If Validated This is Huge News on Leucine -- A Paradox Solved?

So many paradoxes around leucine – The Most Essential Amino Acid – But the most powerful stimulant of MTOR – Can’t build muscle without it – but stimulates Insulin secretion . . .

Been avoiding Leucine in fasted state and consuming post workout, but this video has me rethinking that.

What do others think and know here?


Layne Norton was on Andrew Huberman’s podcast and briefly talked about Leucine role in Mtor. It might be of interest to you as Norton did a lot of his graduate work on Leucine


Rapamycin is a wonder drug in the sense that it lets us have our cake and eat it. What I mean is that the lifespan and healthspan strategies conflict. Strategy A for a 40 year old male might involve castration, caloric restriction, fasting, leucine restriction, etc. The strategy A man ages slowly but suffers from frailty. Strategy B man lifts heavy, takes TRT and perhaps HGH, and consumes high leucine, etc. He dies in his early sixties of heart disease or cancer, but he looks great in the casket. Rapamycin and associated molecules may be the only intervention that fights both aging and frailty at the same time.


Dudley Lamming says that isoleucine is worse than leucine in his latest ARDD2022


So, what are we to do?
“The difference between isoleucine and leucine is that isoleucine is an essential amino acid that is important for energy production, while leucine is an essential amino acid that is important for muscle growth and recovery. Both are found in animal proteins, but leucine is typically found in higher concentrations than isoleucine.”
Most animal proteins contain around 3-5% isoleucine by weight.

So, the fat man tells you how to eat? :sweat_smile:

Low protein in the elderly results in sarcopenia and frailty.


I was interested in his saying that the concentrations of leucine needed to activate mTorc are fairly high, in excess of 1mM (12:00 in video), while the doses they give get them to 0.5mM and levels after a good high protein meal are typically 0.25 - 0.3 mM. This raises SIRT1 and SIRT3, he says, without raising mTORC.


I believe that is true and in fact, the video tells me that it would take more protein than even a protein-rich meal has to raise leucine to levels that would raise mTORC.

In any case, lower protein intake is associated with better longevity in younger people rather than older people.

“Conclusions: Our findings suggest that a high consumption of dietary protein is inversely associated with frailty in older adults.”
“The meta-analysis of four studies indicated that older adults with sarcopenia consumed significantly less protein than their peers with no sarcopenia”


Yes exactly – that’s the revelation here – Leucine in moderation (up to a high protein meal equivalent doesn’t drive MTOR.

Question is does it shut down autophagy?

But regardless I’m going to be much less concerned about taking Essential Amino Acids - or protein rich foods in an already fasted state.

I must be missing something. If you’re fasting, how are you getting Leucine?

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In a daily intermittent fast (let’s say eating in a 4/5h. window from 8:00AM forth) you can/should have as much protein intake as in previous non-fasting days. The ideal program is to have as much nutrients, vitamins, aminoacids, proteins, … but in a much shorter period of time every single day, IMHO.

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I think Peter Attia would refer to your strategy as time restricted feeding instead of fasting, but I get your point and it makes sense. It serms like we are looking for protein sources that are high in Leucine, but low in methionine. Leucine appears to be even more of a paradox now. Leucine promotes heathy growth, but extends lifespan in mice in combination with things like Resveratrol. The Blagosklony thesis in a nutshell is that mtor related growth accelerates aging. We now have at least three things that promote muscle growth yet slow aging. Rapamycin, exercise, and leucine. Any others?


Good point – to be precise, going to be less hesitant to take Leucine or Essential Amino acids as a supplement while in a fasted state – concern was/is getting out of autophagy or ketosis.

I get most of my leucine from non food sources like below – am I still fasting if I have 5 grams of this?

Aminos Capsules – Kion?

If you are fasted and ingest some protein your liver will probably kickstart some gluconeogenesis to replenish glycogen stores. I guess that if your quadriceps muscles were glycogen depleted, such as from a hard bicycle ride, you might stay in ketosis anyway. But why only 5 grams? I think you would want thirty grams or more to get any muscle protein synthesis going. So my approach is stupidly binary. I water only fast, or I eat like a clydesdale. Is this good? Probably not.

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Maybe add some more glycine if you want the positive effects of leucine supplementation without the downside.
"Glycine is in fact the only acceptor for methyl groups, and can in that way clear an excess of methionine. Too much methionine is not healthy: methionine is converted into homocysteine, a substance that has been associated with accelerated aging and aging-related disorders (R). Glycine can reduce methionine levels in the blood. "


I thought one of the main goals of fasting was to avoid protein, especially leucine.

Don’t think so, not in my case anyways. No, I think it is mainly to avoid glucose. It gives the pancreas a rest and promotes ketosis which is why most people do keto. (Short explanation as it is more complex than this.)

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Well if nominal amounts of leucine (up to the amount in a “high protein meal”) is not stimulating MTOR then seems like autophagy and ketosis can continue after consuming Leucine . . . .

I always assumed that the glucose regulation loop and the mtor loop were different although related. Assume you have fasted for 3 days and are in ketosis. If you eat protein, your liver can make glycogen from that meal and switch from burning ketones, but if that meal is mostly leucine, mtorc1 may remain low. Is this correct?

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I’ve come to the same conclusion. I’ve lowered my whey intake and substituted instead with collagen peptides.


For you all who take magnesium glycinate, are you considering the mass of glycine as part of your intake? Am I wrong in thinking you get around 1700mg glycine per 2g dose?

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