Intermittent fasting protects against Alzheimer’s disease in mice | Hacker News Reader

Intermittent fasting protects against Alzheimer’s disease in mice

nature.com

106 pointsdanielmorozoff31 comments

Alzheimer's is sometimes called "type 3 diabetes." If the body stops responding to insulin signals to pull glucose out of the serum to use for energy (insulin resistance), then the brain might chronically get less energy. By weight, the brain is the organ that uses the most glucose of any other organ. The brain is responsible for about 20% of your body's total glucose use, despite being only 2% of your body's weight.

Intermittent fasting usually kicks you into ketosis. Ketosis is when your body runs out of glucose and it metabolizes fat in the liver to use for energy, including the brain, which starts getting 66% of its energy from fat. You're on HN so you probably already know that. It also changes the krebs cycle, and eventually it changes how your body processes ketones themselves, but the important switch is in your brain.

Nutritional ketosis is a form of "fed" ketosis, where you mainly don't eat glucose, and eat more fat, and your body enters a similar state as fasting, except you don't have to be hungry. Nutritional ketosis is also distinguished from "starvation ketosis" (like from fasting) by the quantity of ketone bodies in the serum.

Alzheimer's patients on a ketotic diet show improvement (https://pubmed.ncbi.nlm.nih.gov/33622392/)

Could a nutritional ketosis diet be preventative against Alzheimers?

I sometimes hear stories of friends who eat generally "healthy," and aren't overweight, shocked to learn they are pre-diabetic.

This is the limit of my knowledge, and I know this is an incomplete picture. From my limited view, this is why I strive to be in nutritional ketosis.

This talk by an actual neurologist intersects much of what you're speaking to, but not through a "type 3 diabetes" lens. More of a "tumor growth and neurodegenerative diseases are caused by mitochondrial dysfunction, and fasting is our most powerful tool for straightening out misbehaving mitochondria" perspective, if memory serves.

My impression is that ketogenic diet alone is insufficient for lack of aggressive autophagy/mitophagy fasting triggers. But I'm just a lowly software dev, this shit is not at all my wheelhouse. It doesn't surprise me though that our cells need regular spring cleaning, my home certainly does. Apparently we evolved to opportunistically do that internal spring cleaning in times of scarcity...

Worth a listen:

https://www.youtube.com/watch?v=jK0BkTPUGQY

This could be tied to the infectious hypothesis of Alzheimers too - fasting for a period of time effectively 'resets' the immune system [1]. The infectious hypothesis is often associated with herpesviridae so I wonder if there's any studies that show an impact from intermittent fasting on chronic HSV.

[edit] And yes this study was done both both mice and humans.

[1] https://thesource.com/2018/11/21/fasting-for-72-hours-can-re...

The "type 3 diabetes" hypothesis is a great theory but has never been proven conclusively as the reason behind AD.

That paper you linked to had 26 participants.

Anecdotally, my grandfather, who was bedridden with advanced dementia for the last years of his life, tended to be far more lucid before breakfast than at any other time of day. Knowing of the type three diabetes hypothesis, I surmised that this could be, at least partially, a result of the overnight fast, during which his metabolism likely stabilised to a degree, although it's unlikely that he'd have fully entered ketosis. I suggested that he be switched to a ketogenic diet, at least for a few weeks, as a trial, but this was considered to be a ridiculous idea by his carers, and was never done, unfortunately.

If it's any reassurance, it most likely had nothing to do with fasting and everything to do with the disease itself.

Dementia patients will have bigger symptoms later in the day, peaking at dusk.

> I sometimes hear stories of friends who eat generally "healthy," and aren't overweight, shocked to learn they are pre-diabetic.

Yes sometimes it seems people are not aware that it can be organic, locally sourced, home made from whole ingredients, vegan, if it’s a pastry it’s still “unhealthy” (if it’s not occasional).

At least someone knows the science.

The wealthy owners of senior homes for mice keep on winning.

But more seriously the idea biological beings have adapted to going hungry for a set period each day (say only eating between 9am to 5pm), without starving themselves, fits well into an intuitive model of life (hunting, scarcity, etc).

It’s a cliche that weight loss and health requires being irrationally hungry all the time, or some unique physical ability, but like strength training where you can eventually squat 250+lbs with some practice I can see intermittent fasting as something you eventually build as a habit.

I say this from experience after trying a couple of times with both gym/fasting. Don't expect going hungry each night for a week is the quick Tiktok-esque solution to being fit. The initial habit building is easy... the hard (but rewarding) part is building a lifestyle that maintains it long term. I personally enjoy the gym more than changing food intake, but the latter (or keto) seems more valuable.

> I can see intermittent fasting as something you eventually build as a habit.

I've been doing intermittent fasting for a decade, through my 20's, I also stay pretty fit, but am not as consistent at keeping an exercise routine as I'd like. I've been extremely consistent about the diet for the last 5 years. Like I only have cheat days if there is a super important reason, usually being sick or when I'm backpacking. I don't think about it at this point, I have one meal, dinner, and that's it. If I'm weightlifting I might eat an early dinner and 2-3 hours later a second dinner, but I've needed this less since I started having whey protein isolate shakes on days I lift. I've even done some extended water fasts up to days; my experience is that doing these(I had to work up to it, the first time I tried fasting 3 days I quit after 2) on top of consistent IF makes the shorter fasts completely fade away.

I'd highly suggest that if anyone really wants to give IF a fair chance, kick sugars out of your diet--not just added sugars, but anything sweet (e.g. eat sour fruits)--before you go for it. Sugar is insanely addicting. I also suggest starting every day with the game plan being "I'm only going to eat one meal", but if the meal doesn't satiate you, you can fall back to a looser fasting regime, like 20/4 or 18/6.

I first became interested in fasting as a kid, when I saw a documentary on PBS about the evidence that calorie restriction extended life spans. I waited until I was convinced I was done growing, as I didn't want to stunt my growth, but have been at it since around 20. I've been veg since 15, I wish I enjoyed the gym as much as I enjoy dieting, I guess the grass is always greener.

What time of day do you have your dinner? Do you get hungry in the afternoon? When I work out consistently I find it hard not to eat a lot.

The OMAD thing seems unattainable with my current lifestyle. But I have a very healthy friend who swears by it as well. Personally not eating at night seems to be more than enough of a sacrifice. Not eating an early breakfast comes natural to me.

I try to eat between 6 and 9PM; I try not to eat to close too bed time as it does seem to affect my sleep quality. I've also found it helps to start with a piece of fruit--today a handful of blackberries. If I'm trying to gain weight I make a point to eat on the earlier side to spread my dinner out.

Socially I use the same approach that I do for being vegetarian. I don't outright declare it, I simply just decline, "I don't eat break/brunch/lunch/this early/meat/fish." goes over a lot better than, "I'm on X diet/eating schedule".

Interesting. So when you go out to a restaurant you just order a soup or a drink or something?

Exactly. It was kinda awkward at first, but after the first dozen or so times doing it I realized that the servers don't really think that much of it. Most of the time when asked what I'd like I just say, "Oh, I'm okay with water." It might make a difference that I live on the West coast(California), so special diets are pretty normal.

I find 1-2 espressos in the morning and afternoon will keep me from wanting food at all until dinner. Even after workout.

I usually eat after 6-9 pm as well as I go to bed at 9 to wake at 5.

So basically just another confirmation that insulin resistance is a huge problem and that combating it with (in this case) intermittent fasting propagates into things like reducing incidence of Alzheimer's disease.

Most fascinating is that the addition of sarcosine to the diet was able to mimic intermittent fasting responses. Sarcosine has previously shown psychoactive effects at ameliorating schizophrenia and depression in humans.

https://www.frontiersin.org/articles/10.3389/fphar.2022.8841...

I've stopped eating breakfast years ago. After a month or so the body adapts and you just stop being hungry in the morning. Most of the stuff people eat for breakfast is unhealthy anyway.

Keeping my bias aside. It’s amazing that some religions prescribed fasting for variety of reasons. Here is a mysterious quote from Quran:

"...But to fast is best for you, if you only knew." -- Surat Al-Baqarah 2:184

Did we have any ideas about the benefits of fasting back then?

"They're keeping secret this ONE WEIRD TRICK to get into heaven. If only you knew!! Click here to convert to Islam"

but 8th century

Yeah that and shortages and rationing

The ark of the covenant is a capacitor.

Lucky for the mice.

Given the all recent advances in medicine for mice, they should be nearly immortal at this point.

They are!

https://www.scientificamerican.com/article/immortal-line-of-...

The Weinstein podcast on lab mouse telomeres is pretty interesting. I’ve heard various refutations claiming it doesn’t matter, but my grug brained undergraduate biology training tells me that maybe it does and the bigbrain sophistry is a case of trying too hard to rescue now questionable research.

Short version is that for a long time scientists thought mice had naturally long telomeres, but actually that is just an unintentionally selectively bred for trait in lab mice, because wild field mice have normal mammalian telomeres. And supposedly the upshot of that is lab mice are really good at cellular regeneration. Which means unless an experiment kills them some other way they inevitably die of cancer.

> unless an experiment kills them some other way they inevitably die of cancer.

Doesn’t this only apply to Lewis and Sprague Dawley rats? Edit: and DuPont’s OncoMouse

I don’t know. Like I said my bio is limited to having been awake in class as an undergraduate and doing some basic lab work like PCR and gel electrophoresis. Oh and sexing fruit flies. Who doesn’t love that fruit fly sexing?

The claim in the podcast I’m referring to is that the very long telomeres allow an exceptional regenerative capacity. Weinstein’s theory is that senescence is basically an anti-cancer defense. If a cell becomes cancerous and then burns through its telomeres dividing, it will grow to be a mole and then stop. Incidentally that’s supposedly why symmetrical moles are ok and asymmetrical moles are scary. An asymmetry suggests that one of the cells in the benign tumor has mutated to start dividing again. Obviously that would be bad.

https://twitter.com/justsaysinmice

Good to know, I'll change my hamster diet today.

Great news for mice!

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