Brain aging shows nonlinear transitions, suggesting a midlife "critical window"
153 comments
·June 3, 2025caleb-allen
stubish
So, an specialist with ketones published a study related to ketones.
reedf1
So, a specialist with ketones published a study related to ketones; which they stand to benefit monetarily from.*
That doesn't necessarily mean the research is suspect in itself - but there is a reason we need disclosures like this.
"Competing interests: The intellectual property covering the manufacture and use of the ketone ester is owned by the University of Oxford and the NIH and is licensed to TdeltaS Global Inc. K.C., as an inventor, receives a share of the royalties under the terms prescribed by each institution. K.C. is a director of TdeltaS Ltd., a company spun out of the University of Oxford to develop products based on the science of ketone bodies in human nutrition."
bonoboTP
On the other hand, in the counterfactual case the reverse critique would also be possible: if he's so sure about his science claims, why doesn't he put his money where his mouth is?
briansm
Bit ironic when the path to ketosis is fasting (i.e. not using products).
passwordoops
Thought it looked too easy and clever just from the abstract
kirykl
Doing keto long enough however, your kidneys might wear out before your brain
3abiton
It depends how you do it. My current approach relies on intermittent fasting for 18 hours (save it for coffee and salty water), and accasional 24-36 hours fast (approx every 6-8 weeks). Not a keto diet, but helps with training Ketons.
random3
why salty water? does milk/cream in coffee make it not fasting?
eptcyka
Anything that kicks off your metabolism will make it not fasting.
mistrial9
> does milk/cream in coffee make it not fasting
almost certainly yes, that breaks the fasting .. milk specifically is fed by mothers to their young to gain weight a.k.a. not fasting
XorNot
The milk in coffee is a pretty substantial number of calories, particularly if you have a programmer coffee habit.
throwcarsales
I hear this from barely healthy people all the time. Omg you're having too much lemon juice, too much salt, too much meat, too much butter, too much stinging nettle tea, skipping too many meals, on and on and on. Yet anyone I finally convince to eat like be literally changes their entire life so positively their entire world view and opinions about the medical field and government changes. Oh yes I'll worry about my kidney because I've stopped ingesting health destroying chemicals in basically all mass food, and focused on beef and fasting.
fransje26
Did you know that if you replace coffee with water in the morning, you can remove up to 95% of what little joy you had when you woke up?
al_borland
I only recently tried coffee for the first time in my 40s. I didn’t understand the appeal, but I suppose it’s an acquired taste.
What I’ve seen over the years from occasionally being around coffee drinkers in the morning didn’t look like joy. It looked like addicts, unable to function and singularly focused, until they acquired coffee in the morning. When outside of their normal environment with quick and easy coffee, this seemed like an annoying burden to deal with.
I had a caffeine addiction from soda when I was in high school, which I broke in college. It led to chronic headaches if I didn’t have enough. In high school I didn’t put 2 and 2 together to know why I was getting the headaches and my dad was trying to push to take me to a neurologist.
Nothing about my experience with was joyful, nor has it looked like joy when someone wakes up in an unfamiliar city and is frantically looking for the nearest cup of coffee before they can talk about anything else. I’ve seen this from multiple people on multiple occasions.
npteljes
I like this saying a lot, but I have found the opposite by experience. I stopped drinking coffee recently, and frankly, I found that coffee didn't add much positives to me, aside from the feeling of looking forward to drug myself. The evaluation of its effects after ingestion is bleak - my mood improved after 10 minutes for like 30-60 mins, then I was back to my normal feelings. I sweat a lot more, was more jittery, and much more irritable throughout my entire rest of the day. Which I didn't even know about, since I have been taking caffeine daily for 20+ years now.
circlefavshape
So how many people have you finally convinced to "eat like be"? And what age are you?
rexpop
> the medical field and government
Nothing about industries that have captured legislature?
Bayer/Monsanto (pesticide exposure, water contamination, cancer risk), Tyson Foods (antibiotic resistance, air and water pollution, respiratory illness), American Crystal Sugar Company (obesity, diabetes, heart disease), Koch Industries (pollution, weakened environmental standards), ADM (antibiotic resistance, pollution), Bunge Ltd (antibiotic resistance, pollution), Nutrien (fertilizer runoff, water contamination, cancer risk), Corteva (pesticide exposure, water contamination, cancer risk).
carlmr
This is so on point, the big money in ag is pushing a lot of these conspiracies. If that's your argument for your diet, it's a shaky one.
I will go that far to admit I don't know what's the healthy diet in the end, because there's too much industry influence anywhere you look.
jajko
Swinging from one extreme to another without a good research to back it up, always a sign for a good long term move for sure. But its good, please do some research on your body for the rest of mankind, we thank and salute you. I just hope you get your meat consistently in standards that pretty much surpass what we consider "bio" in say EU or Switzerland in most aspects.
You know, there is some middle ground. In southern Europe, people have consistently healthy diets without resorting to such extremes, while eating food that tastes massively better than what a general US consumers buy / are willing to spend money on.
I just returned from 1 week vacation in Italy, thats always a trip to a small universe of healthy gourmet food. That experience is unfortunately not very transferable outside country borders but can serve as great inspiration - ie pasta ins't very healthy unless cooked al dente, then it becomes much better for the body.
daerogami
> ie pasta ins't very healthy unless cooked al dente, then it becomes much better for the body
That sounds absurd. I think you have been lied to.
drawfloat
The government?
somenameforme
The FDA claims a sedentary 40 year old man needs 2400 calories a day, the same as a 17 year old incidentally. [1] Or that everybody just needs 50g of protein a day. [2] Then there's the fat vs sugar food pyramid nonsense that led to more than half a century of health degradation.
[1] - https://www.fda.gov/media/112972/download
[2] - https://www.fda.gov/food/nutrition-facts-label/daily-value-n...
ultrarunner
The government shapes diets both through guidance (food pyramid, “plates”, etc) and regulation. For example, a major criticism revolves around farm bill payouts that incentivize corn production, leading to cheap fructose that finds its way into everything.
LPisGood
Live long enough and you turn to dust I guess.
Terr_
I aspire to the "One Hoss Shay" approach. [0] Nothing is unnecessarily overbuilt, so everything works perfectly for a hundred years... then it all collapses to dust simultaneously. :P
[0] https://www.gutenberg.org/files/45280/45280-h/45280-h.htm
irrational
That was nearly my great-grandfather. Completely healthy until he was 103. Didn’t need glasses, walked without support, lived alone, completely there mentally and had a fantastic memory. Then he got shingles which affected his throat so eating was painful. He was dead two weeks later. Went from completely healthy to dead practically overnight.
uoaei
Joni Ernst already proved just how unpopular this line of rhetoric can be.
esseph
Well humans don't seem to really learn anything that spans more than a generation or two, so there's plenty of time.
pstuart
It's not the fact that we turn to dust -- we all understand that; but denying healthcare because you're gonna die anyway is messed up.
snthpy
That has been a concern of mine. What is the latest on that?
ycombinete
I'm not sure what the stats are, but my anecdote is that two family members who did long term keto have both developed permanent renal problems in their 60s. They can now eat only very little protein.
The one person's Dr. told her that the main issue is that she was eating way too much protein. Which might mean she wasn't doing Keto quite right. But I don't know enough about the diet myself to say for sure.
snthpy
Thanks, that's very interesting.
I was concerned about that and had my liver checked a couple of years ago but it might have been too early then. I'll brush up on that.
rxtexit
My guess would be this is just nonsense.
No one has an eating too much protein problem. The average person has a sitting on their ass problem that leads to all kinds of health issues, especially when combined with a too many calorie problem.
There is absolutely no evidence that long term high protein consumption leads to these things.
NotGMan
That's a myth.
Also high protein consumption is not a problem for kidneys.
There was a lot of bad science, this "protein is bad for the kidneys" comes from people who already had kidney issues from other reason beforehand, not from healthy people.
casenmgreen
I'm not sure I understand the method.
Is it correct that the study looked at the effect of a single (large) dose of ketones, rather than ongoing consumption?
As I understand it, dosage was 0.395g per kilo of body weight (so about 27g for 70kg subject), and that was it - with measurements of brain activity before and after.
No indication of duration of effect?
I Googled and have found a product on Amazon, which is asking about 30 USD for that dose, which would make daily 900 USD a month (!)
casenmgreen
Been looking into this.
Looks like blood concentrations peak about 30 mins after ingestion, then back to normal after about 120 minutes.
No info about how this relates to effects or duration of effects on cognition.
ImHereToVote
You can make your own ketones by downing some MCT oil. Cheap AF. Just have to be somewhat fasted.
Kiyo-Lynn
I initially tried keto just to lose weight. But to my surprise, after about three weeks, I started feeling much clearer mentally, and overall just lighter, like something had lifted.
Back then, I thought it was just a coincidence. Now, reading this paper, I’m starting to think it might really have something to do with how the brain gets its energy.
jvanderbot
Have you heard of "Carb comas?" You're missing those now. And it's quite a relief.
anonzzzies
What are those supplements as I find a keto diet impossible to maintain.
bionhoward
MCT oil could be one option because it’s a shorter chain saturated fat with a number of carbons divisible by 2,
I forget the reason this is better for ketogenesis than longer chain triglycerides, Google answers didn’t seem like what I had learned about it.
Avoiding high glycemic index carbs (sugar, dairy, starch) is a big factor. Also, water: beta oxidation of fat to make the ketones, is a hydrolysis reaction
https://en.m.wikipedia.org/wiki/Ketogenesis https://en.m.wikipedia.org/wiki/Beta_oxidation
> Ketone bodies are not obligately produced from fatty acids; rather a meaningful amount of them is synthesized only in a situation of carbohydrate and protein insufficiency, where only fatty acids are readily available as fuel for their production.
marstall
they used this product in the study - looks like subjects were geven about a 1/4-1/3 of the large bottle they sell, which is around $40 https://ketone.com
cmiller1
Absolutely terrible science, the conclusion is a bunch of mechanistic speculation passed off as causal inference, just more keto bro grifters trying to pretend to be scientists.
adaisadais
Can someone give me a TL;DR?
tom_
If you're worried about your brain, reading the entire article might be good exercise for it.
jader201
So is that the TLDR of the article?
/s
aldanor
Keto diet makes your brain use ketones instead of glucose for fuel which results in slower brain aging when you're 40-50.
bravesoul2
I wonder is keto on then off better or always on.
On then off might let you get more variety in.
moi2388
Variety is the spicy of life, and all things in moderation.
aldanor
It's like asking if on and off cocaine is better than always off... sugar being a sort of cocaine-like thing for the brain.
One thing to note here is that ketosis may be achieved by diets less strict like MAD etc.
BennyH26
TLDR;
• As people get older, their brain connections start to break down faster in midlife (around 40–60 years) because brain cells don’t use sugar as well. • Giving the brain a different fuel called ketones can help keep those connections strong during this middle‐age window. • This suggests that helping the brain get fuel in midlife could keep it healthier and slow down memory problems later on.
You can ingest ketones on their own (generally expensive supplements), but this article is more interesting in that a ketogenic diet (very low carbs) may have similar benefits.
null
_Algernon_
The article has an abstract. That is the tldr
ivape
Here's my regular Claude prompt:
5 bullet points, make sure I fully understand everything in 5 bullet points:
(My deliberate buzzfeedification of the Internet)
---
- Brain aging isn't linear - it follows an S-curve with key milestones: onset ~age 43, fastest decline ~age 61, then plateau.
- Insulin resistance drives it - metabolic problems (high blood sugar) appear first in midlife, before vascular or inflammatory issues.
- Neurons can't use glucose but could use ketones - gene analysis shows aging brain regions have high insulin-dependent transporters but also ketone transporters.
- Ketones reverse aging effects, but only ages 40-60 - ketone supplements significantly helped younger/middle-aged brains but did nothing for 60+ year olds.
- There's a critical intervention window - the 40s-50s appear to be when neurons are stressed but still saveable, suggesting early metabolic treatment could prevent dementia.
xk_id
Against site rules to post generative text
selcuka
Where does it say that? Besides the GP clearly discloses that it is LLM-generated.
falseprofit
If it isn’t, it should be. No one asks in a forum because they want to hear from an LLM.
xeonmc
You can also get ketones in nail polish removers.
refulgentis
Well, yes, but not in a way that is particularly helpful. :)
This isn't as funny or faddish or odd as it sounds at first blush.
It's a well-recognized and effect help with epilepsy. My sister went on such a diet growing up and it helped. No more 20 minute seizures.
ndesaulniers
[flagged]
K0balt
FWIW I definitely noticed a downturn in my feeling of well being when I stopped huffing acetone.
1Sebastian
[dead]
throwaway984393
[dead]
bethekidyouwant
“Ketones, whether produced endogenously through fasting or low-carbohydrate/high-fat diets or administered exogenously as a supplement, have been shown to improve age-related cognitive decline (23–25) and to restore insulin-resistance-induced deficits in axonal conduction velocity” - Another win for the gym bros
dottjt
As someone who has been weight lifting for the past few years and previously was really into keto diets, one thing I've realised is that carbs are simply necessary in order to have the energy to push very heavy weights. Fat just doesn't give you the required energy to do so.
With that said, if you're only pushing moderately heavy weights or if you're a beginner and you're starting out with low weights, then it usually can be done.
Though the compromise is usually to eat high carb/low fat on workout days, and low carb/high fat on rest days. Fasting as well helps a ton.
nkozyra
Carbs are extremely helpful for strength, but there's a middle ground between ketosis and the standard American diet.
Most who lift and do low carb time their carbs before and after workouts for specifically this reason. Some also do carbs before bed.
But the rest of the day is close to no carbs. This still works. You can get < 100g of carbs a day and not have strength and energy negative impacts.
dottjt
> Most who lift and do low carb time their carbs before and after workouts for specifically this reason. Some also do carbs before bed.
This is exactly what I do. I have a have a pre-workout carb meal to try and compensate.
Though one interesting thing I've noticed is that I've intentionally had to eat carbs as my body fat percentage has decreased. Otherwise I feel very low energy (though to be fair, I think part of it is that I'm still very active on my rest days, usually doing 20 - 30k steps). I think with higher body fat my body could simply burn that fat for energy, whereas that surplus simply isn't there.
ludicrousdispla
I would rewrite your last sentence as:
You can get < 100g of carbs a day and not have negative impacts to your strength and energy.
anon291
Meh. I agree keto is too much ,but a standard 'low carb' diet is closer to how we should be eating instead of the carb heavy diet that is typical. You don't need THAT many carbs to feel energetic. But yeah some is nice
Marsymars
It’s kinda tough to get a good baseline of what people are talking about without real numbers - like I’d personally rate my carb consumption as “moderate” - I don’t eat meat so it’s tricky to meet my Calorie needs by cutting out rice and increasing my bean consumption. OTOH the added sugars in my diet are practically zero.
arvinsim
I wonder if that is really true globally. You can't really escape carbs in some cuisines like Asia and some of them are really doing just fine.
dottjt
What you're saying makes no sense without context. You say "we" but someone who's extremely active vs extremely sedentary are going to require different macros to compensate.
Of note from the "Acknowledgements" section:
> K.C. is a director of TdeltaS Ltd., a company spun out of the University of Oxford to develop products based on the science of ketone bodies in human nutrition.