Shawn, Kev, Michael - a great topic area. This question, to my knowledge, has not been directly investigated. William Apro and Eva Blomstrand did a great job with signalling http://www.ncbi.nlm.nih.gov/pubmed/20528801. However, signalling responses do not necessarily mirror changes in MPS. We (Stirling and Exeter) have some interesting data imminent so watch this space.

be careful of the supplement industry.

Many of the products marketed have pseudoscience behind them and are not really worth the money.It is not difficult to get a supplement product on the market.

Essentially, there maybe no study for the current ratio used.

You're right on the point.

I believe that in 2013 there should be more than only marketing hype behind the $100B ($30B in US) of the supplements industry.

There's only one research supported ratio and it's 2:1:1. The same ratio that naturally occurs in muscle. Of course there is data on leucine alone, but if used consistently the thought is you will deplete the others and it could be counterproductive long run if used chronically. Further, there is benefit to the others. Isoleucine for example may enhance insulin sensitivity thereby increasing the efficacy of their action.

Simple answer, until research shows otherwise...2:1:1. My advise is 7g, which would provide 3.5g of leucine, a dose that has been shown to maximize MPS. There may be synergy with other leucine metabolites like HMB, HICA, KIC, etc. but that data is still in its infancy at this point.

Thanks for a great contribution Shawn. Can you share your sources?

In 2011, Pasiakos et al. proved a leucine enriched AA blend (other AA's). 3.5g of leucine but in 4:1:1 ratio in regards to isoleucine & valine. See picture.

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis.

http://www.ncbi.nlm.nih.gov/pubmed/21775557

I dream of the day we will see the true optimal BCAA ratio and dose, or better, for each sport. (ig: In terms of numbers 9g of 3.8:1.3:1 for bodybuilding, 8.5 g of 3.1:1.4:1 for football, 7.5g of 2.8:1.5:1 for tennis, etc...

Of the 2:1:1 BCAA studies? I didn't know there was a 4:1:1 in human athletes. Like I said there's studies with leucine, and leucine enriched protein, and EAA studies that have a variety of ratios. Leucine works. What is optimal for a BCAA blend? To this point we'd say 2:1:1. Unless there's clear data showing otherwise.I will look that up, good to know. There is a dearth of data on the 2:1:1...based on the occurrence in muscle...for 20 years plus now. I am not sure what I should provide resources for.

Agreed on the actual specific dose for sport, etc, but then exertion, body type, diet (especially consumption of other aminos), acute diet (ketogenic or high protein?), etc. would make it complex even at that.

The 3.5g of leucine being optimal has been shown in a variety of ways. The range seems to be 2.0-3.5g, but just as I mentioned before with all those factors it's tough to simply say that. But, if I was to try and ensure MPS, I'd say take 3.5g fairly quickly (e.g. not sipping over a long period), either with 35+g of Whey or 7g 2:1:1 BCAA or 3.5g of leucine itself)

Kevin what would you like sources for the 2:1:1 ratio being most understood/studied? Isoleucine and insulin sensitivity? Optimal leucine dose? The leucine metabolites?

I'm not sure what you'd like citations for, but when I have a chance I can do that. This could turn in to a thesis, but I'll try.

Apologizes for the confusion Shawn, the 4:1:1 ratio I was referring to was in an EAA. You're right that all the factors that would affect, maybe in 10 years from now there will be an equation including all those parameters.

At this point I would benefit from links to most topics you're mentioning (assuming they're accessible online):

-Isoleucine and insulin sensitivity

-Optimal leucine dose

-The leucine metabolites

and the 20+ years old article before death of data.

I have not been around researchgate long enough to understand if I'm being too pushy or demanding, feel free to let me know if so. I'm really passionate about this topic.

Shawn, Kev, Michael - a great topic area. This question, to my knowledge, has not been directly investigated. William Apro and Eva Blomstrand did a great job with signalling http://www.ncbi.nlm.nih.gov/pubmed/20528801. However, signalling responses do not necessarily mirror changes in MPS. We (Stirling and Exeter) have some interesting data imminent so watch this space.

Hi all. I am responsible of the first oral supplement of only BCAA gone to market, it was 1980-1981, and in Italy, by an italian firm, Bracco Pharmaceuticals. I would not resume the animal studies I did using the so called Fisher's solution that brought me to do that. Helas, many publications before internet appeared should be considered fully lost... I will summarize the full story behind the 2:1:1 ratio. The ratio 2:1:1 was established a priori by me after observing absorption curves of pure leucine, and plasma behaviors of the other neutral AAs. Studies started in 1978, under my protocol, in patients with recurrent episodes of hepatic encephalopathy. Primary end point was prevention of recurrence of episodes of hepatic coma. Pharmacokinetics of ingestion of different loads of BCAA in that ratio has been published, and the modifications of other aminoacids, as I remember, have not.

I had and still do not have notice of any work with those ratios before mine. We tested 16 grams a day for one year in cirrhotics in an open study, an observed a series of data that have led to further developments. One of the most interesting was the efficiency of this formulation, and in those dosages, to reduce neutral aromatic aminoacids concentrations. Erroneously, we then thought this was an efficient target for prevention of hepatic encephalopathy. This was coupled to increased plasma protein synthesis, and clinically aptients referred less astenia. this led, in turn, to observe that urinary creatininuria, extremely low in those patients, was progressively increased and parallelled better physical performance. On those days, I had to face many young patients referred to observation with altered liver enzymes due to improper use of anabolizing steroids . Most were body builders. Being the only to have large amounts of that formulation of BCAA, I exchanged suspension of steroids against giving adequate amounts of BCAA and strict biological and biochemical follow up. Thus, empirically I could establish ratios between dietary proteins and increasing amounts of BCAA to achieve maintenance or growth of muscles in training athletes, thanks to the total , maniacal, respect by those atheletes of dietary daily introduction. They ate for months any day of the week exctly the same foods, and for months. At he end, those studies allowed to understand that BCAA are just a part, percentually relevant but not the sole one, responsible for maintenenance and promotion of protein syntheses. All esential amino acids should be present, although in stoiciometrical ratios extremely different and peculiar among them, to allow syntheses.Texas University group in san antonio has done a lot of magnificent works in this sense. In my profile many of the papers linked to this evolution could be found, but this is the true simple story of the 2:1:1 ratio!

And, please, revise critically your opinion that in muscle proteins (which one? Actin? Myosin?) would be stoichiometrically leucine 2 while leucine and valine 1...I have serious doubts about that.

I recently started a discussion on the competitive inhibition between BCAA described in some studies, still I maintain the doubt as to exist a difficulty in leucine because of the content of Ile and Val the ideal ratio would be significantly higher concentration of Leu compared the Ile and Val order to have a benefit MPS. Yourselves can give your opinion on my question :)

Article Leucine supplementation of a low-protein mixed macronutrient...

Hi Mei-Lei,

As Dr. Witard has already indicated, signalling responses do not necessarily mirror changes in MPS. More importantly, if you're asking for practical reasons and not for some purely biochemical reason, MPS itself is not a good predictor of net protein accretion or strength gains, particularly provided adequate high-quality protein intake. See for instance:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089431

https://www.researchgate.net/publication/6850668_The_Effects_of_Protein_and_Amino_Acid_Supplementation_on_Performance_and_Training_Adaptations_During_Ten_Weeks_of_Resistance_Training

Article The Effects of Protein and Amino Acid Supplementation on Per...