Root cause of Alzheimer's may be fat buildup in brain cells, research suggests
medicalxpress.com
medicalxpress.com
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 :)
While the inverse occasionally has been true, generally people who I consider in good shape appear to eat less, and less greasy food.
So while there might be exceptions it seems to be a damn good rule of thumb to me.
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.
The danger is two fold
1. People don't eat fatty foods which have solid evidence for their benefits (e.g. Virgin olive oil)
2. People substitute the lack of fats with sugar, which I believe (not an expert) has a lot literature linking it with obesity
Your question isn't refuting OPs claim: the people you are observing to be fat are fat because of their carb/sugar intake, not fat.
i.e. if you just fed someone large amounts of protein and fat they would be lean; it is the sugar and carbs that make them fat.
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.
The inventor of diet famously lost a contest for being too lean.
You cannot explain it otherwise (without showing a undiscoverd way humans can convert carbs into fat).
> i.e. if you just fed someone large amounts of protein and fat they would be lean; it is the sugar and carbs that make them fat.
This is dangerous. It may work on the short term, but it is very dangerous on the long run.
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.
As opposed to being reliably obese? What's your baseline? I recently checked the average weight of men and women and I am honestly shocked.
The risks of obesity are well known. Also, you do not get obese by lack of a keto diet. One usually gets there with a rubbish diet.
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.
> Years ago the American diet was supposed to be healthy
The result of lobbying. True nutrition experts knew all along.
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."
https://courses.lumenlearning.com/suny-ap2/chapter/lipid-met...
The conclusion being: "Humans are great at lipogenesis. That's how we store excess energy."
> 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.
From:
https://www.sciencedirect.com/topics/agricultural-and-biolog...
Believe what you will. "It is said" wrt sumo fighters does not sound very scientific.
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.
[0]https://my.clevelandclinic.org/health/diseases/22658-diabuli...
Plants have carbs in starch. Mammals evolved away from starch to store and use triglycerides.
During fasting, the human body is able to survive for months without food.
Thus months of lipid metabolism
Hibernation?
For short term glucose storage is preferred by mammals bodies that i know of.
A large amount of protein would make them fat - experiments have shown that about 8% of ingested protein gets converted to glucose in the liver:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636610/
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.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.
Homeostasis is amazing.
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.
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.
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.
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)
That is simply not true for people that are already obese.
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.
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.
[1] https://proteinpower.com/ [2] https://www.youtube.com/watch?v=7MTNJNAZPiw
perhaps not coincidentally, this variant also comes with a higher risk of Alzheimer's disease
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 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!
I also have Alzheimer’s in the family and this hypercortisolism discussion feels familiar to me.
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.
> Food of yesteryear wasn't really better/healthier than now.
Not all food was. But Okinawans do pretty well for a long, long time.
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.
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.
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.
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?
I ask because one of the hallmarks of insulin resistance is the presence of lipid droplets in close proximity to mitochondria [0].
> 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.
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]
[1] https://link.springer.com/article/10.1007/s00424-005-1509-0
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.
I've even had some people tell me I can't be diabetic because I don't have much, if any, extra fat.
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.
Highly recommend. I think is what you are looking for.
“Mental disorders are metabolic disorders of the brain”
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.
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.
The article's peer reviews (on PubPeer) list a few analytic issues that call the findings into question:
https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D4...
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.
[0] https://pubpeer.com/publications/59F515775D10D854ABB7F4B31D4...
Edit: Oversimplified, but: Less, calories, less fat? Excess calories, more fat?
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.
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.
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.
It seems counterintuitive, and opposite of what is promoted.
I'll have to check it out more.
But from AHA, this is enough of a dramatic result to at least follow up on.
8-hour time-restricted eating linked to a 91% higher risk of cardiovascular death
https://newsroom.heart.org/news/8-hour-time-restricted-eatin...
Have you looked?
"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/
Or this one: https://www.nih.gov/news-events/news-releases/nih-study-show...
There are many many other studies and articles, as the insulin-fat storage connection is very well documented
There is also research showing improvement in Alzheimer's disease symptoms. [2]
[1] https://pubmed.ncbi.nlm.nih.gov/11931352/
[2] https://www.sciencedirect.com/science/article/pii/S221287782...
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.
My dad passed from dementia. That’s the best diagnosis we got. He wouldn’t go in under an MRI machine.
He had horrible , infected teeth. They were badly infected.
There’s linkage of poor oral hygiene and Alzheimer’s.
https://www.health.harvard.edu/mind-and-mood/good-oral-healt...
If I had know this sooner, I would have pushed harder for him to have those bad teeth extracted and had him start using a water pik.
I worry that what he died of was preventable.
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.
There is also research showing improvement in Alzheimer's disease symptoms. [2]
[1] https://pubmed.ncbi.nlm.nih.gov/11931352/
[2] https://www.sciencedirect.com/science/article/pii/S221287782...
Remember that only 100 years ago you could die from an infection.