Cholesterol 101

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Recently by Mark Sisson: Setting Yourself Up to Win: A Body By Science Approach


Before we get into the big job of interpreting cholesterol numbers, let’s review what cholesterol actually is.

Cholesterol is cholesterol: a waxy steroid of fat that serves as an essential structural component of cellular membranes and in the production of steroid hormones, vitamin D, and bile acids. Contrary to what the terminology indicates, there’s actually only one “type” of cholesterol in the human body, and it’s called, quite simply, cholesterol. What we think of when we use the word “cholesterol” is actually a lipoprotein — a fatty conglomerate of protein and lipids that delivers cholesterol and fat and fat-soluble nutrients to different parts of the body. It’s not just free cholesterol floating around in your blood; it’s cholesterol bound up by lipoproteins.

So LDL, HDL, VLDL, all those (in)famous measurements we get at the doctor’s office are just different types of lipoproteins. They’re not actually cholesterol. I discussed this briefly a couple years back, and there’s always Griff’s big primer in the forum, so take the time to go check out both. And also take a peak at The Definitive Guide to Cholesterol for review.

Okay, let’s talk about the most commonly bandied-about cholesterol numbers: LDL-C and HDL-C. What do they really mean? What are they actually measuring?

To understand what these numbers mean, let’s play the freeway analogy game. Both LDL-C and HDL-C, the standard, basic readings you get from the lab, do not reflect the number of LDL or HDL particles — the number of lipoproteins — in your serum. Instead, they reflect the total amount of cholesterol contained in your LDL and HDL particles. Hence, the “C” in LDL/HDL-C, which stands for “cholesterol.” Measuring the LDL/HDL-C and then making potentially life-changing health decisions based on the number is like counting the number of people riding in vehicles on a freeway to determine the severity of traffic. It’s data, and it might give you a rough approximation of the situation, but it’s not as useful as actually counting the number of vehicles. A reading of 100 could mean you’re dealing with a hundred compact cars, each carrying a single driver, or it could mean you’ve got four buses carrying 25 passengers each. Or it could be a couple buses and the rest cars. You simply don’t know how bad (or good) traffic is until you get a direct measurement of LDL and HDL particle number.

Say you go ahead and get those particle numbers directly measured. You’re still limited, because that is just a single datapoint from a specific time in your life/day/week. Analogies are fun and helpful, I think, so let’s take this traffic and freeway stuff further. To get an accurate idea of traffic, you need constant updates, right? Imagine you counted the number of cars on the freeway at 12:05 on a Saturday afternoon four weeks ago. That’s great, but what does it tell you about traffic at 5 PM on a Thursday? Even though it’s the same stretch of asphalt/artery, we can’t divine much at all from that single measurement. You need more data points. That traffic fluctuates wildly is entirely uncontroversial. Any southern Californian could tell you that. But did you know that LDL, HDL, and total cholesterol readings in the same person can fluctuate just as wildly, oftentimes enough to move that person from “desirable” to “high risk” and back to “desirable” lipid status without any nutritional or lifestyle changes in the span of a few mere weeks?

In biology, a single snapshot rarely, if ever, tells the whole story. Who woulda known?

But just because the standard cholesterol test is but a snapshot of a dynamic system in flux doesn’t negate the potential usefulness of getting your cholesterol checked. As much as Conventional Wisdom has gotten things wrong when it comes to cholesterol and heart disease, the two do have a relationship together. There is a connection; contrary to what the AHA might think, we just don’t have it ironed out yet. In my opinion, the most persuasive hypothesis about the real causes of atherosclerosis and heart disease comes from Chris Masterjohn and is highlighted in his recent AHS talk, “Heart Disease and Molecular Degeneration,” and on his blog. It’s a synthesis of the two prevailing notions regarding cholesterol and heart disease — the one which says elevated blood cholesterol plays no causal role in heart disease and the one which says elevated blood cholesterol is the primary cause of heart disease — and it goes something like this:

LDL receptors normally “receive” LDL particles and remove them from circulation so that they can deliver nutrients and cholesterol to cells, and fulfill their normal roles in the body.

If LDL receptor activity is downregulated, LDL particles clear more slowly from and spend more time in the blood. Particles accumulate.

When LDL particles hang out in the blood for longer stretches of time, their fragile polyunsaturated fatty membranes are exposed to more oxidative forces, like inflammation, and their limited store of protective antioxidants can deplete.

When this happens, the LDL particles oxidize.

Once oxidized, LDL particles are taken up by the endothelium — a layer of cells that lines the inside of blood vessels — to form atherosclerotic plaque so they don’t damage the blood vessel. This sounds bad (and is), but it’s preferable to acutely damaging the blood vessels right away.

So it’s the oxidized LDL that gets taken up into the endothelium and precipitates the formation of atherosclerotic plaque, rather than regular LDL. OxLDL, poor receptor activity, and inflammation are the problems. But since measuring oxidized LDL in serum is difficult (oxidized LDL gets taken up out of serum and into the endothelium rather quickly) and expensive, we need other, more realistic, more obtainable methods. We need to work with what we’ve got. It would be great if a doctor could quickly order up an “LDL receptor activity” test, but I don’t see that happening anytime soon.

Enter the various lipid panels.

First up is your basic lipid panel, the standard test the average doctor is going to order for a patient. If you go this route, you’ll typically get four measurements: total cholesterol (TC); high density lipoprotein cholesterol (HDL-C); low density lipoprotein cholesterol (LDL-C); and triglycerides.

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