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

[0:06]And when I first had my ApoB measured, it was 115mg per deciliter. Today it's slightly below 70 and that's a drop of nearly 40%. I had the same impact with my LDL-C, which is the bad cholesterol. And I'd say one of the biggest reason the lever I'd the least want to give up is a cholesterol drug most people have never heard of. A drug I take every single day and it's not a statin.

[0:40]Of course, it didn't do that alone. So I'm also going to share two other levers that I pull to optimize my lipid panel on top of this specific drug. Hi, my name is Dr. Kevin Tran I'm a doctor of pharmacy. I carry two copies of the ApoE4 gene, which is the gene variant most strongly linked with Alzheimer's disease and cardiovascular disease as well, because mainly of the way the ApoE protein carries lipids across the body, this is why it's so important to have your lipids under control.

[1:15]In any case, I built and created the Phoenix community to help us APOE4 carriers, beat the odds, and defeat Alzheimer's In this video, I'm going to cover these three different levers that I pull to control my lipids and actually still enjoy life. Without having too many drastic measures that would just kill my happiness.

[1:38]All right, let's dig into it. The number one lever that I pulled is the diet. Of course, there is no miracle here. If you want to control your cholesterol, you definitely need to fix your diet. Number two is something that I realize not so many people do and it's such a quick win.

[1:54]It's Psyllium husk And number three is ezetimibe which is I believe, the standout. And it's the one that is doing the heavy lifting on my ApoB. In the next half hour, I'll show you exactly what I did. All the peer reviewed evidence behind each lever, including a study of more than a million people, published in 2025, that changes how we should talk about this drug and the brain, plus a brand new guideline and two trials from this year.

[2:22]With all the actual lab documents before and after. So you can see this isn't just theory. And I've seen the results across not only for myself, but also a lot of Phoenix community members when they are using our apps and uploading their blood work, we see dramatic positive results with these interventions.

[2:40]So every optimal number that I'll put on your screen and that I'll talk about are the exact range Phoenix members see inside our bloodwork module, which is always tighter than what your standard labs call normal. This is extremely important. The average normal range that is showed on your blood work is not optimal for us.

[3:04]APOE4 carriers, those were designed for the general population and not for us. Our optimal values are way lower, and if you have access to the Phoenix community, you can just upload your lab work in our app and get the optimal values and the interventions that can lead you. All right.

[3:18]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.

[3:42]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 25% of the people carry at least one copy of E4, and about 2 to 3 percent carry two copies.

[4:01]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 preferentially binds to large, triglyceride rich VLDL particles, and that is not a trivial variation.

[4:27]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 or ApoE3 at transporting brain cholesterol. So basically our lipid ApoE4 taxi is showing up to fewer stops, carrying less cargo and delivering it to the wrong place.

[4:49]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.

[5:10]So typically Phoenix members will do a blood work every three months, and that is typically the time you take for all these interventions to show up in your blood results. So in your blood work, what will we will see is that APOE4 carriers tend to run higher cholesterol.

[5:26]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.

[5:45]So 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 level different gene means different risk trajectory That's APOE4 for you. And there's also one more layer That's APOE4 for you. And there's also one more layer I want you to hear before you go further in 2025.

[6:11]So not that long ago the journal Nature Medicine published something remarkable. They tracked 5,700 people over decades and ran full metabolomic analysis, and they isolated APOE4/4 homozygotes. So people like me as a distinct genetic subtype. And in that distinct subtype, certain lipids, specifically cholesteryl esters, and sphingomyelins were more strongly linked to dementia risk.

[6:37]Then they did something quite clever. They asked, does diet move these metabolites or not? And the answer was yes, but the effect was amplified in APOE4 homozygotes. So the quote that I have for you is adherence to the Mediterranean diet more effectively modulating dementia-related metabolites in APOE4 homozygotes, suggesting targeted prevention strategies.

[7:00]A quick translation: if you are an APOE4 carrier, what you eat matters more than it matters for the general population. That's lever one, and it's where I started. That's lever one, and it's where I started. I want this to really connect with you, because a lot of different studies have shown that us APOE4 carriers benefit more from lifestyle interventions than the general population.

[7:21]So whatever you do has a stronger impact than the general population, which hopefully gives you a lot of motivation to implement these interventions. Okay, Before I walk you through what I did, Let me show you exactly where I was starting from. So we're looking at December 2024. Here is my panel.

[7:39]If I took this panel to any doctor, they'll tell me it's fine. LDL at 139 is borderline high on conventional ranges. HDL is actually good. Triglycerides are low, hs-CRP is very low risk. I'd get a handshake and you know see you next year for your next annual checkup.

[7:58]But the thing is, I'm not the average person, right? I'm an APOE4/4 carrier. And here's something I want to be precise about. These two copies of APOE4 carry roughly 15x increased risk for the general population. If you are Asian like me, that goes up to 33x versus any APOE3/3.

[8:16]So for someone with my genes, the target isn't borderline. The target must be aggressive. And it starts decades before any doctor would normally flag me. T he brand new 2026 ACC/AHA Dyslipidemia guidelines puts the LDL targets below 70 for high risk patients and below 55 for the higher risk.

[8:38]Now, to be fair, those risk tiers are built around heart disease, diabetes and risk calculators not APOE genotype. On paper an asymptomatic 30 or 40 or 50 year old isn't high risk, but the same guideline leans much harder on lifetime risk and earlier prevention. And that's the lens I apply to myself.

[8:56]So inside the Phoenix Bloodwork Module, our ApoE4 optimal band for ApoB is 40 to 70. And as a 4/4, I would tend to aim for at least below 60 ApoB is the single best predictor of atherogenic particle burden better than LDL-C. So I'll focus on that more than LDL-C.

[9:16]And at that point in time, my ApoB being at 96 meant that for every deciliter of plasma, 96mg of atherogenic lipoprotein particles were circulating, which leads to irritation in the arteries and potentially contributing to amyloid pathology decades upstream of any symptoms that might appear. Plus, another problem that I had was my HbA1c was at 5.9, so officially pre-diabetic, whatever that means ApoE4 carriers are at elevated risk for insulin resistance, and insulin resistance multiplies Alzheimer's disease risk.

[9:49]So basically, I had two problems converging. That's when I realized that I carry APOE4, that's when I made a plan. That was my very first test after I realized I carried the gene, right. The first lever that I applied in this plan is the diet. There is no radical transformation there.

[10:07]A specific set of shift that I could hold for several months or years, because longevity of interventions matters more than intensity. So any type of intervention you want to take into account your lifestyle. Do you have kids that are also eating reviewed? You go out usually because you don't want to live a miserable life, or you are trying to optimize everything all the joy out of your life.

[10:29]And me, I used to be or at least I hope I'm still I hope I still am a foodie Even though now I'm still trying to take care of what I eat much more. But the framework I use is basically Mediterranean leaning, so not the full on Mediterranean diet as a branded program.

[10:50]I mean the actual eating pattern, the research track. So I have tons of olive oil and that will be my primary fat. So those extra virgin olive oil, a lot of fatty fish at least once every day, legumes, almost daily leafy greens, cruciferous vegetables, every meal. Nuts If I want to snack very or no sweets at all, and whole grains in very modest portions when I'm exercising and when I'm doing cardio so I can burn that.

[11:22]As you. I've been on and off keto diet, but I will not cover that today because we have other videos that cover the keto diet elsewhere. But that's kind of why if I'm not doing a keto diet, and I also made four specific move. The move number one is I cut saturated fat very aggressively.

[11:41]So no more butter, no more cheese. And I'm French So that really saddened me. No more fatty cut of red meat, which means no more ribeye no more tomahawk Those were reserved for very special occasions like birthdays and so on. Why? Because the Dunk and Driscoll study I just quoted found that blood cholesterol in APOE4 carriers appear more responsive to changes in dietary cholesterol and fat consumptions than in non carriers.

[12:08]Meaning Alzheimer's risk from APOE may be at least partially modifiable, which is a good news, right? So if our biology is more responsive then my dietary lever has more leverage. So I basically added on that move number two I upgraded my fat sources. So again extra virgin olive oil became the default. Avocado I love avocado with my salmon nuts seeds basically more mono and poly unsaturated fats and less linoleic heavy seed oil or none at all.

[12:37]If you can, try to avoid absolutely avoid any like fried food and so on, which we use like heavy seed oil and really bad for you move number three. And that is linked to level number two. I loaded soluble fiber into every meal. So sometimes I would have some oats.

[12:53]I would have some lentils and beans. Basically food that feed your gut and bind cholesterol. Oh yeah. I also really love kimchi and started eating much more kimchi. And the other power tool is psyllium husk will get there in a minute. But the dietary base kind of matters here.

[13:09]Move number four I drop liquid calories and refined carbs. This was likely the lever that moves my HbA1c from 5.9 to 5.3 more than anything else. Which means no more soda, no more alcohol. Actually, I stopped drinking. No fruit juices. I don't know why, but when I grew up in France, I don't know why, but when I grew up in France, it was supposed to be healthy, to eat, to drink orange juice and all sorts of juices.

[13:34]But actually I just downing sugar without the fiber. And this gives you a glucose spikes. That is extremely bad. So drop everything sweet in your liquids and drop alcohol of course. So what we have is not randomized control trial on Mediterranean diet for APOE4/4 homozygotes specifically, I don't think a lot of studies target us APOE4 carriers, unfortunately, at least not yet.

[14:01]And that's what we're trying to do with Phoenix to have more of these trials, even those that we can run ourselves. But what we have is a 2025 Nature Medicine cohort, which I just cited before, showing amplified metabolic benefits in homozygotes and a consistent body of observational data showing Mediterranean diet adherence reduces cognitive decline across population.

[14:22]So you can probably have this as a no regret. So diet alone would probably have moved my LDL by around 15, maybe 20% making those changes. That's kind of consistent with the literature. It goes between 10 and 20% depending on how bad and how good your diet was before.

[14:43]So for an APOE3/4 person that might be enough. But as a 4/4 I wanted more. Which brings us to lever two, the one a lot of people overlook, and I feel like it's one that is the easiest to implement. I'm talking about Psyllium husk Basically, that's the hulled seeds of a plant called Plantago ovata.

[15:03]I didn't know that. I just did that for the video So it's been used medicinally for centuries. Actually in the US it's sold as Metamucil, in Europe as Fybogel. Actually in the US it's sold as Metamucil, in Europe as Fybogel. You have tons of different salts. In health store you can buy as pure bulk powder.

[15:19]Most people think of it as a fiber supplement for regularity. And that's the least interesting thing it does, because what it actually does And that's the least interesting thing it does, because what it actually does is that psyllium is a viscous, soluble fiber, is that psyllium is a viscous, soluble fiber, and when you mix it with water, it forms a gel.

[15:33]That gel matters because inside your small intestine, that gel traps something critical: bile acids. Your body makes bile acids from cholesterol. Normally 95% of those bile acids get reabsorbed back into your bloodstream after they've done their job digesting fat. It's one of the most efficient recycling system in our physiology actually So Psyllium breaks that recycling.

[15:55]It traps the bile acids in the gel and basically escorts them through the colon and out of your body. So your liver says, hey, I'm running low on bile acids. I need to make more. And guess what happened? To make more bile acids, it needs more cholesterol. And where does it get it?

[16:11]It up regulates LDL receptors on hepatocytes and pulls the cholesterol, specifically LDL, out of your bloodstream to make more of these bile acids. So that's the mechanism. And here's the critical detail. Most supplements marketers won't tell you this mechanism only works with viscous fibers. Inulin doesn't do it. Wheat dextrin doesn't do it FOS doesn't do it. Insoluble fibers like wheat bran doesn't do it. So let's go to a 2017 review bran doesn't do it. So let's go to a 2017 review in the Journal of the Academy of Nutrition and Dietetics high viscosity fibers, for example, gel forming fibers, which are beta-glucan, psyllium, and raw guar gum, exhibit a significant effect on cholesterol lowering and improve glycemic control, whereas non viscous soluble fibers

[16:55]inulin, fructooligosaccharides and wheat dextrin, and insoluble fibers like wheat bran do not provide these viscosity dependent health benefits. So when your gut influencer tells you just eat more fiber, that's actually correct. But it's very imprecise. For cholesterol lowering, you'll specifically need like psyllium, beta-glucan or any comparable viscous fibers.

[17:17]Now how much does it actually move the needle? A 2018 meta analysis in the American Journal of Clinical Nutrition pooled 28 randomized controlled trials looking at close to 2000 participants. The median dose was around ten grams a day, and psyllium reduced LDL cholesterol by 0.33mm/l. So that's about 13mg per deciliter.

[17:40]And it reduced ApoB by 0.05g/l. That's around 5 milligrams per deciliter. Which is not bad for something that you just put in your food right before. I feel like this is such a good result for like almost no pain whatsoever to do, and it doesn't change your lifestyle, right?

[17:59]2024 Meta Analysis. In Nutrition Research, reconfirmed this 29 RCTs total cholesterol down 0.28mm/l. LDL down 0.35 mmol/L. Roughly 7% reduction in cardiovascular event risk. And in 2023, a dose-response meta-analysis, the largest to date 181 trials, over 14,000 participants, gives us a clean per dose number for every five grams per day of soluble fibers, LDL drops by about 5.5mg per deciliter.

[18:29]But here's what made psyllium a no brainer for me. But here's what made psyllium a no brainer for me. Specifically, remember my HbA1c at 5.9, which led to me being pre-diabetic? Well, a 2015 meta-analysis in AJCN looked at psyllium in three population healthy people, prediabetes and type two diabetes.

[18:45]In type two diabetes, psyllium reduced fasting glucose by 37mg per deciliter and HbA1c by 0.97 percentage points. The effect scales with baseline glycemic control. So the worst your blood sugar, the more psyllium helped. In healthy people with already perfect glucose It did nothing because wise that's a feature, not a bug.

[19:05]It means psyllium doesn't drop your blood sugar if you don't need it. So for me with that bad HbA1c, psyllium before meals isn't just for cholesterol. It was also for the glucose. So you get two for one lever So from now on every time I eat or even when I go out eating, I carry So from now on every time I eat or even when I go out eating, I carry like these little things where I have my psyllium inside.

[19:26]And if you can see like it's the powder that's around enough for one dose, I just put it in a cup of water, mix it. Yes, it looks weird. In the restaurant, people will ask a lot of questions, but it's definitely worth it. So I carry always like these around when I'm eating out, especially when I'm traveling. All right. Cool.

[19:42]Now you came for this video. Especially for one specific drug ezetimibe. That's lever number three. So I'll say that very plainly. I believe that ezetimibe has been the single best lever I've pulled. Stacked with diet and psyllium is the biggest reason my ApoB is down close to 40% from where I started, from 115 to around 70.

[20:03]If I had to drop two of my three levers tomorrow. This is the one I would keep. Ezetimibe is a once daily oral cholesterol lowering drug. I take ten milligrams. It's been FDA-approved since 2002, so you have a lot of history and most people, including most doctors, actually do not appreciate what it actually does.

[20:22]actually do not appreciate what it actually does. First of all, Ezetimibe is not a statin. it works completely differently. Statins work in the liver by blocking the enzyme that makes cholesterol. Ezetimibe works in the gut by blocking a protein called NPC1L1 that absorbs cholesterol from your intestines into your bloodstream, both dietary cholesterol and the cholesterol, your liver dumps back into your gut through bile Ezetimibe blocks both of them.

[20:51]Think of it this way. Psyllium traps cholesterol in your gut. Ezetimibe prevents whatever's left from being absorbed. Diet reduces the input of cholesterol. You are taking the same pathways at three different points. So what does it do to your lipids? A 2009 meta analysis in the Journal of Internal Medicine pooled 8 Randomized Control Trials. Ezetimibe monotherapy.

[21:12]reduced LDL cholesterol by around 19% compared to placebo. That's what I expected personally. But the question you're probably asking is, does it actually prevent anything? Or is it just, you know, moving numbers on your paper, on your blood work paper, which doesn't really matter in the So for that, we look at EWTOPIA 75, a randomized controlled trial published in circulation in 2019, and 3,796 Japanese patients, all 75 and older, randomized to ezetimibe monotherapy or dietary counseling alone Then you have Median follow-up four years after. The hazard ratio for the primary cardiovascular endpoint 0.66 the confidence interval 0.50 to 0.86. P-value of 0.002.

[21:58]Basically a 34% reduction in cardiovascular events on ezetimibe alone. No statin. That's the only RCT proving ezetimibe alone prevents cardiovascular events. It was in all the Japanese population. It's not really my or your demographics, I believe, but the mechanism is kind of the same for everyone. So let's talk about the APOE4 questions.

[22:18]There is actually a small 2007 study. Only 28 patients with APOE3 versus 28 with APOE4 that specifically tested whether ezetimibe works the same across ApoE genotype. And good news for us, it does. The LDL reduction in APOE3/3 was 22.8%, and in APOE4 carriers, it was 19.6%. It's not really a statistically significant difference because of a very low volume of of patients.

[22:45]And the quote is ezetimibe significantly improved. Lipid and lipoprotein profiles from baseline, irrespective of APOE3/3 or E4 genotype. Good. So now we know ezetimibe works for APOE4 carriers. It's not really a surprise, but it's always good to validate that right. Here's where it gets very interesting. In 2024.

[23:03]that right. Here's where it gets very interesting. In 2024. So much more recently a paper in Aging Biology looked at what ezetimibe might do beyond cholesterol. So the authors, Ganne and colleagues mined clinical databases and found that ezetimibe was associated with a sevenfold reduction in Alzheimer's and related dementia risk.

[23:20]Let me be careful. This is observational data. It's not randomized trial and it's retrospective database mining. So to explain it a little bit observational data you come with tons of confounders right. It could, for example, mean that people who are taking ezetimibe also care about their health. They might have more income.

[23:42]They might visit the doctor more often, which means that they are more healthy and so on. So tons of confounders. But that sevenfold effect size is insane, right? It's really unprecedented. And when something looks too good, you still have to be a bit skeptical. So the authors themselves say double blind randomized trial of newly enrolled patients will have to be conducted to establish a causal connection.

[24:04]So on its own I'd file that under: interesting, unproven, but still sevenfold for just one small pill that you are popping every day, it's kind of good if it works right. The great thing is that it didn't stay on its own that study in 2025. and this is the study that actually moved me The journal, Alzheimer's & Dementia published the strongest test of this idea we have.

[24:29]Researchers led by. Nordestgaard group in Copenhagen used a method called Mendelian randomization across more than a million people. So I think we mentioned that in several other videos but here's why Mendelian randomization matters. Some people are born with a gene variant that makes a specific protein a little less active for their entire life.

[24:50]If you study those people, you get something close to a natural, lifelong randomized trial free of lifestyle confounders that wreck ordinary observational studies or things that I mentioned earlier right income, how much they care about their health, and so on, because that's a gene that changes something, and you can assume that everything else is equal So the researchers looked at the gene for NPC1L1, which is the exact protein.

[25:15]ezetimibe blocks. And people whose genetics mimic basically taking ezetimibe, lifelong have dramatically lower dementia risk. An odds ratio of 0.18. For every 1mm/l drop in non-HDL cholesterol through that pathway, the statin target pointed the same direction. The conclusion in their words: genetic lowering of non-HDL cholesterol via HMGCR or NPC1L1 and CETP reduces the risk of dementia.

[25:44]So this is not complete Absolute proof that the pill cuts your dementia risk Just be careful here. It basically measures a lifelong genetic effect, not a few years on a tablet that you can take. It's what scientists call target validation. And the effect was strongest for vascular and unspecified dementia, a bit weaker for Alzheimer's specifically.

[26:03]But if you pair it with Ganne signal that we mentioned earlier and the mechanism story underneath, you've got something interesting and unproven that we mentioned before to, you know, the same target lit up from two completely different directions. Now it becomes something that is really worth considering. And here is the mechanism story, because I believe that's very important for you to understand the mechanism behind all this.

[26:25]The Aging Biology authors proposed three: one, lower plasma cholesterol the same as statins. Number two is that ezetimibe disrupts the interaction between a protein called 14-3-3 gamma and hexokinase And that disruption reduces protein aggregation. So that's the kind of aggression that drives neurodegenerative disease. Three, ezetimibe restores autophagy, which is the cellular cleanup process that removes damaged proteins.

[26:51]So the drug might be doing more than lowering cholesterol. It has other pathways. It might be helping clear the aggregation that APOE4 carriers are particularly vulnerable to. It's still a hypothesis. The million-person genetic data is the strongest leg it stands on. It's not complete proof, but it's very close.

[27:09]Now what about safety side effects and so on. So, A narrative review, published in Current Cardiology Reports in December 2025, synthesized the cognitive outcome literature for all lipid lowering drugs. The conclusion on ezetimibe direct quote monoclonal antibodies PCSK9 inhibitors, ezetimibe and bempedoic acid appear neurocognitively safe and peripheral cholesterol lowering does not starve your brain.

[27:35]So from Mahley's 2016 review in Arteriosclerosis Thrombosis, and Vascular Biology there is essentially no cholesterol that enters the brain from the peripheral circulation. So your brain makes its own cholesterol. The blood brain barrier keeps the two system extremely separate. that's why I'm very comfortable taking ezetimibe as an APOE4/4 carrier.

[27:54]The drug lowers peripheral cholesterol. It doesn't touch the brain cholesterol pool, which is very important. So before I show you the results, I need to flag three things from this year that changes how this conversation should sound in 2026. Because I'm recording this video in May 2026, and the Ezetimibe evidence picture has shifted faster than any other interventions I actually follow.

[28:16]So first, in March 2026, the 2026 ACC/AHA Dyslipidemia guideline. This is basically the first major US lipid guidelines since 2018. Three things to know. One is that high risk patients should target LDL below 70 and very high risk below 55. Now. And being fully honest, those tiers are built around heart disease and diabetes not APOE genotype.

[28:37]so the guideline wouldn't formally call it for us. But it leans much harder than before on lifetime risk and starting earlier. And that's exactly the logic I would apply for APOE4 genotype. Two. ApoB is now endorsed to help guide non-statin therapy decisions. When to add ezetimibe, bempedoic acid, or a PCSK9 inhibitor ApoB has finally been pulled into the mainstream algorithm.

[28:59]And that is great. And number three, ezetimibe is explicitly listed as a first line non-static add on. Because when I was still in medical school ezetimibe was kind of no one really cared about it. Like the cousin nobody invited to dinner, it was all about statins. Now that after March 2026, at least in the US, it's at the table.

[29:21]A second interesting thing. Also in March 2026, a lot of stuff happened in March. The Ez-PAVE trial was presented at the American College of Cardiology 2026 Scientific Sessions, simultaneously published in the New England Journal of Medicine. Lee and colleagues randomized 3,000 plus patients with established atherosclerotic cardiovascular disease across 17 sites in South Korea to one of two LDL targets below 55mg per deciliter or below 70.

[29:51]Treatment was statin alone or statin plus ezetimibe, PCSK9 if needed. After three years, the median LDL in the aggressive arm was 56, in the conventional arm, 66. So ten more and the primary composite endpoint cardiovascular death, nonfatal MI, nonfatal stroke, and any revascularization or hospitalization occurred in 6.6% of the intensive arms versus 9.7% of the conventional arm.

[30:18]So the hazard ratio was 0.67. Confidence interval 0.52 to 0.86, which is a 33% relative risk reduction driven primarily by reductions in nonfatal MI and revascularization. So this was one of the first trial to randomized patients directly to two different LDL targets, head to head in a population.

[30:39]So and the way most patients got to those low numbers without exploding their pharmacy bill was ezetimibe added to the statin. The trial recommended uptitrating the statin and adding ezetimibe before reaching for a PCSK9 inhibitor. Number three April 2025. That is published a year ago now, but only now reshaping practice.

[31:00]The SWEDEHEART which is a registry analysis in the Journal of the American College of Cardiology, 36,000 approximately patients in Sweden's national post MI registry. Three groups: early ezetimibe added within 12 weeks of the heart attack. Late ezetimibe, or no ezetimibe at all One year MACE rates per 100 patient years 1.79 in the early group, 2.58 in late and 4.03 in the no-ezetimibe group.

[31:27]So the hazard ratio for cardiovascular death at three years in the no-ezetimibe group versus early combination was 1.83. This entire thing means patients who never got ezetimibe were 83% more likely to die of cardiovascular causes. The authors concluded that delaying combination therapy or using statin monotherapy was associated with avoidable harm.

[31:50]So to be fair, both the Ez-PAVE and the SWEDEHEART are secondary prevention populations, meaning those are people who already have heart disease or have had a heart attack. That's not me. That is probably not you, I'm guessing. So. I haven't had an event because I'm still quite young, but I'm a primary prevention APOE4 with elevated baseline lipids, so I treat these as the direction the field is moving.

[32:15]elevated baseline lipids, so I treat these as the direction the field is moving. It's not proof about my exact situation, but the signal that it sends across all three papers on the same way. Earlier lower And ezetimibe inclusive. That's why I'm not waiting until I'm much older to think about this.

[32:28]And that's why I'm on ten milligrams a day, probably for the rest of my life, unless some other evidence come out that I shouldn't. So now let me show you what these three levers diet, psyllium, ezetimibe actually did. And I'm going to grade myself against the Phoenix ranges not the standard laboratory ranges, because that's the honest bar.

[32:47]So three panels, what you have in December 2024, May 2025, five months in and August 2025. Eight months in last year. Because those were the initial moment when I started to take ezetimibe and I started actively working on my ApoE4 because, as a reminder, I actually realized I carry ApoE4 in December 2024.

[33:08]That's when I started to to all of this. And next to each number, I'm putting the Phoenix optimal range. So the exact band or member see in the bloodwork module again, which is tighter than what your labs call normal. So on these three markers I'm fully inside the Phoenix optimal band HDL 73 against a target of 60 or higher for men, triglycerides 56.

[33:29]So that's at the center. Lp(a): 2.9 That's great. That's mainly genetic. I got lucky there on that last one. On the rest. I wasn't optimal yet, but I was knocking on the door. Now nowadays it's way better. LDL dropped from 139 to 93, so that's a 33% fall a 46 point drop.

[33:51]The optimal will be below 80. So I'm still above total cholesterol. I need to go slightly below. I would still need to lower my HbA1c more. I believe right now I am at five or something. So it happened, but it took a bit more time for me. Again, these are the lab results only eight months after starting because I feel like this is more relevant for you rather than looking at something two years And you know, here's the thing.

[34:17]It's why our ranges are tighter than your lab's every one of these biomarkers would have your doctors tell you, okay, it looks great. See you next year. Right from any standard panel. And using all the research, we know that we have to be more aggressive. Now because Phoenix optimal for ApoB is 40 to 70.

[34:36]I still needed to bring that lower. And I did more drastic diet changes. And now I believe it's around 65. If I'm not wrong. So I'm like very close. But I've been taking ezetimibe for nonstop for this entire duration. And my plan is to push it under 60.

[34:56]So that's my goal for the next, let's say, six months. I really believe in not trying to be too aggressive too fast, which is what I tried to do early on I basically loved eating and then I felt very guilty every time I would eat food. That doesn't go into a very strict protocol like fish and so on, but that made me extremely, extremely miserable.

[35:21]So now I'm letting myself like it'll be cleaner. I ate sometimes like ice cream, sometimes have some ribeye, sometimes have a glass of wine here and there. I am way happier that way. It's way more sustainable and depending on your targets, you might want to do that because it's a marathon.

[35:36]It's really not a sprint. Have a very good baseline. Hold it. 90-95% of the time and 5% of the time just go crazy. It's fine. Like you need to live a little right? Especially if you like drinking or eating like me. I think that's more important to keep also your mental health too in check by not having something to drastic.

[35:57]All right, now, since we're talking about ezetimibe, I'm a doctor of pharmacy. So let me go a little bit more on things that you should really hear clearly. Number one, those three levers that I use acting at once means I really can't precisely tell you which one moves what.

[36:15]Even though that's what our Phoenix app is doing, looking at all the data across members to try to quantify the effect size of each intervention. So ezetimibe by itself normally would drop LDL by about 18%, psyllium adds roughly another 5 to 10%. I guess diet is very, very variable depending on how your diet was before and after.

[36:36]So my read here is that ezetimibe did heavy lifting on ApoB, Psyllium and diet stacked on top. I can't cleanly separate them without A/B testing myself. I'm not willing to do that. So I chose transformation over dissection, which is probably what you want to do as well. Like stack a few things.

[36:53]If it works, pick the ones that you can comfortably stay with and continue with. Number two is I'm not on a statin. It doesn't mean that statins are bad. You have a lot of studies. For example, the 2024 Neurology study found that statin initiation in APOE4 carriers reduced Alzheimer's risk by 40% with no dementia benefit in non-carriers.

[37:12]So this study provides Class II evidence that among those aged 65 years old, statin initiation was associated with a reduced risk of Alzheimer's disease, especially in the presence of an APOE4 allele. I'm not on one yet. I may add one in the future. The door is open, not closed.

[37:27]We have another video with Doctor Grant Fraser where we cover all the lipid panels, and he has an aggressive strategy with swapping different statins in that you might want to watch if you're curious about statins. Number three is where I personally stand against the Phoenix range. I am close to it for some of it, but not completely there.

[37:47]And that's again a personal decision to still enjoy life a little bit. Number four. And the strongest brain evidence that, you know, the million-person Mendelian randomization is target validation, not a drug trial. It does not prove that taking ezetimibe for a few years It will do the same as someone with the same genetic mutation.

[38:06]That led to seven fold lower Alzheimer's risk You have to remember that the effect was strongest with vascular dementia. It's a bit weaker for Alzheimer's but honestly, it's super high and high enough to really consider Ezetimibe Five, on psyllium specifically, there is no randomized trial there. It's a supplement.

[38:26]There's probably no money in the market for people to run a trial on this. But again, it's a very low/no regret move for me and probably for you. So definitely consider it. And six, that might be important. My ALT on my panel was 64 which is quite above the reference range.

[38:45]It's not really clinically alarming. It's not a reason to stop, but sometimes ezetimibe can nudge liver enzymes. So if yours rise meaningfully, you might want to check that. And you might want to let your doctor All right. if you are an ApoE4 carrier summarize, here's the blueprint I'll hand you.

[39:02]These are the exact APOE4 optimal ranges Phoenix members see every time they open their bloodwork module. I am putting the link in the description. I have a free PDF for you where you can download the ApoE4 Blood Work Blueprint. So look at those, download it. That will give you everything that you need to bring to your doctor.

[39:22]And again start with the levers that you can hold for years, not weeks. Diet is lever number one. Psyllium before meal is completely free. It's evidence backed. It's very easy, not completely free, but very cheap and looking at Ezetimibe is probably the one that moves my ApoB. I will link every study below.

[39:43]Every lab panel is already in the video. If you want to go deeper into your APOE4 lipid strategy or more, join the Phoenix community. This is where we do exactly this. We experiment. We validate across everything else, all the different biomarkers that you need to optimize as an APOE4 carriers.

[40:02]We have 27 different biomarkers that are APOE4-optimized. So not just LDL-C, ApoB, but many more. And I believe that it's really worth the investments. That's at least what our members tell me every day. That is the best investment they've done for their health. And I am building Phoenix very fast, so I would love to have you in, especially if you're still watching the video right now.

[40:24]Remember, your genes load the gun, You decide to pull the trigger or not, and you have full control over whether you can beat the odds or not. All right, I'll see you in the next video. Bye!