99 replies to this topic

[green]

So basically nobody really knows when autophagy begins in humans fasting longer than 24h. It could take 36 hours it could take 120, I didn't know if I should keep going after 72 hrs today or what, but I think I've already made the decision to break it after 72. 

 

 

I recall Rhonda Patrick saying that many people are basing the "three day period"  on the mouse studies  My recollection is that she thought the comparable human period was longer - four to five days ( She also made the standard disclaimers that your doctor should be consulted first and should supervise.)

 

I think this was stated on the last Tim Ferriss  Q &  A

 

http://tim.blog/tag/rhonda-patrick/  (Episode 237)

 

 

I don't know that I could even make three days.   I wonder at what point does muscle loss generally starts to happen if you're already lean (7-10% body fat)

[Nate-2004]

I'm 17% but I don't think I wanna go that far. It seems way too long to go without more research confirming this to convince me.

[pone11]

There is a great mouse study on this topic that shows at the hour autophagy starts there is a dramatic surge in free amino acids.  That makes perfect sense, since autophagy is tearing down defective or unneeded proteins in the cell and releasing the processed proteins as free amino acids.  Figure 3 shows the rise in free amino acids:

https://www.ncbi.nlm...les/PMC3149698/

 

Assuming you have the funds, you could do a study where you fast.  Measure your FAA at the start to establish the baseline.   Test again at 12 hours and then every two hours after that to get the approximate time when the shift to autophagy begins in full force.   Later studies can look at that time period with shorter testing intervals.

[Nate-2004]

Wouldn't free amino acids activate mTOR again?

[pone11]

Wouldn't free amino acids activate mTOR again?

 

It's a great question and I have wondered the same.  If you look at the study I linked, what is fascinating is that the surge of free aminos from autophagy does NOT stimulate insulin.   So it looks like a lot of the insulin responses from protein may be mediated by sensors of food intake in the gut, and autophagy may be bypassing those signals.   This study suggests that the MTOR signaling has an insulin and amino-mediated pathway:

http://www.jbc.org/c...6/41/38052.full

 

What I guess we need is a study like the one I posted that looks specifically at MTOR activation during autophagy.   Let us know what you find.

[Michael]

There is a great mouse study on this topic that shows at the hour autophagy starts there is a dramatic surge in free amino acids. Figure 3 shows the rise in free amino acids:
https://www.ncbi.nlm...es/PMC3149698/

 
That's a good find. If this is confirmed, researchers could begin using such a surge as a surrogate marker for a surge in autophagy, and we'd be able to track the time-course of such in fasting humans without having to resort to chopping people up.
 

Wouldn't free amino acids activate mTOR again?

 
An interesting question: a small boost in mTOR might be a feedback mechanism that puts the brakes on autophagy, rather than letting the tissues just tear themselves to bits. It would be good to know what the surge looks like compared to a normal meal. IAC, however, it can't be all that strong, as (a) clearly no one is actively building up tissue durign prolonged fasting, and (b) as pone11 semi-indicates, you do need some insulin and other anabolic signaling to fully engage mTOR.

[pone11]

 

There is a great mouse study on this topic that shows at the hour autophagy starts there is a dramatic surge in free amino acids. Figure 3 shows the rise in free amino acids:
https://www.ncbi.nlm...es/PMC3149698/

 
That's a good find. If this is confirmed, researchers could begin using such a surge as a surrogate marker for a surge in autophagy, and we'd be able to track the time-course of such in fasting humans without having to resort to chopping people up.
 

 

Exactly right, and I have shouted about that study in many places, but no one seems to get excited about it.

 

The thing is that this marker is available to biohackers as well.   All you really need to do is track one of the individual amino acids as your fast extends.  Maybe measure that once every two hours and get a rough idea of where the amino surge is occurring.  Then repeat the test with hourly testing around the time you expect the surge, in order to narrow in on it.

 

Like everything else in biohacking, people exert huge efforts to discuss the idea of autophagy and fasting, yet invest almost zero effort into measuring any specific outcome.  Frustrating.

[Nate-2004]

I've been drinking green tea and taking extract during the fasts, there seems to be a lot of conflicting confusion though around whether this promotes or inhibits autophagy. Which is it? Should I avoid the green tea catechins during fasts or not? I really wish more research could be done on the fasting stuff especially in the aging arena.

[Nate-2004]

So here's a new problem I'm facing. I was about to go on another extended 5 day fast starting tomorrow. Like before I had planned to just drink green tea and water during the morning and early afternoon every day of the fast. They say green tea inhibits mTOR and thus promotes autophagy... does it?

 

Thing is green tea also has the relaxing nootropic feel good amino, L-Theanine. Which I out of curiosity I googled with mTOR and discovered that it activates mTOR. What a conundrum. This sucks. Either I just go with black coffee which, compared to green tea I'm not a fan of, or I just don't fast.

 

Apparently according to this guy, nobody really knows how long a human being has to go nutrient deprived before autophagy begins in any particular region of their body.  Also this guy says that even fats, through beta-oxidation, lead to increases in Acetyl-CoA, which we don't want when it comes to getting protein deacetylation and thus autophagy. The guestimation they make based on mouse metabolism compared to humans, is definitely far beyond 36 hrs. I tend to believe them. I'm guessing to really get benefits you have to go 5 to 7 days without, a few times a year.

 

So apparently Green Tea promotes autophagy but L-Theanine, which is in Green Tea, inhibits autophagy, or rather, EGCG inhibits mTOR while L-Theanine activates it. Talk about trying to lift the stool you’re sitting on. I was about to go on a fast and drink nothing but water and green tea, but nevermind I guess I can’t. Or I'll just settle for black coffee but damnit I'm not happy about that.

 

Maybe I should just forget fasting and wait till I can get my hands on something like rapamycin. It would suck to put myself through 5 days of misery only to discover that it wasn't doing what it was supposed to.

 

 

Edited by Nate-2004, 06 August 2017 - 05:31 AM.

[sthira]

It's all a grand journey of personal experiences, Nate, since nutrition scientists can't or won't study controlled fasting in humans. But I think anecdotes are important and instructive -- assuming honesty amongst practitioners.

But again, for the nth time, during a two day fast in a rodent that rodent will lose around 20% of its body weight. It'd take us weeks of fasting to go from, say, 150 pounds of body weight to, say, 120 pounds of body weight. Nutrition scientists say no one will do this, or it's too hard for them to study. I beg to differ -- I've been on fasting retreats with dozens of motivated people -- we can be recruited, they won't or can't do it for reasons of their own.

Meanwhile, keep on aging, folks.

[Nate-2004]

Yeah they claim they can't find people but we're right here. I would do it just to know what the answer is on all this. It's not worth doing for me really if I don't have any clue if I'm even doing any good much less harm.

 

I think I've decided to wait on the 120 hour fast till next week, I'm still recovering from my bike accident I probably should wait till I'm completely healed.

[mrkosh1]

I'm very interested in this topic, because I like the idea of longevity and youth inducing activities we can participate in for zero cost or even negative cost (fasting saves money on food). Recently, I fasted for thirty six hours, and I've fasted several other times for sixteen to twenty four hours. What I've experienced is that after twenty four hours, the fast becomes easier. In fact, on my thirty six hour fast, I woke up at the thirty six hour mark with no hunger, limited fatigue, and felt like I could go on for several more hours or perhaps another day with minimal effort. Not all fasts would go so easy, I guess. 

 

Autophagy and the induction of human growth hormone are my two main interests when it comes to fasting. The boost in human growth hormone levels after a period of fasting (even simply skipping breakfast and perhaps having black coffee or tea) in verifiably documented, although seemingly variable to a significant degree. When it comes to autophagy, I'd love to know how long I need to fast to significantly boost the process. This is a question that needs a specific answer. Perhaps I can break things down a little more.

 

1) Is there any evidence whatsoever that a period of short term fasting boosts autophagy to any degree (in any organ or tissue)? 

2) What is the minimum length of time that has been proven to boost autophagy to any degree (even ten percent would be significant)? 

 

Now for two slightly different questions.

 

3) Would extensive exercise accelerate the onset of autophagy reducing the period of time that would be required for it to begin?

4) After a period of autophagy, how long of a period of "re-building" and healing (allowing the body to produce healthier cells to replace those that were destroyed) should be utilized before another bought of fasting? 

 

I would really like answers to the above questions. Without any citations, here is my crazy guess that should not be taken too seriously. I get this from reading a decent amount of material on fasting, autophagy, and related topics.

 

I think anytime the body's energy supplies are close to fully delepleted so that ketosis kicks in that autophagy will be boosted at least to some minimal extent. A full day of fasting with extensive exercise might be enough to induce some level of enhanced autophagy. The second day of fasting might be about keeping the autophagy going for a while. In the typical modern diet of eating almost around the clock which keeps glucose at high levels (producing the diabetes epidemic) very little autophagy takes place, increasing the rate of cancer and other diseases. So, even if a day or two of fasting isn't optimal, it's at least better than nothing and will reduce the chance of disease and cancer to some extent compared to a person who never fasts and keeps their blood sugar constantly elevated eating processed sugar all day (even if only hidden in other wise "healthy" foods). 

 

 

[mrkosh1]

A note about black coffee.

 

I grew up drinking my coffee with a ton of cream and sugar. I mean a lot of cream and a lot of sugar. People would say that, "I see you take a little coffee with your cream." 

 

For example, for many years, before work, I'd go to a fast food joint, order a large coffee, and stand there opening a dozen packets of sugar and dumping them into a large coffee before opening approximately ten half and half cups and placing them in my cup. 

 

Then, during an attempt at dieting, I forced myself to abandon the sugar, pretty much cold turkey. The coffee tasted nasty and bitter, but the cream at least mellowed it out a little and prevented the occasional heart burn and indigestion from the coffee. Over time, I got used to the coffee. If I ended up accidentally ordering coffee with cream AND sugar, it would taste fast too sweet, almost sickeningly. This habit of only using cream more or less stuck, except for the periods in which I drank black coffee, which I'm about to go into.

 

Don't get me wrong, I would from time to time order something like a "frap" from Starbucks or McDonalds. In a frozen drink with lots of crushed ice the sugar content did taste good. But when it came to plain brewed coffee, I stopped adding sugar except in extreme occasions when I was under a huge work load and I needed an energy boost (which I know from sugar is only temporary and at the cost of increased insulin, weight gain, etc). 

 

On and off, when the cream in my coffee seemed to be slowing weight loss, I'd force myself to eliminate it for a day, or two. Usually, I'd revert back to adding cream very quickly after my weight began falling. I think cream in my coffee is what can cause weight loss plateaus for me. Once I break the plateau, I can start adding cream and still lose weight.

 

However, since I've experimented with fasting, if I'm going to fast for a period of time, I drink my coffee black. This is because milk has lots of fat and "free fatty acids" cause growth hormone to stop being secreted. This morning I had two cups of black coffee. And, interestingly, when I'm on a fast black coffee doesn't taste as bad. I actually wanted a second cup. I also consider as a fasting aid or "drug" while fasting to boost my metabolism, reduce hunger, and get the most out of my fasting. 

 

Additionally, I want to say that Folders "Morning Blend" is my preferred type of coffee. I can barely drink very dark roasts. If someone can't drink a dark roast black, I'd suggest they find a very light roast. 

[Nate-2004]

In a further effort to find other means of inducing autophagy I found this study on heat stress and induction of heatshock proteins. Autophagy is induced in older mice with fewer heatshock proteins. Heat stress apparently induces autophagy in hepatocytes but the amount of HSP inducted to protect protein structure is lost due to increases in RNS and ROS. These things could be offset by sulforaphane perhaps, or gamma tocopherol but it may be a timing thing. This study postulates that in humans post exercise it's a homeostasis thing, HSP inhibits autophagy. 

 

I've been sitting in the sauna a lot for the past several months now. 

 

Just to avoid exogenous AGEs like pentosidine, I'd go with a lightly roasted coffee anyway.

 

Edited by Nate-2004, 06 August 2017 - 04:30 PM.

[RWhigham]

Without hunting up references (I'm otherwise occupied) I'd like to state what I recall.

 

There are 3 phases to autophagy. The 2nd takes longer to get started than the 1st, and the 3rd takes longer to get started than the 2nd.

• First the cell cleans up unneeded and malformed molecules (proteins and various other molecules).
• Second, the cell cleans up excess and damaged organelles such as mitochondria, excess liposomes, etc.
• Third, the cell cleans up lipid droplets (although lipid droplets behave a lot like organelles it takes longer to start destroying them)

Lipid droplets filled with polyunsaturated vegetable oils often build up over the years until they eventually clog up the cell so it doesn't work right. Based on short term studies, cardiologists celebrate LDL being lowered by dietary polyunsaturated fats--but the long term prognosis of lipid droplet build up is very bad.

 

For good results, a fast has to last long enough for the 3rd phase to kick in--perhaps a minimum of 20 hours, but a 20 hour fast would only get a little of each phase done. Hence the need to repeat 20 hr fasting daily, else weekly fasting for 48 hours, else monthly fasting for 3-4 days.

Edited by RWhigham, 09 September 2017 - 07:06 AM.

[Michael]

Lipid droplets filled with polyunsaturated vegetable oils often build up over the years until they eventually clog up the cell so it doesn't work right. Based on short term studies, cardiologists celebrate LDL being lowered by dietary polyunsaturated fats--but the long term prognosis of lipid droplet build up is very bad.

This isn't actually how this works. Lipid droplets are in any case very poorly-understood critters. The formation, size, and persistence of lipid droplets is regulated by a variety of things, of which fat intake is a very minor one; eg, they form and expand in response to obesity and insulin resistance — but also in response to regular exercise. But they then behave very differently in the former conditions than the latter.

 

The composition of lipid droplets doesn't simply reflect dietary intake; and saturated and unsaturated fats both promote lipophagy at the regulatory level, beyond their presence in lipid droplets, via different mechanisms: in general, unsaturated fatty acids stimulate autophagy and protect against apoptosis, whereas saturated FA inhibit it and promote apoptosis (but there are poorly-understood exceptions).

[RWhigham]

Deleted accidental unfinished post

 

Edited by RWhigham, 10 September 2017 - 08:54 PM.

[RWhigham]

i'm going to take time to answer the sweeping statements with no references (except himself and he is an authority) in the preceding post from Michael, our resident SENS and CRAN expert.

 

This isn't actually how this works. The composition of lipid droplets doesn't simply reflect dietary intake; and saturated and unsaturated fats both promote lipophagy. 

 

Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes

The unsaturated fatty acid, oleic acid, promoted the formation of triglyceride-enriched lipid droplets. In contrast, the saturated fatty acid, palmitic acid, was poorly converted into triglyceride-enriched lipid droplets

The role of lipid droplet formation in the protection of unsaturated fatty acids against palmitic acid induced lipotoxicity to rat insulin-producing cells

Long-chain unsaturated NEFAs strongly induce the formation of lipid droplets ...   On the other hand the saturated NEFA palmitic acid only induced minor lipid droplet formation ...

 

Take away: LD's form from unsaturated fatty acids

 

Lipid Droplets in Health and Disease

LD biogenesis is stimulated upon an increase in intracellular free FA levels.

Uptake of individual fatty acids into adipose tissue in relation to their presence in the diet

Shows that adipose cells store dietary fats in the preferential order: monounsaturated, n-6 polyunsaturated, saturated. So with what most people eat, the FA's stored and then released by adipose cells are mostly not saturated and will stimulate LD biogenesis--directly related to a diet high in unsaturated fats.

 

Take away: Dietary unsaturated fats increase LD's

 

The single large "LD" in an adipose cell is in a constant state of simultaneously storing and removing (via lipolysis) fatty acids and glycerol molecules from the LD. There is no lipophagy there. The adipose LD is much too large. On the other hand, non-adipose cells make relatively small LD's. They appear to change size through fission and fusion much like mitochondria, and the smaller ones are easily degraded.

 

Lipid Droplets in Health and Disease

overall lipid content that recycled via autophagy, contributed to the growth of LD's.

 

Take away: LD's grow in size during earlier phases of autophagy.

 

Recent investigations defined another selective form of macroautophagy termed “lipophagy.” 

Pharmacological or genetic inhibiton [sic] of lipophagy resulted in elevated TAG concentrations, increasing concomitantly LD numbers and size.

 

Take away: Without lipophagy LD's continue to grow in size and number.  (in spite of "lipolysis" mentioned below)

 

Lipid Droplets in Health and Disease

Accumulation of LDs in tissues in high amounts may cause chronic inflammation which is identified as one of the hallmarks of obesity-related metabolic disorders.

 

Take away: Accumulation of LD's will eventually cause disease

 

Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis 

Chaperone-mediated autophagy (CMA) selectively degrades a subset of cytosolic proteins in lysosomes. A potent physiological activator of CMA is nutrient deprivation, a condition in which intracellular triglyceride stores or lipid droplets (LD) also undergo hydrolysis (lipolysis)  This shows that autophagy puts adipose triglyceride lipase (ATGL) onto the surface of LD's and requires an active LC3 autophagy gene.

ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism  This shows that SIRT1 is required together with ATGL on the LD's for lipophagy to occur.

 

Take away: Autophagy is a prerequisite for lipophagy.

The LD lipolysis from nutrient-deprivation that is mentioned doesn't seem to prevent LD accumulation when autophagy is inhibited.  

 

ATGL promotes autophagy/lipophagy via SIRT1 to control hepatic lipid droplet catabolism

The role of autophagy in LD metabolism was unclear until Singh et al. showed that inhibiting autophagy in the liver promoted LD accumulation and attenuated oxidation of the hydrolyzed FAs.

 

Take away: Again LD's accumulate without the autophagy

 

In conclusion

• LD's contain mostly unsaturated fats that were at some point consumed 
• When LD's are not removed, they grow in number and size and result in disease.
• LD removal must be preceded by autophagy
• In the early stages of autophagy LD's grow in size, so it likely takes awhile before lipophagy kicks in
• It appears to be lipophagy, not LP lipolysis, that is enabled by autophagy

Edited by RWhigham, 11 September 2017 - 12:37 AM.

[Nate-2004]

Without hunting up references (I'm otherwise occupied) I'd like to state what I recall.

 

There are 3 phases to autophagy. The 2nd takes longer to get started than the 1st, and the 3rd takes longer to get started than the 2nd.

• First the cell cleans up unneeded and malformed molecules (proteins and various other molecules).
• Second, the cell cleans up excess and damaged organelles such as mitochondria, excess liposomes, etc.
• Third, the cell cleans up lipid droplets (although lipid droplets behave a lot like organelles it takes longer to start destroying them)

Lipid droplets filled with polyunsaturated vegetable oils often build up over the years until they eventually clog up the cell so it doesn't work right. Based on short term studies, cardiologists celebrate LDL being lowered by dietary polyunsaturated fats--but the long term prognosis of lipid droplet build up is very bad.

 

For good results, a fast has to last long enough for the 3rd phase to kick in--perhaps a minimum of 20 hours, but a 20 hour fast would only get a little of each phase done. Hence the need to repeat 20 hr fasting daily, else weekly fasting for 48 hours, else monthly fasting for 3-4 days.

 

That last assessment of time, where are we getting those numbers? 20 hrs, 48 hrs, etc. Is that for mice or humans?

 

Second question, do you mean fast for 20 hrs, eat, then fast again for 20 hrs? AKA warrior diet?

 

Third question, is this lipid cleanup all due to mTORC1 inhibition or Tyrosine Kinase inhibition or another pathway?

Edited by Nate-2004, 11 September 2017 - 05:24 PM.

[RWhigham]

That last assessment of time, where are we getting those numbers? 20 hrs, 48 hrs, etc. Is that for mice or humans?

 

Second question, do you mean fast for 20 hrs, eat, then fast again for 20 hrs? AKA warrior diet?

 

Third question, is this lipid cleanup all due to mTORC1 inhibition or Tyrosine Kinase inhibition or another pathway?

 

 

I took 20 hrs from a dissertation which tragically I can no longer find (very upsetting).  20 hrs may not work for everyone,

 

A person on a low insulinogenic diet (a subset of low carb) should get into autophagy relatively fast. On the other hand, it may take much longer and be much more difficult for a diabetic to ever get into autophagy which may add to their difficulties.

 

Insulin and Autophagy

Progressive alterations in lipid and glucose metabolism during short-term fasting in young adult men

Of the total increase in lipid kinetics, 60% occurred between 12 and 24 h of fasting; the greatest interval change occurred between 18 and 24 h of fasting. ... Of the total decline in plasma insulin, 70% occurred within the first 24 h of fasting

 Autophagy – the housekeeper in every cell that fights aging   (anti-agingfirewalls.com - Jim Watson 2013)

Autophagy now appears to be a downstream event following insulin/IGF-1 pathway down-regulation, mTOR inhibition, Klotho activation, AMPK activation, Sirtuin dependent protein deacetylation, and histone acetyl transferase inhibition.  Autophagy explains in part, the beneficial effects of caloric restriction, caffeine, green tea, rapamycin, resveratrol, metformin, spermidine, lithium, exercise, hypoxia, Torin-1, trehalose, and a host of other natural and synthetic compounds.

 

Takeaway: Low insulin is associated with autophagy and can occur in 24 hr.

 

Josh Mitteldorf  has discussed all different sorts of fasting, including the interesting "fasting mimicking diet"

 

Mice

24 hr increases autophagosomes indicating autophagy

Protein turnover via autophagy: implications for metabolism  From the full pdf  behind paywall)

Active autophagosome formation was observed in skeletal muscle, liver, heart, exocrine glands such as pancreatic acinar cells and seminal gland cells, and podocytes in kidney after 24-h food withdrawal.

Mice brain

Short-term fasting induces profound neuronal autophagy   Autophagosomes increase in the brain after both 24 and 48 hr fasts

There was a substantial increase in signal in the cell bodies of Purkinje neurons at both 24 and 48 hours.

(This study controverts earlier beliefs about autophagy in the brain) 

 

Edited by RWhigham, 12 September 2017 - 08:16 PM.

[Nate-2004]

Informed Consent removes the ethical problems of experimenting on humans yet scientists continue to avoid testing fasts on human beings based on so called "ethical" issues, which, is obnoxiously absurd. There are plenty of people who already fast or would be willing to try it and would even consent to biopsies, informed on any risks that might entail. There is no excuse not to be testing on humans at this point much less any point in history. Mice do not represent a valid metabolic model that can even be remotely compared to humans. What happens in mice very rarely carries over to humans, especially around nutrition, insulin and fasting. 

 

I shared this on another post I'll share it again because this guy is quite knowledgeable about this, and is himself doing a human trial on various modes of fasting and keto to get at least some of this information.

 

Edited by Nate-2004, 12 September 2017 - 08:23 PM.

[sthira]

Informed Consent removes the ethical problems of experimenting on humans yet scientists continue to avoid testing fasts on human beings based on so called "ethical" issues, which, is obnoxiously absurd. There are plenty of people who already fast or would be willing to try it and would even consent to biopsies, informed on any risks that might entail. There is no excuse not to be testing on humans at this point much less any point in history. Mice do not represent a valid metabolic model that can even be remotely compared to humans. What happens in mice very rarely carries over to humans, especially around nutrition, insulin and fasting.

The CR people report that both non-human primate CR studies and human CR studies are too difficult to perform because of the long lengths of time required, and then high costs of CR studies.

But what I don't understand is why not study healthy human volunteers interested in slowing aging via fasts. Fasting experiments in healthy human volunteers needn't be difficult, time consuming, or expensive. And fasting studies -- even in citizen science projects -- might be relevant to human health.

Administer whatever blood tests we think we know about now (standard blood panels, OGTT, IGF-1, IGF-BP3, whateva..) then fast healthy human volunteers for varying lengths of time (24, 48, 72, 96 hours fasts, whateva, sky's the limit...) then test blood before, during, immediately after, and then a few weeks again after fasts. Why not? We could probably design citizen science projects right here, through this site. There aren't enough willing fasters? No one thinks "fasting" is worthy of pursuit?

The reasons that baseline studies of fasting aren't done in a wide cultural variety of healthy human volunteer subjects remains mysterious to me.

Meanwhile, you could perform your own easy N=1 studies on yourself with your doctor's participation; you pay for your own relevant blood tests. This is what I'm currently doing. But it'd be much more worthwhile for groups of individuals of many ages and backgrounds to do this, then maybe we'd learn something new. Who cares if the results aren't publishable.

But, search for clinical trials offering fasting studies (https://clinicalconn...6/en-US/fasting) and nothing turns up.

What am I not understanding?

[Nate-2004]

I will participate if someone wants to organize. I will be starting keto soon anyway and plan to fast before to get a ketosis jump start.

[xEva]

But, search for clinical trials offering fasting studies (https://clinicalconn...6/en-US/fasting) and nothing turns up.

What am I not understanding?

There is not much to sell in fasting. ..and the US model cares only about making money.

 

 

@Nate: congrats, you're proving yourself as a fast learner

Dr. Bikman interview was very interesting. I especially liked his insight about exogenous ketones. It reminded me the hype about the much anticipated "CR mimetics" that was a popular topic of discussion here years ago, when the forum was alive. They were supposed to up the autophagy and give you all the benefits of CR while you keep stuffing your face to the fullest, as usual. I always  thought the idea was abhorrent and had only one question: But what about all the nutrients already in the bloodstream, what will be their fate, if instead of using them the cells were forced to do autophagy?

 

To my mind this conjured up the picture of a huge hotel, with many many rooms, all occupied by guests who all ordered room service but then decided that they had plenty of leftovers in their rooms and they'd rather clear that instead. In the meantime, the food is already delivered, cluttering the hallways with carts and trays left outside their doors.. Just sitting there... waiting for rats and roaches to start scurrying around... Scary stuff, no? 

 

But thankgod for insulin! It says to the cells in no uncertain terms: drop whatever you're doing and clear all that stuff from the hallways NOW! ..oops I meant the bloodstream of course. 

 

Still, with the constant focus on specific molecular pathways, most people can't zoom out and see the forest for the trees. I thought the interviewer was about to ask if that pesky insulin could just be turned off somehow. (good thing he did not, no? )

[normalizing]

why would you fast when you can just go ketogenic? its about the same thing from results i have seen in studies, of course done on mice only, but it seems CR and ketogenic diet work similarly. except, in one your stomach shrivels up and groans and the other, you are all full of fat.

[xEva]

but you still need to fast, at least a couple of days, to induce ketosis. It takes weeks on a diet.

 

but if temporary hunger is such an unbearable thing, why not use appetite suppressants? they work by inducing autophagy and likely also lipolysis. The thing is, if you have not eaten in a while and yet you're not hungry your body is getting its nutrients somehow. How?

[Nate-2004]

Easy for you to say xEva, I think not eating comes way too easy for you. People are looking for mimetics because when most people stop eating for a couple of days they're miserable. I know I am. Innovators are driven by having their cake and eating it too, no pun intended. I keep trying to fast and I just can't function at all, my work and my life take brain energy. While I'd probably jumpstart keto with a fast anyway, most people just don't have that kind of will power to push themselves through something so understandably awful. I know you can't understand how miserable it is, because I've tried to explain it to you, but for many people it is utterly unbearable and they would rather just spend weeks on keto than try to fast first. I have enough trouble with keto but at least that's more bearable than fasting.

 

All that said, nobody knows when, in humans, autophagy starts, where the benefits start or end and I think until they do, people are going to be less willing to try something so harrowing until they can grasp a tangible end goal.

[normalizing]

but you still need to fast, at least a couple of days, to induce ketosis. It takes weeks on a diet.

 

but if temporary hunger is such an unbearable thing, why not use appetite suppressants? they work by inducing autophagy and likely also lipolysis. The thing is, if you have not eaten in a while and yet you're not hungry your body is getting its nutrients somehow. How?

 

probably from nutritious dying bacteria cells in the gut. i assume since bacteria constantly feeds from food we consume, they are nutricious enough on their own when dying and being reabsorbed by the body. i assume only this that starvation probably depletes you completely of any bacteria

regarding ketosis, this is another good thing; http://www.medicalne...cles/319375.php

[xEva]

 

but you still need to fast, at least a couple of days, to induce ketosis. It takes weeks on a diet.

 

but if temporary hunger is such an unbearable thing, why not use appetite suppressants? they work by inducing autophagy and likely also lipolysis. The thing is, if you have not eaten in a while and yet you're not hungry your body is getting its nutrients somehow. How?

 

probably from nutritious dying bacteria cells in the gut. i assume since bacteria constantly feeds from food we consume, they are nutricious enough on their own when dying and being reabsorbed by the body. i assume only this that starvation probably depletes you completely of any bacteria

regarding ketosis, this is another good thing; http://www.medicalne...cles/319375.php

 

 

The link is not about ketosis but omega3 and gut bacteria.

 

Re your answer -- ?! shocking    sounds like you need to review GI tract, where most of bacteria reside, and where/how digestion/absorption takes place.

 

and I intended my question as rhetoric. I was driving at you recalling experiences when you lost appetite and hoped that this would lead to realization that whenever that happened --for whatever reason-- the body was living off liver glycogen supplemented by autophagy in tissues that needed it most. In other words, you were fasting -- without hunger pangs!

 

Lets see, when we tend to lose appetite:

some infections, fever, poisoning, trauma,  inordinary dose of radiation...

what else? 

ah! heat stroke (or just overheating)

there must be more..

enlarged spleen.,

 

Or take hormetics or appetite suppressants. They must press the right kind of metabolic buttons -- otherwise how do they work?

 

Black coffee and cigs always worked for me, though there are healthier choices out there. Why not use them, when you want to fast?

[sthira]

...starvation probably depletes you completely of any bacteria

Fasting for a couple of days or weeks isn't starvation. We slob moderns in privilege can go quite a while on nothing but liquid:

"A 27-year-old male patient fasted under supervision for 382 days and has subsequently maintained his normal weight..." https://www.ncbi.nlm...les/PMC2495396/

And when we finally do kick the bucket and inevitably lose dreamy immortality, billions of bacteria will begin doing their thing -- breaking down cells. Dead human bodies are yumola for creatures large and small:

"As the cells die, bacteria within the body begin breaking them down. Enzymes in the pancreas cause the organ to digest itself. The body soon takes on a gruesome appearance and smell. Decomposing tissue emits a green substance, as well as gasses such as methane and hydrogen sulfide. The lungs expel fluid through the mouth and nose.

"Insects and animals certainly take notice of all this. A human body provides sustenance and a great place for insects to lay eggs. A fly trying to find its way in this crazy, mixed-up world can eat well on a corpse, and then lay up to 300 eggs upon it that will hatch within a day..."

http://science.howst.../body-farm1.htm

https://youtu.be/DrQRS40OKNE