Not longevity in the general sense, but in the cardiac disease and mortality sense, yes, it's pretty firmly established. It's also an area that attracts a lot of quackery, is somewhat hard to study (for the normal reasons that a lot of nutrition stuff is hard to study).
And it's an area where there is legitimate nuance: we only measure LDL-C partly because it's easy and available, there are other ways of looking at blood lipid particles we could be measuring that might be more effective (like ApoB), it interacts with other things like insulin, inflammation, metabolic health, blood pressure.
But all that said, the case for high LDL being bad for heart attacks and strokes is very strong.
To me the strongest short list of evidence is simply:
- People who have familial hypercholesterolemia, from different genetic causes/pathways, all have massively increased heart disease at young ages.
- People who naturally have a disabled PCSK9 gene have extremely low LDL levels, where PCSK9 is directly involved in the liver's ability to clear LDL from blood, and these people also have incredibly low incidence of heart disease.
- Modifying cholesterol levels via PCSK9 or statins both have very strong evidence that they work on people who have heart disease, we have many RCT involving people who have already had one heart attack, and they have clear dose response curves: the amount of LDL reduction is directly proportional to risk reduction. We have less clear evidence on healthy people and from diet but those people are just a lot harder to study.
It's true that not everyone with high LDL develops plaque and we don't know why, but I feel a lot of "lipid hypothesis skeptics" tend to swim around in the gray areas and just don't interact with the more smoking gun bits of evidence that have to be explained away if you are going to say that LDL has no effect.
I actually just responded with almost the exact opposite, but maybe I'm the "lipid hypothesis skeptic".
Seeing as the threat is calcium build-up in the arteries, and because cholesterol is a vital component of health, I believe that if you are in good health, and don't have a history of heart-disease, or have diabetes or other auto-immune disease which increases risk of atherosclerosis, lowering cholesterols is an in direct measure.
It's about understanding your personal risk and making decisions based on that.
I actually don't think your response is the exact opposite, but you touch on some of the skeptic stuff, so I'll respond to here:
First of all, I agree with your points that you should consider the individual. My long term interest in this is also from being a very fit, low blood pressure, metabolically healthy person who always had at least somewhat elevated LDL (sometimes very elevated) that doctors would flag.
PCSK9 people are as close to a natural experiment on the effects of life time low LDL as you will get and they get near total protection, even when they have no other risk factors. People like smokers, hypertensives and diabetes have ~90% less than other high risk people, but people without any of those factors also have significantly less heart disease. People with two broken PCSK9 genes have close to zero LDL and have noticeably completely plaque free arteries as adults. I do think this does pretty fatal damage to the theory that you must have some other health issue for LDL to be bad.
It's very likely that "LDL-C" the lab measurement isn't as good as measuring ApoB, but for most people, they are concordant. And ApoB is a different way of looking at low density lipids, by particle count instead of weight. Dietary stuff like the fats in the article that lowers LDL measurements typically also lowers ApoB in most people.
So, in part, I agree that more precise biomarkers can help adjust individual risk. But most people are concordant. And the evidence that the underlying "low density lipids", no matter how you measure them, are causally part of the disease process is very strong.
> People with two broken PCSK9 genes have close to zero LDL and have noticeably completely plaque free arteries as adults. I do think this does pretty fatal damage to the theory that you must have some other health issue for LDL to be bad.
i'm not sure i follow this extrapolation from low-ldl individuals to any direct statement about causes and effects at higher ldl levels.
if there was, for instance, some thought-harmless virus endemic to a large portion of the population which somehow caused plaque buildup but only at sufficiently high ldl levels, people with naturally low levels their entire lives would still have plaque free arteries and we would still, as we do, see a broader range of plaque buildup among people with high levels. how do you propose to distinguish this hypothetical (and admittedly most likely biologically incoherent) explanation from yours by only looking at people with naturally low levels?
your assertion that such individuals are an excellent approximation to an experiment on the arterial health effects of lifetime low ldl seems reasonable enough, but you then appear to draw unfounded conclusions about the nature of potential inverse effects at higher ldl levels.
The point I was making re double variants having even more apparent protection is simply that these people continue the dose response curve you expect to see all the way to the extreme low end. Single variant people have massive protection, double variant people have essentially 100%.
You are correct that it doesn't rule out lipids + unknown additional factor(s). However: If there is a mystery factor, it must be close to universal. We know from autopsy studies of non-cardiac deaths that fatty streaks are present in virtually all children and that by 30 most people have advanced fibrous plaques (including soft plaque invisible to calcium score tests). The double variant people don't. So LDL is at minimum a necessary, limiting factor.
It also doesn't exclude that there is some more specific subset of the low density lipids that cause problems (this is what switching to ApoB testing is supposed to get at). Which is actually where we are at in the first place with LDL-C measurement being a refinement over previously looking at total cholesterol.
Where I'm at in the Sierra, March is typically very close to as snowy as Dec/Jan/Feb and the snowpack is still increasing, not decreasing. Late March is typically the peak depth. March avg snowfall is 62", this year we got 1", the driest March on record, on top of it being incredibly warm.
As a naive tourist, I did not know this. I drove up to Sequoia National Park in March 2011 hoping to camp. The roads were plowed, with eight feet tall snow on either side of the road. I drove up to a visitor center and asked where to camp. The park ranger said I could camp anywhere I wanted. Maybe he assumed I knew what I was doing. But I did not. After walking around the parking lot for a bit, with nowhere else to go, I drove out.
European cheese producers have their own costly methods of managing raw milk cheese safety. They have much more surveillance of the entire process, like rapid testing of milk for STEC (the microbe involved in this outbreak) and adding bioprotective cultures during milk production. In France there is an extensive monitoring/alert system. They aren't just YOLO-ing it.
The earliest neural network work on perceptrons was done in an applied contract lab for the US Navy, it was not done in an academic setting.
Backpropagation has been reinvented multiple times, because it is a basic application of the chain rule. The earliest recognizable usage of it is in control theory at NASA during the Apollo program.
It's a mistake to be dismissive of academic work which has been very important, but it's equally a mistake to think that academia is the sole source of foundational work.
Most Tahoe buildings are not A-frames, 500-800" snow years are big years, not average, and also those are resort numbers, not towns where more houses are. Modern buildings in Tahoe are engineered to hold very high snow loads, typically have a lot of snow on the roof, you need to do snow removal as needed.
I live in Mammoth where the town is significantly snowier than say Truckee or lake level Tahoe. The grocery store is open and operating normally no matter how snowy it is. Including the 22/23 winter when 695" fell in town. Lots of buildings did collapse that year though and snow removal was a constant struggle.
But A-frames or other very angled roofs are not typical here, roofs have to handle 300 lbs/sq foot, and there are requirements for where a roof is allowed to shed to. Typically they will angle in one direction to control where shedding happens. Keeping the snow on the roof also provides insulation, in a typical snow year we may do basically no removal and just have a blanket of snow on the roof the whole winter.
When I did strength sports and would eat ~180g protein a day (which for me was 1.8g/100kg), I ate a lot less meat than you would think, I was carefully tracking all my food for a while and you have to count the whole diet.
In that study they eat > 1.2g protein/kg body weight, but 43% of that is "plant sources", meaning grains, legumes, fruits and vegetables. Like one serving of oatmeal is 6g, things you don't think of as "protein" add up and you have to count them. The athletes in that study are Dutch and 19% of their protein intake came from bread.
But what always happens with protein recommendations is that they say "x grams protein/kg bodyweight" but people hear "protein is meat, you are telling me to eat x grams/kg bodyweight of meat." Very few people ever look closely enough at their diet to develop an intuitive sense for counting macros.
Yes, but the standards aren't based on "the best protein to absorb", they are based on whole diet consumption. Studies like the one I linked to are where the recommendations come from. It is a misunderstanding to read a recommendation for 1.2g/kg (or whatever) as saying that the 1.2g is supposed to all be meat quality protein. It's supposed to be the protein in your total mixed diet.
Your diet contains many sources of protein lower quality than beans (as in the linked study with high level Dutch athletes getting 19% of their protein from bread), you do need to count those. They do add up and if you don't, you end up assuming you need way more protein than you do.
but then how do you know how much protein you should eat ?
if I'm eating bread, pasta and other cereals, I may exceed the 1.2g/kg recommendations but the PDCAAS (Protein Digestibility-Corrected Amino Acid Score) of these would make it in truth closer to 0.6g/kg.
Someone else eating mostly meat would get in total 1.2g/kg protein but also 1.2g/kg when PDCAAS is accounted for.
Maybe it's to simplify the calculation to the average user but it feels misleading, you can't know for sure the proportion of cereals in somebody diet.
Well, that's exactly the problem with focusing too hard on one macro nutrient recommendation out of context of other balanced diet recommendations.
Adding lean meat, dairy, eggs to protein poor diets is good, I love all of those things. Trying to hit a high protein target and understanding this to mean having to eat all or mostly meat is simply over correcting in a different direction.
And meat isn't a perfect PDCAAS! Beef is 0.92 close to soy at 0.91. Milk, eggs, soy protein (isolate), whey are 1. Beans are 0.75.
There's even more nuance, beans are partly lower because they are low in methionine, the essential amino acid that adults needs far less of than any other amino acid and that you don't need more of. In the context of a whole diet, it's not 92% of every gram for beef and 75% of every gram for beans, it doesn't work that way.
Relatively small servings of animal foods add up to a lot of protein, like some other comment was freaking out about needing to eat 4 hamburgers or a 16 oz steak to hit the (very modest) goal of 90g in a day. But something like, 1 egg + 1 can tuna + 1 serving Greek yogurt == 42g, is already at half the goal, much of the rest of it will fill out just fine from a balanced set of other non-empty calorie sources.
It's sort of an RNN, but it's also basically a transformer with shared layer weights. Each step is equivalent to one transformer layer, the computation for n steps is the same as the computation for a transformer with n layers.
The notion of context window applies to the sequence, it doesn't really affect that, each iteration sees and attends over the whole sequence.
Thanks, this was helpful! Reading the seminal paper[0] on Universal Transformers also gave some insights:
> UTs combine the parallelizability and global receptive field of feed-forward sequence models like the Transformer with the recurrent inductive bias of RNNs.
Very interesting, it seems to be an “old” architecture that is only now being leveraged to a promising extent. Curious what made it an active area (with the works of Samsung and Sapient and now this one), perhaps diminishing returns on regular transformers?
And it's an area where there is legitimate nuance: we only measure LDL-C partly because it's easy and available, there are other ways of looking at blood lipid particles we could be measuring that might be more effective (like ApoB), it interacts with other things like insulin, inflammation, metabolic health, blood pressure.
But all that said, the case for high LDL being bad for heart attacks and strokes is very strong.
To me the strongest short list of evidence is simply:
- People who have familial hypercholesterolemia, from different genetic causes/pathways, all have massively increased heart disease at young ages.
- People who naturally have a disabled PCSK9 gene have extremely low LDL levels, where PCSK9 is directly involved in the liver's ability to clear LDL from blood, and these people also have incredibly low incidence of heart disease.
- Modifying cholesterol levels via PCSK9 or statins both have very strong evidence that they work on people who have heart disease, we have many RCT involving people who have already had one heart attack, and they have clear dose response curves: the amount of LDL reduction is directly proportional to risk reduction. We have less clear evidence on healthy people and from diet but those people are just a lot harder to study.
It's true that not everyone with high LDL develops plaque and we don't know why, but I feel a lot of "lipid hypothesis skeptics" tend to swim around in the gray areas and just don't interact with the more smoking gun bits of evidence that have to be explained away if you are going to say that LDL has no effect.
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