Molecule produced during fasting has anti-aging effect on vascular system | Hacker News Reader

Molecule produced during fasting has anti-aging effect on vascular system

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255 pointssahin-boydas142 comments

Can we update the title to reflect the research by adding "in mice" at the end of it?

The effect of calorie restriction on aging in rodents has been known since the 1930s. Which does not diminish the value of identifying the precise molecule that triggers this, but it does mean that this shouldn't necessarily be used as justification for a fasting diet.

"It has been known since the 1930s that reducing the number of calories fed to laboratory rodents increases their life spans. The life extension varies for each species, but on average there was a 30–40% increase in life span in both mice and rats.[30] In late adulthood, acute CR partially or completely reverses age-related alterations of liver, brain and heart proteins, and mice placed on CR at 19 months of age show an increases in life span.[78] "

https://en.wikipedia.org/wiki/Calorie_restriction

Here is one monkey on an unrestricted diet and one monkey on a restricted diet years later:

http://www.slate.com/articles/health_and_science/medical_exa...

That article in its entirety is interesting, because there are not two but four monkeys from two different studies. Two on "restricted diets," and two on "unrestricted diets."

In one study they fed both monkeys a highly processed diet of 30% sucrose. In the other study they fed both monkeys a less processed diet of 4% sucrose.

The monkey with the poor health outcome was the one allowed to eat as much as it wanted of the highly processed 30% sucrose diet.

So the "calorie restriction" seems to more likely just mean "don't eat more than 4% sugar, unless you are on an extremely calorie restricted diet."

This only applies if you live a sedentary life with nothing to do all day. You can't draw any conclusions beyond that.

I'm no expert, and I might be wrong, but generally I would argue against extracting conclusions (even layman conclusions) from two studies of a different species (!) with a sample size of 2 (!!!)

It has been shown that longer lives occur in many species, from yeasts and c.elegans, to primates. Pubmed fetches lots of articles (arguing for both sides) given a search like 'caloric restriction aging'

So what is your point exactly?

That this result is likely to generalize from mice to other animals.

I'm on a day 4 of a water-only fast and have completed a two-week medically supervised fast as well as many other shorter fast.

As an anecdote, I can say water-only fasting in combination with a high nutrient density plant-based diet has helped me overcome some serious allergies and other health conditions. As an added bonus, I've lost 65 pounds from my peak weight over the last few years and my weight has been stable. It's not a panacea, but I've found it to be a net benefit.

For those interested in a deeper dive on the benefits of water-only fasting and diets that try to mimic its benefits, as well as time-restricted feeding, see:

Valter Longo, Ph.D. on Fasting-Mimicking Diet & Fasting for Longevity, Cancer & Multiple Sclerosis [1]

Dr. Valter Longo on Resetting Autoimmunity and Rejuvenating Systems with Prolonged Fasting & the FMD [2]

Dr. Satchin Panda on Time-Restricted Feeding and Its Effects on Obesity, Muscle Mass & Heart Health [3]

Dr. Satchin Panda on Practical Implementation of Time-Restricted Eating & Shift Work Strategies [4]

[1] https://www.youtube.com/watch?v=d6PyyatqJSE

[2] https://www.youtube.com/watch?v=evGFWRXEzz8

[3] https://www.youtube.com/watch?v=-R-eqJDQ2nU

[4] https://www.youtube.com/watch?v=iywhaz5z0qs

[Edit to fix typos and formatting]

Very interesting to hear your successes in light of the immune cell turnover effect that prolonged fasting seems to have (Valter Longo's research).

FYI: these episodes also have a transcript and show notes not available at the youtube URL. Here they are...

[1] https://www.foundmyfitness.com/episodes/valter-longo

[2] https://www.foundmyfitness.com/episodes/valter-longo-2

[3] https://www.foundmyfitness.com/episodes/satchin-panda

[4] https://www.foundmyfitness.com/episodes/satchin-round-2

This discussion may also be relevant to ketogenic diets where BHB is produced. See these two episodes focused on research on the ketogenic diet...

• https://www.foundmyfitness.com/episodes/eric-verdin

• https://www.foundmyfitness.com/episodes/dominic-dagostino

Thanks for the transcripts! I'm extending my fasts to a minimum of 5 days from now on as, from what I've understood, the immune cell turnover appears to really start kicking in on day 4 and 5.

why are allergies supposed to be affected by fasting?

Some people are allergic to so many things, with such sensitivity, that nearly all foods contain some percentage of something they're allergic to (even if it's only trace amounts). In that case, consuming nothing but water effectively assures a food allergy-free experience for the duration of the fast. If they're allergic to things found in water as well, then I'm not sure what the best solution is.

I actually drink distilled or deionized water during my fasts. This is what was available on my first long fast and I've done it since.

Valter Longo's work has shown that fasting causes a destruction of immune cells that get renewed from progenitors (absent the autoimmunity) after the refeeding phase. The mechanism has been shown to help with an animal model of multiple sclerosis called experimental autoimmune encephalomyelitis.

It's a very elegant, most likely conserved mechanism that may generalize to virtually all diseases of autoimmunity and not just multiple sclerosis. However, that obviously needs to be proven clinically before you can say that and it might take a while.

Also, the conversion of animal research to human has another challenge: rodents have a faster metabolism. To have any hope of recapitulating those type of effects, you really have to go a while without food.

There seems to be a more medically safe way of probably tapping into mostly identical effects though, which is a "fasting-mimicking diet." Ultra low calorie, fits a specific macronutrient profile.

Read the show notes for this episode or watch the video... https://www.foundmyfitness.com/episodes/valter-longo-2

Thanks, couldn't have said it better myself.

I was initially pretty concerned about the safety of water-only fasting. It appeared so extreme. After spending two weeks fasting with others who are either ill with different conditions or very healthy, I realized that it's relatively safe given good medical supervision.

When fasting on my own, I haven't fasted longer than 5 days, and I know what to watch out for now:

- I check my blood pressure and heart rate every morning

- I get up very slowly (as you can get light headed and fall if you're not careful)

- I bathe without taking a hot shower or submerge my body in hot water as this can lead to low blood pressure as well.

thanks, but I still don't get: aren't most allergies due to hereditary factors? If so why would they be cured by resetting the immune system?

Given that Dr. Longo promotes a diet that contains some calorie intake (~500 daily), why did you decide on water only fast? I am trying to choose between those two options myself.

I've completed a few water fasts before I came across Dr. Longo work. The main reason he created the FMD is because they couldn't get people to volunteer for a water-only fast and then compliance was an issue. I'm now used to water-only fasting and hunger goes away completely by second or third day. I've heard anecdotally that hunger doesn't subside as well for everyone on the FMD as you're still eating, but haven't tried it myself.

This is the first time I'm working intensively during the fast (I worked through the weekend) and I've been incredibly productive. I also prepared really well: I was eating more than a pound of dark leafy green a day for the last month (in two high micronutrient smoothies for breakfast and lunch) and I used a sauna everyday for the week before the fast. I feel better today than I have in a long time, my energy is excellent.

That's not to say there aren't any side effects, I had some pretty bad lower back pain which made getting to sleep last night difficult, but I've come to expect it and it comes and goes throughout the day usually starting on the third day. I occasionally have some heart burn as well, but it hasn't been as bad this time. My first fast was the most difficult, but it was medically supervised at the True North Health Center in Santa Rosa, California. They supervise in-patient water-only fasts up to 40 days.

Thanks! Dark leafy greens make total sense, but why sauna is good before the fast? Also how long and how frequent your fasts usually are? 5 days 4 times a year as Dr Longo suggests or something else? BTW I did FMD twice and the feel of hunger doesn't go away. I also suspect this happens because of the constant food intake.

I had a recent flare up of my condition and sauna helps to alleviate the symptoms and shorten the duration. Water fasting also helps and this is the first time I have tried sauna before fasting. Perhaps coincidentally, this is the water-fast I've felt the best on. I don't fully understand the underlying mechanisms but there's some amazing research on how hyperthermic conditioning initiates a whole cascade of physiological adaptations which are partially mediated by heat-shock proteins, increase of growth hormone, and improving insulin sensitivity. For more information on benefits of hyperthermic conditioning, see:

1. https://tim.blog/2014/04/10/saunas-hyperthermic-conditioning...

From the article above:

Just a few of the physiological adaptations that occur are:

Improved cardiovascular mechanisms and lower heart rate.

Lower core body temperature during workload (surprise!)

Higher sweat rate and sweat sensitivity as a function of increased thermoregulatory control.

Increased blood flow to skeletal muscle (known as muscle perfusion) and other tissues.

Reduced rate of glycogen depletion due to improved muscle perfusion.

Increased red blood cell count (likely via erythropoietin).

Increased efficiency of oxygen transport to muscles.

Here are some related videos:

2. https://www.youtube.com/watch?v=eWKBsh7YTXQ

3. https://www.youtube.com/watch?v=aHOlM-wlNjM

As for duration, 3 to 5 days, though from now on I'm likely to do minimum 5 days fasts as after reviewing Dr Longo's research the immune benefits and increased autophagy appear to really kick in on the 4th and 5th days. Frequency, I would say I average 3 to 4 times a year. This frequency just happens to coincide with Dr Longo's recommendation as I only more recently came across his research.

Thanks for sharing that you also noticed that the hunger doesn't go away on Prolon.

[Edit formatting]

Thank you for the elaborated answer!

I know it's just one data point, but I've been doing a very mild form of intermittent fasting (more time-restricted eating) since June, and have been very happy with the results. (I stop eating by 8pm, don't start again until noon, but haven't done much in terms of changing what I'm actually eating.) At 5'5", I went from 156lbs. to 143 (goal is 135), and it's been relatively easy.

Your mileage may vary, of course, but I feel great. This was inspired by a paper I read (I believe linked-to in this article, but I'll have to track it down later.)

https://www.the-scientist.com/features/running-on-empty-3143...

Close your eating window to 4 hours and eliminate carbs. You'll drop weight incredibly fast. Delay lunch until 1-2pm and then have an early dinner if you can't bring yourself to eating just one meal a day.

I did this and it is amazing, but I failed to keep it up long enough to become my normal.

> but I failed to keep it up long enough to become my normal.

And that's exactly why you want to keep it to a moderate 8pm to 12 noon fast. Its not hard to do, you lose a little bit of weight each week. You end up healthier with minimal pain or change to life-style.

yep I’ve found that moderation is my key to keeping up with anything like this. If I don’t exercise too hard, I’m inclined to come the next day or the day after. I’m on a very similar time restricted eating now, and it’s been sustainable because it’s not too extreme. I’ve experienced great results from it as well. I eat whole milk by way of coffee and then eat 1000 or so calories between 12:30 and 7 or 8 pm.

> If I don’t exercise too hard, I’m inclined to come the next day or the day after.

Heavy weights 1x per week. Consistent, light and fast training is optimal (~50-60% max) via "Train Smarter with Firas Zahabi -- Consistency over intensity" https://www.youtube.com/watch?v=vR0m0Vt3JF4

But you're also not triggering ketosis much if at all. The benefits of that go far beyond weight loss. There are test strips you can use to see if you're in ketosis.

What are the benefits of ketosis that you don’t get with 8-12 fast, lots of veggies, and low sugar diet?

There's two things being mentioned here, going low-to-no-carb, and going to a time-restricted eating schedule.

My understanding is that ketosis is a function of low/no carb eating; I think further that in time-restricted eating, if you're losing weight, it's primarily from simply taking in fewer calories overall.

Have I misunderstood?

Doing the 16:8 restricted eating time thing has nothing to do with ketosis.

Losing weight fast is not a desirable goal. You can lose considerable muscle mass, even around your heart which is obviously dangerous.

This is FUD. Please cite your sources.

While not healthy to literally starve yourself, getting your calories from stored fat is absolutely safe. There are dozens of documented cases of people subsisting on vitimins/broth and their own fat for over a year. Proper electrolytes all but eliminate most issues you suggest, only applicable to a pure starvation diet. Conflating the 2 is either uninformed or dishonest.

In general, muscle is 'consumed' before 'fat'. Quotes since it is more complex than just what regular muscle and fatty tissues do.

> While not healthy to literally starve yourself, getting your calories from stored fat is absolutely safe.

No one will disagree with you there, but for most normal healthy people with regular muscle/fat content (or a bit too much) it takes a while for your body to decide it is a good idea to start creating toxins (ketones, which are quite harmless in smaller quantities) which are the result of fat conversion in a starvation diet.

If that is true, then why even have fat instead of extra muscle?

Burning muscle before fat makes no evolutionary sense.

> If that is true, then why even have fat instead of extra muscle?

Higher density, lower basal metabolic rate increase.

> Burning muscle before fat makes no evolutionary sense.

The chemical pathway for getting energy from muscle is much shorter than the one to get energy from fat.

So our ancestors would just die of starvation and get weaker and weaker, while keeping their fat stores?

No, but the optimum solution to survive long term starvation is to dump as much muscle mass as possible to minimize your daily calorie burn. Alongside that the body minimizes the energy spent fighting long term problems like cancer by reducing the amount of antioxidants produced etc.

Some strength is still required, so their are feedback mechanisms limiting this loss. However, on a diet you are not in pure survival mode so you probably don't want to make those same sacrifices.

Huh. That actually makes a lot of sense. It’s the inverse of “build muscle to burn more calories”.

That's a myth. Extra muscle doesn't contribute very much to resting metabolic rate. Fat isn't metabolically "free" either; it takes a lot of energy just to move adipose tissue around.

https://muscleevo.net/muscle-metabolism/

In starvation it's calories not pounds that's critical, also it's not a question of resting metabolic rate alone.

Fat contains contains more than twice the energy per lb and every motion you do requires energy to move every lb of body weight. Net result storing energy in Fat takes ~1/3 the energy to maintain.

So, sure it's not a huge difference per day. But, the difference between dying in 100 days or 100 + X days could make a huge difference.

You're gonna need to cite some sources. Our side has studies to show you're wrong, and so far you've got nothing but your anecdotes.

“Within FFM, skeletal muscle (-5%)”

"Thirty-two nonobese men underwent sequential overfeeding (1 wk at +50% of energy needs), CR (3 wk at -50% of energy needs), and refeeding (2 wk at +50% of energy needs). AT and its determinants were measured together with body composition as assessed with the use of quantitative magnetic resonance, whole-body MRI, isotope dilution, and nitrogen and fluid balances." https://www.ncbi.nlm.nih.gov/m/pubmed/26399868/

So, over 6 weeks they had zero calorie deficit but even 3 weeks of starvation result cost them 5% of their skeletal muscles lower metabolic rate, and presumably increased fat. Note: Interment fasting has nothing to do with this, it takes the body several days respond to starvation a few hours don't matter as long as net calories over 2-3 days are maintained.

PS: What studies? I see a linked to an article about people over estimates of mussels energy requirements not a counter argument. You’re demonstrably wrong from both experiment and basic biochemistry.

That's actually different, you're talking about calorie restriction (-50% of needs), what we've been discussing is fasting (0% of needs). There are substantial physiological differences between the two modes, and that study is not relevant to this conversation. Fasting actually improves your body composition (reduces proportion of fat : muscle) [5]. Further, even if you regain all the weight you lost, you'll still have a better body composition after fasting vs. CR [6].

Speculatively, even the reduced amount of food will suppress HGH production - while total abstention yields many hundreds of percent increase in levels [3, 4]. HGH is known to be responsible conserving muscle and improving body composition.

It's been shown in studies that fasting raises your metabolic rate [1, 2] (again, offer not applicable to CR, by your own study and some others I don't have on hand right now). This is likely due at least in part to the production of norepinephrine during fasting. This further substantiates my point that we're talking about two different modes of operation.

CR != Fasting.

FWIW I agree with you, reducing your calorie consumption 50% but maintaining your 3-a-day plus snacks eating schedule is not great for you ("starvation") and likely damn hard to stick to. Weight Watchers themselves published a study that showed it just doesn't work. [7] This is what they were testing during the Minnesota starvation experiment and that didn't go well, to say the least. What my review of numerous studies indicates, is that the relationship does not extend to reducing your caloric intake 100% (obviously, intermittently for some value of intermittent). What it appears is being re-discovered is that it's not how much you eat, but what you eat, and how when/how often.

[1] https://www.ncbi.nlm.nih.gov/pubmed/14066725

[2] https://www.ncbi.nlm.nih.gov/pubmed/10837292

[3] https://www.ncbi.nlm.nih.gov/pubmed/3127426

[4] https://www.ncbi.nlm.nih.gov/pubmed/1548337

[5] https://www.ncbi.nlm.nih.gov/pubmed/17413096

[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042570/

[7] https://fatfu.wordpress.com/2008/01/24/weight-watchers/

I specifically commented on someone saying “our ancestors would just die of starvation”. So, if you want to talk about short term fasting then that’s cool but really not related to this thread of conversation.

Anyway, I agree under 2 weeks of fasting is not starvation. The body does not go into starvation mode over a few days becase it’s extremely expensive to cycle building up and removing skeletal muscle.

PS: It generally takes 24 to 72 hours for food to move through your digestive tract. In the very short term fasting you get excess energy because digestion takes energy. But extend that for 3+ weeks and very different things start happening.

My reading implies that the number of muscle cells does not change and that protein in the muscles is rapidly rebuilt upon re-feeding.

Entering 'starvation mode' from studies appears to happen around day 3-5 of fasting, there's charts in the links I provided. That's when the new energy distribution is in full effect and the brain is deriving most of its required energy from ketone bodies. If you have some interesting stuff to read about another shift that happens around 2 weeks I'd love to check it out, I'm always looking to learn more about this stuff. When 'starvation mode' switches to dying mode appears to be when all your fat stores are exhausted and the body no longer has fat to consume for energy. If you're obese that can be 12 months away or more. Most people who fast for long periods note the switchover happens when their breath turns sweet and a real feeling of hunger returns -- that's obviously when they break the fast so as not to die.

PS Read that closely, muscles don't burn 10x the calories of fat, but they do burn more. Actual study demonstrating what I am saying: https://www.ncbi.nlm.nih.gov/m/pubmed/26399868/

What is long term starvation in this context? Is a week already long term? The second point also goes against what I recall reading about cancer in calorie-restricted animals (I may be wrong).

The basal metabolic rate angle is interesting, did not directly come to mind.

3 weeks at 50% calorie restriction = 5% skeletal muscle loss. This true even though it was surrounded by 3 weeks of 50% calorie surplus

https://www.ncbi.nlm.nih.gov/m/pubmed/26399868/

That is absolutely not true. How do you plan to get food when you have the same amount of fat, and way less muscle to drag it around with? You'd be a blobby puddle until someone came to save you. That's not realistic, we'd all be so dead.

> In general, muscle is 'consumed' before 'fat'.

Where did you glean that information?

Here's my source that contradicts your statement: https://idmprogram.com/fasting-and-muscle-mass-fasting-part-...

> it takes a while for your body to decide it is a good idea to start creating toxins (ketones, which are quite harmless in smaller quantities) which are the result of fat conversion in a starvation diet.

Ketones are created when your body doesn't have sugar to convert into energy. This process can take as little as 12 hours, and in no way whatsoever requires a "starvation diet"

In general, muscle is 'consumed' before 'fat'. Quotes since it is more complex than just what regular muscle and fatty tissues do.

Not "in general." Only specifically in cases of starvation or caloric deficit. In general, your body burns carbs, then fat, and then muscle. Muscle is by far the least efficient energy source, so the body spares muscle in normal circumstances and only consumes muscle in times of extended caloric deficit, like fasting, starvation, marathons, etc.

> In general, your body burns carbs, then fat, and then muscle. Muscle is by far the least efficient energy source, so the body spares muscle in normal circumstances and only consumes muscle in times of extended caloric deficit

This is a common belief but it's not true. You can't prevent your body from burning muscle in any kind of caloric deficit, you can only stimulate protein synthesis to counterbalance it by 1) ingesting high amounts of protein and 2) resistance training.

Some muscle is consumed in a state of caloric deficit, yes. But muscle isn't the body's first choice for fuel until you enter into a state of extended caloric deficit. If the opposite were true, then triathletes would consume a pound or more of muscle during their training activities and especially during competitive events, instead of burning visually significant quantities of fat.

> But muscle isn't the body's first choice for fuel until you enter into a state of extended caloric deficit.

I'm honestly puzzled how people in this thread got the idea that I said that muscle was a preferred fuel. Literally no sequence of words I actually used imply this statement.

Yeah, sorry bud, you're just not in the right on this one. Your body always turns over muscle, sure, so some is going to be consumed. Your body produces huge quantities of HGH during starvation specifically to conserve protein and protein consumption goes down during fasting compared to steady-state. Otherwise our ancestors in periods of famine would turn into fatty puddles unable to drag themselves around. Starving means you need to get food, that's why noradrenaline levels go up, HGH production spikes (which many studies show changes your body composition to favor muscle over fat), your body switches to consuming primarily fat, and yes, some protein but not all protein is muscle. Your body also switches to producing what little glucose it actually needs via gluconeogenesis - which has many feedstocks including the glycerol backbones from triglycerides and yes, protein.

But to say your body prefers to burn muscle over fat when starving is ridiculous, and just not supported by facts.

[1] https://idmprogram.com/fasting-and-muscle-mass-fasting-part-...

> Yeah, sorry bud, you're just not in the right on this one. Your body always turns over muscle, sure, so some is going to be consumed

So you say I'm wrong, and then immediately agree with me? You have a strange way of disagreeing with someone.

> But to say your body prefers to burn muscle over fat when starving is ridiculous, and just not supported by facts.

Please quote the passage or link the comment where I said that.

Ah my bad I think I replied to the wrong post. I’d delete but I stand by my points just not which post they were at, so will keep.

Ketones aren't toxins in this context, they're literally food.

Shouldn't you cite your sources as well?

I should have, I was busy or lazy.

Here's a pretty good meta-analysis:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970209/

There's a lot of conflicting data. However I think the general thrust is that you should not try to lose weight unless you are accurately measuring how much lean mass you are losing. Otherwise it's very easy to lose a lot of muscle, which is probably not healthy unless you are extremely obese. Crucially your current body composition matters quite a lot. People under 10% body fat are going to start losing really important vital body mass. People over 25% body fat will lose mostly fat. But people have wildly different body compositions and a BMI of 25 doesn't mean 25% body fat. Again, accurate measurement is crucial.

Personally, I focus on maximizing a variety of physical measurements. (How long I can hold various yoga poses without discomfort, how many situps I can do, how far I can bike/walk/swim before I begin to feel fatigued, etc.) I definitely think optimizing weight downward is a poor strategy for improved health.

You can avoid losing muscle during a diet by doing resistance training: https://sci-fit.net/bulking-deficit-gaining/

Increasing protein intake also slows lean mass loss considerably as well, even without resistance training.

What's the difference between fasting (especially extended fasting) and "literally starving yourself"?

I only hear good things about the former.

Fasting has a time limit.

> While not healthy to literally starve yourself, getting your calories from stored fat is absolutely safe.

Sure, if you can guarantee that you're burning fat. That's clearly not what I said, because "weight loss" does not necessarily entail "fat loss". If all you're doing is looking at the scale, unless you take certain precautions, then you're also losing muscle mass. Doing this "quickly", which was another qualifier I stated, can be dangerous.

> Proper electrolytes all but eliminate most issues you suggest, only applicable to a pure starvation diet.

You need more than electrolytes to prevent muscle loss. Devoting more of your caloric budget to protein slows muscle loss considerably, and adding resistance training can prevent muscle loss entirely.

But like I said, just focusing on rapid weight loss with no other considerations is dangerous.

He's right, it's FUD. Studies [1] show that protein consumption goes down over the course of fasting, and that only makes sense. To borrow an analogy from [1] if your body is storing up energy for a rainy day like logs for a fire, when the power goes out are you going to chop up your axe and couch for firewood? Of course not, that's insane.

Evolutionarily, it makes the most sense to conserve your muscle so you can hunt down and kill food, not waste away into a fatty blob and make it a few extra days until what, someone finds you? That's why your body's HGH production spikes to hundreds of percent of baseline, to conserve your muscles.

Protein is always consumed as muscles turn over, but most tissues in your body can consume glucose OR ketones -- even your brain can switch over to consuming ketones as its primary source of energy. The remaining glucose requirements are met via gluconeogenesis, from multiple sources, including the glycerol backbone of triglycerides. However, there's plenty of non-muscle sources of protein in your body too and they are most definitely consumed as part of autophagy.

[1] https://idmprogram.com/fasting-and-muscle-mass-fasting-part-...

Re-posting my study pile for those interested:

ADF succeeds in the reduction of insulin resistance/type II: https://www.ncbi.nlm.nih.gov/pubmed/15640462

Fasting increases metabolic rate: https://www.ncbi.nlm.nih.gov/pubmed/14066725 and https://www.ncbi.nlm.nih.gov/pubmed/10837292

Fasting dramatically increase HGH production: https://www.ncbi.nlm.nih.gov/pubmed/3127426 and https://www.ncbi.nlm.nih.gov/pubmed/1548337

IF (1 meal per day) improves body composition even when the caloric intake remains unchanged: https://www.ncbi.nlm.nih.gov/pubmed/17413096

Body composition is better after fasting than caloric restriction even in the event of equal amount of mass re-gain (i.e. regain after CR is fat, after ADF is muscle/lean): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042570/

A mouse study showing ADF improves metabolic markers without change in caloric intake, but of course, it's mice, so YMMV: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5872764/

It's not FUD, none of your sources are relevant for the context of this thread, and you and the other poster have completely misunderstood this context.

Note that a good way to tell if your body is burning muscle is that your sweat/urine will start smelling like ammonia.

https://www.bodybuilding.com/content/what-is-that-ammonia-sm...

Wow! 20 years ago I was helping my ex father in law with some construction work. He and all of his buddies were tweakers and a lot of them smelled funny. I always thought it had something to do with meth but now I'm guessing they were just burning muscle.

Losing weight too fast is bad, but a 500 cal/day deficit is healthy and can drop a pound a week. It is important to exercise and preferably train with free weights to maintain muscle mass. It's actually possible for untrained men to gain muscle while losing weight (haven't seen results for women).

>> Losing weight too fast is bad

I disagree. If you can find a reference it must also be one where the subjects were in ketosis or it doesn't count.

> You can lose considerable muscle mass

BCAA

BCAA are not zero calorie, contrary to popular wisdom, so you can't consume them during a fast. It's a regulatory loophole that amino acids don't need to be counted towards the caloric total.

If you do intermittent fasting (16-24h), you can eat it during the non-fasting periods and it should help with muscle loss. Also, you can do HIIT during longer fasts to keep muscles "in demand" so that proteins aren't recycled by your body to usual extent. There was some study about it somewhere...

Yes, resistance training and high protein intake minimize muscle loss in a caloric deficit.

Did anyone here try the "Fasting Mimicking Diet" yet?

https://prolonfmd.com/fasting-mimicking-diet/

(not affiliated)

I've also found the benefits of intermediate fasting. Lost about 16 pounds in 2 months.

I have an 8-hour feeding window, but I try to start the day with low-carb food, such as some nuts and an egg. Then after one or two hours, I will eat normally (some bread, banana etc.)

Summarized: 8 hour feeding window, 6-7 hour carb window.

I specifically don't want weight loss greater than 1-2lbs/wk -- slow and steady wins the race.

Trying to change a very complex set of equilibria too quickly is a recipe for disaster.

Ability to maintain a diet is more important than the speed of weight loss.

You showed yourself that while it was fast, it was difficult to maintain. This sounds like a less effective diet.

I know people who did it and they tell me it takes at least a few weeks or a month before you just plain lose the appetite and it becomes the norm. Habits are hard to change, even when the change positively affects the quality of your life.

I’m 55 6’1/2” I’ve always done weights but only about 1 hr per week because of family long work hours etc. 1 year ago I moved from UK to Portugal (brexit), I was 95 kg 209 lbs, was disgusted with my self and wanted to get beach presentable body back. So I tried one meal a day - results were astonishing lost 10kg in 6 weeks. I’ve kept it going with a few cheat days 1 or 2 days per week and kept at around 86 Kg 189lbs. By far the easiest diet i’ve tried, I find it much easier to just not eat than to eat small portions, low carb also worked for me before but so difficult to maintain. I eat what I like now, inc pizza fries burgers etc though I try and eat lots of veg 4 meals a week. Just lots of black coffee lots off water and Himalayan salt rest of the time. My colleague was in early stages of type II diabetes taking Metformin etc, he tried the same and it completely cured him with 8 weeks, his doctor couldn’t believe it.

>haven't done much in terms of changing what I'm actually eating.

Sure about that? Pretty unlikely you’ll lose weight if you’re consuming the same calories

It's entirely possible to consume fewer calories "automatically" by making simple dietary changes that don't involve tracking calories. Thermodynamically, a calorie is a calorie, but it turns out the physics picture misses the point of recommending how to eat for weight loss and good health. Nutritionally, a calorie is emphatically not a calorie.

Calories in different macronutrient forms (protein, fat, simple carbs, complex carbs) have different effects on metabolism, satiety, insulin secretion, and mood. These differences in turn alter caloric intake. Cutting out refined starches and added sugar is more effective for long-term weight loss than obsessing over caloric intake, e.g., https://www.nytimes.com/2018/02/20/well/eat/counting-calorie...

I hate this:

"we are working on finding a new chemical that can mimic the effect of this ketone body's function"

They know what the molecule is and it works in mice. I presume they want to find a patentable molecule to mimic the natural one.

Well yeah, if it's not salable what's the point in spending anytime on the research?

And they know it can be made in the body, free of charge, by changing eating schedule. Sounds like maybe convincing people to change their eating schedule is the way to go?

But, but, we can sell them lots of food and diet pills!

Can anyone read the study and actually tell how long or what kind of fasting did it take to gain those results? The article just quotes a scientist about fasting for 24 hours.

I was browsing through exactly for this.

Since the benefits seem to be linked to ketosis, I believe we’re talking about fasts longer than 1-3 days, since that’s typically how long it takes to reach ketosis. So anywhere from 1-14 days, I would think.

You can reach ketosis without fasting, it's worrying that both this article and it's source are not really clear on the methodology.

This the actual source:

"Here we report that β-HB promotes vascular cell quiescence, which significantly inhibits both stress-induced premature senescence and replicative senescence through p53-independent mechanisms.

Further, we identify heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a direct binding target of β-HB. β-HB binding to hnRNP A1 markedly enhances hnRNP A1 binding with Octamer-binding transcriptional factor (Oct) 4 mRNA, which stabilizes Oct4 mRNA and Oct4 expression. Oct4 increases Lamin B1, a key factor against DNA damage-induced senescence.

Finally, fasting and intraperitoneal injection of β-HB upregulate Oct4 and Lamin B1 in both vascular smooth muscle and endothelial cells in mice in vivo. We conclude that β-HB exerts anti-aging effects in vascular cells by upregulating an hnRNP A1-induced Oct4-mediated Lamin B1 pathway."

https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)3...

I read it too, and there is absolutely nothing new. Pick any protein network database, and all these actors are already linked. Basically, you could have written the same conclusion without sacrificing any mice.

You definitely don’t need 1-3 days to reach ketosis, your previous diet macros have a huge impact on this. My blood ketones are at 1.2 mmol/L right now after 7 hours of sleep.

Well, the fast lasted for 72 hours, but it's important to note that the subjects were lab mice, not humans.

From the paper:

Mice strains

C57BL/6J mice were purchased from the Jackson Laboratory. All mice were housed in temperature-controlled rooms with a 12 h light-dark cycle and given free access to water and food. After starvation for 5 h, 8 weeks-old male mice were injected intraperitoneally with PBS, β-HB, or S-β-HB (1.5 g/kg body weight in PBS). In parallel, 8 weeks-old male mice were randomized and fed a regular chow diet or fasted for 72 h. Then, the mice were sacrificed. Tissues were collected for gene expression evaluation in various organs including the aorta, liver, heart, brain, adipose, and kidney (n = 6). All animal protocols were reviewed and approved by the Institutional Animal Care and Use Committee at Georgia State University.

https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)3...

Also note the slightly confusing setup of the study. Some mice were first fasted for a short time (5 hours) then injected with the tested molecules. Then a different batch of mice were fasted for a longer period of time (72 hours). The second batch where tested blindly and at random, the first one where not. To me, that sounds very strange, but I'm not a biologist, so.

All the other studies I’ve heard about said that the benefits of fasting kick in pretty quickly, with 24hrs being plenty to get quite a few benefits.

Edit: personal experience and some scant scientific evidence seems to point to there being a significant difference between men and women on this one. Men seem to accrue more benefits with longer fasts (diminishing returns though), women seem to get metabolically stressed earlier on. More studies are needed though.

Not all of the benefits. There are some significant benefits to the immune system that require at least 72 hours of fasting in humans.

https://www.fightaging.org/archives/2014/06/fasting-can-be-u...

Peter Attia is an interesting person to listen to discussing ketosis and fasting; in [1] he only eats fat for a week followed by a 1 week fast and a further week of ketosis afterwards.

In [2] he specifically talks about the benefits of Ketosis in depth with one of the leading experts in this field.

[1] https://peterattiamd.com/ama02/

[2] https://peterattiamd.com/domdagostino/

He doesn't eat anything for 1 week in 4?

For 1 week at the start and at the end he eats no sugar or carbohydrate.

For 1 week he the middle he drinks water and takes magnesium.

That's it.

it was just a one time experiment as he wanted to do a 7-days water only fast and decided it would be better/easier to do a 7-days keto diet the week after and the week before. It's not something he does continuously all year long.

Relink to [1] perhaps, which is the original source without any anti-adblocking nonsense?

[1] https://news.gsu.edu/2018/09/10/researchers-identify-molecul...

I do fast once in a week and I have seen good benefits. I have been doing this since 2014. This is what I do: Dont eat breakfast, lunch or anything till dinner. (Some people skip breakfast and dinner). Though I do drink lemon juice once in the day.

I obviously lost some weight, but more importantly it developed habit to ignore temptations. I find my self more relaxed overall.

All these different supposed anti-aging molecules that our body already produces.. e.g. nad+ also

I would love if these could be used to slow or even halt aging but i would worry there is reason the body doesn't produce more of these. It's been said before but would we be leaving ourselves open to more cancer?

>> i would worry there is reason the body doesn't produce more of these.

It's starting to look like the reason is the modern diet. And by modern I mean what we shifted to with the advent of farming several thousand years ago. 3 meals a day with high carbohydrate content. This puts you into the mode of converting carbs to fat for storage and never gives the opportunity to go into a mode of retrieving fat for energy. One specific reaction to eating carbs is an insulin response, which can last several hours. It's looking like people weren't design (evolved) to live that way. Type II diabetes (insulin resistance) is looking entirely preventable and perhaps reversible if one goes keto. You're just not going to produce the chemicals needed for one mode of operation when you're telling the body to do something else. These diets are proving that you can get it to produce another set of chemical in clinically meaningful quantities.

https://theoutline.com/post/6133/the-keto-diet-is-a-recipe-f...

I have observed a surge in articles related to fasting (all of them are positive about it). Has there been new breakthrough in the field?

It might just be the post-Soylent diet fad in tech:

https://www.theguardian.com/lifeandstyle/2017/sep/04/silicon...

If its anything like technology, dieting probably suffers from baseless trends which become self-sustaining at a certain point.

Well fasting has been a trend since I don't even know, well before ancient greece at least. Western culture != entire world.

fasting has been common in the western world since forever too.

But that has nothing to do with the fact that it's a nutritional fad these days, much like paleo was the hip-est thing a few years back, and the mediterranean diet was en vogue before that etc.

Just the same, the current diet / dieting of most Western peoples is not sustainable. There's always noise and opportunists. That doesn't the rest of us should try.

Ultimately, for me, these articles boil down to me being willing to change my relationship with food. The more I eat for health, and less for pleasure, the better off I'll be.

It must be an up-and-coming Internet trend/meme (a la what color is the dress?) in the health community. One of my coworkers just transitioned from a ketogenic diet to intermittent fasting.

I'm not so sure. IF was in "fad" mode several years ago. The IF sub-reddit is already 6 years old. Now it just appears to be something that people are rediscovering because of posts (mainly on social media) about this type of research. There's nothing "new" in IF in terms of the approach to diet.

Here's an HN submission from 2012:

https://news.ycombinator.com/item?id=4341091

It won't last - how do you make money off a fasting diet? There's nothing to sell, unlike WeightWatchers, Shakes, Juice diets etc.

Unless someone sells fasting chewing gum or something.

You sell calorie free "cleansing" drinks.

Ah yes of course. There is some interesting research into the benefits of Dihydrogen Monoxide with Hydroxyl Acid extracts, zero calories and can help extend a fast for days. Patent pending.

Be careful, though. Prolonged expose of Dihydrogen Monoxide to the lungs has been shown to cause death. It also rusts metals and dissolves many other materials.

I think may schools have been shown to have Dihydrogen Monoxide contamination in their cafeterias and restrooms.

Plus it was found to be the main component of cancer cells, so I'd be really cautious here.

For ketosis, you are allowed to eat carbohydrate less food. So, cheese is fine.

But then your LDL will rise up, thereby negating any cardiac benefits...

Diatary and Blood collesterol are not casually linked as many erroniously assume. Easy mistake.

I don't want to get into a heated nutrition debate because it's such a mess divisive landscape, but wanted to share the other side, which looks compelling: https://nutritionfacts.org/2016/03/22/the-effects-of-dietary... And another interesting piece of science pointing at causation rather than correlation regarding LDL and CAD: https://nutritionfacts.org/video/how-do-we-know-that-cholest...

“While the low carb, ketogenic diet did not lower total LDL cholesterol, it did result in a shift from small, dense LDL to large, buoyant LDL, which could lower cardiovascular disease risk.”

Low carbs diet also increase HDL.

Here is an article that goes into a little detail : https://www.ruled.me/the-ketogenic-diet-and-cholesterol/

I'll offer to take your money so you can't use it to buy food. For a fee, of course ;)

There is a market writing books, articles, and spamming hackernews with it to promote said books and articles. I am yet to see a good, accepted study linked though.

Has the surge been all year, or only the past few days? The large Jewish fast, Yom Kipporim, starts tomorrow evening and people love to find scientific explanations for their strange habits.

If my comment sounds condescending, then be there no mistake: I'm Jewish and I'll be fasting.

it has been growing for the past decade. me and several people I know regularly fast for health benefits and not religion.

This was when it hit the mainstream for me https://www.bbc.co.uk/programmes/b01lxyzc a BBC programme in 2012

No, it’s just fasting bank holiday in Switzerland.

Coincidentally, Yom Kippur [1] begins tomorrow, when observant Jews fast for approximately 25 hours.

[1] https://en.wikipedia.org/wiki/Yom_Kippur

No food, no liquids, no water.

Is fasting with water less effective?

Less effective in what sense? If one included drinking water, bathing/cleaning, or sexual relations it wouldn't be a proper religious fast, unless one is excepted from it, e.g. due to health issues. There are no degrees of effectiveness so to say.

I meant religous fast versus an occidental fast...

I am in a study by Stanford University to only eat during a ten hour period each day. So far, I am sleeping better but subjectively that is all I can say.

I do personally believe that in the past occasional 20 to 24 hour fasting and not eating after 6pm has increased my feeling of being healthy. My personal experiences don’t have much meaning so I am looking forward to more proper scientific studies in the future.

I would've thought most people eat within a ten hour window (8-6p, 10-8p, etc), though probably only if you ignore snacking.

Looking up details of the study design, the molecule in question, β-Hydroxybutyrate, was tested in vitro on human tissue, and in vivo only on mice, so, as usual, wait patiently to see if there is any confirmation in, say, a large-scale study of a human population.

The researchers tested the efficacy of β-hydroxybutyrate against cellular senescence in vitro on human umbilical vein endothelial cells and human aortic smooth muscle cells, and they observed the beneficial effects of this molecule in vivo: by injecting β-hydroxybutyrate into fasting mice, the scientists were able to alleviate the senescence of the animals’ aortae.

https://www.leafscience.org/molecule-appears-to-have-anti-ag...

How does it fit with intense anaerobic exercise? Is it safe to do? Can I expect dizziness?

I have definitely experienced dizziness and feeling faint while fasting.. I'm not sure it's safe to exercise.

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