Some fasting questions

(KCKO, KCFO) #21

Good question since no one has come up with a way to measure it.

I am frustrated by the debate of it starts at 12 hrs. and builds to 36 hrs. then levels off OR it doesn’t start til 36 hrs. and then just keeps going.

(Doug) #22

:+1: And toonewtoketo said he’s doing keto for fat loss and eating once a day - so with that in mind we’re really not talking about autophagy. But then the thread takes a turn… :smile:

Totally agree. I don’t think there’s ever been any compelling argument presented as to how coffee would actually mechanistically slow autophagy much.

Not eating and not taking drugs doesn’t present much profit opportunity for food processors or pharmaceutical companies, so sponsored studies are few and far between, here. :rage: There are ways to measure autophagy - literally just counting the autophagosomes and lysosomes, measuring certain proteins that are precursors of autophagy, that go into building autophagic structures, etc.

GKI would only work when somebody goes from a carb-heavy diet into fasting. Somebody eating really low-carb could have low GKI and be eating multiple times day.

(Can’t help myself - mini rant about ‘Siim Land’ - this is really just a marketing effort, IMO. There’s the young, handsome Estonian face, but it’s all about selling stuff and getting money from webpage views. The Facebook account with that name and face was in one of my groups - ‘Extended Fasting and Autophagy for Healing’ - and the person who posted things was dumber than a bag of hammers. I’ve seen the Siim Land account post YouTube videos with 100% incorrect, easily verifiable-as-false stuff where the science is undeniable, and yet they’re denying it - they’re just copying the same incorrect stuff from other video makers and bloggers, even word-for-word.)

That said, I do think that the evidence thus far shows that coffee either increases autophagy or at least doesn’t down-regulate it.

We do know some things about autophagy. It’s going on or supposed to be going on at a low basal level in some of our tissues all the time. Exercise increases autophagy in skeletal muscles, but this is largely unrelated to diet.

Dietary changes and increasing autophagy - the up-regulation of autophagy is primarily controlled by the nutrient-sensing kinases, mTOR and AMPK. Under fasting or ‘starvation’ conditions, mTOR is substantially de-activated while AMPK is activated. This is the most important control for autophagy. Insulin and glucagon levels also make a substantial difference - for more autophagy we want more glucagon and less insulin, just as we want AMPK higher and mTOR damped down.

You commonly hear that for humans “autophagy peaks at 3 days” (of fasting). Somewhere, this got started and it appeals to people, but I’ve never seen anything that really supports the notion.

In a mouse - yes, different than a human but also a mammal and very similar to human operation on a cellular basis for most things - autophagy is still increasing after 2 days of fasting, and at this point the mouse is halfway or more to death from starvation.

At 12 hours of human fasting, the small intestine may not even be emptied yet. The stomach has to empty, and then it takes a while for food to leave the small intestine - it doesn’t empty out all at once like everything is going through it like a ‘plug.’ There is also a ‘post-absorptive’ phase after the digestion of food is mostly complete - blood chemistry takes some time to move from substantially the ‘fed state’ to the ‘fasting state.’ After that, glycogen depletion begins, and this can take a day or two.

@ctviggen made the good point that the body is rarely binary. ‘On/Off’ switches are not being slammed around here. I would boil it down this way:

18 - 24 hours: Maybe autophagy is being stimulated a little bit. Coming from a keto diet could make some difference here, i.e. insulin/glucagon is likely more favorable. But the elephant in the room is that until recently protein was being consumed, and that’s the biggest down-regulator for autophagy there is. (There is a decent argument that fat, due to its vastly less effect, may not matter too much, i.e. ‘fat fasting’ could mean substantially the same increase in autophagy. What difference would there be, between eating exogenous fat and “eating our own fat”? It’s a question.)

Day 2 - Day 3: Glycogen gets depleted and the body now really knows that fasting is the deal. Autophagy is increasing.

Beyond Day 3: Insulin continues to decline and glucagon continues to rise. The picture, there, and for mTOR and AMPK, continues to get more favorable for autophagy through at least 5 or 6 days of fasting. If it’s still going up in a mouse at 2 days, then that would equate to a month or many months for a human. I’m not saying that human autophagy is still increasing at a month or more of fasting - I don’t know this and I don’t think it’s been studied, certainly not well studied. But I do think that without some fairly sound evidence or reasoning it’s nonsensical to assert that human autophagy peaks at 3 days, for example.


Can’t stand that guy, he’s an “expert” in everything. Yet clearly doesn’t have a clue. He’s been on a couple podcast over the years and aside from me usually bailing because I can’t listen to him for long every time you could tell the person interviewing him was having a WTF moment once he started going.