How long to fast for autophagy?

(BuckRimfire) #1

My spousal critter likes to fast for weight management, and I like it because I enjoy a pointless stunt. We typically fast for 35-38 hours, because that’s the term she likes best (I’d be happy to go another 10 to 24 hours).

You can’t swing a dead raccoon without hitting someone who says autophagy is the greatest thing since giving up bread, but is a 36 hour fast enough to be significant?

(Bacon is a many-splendoured thing) #2

I’m not sure how one would determine this. Autophagy is a catabolic process, so it’s likely to be favoured on a ketogenic diet, as well as when we fast. But catabolic and anabolic processes go on all the time, regardless. They have to, or we wouldn’t survive. So there’s always some autophagy happening. I guess fasting just makes it more prominent. Given how similar fasting and a ketogenic diet are, metabolically speaking, should we really worry too much about our rate of autophagy?

(Joey) #3

@BuckRimfire I’ve got no idea. I just liked your post because it was so much fun to read.

(Autophagy means eating your own dead. What’s the rush?)

(BuckRimfire) #4

If you can’t be smart, at least be funny!

(Doug) #5

Versus nothing, and especially coming from a ketogenic diet, maybe a little. Having less stored carbohydrates in the body will likely reduce the time for a meaningful increase in autophagy by a few hours, but at 36 hours it’s still doubtful. There’s the whole sequence to go through - emptying the stomach, the small intestine, the ‘post absorptive’ phase where insulin declines and glucagon rises, depleting the stored glycogen, and the gradual increase and activation of AMPK while mTOR decreases and is suppressed (those last two are the most important regulators of autophagy).

If eating ketogenically beforehand, then insulin/glucagon should already be better versus a high-carb diet, and there likely will be less stored glycogen to deal with, but the overall picture isn’t much altered.

There isn’t a switch going from full Off to full On for increased autophagy. It’s a slow increasing curve, and at 36 hours maybe it’s rising a bit, but by far the largest gains are to come. Similar to people taking 3 or 4 days to really get into ketosis, I think the 3rd day or later is when we should look for substantial increases in autophagy. Nutrient deprivation is what does it, and the question is when has that really occurred enough.

There’s a shameful lack of human studies on this. The conditions for higher autophagy like insulin/glucagon keep getting more favorable past 5 days of fasting. If there is peak for it, we don’t know where it is. But for comparison, in a mouse autophagy is still increasing after 2 days of fasting, at which time the mouse is halfway or more to death from starvation. Nobody knows if there’s a proportional timeline in humans, but it would obviously be weeks/months for us.

Remarkable stuff happens during and after a fast. The one study I saw about human growth hormone had it peaking at day 26, I believe. Not saying that a given person should fast for that long, but for fasting in general there are beneficial changes that occur in the refeeding period after fasts of 3+ days.

We don’t know how great, in general, and especially on an individual basis. Autophagy does appear to be beneficial with some types of cancer - I’d say that’s the number 2 area. Number 1 is for dementia/Alzheimer’s disease/cognitive decline.

Autophagy is supposed to be going on in a minority of our cells, mostly a portion of our nervous system (where the cells are ‘post-mitotic,’ i.e. they can’t divide and make more of themselves). Since we’re stuck with those cells, some “house cleaning” needs to be going on all the time. The failure of this is thought to heavily contribute to dementia. Old, faulty, damaged protein structures accumulate in the cells and screw them up; this is the brain not working so well anymore. Autophagy scavenges these structures.

The individual needs to assess their own risk. Family history of dementia? People are living a long time now - what’s going to happen?

:smile: No death required!

(Joey) #6

Excellent point. Any form of self-cannibalism counts.

(Doug) #7

Indeed - ‘self-eating.’


There’s no way to know, but as @PaulL said, autophagy is always happening, it’s part of our normal process. Fasting just puts some extra fire on it. Autophagy became a fad within a fad, sounds great, but in reality it’s something people do, claim how amazing it is, but can’t back any of it up.

I rarely fast anymore due to losing a lot of muscle mass and lowering my RMR, but I do still do PSMF’s. I do however like the idea of autophagy for obvious reasons. But I don’t see how I can’t accomplish the same thing (aside from what’s happening anyways) with Senolytics.

Then there’s the fact that most of the claims are that we’re not going into a state of autophagy enough or possible deep enough because of our overall bad health in modern life, which could very well be true, but if you are healthy and eating right, does it really matter? Who knows?

(Doug) #9

That’s really not it. In some parts of our bodies - a minority - it’s supposed to always be occurring at a low, basal level. Most of our body is not that way - it has cells that divide and multiply, the ‘good’ new ones crowding out the old ones and diluting any bad effects. For the remainder - most importantly parts of the nervous system - the cells can’t do that, and that’s where constant autophagy is needed. Can’t replace the cells so we gotta clean them up.

In certain tissues there are other ways to start/increase autophagy. Exercise induces it in skeletal muscles, for example. But the main deal, by far, is concerns relating to dementia and cancer.

The way the body gets rid of the bad stuff that damages the nervous system cells that are involved with cognition and general brain function is autophagy. When this fails or isn’t working well, the bad stuff builds up, amyloid plaques and tau protein neurofibrillary tangles.

We certainly don’t know everything here, but we do know that this is physical reality - that an Alzheimer’s disease brain, under a microscope, shows the bad stuff - plaques and tangles - and that the patient’s behavioral symptoms correlate. More of the bad stuff, more effect on the patient. Neurons die and synapses are lost.

It’s definitely a guess, and hopefully as individuals we don’t suffer cognitive decline.

Dementia affects a lot of people, unhealthy and healthy alike. Americans, once we get past 70 years old, have about a 1 in 7 rate of dementia. On my father’s side, my grandmother and grandfather lived to be 100+ and 97, fairly healthy until the end, but they definitely had dementia their last decade or so. My father showed the first signs of it in his 50s,but remained very healthy, not obese, and very strong (even at age 85), until dementia outright killed him. We 4 kids are older than when our dad was showing signs, but indeed - who knows?

Fasting’s not for everybody, but talk about a perfect way to be in ketosis - you’re burning nothing but your own stored fat after a point. My opinion - if one can go 36 hours, then one can go 3 days or more, and at that point the body really is ‘emptied out’ and knows there’s nothing in the pipeline, so it’s going to be going after the bad stuff, to recycle it.

(BuckRimfire) #10

Heh. Those are the Big Two.

The S.C. is more immediately interested in weight control, but she just finished (a scant two months ago) her first series of seven chemo treatments for ovarian cancer that cropped up last May. Great response to chemo but that #$%@ stuff tends to return quickly after treatment in many cases, so anything that potentially minimizes that and/or synergizes with other treatment is of interest. We’re over four years into (somewhat sloppy) keto/low-carb, and she wants to continue that for the same reason.

For myself, the only reason to do any of this, other than as a gratuitous stunt, is dementia. I expect the demonstration of the benefits for avoiding dementia to be shown either too late (for me, I’m 58) or never, but it’s worth a shot. My dad developed dementia at around 80 and went downhill badly, and my mom is about 85 and can still kinda function, but has been showing signs for several years and will need to move to assisted living soon. So I’m hoping to avoid that entirely, and while I’m willing, in principle, to do that kinetically if I see the early signs and have the means to do so, I know people generally have a bad track record of following through with those plans. So, if a “weird” diet helps, I’m all for it!

The S.C. wants to fast today and again on Sunday. We did that plan a couple of weeks ago and it worked well for her.

Regarding muscle loss: My plan is to do a light (one set to failure) but thorough weight training session each fast day to tell my muscles “Don’t die!” As opposed to my usual method which is two or three (rarely four, when the weather is really crappy) days a week of 3 to 5 “drop sets” where you go to failure, immediately switch to 5 # less weight and repeat, and only doing around four different lifts, plus usually a couple of sets of dips or pushups with body weight only, doing different mixes of lifts on different days. So, on fast days I’m trying to get lower volume/intensity but more complete coverage of muscle groups.

(BuckRimfire) #11

I’m far from an expert on AD, but I believe there’s still a hot controversy about whether the amyloid tangles are a cause of disease, or a symptom of it that’s not the crucial factor. Seems like the contrarian opinion was very fringe for a long time, but treatments targeting plaque have had little efficacy and the recent fraud revelations were about plaque, IIRC, so the contrarians seem to look a bit less kooky now!

(Bacon is a many-splendoured thing) #12

A number of prominent researchers on Alzheimer’s Disease have taken to calling it Type III diabetes, to emphasise the idea that it’s a form of insulin-resistance of the brain. (Apparently the brain needs insulin in order to absorb glucose, but ketones enter brain cells by a different route.) The plaques and the tangles seem to be an effect of the disease, not the cause of it. The last thing I read suggested that even in cases where it is too late to reverse much of the damage, a ketogenic diet can still help to improve a patient’s cognition.

According to Chris Palmer, many of the mental diseases plaguing our society are the result of metabolic damage to the brain, and this also seems to be the case with neurodegenerative diseases, as well. After all, he says, a ketogenic diet can be helpful in controlling seizures, and we use anti-seizure drugs to treat other mental or neurodegenerative conditions all the time, so why shouldn’t keto work for those diseases, too?

(Doug) #13

Maybe there is controversy - I’d like to see the position that something else drives dementia. Not exactly light reading, but this is representative of what I’ve seen in a number of places:

During the past dozen years, a steadily accumulating body of evidence has indicated that soluble forms of Aβ and tau work together, independently of their accumulation into plaques and tangles, to drive healthy neurons into the diseased state and that hallmark toxic properties of Aβ require tau. For instance, acute neuron death, delayed neuron death following ectopic cell cycle reentry, and synaptic dysfunction are triggered by soluble, extracellular Aβ species and depend on soluble, cytoplasmic tau.

It’s straight-up saying this stuff triggers neuron death and synapse failure.

Good luck to her. My mom had uterine cancer at age 72, chemo knocked it down for a good while, then 10 years later it returned and spread.

Autophagy and fasting helps in the fight against some cancers, but is not indicated for some others; it actually appears to help the growth of cancer cells there. A year or two ago on this forum we had a discussion about it - something like 100+ types of cancer and with 5 or 10 or 15 of them fasting probably isn’t a good idea.

Indeed, Paul. High insulin and blood sugar apparently have a very wide range of bad effects.

(BuckRimfire) #14

Ten years would be a pretty good run, relatively. We’ve read that many cases return in months or a year or two. She’s 62, so another decade wouldn’t be ideal, but better than less.

(BuckRimfire) #15

I don’t remember that thread off the top of my head. I should dig for it.

(Polly) #16

There is also apoptosis. Regulated cell death and replacement.

(Bacon is a many-splendoured thing) #17

Yeah. I guess, strictly speaking, “autophagy” really means more the breakdown of proteins into their constituent amino acids.

BTW, I learned that every protein has a designated lifespan, ranging from seconds to years. Fascinating!

(Oliver ) #18

Hm interesting topic and something that has been on my mind for quite some time. Now it was a while since I did a pure water fast. That said I have been playing around with that from time to time have very low calorie days (something maybe between 500-800 calories in total) thinking that I might achieve similar benefits as if I would with a water fast.

(Bacon is a many-splendoured thing) #19

Unlike actual fasting, restricting calories can backfire, since it is a signal to the body that there is a famine going on. Its response is to lower the metabolism and retain as much of its reserves as possible, which is not what you want if you are trying to lose excess fat.

Fasting and nutritional ketosis are very similar metabolic states, since the body is in fat-metabolising mode and is producing ketones. The main difference is that ketones tend to be a bit lower in nutritional ketosis and a bit higher in fasting ketosis—and, of course, on a ketogenic diet one is eating to satiety, whereas when fasting one is not eating at all.

(BuckRimfire) #20

Further reading on Paul’s point, by Jason Fung, who literally “wrote the book” on fasting (not that he’s guaranteed to be right as a result; wrong people write wrong books all the time!) There’s a kinda tortured acronym in there that he uses to call dieting “CRaP,” but we’ll forgive him.

He recommends (elsewhere, maybe not restated in that linked essay) that if you are going to have some calories on a fast day, like cream and/or other fat in coffee, that you keep it under 500 Calories.

I take my tea in the morning black (or green, as the case may be; I’ve been trying to moderate my caffeine dose lately with green tea and a little less of it) so I can have that with virtually no calories, but my spousal critter likes a huge cup of coffee with about four tablespoons of cream and one of coconut oil, which is about 350 Calories. That’s not a water fast, but Fung would still consider it a “fast day.”