Fasting Improves Physiological and Molecular Markers of Aging (2019) | Hacker News Reader

Fasting Improves Physiological and Molecular Markers of Aging (2019)

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131 pointsTomte112 comments

I really urge people to do a multi-day fast a few times a year. I wrote a little guide about it that I shared previously [1].

You can wonder about these longterm positive effects, but it's sort of a Pascals wager. You lose absolutely nothing and it could have significant upside. Worst case, it makes you confront your relationship to food and offers a great mental challenge.

One cool thing that you learn is that there is a maximum hungry you get. It doesn't ever go past that point (and you've felt it before without fasting). Even better, it ebbs and flows. You won't be in a state of "OMG I am starving!!" all day long. It hits at normal eating times, and then retreats to the background.

Anyway, just try it.

[1]https://www.nicholasjrobinson.com/blog/general/five-day-fast...

The more studies pile up, the less it seems to matter the length of a given fast, but more the total time spent in a fasting state relative to a fed state.

So as a taster, you can do multiple 24-hour fasts and get the same experience from a health point of view (everything else is different, though).

That said, at some point, I’m interested in trying a multiple-day fast myself but haven’t taken the plunge yet.

> The more studies pile up, the less it seems to matter the length of a given fast, but more the total time spent in a fasting state relative to a fed state.

Yes, I've noticed this as well. Personally I fast for 17 hours every day and I've noticed I feel the benefits without negative consequences. Once in a while I'll go for a 3 day fast but aside from the personal challenge accomplishment I don't notice a major gain. My experience is all very non scientific. For the more rigorous science, I usually look to Peter Attia[1]

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

> you can do multiple 24-hour fasts and get the same experience from a health point of view

NO, that's incorrect. The length matters a lot. In fact, a major change occurs after the 2-3 day mark, when body glycogen stores are depleted and your body shifts to ketosis etc. Another major marker has to do with when a much coveted state called autophagy is activated.

I have not heard this. Can you share more? I’m familiar with ketosis but unfamiliar with it in conjunction with fasting. Or benefits for otherwise healthy people. Ketosis has lots of downsides for normally healthy people.

Ketosis is literally the start of starvation, so I'm dubious of widespread health benefits. I know it is extremely beneficial to people with a history of seizures, but that's it.

> Ketosis has lots of downsides for normally healthy people.

I've been considering trying ketosis but all I've heard are good things, what are the downsides?

The most significant downsides are psychological and kidney stones, plus its literally (by definition) your body’s signal of starvation.

https://en.wikipedia.org/wiki/Ketosis#Safety

Oh and this gem from the article on starvation.

> After two or three days of fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement for glucose. After fasting for three days, the brain gets 30% of its energy from ketone bodies. After four days, this may increase to 70% or more.[11] Thus, the production of ketone bodies cuts the brain's glucose requirement from 80 g per day to 30 g per day, about 35% of normal, with 65% derived from ketone bodies. But of the brain's remaining 30 g requirement, 20 g per day can be produced by the liver from glycerol (itself a product of fat breakdown). This still leaves a deficit of about 10 g of glucose per day that must be supplied from another source; this other source will be the body's own proteins.

This is the biggest reason I've never done more than toy with ketosis is the body consuming muscle for protein to supply that remaining 10g of glucose per day. Esp. because 1 lb of muscle only 1,800 Cal vs 3,500 Cal / lb. Fat.

There's nothing in the article you linked to support your claim that it's "literally your body’s signal of starvation". It does happen during starvation, but that's it.

The first two phases of starvation are defined in terms of ketosis. It is by definition the start of starvation.

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

Phase one: ... After that, the body begins to break down fat and protein. Fatty acids are used by the body as an energy source for muscles, but lower the amount of glucose that gets to the brain. Another chemical that comes from fatty acids is glycerol. It can be used like glucose for energy, but eventually runs out.

Phase two: Phase two can last for up to weeks at a time. In this phase, the body mainly uses stored fat for energy. The breakdown occurs in the liver and turns fat into ketones. After fasting has gone on for one week, the brain will use these ketones and any leftover glucose. Using ketones lowers the need for glucose, and the body slows the breakdown of proteins.

Ketosis being present when starvation occurs does not mean that starvation occurs every time ketosis is present. A in B doesn't mean B in A.

It seems we're arguing semantics here. My point is that it is biologically indistinguishable from starvation at this point again by definition. Without an interview a doctor could not tell the difference.

Your point seems be an objection to the use of the word starvation because it doesn't progress to the later stages due to maintenance of available fatty acids. And that it can be useful and therefore the word starvation is inappropriate. Does this sum it up?

No, we're not arguing semantics. The definition of starvation, according to wikipedia, is: "Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life.". However ketosis can occur at a normal caloric energy intake. Also from the article: "The symptoms of starvation show up in three stages. Phase one and two can show up in anyone that skips meals, diets, and goes through fasting.". But you can get into ketosis without fasting or skipping meals. I'm not sure what "diets" means here. If it means "following a non standard diet", that would cover low carb diet. However if it means "reducing your caloric intake for health/aesthetic reasons", it wouldn't cover it.

That’s interesting but I was planning to eat, which means that those 10 grams of protein would come from food. Unless I missed something important there?

ketosis increases risk of kidney stones, which is a pretty huge downside given that many people describe kidney stones as more painful than childbirth

That certainly doesn’t sound fun! Thanks, I obviously need to do more research.

This has been my personal experience. Things go strongly ketogenic around day 3. It’s an experience worth having at least once in your life, even if you’re not interested in a ketogenic diet. The longest I’ve fasted is 7 days, and things felt quite a bit different between day 2 and day 4.

I find that physically you are fine when you do this: you can walk around, do house work, etc... but mentally you are shot.

I would love to try this - but certainly dont have 5 consecutive days where I can be a mental vegetable.

The brain needs constant fuel. Anyone experience this as well?

I found my experience to be the opposite. I had clear mental focus, but felt physically drained of energy the entire time. I did a 3.5 day water fast, with the majority of my fluids from water/tea with salt for electrolytes.

My sleep was pretty terrible up until the last night, when I got a solid 8 hours without waking up once. I usually wake up 8-10 times a night, so this was a huge breakthrough. I also regained my energy on that last half day and felt incredible.

What type of fasting did you do, and what liquids did you drink?

I generally find myself sharper, more alert and with much more energy. This continues the longer your fast lasts, up until day 7ish in my case.

Your noradrenaline levels spike when fasting, and it can make it hard to sleep - too juiced haha.

If you're finding yourself tired, it could be a lack of electrolytes. Try a teaspoon of salt in a pint of water. I tend to drink coffee when water fasting, which has an outsize effect.

Same. It makes sense to me intuitively: when you're hungry, you go into an alert "hunting mode". My sense of smell is normally very weak, but when I am hungry it increases by a factor of 100.

(Consider using “I” instead of “you”.)

I have found that once I become fat adapted, I no longer suffer from mental clarity problems. It takes a couple of days without carbs to get there for me.

Naps help. Plan your day around one or even two naps.

Also watch your electrolytes. Salt, potassium and magnesium can greatly affect energy levels.

> The brain needs constant fuel. Anyone experience this as well?

That is true, however that fuel does not need to be glucose. As far as I understand it, people eating 3 meals a day and snacks (all containing carbohydrates), their body is not used to relying solely on fat/ketones for energy, and it takes time to adjust.

Also, it's very important when fasting to ensure you're replacing water and electrolytes since once you've burned through your stored glycogen you will have lost quite a bit of water. If you're feeling light headed or out of it, that is one of the causes, whether you're starting a ketogenic diet or fasting.

When I'm fasting I use an electrolyte mix which has sodium, magnesium, phosphorus, potassium and calcium. One of the main reasons for refeeding syndrome is that electrolytes are depleted, and when someone eats again, their cells take up what little electrolytes are left in the blood, which leads to dangerously low levels.

To be precise, some of the fuel does need to be glucose. There is no such phenomenon as solely relying on ketones for energy, and the brain is especially glucose greedy.

In a sufficiently fasted state, all of that glucose will be endogenously produced rather than coming directly from food, but it does need to be there.

Endogenously, from the fat/glucose pathway. Not sure that any glucose is required to be consumed directly. But we do love sweets, and fat cells love saving energy.

I did a weekly "don't eat anything on Sunday and don't eat until Monday lunch" for about a year. Sunday afternoon/evening I'd be kinda groggy and grumpy. I'd wake up on Monday morning completely locked in - it felt like a high dose of adderol without ANY of the side effects. I'd get 2 days worth of work done in a morning. I'd always be bummed Monday afternoon because as soon as I ate the focus went away.

In my experience, it seems the brain gets addicted to having a constant flow of glucose streaming into it (it's the most expensive organ to run, calorically) and it gets to think a lot more when it has its fuel. This isn't necessarily healthy, especially if left unchecked for a long period of time. Part of the benefit I believe I've gotten from fasting is re-training my brain to work well in a variety of glucose levels (including very low).

These days, I can feel my body switch modes when I enter a low-glucose state. It's a certain type of relaxation that feels like my brain just stops running certain programs. For example, it can't afford to hold on to dramatic, powerful emotions in that low-fuel state, and so it stops running its "replay enraging memories" program, so to speak.

You're correct that the brain needs constant fuel, but we have an unbelievable source of fuel in our bodies called fat. Increasing the metabolism's flexibility, such that it can gracefully tap into that massive fuel source, has had a noticeable impact on my mental and physical health.

IME, it's more like a hump you have to get over, for what that's worth.

It takes about a day for me to break through this.

I do prefer resting physically when fasting, but the mental clarity is unparallelled after 24 hours.

Wait. Why is it possible fasting has upsides, but it is not possible it has downsides?

You could ask the same question about eating 3-4 meals per day.

This is a relatively new phenomenon for humans - starting in the 1700s. Feast/famine is how we used to live. The Romans ate one meal a day and frowned upon breakfast, for instance - their default was what we would now consider OMAD fasting. [1]

[1] https://www.bbc.com/news/magazine-20243692

Just because you can ask the same question about eating 3-4 meals per day DOES NOT mean that we can automatically assume that fasting might be better but is definitely not worse.

It could be better, worse, or the same.

We don't know. And there's no reason to assume that it might be better while it is definitely not worse (and therefore an obvious choice).

There are reasons to assume it might be better. It dramatically raises HGH levels [1] which improves body composition (increases the proportion of muscle to fat), improves insulin sensitivity, lowers blood pressure and reduces general inflammation / oxidative stress - even in the absence of weight loss [2]. It also burns fat (obviously, since there's nothing better to burn when fasting) which for the vast majority of folks is strictly better than the alternative.

There's a lot of compelling studies being done at the moment, including the interaction of fasting with the immune system. [3]

> Last week, in a paper just published in the New England Journal of Medicine [4], Rafael de Cabo and Mark Mattson reviewed multiple strategies for fasting that have been tested in the years since Longo's study. The news continues to be very encouraging: intermittent fasting is good for you.

I'm not saying it's conclusive but to suggest there's no reason to think it might be better is disingenuous.

There's been some pretty interesting studies over the last few decades (few and far between, but interesting) - and the idea of fasting for heath is enjoying something of a renaissance in nutrition research these days.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC329619/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990470/

[3] https://www.forbes.com/sites/stevensalzberg/2020/01/06/can-i...

[4] https://www.nejm.org/doi/10.1056/NEJMra1905136

> I'm not saying it's conclusive but to suggest there's no reason to think it might be better is disingenuous.

I didn't say there's no reason to assume it might be better!

I said there's no reason to assume it might be better AND that it is definitely not worse.

I suppose that might be true, but I'm not sure how one would go about and prove a negative like that. Especially in the field of nutrition science which has famously alternated between calling coffee the Devil's Hot Bean Juice and the Second Coming. Current consensus appears to be, based on a 1.2 million person meta analysis that 3-5 cups per day reduces the risk of cardiovascular disease. [1] I suspect in reality there are just too many factors to do that.

[1] http://circ.ahajournals.org/content/129/6/643.long

From an evolutionary perspective, our bodies were designed for fasting. They were NOT designed for 7-8 decades of plenty.

Devil's advocate: From an evolutionary perspective, our bodies were designed as mere vessels to propagate our genes.

They were not designed to survive 7-8 decades regardless of diet, because by this time reproductive success (and therefore fitness and pressure) is zero for women and almost zero for many men.

Devil's advocate against this point: Grandparents might increase the reproductive success of their children's children, helping their genes propagate in accordance to Kin theory.

Devil's advocate against Devil's advocate of this point: Grandparents might also decrease the reproductive success of their offspring, since they must care for their own children as well as their parents. Hence, the near inescapable phenomena of dementia as age increases into the 100s, and the trait of Senicide (ex. Ättestupa) in many cultures.

My point being, maybe it is best to avoid categorical statements about "evolutionary perspectives."

edit: Correction, Ättestupa is mythological and not a good example of Senecide. The wiki for senecide has many other examples, however.

I'm afraid I have to disagree with your point.

From an evolutionary perspective, “vessels to propagate our genes” carries a lot of baggage with it, including the need to be healthy enough to take a baby to term, care for yourself/other family/group members, and raise it until it reaches sexual maturity, all of which require efficient energy gathering, storage, and usage strategies.

> My point being, maybe it is best to avoid categorical statements about "evolutionary perspectives."

Indeed, it's a wide, complex topic that I only know a little about, and I only had time for a brief comment.

BTW love your chain of devil's advocate statements. More people should think/counter that way.

Thank you! I am trying to argue with myself more. Partly because I can be a bit of an opinionated know-it-all which is unpleasant and very foolish!

Also I think about how young we are as a species that uses the scientific method to question our reality.

Maybe all of my knowledge today will not stand the test of time, and will be considered just as silly as someone from the 1600s seems to me today? (ex. A natural philosopher that believes in abiogenesis)

But a mutual respect and bond can exist if we both strive to prove ourselves wrong, adapt, and grow.

Of course, it has downsides—the length of the fast matters a LOT. Too long, and it’s starvation which has considerable downsides as I’m sure you’re already aware.

The biggest takeaway that I’ve gotten recently is that our bodies are literally designed to take fasting into account. Specifically, our vascular system is terrible at doing cleanup and nutrient delivery at the same time. So it needs ample time to do both.

> Specifically, our vascular system is terrible at doing cleanup and nutrient delivery at the same time.

I'd not heard this before, sounds cool. Do you have a reference handy? Thanks.

Here’s one. It’s not said directly, but that was my take away reading several articles along these same lines. https://www.sciencedirect.com/science/article/pii/S156816371... and one specifically about cancer https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322...

I like to fast for a couple days, simply because I find it helps a lot with mental clarity. However, I think you make a good point.

Fasting absolutely can have downsides. The link in the comment you are replying to, for example, recommends a five day fast which is a lot longer than I've ever seen recommended.

The first obvious downside is that people with health conditions like diabetes, underweight, immunocompromised, etc. need to consult a doctor first. They would probably call a 5 day fast with zero intake of food or electrolytes needlessly reckless with little evidence to support it over a shorter fast.

Medical studies also tend to be of poor quality and don't stand up to meta-analysis by organizations like Cochrane. For example:

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD...

https://www.cochrane.org/CD013496/VASC_does-limiting-times-y...

The Mayo clinic also argues theres not enough high quality evidence even on intermittent fasting at this point to recommend for or against it in weight loss (where you think it would be of obvious benefit):

https://healthletter.mayoclinic.com/issues/july-2020/is-inte...

Speculating on in-vitro effects and microbiological mechanisms scaling to result in things like cancer prevention or life extension seems like a fools errand.

People saying "oh but it's natural" are also making a naturalistic fallacy. It was also "natural" for much of human history to be infested with parasites and ravaged by disease. Natural is not necessarily good.

> People saying "oh but it's natural" are also making a naturalistic fallacy. It was also "natural" for much of human history to be infested with parasites and ravaged by disease. Natural is not necessarily good.

I think you are committing a fallacy here too. The naturalistic appeal is not about how things were before, but in what conditions we evolved. For example, we could try to eliminate every single germ everywhere, but that would make our immune system weaker, because our immune system can adapt itself. Vaccines are a way of leveraging that knowledge about our immune systems. Same thing about light: we spent most of our evolution time following the Sun cycles, and now we see that people that work shift hours are in a worse condition than people that don't.

A big difference between the way we fast today and the way people may have faster before is that we don't have to hunt or gather for our food, we have certainty about the presence of food at the end of a fast. Though by writing that, I wonder if early humans felt constantly the need for food and the fear of not finding it. I don't even know if animals do.

The biggest downside is that I don't get to eat delicious cakes for hours or days.

> but it is not possible it has downsides

I remember reading somewhere that anorexia used to be more common in highly religious communities where ritual fasting was encouraged: the devout would fast so long that they would find themselves unable to eat again when the fast was over. If you go too long without eating, you can actually lose the ability to do so. I don't suppose that can happen after just a two-day fast, but it does seem like a "possible" downside to me.

I used to do 16/8 or 18/6 and it's pretty easy. I still usually don't eat breakfast because it makes it easy to get > 12 hours fasted.

A few months ago, though, I started doing a 24 hour fast every week. It takes some planning but it's surprisingly easy. I'm damn hungry by the end, but it's never been an issue. I'll even work out and lift heavy 22+ hours into the fast without a noticeable decline in strength. I have no plan to stop doing this.

I'm curious what planning you mean? I do it without planning and haven't had an issue.

Planning my social life around it. I'm not as fun at dinner if all I can have is water.

I love fasting and typically I have one meal and fast for 22 hours a day, but please be careful with multi day fasting.

I drink a lot of water and on two occasions on 60 hour fasts I passed out cold, falling to the ground and chipping one of my front teeth in the process, but it could have ended much worse.

I eventually figured out I was not consuming enough electrolytes relative to my water consumption, I still recommend long term fasts but please do more research than I did and be careful.

I have kept that chip in my tooth to this day to remind me my naivety and how lucky I was.

The study in the OP is specific to alternate day fasting though, which is generally much more tolerable than straight-up multi-day fasts, and can be done over a much longer term.

How do you overcome upset stomach? If I don't eat for half a day my stomach starts to hurt.

I have history of diabetes in my family ( south asian) I took the 23andME test and the report said i have a pre-disposition to diabetes at around age 50. I am 50 now. I have been working out running most of my life but started doin less miles and i packed on a few pounds maybe i was like 188-192 and i am 5' 11" About 2 years ago i was diagnosed with pre-diabetes the doctor said you need to get you A1-C down. I was like i have been working out all my life and now this! ok so i started looking into IF ( found some good videos by Dr Jason Fung) so i tried it and started not having breakfast ( I was eating a chocolate croissant from trader joes typically) i went black coffee. Giving up breakfast was damn hard after 6 months i got used to it so the next jump was giving up lunch i got hunger pangs and it was very very painful NOT to eat lunch but to my surprise i got used to NOT eating lunch and fast forward 2 years today i fast all day and my first meal is 5pm and usually a big salad and i feel fantastic all the hunger pangs are gone now i don't know how to explain it but water is sweeter and even black coffee taste sweet to me i am down to like 170 now and have an unusual mental clarity from NOT eating i know it sounds funny but i just do. Headaches go away. IF worked for me and i tell all my friends to at least try it and if you don't feel better than stop. SO I eat around 5pm and last meal and maybe a snack around 9pm. I don't eat after 9pm until the next day 5pm. Next goal is to try a 48 hour fast wish me luck. I feel f-in fantastic! -2cents.

> Water is sweeter.

This is something I've started noticing with IF too. Depending on where I am with my fast a glass of water can come across as very sweet, cloyingly. But not sweet like glucose/fructose (sugar). More like an impression of sweet or maybe like a diet soda.

I hate when it happens because I don't like the flavor at all and need to force myself to finish my water at that point. For some reason it usually happens at the end of the day for me. It's usually gone by morning.

And it can't be something in the water because I switched to reverse osmosis RO filtered water like a year ago because I'm quite sensitive to flavors in water.

Having a remote job was what initially helped me get over the breakfast and lunch humps you mention in this well written post. I'm not sure I would have gotten to my current IF stasis if not enabled by that. Thanks for taking the time to write this post.

Are you on a particular type of diet, e.g. low-carb ?

People in the control group of this study start with an average BMI of 25.2, the ADF groups with 25.48. Common BMI ranges classify scores greater 25 as overweight. Are there any studies of effect of fasting on normal weight people? Anyone here with a BMI of 20 that has experiences to share?

My BMI is 21.0 (6'3", 168lb), and I've done OMAD (one meal a day) intermittent fasting for about a year. Mostly I did it for digestion, which has improved significantly. I would say that it's also helped to control my weight, which would bump up about 10lb otherwise. Effects on energy/focus are mixed: there's less of a mid-day slump, but also I think overall energy levels have been somewhat lower.

Whats your waist to height ratio at that weight if you dont mind sharing.

I am 6'3 300lb and .61 W:H and want to get down to .5

Thanks for the insight. Losing 10 lb sounds actually like a negative to me since I don't aspire to have a BMI of 18. But I would like to test it for the energy level. Well, maybe I should try it a few Saturdays.

They’re starting to study the effect in normal BMI people. But the takeaway I’ve had is that it should have similar benefits as long as you avoid going into ketosis (which is admittedly more difficult the further below BMI 20 you are).

https://nutritionj.biomedcentral.com/articles/10.1186/1475-2...

After trying partial fasting periodically for years, I hit in something earlier this year that works for me: eat only two periods each day, from 8am to 9am and from about 4pm to 5:30pm. This supposedly has two benefits: 1) by not eating for about five hours before going to bed I get much more deep sleep which starts soon after I fall asleep 2) avoids snacking between meals which is hard in the digestive system.

I started a full time job last month and with a more busy schedule I have temporarily stopped this eating schedule but plan on getting back to it. A device like the Apple Watch can let you know when you are in deep sleep and the positive effect on sleep with this two big enjoyable meals a day plan are verified, at least for me.

When I see studies like this, I always wonder if you might get the exact same benefits and more by just going for a run. When I run for more than 90 minutes without taking in carbs, my body goes into a ketogenic state very similar to a multi-day fast. And exercise has additional benefits that simply fasting doesn't.

Kinda, but only indirectly as I understand it. The more I read the more it seems to matter the time spent in a fasting state relative to a fed state.

So a run could work if you’re not overeating, but if you’re regularly overeating it wouldn’t work because you might use up your food, but then immediately resupply or have eaten too much prior to it and it takes hours to finish nutrient delivery.

Mostly though they’re complimentary processes neither directly involved with the other.

The latest science in Rats says no. I don't have the exact article available but it's discussed at length in this podcast recently.

https://www.foundmyfitness.com/episodes/mark-mattson

As I’ve said in other comments what seems to matter is the ratio of time spent in a fed state (body delivering nurtrients) vs a fasting state (body using fat for energy, depleting stores of things and doing housekeeping).

From that perspetive running could help, but only from the point of view of possibly getting you to the fasting state more quickly (a kind of kickstarter), but it would be easy too derail that by eating to soon or a hundred other things.

I don't have time (nor the endurance) for a 90 minute run, so could you combine the two? I often do a 14 hour fast and then go for a 20 minute run combined with some calisthenics on my lunchbreak before eating. How can you tell your body is in a ketogenic state?

I can definitely say the first few times I exerted a ton of energy after not eating for 12+ hours I felt like I had the flu for a few hours, but now I don't really get that.

They sell test strips that supposedly detect ketone bodies in urine although I don't know if they're reliable.

Personally my breath starts smelling like shit when I enter in ketogenic state.

When I was reading more about this most of the anti-aging benefits of fasting where explained by your body going into autophagy. I don't think just depleting your glycogen has the same effect and I didn't find any other reliable way of going into autophagy that didn't involve not eating for 36 hours.

Also a 90 minute run can have other side effects on people that just don't have the body for it. Even being fit and in my mid 20s and running with proper gear and on dirt and sometimes with a coach I developed plantar fasciitis in my 30s, I can do 10/15 minute runs and can hike and sky but I wouldn't risk a 90 minute run.

Spent a few months reading about this stuff back in 2019 and basically concluded you can get roughly the same benefits from intermittent fasting / time restricted eating, caloric restriction and keto.

Fasting for 24-48 hours however triggers autophagy, which is quite significant; I don't think (but don't know if) you would get that from your runs.

You're definitely right about the many benefits of exercise, though. This is one of my favorite articles, and it only covers the benefits to the brain:

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

It helps with working memory, depression, self esteem, ADHD, alzheimer's, drug addiction, and the list just goes on and on...

>When I run for more than 90 minutes without taking in carbs, my body goes into a ketogenic state very similar to a multi-day fast.

That seems rather implausible. Do you actually test your ketones in both conditions, or is this just some subjective assessment?

I took this a subjective feeling of the experience, but I agree with you. It is almost literally impossible (some high level athletes can accomplish it, I believe, but not after 90 minutes) to actually enter a ketogenic state from exercise.

That is the normal state of ultra endurance athletes during long runs[0]. A lot of training stimulus is fat adaptation. Coaches will tell you that you begin to exhaust your glycogen stores beyond the 90 minute mark, and I can tell you subjectively that the body switches over around then. I have done fasted runs up to 3 hours before. Runs of that duration are physically impossible without burning fat as fuel.

[0]: https://www.tandfonline.com/doi/abs/10.1080/02640414.2019.17...

The full text of your link shows the athletes didn't have elevated ketones until the second day of the race. After 80km, or about 12 hours of running, on an energy deficit.

A few years ago I realized that eating made me feel bad, or just took a long time to digest. So I started skipping breakfast. A year ago I cut out dinner too, so I just eat once a day - usually late afternoon, and usually a large meal, probably close to two normal meals. Overall I think it's a better lifestyle, but I do feel more tired than I used to.

This was true for me, but not really until I turned ~45. Confounding factors do include some changes to my consistency with working out due to some feet issues I started experiencing, but I just felt "full" all the time as well as foggy. I do ~16-18 fasted most days and feel much clearer/better.

I'm a huge proponent of intermittent fasting. After being skeptical at first, I felt I had more energy and was being more mindful about the type of foods I ate. The mindfulness alone may have been the catalyst, but even so, I'll chalk that up as a win.

In case it helps anyone else, I signed up for the Intermittent Fasting guide at www.howtostartfasting.com for the accountability and guidance and thought that was definitely one of the reasons I was able to stick to it and see the benefits.

It's designed for folks who are shift workers and have a changing schedule, but obviously still works and is easier if you have a regular schedule.

Same here. I’ve done both traditional calorie restriction with exercise and now alternate day fasting ADF. And I was extremely skeptical to begin with especially from an athletic point of view.

But now I’ll say ADF wins hands down for its simiplty and effectiveness. It’s 10% of the work/effort and 90% of the benefits.

Shhh why are they telling everyone about my secret weapon.

I am so sharp when I’m fasted.. easily become a force multiplier. Maybe a little more agro.

Also, I burn ~2000kcal without doing anything new? When a heavy workout burns what 500-1000 kcal.

I don’t need to sleep as much either. I wish I had learned more about the connection between my diet, biology, etc and my productivity when I was younger. And yes, I’ve started to look younger too.

Can’t wait to see the research evolve in this area.

My experience with AF was different. After years of doing all kinds of Fasts (2-12 day, dry fasts, OMAD, 16-8 etc), I experimented with AF. For approximately 3-4 months I did AF with a 1800 Kcal refeed (1 meal). What I experienced was a lot of muscle loss and a messed up metabolism, always starving and feeling like complete shit. It took me about 8 months to fix.

What I surmised is that with AF you don't enter a true fasted state but a gray zone, so it's more like starvation than fasting where a multi day fast (48 hours or more) seems to get you into a state that is muscle sparing.

What was the macronutrient breakdown of your meals? I heard evidence that if you reduce carbs you keep more muscle weight.

> I did AF with a 1800 Kcal refeed

So 900 kcal/day, that's a hell of a deficit. Why not target a more reasonable average?

Recent podcast that goes in-depth on this subject:

https://www.foundmyfitness.com/episodes/mark-mattson

I used to skip lunch for years and it always felt great. I like to see studies on fasting but I have to ask: how do you deal with the hunger when fasting with 24h? How does that affect your mood?

Everyone’s different, but I can go a while without food and not have it bother me. It’s not uncommon to go a day without it and not really notice. I hear people talking about getting “hangry” but I don’t personally relate to the that feeling at all. I don’t even know what that’s like, or how common it is to feel that way. If anything, I just get tired.

I wonder if feeling hangry is correlated with blood sugar level crashes when eating carb-heavy meals.

I've noticed that I get worse hunger if I eat more often, especially if I just eat bread to postpone the hunger. For some reason, the hunger I feel when on a lower-carb diet is much less pressing, and can be easily ignored for quite a while.

Carbs are also addictive to me: I sometimes notice that I want to eat even when I know I'm not hungry, so I have to make sure I don't make snacks too available.

Most days, I just eat once because it's an easy rule to stick to. I might have a snack if I've taxed my brain and feel like I need the extra fuel, but usually one meal is plenty.

Ideally you need an electrolyte mixture after the first day e.g. potassium/magnesium/sodium or else you start to feel like shit.

I fast for 36 hours every week, from Sunday evening until Tuesday morning.

To admit it, sometimes I'm overly tempted and I don't make it.

It has kept my A1C levels very low. My normal blood sugar is in the 120-140 range, but always below 100 on Tuesdays.

I have read elsewhere that fasting can pull A1C down by .5 easily, and that it also triggers a cellular process called "autophagy" that is very helpful.

I was worried about this too, but I’ve been alternate day fasting ADF (eat dinner at the normal time, go to bed and don’t eat the entire day, eat normally the following day) for two weeks now (and down nearly 6 lbs so far to 215lbs), and it hasn’t actually been a problem. I get a bit hungry by the end of the day, and sometimes I’ll have a protein shake to tide me over.

But mostly I’m just looking forward to my meals the next day. And by the next morning I’ve started to become indifferent to food. I’ll have breakfast, but I don’t feel deprived, food seeking or anything.

Also studies on ADF actually allow participants to eat 25% of their daily calories (or up to 500 Cal) and still be on diet. I’ve taken advantage of this once and had a single McD cheeseburger for dinner. So it was nice having the option as backup if I got really hungry.

It makes me great if I don't feel eat anything until the evening. I am much more energized, less sleepy, and productive. If I eat through the day, especially if I do breakfast, I feel tired, sleepy, and hard to focus on anything good. Thus, I've never understood the classic "breakfast is important" argument that old ones day, as it has always been the opposite for me.

I sometimes fast 24h and it feels awesome, I literally feel that I'm much more healthier both physically and mentally.

The sleepiness you feel is probably your body's response to large intake of carbohydrates and the subsequent spike in insulin. Increasing the amount of protein and fiber in your meals will decrease this feeling, as will exercising after your meal.

Breakfast is important if you are going to be physically active during the day since it provides the fuel to sustain it. The reason it's become less important is because many of us are extremely sedentary.

Yeah the sleepiness usually comes from carbs; if I take fibers/protein it feels better.

Maybe anectodal but still, even if I'm physically active the whole day (unless I'm snowboarding with a tshirt 9-17) I really feel better off eating nothing. I feel the urge to eat after physical activity, but not before. If I eat (and I'm not planning to burn 2000+ active calories) I'm still better off on not having any breakfast but just water and perform MUCH better on physical/mental activities.

IME - hunger and mood start to separate. Hunger fades away into a shadow of its former self. There is less energy to be joyous in a fasted state, but there is also less energy to be upset. I find a certain bliss in that.

I’ve researched all over and no one seems to know. I think autophagy isn’t well understood yet:

Does black coffee during a fast break autophagy? Flavored seltzer, tea?

Are vitamins ok during a fast? Fish oil?

I don't think autophagy is a binary state. It fluctuates over the day, and increases when fasting.

Many vitamins are fat soluble so taking them while fasting is pointless.

I think no one knows because the exact threshold is different from person to person. I've seen it suggested (in relation to 16:8 or 18:6) to do water only for a while and then test each stuff independently to see what triggers a hunger pang half an hour later.

It's funny to me that the article doesn't mention the word "muscle" anywhere. It seems a diet like this would reduce muscle mass, which may be a large contributor to the decline in body weight mentioned in the study.

Lots of evidence shows that if you fast you lose fat before you lose muscle. One exception to this is if you have a low caloric intake mostly from carbohydrates. I am not a doctor but what I understood was that when you eat carbs it puts your body in a mode of storing it as fat but if you remove the carbs it tells the body to pull from fat stores.

> I am not a doctor but what I understood was that when you eat carbs it puts your body in a mode of storing it as fat but if you remove the carbs it tells the body to pull from fat stores.

Not a doctor too, but from what I've read it's due to insulin. Carbs usually raise insulin, proteins can raise it too.

It's not that simple unfortunately. Basically, as I understand it, your body(liver) puts out a call for energy and whatever happens to pick up the signal first will respond. In the same way you can't spot reduce fat (can't choose where you want to lost fat from).

So this means, unfortunately, you will lose muscle while losing fat. Fortunately it is significantly more difficult to extract protein from muscle, so it responds much more slowly than fat.

The minimum seems to be about 40 g (~150 Cal) of protein per day (I don't remember where I got this number, sorry.), but can be as high as 10-30% of Calories supplied by the body.

There are a lot of things you can do to counter and minimize most this though. Working out to signal to your body the muscle mass is still in use and protein shakes (no fat, no carbs) are the most obvious.

Without diving too deep into a naturalistic fallacy, it would be a terrible design if the body started tearing down its muscle immediately upon fasting, when it has months of energy in the form of body fat.

Anything new here?

Previous discussion: https://news.ycombinator.com/item?id=20812636

Another ancient wisdom rediscovered in modernity

Mechanistically, one could hypothesize "of course".

Cellular respiration and its various reactions take in highly oxidative oxygen and turn it into ATP. The more we run this engine, the more work it does.

Active pathways have some probability of breaking, especially those that generate reactive molecular species. Higher probability of eventual disease state. DNA damage, intracellular buildup, etc.

The more you drive a car, the more wear and tear it receives. Over time, all of those explosions in the combustion chamber will do damage. So too, our cellular physiology and molecular biology.

By that reasoning exercise should age us faster.

In some ways it does!

Exercise increases the presence of reactive species, which can negatively impact DNA and other molecules [1, 2].

We know exercise to be mostly beneficial, but you can't discount that it does damage too. It's just that the benefits exceedingly outweigh the downsides.

Your body is going to die no matter what. Everything you do involves chemistry, and eventually entropy will win over your body's attempts to minimize it. There are behaviors that will optimize for longevity and health, though.

[1] https://www.frontiersin.org/articles/10.3389/fphys.2016.0024...

[2] https://pubmed.ncbi.nlm.nih.gov/11327321/

And just as exercise is more complex than just tearing your muscle fibers, fasting is more complex than just slowing your metabolic rate. You could make a similar (but wrong) “of course” argument that, while fasting, the body doesn’t have enough energy to repair itself, so it decays faster.

All I’m getting at is that this is a really complicated topic, and that the benefits of fasting go beyond just temporarily lowering your metabolism.

That’s also kinda true (not the energy part, but the rest). Some of the studies I’ve read heavily imply this “decay” (clearing out trash) allows the body to kill off pre-cancerous cells and do other housekeeping things that it can’t do when the vascular system is busy doing nutrient delivery.

This can happen with regular meals that a just a bit too big and a bit too regular. So just as it’s finishing up the rounds you’re adding new nutrients to be delivered. Apparently your body needs at least a few hours daily where it can focus on housekeeping tasks.

I’ve come up with analogy of the same vehicles doing package delivery and garbage collection. So if they’re constantly busy will the former the latter will be neglected and things start to pile up.

Exercise has anti aging effects because the body generates more anti-oxidants in response to increased oxygen intake.

Exercise is big but limited time oxidative stressor. Body's response to it generates benefits.

Antioxidants, like taking vitamin C supplements with exercise are shown to reduce some benefits of exercise.

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