Intermittent fasting in mice improves long-term memory retention | Hacker News Reader

Intermittent fasting in mice improves long-term memory retention

kcl.ac.uk

159 pointshappy-go-lucky140 comments

I have been doing intermittent fasting with 8 hour "feeding window" for probably 10 years now. There are all sorts of different more or less believable facts about intermittent fasting. I won't get into any of them. I can just say that for me with my goals, it works. I can keep a lower bodyfat percentage while keeping muscle mass, year round than I could with any other "diet".

My main issue with any other "diet" or philosophy has always been my huge appetite. When I ate 6 times a day I was always hungry because the portion size was too low. I have a huge appetite and loves to eat big portions. When I only have 2-3 meals a day, then they can be substantially larger.

If you have trouble eating enough good food already, then IF is not for you.

If you want the alleged health benefits, whether they occur or not, then try a day or two of fasting. But the daily fasting should only be used if it somehow fits your life, schedule and goals.

The right "diet" is the one you can consistently adhere to.

> The right "diet" is the one you can consistently adhere to.

This is incredibly important. Having managed to lose a lot of weight, gradually, and then keep it off for several years, the key for me was finding something that fitted into my life and to which I could stick. I also gradually changed things, rather than doing a big-bang change.

My problem over the last few years has been the effect of having children. Between the sleep deprevation and the change to my schedules I found it a lot harder to stick to my previous routines, resulting in me falling back into old habits. I'm now trying small changes, starting with at 10/14 routine, which I'll probably make more strict (8/16) in the future once it's become habitual. If nothing else I'm finding I sleep better than when I ate later in the day, which improves my will-power, and having a period of being hungry makes resisting snacks easier during the eating period.

Good habits are hard to form and keep, and bad habits are even harder to break permanently. You have to be kind to yourself and take your time if you want those changes to be for the rest of your life. Losing weight is simple, but hard.

My problem with IF is that I need energy in the morning because of bicycle commute, and I also want to have a warm meal in the evening after I come back from work. This could only work if the feeding window was 10-11 hours wide.

Ouch, it hurts me to read this.

Try biking harder/longer so that you use up all your blood sugar and convert your metabolism from glycogen to ketones.

Going on an hour or longer run is part of my secret to extended fasting. Exercise-based switching of your metabolism makes the first and second day of fasting NOT suck so bad.

So that's literally the opposite of your assumption, that the exercise makes you "need energy." If your like 99% of people, you already have plenty "energy" throughout your body.

What are you actually experiencing?

Blood sugar withdrawal. Your "need" for energy is actually a craving for the high glycemic ingredients in your food that cause physical addiction like symptoms, like feeling "hungry." And you may find it surprising that "hunger" isn't one of the things people experience on an extended fast when properly hydrated.

Your "need" is easing the pain of withdrawal. Not anything to do with "energy."

Edit: my SO informed me that there are some situations where woman benefit from certain foods after exercise for hormone regulation. But she also concurs that the evidence is pretty clear that men were built for intermittent fasting.

Maybe you're simplifying for the sake of brevity, but this notion of "use up all your blood sugar" and "switching" (as if binary) between glucose and ketones is pervasive and frustrating. That is not how things work.

Unless you have some metabolic disorder, after your hour+ run your blood glucose is still going to be within, maybe on the low end of, the normal range. Even if you've completely depleted your liver of glycogen, which is unlikely for anything short of marathon distance unless you were already low. If your blood sugar was low (never mind gone) you'd be in serious trouble, dead before long if not rectified.

It could be mostly an habit/mental thing. I go to the gym fasted (anywhere from 10 to 20hr fast) and I ohp/squat/deadlift moderately heavy weight for 60-90min. I also commute by bike fasted

Your body doesn't run out of energy that fast, we've just became very used to over feeding

The data on Time Restricting Eating shows that you most probably will experience benefits even with a feeding window as wide as 12 hrs. I do 10hrs and it's been very good for me.

If you're healthy enough to "bicycle commute", you might not need IF in the first place...

It's surprisingly difficult to get rid of 15lbs of extra weight I gained during COVID, even with 2 hours of cycling a day.

I think people greatly over estimate how many calories you burn while working out. It's very little, unless you're able to train the entire day I doubt the average person is burning many calories from moderate exercise.

Not trying to say exercising isn't worth while, it is but using it as the sole means of weight loss isn't fruitful gotta change the diet as well.

Ugh, you're so right and I have to add:

STRENGTH TRAINING FIRST!

If you only do cardio, ie bike and run, then you are actually WORSE OFF.

Calories burned is directly proportional to muscle mass!

Air squats. Pushups. Crunches. Ten of each of those a day. It can be done in 60 seconds. 10X that and you'll be shredded without running or cycling a day in your life.

Yes to strength training first. However, please be careful doing only highly repetitive exercises like pushups and crunches every day - it's a good way to develop joint injuries as you get older. Build up slowly and switch it up - like a healthy diet, variation is the key to longevity!

From personal experience, reducing calories intake is the only thing that works. Exercising only burns a noticeable amount of calories to if you are a really good or elite athlete who does a lot of hours everyday at a very high intensity.

Anyway, exercising is always necesary to keeping muscular mass.

Try using smaller plates at meals (not kidding), and/or adding a 30 min walk after dinner.

Could do a fasted ride? How long are your commutes?

1 hour (one way).

Pre-covid I was cycling a minimum of 25km/day. For 8+ years. I've always been a fat bastard.

IF including 2-week (water-only)fasts during a 3-year period had no noticeable benefits besides 10-20 pound drops at the start. (Keto-only on & off provides brief weight loss.)

My point, "decent" exercise doesn't guarantee weight loss.

I only eat lunch and dinner and while my morning commute is simple, when I go on a day hike, my diet doesn't change..

  If I were starting IF while hiking every day, I would probably have snack in the morning at first but reduce and then eliminate it.

One of those is a need. The other is a want. Everything is a tradeoff.

IF fits my natural appetite and is easy for me to adhere to. My problem with it is I've discovered eating a small breakfast (~250 cal) immediately when I wake up is the single greatest aid to keeping my sleep schedule stable. On IF, when my meals are at ~ 1 PM and ~7 PM, my tendency to sleep in/stay up/go on a >24 schedule is amplified.

If I instead do "morning IF" and just eat breakfast and lunch, I'm lethargic in the morning and afternoon and hungry to distraction in the evening.

> When I only have 2-3 meals a day, then they can be substantially larger.

Most people only have three meals a day right ? Breakfast, lunch and dinner.

Most of the people have snacks and coffee in between 3 meals.

That chocolate bar doesn't count as a meal. Donuts aren't meals either.

The calorie counts would beg to differ

Snacking throughout the day is very US specific.

I really want intermittent fasting and low carb diets to have the benefits claimed, but having done both for extended periods on and off for years, if I'm perfectly honest with myself, the truth is I haven't seen any benefit at all, and a careful review of research in humans as opposed to rodents seems unable to back either of them up.

Low carb especially for me anyway leads to undesired hormonal states with SHBG through the roof and just general prolonged brain fog and low performance and energy. (the opposite of what advocates claim)

I do believe doing the occassional extended two-three day fasts for autophagy can be beneficial and anectodally I do see beneficial effects from those... but other than that I just eat varied healthy food usually three meals a day and I find that works best for my mental and physical performance, body composition etc. YMMV!

Glad to see more skeptics on here. I do 3-day water-only fasts (not intermittent, just 72 hours straight) once a month. I get very little noticeable benefit if any. For me, the benefits are all "soft" benefits - willpower practice, realizing how little I actually need to eat, and very, very minimal fat loss if I walk for 8 hours on the last day.

Do wish all the magic, memory, autophagy, cancer-prevention, more HGH things were true though, but it does seem like they are blown out of proportion if there at all.

I wonder if the difference in experience might be related to how close one is to diabetes. A lot of people are in various stages of pre-diabetes, I've had fasting blood sugar measurements around 110 mg/dl, which is considered pre-diabetic. I've done keto and a little bit of fasting and experienced the seemingly magical effects.

Another possibility is that other people are getting into ketosis and you aren't. For me, the "recipe" to get into ketosis can vary a lot based on how much I've been exercising and eating carbs before I attempt to limit carbs or fast.

Purely anecdotal, but interesting coincidence - walked with friend yesterday, and he knows someone who lowered their blood sugar permanently by doing intermittent fasting. This makes sense, since fasting moderates insulin resistance. There is an ok book about it by a liver/kidney doctor. Can find if interested, don't remember name offhand. I found it to be good even though I am obviously not a fasting fanatic.

>and a careful review of research in humans as opposed to rodents seems unable to back either of them up.

Well, research might not say that IF or low carb have X or Y benefits. They might very well not have any major benefit by themselves.

But they very much say that lower BMI has tons of benefits, from heart to cognition.

So if IF and/or low carb helps you achieve this BMI, then you should (and would) have had those other benefits too.

Since I’ve gotten into serious cycling and learning about exercise science, I’ve realized how utterly ridiculous and harmful the low carb fad is. Carbs are the most efficient fuel you can give your body and usually the only source of fuel for your brain (by way of glucose). Being in a state of hypoglycemia frequently seems quite bad for normal people and outright dangerous and counterproductive for athletes. Having “bonked” on a few long rides because I didn’t refuel enough on the ride has really driven home the importance of eating carbs for energy. It’s a very unpleasant state to be in. I would never recommend a low carb diet to someone wanting to lose weight. Couple a low carb diet with fasting and exercise and your body will not just get energy from your fat cells, but also your muscles, and it can cause other unwanted outcomes like less healthy skin and hair.

One meal a day combined with keto helped me to lose 30 kg in 9 months practically without effort. As soon as I went off it (because of changes in life) I gained back 6 kg, now I'm at least trying to do OMAD but it's hard without keto, because the sugars make me hungry.

Not making claims about you, but simply skipping meals and eating more fat seems naive.

& other things matter, like gender, other genetics, and your macros.

YMMV, sure, because when I am low carb (less critical, more of a YMMV), high protein (critical), workout/lift (critical), count macros (critical) and fasting (less critical) I become the best version of myself. Mentally, physically.

I've had the complete opposite experience.

I'd be willing to bet you sacrificed micronutrients to meet your macronutrient goals.

Your low T could've been solved by adding a little maca root to your daily smoothies, which should contain all the essential micro-nutes your sacrificing to meet your macro-nute goals.

And yes, you can have a smoothie on keto with minimal high glycemic carbs that fulfills any deficits left by a strict high-fat diet.

I'm only advocating that you not knock something that is clearly working. Sorry you gave up on the holistic approach, but someone should've told you, it's not a solution, it's a practice. And the issues you had were a chance to improve your practice. You could accept the challenge, and expect to recognize and solve problems with constant adjustments to your diet, or keep up whatever your doing that works for you. Good luck.

> a calorie restricted diet via every other day fasting

So this isn't the same as the 'intermittent fasting' practiced by a lot of folks where you only eat in a short(8 hour) window every day.

Personally I did the 8 hour window a couple times in life. After the last time trying it, I'm now "carb intolerant" and seem to suffer from reactive hypoglycemia and postprandial somnolence(i.e. dead after meals). IF didn't do anything for me, weight wise, so I can't really recommend it to anyone. YMMV.

>So this isn't the same as the 'intermittent fasting' practiced by a lot of folks where you only eat in a short(8 hour) window every day.

IIRC this is pretty much always the case in scientific literature. The common practice is referred to as time-restricted eating, while IF is always some form of 24+ hour fast.

Thanks for pointing this out. Ever since I've done my first large stretch of the Keto Diet before the pandemic and lost roughly 30 pounds, I've developed a weak bladder. I don't know how this happened or if this is even remotely connected, but running to the toilet after every other glass I drink is something very unusual for me and certainly wasn't the case before the diet. Your comment just made me make the connection between the diet and the condition. I still think overall it's a net benefit to my health and I'll go back on the Keto diet in a couple of days to lose some more weight, but I think it's certainly possible there are some adverse effects that aren't really talked about or studied yet.

The a major cause of a ‘weak bladder’ outside of prostate issues is urge incontinence, that is, just paying way too much attention to the sensation of needing to urinate and so having increased frequency due to that. In order to overcome this, it’s essentially training yourself to push longer and longer in order to reset your sensitisation.

Of course, obvious disclaimer that I have no idea if this applies to you and your situation, but something to consider if you haven’t had this investigated. But keto with increased hydration could have inadvertently sent you this way

I once talked to a physical therapist who specializes in pelvic floor muscles who basically says the same thing you did. Exercising the pelvic floor muscles will help, but changing the mindset helps even more.

Also worth noting is the fact that when your body stores glycogen, it does so by binding it to water molecules in a ratio of 1g glycogen : 4g water (iirc). So increasing your carbohydrate intake also increases the amount of water you retain.

Transitioning to a lower carb intake and utilising some of that stored glycogen releases the water molecules and increases the amount of circulating water molecules in your system, some of which will be excreted.

So yeah, you should notice an increase in urination when transitioning to a lower carb / keto style diet.

Which of course, is also the majority of the quick weight loss that one notices in the first few weeks on a keto diet...

Personally I don't consider reduced tissue hydration something I desire so I no longer favour keto diets but each to their own.

I have roughly the same thing, and while I never followed any actual keto diet, I do maintain a relatively low-carb diet. After not eating many carbs for a few days and losing some weight I also have to urinate quite frequently. That need goes away if spend a few days eating a lot of carbs (holidays where I overeat whatever I want, for example), so I'm not particularly worried about it. My guess is that it's a result from not having much to hold the fluid around in my body, so it goes straight to my bladder. Also a lot of caffeine and liquid consumption in general

Do you have proteinuria (protein in urine) which can cause painful urination and feelings of urge to urinate? If so you may want to be wary of high protein diets like keto, and maybe see a kidney specialist to make sure your kidneys are in good health...

Could reactive hypoglycemia and postprandial somnolence also come from bad lifestyle? At some point I was on that kind of schedule.

I tried it for a while, but I never could make it stick (12-8 pm was my window).

What worked for me for energy levels and mood was keeping it to a solid breakfast, lunch, and dinner of healthy food (high protein, no simple carbs) with no snacks in between.

I've been on intermittent fasting for > 2 years now, and I don't remember my memory improving.

Perhaps it has improved but you don't remember how it was before... oh, wait...

> Fasting is the willful refrainment from eating and sometimes drinking.

Mice dont fast, they're being starved in captivity.

Interesting results non the less.

Seems like there’s numerous conflicting studies regarding intermittent fasting especially when different fasting periods are taken into account. Is there any conclusive research regarding just having 2 meals a day? That seems to be the easiest to integrate in day to day life.

Is it even possible we ever end with conclusive research that could be applied at large scale ? I think you won't have much choice than try and see if it works for you specifically.

We could have more lab mice studies, but it wouldn't account for actual humans' different metabolism, include lifestyle (work, daily rhythm, mental state), actual food intake, genetics etc.

Looking at other human related health subject, for instance we haven't hit any conclusive point on any specific food that is widespread today. Everything regarding fat, proteins, sugar etc. is still small scale, extremely biased, often politicized and producing contradictory results. All we know for sure is that "too much" is not good, and that's after decades and decades of research.

I think it's hard but absolutely posssible, but the quality of statistics in nutrition research depresses me. Good work exists, but the publication incentives do not lead it to rise to the top, meaning the correlation between study quality and study size isn't good. AFAIK, and I am not up-to-date, there are no large studies that (i) are constructed to gather data on enough variables and (ii) do the data gathering well-enough that the data won't be too noisy.

I'd love to learn that I am wrong.

For me it involved skipping breakfast. It was an easy transition, because normally I'm not hungry in the morning anyways. I would eat breakfast mostly out of force of habit.

Same for me. In addition to that, having breakfast actually caused me to get hungry again pretty quickly and generally start feeling terrible if I then didn't eat again, whereas without it, I could pretty much go all day, no problem.

Exact same experience here.

I can easily go from 8 in the evening to 11-12 the next day without eating. Maybe a bit of water or some caffeinated sugar-free drink in the morning.

BUT, if I eat a bowl of oats (as recommended) at 8, I'm _hungry_ at 10, like starving-hungry.

I can also just eat a large-ish lunch and go until evening pretty easily.

This has been my experience over many years of restricting my consumption window. I also find I get mid-morning and after-lunch energy wells if I have an early breakfast, not so much if my first meal is after 10am.

Breakfast actually made me feel physically ill for a while when I was in my early 20s, so I skipped it out of necessity. I think it had something to do with insomnia. Keeping down half an apple was a struggle. So I basically starting skipping entirely.

These days a single coffee with some milk is enough until lunch, whenever that is. I can eat breakfast (or at least brunch) decently well now, but like you say I just get hungry again anyway. And if I'm going to the gym any time before 1pm I try to eat nothing beforehand or I just feel worse.

I wonder how much that splash of milk in my morning coffee breaks the magical fasting spell.

This opinion gets repeated a lot. I’m the complete opposite. I wake up wanting food and have made dinner my skip meal. Seems to work well for me.

Not an expert, but from reading studies I suspect that the specifics like which meal to skip can vary by person. Which makes sense since we all have unique physiology. Eg, some people are natural night owls vs morning people. There’s plenty about the body we don’t fully understand, but executing discipline to follow a generally-healthy eating regiment likely has both direct physical benefits and benefits from a sense of control and well-being.

Everyone is different, do what feels right for you

I did one meal a day for a few years and lost an OK amount of weight and felt pretty good. But then I fell off the wagon and it wasn’t easy to start up again.

So now I’m trying a 48 hour fast once a week, and not changing much else. Starting week 5 tomorrow, and it’s looking promising so far.

> But then I fell off the wagon and it wasn’t easy to start up again.

Just wanted to say, based on my extensive experience with fasting, this is normal. There seems to be a psychological barrier about how easy it 'should' be or 'used to' be, and you beat yourself up about it which makes things even worse.

Every time I've made a habit of extended fasting, or prolonged intermittent fasting, and taken a break longer than 6 to 9 weeks, restarting is very... very hard.

I'm curious if you considered a 4 day fast every other week instead. The first two days are the hardest days of an extended fast (hungry, lethargic), so you might find this approach easier and more beneficial.

I’ve found coffee and the occasional 200mg caffeine pill with 400mg of L-Theanine helpful to push through the first day of a multi day fast, when your body is complaining about burning up its glucose reserves.

I’d love to give this a try, do you not workout during these or?

Yes, I work out daily, 30 minutes on a row machine, 30 minutes strength training. Strength training has been found to protect muscle tissue from wasting during fasts, and the cardio is because I enjoy it.

I did the same thing but I just went to 80~85% of my usual lifting weights and a 3km walk in my lunch breaks.

That's an interesting idea. The only thing that would give me pause is I know I'd get a lot of "Oh, look, dad is being weird and not eating dinner with the family all week again". The 48 hours is basically "hey I'm skipping dinner tonight".

How’s your energy level throughout the 48h fast?

I feel pretty good, the only issue is just a sort of stomach discomfort that isn't quite hunger and not painful. More of an "empty" feeling. But mentally I am focused.

I don't have any hunger the whole time as long as I don't drink any coffee. For some reason it makes me ridiculously hungry and I just give the whole thing up.

Coffee is high acidity and I remember reading (can’t source) that it should not replace breakfast for that reason.

Wondering if replacing it with green tea could provide some of the caffeine in less acidic form.

I’ve had one meal a day for years. We just eat around 7p and I have a milky, unsweetened coffee in the mornings. After a while you don’t even feel the urge to eat lunch anymore so there’s no chance of “falling of the wagon” as another GP has mentioned.

The autophagy research that won the 2017 Nobel Peace prize lead to the explosive interest in fasting for cellular health/longevity.

There are now thousands of studies published per year related to fasting and autophagy. IF is a byproduct of this interest.

Autophagy isn’t generally reached with most IF schedules (generally around the 24 hour mark and peaking around the 36 hour mark), but a lot of these studies are measuring other possible benefits and bio markers of IF.

The answer to your question depends on your goals, but if you are fasting because of the hype around longevity I would suggest focusing on 2-3 day fasting periods rather than IF.

Could you share some supporting articles regarding 2-3 day fasting?

this cites some research for what happens during the stages of fasting.

https://usetemper.com/learn/metabolic-step-by-step/

Studies also seem to show that the trigger mechanism for many of the benefits is caloric restriction and not the fast.

As when fasting we do need to eat at some point.

Please define conflicting (largely positive but under different conditions, or something else?), and list the studies in question.

> having 2 meals a day

Intermittent fasting isn't about reducing the number of meals, or in theory the total calorific intake, but rather the window in which food is consumed. That said, it's entirely possible that one influences the pother.

You have to have enough of a food shortage to get your body to shift into more autophagy/catabolism. It doesn't really matter how often you eat as long as you can generate that shortage. The initial studies had long/significant calorie restriction, and all the fasting schedules are ways to make them more tolerable.

I came to a conclusion two meals a day after finding out where the three meals a day concept originated.

The intermittent fasting in this study was every other day feeding by the way.

I find that to be one of the hardest regimens.

Agree. I'd rather do One Meal A Day, or 5 days Fasting 2 days fed, or basically anything but every other day.

Of course, I'm not locked in a cage in a lab with no choice.

I love IF. It is hard for a lot of folks to get into though. Your body is used to eating three meals a day so for the first two weeks your body will get hungry during those meal times. You don't actually need those meals. Your brains has just been trained to expect them. So many people stop because they say they cant handle the hunger during the fasting window but... It goes away.

Check out citravarin as a way to manage habitual appetite during that transition.

I experimented with fasting almost a year ago now, from OMAD all the way to 6 day fasts. My only motivation was to lose weight and I figured working from home was the best chance I'd have to actually go through with it. I lost around 35kg and I'm finally at a healthy weight for the first time in my life. Of course I'm very happy with the results, but I didn't experience any benefits people mention concerning mental clarity or more energy. To be fair I also didn't feel much worse than usual after a few weeks of starting.

What did give me more mental clarity and energy was eating well and exercising regularly, something that I had to come to terms with when transitioning back to a more traditional diet else I'd just end up putting the weight back on.

This result seems to tie in with the mounting evidence of a link between diet and mind health. Specifically insulin response, which improves with fasting. E.g. Some scientists now calling Alzheimers Type 3 diabetes: https://en.wikipedia.org/wiki/Type_3_diabetes

According to two books I just finished, Lifespan and Why We Get Sick, even an 18 hour fast (skipping breakfast) is enough to see possitive improvements. Partly due to the dawn phenomenon, where our glucose and insulin rises with dawn and peaks around breakfast time, making breakfast the most dangerous meal, if your goal is avoiding fat storage.

> breakfast the most dangerous meal, if your goal is avoiding fat storage.

That's counter to the evidence.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658129/

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

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756673/

https://pubmed.ncbi.nlm.nih.gov/25724569/

https://pubmed.ncbi.nlm.nih.gov/23512957/

https://pubmed.ncbi.nlm.nih.gov/9040548/

https://pubmed.ncbi.nlm.nih.gov/26948400/

I recommend that most people skip breakfast because it's the easiest way for most people to fit a fasting window in around their work schedule. However, if you have more flexibility, it looks like there's a marginal benefit for body composition and metabolic fitness to having your eating window in the morning.

I scanned them but I dont see which of these studies are testing the dawn phenomenon? Which is what I am talking about.

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

The "dawn phenomenon" (predictable early morning hormone and blood glucose changes) is definitely a thing. But the implication/interpretation that therefore morning/breakfast is the most dangerous time to eat, is wrong. Those papers directly test that hypothetical implication.

I swear there's like two dozen "causes" for Alzheimer's.

There has been at least one rigorous (if small) trial of intermittent fasting in humans which found no significant benefit: https://jamanetwork.com/journals/jamainternalmedicine/fullar...

Although not significant, the numerical data on the side of intermittent fasting certainly didn't seem to show a signal for harm, and maybe for benefit, so if you could figure out how to do this in a low-cost way, it would be interesting to randomize a larger group. (Still implies a small effect size.)

The study you linked can't be described as rigorous. They only have 2 groups, without a control group. And they only give them the advice to eat between 12pm till 8pm, and the other group to eat 3 meals a day.

They found there was significant decrease in weight for intermittent fasting group.

The reason they give that intermittent fasting has no effect is because the other group also lost weight, although less.

But since both groups got instructions the study is lacking a control group.

Therefor we shouldn't compare both groups. What is left is to look at intermittent fasting by itself. And there they found what they call significant decrease in weight.

Studying human diet is notoriously difficult. Randomizing people who want to lose weight to 'keep doing everything how you have been' is not going to be a study that anyone enrolls in, so I think this study's methodology was thoughtful and realistic.

The only genuine methodological critique I'm aware of for this study is its sample size.

A 24 hour fast for a mouse is like a 2 week fast for a human. Hard to say that this would result in the same outcome for humans. I've also read that lab mice are nothing like normal mice.

This has got to be HN's favorite intermittent fasting meme. It combines a "well actually" with a false sense of mathematical precision - both are crack for HN. But it's more false than true.

The truth in it is that mice lose a greater percent of their body mass in the first 24 hours. Also mice will die if deprived for food for ~5 days. So at 24 hours, they're much closer to death than a human.

But that's not really what we care about with IF. Most people care about the metabolic transitions prompted by fasting,[0] which are strikingly homologous across mammals. The variance that does exist is pretty well captured by the models that underlie those metabolic stages. This article is about something going on in the brain, which is harder to assess in humans for obvious reasons. But one of the big benefits of fasting that kicks in around the 24 hour mark is macro-autophagy. We know macro-autophagy is occuring in the brains of mice by 24 hours [1] and we know that macro-autophagy has a similar time course in humans and mice in the tissues we're able to sample.[2]

[0] https://usetemper.com/learn/metabolic-step-by-step/

[1] https://pubmed.ncbi.nlm.nih.gov/20534972/

[2] https://www.tandfonline.com/doi/full/10.1080/15548627.2016.1...

I mean, based on my extended fasting experience I'd say it's something that's worth exploring. I can't speak specifically to memory, but the mental clarity whenever I fast longer than a few days tends to be awesome.

A seven day fast is something I'd encourage everyone who's otherwise healthy to try at least once in their life.

I tried fasting Tuesdays and Thursdays for a few weeks in college. A couple weeks after I stopped I had severe and sudden dizzy spells for months. I’m not willing to try again unless I go hand in hand with a doctor.

That sounds interesting. Do you have any tips or guides to get started, or is it more like “just stop eating”? I have never fasted for more than some hours before.

I'd start with "just stop eating" and then solve for any issues that pop up for you because people have a lot of different reactions. For me, I do alternate day fasting... sometimes 2-3 days of fasting in a row. I had some common issues such as not being able to sleep and diarrhea while fasting. So instead of 0 calories, I eat a bowl of oatmeal (high fibre) on my "fasting days". Also, when weight training while fasted I'd feel so light-headed I'd have to stop. But I fixed that by drinking 1 bottle of Gatorade (some calories + hydration + electrolytes) before exercise. You'll just have to find what works for you. Other patterns are 5:2 (2 days of fasting) and one-meal-a-day. Sometimes after a break from fasting, I'd get too hungry the first day back on fasting so I'd ease into it with one-meal-a-day.

You should have some salts to keep well hydrated, also be healthy and don’t have any problems like diabetes, or with your kidneys. Anything over 36-48 hours would be better to check with a doctor first.

Anecdata:

The only times I've got dizzy when '24h water fasting' are when I've been eating normal/high amounts of carbs in my diet around the fasts.

I've been doing a few days/week of 24h water fasts again, but on a very-low-carb diet, and can report no dizziness whatsoever.

An additional benefit (also mentioned by others) is that I don't have any insatiable hunger pangs on the water fasts (which I did when I attempted them on a normal/high carb diet).

Obviously your mileage may vary (etc etc), but for me, it's all about removing carbs. It's the difference between water fasting being (honestly) easy .vs. A herculean feat that I couldn't manage.

I wonder if there is any benefit from shorter periods, since I do not have the body fat to easily sustain a 2wk fast... also sounds like a good way to lose a lot of muscle?

The body protects its nitrogen. You do lose some lean tissue mass but its relative share goes down with fast time (as long as you have the fat stores) and compared to a lean person it's less from the onset.

This is true, mice must eat much more often.

Aha, and so now this link is on HN and if questioned users would obviously deny the existence of this effect in humans until proven - still the assumption in the comments here is that this would work in humans too.

Mental clarity is due to body entering Ketogenic state.

You'd observe the same if you go on a keto diet

It's easier if you first go on a keto diet and then you put your body through intermittent fasting

Ketosis requires fairly long, continuous periods of carb restriction. I’m not totally convinced that intermittent fasting windows are long enough to provoke ketosis. Im aware that ketosis isn’t a binary state, but it approaches being one, right?

> Mental clarity is due to body entering Ketogenic state.

Or due to being jacked up on cortisol which stays high when you don't eat.

That's the reason why prolonged fasting (longer than a day) doesn't work for me - it ruins my sleep and I feel a lot more jittery and stressed after the first day.

Daily fasting (20 hours not eating or 1 meal a day) is a lot easier but you don'get a lot of ketosis when the fasts are that short unless you're already on a low carb diet.

> It's easier if you first go on a keto diet and then you put your body through intermittent fasting

Source? From personal experience I'd say this is not rooted in any fact. Considering many don't consume the majority of the foods in Keto as a lifestyle, not a diet, it's unfortunate to see this type of misinformation.

This is similar to an approach in a clinic run in Toronto by Jason Fung that puts patients on a Keto diet for a few days before they begin fasting for five days.

If I recall correctly, the purpose is to acclimate the body to running on ketones. Most of the patients are poor and live in “food deserts”, so they are encouraged to eat as much eggs and bacon as they want (with avocado, if it can be found.) The process is described by Megan Ramos in a 2018 podcast [0].

The science on fasting is sparse (but improving) and anecdotal evidence is common in health discussions. Fasting is divisive because it works great for some and is a non-starter for others. I’m sure that the Keto-before-fasting approach could be great for some and difficult for others, but we just don’t have the research to give us the hard numbers.

[0] https://podcasts.google.com/?feed=aHR0cHM6Ly9kaWV0ZG9jdG9ycG...

We also know that Ketogenic diets are not particularly healthy via promotion of consuming high quantities of unhealthy fats [0].

[0] https://www.mayoclinic.org/healthy-lifestyle/weight-loss/in-...

There are downsides to any diet. Keto has the huge upside of cutting out nutrient-poor highly processed foods that many people do not even realize are unhealthy.

Also, the idea of “unhealthy fats” is debatable [0], but that is besides the point: the largest downside to Keto is restricting a moderate amount of carbs from healthy choices, from your citation:

> meeting the diet's requirements means cutting out many healthy foods, making it difficult to meet your micronutrient needs.

[0] https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-mi...

Leaning in on old data and recommending people eat copious amounts of saturated fats is just as poor a diet choice as highly processed foods. [0]

[0] https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-h...

Is a ketogenic state something healthy to maintain continuously or should it also be intermittent? And are diets that invoke ketotis healthy long term? I can't seem to find much on this. It seems that a lot of the foods in keto diets have their own long term health drawbacks.

The only honest answer is "we do not know", w.r.t very long term dietary ketosis. I would be skeptical if anyone claims absolute certainty on this.

Kids who were kept on such diets, would normally transition to normal diets, they apparently either outgrow epilepsy or can take drugs to control it once they get older. None of the kids preferred to stay on it for life either, I've been told (altho that neuro's sample would be small), it is quite burdensome.

Encouragingly, many mountain tribes eat primarily meat/fat based diet, and the same goes for Inuit tribes in the Arctic. They eat such diets for their entire life, and mountain tribes often have quite long lifespans on primarily sheep meat/fat and some greens. a little bread/starch every now and then.

So maybe it is safe for some period of time. It is not clear what health risks you accept as trade-off, nothing is free.

Intermittent fasting on the other hand is extremely safe and is privately practised by several physicians I trust. They all seem to be in great shape for their age, fwiw.

Having been on keto for 3 months, I don't think it's that big of a deal. It depends of course what you eat, but if you just eat "normally" with carbs left out and lots of veggies of course, in my case the end result of quite the same. Only difference is I'm losing fat at an increased rate. I can exercise as normal in the gym and so on.

And yeah, I'm using intermittent fasting too. Happens quite naturally and I guess that plus evening runs around the block really burn those calories.

Short answer: talk to a doctor first.

Long answer (this is not medical advice): certain risk groups (related to kidney and liver function) should not observe a keto diet without consulting with their doctor. The long term risks of an animal protein heavy keto diet are unknown (think colorectal cancer from red and processed meats, including those with nitrates used in their production). Be mindful of electrolyte and water consumption while on a keto diet.

I’ve been doing keto (lazy nowadays, I guesstimate carbs of meals and try to stay under 20g a day) for 8 years, health and energy levels improved (in addition to losing 30kg, but that was front-loaded in the first year). But that’s probably the side effect of being far more aware of what I’m eating, I’m almost 100% positive that I eat far more veggies than before, my diet wasn’t the healthiest.

There is probably no “right” answer on this, at least I didn’t find one when I tried Keto a few years ago. Probably best to try and see how you feel tbh

> Mental clarity is due to body entering Ketogenic state.

This is a bold claim? How are you defining or measuring mental clarity?

Do you have any evidence you can provide that intermittent fasting can actually induce a state of ketogenesis?

I don't but you can buy breath or urine analysis devices/kits that will tell you if you are producing high levels of ketones so you could see for yourself.

I wonder when the Apple Watch will get ketone detection. "Just pee on your watch" :D

haha. we'll need a new Ingress Protection (IPee) rating to cover new fluids.

There seems to be a lot of pseudo-science around intermittent fasting.

In particular I've heard people say things like "You can take black coffee", or "You can have sugar-free lemonade with no calories", or "As long as you don't consume more than 5 calories (or some other small number) your body remains in a fasted state".

Yet I've heard in reality you can basically only consume water and nothing else during your fast in order to not break the fasted state.

> Yet I've heard in reality you can basically only consume water and nothing else during your fast in order to not break the fasted state

I don’t think that’s true. AFAIK main thing is to not stimulate insulin production so while many sweeteners might break the state lots of things have effectively no insulin response (for example pure coffee).

What's the metabolic difference between black coffee and water that breaks the fasted state?

Black coffee shouldn’t have calories, but it apparently does trigger metabolic responses in the brain, gut and liver.

Most people debating things like coffee, tea, lemon, even fish oil (which definitely has calories) have lost the forest for the trees, and they often can’t explain why they are fasting in the first place or their goals.

Unless you induce diarrhea, there’s food residues in the gut which keep adding to your energy bottomline for up to a few days. It’s unlikely that having a coffee or a supplement has a noticeable impact on your fasted state during intermittent fasting (when fasting 3+ days, things are different). To be sure, one could just measure serum insulin and ketone levels. Coffee will raise blood sugar, but it’s also lipolytic, so it’s both „bad“ and beneficial.

Nitpicking perhaps, but there's definitely measurable food energy in black coffee. A small mug of paper-filtered might be <1 kcal, but a double espresso might be 5+.

Anecdatally, on OMAD for 6 months (23h daily fast), with just espresso in the morning, and one meal late in the day, net have lost about 30 lbs. The weight loss slows down as your metabolism adapts. It is a way to get my total caloric intake down, as I just enjoyed eating too much and having to exercise discipline 3x+ a day is a losing battle. Out of sight, out of mind, etc.

Any perception of new mental clarity comes from how I relate to hunger, which I can mentally translate to a kind of excitement, similar to what some people can also do with fear. The clarity could easily be attributed to attitude and a choice that mitigates suffering. There probably isn't nutritional magic involved.

Yes, if all of this is just a way to get me to eat fewer calories, and that's all that's really happening, so be it. I've had several people scold me saying "You know you're just losing weight because of the calories, right?" and I'm like, so? Great!

I can't diet. Been trying that all my life and it's never going to happen. It's uncomfortable and socially inconvenient to be constantly weighing my food and passing up dinner invitations and never feeling satisfied. So I just don't eat a couple days a week and then forget about the rest.

Not a scientist, but I think this is one of those highly individual things.

Some people can drink X and stay in ketosis. Others can't.

This makes scientific studies on ketosis a pain to do, because we don't know whether something works at all or is it just due to individual differences.

My guess is that this is due to gut/intestine flora, but that stuff is still a complete mystery. Maybe we'll figure some of it out this decade.

David Sinclair (author of Lifespan) talking about Intermittent fasting benefits: https://youtu.be/jhKZIq3SlYE?t=2939

Forget this, just use Anki.

Another study that doesn't adjust for lifestyle differences. Did they consider that the mice who fasted may have already been eating healthy, getting exercise, and avoiding alcohol? These things could also improve memory, and of course the article doesn't mention it anywhere.

Great job, scientists. "It is difficult to get someone to understand something when their salary depends upon their not understanding it."

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