As a former Alzheimer's researcher, this is a big fucking deal. It puts together a lot of clues (APOE risk, microglia) and finds a theory that makes a lot of sense. All around the world, there are labs pulling late nights trying to figure out how to drug this.
Been studying folks with only one working CYP21A2 due to the resulting atypical adrenal function and I noticed that their dna also contains all the genetic variants associated with Alzheimer's (some are beneficial in this case). Inquiring about the family tree of the single CYP21A2 I have yet to have someone tell me of an ancestor that died of Alzheimer's. But the family members with two good CYP21A2 (and all of the other typical Alzheimer's genetics) are the ones that end up with Alzheimer's. And for good measure, when someone has 3 CYP21A2 nearly always they will get Alzheimer's. (they also end up with Hypercortisolism).
Subclinical Hypercortisolism has a long association with Alzheimer's. A deficient CYP21A2 and the decreased incidences of Alzheimer's is not talked about other than the fact that it isn't associated with Subclinical Hypercortisolism, but Subclinical Hypocortisolism instead.
All of the known indirect early preventative measures for Alzheimer's result in shifting from Subclinical Hypercortisolism towards Subclinical Hypocortisolism.
This was not my intended area of study, but the pattern is interesting and curious for your thoughts.
I'm really uninformed about this topic, but I'll second the request for info about this!
I have Alzheimer's on three sides of my family (really banking on the fact that I take after the 4th grandmother who was sharp as a tack till 98), and while I haven't ever looked into a diagnosis of hypercorticolism, thanks to very early (in utero/neonate) trauma, my parasympathetic nervous system never learned how to clear cortisol like it should, which I'm working to remediate now.
I've been operating under the assumption that Alzheimer's is a high risk in my future, but I'd love to know more about what any experts would say I could even try to do by lifestyle change or preventative treatment!
Assuming your psychological state of mind and your heart health is relatively good, whole body cold water plunges/swimming 3 times a week for 2-3 minutes, has been shown (in relatively small studies) to have many positive effects on various endocrine system functions, including cortisol levels.
I don't know if you've seen the documentary 'My Octopus Teacher', but the subject spends an entire year diving in frigid water. His voice and general presence are so peaceful, it's almost comical. I joked at the time I saw it that he must have no cortisol left.
Do you know if water-only fasting is a good way and/or necessary way to help stave off or even allow regression to occur?
An anti-inflammatory diet, inflammation being known as one of the ~5 root causes of Alzheimer's for awhile now, like a ketogenic diet has been known to be beneficial - but water fasting will not only lower inflammation as much as possible, it will also arguably would cause more of the fat reserves to be used up - but whether that includes fat buildup in the brain too?
>> The idea that eating fat leads to higher body fat is the most dangerously-wrong health misconception in history.
Modern equivalent of medieval leeches and enemas for "fever" (almost anything was called a 'fever' back then) and eating goat testicles for potency. Eating them raw obviously :)
Medical leeches are still very much a thing. They’re used to help improve venous circulation after plastic surgery around reattached body parts, help with burn recovery, etc
Because of homeostasis: dissolved substances like fats in the bloodstream are regulated within bands, and beyond certain limits the amount ingested doesn't translate to more: it's excreted or winds up elsewhere. Your metabolism may cause states worse than other people, sure. But that pound of butter you ingested isn't directly causing rises in the bloodstream to infinity. It's long-term accumulated burden and excess over time.
Cholesterol levels don't track intake directly. Lowering cholesterol and fat in diet needs to be done in consultation with somebody who understands your metabolism. Some vitamins are fat soluble. Some fat is beneficial.
While I always knew that sugars where the main culprit for body fat thanks to a highschool biology class, I have never understood why fat is less of a problem so thank you. Could you link me with sources or search keyword in order to know more of what the body is doing with excess fat ?
I tried "what does the body do with excess fat" and I think it covers it. For sure, you get higher triglycerides floating around in the bloodstream, and the liver is under stress. at the extreme end, its Steatorrhea which is .. unpleasant (olestra goes to the same place)
The lymphatic system is also involved.
So it's not entirely "eat as much fat as you like" by any stretch. It's more that over time, the body tends back to a baseline model. Continual high levels of fat which cause surplus in the bloodstream are heading to arterial blockage and isn't good, but the relationship of fat ingested to fats in the blood is a more complex path. "it depends"
I'm not a bio scientist or a med. Happy to be corrected.
> I've never seen anyone who's obese and having a diet that made me go "huh that's odd how can they be obese?"
Are they eating fat _or sugar?_ The body will aggressively squirrel away any unused sugar as fat. As one example, a Big Mac contains 7g of _added_ sugar. Fries? Coated in dextrose. Sugar is added to damn-near everything.
"Starch and glucose efficiently stimulate insulin secretion, and that accelerates the disposition of glucose, activating its conversion to glycogen and fat, as well as its oxidation. Fructose inhibits the stimulation of insulin by glucose, so this means that eating ordinary sugar, sucrose (a disaccharide, consisting of glucose and fructose), in place of starch, will reduce the tendency to store fat. Eating “complex carbohydrates,” rather than sugars, is a reasonable way to promote obesity. Eating starch, by increasing insulin and lowering the blood sugar, stimulates the appetite, causing a person to eat more, so the effect on fat production becomes much larger than when equal amounts of sugar and starch are eaten"
From https://raypeat.com/articles/articles/glycemia.shtml
But I suppose that plenty of fats are healthy and part of a balanced diet. And someone who eats nothing but refined sugar is more likely to be over weight that someone with a high % of fat in their diet.
No they wouldn’t stay lean. If you fed someone more calories than their body uses to maintain its current weight, they would get fat eventually. Regardless of whether they eat carbs, fat or protein.
Let's say you're being fed just the amount of calories your body needs to maintain. What influence on body fat has the distribution of carbs, protein and fat from food then?
My point was that regardless of what you eat, if you eat more than your body expends, some of the excess will be used to produce fat and you will gain weight. If you lead a sedentary lifestyle and eat 3000 calories of nothing but lean meat per day, you will gain weight.
You are right that different foods (macronutrients, more specifically) have different thermic effects and therefore require different amounts of energy to metabolise. Protein takes more energy to process than fat. This does not change my overall point.
Not much for getting lean but it's easier to overeat carbs and fats are calorie dense. That said you need to eat a mix of the three to be healthy because they all have important body functions.
You're so wrong. With only protein and fat, they would not be able to gain much weight. I've tried to gain weight on low carb/high fat, and it doesn't work. I was uncomfortably full after every meal. My tracking showed a significant calorie surplus, but my body wasn't absorbing it. Adding in more carbs made a huge difference. Hormones tell your body when to store fat.
Did you know that bodybuilders in the 1950's(before anabolic steroids) used the egg and steak diet before contests as cutting diet to get lean? They would eat, as the name suggests, large quantities of steak and eggs with butter and have a carb refeeding day every 4 days. They would get really lean on a very high-calorie diet, think 4000 to 6000 calories.
The inventor of diet famously lost a contest for being too lean.
The authors calculated that ∼18 g (79%) of the 23 g of ingested protein could be accounted for by deamination; thus those carbon skeletons were available for gluconeogenesis and release of new glucose into the circulation. The remainder, presumably, was used for new protein synthesis.
The total amount of glucose entering the circulation from all sources was calculated to be 50 g over the 8-h period. However, only 4 g (8%) could be attributed to the ingested protein.
I think you misread that experiment. It appears that some quantity of protein was converted to glucose, but that it wasn’t dependent in the quantity of protein consumed.
> Humans are bad at lipogenesis: we can only convert tiny fraction of the carbs into fat.
Because historically food is scarce or difficult to obtain, in general organisms develop mechanisms to make good use of it: when excess food ("energy") is available, it is stored rather than wasted.
This is also true in particular for mammals, and for humans. It's quite obvious that humans are very effective at storing excess energy.
It is said that sumo fighters maintain their body mass (muscle + lots of fat) by eating rice (i.e. carbohydrates) and protein.
Lipogenesis (fat generation from carbohydrates) takes place mostly in the liver.
"Excess acetyl CoA generated from excess glucose or carbohydrate ingestion can be used for fatty acid synthesis or lipogenesis."
Nope. If humans eat both carbs and fat (most of us do), the excess calories of fat goes mainly into the storage (or plaques to your arteries), while the carbs are used in the sort term (converted into glucose).
> Lipogenesis is mostly derived from carbohydrates and is a relatively minor contributor to whole-body lipid stores, contributing 1–3% of the total fat balance in humans consuming a typical diet.
The human body doesn't need to store excess calories. It could store the excess calories or it can excrete energy through urine(glucose, ketones)
Or it can ramp up metabolism, there are many scenarios. Not all lead to adipose tissue growth. Why not muscle growth, which is somehow always overlooked in these discussions.
Funny enough adipose tissue and muscle growth are both through hormones. If testorone and hgh are high then muscles growth will prioritised over adipose tissue.
People with type 1 diabetes have figured out how to stay thin after eating copious amounts[0]. They won't inject themselves with insulin. Unhealthy, sure, but they won't store calories, as adipose tissue (fat cells) remain inactive, even though blood glucose is dangerously high.
Just looking at calories is simplification, and is just for general guidance.
Ketosis is probably our rudimentary "wintersleep mode". Rudimentary as we are basically tropical animals (look at our lack of fur).
We should not eat for ketosis. But we can eat (restricted to fat and protein) and still stay in ketosis, which is marketed as the keto diet and is not well tested in long term studies. You are a guinea pig when you do this long term.
For me I went keto because I had a problem with sugar addiction going back since childhood. I managed to maintain a healthy weight through exercise etc but as I aged I felt that my bodies ability to handle sugar was decreasing, and it had significant impact on my energy levels, physical appearance and digestion.
Keto not only simplified my diet but massively improved my digestion, and helped me form more awareness of risks of sugar.
Regarding no long term studies.. its hard to believe much these days I rely on body feedback. Years ago the American diet was supposed to be healthy, look how that science turned out.
I'm glad it works for you. I'm not keto hating, I just find people advising to do it long term to be on the quacky side (there simply is no such evidence).
> Years ago the American diet was supposed to be healthy
The result of lobbying. True nutrition experts knew all along.
"Being fat" and having too much fat (or the wrong kind of fat) in the blood or brain are not equivalent. Eg people with high cholesterol can be quite slim also.
Your body can't take fat from plants and animals and directly embed it into fat calls. The metabolism of ingested fat takes much more steps than say sugar, which can be directly absorbed into fat cells and also raises insulin resistance. Sugar and refined carbohydrates are a far bigger reason for obesity than fat consumption or "greasy food".
People get fat through consuming more calories than they burn for energy during the day. There are extra but around the edges but no matter the ratio of fat to carbs to protein, if someone consumes (food or liquid) 3,000 calories a day but only burns 2,500 calories a day then a decent portion of that 500 cal difference will get stored as body fat. You could eat 0 calories of fat but if that total of carbs and protein is over your energy burn then over time you will add body fat.
I believe most people gain excess body fat through eating a little bit more than they need each day and then two or three weeks a year they eat and drink much more (holiday, Xmas, birthday etc), rather than consuming vast amounts of food day in day out of the wrong macro nutrient make up.
The calorie hypothesis isn't the most likely from all the research I've done. The calorie as a unit of measure doesn't even make much sense IMO.
A calorie is measured by burning food a specific distance away from a specific amount of water and measuring how much the water temperature rises. It's based on an assumption that the body uses all energy in the food the same, and that fire is analogous to the complex process from digestion to energy use in the cell. The calorie as a measure effectively equates the body to a coal power plant.
Anyone who tracks their calories daily for a long period of time will see that when they eat more they gain weight, when they eat less they loose weight.
Like I said above, there are other aspects that can factor but “calories in calories out” accounts for 80% of weight loss and weight gain (applying the broad brush of the 80:20 rule)
If a calorie is a calorie, would you agree that I would be just as well of eating 1800 calories of fat rather than a balanced diet? Could I stick to 1800 calories of gasoline?
We can't simply burn food and deem that an accurate analog to how the body processes and utilizes different food. Ask anyone that live(d) primarily on rabbit meat.
And to be clear, the 80:20 rule is am extremely broad and inaccurate rule of thumb that isn't useful when applied to something specific. You can't claim that calories in equals 80% of calories out because Paredo.
But it does depend on the type of foods. For example, let's take a serving of almonds listed at 160 calories. Your body may only absorb 120 (depends on the person) of those calories to be burned due to the fiber in the almonds. While foods with sugar and little fiber, you get close to 100% of the listed calories.
Sure, and that kind of thing falls into the 20% of the 80:20 rule of most things. The vast majority of people loose or gain weight based on their calorie in take / expenditure
There are exceptions, I have the APOE 4/4 variant gene which results in my metabolism not dealing with saturated fat as well, and eating saturated fat does end up raising my bad cholesterol among a bunch of other terrible side effects
perhaps not coincidentally, this variant also comes with a higher risk of Alzheimer's disease
We've probably done more harm with the similar, and also incorrect, assumption that eating more saturated fats go directly to the blood and clog arteries.
Can you point to some evidence that increased saturated fat consumption does not increase LDL? Or that there is no link between serum LDL levels and plaque build up? Or are you making a different claim?
Dr Michael Eades is a good gateway toif you're interested. He wrote a book a while ago now titled Protein Power [1], I think he is working on an update/sequel as well.
At the high level, my basic claim is that the idea that dietary saturated fat directly leads to heart attack is incorrect. The history of this claim dates back to President Eisenhower. After having a heart attack while in office he wanted to tell the public how he could avoid the same fate. Researchers cut corners to meet political targets, ignoring data that disproved their hypothesis and claimed that plaque found in cadaver arteries was made of saturated fats and that it got there due to the person's diet.
The claims weren't backed up by the studies used and we were told that this was now a known fact when it wasn't. We've spent many decades since avoiding saturated fats in favor of unsaturated fats, which are highly oxidative and have concerning side effects when run through the Krebs Cycle.
Dr Eades also has a few interesting talks on the subject when he walks through the Krebs Cycle and the difference of saturated and unsaturated fats in case that's helpful. I think [2] is one I watch years ago, though he has other similar talks on YouTube as well.
Per the Nature paper, this fat is believed to be part of an immune system response and not related to your intake or total body fat. It is also far from clear that eliminating the production or use of this fat during a microbe invasion would lead to more or less dementia down the road (a good reminder that clinical trials are useful and also risky). This work shows a very refreshing and solid hypothesis and lots of people work on it, but it’s not reason to start changing diets.
Yeah, I almost wish I hadn’t asked given the comments. Really points at an interesting mechanism though. Hopefully this means some kind of preventative or even treatment is possible.
More likely we'll need to start paying attention to sugar intake. I've heard researchers call Alzheimer as "type 3 diabetes". This makes total sense to me since sugar consumption is a big driver of body fat accumalation.
Or you know the article on highly processed foods that made the home page the other day: https://news.ycombinator.com/item?id=39746915 ... Could the seed oils thing be a bit much? Sure. Could canola and its use be part of the problem as a highly processed food. Maybe. Is any one doing the research? None of us know...
Why people have some aversion to seed oils, a highly processed food: "Canola oil is made at a processing facility by slightly heating and then crushing the seed.[34] Almost all commercial canola oil is then extracted using hexane solvent, which is recovered at the end of processing. Finally, the canola oil is refined using water precipitation and organic acid to remove gums and free fatty acids, filtering to remove color, and deodorizing using steam distillation. Sometimes the oil is also bleached for a lighter color." https://en.wikipedia.org/wiki/Rapeseed_oil
A lot of things don't when you describe them in such detailed, clinical ways.
You can also buy (just like you can with quality olive oils) cold pressed canola which is manufactured simply by crushing the seed. The seed oil folks would have it that this is no better, AFAICT.
Having a conversation in a very public place can certainly end up promoting ideas
Take a popular piece of media, inject a conversation about fringe ideas with some crackpot that would have very limited reach otherwise. This gives very high visibility to very fringe ideas.
Giving undue weight to fringe viewpoints is promoting those viewpoints.
Promotion: "activity that supports or provides active encouragement for the furtherance of a cause"
Simply discussing an idea, even giving undue weight, is not promotion.
Conflating the two is dangerous as it provides justification for censorship. The free exchange of ideas and information is the only way a democracy can survive.
If the idea is bad or wrong, it will be debated and ultimately defeated in the marketplace of ideas.
> If the idea is bad or wrong, it will be debated and ultimately defeated in the marketplace of ideas.
This implies the existence of a marketplace of ideas where people can freely trade thoughts.
It was not the case in the past (i.e. you go to jail or are excommunicated for dissent), and it is increasingly not the case in the modern world (i.e. the algorithm is telling you what they want you to hear).
You cannot have a free marketplace of ideas in a world where the forums these ideas are being discussed have an incentive of causing conflict and keeping you engaged.
This is not an attack on you or anything, I just think we should all be more aware that everything we hear today has an agenda hidden behind it, which is malicious more often than honest.
> If the idea is bad or wrong, it will be debated and ultimately defeated in the marketplace of ideas.
Sure, and I have a bridge to sell you.
The marketplace of ideas is a myth predicated on the willingness of participants to promote and evaluate their ideas honestly, and due to that honesty to stop promoting such ideas when they are shown to be wrong or inadequate. It requires participants to even be interested in how good their ideas are and be open to discussing them and changing views if these ideas are found wanting.
Observing real life, what we have is people flooding the zone with unmitigated faeces, either for profit or idealogical motives. They are uninterested in whether these ideas are true, good or even useful, whether there are 'better' ideas, and they often dominate through volume and repetition. Tribal cohesion ensures the spread of ideas as much or more than honest debate.
The marketplace of ideas is dead, if it ever really existed. A fairytale for children.
> If the idea is bad or wrong, it will be debated and ultimately defeated in the marketplace of ideas.
And saying "Rogan promoted quack doctor making nonscientific claims again and thus the idea spread" is necessary part of that process. Too many people think that "marketplace of ideas" means "I get to spread lies and other side can not say that I am a liar".
When you have a massive megaphone, your choices have impact at scale.
So "having a conversation" is functionally identical to promoting, as is "just asking questions" if you're Tucker Carlson, or "exercising your free speech" if you're Elon Musk amplifying easily disproven talking points about immigration, etc.
The problem with Joe Rogan is that he's not smart and his audience is not smart. He's a pseudo-intellectual. He gifts crackpots an enormous audience of gullible people. He lends credibility to them with softball interviews devoid of critical analysis. He's spoon-feeding suckers what they want to hear. He couches it all in a thin veneer of balanced reporting and barstool philosophizing, under the guise of fairness, but he's elevating ideas that have no business being elevated. It's even worse than outright promotion.
If he’s not smart why’s he so successful. Why did he have a job hosting fear factor. A job hosting UFC. A job being a stand up comic. He’s also short - which I thought meant the cards are stacked against you? He also has a black belt. They don’t give those out. He currently has the biggest, arguably most successful podcast of all time.
But he’s not smart right? Years and years of winning but he’s not smart.
You are capable of thinking and you are smart but that doesn’t mean you are right. Don’t conflate the two
How can one conclude he isn’t smart? Are you politically charged against him. Has he wronged you or your loved ones? Would you say he was not ‘smart’ if you had write a report for a 3 Letter agency?
You can get to the top once if you’re lucky. But if you keep ending up there…
I’m on the same page as you regarding the anti-“saturated animal fats” crowd, but I actually don’t mind them. My animal-based cooking oil spend would be a lot higher if everyone stopped buying plant-based oils.
Far fewer people can downvote than can upvote, though. You generally have to post something a little more evocative than "slightly non-consensus".
But even taking your argument at face value, even if you take pride in having annoyed people for having expressed an opinion you find valuable, it's boring and petulant and ugly to then brag about it. Surely you can't be arguing for that kind of behavior.
Yeah once it becomes clear you’re in the kind of forum I am talking about the satisfaction doesn’t come from the presumed effect on others but the signal that you actually may have said something important.
> The matched subjects who ate meat (including poultry and fish) were more than twice as likely to become demented as their vegetarian counterparts (relative risk 2.18, p = 0.065) and the discrepancy was further widened (relative risk 2.99, p = 0.048) when past meat consumption was taken into account
> While we did not find statistically significant evidence to support an association of consuming relatively more plant- and fewer animal-based foods with the risk of dementia, our HR of 0.93 (95% CI: 0.86–1.01) for the hPDI cannot rule out a subtle beneficial effect of healthy plant-based eating on the brain.
"cannot rule out a subtle effect". Otherwise not statistically significant. Great.
I get migraines from plant and seed oils, my thought on this is, that they're kinda rancid. You can't get them fresh enough in the supermarket. The one oil I didn't get strong migraine from was fresh olive oil.
You're also looking at a time-window of 1-5 days, depending on your metabolism.
I'm not an expert, but I've been reading lately that the plaque vector has been so well studied because it's the only direction that has been able to get funding. Conspiracy aside, this seems like a more common thing now - someone has a little bit of possible progress, and no one will give any money to any other thing, often at our detriment.
No. The brain is about 60% fat. It’s not about having fat in your brain, it’s about having AND amyloid plaques AND fat in specific locations AND probably a whole host of other factors.
Does eating healthy food instead of highly saturated fats provide health benefits? Yes. Does having too low levels of body fat lead to health problems? Also yes.
> All around the world, there are labs pulling late nights trying to figure out how to drug this.
I dont know why, but I've been under the impression for years that it was fat build-up. I remember I saw images of alzheimer brains with clogged arteries.
Sure drugging would be nice, but why not figure out what in our modern diet and habits is responsible for this? Why not tell people that the insane amount of oils/fats we consume (in comparison to our primate animal relatives) is killing us and/or making us sick?
Folks have had different sorts of dementia for centuries, though. We simply didn't have the knowledge nor the tools to differentiate one from another and tended to call things by different names.
Not as many people die young now, either, so more folks are actually getting diseases that present in old age. You can't observe many old folks if there aren't any, and you won't notice as many diseases that hit mostly women if a lot of women die in childbirth.
And a note: Food of yesteryear wasn't really better/healthier than now. It was different, more risky, and for most folks, was just made of whatever they happen to have and not very varied.
It's not a modern disease, it simply has exploded in occurrence. This explosion is modern. This is likely due to our diet. There's a book called "the blue zones" that dives into healthy diets and lifestyles that have historically helped people grow old.
> Food of yesteryear wasn't really better/healthier than now.
Not all food was. But Okinawans do pretty well for a long, long time.
"Back when Alzheimer's disease was first identified by Alois Alzheimer, he noted that in addition to the plaques and tau buildup, there was also a buildup of fat droplets in brain cells. Since that time, little effort has been made to determine whether they might be the cause of the disease."
I'm not medical researcher but I find this statement incredible. It's over 120 years since Alzheimer did this work. Why the fuck is it just becoming a big deal now? Surely this info was in the literature back then so why was it ignored and not followed up decades ago?
With Alzheimer's we've witnessed over many decades seemingly any number research leads that have gotten nowhere and have ended up as dead ends yet it's only now that we're following up an ancient lead that should have been researched many decades ago.
As a lay onlooker, such revelations only further shake my faith in medical research. Every week there are many high profile PR announcements and research papers with the promise of major medical breakthroughs yet the vast percentage come to naught, or what's reported is such a miniscule incremental step towards actual medical treatment that an effective treatment might not be realized for decades, if at all.
Why is medical research allowed to be hyped like this? Much of the reason why the public's faith and trust in science is at an all-time low is the undeliverable hype from medical research. After decades of hyped promises about cures and treatments which aren't delivered or that fall short of the promise people no longer believe or researchers. People are just fed up with promises that aren't delivered.
It's not only research into Alzheimer's that the public feels as having fallen short, it's almost the full gamut. Take cancer research for instance, it's been grossly over hyped for many decades.
Let me explain:
I recall as a child in the 195Os before starting school, my mother took me to a movie matinee, there was a main feature and newsreels. I clearly remember two of the newsreel stories, one was on rockets and warfare and the other about cancer research. After the matinee I ask my mother about cancer and so as not to worry me she said "it's a rare disease you'll never have to worry about."
A couple of years later when I was about 7 or 8, we were on holidays at my grandmother's place and I saw that her next-door neighbor was quite ill and my grandmother told me she was dying of cancer. That's when I found out my mother had lied to me, and even at that age I was shocked and upset that she'd done so.
I've always remembered those incidents so ever since I've taken note of articles and reports about cancer in newspapers, popular science mags such as SciAm, New Scientist, and in professional journals such as Science and Nature, etc., and whilst I've not taken count, there has been many thousands of them over those many decades. Almost every one of these reports has made claims about 'promising research' or a 'possible cure' for cancer.
Let's look at the facts, the vast majority of those reports and research papers has come to naught! As a guesstimate, I'd reckon that if the research in 0.1% of them had actually been positive and even partially successful and led to actual treatment that was effective then cancer would either be cured by now or at least a very manageable disease. Well, as we all know, that hasn't happened by a long measure. Yes, some progress has been made but it's a drop in the ocean, as about one third of the population still dies of cancer. No matter how one massages the stats that's not success.
Fact is, whether it's cancer, Alzheimer's, drug research or other medical research, there's a never ending stream of reports that promise much, much more than they ever deliver.
Another form of disingenuous hype in PR releases and medical research papers is that the title and abstract are often over hyped. Words like 'significant' or 'large improvements' are used when referring to some procedure or outcome. A full reading of the text shows the actual figure as low as 5% or so. In my opinion that verges on scientific fraud. It won't fool any researcher who reads the paper but it will a newspaper editor who only reads the title and abstract (he/she likely won't understand the body text anyway). Right, the hype goes straight through to and misleads the public.
It's time the medical industry
took away the rose-colored glasses and stopped the hype and bullshit about medical research. It's time medical researchers stopped publishing for the sake of it, or for career advancement, or to obtain increased funding.
Publishing substandard research or research that's going to end up a dead end, or can't result in treatments for decades is not only unethical but it's unfair on those who are ill, it gives false hopes that come to nothing.
Finally, the quote above backs up what many of us lay people have thought for decades, which is that much medical research is either uncoordinated and or badly misdirected.
Medicine is hard. Unlike, say, physics, you cannot experiment on people except in very specific circumstances. Rats, mice, chimps etc. aren't people, so researchers work on "animal models", but in many cases you're just giving lab rats an Alzheimer-like disease and curing them of an Alzheimer-like disease, which is nothing like curing actual Alzheimer in actual humans. (Yes, animal models often involve inducing a "fake" disease in animals — testing treatments for psoriasis involve giving imiquimod to genetically modified rats, for example. This activates some of the same immune pathways, but it ain't psoriasis.) Alzheimer is particularly hard because we can't really study what's going on in the brain while people are alive, and when they're dead and can be dissected, we can only see the remnants of that activity.
If science has been hyped up too much, I think we have the media to blame, not scientists. Media turns very early, pre-clinical, merely promising research into headlines like "Could This Promising New Discovery Be a Cure For X?" Meanwhile, tons of progress is being made; you probably just don't notice it. Monoclonal antibodies (like Humira) for autoimmune disorders like Crohn's, ulcerative colitis, arthritis, psoriasis, etc. have been complete game changers for people with autoimmune illnesses that involve the overexpression of certain cytokines like TNF. Same with JAK inhibitors and PDE4 inhibitors. There are tons of things with good treatments now, but you probably don't hear about them because it's not that sexy and therefore not covered by media. As for cancer, it's not a single, monolithic disease, but a whole lot of different ones (melanoma, lymphoma, leukemia etc. all have different causes). Huge leaps have been made with some (like melanoma), and for many cancers a lot more people are surviving than the 1950s when chemotherapy was in its infancy (methotrexate, the first chemo agent, was discovered in the late 40s) and most attempts to treat cancer involved surgery.
There's a really interesting paradox where, compared to healthy adults, intramuscular lipid droplet storage near mitochondria is increased in:
1) People with obesity
2) People with type 2 diabetes
3) People who do endurance exercise
Even though #3 is highly protective against #1 and #2. The best explanation I've seen is that the important difference is why the lipid droplets are being deposited [1]
If I am rich enough to have a down payment for a Bay Area house I’ll be tremendously in debt. But that wouldn’t put me in the same boat as someone with oodles of credit card debt.
I’m guessing in endurance athletes it’s there because it’s about to be used. In the obese it’s there because they’re running out of places to put fat.
Right - but even then, if a super fit endurance athlete stops exercising, they don't immediately become diabetic. The upstream cause (what biochemical stimulus is driving the fat deposition?) is probably where the key insight lies.
If I recall correctly there were some studies that actually showed endurance runners have higher type 2 diabetes risk. And the suspect cause was the diet, specifically the carb loading practice and the abuse of high sugar products during the activity. So the three categories may actually share the same baseline, insulin resistance. It was quite controversial when it emerged (see Tim Noakes story), not sure if it's more accepted these days.
Well yeah. You’re measuring the output to a multi-variate function. There should be no expectation that this one output drives other occasionally correlated outputs to other functions.
Doesn’t diabetes mean that the cells has to extract more energy from those lipid droplets instead of from the glucose pathway impacted by the diabetes? Thus in the cases of 2 and 3 those droplets is an additional significant source of energy.
I also think that in the case of 1 the cells may be starving on glucose pathways (pre-diabetes), similar to 3 during the exercise and to 2 in regular situation, and that causes the over-eating while all that food doesn’t feed the cells because of the original issue and thus goes into fat for storage and into the lipid droplets way of feeding the cells to workaround the original glucose pathway issue.
sleep problems (like sleep apnea) affect insulin resistance and weight gain. This goes with other evidence that not sleeping correlates with alzheimers. So the fat buildup correlates in a different way.
> A recent report showed that innate immune triggers (for example, Escherichia coli and Salmonella) induce LD formation in peripheral macrophages as part of an evolutionarily conserved antimicrobial defence in which LDs coated with antimicrobial proteins, such as cathelicidin (CAMP), kill bacteria8. We speculate that a similar programme can be triggered in human microglia exposed to Aβ, LPS and other innate immune activators and disrupt brain homeostasis. Protein aggregates found in other neurodegenerative diseases may trigger the LDAM state. For example, alpha-synuclein binding to TLR2 and TLR5 induces microglial NLRP3 inflammasome activation, which is a shared signature seen in LDAM36. Given that we recently identified that LDAM are abundant in the ageing mouse brain, LDAMs may also be triggered by hitherto unknown protein aggregates and innate immune activators which accumulate with age. Interestingly, the most enriched pathway in human LD-containing iMGs is ‘cellular senescence’, similar to lipid-laden ‘foamy macrophages’ in atherosclerosis which have a senescent phenotype and are drivers of pathology37. Perhaps in the natural ageing of various organs, LD-accumulating tissue-resident macrophages represent a general class of senescent myeloid cells which are drivers of tissue inflammation.
It could be a lot of things, and there might be multiple pathways that lead to this state.
Many studies show that berberine can significantly lower blood sugar levels in people with type 2 diabetes ( 8 ). It seems to work via multiple mechanisms and may help ( 9 , 10 ): decrease insulin resistance, making the blood sugar-lowering hormone insulin more effective.
I wouldn't call it metabolic if parts were missing or otherwise had communication malfunctions without any issue in acquiring/using energy itself.
But I'm sure lots of things go wrong when the brain doesn't get the energy it needs and is forced to compensate.
Even more to the point: If something generalizes without a qualifier like most/many/some/can be, there might be an implicit "all/every" (or careless communication) and that makes it all suspect.
Hrmmmmm the controls for the first 2 graphs appear to be the same and they're called out for it [0].
But it could very well be that they're supposed to be the same? Authors may just need to better highlight why the same control is allowed to be use for comparing 2 different result sets.
I suggest changing the title to something like: "Link Between Brain Cell Fat and Alzheimer’s Could Pave the Way for Innovative Treatments". Also here is the original Nature journal reference that can be linked to instead: https://www.nature.com/articles/s41586-024-07185-7
Fasting seems like a solution because in the fasted state your body doesn't need to produce insulin. Your body needs insulin to push fat into cells. Your pancreas gets a break, and perhaps sensitivity improves when you go on an extended insulin-free holiday.
I'm no biologist but it's my understanding that insulin causes cells take up glucose, not fats. And I don't see anyone suggesting insulin or the pancreas is involved in any of this. So what does the pancreas have to do with Alzheimers?
"Although many factors affect fat cells, the hormone insulin exerts dominant anabolic control. Insulin decreases the circulating concentration of all major metabolic fuels by stimulating glucose uptake into tissues, suppressing release of fatty acids from adipose tissue, inhibiting production of ketones in the liver, and promoting fat and glycogen deposition."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082688/
It depends what cells we're talking about. Thanks to insulin, glucose can be stored in the liver and muscle tissues as glycogen. In folks with poor insulin sensitivity these cells do not respond as effectively to insulin, and their uptake and storage is reduced, leaving more glucose in the bloodstream. In the obese, it's also likely the liver and muscle tissue glycogen stores are near max capacity. In this case insulin facilitates the uptake of glucose into adipose (fat) tissue through a process known as lipogenesis. When I wrote "insulin pushes fat into cells" that's what I meant.
The insulin protein promotes glucose (not fats) uptake into the muscles (~75%), liver (~15%), and other tissue (~10%) to aggressively lower blood sugar levels back to a total circulating amount of ~5g.
In the obese, glucose is preferentially directed to adipose tissue for storage as fat. This is due to both insulin resistance, and to the limited storage capacity in muscles and the liver for glucose in the form of glycogen. I was writing colloquially and intentionally left out details like lipogenesis, which in retrospect probably wasn't a great idea.
Except there's literally a result out this week linking fasting (specifically 16+ hour intermittent fasting) with a 91% increase in cardiovascular disease deaths, which if it holds up would utterly swamp any incremental improvements to alzheimers risk.
No free lunch in personal health decisions, alas. Really the only good advice is stick to well-established science, be healthy in general, avoid internet advice, and don't sweat the small stuff.
The results unfortunately are too vague to support that interpretation.
There was no causal linkage because they couldn't determine why people were fasting: suppressed appetite due to illness, suppressed appetite due to being a smoker (which is very common), skipping meals due to poverty.
It also found that while cardiovascular deaths increased by 91% overall deaths were completely unchanged...which is a bit difficult to reconcile.
> The results unfortunately are too vague to support that interpretation.
I think you completely missed the point. Sure, it's a new result and being an outlier needs to be treated with care (which I believe I said). It's still a more rigorous finding of health effect than anything in the grandparent's comment about how you should fast to avoid Alzheimer's. Ergo advice like that is bad.
As per the Nature paper, this is an immune system mechanism with these particular “fat” particles presumed to help fend off an invading microbe. So no, it doesn’t matter how much fat or not you have to begin with as you cannot as easily reduce the immune system ability to do its work, and even if you did somehow manage to stop this particular immune response it is far from clear if you would get more or less dementia as a result.
In addition to weight loss, fasting can reduce activated microglia in the brain which could play some part in this, as microglia was mentioned in the study.
You should word this better. But I think Fasting helps because of autophagy, I don't think these are exactly related. I thought autophagy takes out proteins too.
GLP-1s definitely cross the blood-brain barrier - work by affecting the GABAergic CNS and making you not hungry so you stop eating and lose weight. They don't independently do anything to make you slimmer. Basically what you're suggesting is people lose weight, which, I agree.
First it would be good to know if you have genetic predisposition. I think mosts comercial DNA tests available test for APOE4 variations.
Second I would read on the research of Dr. Dale Bredesen. He has been studying how to map all the underlying factors that can lead to Alzheimer and how to test/treat markers that are associated with the disease.
According to him Alzheimer's disease is like a roof full of holes. You need to test and treat each individual hole to make sure it's not leaking.
This is good advice. Be aware that while APOE variants are the most well known and common causes of a genetic predisposition to Alzheimer’s, there are several others, including some 100% penetrance, dominant gene mutations that cause it. Unfortunately I have very significant experience with one of these. Generally it would be common enough in your family (roughly 50% of people getting it), that you’d have reason to suspect one of these gene mutations.
Even if Dr Bredesen is misdiagnosing the causes of Alzheimer's, his recommendations are still just the basics of healthy living. Like exercise, getting enough sleep, good dental hygiene, etc.
> My aunt started showing symptoms of Alzheimer's. My grandfather passed from it. Is there any thing to do in order to prevent or delay the disease?
Similar to ASCVD it takes decades to manifest and lots of the traditionally healthy lifestyle activities help delay or prevent it (diet, sleep, exercise). Unfortunately once someone is showing symptoms it's very late in the game.
I try to follow that lifestyle and push my mom and dad to it, they both workout and exercise. I don't think they work their brain that much though. I've been pushing them to take a course or something like that.
There was a paper years ago saying in some Autopsies they found signs of Alzheimer's being 'repaired' in people who stayed mentally active. Anecdotally the people in my family that had it stopped engaging their brains in deep ways before it happened. Surely that's no silver bullet or everyone would do it, but thought I'd share
As the study points out, we don't even know the mechanism that causes Alzheimer's. Anyone claiming to be able to sway your odds one way or the other is flat out lying because they don't know either.
She is a media personality first and foremost, peddling a book, speaking circuit, private trainings, etc for her fad diet. As for her credentials, remember Dr. Oz was a doctor too before he saw dollar signs.
Another theory is that Alzheimer's is caused by the brain becoming insulin resistant. Some researchers even argue that Alzheimer's should be called type 3 diabetes.
Fatty cell infiltration occurs when the stem cell niches don't fully convert into its end cell both Glia and Neuron. This would then indicate that TZDs can be effective in promoting the correct differentiation
Is this correlated with obesity demographics, i.e. Japan/US/EU statistics? I can’t find reliable numbers per country, most sources conflate the different types into dementia.
The latest approved Alzheimer’s drug, Lecanemab, shows a cognitive benefit. It’s modest, but there are already successors in the pipeline that have shown promise (e.g. donanemab). They’re baby steps, not at all cures, and have significant side effects, but “everything we try doesn’t work at all” isn’t really true the way it was even a few years ago.
I couldn't find any example of him claiming anything related to fat accumulation in the brain. Could you link to an example or copy/paste a quote that you're referring to?
That's not a broken clock, that's a clock that's set to the wrong time. Unless it remains 10 minutes behind, even when you set it 10 minutes forward, which would be a great prank gift.
