Thread by @ck_eternity_

CHOLESTEROL AND HEART DISEASE

The last few months I've been researching cholesterol and heart disease extensively, including interviewing various experts in the field, in this thread I'll be summarizing my findings and opinions

THREAD //

Before I begin, I want to make it clear that I'm not here to debate anyone

This is a controversial subject in many ways, but I've approached this with an open mind and will be including studies to support my positions

If you disagree with me, that's fine, to each their own

I also will not be speaking on heart disease medications like statins

I think there are pros and cons of any drug/medication, and at this point I have not researched these drugs in enough depth to put out an opinion on their use

Now without further ado, let's jump right in

Cholesterol is probably the most well-known molecule associated with heart disease in the body

As a result of this many people are terrified of cholesterol in general, while others deny any link between cholesterol and heart disease whatsoever

As with most debates like this in nutrition, both of these extremes are inaccurate and lack nuance

To understand the relationship between cholesterol and heart disease, first it's important to understand cholesterol's role in the body and how its metabolized

About one third of cholesterol in the body is derived from diet, while the rest is synthesized in cells through a 30-step energy intensive process that relies on oxygen, acetyl-coA, and ATP

Most cells in the body can synthesize cholesterol, but only the liver can degrade it

Because of how cholesterol metabolism is spread out throughout the body, cholesterol has a few different transport systems

Its transport relies on the use of different lipoproteins (lipid/protein conjugate particles), which fall into three categories: chylomicrons, LDL, and HDL

Chylomicrons are responsible for dietary cholesterol transport

LDL (low-density lipoprotein) is created in the liver and carries cholesterol to peripheral tissue via the bloodstream

HDL (high-density lipoprotein) transports cholesterol back to the liver for disposal

Cholesterol has a few interesting roles in the body

It's used in the synthesis of steroid hormones, has a neuroprotective role through the production of oxysterols and neurosteroids in the brain, and is an essential component of cell membranes allowing them to maintain fluidity

Similar to blood glucose, when cholesterol is regulated properly it causes no issues and actually has a protective effect on health

Problems begin to arise when cholesterol becomes dysregulated, there are a few different dietary and lifestyle factors that influence this:

Saturated fat increases levels of both LDL and HDL by inhibiting the binding of lipoproteins to the LDL receptor, which is used to regulate cholesterol absorption into cells

When this receptor is blocked the liver releases more LDL than normal
pubmed.ncbi.nlm.nih.gov/9478045/

Trans fats found in many processed foods and hydrogenated spreads also elevate LDL levels through a similar mechanism

There are a number of other lifestyle changes that alter cholesterol metabolism and heart disease risk in other ways, but we'll get to those a bit later

Note: as opposed to saturated fat, dietary cholesterol has little to no influence on blood cholesterol, cutting dietary cholesterol out completely only results in approximately a 10mg/dl maximum reduction
healthline.com/nutrition/diet…

Now this is where things get interesting

When LDL is elevated outside the normal range, it's associated with an increased rate of CVD

This is the most well-researched heart disease mechanism and is clearly established in both RCT and epidemiological data
jamanetwork.com/journals/jama/…

When we look deeper it turns out this mechanism isn't quite so simple

Increased LDL doesn't operate in a vacuum, inflammation must first increase endothelial permeability, which then causes LDL to create a build-up of plaque in the inner membrane of the arteries

Besides that, not all forms of LDL are equally able to pass through the damaged endothelium

LDL ranges in density from very large dense LDL (VLDL) to small dense LDL (sdLDL)

The smaller and more dense LDL particles are the more likely they are to implant in the arteries

Interestingly, saturated fat doesn't seem to influence the size of LDL particles produced, only the amount produced

Factors that do increase sdLDL production most notably include high processed carb/sugar consumption, and higher consumption of trans fats
medicalnewstoday.com/articles/small…

Beyond LDL particle density, another process that influences how LDL cholesterol behaves in the body is cholesterol oxidation

When cholesterol is oxidized, it appears to play a much greater role in the accumulation of arterial plaque/damage
ncbi.nlm.nih.gov/pmc/articles/P…

While this may sound simple enough, it's not as easy as just taking some extra antioxidant supplements

Essentially every form of oxidative stress has been suggested or shown to contribute to LDL oxidation, so this needs to be targeted holistically
ncbi.nlm.nih.gov/pmc/articles/P…

One commonly suggested strategy to protect LDL against oxidation is eliminating PUFAs like linoleic acid

While I understand the logic behind this, since PUFAs are more prone to oxidation than saturated fats (SFA), this approach doesn't seem to hold up in studies

This study particularly showcases the effects of different fatty acid saturations in LDL particles

Interestingly BOTH polyunsaturated and saturated fats show equal rates of cholesterol oxidation, while only monounsaturated fats were actually protective
ahajournals.org/doi/full/10.11….

This study supports this conclusion as well, finding that olive oil (higher in MUFA) showed the most protection against LDL oxidation

It also noted that the amount of SFA present in LDL didn't change based on diet, so more SFA intake isn't protective here
pubmed.ncbi.nlm.nih.gov/11840183/

So the best strategies to minimize any potential harm from LDL seem to be:

- minimizing processed carbs (less sdLDL)
- minimizing trans fats (less LDL, especially sdLDL)
- balancing saturated fat intake with monounsaturated and polyunsaturated fats (olive oil = ideal ratio)

Before diving in to other ways to minimize heart disease risk I'd like to briefly touch on the issue of saturated fat intake

I've already demonstrated that saturated fat increases LDL and doesn't protect against LDL oxidation, so does this mean it should be avoided?

Essentially this seems to be a case of "the dose makes the poison"

When balanced with MUFA and PUFA in the ratios found in many foods like olive oil, saturated fat does not appear to cause much issue, while isolated animal fats seem to cause the most increase in heart disease

It's also worth noting that saturated fat increases both LDL and HDL, without increasing sdLDL formation specifically, this means saturated fat intake is likely far more of a risk factor when paired with other risk factors like smoking, processed carbs, or trans fat

That said, high animal fat consumption does still show an association with heart disease on it's own

This seems to indicate that while VLDL is less likely to cause plaque build-up, the elevated LDL cholesterol in general from saturated fat can still contribute to heart disease

I'm sure you're wondering why this would be an issue, given the fact that humans have been consuming saturated fat forever... right?

In reality this doesn't seem to be the case, similar to how fruit has been bred to contain as much sugar as possible, animals now hold more fat

We also see here that wild game contains roughly 2x the unsaturated fat content of domesticated meat
pubmed.ncbi.nlm.nih.gov/21471535/

And here that organ meats, which make up a significant portion of hunter-gatherer diets, are also much higher in unsaturated fat
mdpi.com/2304-8158/9/7/…

Now this doesn't mean we have to avoid animal fat completely, but if you want to follow a true ancestral diet that means balancing saturated fat with unsaturated fat, and eating more lean meat, seafood, and organs, not overly fatty muscle meat like low-quality domesticated beef

At the end of the day it comes down to eating real whole food, not isolated fats or processed junk food which pairs processed oil, trans fats, and excess carbs

I still use butter on occasion myself, but not most days, my first choice is always olive oil

Avocado oil also seems to have a similar ratio of fatty acid saturation to olive oil

Cooking oils higher in PUFA like sunflower oil can be deployed as well, just opt for cold-pressed and avoid prolonged cooking with them at high temps to avoid excessive aldehyde creation

Coconut oil also seems to be preferable to butter from a general LDL perspective

Though it will still increase, it it doesn't do so as dramatically and doesn't seem to hold the same association with heart disease
ncbi.nlm.nih.gov/pmc/articles/P…

Milk and cheese seem to work similarly

Lastly, always remember that while LDL is relevant, it certainly isn't the only factor associated with heart disease

Your level of HDL, triglycerides, homocysteine, free iron, inflammation, oxidative stress, and insulin resistance can all also play a role

Exercise and supplementation of nicotinic acid (flush niacin) both increase HDL to some degree, and black seed oil mildly reduces LDL without impacting HDL

HDL is decreased in cases of high blood sugar/insulin resistance, and by smoking

Elevated triglycerides can occur downstream of insulin resistance, or obesity/visceral fat storage, as well as hypothyroidism (though elevated triglycerides also seem to contribute to hypothyroidism)

Black seed oil, caloric restriction, and exercise may low triglyceride levels

Iron accumulation also has a role in LDL oxidation
pubmed.ncbi.nlm.nih.gov/7925932/
And iron dysregulation also drives homocysteine production
scholar.google.com/scholar_url?ur…

This is a comprehensive article I wrote on my personal approach to correcting this:
multiflora-herbs.com/blogs/news/fre…

Lastly homocysteine is elevated when some aspect of methylation is impaired

Normally homocysteine is cleared using B6, B9, B12, and betaine (produced from choline in the liver) as cofactors, but when these processes are impaired it can create cardiovascular damage

I believe the iron and methionine content of red meat plays a significant role in its ability to increase heart disease

Without the proper cofactors found in organs like liver, methionine is metabolized into homocysteine and this process is accelerated by free iron

As you can see it's not as simple as LDL cholesterol automatically causing heart disease, but it is definitely a significant factor

We need to approach this issue holistically, taking LDL into consideration along with HDL, inflammation, iron dysregulation, etc

This is my approach to preventing heart disease:

- balance meat with plants
- balance red meat with lots of organs and seafood
- focus on whole food carb sources like fruit, root vegetables, or sprouted legumes
- olive oil > butter
- exercise often
- daily sunlight exposure

There's certainly more you can do as I've discussed, but these are some simple changes that show positive results in various studies

I'll likely write up a full article where I can expand on this topic more in depth, but for now that's all I've got

Thanks for reading 🙏❤️