Rhonda: Are you familiar with, like, any of the dietary nutritional research on IGF-1 and mTOR and specifically with amino acids and how...

Peter: Yeah. I mean that's, sort of, my biggest obsession, I think, is probably around those topics. So it's complicated. I think we have probably a better understanding of mTOR. I mean I think it's very clear that mTOR is amino acid driven. In fact, what's today? Friday? Last Thursday, eight days ago, David Sabatini and his group at MIT published a paper in "Science" that identified the amino acid sensor for mTORC1. Now, it's always been suspected what it was, which was leucine was the highest affinity, but in fact he's now crystallized that structure. So if you even think about it through the lens of, like, "Why do bodybuilders or people who love lifting weights, want to take Branched-Chain Amino Acids while they're exercising?" The reason is largely through this empirical observation that it enhances muscles growth and/or prevents muscle degradation during exercise.

What I think is really interesting is that we now know exactly what's going on. So the Branched-Chain Amino Acids, there are three, leucine, isoleucine, and valine. It turns out that isoleucine and valine are virtually irrelevant. It's pretty much all leucine. And what's really clever just from an evolutionary perspective is that mTORC in muscle has a much higher affinity for leucine than mTORC1 in fat or in hepatocytes. Now, that's a good thing because you'd like to believe that in times of nutrient deprivation even a trace sign of leucine should preferentially provide the muscle with its growth signal before providing the adipocyte or hepatocyte.

So from a nutrient-sensing pathway, what you could infer from that is too little leucine, probably a bad thing, too much leucine, probably a bad thing. Now, what too much and too little are I think remains to be seen.

The other thing to keep in mind is...you know, because one of the questions a friend of mine asked me recently, actually a mutual friend, Tim Ferris, is "Can we take too much leucine during a workout?" And again, I don't think we know the answer but extrapolating from the animal data I think 5 grams of leucine during a workout, probably not harmful. And it also doesn't stick around very long because when we take amino acids in a workout, if you, sort of, sip them throughout the workout you're taking a free amino acid, so it's got a relatively short stay in the body. In fact, one of the pharmaco interests on this front, which is to treat diseases of muscular wasting, is to actually come up with molecules that are not necessarily more potent agonists of the leucine receptor but would stick around a lot longer. Because that's actually the problem with the nutrition side, is we can't keep leucine around long enough to stimulate muscle growth.