Tom Dayspring, M.D., FACP, FNLA – Part IV of V: Statins, ezetimibe, PCSK9 inhibitors, niacin, cholesterol and the brain

**Peter Attia** (0:04)
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The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top-performing individuals in the world. And this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peterattiamd.com.
Hi, everyone, welcome to episode four of The Week of Dayspring. In this episode, we cover a lot of drugs. We talk about statins, we talk about cholesterol regulation, we talk about ezetimibe, also known as Zetia, and we talk about the most recent class of drugs introduced to this field, a drug, a class known as the PCSK9 inhibitors. There are two such drugs on the market today. We talk about fibrates, and we also talk about the use of fish oil, niacin, or niospan, which has fallen out of favor. This came up a little bit on the discussion I had with Ron Krauss several months ago, and we get re-revisited here. Tom has a very different point of view on this from Ron, so you will be able to determine which of those views that you favor, which camp you're gonna be in on the niacin side. We talk about the role of cholesterol, statins, and brain health. And another thing that I learned was about the futility of using CKs and LFTs to address statin response or ill response. So again, another great example of how I'm doing these shows, but I'm learning along the way. And so I'm confident that any physician listening to this is going to learn something, and that hopefully this becomes kind of a part of your ongoing medical education. So sit back and get ready for episode four.
So while we're on that topic, let's go back and talk about the drug. So we just finished with kind of one very niche story, but when it became pretty clear that there was an association, a strong association, frankly, between cholesterol and heart disease, you now had another target, because as you said, if we went back in time 50, 60 years, if you were astute enough, you would have your patients stop smoking, you would manage their blood pressure.
What was the first drug that was specifically brought to market to target cholesterol?

**Thomas Dayspring** (2:36)
Well, niacin has been used, that infant item forever, without a lot of data, but they knew it changed certain metrics. They were measuring total cholesterol, HDL cholesterol, and the only form of niacin available back then was immediate release, a pretty much intolerable drug for most people, but you could find some people who could take the massive doses needed for that. So that was around, believe it or not, when I was coming up, and total cholesterol was the only measurable thing, and they knew that if it was 400 or something, you were probably in trouble. They gave niamycin to those people.

**Peter Attia** (3:10)
Niamycin, the antibiotic.

**Thomas Dayspring** (3:12)
Yeah, which interrupted the hepatobiliary circulation of cholesterol, and it lowered cholesterol anywhere, no outcome evidence with it. But along came the bile acid sequestrants, which we hinted on, will make you excrete bile acids, which therefore you have to use up your endogenous cholesterol to make new bile acids, so you will lower your cholesterol metrics that you're looking at. And in a crazy long outcome trial, it did seem to work. They pudged a lot of statistics, I think, in retrospect on it, and didn't have the type of statistics. This is the LRC. So there was a little proof that not only what Framingham said is true, cholesterol is a risk marker, a risk factor, depending on how you want to label it. By lowering it, it does reduce clinical events.
To me, the tragedy of that is for the next 20 to 30 years, the only thing that the pharmacological industry focused on was cholesterol as their metric of, that's all we got to do. We got to find stuff that lowers cholesterol metrics or improves cholesterol metrics in one or the other direction. And Bob asks these questions. Do raise HDL cholesterol a milligram or two milligrams per cent, which turns out to have some statistical significance.
So-

**Peter Attia** (4:32)
Potentially without any physiologic significance.

**Thomas Dayspring** (4:35)
Correct, and it's a minuscule thing, so who knows. So that led to just investigation of everything else, and all of a sudden this guy discovers a fungus that has got a property that lowers really potently cholesterol, and that was the statin group, Akiro Endo, a mycologist over there in Japan, who unbelievably has not gotten a Nobel Prize yet, and there'd be no statins without him bringing it to the table and stuff. We wound it, statins lower LDL cholesterol dramatically, pretty low doses, they seem to be safe.