Alzheimer's study shows ketone bodies help clear misfolded proteins | Hacker News Reader

Alzheimer's study shows ketone bodies help clear misfolded proteins

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181 pointsmsie107 comments

As someone with Alzheimer's being quite prevalent on my dad's side [1], I pay attention to pretty much any HN thread on Alzheimer's. But most of them end up not being super conclusive/actionable.

But also ack that Alzheimer's research has been going on for decades, and progress is slow. Still, I look for glimmers of hope anytime I see one reach the front page.

If fasting has even a chance at reducing the risks, would love to know more about the duration/frequency that is needed to be beneficial.

[1] All four of my dad's aunts + grandmother ended up with it, but none of the males to my knowledge, and my dad died at 76 having never been diagnosed with it. The males, however, died relatively young, so it's unknown whether they would've ended up with it.

As a health care worker at least let me assure you the ones who suffer from Alzheimer's in my honest opinion really have no self awareness of what they are going through. They are just in their own little world and slowly moving through life without much insight as to what they are doing. It is heartbreaking for the family and those who care, but for the individual it is not a painful existence.

sounds an awful lot just like people on the spectrum (note: that includes me)

imho everyone is on the spectrum, it's just a question of where (and possibly when)

Thank you for your expert insight though I must confess--if this was meant to be reassuring it has the exact opposite effect... A disease that makes only your family suffer, wow. I thought cancer was bad.

To be fair, death seems pretty much the same.

That is, it's not the dead that are in pain, it's those left behind.

So, while I agree with you, it doesn't seem much worse than death, especially if the family accept/believe that the Alzheimer's patient is actually not suffering.

For example, if my dad lived long enough and ended up with it, had I been convinced that he actually wasn't suffering, it may be less heartbreaking as his son (but still heartbreaking for my personal loss of the relationship with my Dad, and him not knowing me).

It's hard for me to say, having not had someone super close end up with it -- only more extended family. So those closer/more affected may have other thoughts.

> So, while I agree with you, it doesn't seem much worse than death, especially if the family accept/believe that the Alzheimer's patient is actually not suffering.

While I agree that it’s not much different than death, it seems painful to know that family suffers the loss of the same person essentially twice

> it seems painful to know that family suffers the loss of the same person essentially twice

Speaking from second-hand experience -- that is, seeing my father experience the loss of his aunts/grandmother "twice".

One of his aunts was like a mother to him (his mother passed when he was 2, his father when he was 21). I feel that he really only suffered the loss once: when she succumbed to Alzheimer's.

The loss was mostly grieved then, and by the time she passed, he had already grieved. I'm not saying her death wasn't hard. But in a lot of ways, I feel like there was as much relief and peace, as there was suffering from her death. By the time of her death, she had been long gone anyway.

Of course, everyone is different, and every loss/Alzheimer's diagnosis is different. But it seems like you can lose someone you love in a number of ways, and often multiple ways, before their ultimate passing. And each one of those partial losses seem to add up to ~a single loss of mourning/grief, rather than experiencing full grief for each one.

Another example is simply having geographical distance from a loved one. Moving away (or them moving away from you) can result in experiencing (grieving/mourning) a loss. And then once they pass, you've already partially grieved, and the additional grieving is lessened from already having been distanced from them (vs. other loved ones that still live close, and grieve more from having them a part of their lives more frequently).

Again, this is just from my experience/observations from seeing how those close to me have grieved. Others may feel differently.

How would you know the difference between a lack of pain and a lack of ability to communicate it to you?

The end stages are not great for the individual or the family.

Neither are the gradual decline before that. At least there can be time to prepare for the inevitable.

I realize you likely mean your comment as a kindness and I appreciate that intent.

However, as the son of a mother who slowly died from early onset dementia, I can attest that just because the ego self has fractured and scattered into a million pieces does not mean that the afflicted person is in some peaceful state of not knowing. That they are somehow not suffering or in pain. It is just that the afflicted can no longer articulate their suffering in ways understood by the rest of us in consensus reality. If one pays close attention, the reality of their suffering is bright and clear.

One of many many examples was when my mother would compulsively pick up a pen and make rhythmic circles on and off for hours. I would watch her and wonder why. Turns out she had a severe (brutally painful) urinary tract infection and was trying to soothe her pain. She was a much beloved English teacher and writing was her refuge. She was doing her level best to alleviate her suffering.

The thought that a person dying from Alzheimer's is not having a painful existence is radically disconnected from reality.

I respectfully ask you and any caregivers for dementia patients to avoid conflating your own understanding of reality with the actual reality of your patients.

> The thought that a person dying from Alzheimer's is not having a painful existence is radically disconnected from reality.

While I understand your point I think you're talking from a perspective of the other extreme, the one where there indeed was a lot of pain but the person couldn't communicate it. Still, Alzheimer's itself mainly works in your head and it's probably more likely to assume that in most cases caregivers will have at least some means to see if patients are suffering.

The person you're replying to does probably have a lot of experience with sufferers, although, obviously, he also just states his anecdotal experience.

> I respectfully ask you and any caregivers for dementia patients to avoid conflating your own understanding of reality with the actual reality of your patients.

IMHO this would not help, but maybe even create a bigger gap between patients and caregivers. We are humans in the end, and the only thing we can do is to try our best to give them the best care and make the rest of their lives as good as possible. I think, what makes the difference, is being aware that any patient with Alzheimer's or some other kind of dementia could be in a position of not being able to communicate their pain in any way. But it doesn't help to generalize this, stopping to trust your feeling and assuming the worst.

That said, I’m truly sorry for the loss you experienced, and I hope you and your family find some measure of peace. I know how it feels. I hope I don't sound too rude or harsh, it definitely wasn't meant in that way.

You nailed it with this comment. Yes I was giving a generalized statement. I do believe the majority of patients are blissfully unaware and not suffering. They laugh and joke and tell the same story they enjoy telling over and over lol. There are some cases where they seem scared or panicked. In those cases you work on routines that they can fall into and communicate with the doctor and if possible use medications to make them more comfortable.

I worked in a advanced dementia facility for years. Ops mom having undiagnosed UTI is unfortunate but in facility it is much easier to spot for those who are experienced. The frequency of bathroom trips and believe it or not you learn the smell of a persons urine and bowel movements. So when things smell off you investigate.

I can't say I know exactly what the patients are experiencing but I have had years providing care for dementia patients and a huge part of that is family members. I really teach them about burnout and not to feel guilty asking for a break. I praise them for what they do. I am watching family members just as much as I am the clients (I am currently not in facility but work out in the community). Many of the family members are elderly also so may lack full understanding of everything. If they are crying or yelling things like that I discuss with the team strategies how we can make it easier for them.

So much to say here but your comment hit a lot of very good points. Many people genuinely care and want to help. Nothing is perfect and some cases are very hard to manage. I too am sorry to hear op struggled with his mom it is one thing to see it in a client and another to see it in a family member. I wish anyone experiencing it the best.

I am sorry to hear you had such an experience with your mother. Of course I made a generalized statement and that can not be true for everyone. There are also multiple types of dementia and dementia like conditions. Some forms do leave the person confused and scared and calling out and in rough shape for the caregivers perspective. But in general the vast majority of the clients I have worked with did not appear to suffer or be aware of their situation. I worked in an advanced stage dementia facility for almost 8 years.

When a population can not express what is wrong yes sometimes health issues get missed like your moms UTI. But with a lot of experience those things get noticed much faster. Having worked with someone for years as many clients did stay with us for years you get to know their routine very well. Suddenly they are using the bathroom non stop you question UTI. They suddenly start acting very strange - check for UTI. The system is not perfect but there are people out there that care and are doing their best to help those. I advocate for my clients and use my experience and knowledge to help these people get into the best situation possible.

When working with dementia patients you are not just working with the client but his family as well. I currently work in a community setting so see people at home and when I see the wife crying or yelling at the client I sit and ask how they are doing. I let them know that they are a good wife or husband and that getting upset does not mean they are bad. I then tell them that it is however important to recognize when they are burning out and getting frustrated. Thankfully for most of my clients there are services that can let the family get a break. We will do respite visits and the family can leave the house and get some errands done or just have lunch or relax. In those upset moments I help them through the situation and then discuss it with my team to try decide how to best help. Sometimes that means increased service. Sometimes it means they go to a respite facility for a week. Sometimes it even means they get placed into long term care facility.

I am drifting off on this post so again I am sorry about your mom. Dementia is cruel. Care is not perfect. But I genuinely feel for the majority of those who have dementia they just lack much insight as to what is happening.

Thank you for such a thoughtful, considered – and considerate – response. I appreciate your diligent attention to what is surely a highly demanding job. Thank you for your service.

When I went through this with my grandmother, I experienced that too. Like others said, it's important to note that in the later stages it may be hard for the patients to communicate their pain, so we cannot be sure, but at least in my anecdotal experience I would say that I can be pretty sure there was no acute pain involved.

The most important thing for me and others around her was to just vibe with her reality. Just give her the space. Not be mad, but laugh or help, again and again. Like you would do with a baby. Don't expect them to learn, don't expect anything.

Until the very end I think she had a good life. The end, obviously, will have been hard for her, because that's a time where they cannot even live their own little life anymore but probably experience higher pain in general, but that's what it is.

They have plenty of time to suffer between diagnosis and not being able to be aware of the world at all though. Dad had years of depression due to the gradual decline before being incapable of communicating.

My grandfather had Alzheimer's. My grandmother dementia.

My grandfather would, not uncommonly, escape from his care home. He'd be found, miles away, trying to "walk back home" -- and, despite his deterioration, he knew the routes, he was walking the right city streets to get to the right country roads, etc... He wanted to "get home" and make sure his garden was being tended to. Sometimes he'd have shit himself, or pissed himself, but had been walking for hours regardless. That isn't a painless existence. Through what I know of his experience alone, I've understood this to be deeply traumatic.

And my grandmothers experience was something else entirely. I believe I've commented on it here before, but her experience was also uniquely horrific. Bed-ridden, gangrene, do-not-resuscitate orders that were not acknowledged... I am terrified of what they went through.

Personally, I feel that our notions of "pain" don't really get even approximately close to what these patients endure.

They have repeatet panic attacks, when they "wake up" in a foreign place, surrounded by foreign people. Think of "teleported to a strange city" every 3 minutes.

Maybe you only get to see the sufferers when their condition is already advanced? My Dad is in the early stages of Alzheimer's, and knows it, and is really down about it. He regularly goes off by himself to cry. It's pretty heartbreaking

That hasn't been my experience (n=1 thankfully, I hope it never increases involuntary). Lots of confusion, distress, trying to go outside/go back to where they lived when they were children, not recognizing the people around them ("he can't be my husband, my husband is young!").

There are a lot of recent attempts to link Alzheimer's to metabolic diseases and disorders. Insulin dysregulation, liver diseases, LDLs and transport, immune dysfunction, inflammation or sclerosis during extravasation, etc.

We spent an awful long time chasing after amyloid and tau. There are enough eyeballs on these new ideas that I'm hoping we can find a preponderance of evidence soon.

Sticking to a keto diet these days is extremely easy, so I’d suggest trying that first before heading to water fasting which requires relatively more care and preparedness. (Disclaimer: I am not a doctor though and it’s highly possible I misunderstood the article, just offering advice based on familiarity with a keto diet and water fasting.)

there are... probably better forums to be tracking the latest in biology research...

Are there any you can recommend, or are you just saying that from knowledge of the level of biological discourse here?

HN is the best place for this kind of "sensitive" topic in my opinion.

Youtube is full of self-promotion and "experts" that just try to rack up views. Good luck wading through that, and that's even if you find solid videos that aren't just "fad" shorts.

Reddit is, well, Reddit - I need not say more.

Trying to find information about anything medical on any search engine is a bust because there are millions of sites all offering medical information with no way for us to know their validity.

Scientific articles are also just glorified eyeball generators too, so can't trust them.

Reading the actual published papers is out of reach for most of us that aren't knowledgeable in the field.

Finally - real world Doctors are out of reach for most of us, and they'll only talk to you if you make an appointment. But even if you do, good luck having them take this sort of line of questioning/discussion seriously as it's not the normal and rote "diagnosis" function that they enjoy doing - even if they're up to date with recent research. Like lawyers, they safeguard their sacred priesthood's knowledge, and that's why they only "advise" you if you pay up.

>Reading the actual published papers is out of reach for most of us that aren't knowledgeable in the field.

Right, if we can even find the right publication search engine for the right area, then we're likely faced with a paywall with a dollar figure. I'd love a list of free resources for research.

level of discourse. you can just read journals

The natural rhythm? Summer + Autumn feasting - Spring fasting with lean meats, then repeat?

What worked for me was doing two/three days of juice fast first. During this time you clear the colon. Once "empty" it is much easier to maintain the fast.

I usually the water fast for two/three days, and then do one day of dry fasting. If it goes really well I extend it by a day of two.

To get back to my regular diet (which is mostly "WFPB" https://www.doctorsfornutrition.org/general-public/what-is-w... ) from a dry fast, I usually take one day of fruit-only. This to gently start the GI back up.

I cannot recommend doing some fasting yourself enough. It really changed my attitude to food and "feeling hungry". I made some personal bests in sports while fasted!

>Alzheimer's research has been going on for decades

Based on some recent high profile cases so have massive scientific fraud.

Which rises the question: are we on a wild goose chase due to following fraudulent science from highly published "thought leaders" when it comes to Alzheimers disease?

On many other major disease categories we've had many major improvements from biologicals and immunotherapies. RA, MS? Compared to the past, they're a walk in the park. Cancer mortality dropping like a rock for the brutal killers of the past, glioblastoma is still a gnarly death sentence but there's hopeful news on the horizon even for that.

Alzheimers? Crickets mostly, biologicals where the error bars eat virtually all of the alleged observable effects? Sounds like we're barking up the wrong alley.

fyi, You can set up rss feed searches on pubmed and load them into your favorite rss reader for a much better, more up to date feed of what is actually being published around topics you care about. Its dramatically better than anything you will see on hacker news as long as you can get a good set of search topics so its a trickle of hits, nit a firehosex

There was an interesting article the other day mentioning a study where getting a BCG vaccine as an adult seemed to give a 75% reduction in Alzheimer's. The hypothesis being that it can be set off by an infection and the vaccine boosts the immune system. That's a bit of a simplification but the article is here https://www.theguardian.com/lifeandstyle/2024/dec/01/the-bra...

As someone currently on a strict ketogenic diet (gotta cut and get ready for the Christmas fattening)

I can say ketones are something else in the brain. I sat at my desk today for 6 hours straight without even getting so much as a drink of water. I didn't even think about eating. Just in the zone and hyper focused.

A very weird and pleasant experience, that alas can't be sustained forever given how delicious carbs are.

This is something I've been experiencing as well, and I just started exogenous Ketone supplementation three days ago.

Exogenous ketone supplementation? Are you drinking acetone or something?

Not quite. I've been taking Beta-hydroxybutyrate (BHB) salts in powder form, mixed with water. Here is some interesting literature discussing its benefits as a metabolic regulator of proteostasis in aged and Alzheimer-diseased brains:

https://pubmed.ncbi.nlm.nih.gov/37461525/ (same research article referenced in the post link)

I personally take it to manage brain fog due to long-Covid.

This is why I come to HN.

Have you tried a ketogenic diet? Ketones from your own fat cells for free.

did it help? also, before covid did you not have brain fog?

are you taking BHB along with being on a ketogenic diet or do you else eat carbs?

I use that as well. I found that it was a great way to slowly ween myself off caffeine while avoiding the caffeine withdrawals. My sleep is improving a little and I remember more dreams, not sure why.

Interested to know if this ends up helping you long term, thanks.

Except for the fact that my memory goes to crap for a few days every time I go on a keto diet. Is this just me?

A common phenomenon called keto flu. Especially pronounced the first time.

I suggest high electrolyte food, such as a nice salty soup. Seems to help.

I like to do lazy keto (which is easy, just forget to buy snacks after you run out) but always find I'm thirsty and specifically always want miso soup. Maybe that's why.

Don't forget electrolytes while fasting / in ketosis (all three: sodium, magnesium, and potassium).

Totally normal the first days even weeks are a bit fuzzy. Your body is adapting to a completely different metabolic system. It’s very stressful.

Just going calorie negative did this to me. I still eat carbs and it doesn't seem to help.

>A very weird and pleasant experience, that alas can't be sustained forever given how delicious carbs are.

why not? it's just a matter of having access to decent meat/fish, discipline, and ignoring peer pressure at social gatherings.

for me, it takes at least two weeks to recover from SAD-like diet and go back to the kind of state you're describing - high energy, mental clarity, complete absence of hunger, etc. the first week is particularly unpleasant - low energy and constant carb cravings, etc.

I've struggled with "but factory farmed meat and dairy conflict with my moral beliefs" when trying keto. It's nice, but very challenging to do sustainably if you have dietary limits like that.

There are better products. Likely more expensive, but possible.

Go on craigslist and search for cow, beef, and lamb share. You can go visit the farm and verify the animals are happy, pasture-raised cattle.

Our beef came from a cow we can see from our backyard.

> why not? it's just a matter of ..., discipline, and ignoring peer pressure at social gatherings.

Both of which are very dependent on willpower, and as much as we would like to believe we have control over, it's highly affected by emotions depending on the individual.

Great that you can sustain it but phrasing it as an easy thing to do is ignoring the fact that simple things are not necessarily easy to do.

Don't give up! Induction gets easier every time, and you learn lots of tricks/recipes, like keto-ade to feel better during induction, and making oats/flaxmeal tasty for cheap & quick breakfasts. You don't have to commit to long streaks, or feel bad about sunk cost when you cheat. All that progress accumulates.

I've been in and out so often now I can happily switch between keto at home & unrestricted on vacation/occasions. At worst I get 1 day of dopiness starting carbs, and 1 day of mild cravings stopping them, but usually I don't even notice.

I have done keto for a while but have no appetite for it anymore, it's also nigh impossible since I became a vegetarian >10 years ago.

I'm not talking about myself but in general, even though it can also apply to myself (my willpower is not absolutely under my control) but the same advice about discipline and resisting peer pressure is given to obese people as losing weight is quite simple, it doesn't mean doing the simple thing is easy.

Vegetarian keto is certainly possible, but vegan would be very tough. Only 2 out of 6 of my regular meals[1] have meat in them, and I'd probably replace these with tofu and mushrooms if I could tolerate them. There's a world of keto&vege analogues to try for noodles, breads, and pizza bases. IMO some of them are nicer than the carby versions.

I also struggle with willpower and it took me ~10 big attempts over ~14 years before I managed to stay on it long enough to fix my metabolism. I just wanted to spread the message of hope that every attempt gets easier. Mindset plays a big role - I've seen a few people push themselves really hard then declare it impossible and never give it another shot. If you know you're playing a long game, take a break if you're really suffering, and don't beat yourself up over failures, it's easier to try again next time you have the energy.

[1] I've lots of intolerances - whitelisting was easier than blacklisting. Here's the list: flaxmeal porridge, keto bread + cream/cottage cheese, omelette w/ pizza toppings, egg & cheese salad, caesar salad (w/ chicken), mince+vege+cheese mealprep'd casserole

I used to do a very low carb diet that kept me in ketosis. For the most part it was great but the sleep difference concerned me. At the time my life was structured to where I didn't need to be awake at any particular time so my body would wake up when it had enough sleep instead of when an alarm went off. While I usually sleep seven to eight hours when eating a standard American diet, when on low carb, it would end up being only five to six hours, usually closer to five than six. I'd feel completely rested and fine but most days I'd need to take a short ten to fifteen minute nap, during which I'd quickly fall into REM sleep. When waking up from that nap, I'd feel fine, no post-nap grogginess, but it made me wonder if I was getting shorted on REM sleep during my primary sleep period.

It sounds very primal. Sleeping short times in the cave and then catching a cat nap when you can.

> A very weird and pleasant experience, that alas can't be sustained forever given how delicious carbs are.

I’ve been doing Keto for over a decade now, with one cheat day a year (Christmas market mulled wine with family). I can guarantee you it can easily[0] be sustained if one is so inclined. OTOH, 6 hours without water sounds neither healthy, nor like something I’d ever want to do.

[0]: With the caveat, that your circumstances need to allow it. I’ve been working from home and cook all meals myself.

There are so many caveats to your "guarantee" that it isn't really guaranteeing anything.

People are wildly diverse when it comes to food traditions, actual state of intestines and also cravings. What worked for you may not work for a Vietnamese guy who ate rice for 50 years of his life.

Extrapolating carelessly from N == 1 is a bad idea.

You are extrapolating from my message. I disputed can't be sustained. For which a counter example is enough. But I'm not interested in nitpicking phrasing.

"easily be sustained" - for you maybe. I have done keto for long periods, 4 times in my life, and i find it personally extremely unsustainable. Boring, extremely restricting in social situations, and cuts you off from one of the greatest joys in life - the vast array of food, tastes and experiences available to the modern human existence. Casting wide generalizations from your own personal experience is bad, and unfortunately par for the course in any internet discussion of diet.

I wrote "can". As opposed to OPs "can’t". Not "is always".

I also find it hilarious that you assume I’m cut off from one of the greatest joys in life - the vast array of food, tastes and experiences available to the modern human existence. Talk about generalizing from your experience, eh?

It’s because you also wrote “easily be sustained if one is so inclined” which comes across as judging others for not just doing this one “easy”(for you) thing. If that’s not the spirit behind that comment then I apologize for my reaction.

Also it’s just a fact that you can’t eat the vast majority of foods and food experiences. But you’re right , I’m generalizing that food is a joy for most people.

> It’s because you also wrote “easily be sustained if one is so inclined”

Yes, because I, funnily enough, don’t like people over generalizing. Especially with keto I’ve kept hearing stuff like you can’t sustain it, you’ll bounce back etc. So you have to see it in the context of a very much generalizing comment I replied to.

> But you’re right , I’m generalizing that food is a joy for most people.

It is a joy for me as well, and the stuff I tried and experimented has vastly expanded since I started keto, I feel like I gave up very little.

I tried doing a low carb diet and it wrecked my mental health. Worsened my depression and mood swings. It just does not jive with some psychiatric conditions.

What’s your usual breakfast?

Salad, leftovers, bread, or chia seed pudding.

I was diehard keto for over a year straight. Chronic inflammation that I’ve lived with my entire life disappeared totally after a few weeks. I became pretty dogmatic about the whole thing and eventually my body started to suffer. I don’t believe it to be a long term sustainable diet, at least not at the level i was doing it (sub 20g carbs a day).

My blood tests got very worrying towards the latter part of the year and I started to have regular panic attacks and what I can only presume is chronic low blood sugar that ultimately left me feeling pretty lifeless and scared.

Anyways just my personal anecdote to remain cautiously optimistic

What did you see in your labs?

all exclusive diets (vegan/carnivore/keto/etc) are deficient in some vitamins, minerals, and maybe other things (omega-3, specific amino acids, etc).

were you using supplements? on keto in particular, a decent multivitamin and some extra vitamin C, magnesium, and potassium are a must.

My mistake was I gravitated to eating mostly fatty pork and chicken after a year. Turns out those are very high in omega-6’s. Does not play well with my mental health, skin (exacerbated my pollen allergy related eczema), resulted in starting to regain weight around my stomach despite maintaining a loss of 50 pounds for two years, and becoming cold all the time (yes, my thyroid and calories were fine).

After some research on wtf might be going on, I had my suspicions and took an omegaquant test which revealed my circulating phospholipid omega-6 levels were crazy high, just a few percent below their max reference range. Moving to beef only halted my issues after 1-2 months.

I like beef and monotony, but even I can’t eat just beef. I now cycle between keto and carbs (mostly potatoes, carrots, onions and glass noodles, sometimes pasta or bread buns). I generally have carbs near workout days. Now that I’ve shed the omega-6 pounds, I have some tolerance again but end up still mostly use beef, eggs, and frozen seafood blends (no fish, which when farmed tends to be high in omega-6).

Oh, and if you are looking for a salad dressing that isn’t just flavored vegetable oil (high omega-6), give the “skinny girl” brand a try.

I'm at 3 years with occasional breaks. At a certain point my weight wouldn't go lower and I started feeling terrible. I think I was producing more ketones than I could use. I'm not sure exactly what fixed it, but now I'm sustaining a low-carb, low-but-nonzero-ketone mode, and still getting 50-75% of the mental/energy/anti-inflammatory advantages.

I think it was either changing my diet to focus on veges instead of meats (still 15-30g net carbs/day though), or adding artificial sweetener to maybe fool my body to making insulin? The science says that shouldn't happen, but idk what else it could be.

There is a book about effect of keto on the brain: https://www.amazon.com/Brain-Energy-Revolutionary-Understand...

Not sure how much evidence is for claims, but sounds somewhat reasonable.

From the article:

“Early human studies of ketogenic compounds have improved cognitive scores in patients with mild to moderate AD.”

While it requires behaviour changes (for the diet), this is something that's relatively easy to test & validate, and with a good sample size.

Edit: To elaborate -- getting on a keto diet results in production of ketone bodies; the keto diet is (IMO) hard to adhere to, but not impossible.

And if it is ketone bodies in the brain that are important, iirc, you can supplement the body with exogenous ketones (which the article alludes to, and the authors appear to be planning to test) which could potentially help.

If there's a measurable, significant effect with just consumption of exogenous ketones without even having to enter ketosis via diet- wow!

I'm all keto / very low carb for 4 plus years. I have been on dozens of different diets, not an exaggeration. Other than the eat whatever I want diet this has been by far the easiest for me to maintain long term. For me eating just a little bread is an insurmountable goal, but eating none I can do. I wouldn't have always traded carbs for a few extra years of cognitive function, but post addiction it feels like a good deal, if I can still get it.

Would we potentially expect lower rates of Alzheimer's among Muslims then?

This was my initial thought.

Is the month of Ramadan enough have an effect on Alzheimer's or is more frequent fasting required?

There is a (relatively small) subset of Muslims that fast every Monday and Thursday, in addition to fasting the month of Ramadan. Perhaps that’s a better population sample to study?

And how much fasting?

Is intermittent enough? 12 hours? 18 hours?

Or do we need frequent (e.g. weekly or 2-3 times weekly) 24-hour fasting?

14 hours every day is considered great (don't eat late, skip breakfast), a solid 48 hour fast every month or so is also great. Small human studies, for example, have measured 5x to 10x increases in HGH after 48 to 120 hr fasts respectively. Free steroids, basically; the body repairing itself while not being drowned in food all day every day. Telomeres too!

Fasting during Ramadan is only during the daylight hours, so hardly even enough to be considered intermittent fasting.

Am just a hobbyist with some personal investment in AD, but the genetic basis for Alzheimer's seems like too strong a confounding factor to be looking for behavioral differences between ethnic/religious groups IMO.

There does seem to be some kind of link between GLP-1s and Alzheimers: https://pmc.ncbi.nlm.nih.gov/articles/PMC11242057/

Some people also seem to like nicotine-related hypotheses: https://discoveries.vanderbilthealth.com/2019/09/nicotine-to... and hypotheses with other kinds of drugs that have appetite suppressant characteristics: https://jnnp.bmj.com/content/93/10/1080

The whole field is kind of a gigantic mess these days, though. Seems like everyone and their cousin has a pet theory.

I don't think daily fasting heals the body. I believe it has to be multi-day. The Fasting Cure by Upton Sinclair was a nice introduction to the topic for me.

You have to fast for a long time before your body starts fueling you from ketones.

I don't think that is true. Some expert (Dale Bredesen maybe) said somewhere that a healthy person lacking the bad habit of eating late in the evening will tend to start producing and burning ketones during sleep every night.

Also, many experts are saying that if your body cannot burn fats and ketones, which is unhealthy, you can get it start being able to again by restricting carbs for a while.

Yes there's a lot of hormonal / circadian rhythm effects at play in the evening and early morning. Additionally, you fast while you sleep, so extending that period before and after (not eating late, plus skipping breakfast) helps; 14 hours is a solid fasting amount if you keep it up every day.

You don’t need to fast, you just need to stop eating carbs.

Own a strict ketogenic diet right. Feeling absolutely great. Gotta cut down before the Christmas fattening.

If you've eaten at even a moderately good memory care center you'd expect lower rates from Alzheimer's patients too. Blech.

Not an expert, but two differences that most Muslims have which non Muslims don't:

- They don't drink alcohol

- They fast every year

No idea if these help or not.

They are only doing intermittent fasting (from sunrise to sunset), and a lot of them binge eat as soon as the sun is set. Not sure if this can be used as a baseline for a study.

The usual Ramadan regimen for Muslims involves carbo-loading with dates and sugars in the morning, so it is unlikely to get to ketosis by iftar.

Depends, I'd say. The research fraud around amyloids aside, there is still a strong chance that Alzheimer has a genetic link, and in that case you might have to differentiate between Arabic, African, Asian and Western Muslims first.

Only if you find similarities in lower Alzheimer rates among all of them, you can draw a conclusion pointing to something in Muslim culture helping to reduce Alzheimer rates (say, the yearly fasting acting like keto diet, or not eating pork, or not drinking alcohol/consuming other drugs), but if it is only found in specific heritages I'd assume a genetic component... or environmental factors similar to higher natural lithium content in the water leading to lower suicide mortality [1].

[1] https://pubmed.ncbi.nlm.nih.gov/32716281/

Can't remember if this was on HN previously or I saw it somewhere else ... but a few weeks back there was a research PR article about some researchers feeding mice a high sugar/far diet and letting them solve a swimming task, and found that the high sugar/fat diet mice performed worse, and attributed this to memory / cognitive degradation, a la Alzheimers.

They therefore concluded that Alzheimers is effectively "diabetes of the brain" (i.e. with or without concomitant diabetes 'of the body'.)

So this news is interesting, since it both supports the "diabetes of the brain" interpretation, as well as debunking it at the same time (i.e. it's not the high-sugar, but the lack of ketones which you only get when you avoid sugar?).

I wonder if this subtle distinction has any practical importance. E.g., perhaps you don't need to avoid sweets more generally as a diabetic would have to, as long as you have enough days where you produce ketone bodies (e.g. through intermittent fasting?).

Equally, one has to wonder if the whole lack of ketones bad might be a mechanism for diabetes itself ... (maybe this is an actual hypothesis being researched? I haven't done the research to have an educated answer to this).

This doesn't surprise me, I'm long term carnivore and you only need to pay attention to your skin improvements when switching from carbs to fats

Mental health is harder to self diagnose, that diagnosis is better coming from someone close to you, but you should notice changes over time

My friends also think Keto is unsustainable, the way I think it about it is sugar/carbs are more addictive than alcohol, pay attention to the language use "sugar rush" "sugar crash" this is how we talk about addictive drugs not food

You wouldn't tell an addict to have drinks in moderation, once you're out of the woods and stable into ketosis then "normal" foods test like chemicals and hyper sweet to the point of being unpalatable

Could this have an impact on other prion diseases like variant Creutzfeldt-Jakob (mad cow) disease?

It's a horrible way to go. As an early teen my grandma went through it. We would find her hiding from her abusive ex husband who had been dead for forty years. She would call the house at 3am, I was told to not answer the phone and of I did answer to hang up on her nectar she would talk at great length about how she could feel the worms eating her skin in her grave. It was really awful to watch as a kid and I'm sure it was much worse for her. She didn't do well in a home after that and would attack the nursing staff negate she didn't know who they were. That shit of horrifying. I think if nothing else, Alzheimers is one hell of a great reason for assisted suicide.

Can someone with knowledge in the field explain it?

fasting prevents Alzheimer's

Notably in both model animals (nematode worms and mice) they specifically fed them ketone esters, meaning that if the mechanism also works in humans (which seems likely) then this could be used as a drug if people don't want to commit to fasting or keto diets.

IMO hardcore fasting just to avoid certain diseases feels somewhat analogous to chemotherapy to battle cancer. Sometimes it works, but at what cost?

FWIW, you don’t really have to fast to be in ketosis. You just need to get very few of your daily calories from carb intake.

Totally. Doing sprints on a rower after cutting carbs is a great way to plunge into ketosis -- or anything strenuous for long enough time. Have felt the shift while pushing a lawn mower for a while.

OMAD works wonders and is easy to do.

Keeping it up for 2 years now.

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