Which amino acids interrupt autophagy?

[amosmylove]

What I keep landing on is this: AI won't help much if you don't already have enough background to ask the right thing, and once you do, you barely need it.

Even so, after digging into this on my own and then posing the question in different ways, the answers I received were opposites. My leaning is to avoid taking and MICC injections while fasting. Still, can someone sort out these 2 conflicting explanations about what actually stops a fast when autophagy is the aim?

On top of that, for mitochondrial repair and to get the most from autophagy, a 48-72 hour fast appears to be optimal.

What frequency should that fast be done at?

Would BPC-157 or Ghk-cu interrupt an autophagy fast?

And does anyone happen to know whether my 5-htp supplement would also interrupt it?

 

[5byfive]

Throwing a question into Google search is likely the least effective route if what you're after is a 'good' AI reply. Not long ago I spent some time experimenting with various models. ChatGPT in particular appeared highly inclined to fabricate things. If it lacks the answer, or simply to conserve resources, it will lie. Claude comes across as far more truthful. They all have flaws, yet posing a thorough question to Claude will probably yield a fairly reliable answer.

Regarding what you asked, I have no idea.

 

[Vash]

My old routine was a 48hr fast every month. Autophagy only really gets going past 72 hours.

How peps would change any of that, I have no idea.

 

[tubby]

amosmylove said:

What I keep landing on is this: AI won't help much if you don't already have enough background to ask the right thing, and once you do, you barely need it.

Even so, after digging into this on my own and then posing the question in different ways, the answers I received were opposites. My leaning is to avoid taking and MICC injections while fasting. Still, can someone sort out these 2 conflicting explanations about what actually stops a fast when autophagy is the aim?

On top of that, for mitochondrial repair and to get the most from autophagy, a 48-72 hour fast appears to be optimal.

What frequency should that fast be done at?

Would BPC-157 or Ghk-cu interrupt an autophagy fast?

And does anyone happen to know whether my 5-htp supplement would also interrupt it?

Honestly, a hard and fast answer here isn't something I think is available, mainly because autophagy functions more as a broad concept than as a phenomenon that has been studied heavily enough to produce firm conclusions.

As for the items on your list, my expectation is that none of them would interrupt a water fast, provided the amounts weren't unusually large or some indirect mechanism I haven't considered comes into play. When I say interrupt a fast, I mean the situation where, after an extended fast, you consume more than a trivial amount and your appetite returns in a way that's very hard to miss.

If that's a reasonable proxy for autophagy, then I'd be surprised if any of those items carried enough calories to set off such a response.

One more thing worth mentioning: GLPs are somewhat unpredictable, and good data on whether they might support or interfere with autophagy is something I don't think we currently have. I remember a recent finding that a large share of the lean mass lost through GLP-driven weight reduction did not come with a drop in strength, which hints that this kind of weight loss might itself be autophagy or at least share some features with it. That said, this is highly speculative, and my read is that it was more the industry pushing back against the usual "muscle loss" criticism than a rigorous look at what the finding actually signifies.

 

[Devilseye]

This does have a clear-cut response. mTOR is heavily influenced by leucine, which acts as a powerful brake on autophagy. The branched-chain amino acids collectively turn mTOR on, and that shuts autophagy down. That is probably the reply you were after.

 

[amosmylove]

5byfive said:

Throwing a question into Google search is likely the least effective route if what you're after is a 'good' AI reply. Not long ago I spent some time experimenting with various models. ChatGPT in particular appeared highly inclined to fabricate things. If it lacks the answer, or simply to conserve resources, it will lie. Claude comes across as far more truthful. They all have flaws, yet posing a thorough question to Claude will probably yield a fairly reliable answer.

Regarding what you asked, I have no idea.

Yeah, it's clear to me that ChatGPT will fabricate answers rather than admit it doesn't know. I've lost count of how many falsehoods I've caught it in... then it hits me that I'm arguing with a machine, which makes me feel silly yet entertained.

Claude is something I've never tried. I'll check it out. No AI really appeals to me, but if it's sitting at the top of my search results, I'll typically skim some of it before going on to studies, articles, and similar sources. I'm aware that google/moderated search results shouldn't be trusted for anything of real substance, though for straightforward queries I turn to it frequently.

 

[amosmylove]

Devilseye said:

This does have a clear-cut response. mTOR is heavily influenced by leucine, which acts as a powerful brake on autophagy. The branched-chain amino acids collectively turn mTOR on, and that shuts autophagy down. That is probably the reply you were after.

Once you've eaten or taken those aminos, how long does it take before the body shifts into autophagy? Around 12-16 hours, maybe? And when it comes to holding back fasting/autophagy, do these aminos behave like sugars/carbs do?

 

[amosmylove]

Vash_ said:

My old routine was a 48hr fast every month. Autophagy only really gets going past 72 hours.

How peps would change any of that, I have no idea.

What kind of frequency makes a fast lasting 72+ hours worthwhile—maybe just a handful of times each year? I came across an explanation of the ways that can do the body good, and it really caught my interest.

 

[tubby]

Devilseye said:

This does have a clear-cut response. mTOR is heavily influenced by leucine, which acts as a powerful brake on autophagy. The branched-chain amino acids collectively turn mTOR on, and that shuts autophagy down. That is probably the reply you were after.

However, has anyone actually put this to the test? My point is that whatever you bring into your system operates at a systemic level in an extremely tiny quantity. Take 5 grams of sugar as an example (say, 1 or 2 glasses of lemon water)—that's not going to interrupt a fast in any meaningful way. So would a standard MICC injection, containing a modest amount of specific amino acids, really shut down autophagy, and do it in a manner that isn't just a fleeting dip? Of course, if someone goes the IM route, absorption into the bloodstream happens very quickly, so delivering it that way definitely could spike blood concentration fast.

Your observation about signaling is spot on, and I have a hunch that's exactly what OP meant when they first posed the question.

 

[UnusualLLama]

amosmylove said:

Vash_ said:

My old routine was a 48hr fast every month. Autophagy only really gets going past 72 hours.

How peps would change any of that, I have no idea.

What kind of frequency makes a fast lasting 72+ hours worthwhile—maybe just a handful of times each year? I came across an explanation of the ways that can do the body good, and it really caught my interest.

Last year I ran a handful of trials: 3 rounds of 5-day water-only fasting, spread across several months.

The genuine payoff only kicks in after you've pushed past those opening 48 hours or so — not that the early stage gives you nothing, but the shift really begins once your energy reserves are gone, fat becomes the fuel source, and autophagy is underway.

My actual focus, though, was comparing fat reduction against the loss of lean mass and strength. What came out of it: a solid amount of fat got stripped away, while strength held steady — nothing worse than the dip you'd anticipate from running on a different fuel system (I kept up my training and lifting throughout; cardio clearly got harder, yet lifting honestly felt excellent).

What I liked most: once the fast ended, I went through refeeding and then a stretch of normal eating, and the weight did not climb back. No rebound effect — it held.

Extended fasting in particular isn't suitable for everybody, and if you've got other conditions that could make it risky, you clearly shouldn't attempt it.

 

[Devilseye]

amosmylove said:

Devilseye said:

This does have a clear-cut response. mTOR is heavily influenced by leucine, which acts as a powerful brake on autophagy. The branched-chain amino acids collectively turn mTOR on, and that shuts autophagy down. That is probably the reply you were after.

Once you've eaten or taken those aminos, how long does it take before the body shifts into autophagy? Around 12-16 hours, maybe? And when it comes to holding back fasting/autophagy, do these aminos behave like sugars/carbs do?

The cascade of signal transduction that shuts down proteins tied to autophagy operates via protein phosphorylation, meaning fresh protein synthesis isn't necessary. Since phosphorylation is a relatively rapid chemical change, my estimate is that roughly an hour or so could pass after consuming a decent quantity of leucine before effects appear. Glucose wouldn't come close to matching that. It would only slightly elevate insulin and turn on mtor, but you'd need a large amount to actually suppress autophagy. In other words, 1 or 2 grams of leucine would produce effects comparable to tens of grams of glucose. That's at least what the mtor activation data appears to show. My profession is biochemistry, though autophagy isn't my specific area. I'm more of an apoptosis specialist. Regardless, perhaps another person can offer finer detail on the different pathways at play and how strongly they activate mtor.

 

[Devilseye]

tubby said:

Devilseye said:

This does have a clear-cut response. mTOR is heavily influenced by leucine, which acts as a powerful brake on autophagy. The branched-chain amino acids collectively turn mTOR on, and that shuts autophagy down. That is probably the reply you were after.

However, has anyone actually put this to the test? My point is that whatever you bring into your system operates at a systemic level in an extremely tiny quantity. Take 5 grams of sugar as an example (say, 1 or 2 glasses of lemon water)—that's not going to interrupt a fast in any meaningful way. So would a standard MICC injection, containing a modest amount of specific amino acids, really shut down autophagy, and do it in a manner that isn't just a fleeting dip? Of course, if someone goes the IM route, absorption into the bloodstream happens very quickly, so delivering it that way definitely could spike blood concentration fast.

Your observation about signaling is spot on, and I have a hunch that's exactly what OP meant when they first posed the question.

From a biochemical standpoint, yes. A number of proteins have been identified that participate both in the signaling that turns mtor on and in the way mtor shuts autophagy down. The route leading to autophagy is quite thoroughly mapped out at the biochemical level. Autophagy can be observed directly with electron microscopy, so it is not some imagined process. From there you can follow the phosphorylation of particular proteins and check visually whether autophagic structures are still present. That makes the study of autophagic events fairly empirical.

My hunch is that taking bcaa’s would suppress autophagy only for a limited time. That is typically how biochemistry behaves. Signals compete with one another, and whichever is strongest at a given moment prevails. So even though leucine intake might bypass autophagy, in theory you could return to a fasted state a few hours later once the signal is no longer continuous. That, at least, is what I have found when working through biochemical pathways.

 

[tubby]

Devilseye said:


Biochemically yes. There are various proteins known to be involved in both signal transduction for mtor activation and how mtor inactivate autophagy. The pathway to autophagy is pretty well documented biochemically. You can see autophagy occuring through electron microscopy. It isnt an imaginary event. You can then trace back the phosphorylation of specific proteins and see visually if autophagic structures are still observed. So its a pretty empirical study of the autophagic events.

I suspect that ingesting bcaa’s would only temporarily affect autophagy. Thats how biochemistry usually works. You have competing signals and at any one time the strongest signal wins. So while ingesting leucine would shortcut autophagy you could theoretically be back in fasted state a few hours after no continuous signal. At lesst thats my experience in analyzing biochemical pathways.

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Appreciate the explanation. Your reasoning is quite persuasive.