New model could explain old cholesterol mystery

She's 104 years old and survived COVID this summer.

In my experience, as a patient with some unknown problem, the less experienced a physician is, even if they are a specialist, the more likely they are to try to match up your issues with what they know and hand wave away any inconsistencies. When you get to an expert, if there are inconsistencies they will straight up say they don't know what's going on and will start looking into it (running tests, trying different meds, etc).

Check Dr. Malcolm Kendrick long series on "What Causes Heart Disease" (list of all posts from drmalcolmkendrick.org):

https://www.emotionsforengineers.com/2018/01/dr-malcolm-kend...

I suppose there's a genetic component, as no man in my known family lineage has made it past 60.

What kind of exercise: cardio, yoga, resistance/weight training, other? There have been a number of studies showing that regular weight training improves cholesterol numbers (1,2) and I have seen it personally. Regular weight training causes cells to repair/recycle their cholesterol, removing it from the bloodstream. (Cardio may or may not do this as well but I'm a proponent of weight training as the foundation of health.)

Also: after reading the article, I think that cholesterol turnover rate is the key here. Cholesterol that is regularly used up and replaced does not have time to damage your vascular system like cholesterol that hangs around and hardens on your walls.

1) https://pubmed.ncbi.nlm.nih.gov/24174305/ -- Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations

2) https://pubmed.ncbi.nlm.nih.gov/33343671/ -- Regular training has a greater effect on aerobic capacity, fasting blood glucose and blood lipids in obese adolescent males compared to irregular training

Unrelated to this I tried Keto a bit later. I did actual real keto with less than 20g of carbs. Probably higher on the protein side than normal but loooots of fat definitely and eggs and bacon and all the other cholesterol stuff.

All of my other bad blood values completely normalized. Cholesterol went down slightly but not much but LDL/HDL ration improved. I didn't get the test to check for size and makeup of the cholesterol molecules done (not covered/done here) but I bet you it would've confirmed that I had a lot of but mostly the fluffy type of cholesterol (the good type).

This shows that doctor's actually know that a diet and other lifestyle factors are the key to health. Not eating pills.

I do cardio at least 3 times a week and train a form of calisthenics (push ups, pull ups, dips, etc) at least three days a week.

It doesn't really do much for the numbers. I think some people just draw the short straw on cholesterol.

The trick to it is that cholesterol is only one of many subtle risk factors in cardiovascular health. As this article suggests, it's obviously not the case that high cholesterol is universally associated with worse outcomes, and there's no guarantee that improving the test scores will provide any benefit for an otherwise healthy patient. Does the doctor look at the whole person and their exercise regimen and conclude it's not worth medicating for the cholesterol risk? Or do they consider that lowering cholesterol can improve risk even further and so recommend medication? There's actually a protocol here that includes cholesterol as only one factor.

Ideally, a model like the one in this article could help better understand who to actually treat. We know cholesterol is a reliable proxy for risk at population levels, but if it could be ruled out for individual parents that would be very helpful.

Huh. Is this something one’s GP could do or does it require specialized training? The article says it’s unpopular at general practitioner’s offices.

PROBLEM #2: high serum cholesterol is correlated to cardiovascular disease, but eating high saturated fat-diets is not.

ANSWER #2: It appears that studies that assess the effect of a particular diet depends a lot upon the health of the individual prior to the study start; thus, using a random population results in non-significant results.

Note that I agree with you otherwise. I would suspect that a diet high in saturated fats without any supplemental unsaturated fats would result in cell walls becoming so stiff that removal of cholesterol can no longer benefit the cell walls; if this happens in arteries, you get hardened arteries that can lead to heart disease.

https://harvardmagazine.com/2019/05/inflammation-disease-die...

The normal metabolic route is that excess fructose, beyond what the liver can afford to process immediately or store itself, is carried wrapped in cholesterol to fat cells to be stored.

If you take statins, excess fructose gets dumped into your bloodstream not wrapped in cholesterol, which is much worse. It causes oxidation of blood lipids, which have long been known to cause heart and circulatory problems.

Mendelian randomization can sometimes “rescue” causality from large epidemiological studies. Pearl explains how.

High LDL or high cholesterol doesn't mean anything, per se. The HDL:LDL ratio is a little more important but not so much. Triglycerides and glucose levels are a much bigger indicator of health. Inflammation is the biggest indicator, but AFAIK we do not have ways to measure it directly.

HDL, LDL, cholesterol, triglycerides are fats, but are often not directly correlated with dietary fat. There is more and more evidence triglycerides increases as sugar and refined carbs increase in your diet. This is the biggest misconception in dietary history and we're 20 years away from science and doctors to integrate this new piece of information.

So, not experts. (Not in the field they were claiming).

I think it's interesting that all of three of these hinge on the same problem: human variability. I strongly suspect that humans are much more variable internally than conventional science and journalism accounts for.

The scientific method uses statistics which is important for showing aggregate effects but can also obscure variability. And journalists have an incentive to offer simplified guidance that is as widely applicable as possible.

The end result of a lot of information like "Do X" when what it should really be is "If you are like Y do X, if you are like W do Z."

This is a pattern I think of as "the missing parameter" that I see just about everywhere people give advice once I started looking for it. Examples:

- "(Static/dynamic) types don't help programming." For what kinds of programs? Developed by whom? At what scale and timeframe?

- "You (should/should not) use a schemaless database." How big is your dataset? What is the relative fraction of reads/writes? What kind of data? How many users? How much money do you have? What are your failure modes?

- "People should move (to/out) of cities." Which cities? What is the city's transit like? Which people? What activities do they prefer? Do they have kids? What's their economic status? Age? How important is it to be near a hospital?

- "You should eat less salt." For people of what age? Activity level? Diet?

- "Teach by example not generalities." Teach what material? To whom? How important is their understanding? How long should they retain it?

- "Children should go outdoors on their own more." What age? What personality do they have? Where do they live?

Whenever I see people arguing about some generality, what is often happening is that each party has implicitly filled in those parameters with different values, so they are all correct but talking past each other. When I see this happening now, I try to take a step back and figure out what implicit parameters they are assuming and see if there's a higher-level parameterized stance that unifies their arguments.

I think you're being unfair. Most of the time, it's not a major 180, it tends to be smaller course corrections, refinements over current understanding of data, and the discovery of even more correlated complexities.

The issue is people want simple answers, easy to follow guidelines, and guaranteed results. The science just isn't at the point where it can deliver those. So people make up best guesses for them each decade based on where the science is at that point.

A lot of the theory about why LDL is 'bad' is based on the fact that arterial damage is repaired with the stuff, causing plaque. There's no evidence that LDL is causing the damage, just that it has a role in how it's fixed (in an ultimately detrimental way).

By all means let's continue research. But people generally shouldn't rely upon most of it when making dietary choices. A better approach is to conduct your own n=1 informal experiments and determine empirically what works best for you.

There are pretty good reasons to think eating lots of meat is bad for your heart, which they have always blamed on the saturated fat. Now they have having to backtrack, and try to discover what else it is in meat that causes trouble.

From my personal sifting through research, it seems there's a lot of correlation with different diets which shows people with more health problems often have an animal based diet and people with less health problems often have a more pesceterian diet.

What is absolutely not clear is any of the cause/effect. It's also unknown of the nuances.

For example, what else correlates with those? It often is true that people with pesceterian diets are from specific isolated genetic lineages. It is also often true that when they're not, they tend to be individuals that pay much more attention to their overall health, making sure they don't eat too much, eat high quality produce (organic, wild caught, etc), exercise more, and often are more financially wealthy.

Personally I agree with you, but I also agree with the opposite:

> The idea that vegetables/fruits/nuts/seafood products are unhealthy seems to be misguided

Historically, we've always consumed all these things. Meat, seafood, vegetables, fruits, nuts, grains, seeds, human lineage ate all of this for a very long time. Why would any of it be bad for us?

More recently as I've been thinking about this, I'm wondering if it's more related to our modern production of those things, and our changing consumption habits.

Take meat for example, the meat we eat today is very low quality. The animals are themselves unhealthy, fed garbage food, and have a lifestyle unlike their natural one. Can we compare the effect of eating unhealthy meat to healthy meat? We know grass fed beef has way more nutrition than non grass fed beef for example, so there's clearly major differences between eating one or the other.

Now take vegetables, we've not been hard pressing canola into an oil extract and consuming it in high quantity before. This is a modern change.

In fact, I don't even think canola is a plant we would have eaten the seeds off in the past.

So my current thoughts are that low grade produce and processed foods might have a lot more to do with it. And all of the "diets" no matter if you think they are a fad or which affinity you have will emphasize this point: Avoid processed foods and try to get the highest quality ingredients.

In the past, we'd probably eat an animal that had eaten canola itself and processed it for us, and we'd get the canola nutrients through eating the animal.

But also, we wouldn't be eating animal all the time at the quantities we do now. Because winter, and hunting is hard, and lack of preservatives. But also because once we became sedentary, meat was expensive and most people could afford very little of it.

And like I said when we did, it would be this very high quality meat. Very different from what we eat today.

We also wouldn't be consuming all these processed vegetables byproducts, like oils. Appart from those that were very easy to extract, like Olive oils. Everything else that requires modern industrialization to extract it was probably consumed in much less processed forms, such as eating the seeds themselves, or grinding a much smaller amount and getting much smaller amount of oil out of them.

Modernity has brought major changes in that all foods are now of a lower quality, and come in a much more processed form. It made a lot of foods more accessible which mean eating as much as we do is also a modern change. And it allowed us to modify the proportions of what we'd eat, like way more sugar and salt, way less veggies and fruits. In my opinion these are the more consistent factors. So from my readings, I currently conclude the best course of action for your average healthy person is to eat less food overall, eat unprocessed foods of the highest quality (organic, grass fed, wild caught, etc.), In mostly equal quantity of each kind (based on calories), like consume the same calories of meat, fish, veggies, fruits and grains.