So that you don’t get too lost with the abbreviations or get confused by the relevance of one group of amino acids to another, I will be using the following terms. When you see mixed amino acids (MAA) this means all of the amino acids. Within this are the 9 essential amino acids (EAA), which contain the 3 branch chain amino acids (BCAAs). Leucine is one of the branch chain amino acids that has been studied in the most depth, due to its role in stimulating protein synthesis through the mTOR pathway.
Much of the research on protein and amino acids and their role in performance has been done at the University of Birmingham by Tipton and colleagues. They have stated “it seems that the response of muscle anabolism may differ if amino acids are provided as intact proteins or as free amino acids.” For this reason much research has been done trying to find the optimal dose and timing of either intact protein (such as whey), or as free amino acids as either the EAAs or BCAAs. Much research is yet to be done, but we are learning more all the time. One interesting fact that is unknown, is whether or not those who are consuming large amounts of protein with high BCAA content, such as whey, meat and dairy. Will get any additional benefit from free form supplementation however it is likely that many of the beneficial effects of BCAAs can indeed be realized through the consumption of a ‘high BCAA protein source diet’. It is likely that the answer lies in the timing of it, as well as the conditions (e.g. fasted/fed) under which it is supplemented.
Essential vs Non-Essential
Early research ruled out the non-essential amino acids as stimulators of muscle protein synthesis. The graph below shows arterio-venous differences of amino acid nitrogen. The increase in levels for EAAs and Total (MAA) indicates a net uptake into the muscle.
Intact Protein vs Free Amino Acids
Two specific studies have been done, that when taken together give us an idea of both the timing of ingestion and the type (whey vs BCAAs). The first study compared the ingestion of free amino acids before versus after resistance training. In this study they concluded that “the response of net muscle protein synthesis to consumption of an essential amino acid + carbohydrate solution immediately before resistance exercise is greater than that when the solution is consumed after exercise.” The figure below shows the phenylalanine uptake across the leg, which was used to determine net muscle protein synthesis.
Soon after this study was published I remember seeing recommendations of people around the internet and forums saying that “we should all be consuming our protein shakes before training.” The justification was that whey is high in amino acids, and that whey is digested so quickly that it doesn’t matter whether whey or free form amino acids are used. Funnily enough, the second study showed that it does. It concluded “Amino acid uptake was not significantly different between PRE and POST when calculated from the beginning of exercise or from the ingestion of each drink.” They clarified this by referring to their earlier research saying, “Thus the response of net muscle protein balance to timing of intact protein ingestion does not respond as does that of the combination of free amino acids ...”
BCAAs are anti-catabolic
Early studies using the infusion of BCAAs showed a strong anti-catabolic effect. This was later confirmed with oral supplementation of both EAAs and BCAAs, with the BCAAs having the more pronounced effect. These studies are generally carried out with subjects that have been fasting overnight. Therefore if you train early in the morning, it is almost certainly a good idea to consume some BCAAs before your session. The practice of intermittent fasting is on the rise with many of the old myths about breakfast and frequent eating having been ‘busted’. In this instance, individuals might fast overnight, and then extend this fast for many hours. In this instance, consuming BCAAs pre-training again would be well advised. During a fast glycogen levels will slowly deplete which will lead to an increase in protein breakdown if exercise is commenced.
The most interesting study for me on leucine was done by Koopman et al (2005). To put their methods in perspective, for an 80kg individual they would consume 24g of CHO/hour (50:50 glucose: maltodextrin) and 16g protein hydrolysate/hr, with or without the addition of 8g leucine/hour. The amount of protein used had previously been shown to maximally stimulate protein synthesis rates in other studies. In this study there were 3 groups: a carbohydrate (CHO) control, a CHO plus protein (CHO+PRO) group, and CHO+PRO plus added leucine (CHO+PRO+LEU). Here’s what they found:
• Plasma insulin response was higher in the CHO+PRO+LEU vs CHO and CHO+PRO
• Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO+LEU and CHO+PRO vs CHO
• Lower protein oxidation rate in the CHO+PRO+LEU vs CHO+PRO
• Whole body net protein balance was significantly greater in CHO+PRO+LEU vs CHO and CHO+PRO.
• Mixed muscle protein synthesis, measured over a 6-h period of post-exercise recovery, was significantly greater in the CHO+PRO+LEU trial. Compared with the CHO trial with intermediate values observed in the CHO+PRO trial.
Unfortunately, in this study, the beverages given were not isocaloric, i.e. with each consecutive group there was a greater amount of substrate given. Another study has shown no extra benefit of adding extra leucine to whey. However, in this study they only used 3g of leucine. Similarly, they did not have a whey only group but instead compared it to previous results from their lab (it does not state whether the same subjects were used). This is clearly an area that needs more research but leucine is certainly the key player.
As an aside, whether or not carbohydrate (of low or high GI) is needed in the post workout period for either glycogen replenishment or the release of insulin is a debated topic. Protein and specifically the branch chain amino acids taken alone stimulate the release of insulin, a powerful recovery hormone. Consuming a mixture of BCAAs and carbohydrates will elicit an even greater response. The point is whether or not insulin is actually needed in the post training period, due to the fact that uptake of many nutrients is independent of insulin levels, due to translocation of transporters to the edge of cells. However, the abuse of insulin has been used by bodybuilders over the years to increase muscle size to superhuman proportions. This leads to the notion that getting insulin levels as high as possible, albeit transiently, in the post training period might convey greater gains in muscle mass. Certainly there is no effect of extra carbohydrate on either protein synthesis or protein degradation in the short term. However, if you are going to consume any carbohydrate at all, which in my opinion is a very good idea if you are trying to increase muscle mass. The post training period is as good a time if not the best time to consume the majority of your carbohydrate.
BCAAs and muscle soreness
Another area that BCAAs might be of benefit to is the reduction in muscle soreness that is seen after eccentric exercise. Many studies have shown this, as well as an attenuation of the reduction in muscle force caused by muscle damage, however this is still equivocal. This effect while not immediately apparent, can improve gains in muscle mass by allowing you to either increases the number of training sessions per month, or to have better quality training sessions depending on how your routine is set up.
A possible benefit for skinny guys
This article has focused on the mechanisms by which the BCAAs and leucine stimulate protein synthesis. An area which is not generally discussed is that of the use of BCAAs to increase appetite. A number of crazy supplements exist that claim to increase appetite for ‘skinny dudes’, so that they can simply consume the amount of energy they need to grow! Well, BCAAs might just have a role to play here. High levels of serotonin in the brain are thought to reduce appetite along with other effects on feelings of wellbeing and arousal. In the sports science literature, BCAAs have been used to compete with tryptophan (a precursor to serotonin), to delay fatigue. By reducing the brain uptake of tryptophan, BCAAs may therefore increase appetite. This has actually been used in the treatment of food related disorders such as anorexia where appetite is lost.
One thing that must always be remembered is that:
1) Research is based on statistical significance not real world significance. This can play out both ways i.e. 20% higher protein synthesis rates in the post training period may reach very high levels of statistical significance. But in the real world, with hundreds of other factors affecting muscle gain, a study may never actually be able to show how much extra muscle this equates to. It may only equate to 0.5lbs of extra muscle a year, therefore is it really worth it? Or a study may find muscle gain in one group is 2lb vs 4lb in another, yet this may not reach statistical significance. But in the real world I know which I’d take…
2) Research is done under specific conditions that don’t always mimic that of real life, so you need to work out if the group of individuals used and the training protocol and timing can be extrapolated to your situation.
Written by Martin MacDonald.
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