Tom Dayspring, M.D., FACP, FNLA – Part II of V: Lipid metrics, lipid measurements, and cholesterol regulation

**Peter Attia** (0:04)
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Hi, everybody, welcome to episode two of five in the week of Dayspring. This episode, we cover lipoprotein basics, what's lipoproteins and lipids 101 We talk about Gofman and the ultracentrifuge and how we came up with these whole ideas of densities of lipoproteins. We get into very specifics around the lipoprotein structure, their function and their metabolism. We talk about how to measure the lipoprotein and the cholesterol content and what NMR is and how it has changed the game a little bit. We get into the distinctions between LDL cholesterol, LDL particle number and APO-B. There is some confusion here amongst physicians and presumably amongst patients. So hopefully that will clear that up. We get into the biochemistry of lipids and then we talk about sterols specifically as a more broad category.
Now before we could measure anything to do with lipoproteins, if my memory serves me correctly, it would have been the late 40s, very early 50s when the first assays were developed, maybe it was 1951, that could actually just measure total cholesterol. So you would take plasma from a patient, you would presumably in an assay break down all of the lipoproteins and just aggregate the total amount of cholesterol and you would yield that number, which still amazingly shows up on a panel today. You go and get a blood test and it might say your total cholesterol is 200 milligrams per deciliter. So that was, am I correct? That was the early 50s maybe?

**Thomas Dayspring** (2:10)
No, I think they were analyzing cholesterol long before that, because that's a molecule. You can take blood and dissolve whatever you got to dissolve and cholesterol appears. So they had cholesterol measurements for a long, long time. It's like the first lipid anybody could ever measure.
What you're talking about in the 50s is where John Hoffman discovered that, hey, wait a minute, there are no lipids floating around in plasma because lipids are incredibly hydrophobic. Your plasma is water. You can't have lipids circulating in plasma. So lipids obviously have to be within what I call water-soluble lipid transportation vehicles. And that turns out, of course, to be a lipoprotein, a protein-wrapped collection of hydrophobic and amphipathic lipids that just wouldn't be in your plasma unless they're attached to a protein. Peter mentioned albumin. It's a protein. So lipids can attach to albumin and be circulated around and other type proteins. But albumin's the most frequent protein in the blood, so it serves as a carrier. I think an albumin can carry like 17 molecules of cholesterol, a few of phospholipids, too.
So it's a player out there. We got a ton of albumin in our plasmons. You'd be shocked to find out how much cholesterol's in it.
Not quite as much as in lysobacteria.

**Peter Attia** (3:24)
Albumin's kind of an amazing protein. It'll carry hormones. It'll carry just about anything.

**Thomas Dayspring** (3:30)
Yeah, and it has everything to do with osmotic pressures and things like that. So albumin is kind of an essential protein, to say the least, performing many, many functions.
But when John Hoffman, a physicist, by the way, who had, physicists have been playing with ultra-synephuges for a long time separating nerve radioactive particles and stuff, he somehow wound up separating lipoproteins or saw things floating around in a centrifuged test tube that he then identified as the lipoproteins. So if you learn nothing else today, learn the first thing is lipids, for the most part, go nowhere in the human body unless they're a passenger inside a lipoprotein. So if you believe there are a lot of lipid-associated diseases, and I certainly believe atherosclerosis, you cannot have atherosclerosis without a sterol, a lipid being in your arterial wall. And I know that arterial wall didn't over-synthesize sterols, creating a sterol buildup. Somebody had to deliver those sterols there, and that, of course, turns out to be a lipoprotein. And one of the places a lipoprotein should never deliver sterols to, to any serious degree, of course, is your arterial wall intima.
So being a Jersey guy, one of my standard jokes on a lecture circuit was atherosclerosis is just the evidence of illegal dumping, where a lipoprotein, instead of bringing lipids to wherever it's supposed to be bringing, it was bringing sterols to the arterial wall, and over decades, you got a problem. You know, you could do it for a few days, six months, you're not gonna die of atherosclerotic disease.