 mg/kg.
  • Recommended leucine dose is 2-10 g.
  • Combination dose 20 g of both.
  • Further research is needed to determine valine optimal dosage.

Toxicity of Branched-Chain Amino Acids

i

  • No adverse effects were noted in participants in BCAAs studies.
  • Large doses of Branched Chain Amino Acids (> 20 g) cause gastrointestinal pain.
  • They may increase plasma ammonia levels causing fatigue and motor dysfunction.12
  • Their role in causing Amyotrophic lateral sclerosis (ALS) is still under research with some studies confirming this relation (because of the high rates of ALS in athletes) and another studies denying any relation.13-15
  • High doses can predispose to insulin resistance and type 2 diabetes mellitus.

Mechanism of Action

i

Antifatigue effects of BCAAs supplementation:

BCAAs increase fatigue resistance by many mechanisms:

  • Serotonin central fatigue hypothesis: Elevated brain serotonin concentration induces fatigue according to the central hypothesis of fatigue.16-17 Ratio of Aromatic amino acids (especially tryptophan) to BCAAs increases in plasma during exercise which is associated with the central fatigue hypothesis.18-20 Also, exercise was found to increase tryptophan, serotonin substrate, transport into brain cells.21-23 BCAAs compete with aromatic amino acids for uptake into brain cells.
  • BCAAs decrease protein catabolism leading to decreased ammonia production which is a potential fatigue promotor.17, 24
  • BCAAs are an alternative fuel for muscle activities decreasing glycogen depletion.
Protein synthesis stimulating effects:

Leucine activates mammalian Target of Rapamycin (mTOR) that stimulates ribosomal protein synthesis.25 Exercise, insulin and excess calories can also activate mTOR stimulating protein synthesis.26-29 BCAAs supplementation reduces muscle atrophy F-box (MAFbx) which is associated with protein catabolism and atrophy.30 Leucine also stimulates insulin secretion, which is another protein synthesis stimulator and protein breakdown inhibitor.

Branched-Chain Amino Acids Metabolism in Relation to Insulin Resistance

i

  • BCAAs are metabolized mainly in muscles, rather than the liver, in contrast to other amino acids. 31-32
  • TNF-α, starvation and exercises are the most important activators of Branched-Chain α-Keto acid Dehydrogenase (BCKDH), the rate-limiting enzyme in BCAAs catabolism.33-37
  • Leucine mainly enhances muscle protein synthesis, while isoleucine enhances glucose uptake into cells. Valine role is still under research.1
  • BCAAs were found to have antiobesity effects as they enhance cellular glucose uptake, especially in rodent models, but increasing the levels of circulating BCAAs has the opposite effect on blood glucose.
  • Circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic outcomes as they predispose to insulin resistance and type 2 diabetes mellitus. The mechanism linking increased levels of BCAAs to type 2 diabetes mellitus is thought to involve leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), a complex that contains mTOR, which results in uncoupling of insulin signalling at an early stage.38-40

Causes of increased BCAAs levels in insulin resistance:

i

  • Increased protein consumption in the overweight/obese or insulin resistant subjects as an alternative fuel for the body instead of glucose.41
  • The accelerated protein degradation due to loss of insulin anabolic effects, which has been reported in both humans and animal models of insulin resistance.41-44
  • Impaired BCAAs catabolism, especially in adipose tissue, which contributes to the rise in Branched Chain Amino Acids in obesity and insulin resistant states. At least in rats, the increase in serum BCAAs appears to correlate with less activity of the BCKDH enzyme complex in adipose tissue, this enzyme complex appears to be downregulated in the adipose of obese, insulin resistance.45
  • mTOR has been considered as the central signalling molecule mediating the interaction between amino acids and insulin.46-49
  • An association between BCAAs and insulin resistance in normal weight subjects was also found.

Mechanism of Branched-Chain Amino Acids induced insulin resistance

References

i

  1. Branched Chain Amino Acids.Examine.com. http://examine.com/supplements/Branched+Chain+Amino+Acids/. Accessed February 23, 2016.
  2. Lu J, Xie G, Jia W, Jia W. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2013. http://www.ncbi.nlm.nih.gov/pubmed/23385611. Accessed February 23, 2016.
  3. Layman DK. The role of leucine in weight loss diets and glucose homeostasis. J Nutr 2003; 133(1): 261S–267S
  4. Shimizu M, Miyagawa K, Iwashita S, Noda T, Hamada K, Genno H, Nose H. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2012. http://www.ncbi.nlm.nih.gov/pubmed/21744005. Accessed February 23, 2016.
  5. Gualano AB, Bozza T, Lopes De Campos P, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2011. http://www.ncbi.nlm.nih.gov/pubmed/21297567. Accessed February 23, 2016.
  6. Blomstrand E, Hassmén P, Ek S, Ekblom B, Newsholme EA. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1997. http://www.ncbi.nlm.nih.gov/pubmed/9124069. Accessed February 23, 2016.
  7. van Hall G, Raaymakers JS, Saris WH, Wagenmakers AJ. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1995. http://www.ncbi.nlm.nih.gov/pubmed/7473239. Accessed February 23, 2016.
  8. Portier H, Chatard JC, Filaire E, Jaunet-Devienne MF, Robert A, Guezennec CY. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2008. http://www.ncbi.nlm.nih.gov/pubmed/18704484. Accessed February 23, 2016.
  9. Wiśnik P, Chmura J, Ziemba AW, Mikulski T, Nazar K. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2011. http://www.ncbi.nlm.nih.gov/pubmed/22050133. Accessed February 23, 2016.
  10. Shimomura Y, Inaguma A, Watanabe S, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2010. http://www.ncbi.nlm.nih.gov/pubmed/20601741. Accessed February 23, 2016.
  11. Kazuto Tajiri, Yukihiro Shimizu. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837260/. Accessed February 23, 2016.
  12. Elango R, Chapman K, Rafii M, Ball RO, Pencharz PB. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2012. http://www.ncbi.nlm.nih.gov/pubmed/22952178. Accessed February 23, 2016.
  13. Contrusciere V, Paradisi S, Matteucci A, Malchiodi-Albedi F. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2010. http://www.ncbi.nlm.nih.gov/pubmed/19763733. Accessed February 23, 2016.
  14. Gredal O, Møller SE. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1996. http://www.ncbi.nlm.nih.gov/pubmed/24178636. Accessed February 23, 2016.
  15. Venerosi A, Martire A, Rungi A, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2011. http://www.ncbi.nlm.nih.gov/pubmed/21462321. Accessed February 23, 2016.
  16. Davis JM, Alderson NL, Welsh RS. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2000. http://www.ncbi.nlm.nih.gov/pubmed/10919962. Accessed February 23, 2016.
  17. Ament W, Verkerke GJ. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2009. http://www.ncbi.nlm.nih.gov/pubmed/19402743. Accessed February 23, 2016.
  18. Blomstrand E, Celsing F, Newsholme EA. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1988. http://www.ncbi.nlm.nih.gov/pubmed/3227900. Accessed February 23, 2016.
  19. Blomstrand E. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2001. http://www.ncbi.nlm.nih.gov/pubmed/11310928. Accessed February 23, 2016.
  20. Howarth KR, Burgomaster KA, Phillips SM, Gibala MJ. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2007. http://www.ncbi.nlm.nih.gov/pubmed/17581840. Accessed February 23, 2016.
  21. Nybo L, Nielsen B, Blomstrand E, Moller K, Secher N. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2003. http://www.ncbi.nlm.nih.gov/pubmed/12754171. Accessed February 23, 2016.
  22. Blomstrand E, Møller K, Secher NH, Nybo L. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2005. http://www.ncbi.nlm.nih.gov/pubmed/16218925. Accessed February 23, 2016.
  23. Blomstrand E. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2006. http://www.ncbi.nlm.nih.gov/pubmed/16424144. Accessed February 23, 2016.
  24. Jin G, Kataoka Y, Tanaka M, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2009. http://www.ncbi.nlm.nih.gov/pubmed/19216057. Accessed February 23, 2016.
  25. Chang TW, Goldberg AL. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1978. http://www.ncbi.nlm.nih.gov/pubmed/649598. Accessed February 23, 2016.
  26. Hans C Dreyer, Satoshi Fujita, Jerson G Cadenas, David L Chinkes, Elena Volpi, Blake B Rasmussen. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2006. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1890364/. Accessed February 23, 2016.
  27. Kubica N, Bolster DR, Farrell PA, Kimball SR, Jefferson LS. Resistance Exercise Increases Muscle Protein Synthesis and Translation of Eukaryotic Initiation Factor 2Bϵ mRNA in a Mammalian Target of Rapamycin-dependent Manner. JBC. 2005; 280:7570-7580. http://www.jbc.org/content/280/9/7570.abstract. Accessed February 23, 2016.
  28. Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DH. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2007. http://www.ncbi.nlm.nih.gov/pubmed/17277771. Accessed February 23, 2016.
  29. Elmadhun NY, Lassaletta AD, Chu LM, Sellke FW. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2013. http://www.ncbi.nlm.nih.gov/pubmed/23083540. Accessed February 23, 2016.
  30. Borgenvik M, Apró W, Blomstrand E. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2012. http://www.ncbi.nlm.nih.gov/pubmed/22127230. Accessed February 23, 2016.
  31. Shimomura Y, Fujii H, Suzuki M, Murakami T, Fujitsuka N, Nakai N. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1995. http://www.ncbi.nlm.nih.gov/pubmed/7782942. Accessed February 23, 2016.
  32. Suryawan A, Hawes JW, Harris RA, Shimomura Y, Jenkins AE, Hutson SM. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1998. http://www.ncbi.nlm.nih.gov/pubmed/9665099. Accessed February 23, 2016.
  33. Harris RA, Zhang B, Goodwin GW, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1990. http://www.ncbi.nlm.nih.gov/pubmed/2403034. Accessed February 23, 2016.
  34. Kobayashi R, Shimomura Y, Murakami T, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 1999. http://www.ncbi.nlm.nih.gov/pubmed/10524349. Accessed February 23, 2016.
  35. Xu M, Nagasaki M, Obayashi M, Sato Y, Tamura T, Shimomura Y. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2001. http://www.ncbi.nlm.nih.gov/pubmed/11563860. Accessed February 23, 2016.
  36. Shiraki M, Shimomura Y, Miwa Y, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2005. http://www.ncbi.nlm.nih.gov/pubmed/15707973. Accessed February 23, 2016.
  37. Shimomura Y, Yamamoto Y, Bajotto G, et al. Nutraceutical Effects of Branched-Chain Amino Acids on Skeletal Muscle. JN. 2006; 136:5295-5325. http://jn.nutrition.org/content/136/2/529S.short. Accessed February 23, 2016.
  38. Newgard CB, An J, Bain JR, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2009. http://www.ncbi.nlm.nih.gov/pubmed/19356713. Accessed February 23, 2016.
  39. Wang TJ, Larson MG, Vasan RS, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2011. http://www.ncbi.nlm.nih.gov/pubmed/21423183. Accessed February 23, 2016.
  40. Lynch CJ, Adams SH. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2014. http://www.ncbi.nlm.nih.gov/pubmed/25287287. Accessed February 23, 2016.
  41. Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011; 17(4): 448–453.
  42. Luzi L, Castellino P, DeFronzo RA. Insulin and hyperaminoacidemia regulate by a different mechanism leucine turnover and oxidation in obesity. Am J Physiol. 1996; 270(2 Pt 1): E273–E281.
  43. Argilés JM, Busquets S, Alvarez B, López-Soriano FJ. Mechanism for the increased skeletal muscle protein degradation in the obese Zucker rat. J Nutr Biochem. 1999; 10(4): 244–248.
  44. Wang X, Hu Z, Hu J, Du J, Mitch WE. Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006;147(9): 4160–4168.
  45. She P, Reid TM, Bronson SK, et al. PubMed. Bethesda, Maryland: National Center for Biotechnology Information; 2007. http://www.ncbi.nlm.nih.gov/pubmed/17767905. Accessed February 23, 2016.
  46. Haruta T, Uno T, Kawahara J, et al. A rapamycin-sensitive pathway downregulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol. 2000;14(6): 783–794.
  47. O’Connor JC, Freund GG. Vanadate and rapamycin synergistically enhance insulin-stimulated glucose uptake. Metabolism. 2003; 52(6): 666–674.
  48. Pederson TM, Kramer DL, Rondinone CM. Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation. Diabetes. 2001; 50(1): 24–31.
  49. Sun XJ, Rothenberg P, Kahn CR, et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991; 352(6330): 73–77.
  50. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004; 18(16): 1926–1945.
  51. Hara K, Maruki Y, Long X, et al. a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002; 110(2):177–189.
  52. Haruta T, Uno T, Kawahara J, et al. A rapamycin-sensitive pathway downregulates insulin signalling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol. 2000;14(6): 783–794.
  53. O’Connor JC, Freund GG. Vanadate and rapamycin synergistically enhance insulin-stimulated glucose uptake. Metabolism. 2003; 52(6): 666–674.
  54. Pederson TM, Kramer DL, Rondinone CM. Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation. Diabetes. 2001; 50(1): 24–31.
  55. Sun XJ, Rothenberg P, Kahn CR, et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature. 1991; 352(6330): 73–77.
Real Time Analytics
Skip to toolbar