How long after eating before authophagy starts?

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Brian4
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How long after eating before authophagy starts?

Post by Brian4 »

Hey gang,

Was just at Valter Longo's fasting and longevity conference. It was great, and will become an annual event.

In any event, a quick question. We know we enter ketosis pretty quickly after we stop eating (overnight, for example, if we eat dinner several hours before bedtime). I'd heard from many here at ApoE.Info that autophagy also begins that quickly, but was never able to find evidence for that claim. Dale Bredesen also makes the claim, here, for example:

https://www.foundmyfitness.com/episodes/dale-bredesen

at 31:47.

He says twelve hours of fasting is long enough to induce autophagy. I've never found any research in humans that bears on that question.

I asked the researchers at the conference – people who are experts on this – and none of them knew, but their educated guesses as to when autophagy kicked in ranged from 18 to 36 hours, but they also noted that it might take even longer in the brain, since the brain is "metabolically privileged".

It seems an important question, give how many of us are doing daily time-restricted eating for brain health. It may be that fasting two days in a row (or longer) is needed to get maximum benefits from going without food.

Brian
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TheresaB
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Re: How long after eating before authophagy starts?

Post by TheresaB »

That's a great question with blurry answers because from what I've heard, we just don't know. In this interview the Dr Rhonda Patrick conducted with Dr Guido Kroemer, an expert in autophagy, there was this dialogue:
Rhonda: So there is hope for a non-invasive clinically relevant biomarker for autophagy but there still, it seems like there needs to be more work done before that actually happen...before I can go to my doctor and say, "I did a four-day fast. I'd like to see if I've activated autophagy. Can you please draw some blood." Right? We're not quite there yet.
Dr. Kroemer: Yeah, it would be wonderful to have the reward of measuring autophagy as a result of fasting and to get an objective incentive as a biomarker for doing that.
Interesting interview (as are all of Dr Patrick's) https://www.foundmyfitness.com/episodes/guido-kroemer
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Re: How long after eating before authophagy starts?

Post by Chameleon »

I had heard through Dr. Fung's books that it takes around 24 hours.
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Re: How long after eating before authophagy starts?

Post by Brian4 »

Thanks Theresa and Chameleon. C, does Fung cite any studies to support this?

We do know, that, in mice, as the result of tissue biopsies and examination of autophagosomes, it takes 12 hours. Mice metabolism is much faster than human metabolism, which makes me think it takes a lot longer in humans.

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Re: How long after eating before authophagy starts?

Post by mike »

Is it the autophagy that you are looking for, or the stem cell activation that is said to occur after fasting? From my understanding, that does not happen until your Glucose-ketone ratio goes below 1, which can take a few days to up to a week for diabetics running high glucose.
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Re: How long after eating before authophagy starts?

Post by aphorist »

Rhonda Patrick said once she's done breast feeding she's going to begin doing intermittent fasting of at least 2 days at a time. Based on where ketones rise after about 48 hrs, 2 days sounds about right.
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Re: How long after eating before authophagy starts?

Post by PeterM »

I have wondered about the autophagy question for some time. Like Brian I have never had any luck locating research that pins down the minimum number of hours necessary to kick start autophagy. For those interested there is a free online ebook(let) by Ron Migerny (a biology Phd) that deals exclusively with an autophagy approach to delaying degenerative neurological diseases. It's definitely worth a look if you have 15 min. It's broken down into super short chapters many of which can be skimmed or simply passed over. 7-8 pages of reading, max. The guy might be on to something.

https://proteincyclingdiet.wordpress.co ... rwklbxs-1/

The upshot is all neuro diseases are primarily misfolded protein diseases and if you sufficiently restrict protein often enough, you can control the doubling of misfolded proteins that eventually overwhelm the cell. His contention is by keeping protein under 4% you can have your autophagy yet eat too, be it carbs or fat. Just avoid a certain threshold of protein for anywhere between 18-72 hr, then replenish protein. Younger (or more fortunate) people with intact metabolic flexibility might go a low-protein form of carbs route, the rest of us choosing salads, olive oil, avocados, macadamias etc. In any case, it's an easy read, interesting theory, and has plenty of ways to approach diet. Excuse this if it's been addressed before. Couldn't find any reference in Search.
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Re: How long after eating before authophagy starts?

Post by Kenny4/4 »

Define specifically what autophagy is?
We have some image of our body cleaning out unusable matter, dead cells, cancer cells etc. because it can clean house now that it doesn't have to deal with all that food coming in. It seems like the process is more complex than this?

From Dr.Google:
How long do you have to fast for autophagy?
Autophagy is also achievable through intermittent fasting just as easily as longer fasts. Autophagy begins when liver glycogen is depleted, around 12-16 hours into a fast. The rate of autophagy peaks there, and then drops after about 2 days.
Is it true? A good source?

Here is something about fasting:
Even fasts of a few weeks or less can have dangerous consequences. Fasting puts two different types of stress on your heart. First, it cannibalizes cardiac muscle for fuel. The human body does everything it can to conserve muscle during a fast, but inevitably some muscle will be sacrificed at the beginning of the fast. After a few days, the body switches over to using fat, but researchers have discovered that protein (muscle) utilization actually increases again later on, even though fat stores are still available. This protein includes the muscle in your heart: weaken this too much, and heart failure will result.
Is Autophagy worth this?

I can tell you during the end of my run on day 4 of a 5 day fast I may have done something a bit negative for my heart.
We are getting into risky territory people.
Fast a little not a lot is now my stratagy.

I am reminded of the old 38 special song
Just hold on loosely
But don't let go
If you cling too tight babe
You're gonna lose it
You're gonna, lose control
Or as I say -overtraining is far worse than undertraining.
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Re: How long after eating before authophagy starts?

Post by Kenny4/4 »

The protein cycling looks interesting. Very thorough discussion with what "appears" to be some empirical data. The author does say err on the side of not getting too low on protein when reducing intake while cycling.
PeterM wrote:I have wondered about the autophagy question for some time. Like Brian I have never had any luck locating research that pins down the minimum number of hours necessary to kick start autophagy. For those interested there is a free online ebook(let) by Ron Migerny (a biology Phd) that deals exclusively with an autophagy approach to delaying degenerative neurological diseases. It's definitely worth a look if you have 15 min. It's broken down into super short chapters many of which can be skimmed or simply passed over. 7-8 pages of reading, max. The guy might be on to something.

https://proteincyclingdiet.wordpress.co ... rwklbxs-1/

The upshot is all neuro diseases are primarily misfolded protein diseases and if you sufficiently restrict protein often enough, you can control the doubling of misfolded proteins that eventually overwhelm the cell. His contention is by keeping protein under 4% you can have your autophagy yet eat too, be it carbs or fat. Just avoid a certain threshold of protein for anywhere between 18-72 hr, then replenish protein. Younger (or more fortunate) people with intact metabolic flexibility might go a low-protein form of carbs route, the rest of us choosing salads, olive oil, avocados, macadamias etc. In any case, it's an easy read, interesting theory, and has plenty of ways to approach diet. Excuse this if it's been addressed before. Couldn't find any reference in Search.
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Re: How long after eating before authophagy starts?

Post by slacker »

I have to think that some level of autophagy occurs almost regardless of the length of overnight fasting, but probably not enough to adequately reduce damage from oxidative stress. YMMV. Some people can get away with a lot, others not so much.

Dr Sachin Panda is a circadian rhythm expert, has been interviewed twice by Dr Rhonda Patrick (2016 and 2017), and has a new book out (The Circadian Code). I haven't had a chance to start reading the book yet, but looked up autophagy in the index. On page 207:
Autophagy is more active several hours after our last meal (after several hours of fasting and before the first bite of the day), and then slows down when we eat. Time-restricted eating is known to increase autophagy for a few hours during the fasting period.
The last sentence has a footnote to this mouse study. Full article is behind a pay wall, or for subscribers only.
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