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Most people are operating under the assumption that eating saturated fat is bad, and you only do it insofar as you want to taste it. Then, of course, there's a small group of people who love to eat organs and meats and really pack in cholesterol, and they would argue that doesn't matter: even if your LDL is 870, it's not going to impact your health. What's the reality around LDL, HDL, dietary cholesterol, and saturated fat, at least in your view?
First, let's differentiate between cholesterol and fat, just for the listener, because we use these terms interchangeably and I want to make sure people understand. Cholesterol is a really complicated molecule. It's a ringed molecule. I used to know exactly what its structure was, but it could have 36 carbons for all I remember. It is a lipid, so it is a hydrophobic molecule that is synthesized by every cell in the human body. It is so important that if you look at genetic conditions that impair cholesterol synthesis, depending on their severity, they can be fatal in utero. In other words, anything that really interferes with our ability to produce cholesterol is a threat to us as a species. The reason is that cholesterol makes up the cell membrane of every cell in our body. As you know, but maybe the listeners don't, a cell is a spherical thing, and it has to be fluid. It's not just a rigid sphere like a blow-up ball. It has to be able to move in a way that meshes with other cells. It also has to accommodate porous structures that traverse its membrane to allow ions and other things to cross, and it's cholesterol that gives fluidity to that membrane. Cholesterol is also, as you're alluding to, the backbone of some of the most important hormones in our body: estrogen, progesterone, testosterone, and cortisol. So we have this thing that is super important.
Then let's talk about whether you can get cholesterol in your diet. Yes, you can eat foods that are rich in cholesterol. What was known in 1960 somehow escaped everybody's imagination until the American Heart Association acknowledged it a few years ago: the cholesterol you eat does not really make it into your body, and the reason is that it is esterified. I don't want to get too nerdy, but I think it's important that people understand how this works. We have cells in our gut, enterocytes, which are the endothelial cells of our gut, and each one has basically two transporters on it. The first is called the Niemann-Pick C1-Like 1 transporter. The second is called the ATP-binding cassette G5/G8. The Niemann-Pick C1-Like 1 transporter brings in any sterol that fits through the door: cholesterol, zoosterol, phytosterol. Virtually all of what comes in is the cholesterol we produce, which gets taken back to the liver, which packages it into bile and secretes it. That is what aids our digestion. This is another thing I should have mentioned earlier: in addition to using cholesterol for cell membranes and hormones, we wouldn't be able to digest our food without it, because it is what makes up the bile salts. Our own cholesterol is basically recirculated in a pool throughout our body, and this is the way it gets back in, through the Niemann-Pick C1-Like 1 transporter. When it gets in, the body reaches a checkpoint of regulation. The body asks: do you have enough cholesterol? If yes, it lets that cholesterol make its way into the circulation, off the basolateral side of the cell rather than the luminal side, into the body. Alternatively, the body says we have enough cholesterol, and it lets you poop it out. The ATP-binding cassette then shoots it out, back into the luminal side, and away it goes. Not all of the cholesterol in our body is esterified, meaning it doesn't have that big, bulky side chain attached. The cholesterol you eat is esterified, and an esterified cholesterol molecule simply can't physically pass through the Niemann-Pick C1-Like 1 transporter. We probably manage to de-esterify ten to fifteen percent of our dietary cholesterol, so small amounts do make their way into our circulation, but that represents a small fraction of the body's total pool of cholesterol. This was known even by Ancel Keys, the man who turned fat into the biggest boogeyman of all time. Keys acknowledged in the 1960s that dietary cholesterol plays no role in serum cholesterol. It took the American Heart Association another 60 years to figure that out, and even now they acknowledge that dietary cholesterol has no bearing.
So why is it fairly easy to find studies, or at least highly credentialed people from good institutions, claiming that eating saturated fat, red meat, and things rich in cholesterol, to be more specific, is bad for us in terms of our eventual LDL? These are two different things. Saturated fat consumption in many people will raise LDL cholesterol, so it's important to differentiate what saturated fat is. Saturated fat is a fatty acid, a totally different molecule from cholesterol. Cholesterol has a very complicated ring structure, multiple rings stuck together. Saturated fat, SFA, is just a long-chain fatty acid that is fully saturated, meaning it has no double bonds, and it can exist in isolation or in a triglyceride, a triacylglyceride, a phospholipid, or other forms. When we eat foods that contain fat, there are basically three distinctions: is it saturated, is it monounsaturated with one double bond, or is it polyunsaturated with two or more double bonds? The observation that eating saturated fat raises cholesterol is generally correct.