Brain aging shows nonlinear transitions, suggesting a midlife "critical window"
pnas.org
pnas.org
> 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.
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."
> A Systematic Review and Meta-Analysis of Randomized Clinical Trials
>"despite these short-term benefits, FBS did not show superior long-term outcomes compared to CCR."
> However, FBS improved insulin sensitivity, with significant reductions in fasting insulin
The issue, and why I think we’ve seen several high profile fasting advocates stop, is because they weren’t metabolically unhealthy, but were on extreme fasting protocols as if they were.
The way I read it, if you’re significantly overweight and have high insulin levels (type 2 diabetes or pre-diabetes), fasting can help get things under control quickly. However, once a person has regained metabolic flexibility and health, moving to something more balanced is likely a good idea. Just avoiding going back to a lifestyle that leads to chronically high insulin levels. Some amount of fasting probably makes sense, as has been practiced by most major religions in some form for thousands of years, but not to the same extreme as during the intervention.
Try Outlive (very good) and Obesity Code (not bad so far - I'm 3 chapters in).
>However, [fasting-based strategies] improved insulin sensitivity, with significant reductions in fasting insulin (-7.46 pmol/L, p = 0.02) and HOMA-IR (-0.14, p = 0.02)
>Studies have shown intermittent energy restriction to be efficacious in preventing and managing prediabetes and DM, with remarkable improvements in the metabolic and cardiovascular biomarkers of individuals with DM.
That's the key part. Black coffee is key. I also sometimes go with tea or fruit infused water.
In some paradigms you are not even allowed to drink water and call it fasting.
The word fast means multiple things.
almost certainly yes, that breaks the fasting .. milk specifically is fed by mothers to their young to gain weight a.k.a. not fasting
Just keep in mind there's not much research about how this may change metabolism compared to a strict fast.
It may reduce any desired autophagy effects, which are unfortunately not very well-studied in the first place, but it may just es well increase them! I've seen both POVs argued in various articles.
The only actual scientific study I can find (1) does show some interesting effects on various metabolic markers, though (in rats).
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.
It's shocked me that this view isn't more common. Caffeine dependence often looks like addiction to me too, and I honestly don't think it should be as normalized as it is. People should know what they are getting into before they get hooked on the stuff.
I'm personally somewhat dependent on ADHD meds, but at least I've known that and made an informed decision. If I stop them suddenly, it takes me around a week to return to normal-ish levels of energy, but other than that I don't have any headaches or pain or anything. I think for me that's more than acceptable.
Like crack addicts longing for their dose, I've also seen people not able to work as functional adults until they get their precious morning coffee shot, and when on holidays their company ends up becoming a burden, not able to improvise, not able to stay in uncommon situations without a coffee brewer nearby for a couple days.
I'm a coffee drinker, and I take it around 2 to 3 times a week. To be honest, it takes effort to reach those addiction levels; I don't think it can happen without taking coffee every. single. day., which seems way too much honestly. Like "needing to drink hard alcohol every day seems odd"-levels of wrong.
There's nothing about this that requires coffee, but habits require primers and repetition, and starting coffee is that primer, and the socially accepted aspect of it maintains those boundaries so it can be repeated. When we go on vacation, it all goes away.
I used to smoke cigarettes as a young kid, and 90% of the reinforcement of that was the ritualistic work smoke break where you sat and bullshitted with coworkers or friends outside for 15 minutes. Without that, the habit broke easily because smoking didn't actually reinforce or be reinforced by anything joyful.
It is easy to look down ones nose at coffee drinking, but the core tie is rarely some crippling physical addiction so much as a ritual that is itself enjoyable, and we all have those. Any guidance on breaking addiction usually centers on the rituals you've created around your substance.
Exactly. This is why it was so memorable. They made their coffee problem my problem as well. Suddenly the entire morning was a frantic search for coffee. It’s not exactly the vibe I’m going for in the morning.
>I didn’t understand the appeal
My personal appeals are the anticipation of the next dose, and the initial rush I get from it. I feel smart, motivated, and capable during this rush.
Aside from this, I think the smell is great and I really like it cold, with a lot of milk. I quenches my thirst like nothing else.
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).
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.
We do seem to be in a pretty persistent anti-carb phase of diet culture, I wonder when we'll go back to low-fat.
Dont be fooled. Just eat sensibly in amount and composition.
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.
That sounds absurd. I think you have been lied to.
[1] - https://www.fda.gov/media/112972/download
[2] - https://www.fda.gov/food/nutrition-facts-label/daily-value-n...
It is an average. A guideline. And most countries give an average or range. And the US isn't the highest here: The official recommended averages I found after moving to Norway were higher than in the US and much more reasonable to keep to. (I'm female, my averages are lower).
That doesn't mean that the food pyramid is a good thing or that we've been giving good health advice. It also doesn't mean that our health advice is all that good now. We know more than we did before, but nutrition science seems tricky to do and even trickier to communicate well with the general public in ways that most people can follow. And that's before the disinformation from business interests and dealing with outright scams and lies.
But in any sane world, that's like the 90th percentile of calories required when consumed with a carb-heavy american diet and I'd argue almost no sedentary person requires that much. Just plugging in the basal metabolic rate numbers gets something well below that.
For a 40 yo male, 180 cm (5' 10") high and weighing 80 kg (176 punds), it spits out 1800 kcal at complete rest.
That then gets multiplied by a factor of 1.4-1.5 if you're a sedatary office worker, resulting in around 2400-2500 kcal.
This number is for maintaing weight. I used the calculator to find my 500 kcal deficit to lose weight, and based on my actual losses it seems quite accurate.
[1]: https://nhi.no/skjema-og-kalkulatorer/kalkulatorer/diverse/b...
You can easily go +/- 5-10 lbs at my height, just by choosing carbs over protein or fat, and it's not "Fat loss" or body composition, it's water weight associated with converting carbs to something your body can use.
Then a fast day drops you another 5-10 lbs for opposite reasons + burning glycogen stores. And that >10% swing in body "weight" is just noise on the calorie estimates if you plug it directly into such a calculator.
(as an example, if I choose 2000 calories of carb-heavy foods, I will weigh more, increasing my calorie "budget" to maintain weight b/c I eat more carbs, producing a higher weight, further increasing my calorie "budget", etc etc).
I can find 2200 for my 2 meter height, or 2500, or 1800, depending on input weight, and since input weight varies by day, and by caloric intake (due to food weight, water weight, and weight gain), it's not reliable to say the "average" person is healthy with 2400 calories. Because perhaps that person should be eating different foods or have 10 lbs less bodyfat to begin with!
I find you have to reverse-engineer it given what you know to be a healthy weight including muscle and fat composition.
Americans aren't eating anywhere near 3800 calories on average. 2400 calories is already a massive amount of food. That's 15 100g servings of chicken breast (cooked weight) for some baseline of what it means in terms of healthy food. Obviously lots of people are eating lots of junk that makes it easy to bring up the consumption, but it's still nowhere near 3800 on average.
[1] - https://www.ers.usda.gov/data-products/food-availability-per...
At least add like a quarter teaspoon of olive oil, an eighth of a cup of whole grain rice, and a side of like some sweet potatoes with its own seasoning or something.
Straight chicken breasts is like the meme level of what celebrities have to eat to maintain their figure, not what a reasonable human diet looks like. Chicken thighs with the skin on are reasonably healthy.
I'm 6'3", 200 lbs, I lift and I run - I would be in a caloric deficit at 2400 calories.
My wife would be in a huge surplus.
It seems true. Sorry for doubting you.
https://www.usatoday.com/story/news/health/2024/10/14/weight...
I guess the 2400 for middle aged people is not that far off if in the 60s the average was right around there and people were healthier.
As sibling comments have pointed out, 3800 is availability, not consumption, so it's not an indicator of how much people do eat, just how much they could eat.
And since we started letting the government tell us how to eat healthy, not only has obesity skyrocketed, but so have diseases connected with it.
I think it doesn't matter what you eat as long as it isn't super processed. The one thing that's changed a lot in the 90s is more and more convenience food.
But all three are correct, I think: Food has gotten more laden with sugar, seed oils, and carbs because it's processed to be that way after we tried to go Low Fat for so long.
A conscientious vegetarian is probably eating damn near an ideal diet by avoiding all that.
So mostly carbs, but with a lot of fiber. It just goes counter to the current trend in major ways. I looked through the old cookbooks. The biggest difference is no processed foods. And maybe less microplastics.
[0] https://www.gutenberg.org/files/45280/45280-h/45280-h.htm
Technology is moving faster than any human or our societies can keep up with, and that is compounding over and over again.
* I hate the word "should" but in this case we are already contextualized within an implied value system so it is used in a simple determinative manner.
People aren't hanging around consuming more and more healthcare for diminishing outcomes. Instead they're suffering long term or permanent problems from the US denying prompt, proven interventions.
The problem you're talking about doesn't exist.
That said, the OP context was about denying healthcare to "the poors". Period. It has nothing to do with the slippery slope of "lost causes".
Bear in mind that the OP's political party is stridently against any sort of public health care options, and that's what is driving her stance.
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.
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.
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.
The "your kidneys will fall out" nonsense has been circulating since I first started hanging out on alt.support.diet.low-carb in the mid-90s. Probably since Atkins first published his book. It's superstition.
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.
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.
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 (!)
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.
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.
/s
On then off might let you get more variety in.
One thing to note here is that ketosis may be achieved by diets less strict like MAD etc.
• 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.
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.
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.
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.
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.
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.
It’s anecdotal, but I believe I’ve experienced similar effects. During my teenage years and for most of my twenties, my body fat percentage was low because I chronically under-ate (mostly just due to bad habits, though there was a financial component too at one point) and was pretty thin. Energy peaked and valleyed quite a bit with the after-lunch crash being the worst.
After I started working out and adjusted eating habits to accommodate that, my baseline weight jumped 20lbs or so. Some of that was muscle, but body fat percentage increased too. Since then energy levels have been much more even throughout the day, even during periods where I wasn’t working out (e.g. during pandemic lockdown) and I think it’s because there’s always a bit of fat to burn where there hadn’t been before.
You can get < 100g of carbs a day and not have negative impacts to your strength and energy.
> I don’t eat meat so it’s tricky to meet my Calorie needs by cutting out rice and increasing my bean consumption.
Other than eggs and dairy, there is really no good vegetarian protein source. That's my personal opinion. Vegetarian protein comes with a variety of issues.