A handful of useful studies relating to BCAAs and their benefits. I hadn’t actually realised how much of an important role they play in terms of ‘switching on’ anabolic signalling and thought the main benefit for supplementing with them was mostly in replacing BCAAs oxidised during training. All the more reason to take them.
Branched-chain amino acids as fuels and anabolic signals in human muscle.
Rennie MJ, Bohé J, Smith K, Wackerhage H, Greenhaff P.
Medical Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK. michael.rennie@nottingham.ac.uk
During exercise, there is an increase in amino acid (AA) oxidation accompanied by a depression in whole-body protein synthesis and an increase in protein breakdown. Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements. When investigating the effects of AA on the control of muscle protein synthesis (MPS), we showed that increased availability of mixed AAs caused a rise in human MPS to about the same extent as complete meals. Leucine alone (and to some extent other essential, but not nonessential, AAs) can stimulate MPS for a short period, suggesting that leucine acts as a signal as well as a substrate. MPS stimulation by infused AAs shows tachyphylaxis, returning to basal rates after 2 h, possibly explaining why chronically elevated leucine delivery does not elevate MPS clinically. Increased availability of essential amino acids (EAAs) results in dose-related responses of MPS, but, in elderly subjects, there is blunted sensitivity and responsiveness associated with decreased total RNA and mRNA for signaling proteins and signaling activity. Increases of MPS due to EAAs are associated with elevation of signaling activity in the mammalian target of rapamycin (mTOR)/p70 ribosomal subunit S6 kinase eukaryotic initiation factor 4 binding protein 1 pathway, without requiring rises of plasma insulin availability above 10 microU/mL. However, at insulin of <5 microU/mL, AAs appear to stimulate MPS without increasing mTOR signaling. Further increasing availability of insulin to postprandial values increases signaling activity, but has no further effect on MPS.
http://www.ncbi.nlm.nih.gov/pubmed/1636 ... t=Abstract
Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise.
Blomstrand E, Eliasson J, Karlsson HK, Köhnke R.
Department of Surgical Science, Karolinska Institutet, Stockholm, Sweden. eva.blomstrand@gih.se
BCAAs (leucine, isoleucine, and valine), particularly leucine, have anabolic effects on protein metabolism by increasing the rate of protein synthesis and decreasing the rate of protein degradation in resting human muscle. Also, during recovery from endurance exercise, BCAAs were found to have anabolic effects in human muscle. These effects are likely to be mediated through changes in signaling pathways controlling protein synthesis. This involves phosphorylation of the mammalian target of rapamycin (mTOR) and sequential activation of 70-kD S6 protein kinase (p70 S6 kinase) and the eukaryotic initiation factor 4E-binding protein 1. Activation of p70 S6 kinase, and subsequent phopsphorylation of the ribosomal protein S6, is associated with enhanced translation of specific mRNAs. When BCAAs were supplied to subjects during and after one session of quadriceps muscle resistance exercise, an increase in mTOR, p70 S6 kinase, and S6 phosphorylation was found in the recovery period after the exercise with no effect of BCAAs on Akt or glycogen synthase kinase 3 (GSK-3) phosphorylation. Exercise without BCAA intake led to a partial phosphorylation of p70 S6 kinase without activating the enzyme, a decrease in Akt phosphorylation, and no change in GSK-3. It has previously been shown that leucine infusion increases p70 S6 kinase phosphorylation in an Akt-independent manner in resting subjects; however, a relation between mTOR and p70 S6 kinase has not been reported previously. The results suggest that BCAAs activate mTOR and p70 S6 kinase in human muscle in the recovery period after exercise and that GSK-3 is not involved in the anabolic action of BCAAs on human muscle.
http://www.ncbi.nlm.nih.gov/pubmed/1636 ... t=Abstract
Cool huh? But there’s another good reason to supplement with BCAAs – their effect on the central nervous system and how they limit Central Fatigue Syndrome.
Central fatigue is the inability to maintain maximal or near maximal rates of muscle fibre unit recruitment throughout a workout due to increased tryptophan being taken up by the brain. This increase in tryptophan leads to an increase in serotonin which in turn has a ‘relaxing’ effect on the central nervous system and thus inhibits high-end performance. Now good old BCAAs compete aggressively with tryptophan and so can prevent it from reaching the brain in significant enough doses to cause central fatigue.
Branched-chain amino acids and central fatigue.
Newsholme EA, Blomstrand E.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. eva.blomstrand@gih.se
An account of the tryptophan (Trp)-5-hydroxytryptamine (5-HT)-central fatigue theory is provided and an explanation of how oral administration of BCAAs can decrease fatigue on the basis of this theory is given. The rate-limiting step in the synthesis of 5-HT is the transport of Trp across the blood-brain barrier. This transport is influenced by the fraction of Trp available for transport into the brain and the concentration of the other large neutral amino acids, including the BCAAs, which are transported via the same carrier system. During endurance exercise, there is an uptake of Trp by the brain, suggesting that this may increase the synthesis and release of 5-HT in the brain. Oral intake of BCAAs may reduce this uptake and also brain 5-HT synthesis and release, thereby delaying fatigue. Other hypotheses for the effect of BCAAs on central fatigue are included.
http://www.ncbi.nlm.nih.gov/pubmed/1636 ... t=Abstract
A third reason to take BCAAs relates to the by products of their oxidation. When they are utilised during exercise, they breakdown into Glutamine and Alanine. These by products are useful because the Alanine can be sent to the liver for vital conversion into glucose if not enough glycogen is present for the powerful Type IIx fast-twitch muscle fibres, and because the glutamine release occurs at cellular level it has an ability to saturate and volumise the muscle cells providing a greater anabolic stimulus (orally administered glutamine cannot do this to anything like the same degree).
Precursor for the Formation of Alanine & Glutamine
The BCAA's are involved in maintaining glucose homeostasis through the glucose-alanine cycle. The glucose-alanine cycle involves pyruvate (derived from glucose) being transaminated in muscle to form alanine, with the BCAA serving as the main nitrogen source (donors) for the synthesis of alanine (Holecek, 2002).
The newly synthesized alanine is released in the blood stream and sent to the liver where it is converted into glucose through gluconeogenesis. This glucose can then be sent from the liver back to the working muscle to be used as fuel.
The amino acid glutamine has multiple roles in the body. According to Houston (2001), "Glutamine content in skeletal muscle and other tissues appears to have a regulatory role in whole body protein synthesis." Glutamine levels inside muscle govern protein synthesis and nitrogen balance and therefore muscle gain (VanAcker et al. 1999).
Glutamine is also a powerful cell volumizer (Haussinger et al. 1993). An increase in cell volume, also called cell swelling, stimulates many anabolic pathways (synthesis of protein and glycogen) and inhibits catabolic pathways (protein degradation) (Haussinger, 1996). Glutamine is a "nitrogen shuttle" between organs, a fuel for cells of the immune system and intestines, and a precursor for nucleotide synthesis (Holecek, 2002).
Ingestion of supplemental free-form glutamine or glutamine peptides is oxidized by the intestinal tract or taken up by the liver and kidney, all of which is beneficial but supplementing with BCAA can cause de novo synthesis of glutamine inside skeletal muscle (Houston, 2001).
The body's need for alanine and glutamine is increased during exercise is met by BCAA from muscle protein breakdown (Holecek, 2002). Increased muscle protein breakdown equates to muscle loss, which no athlete wants. By supplementing with BCAA, one can deliver the needed building blocks for both alanine and glutamine and spare muscle tissue.
And guess what? There’s more! BCAAs can stimulate the same anabolic pathways as insulin does but independently of insulin action (although BCAAs do also stimulate insulin).
One pathway through which protein synthesis can be increased is the phosphatodyl-inositol-3-kinase pathway (PI3K). PI3K regulates glucose uptake through GLUT4 translocation and also increases amino acid uptake. Insulin, the body's "storage" hormone, works by activating the PI3K pathway.
leucine ingestion causes insulin secretion, but leucine can also directly activate PI3K in the absence insulin (Nishitani et al. 2002), suggesting leucine to have a synergistic role with insulin as a PI3K activator (Layman, 2002). So not only can leucine increase glucose uptake, it can also increase its own and other amino acids' uptake into cells.
These facts suggest that taking additional BCAA with carbohydrates around ones workout will lead to a synergistic increase in glucose and amino acid uptake into skeletal muscle. Leucine can stimulate protein synthesis through insulin secretion and the activation of the PI3K pathway, but can also stimulate protein synthesis through other pathways.
excerpt from: http://www.nimbusnutrition.com/Articles/BCAAs.aspx
One final comment about BCAA ratios. Although many of the anabolic benefits of BCAAs are specifically related to leucine, leucine supplementation alone is not anywhere near as effective as taking leucine in combination with its two other BCAA friends isoleucine and valine. The reason for this is that leucine requires the other BCAAs to function fully, and also that high levels of supplemental leucine alone actually suppress levels of isoleucine and valine.
Most BCAA preparations therefore provide a leucine/isoleucine/Valine ratio of 2/1/1 as this mimics the ratio found in skeletal muscle tissue. This is fine and adequate, however further advantage of leucines anabolic properties can be made by altering the ratio slightly to 4/1/1 without any risk of suppressing the levels of isoleucine or Valine. This is the exact strategy recommended by top coach Charles Poliquin who suggests high level dosing at 0.22g per Kg of bodyweight both before and after training (providing 0.44g of BCAA 4.1.1 in total).
If anyone is further interested in BCAA research, the following pdf is quite informative: http://jn.nutrition.org/cgi/reprint/136/1/333S.pdf
