How Ezetimibe Took My ApoB Down Nearly 40% (APOE4/4, No Statin)

All right, before we get into what I did, I need you to understand why cholesterol is a different problem if you have APOE4, because the APOE protein is basically a lipid taxi.

So APOE4, the gene, actually codes for a protein, the APOE4 protein, and that protein picks up cholesterol and fats in your bloodstream and shuttles them around.

There are three versions of that protein that are linked to the three versions of the gene, the three different alleles, E2, E3, E4.

Most people, as you know, have E3.

Around twenty-five percent of the people carry at least one copy of E4, and about two to three percent carry two copies.

So whether you have one E4 or two E4s, the interventions are the same.

It's just higher stake for us double E4.

So the fundamental difference is that APOE3 and APOE2 preferentially bind to small phospholipid-rich HDL particles.

APOE4 preferably binds to large triglyceride-rich VLDL particles, and that is not a trivial variation.

That is two different lipid trafficking system.

APOE4 is what researchers call poorly lipidated, meaning the cargo isn't loading properly.

In cultured neurons, APOE4 was less effective than APOE2 and APOE3 at transporting brain cholesterol.

So basically, our lipid taxi is showing up to fewer stops, carrying less cargo, and delivering it to the wrong place.

Yes, I know that sucks, but there are tons of things we can do about it.

What does it mean in your blood work? Because as always, what matters is ways that we can track.

So you want functional benefits, but before seeing functional impact, as in better cognition or less brain fog and so on, the easiest and fastest way of tracking if something works is to look at your blood work.

So typically, Phenix members will do a blood work every three months, uh, and that is typically the time you take for all these interventions to show up in your blood, uh, results.

So in your blood work, what we'll, we will see is that APOE4 carriers tend to run higher cholesterol.

The Alzheimer's Disease Neuroimaging Initiative, which is one of the largest Alzheimer's disease cohorts in the world, found total cholesterol was significantly higher in APOE4 carriers versus APOE3 and APOE2.

But here's the finding that changes everything.

Higher total cholesterol is a stronger risk factor for Alzheimer's disease in APOE4 carriers than in non-carriers.

So, uh, we're getting kind of a double whammy here.

The researchers concluded, and this is a direct quote, "Higher total cholesterol may be a significant contributor to Alzheimer's disease risk, particularly in APOE4 carriers who, based on existing literature, tend to have impaired cholesterol metabolism." So same cholesterol level, different gene means different risk trajectory.

That's APOE4 for you.

And there's also one more layer I want you to hear before we go further.