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Cholesterol Confusion

First off, this not intended to be an exhaustive review of cholesterol science. Because, a) you'd get bored, and b) Peter Attia did an insurmountable job of that in his 10 part series here.

The purpose of this article is just to shed a bit of light on a confusing topic to help get readers up to speed on the current understanding of cholesterol measurements and ultimately, some serious relevance to your health and longevity.

Pretty much everybody I know has either been recommended cholesterol meds, or they know parents, grandparents, or friends that have. Our society has been inundated with an absurd ubiquitousness regarding "fattening" foods and heart disease, and I would love for people to be armed with some actual knowledge on the subject that surpasses the "oh, enjoy that steak, good luck with your heart disease" conversation.

And I'm going to try muzzle my inner nerd and not get too science heavy, so stick with me through a few moderately intangible concepts, as I've included pretty pictures to lubricate the assimilation process. So hide the margarine, here we go.

Very few nutrition or medical experts are making recommendations based on the most current scientific data, some are quite a bit farther behind than others. The reasons for this discordance are numerous and will be touched upon later.

The information provided here should be taken as opinion, not medical advice. This opinion, however, is based on an extensive review of published scientific literature, books and other published sources from a small number of true experts, as well as years of intricately analyzing lab tests from clients and watching how values change given specific dietary and lifestyle interventions.

The volume of blood work I have had the opportunity to review is a drop in the bucket, however, compared to cardiologists that do this all day, every day, which is why I defer to their data when possible (and by possible, I mean the inclusion of only cardiologists who actually keep up with, and/or contribute, to current research).

Outdated concepts regarding cholesterol continue to permeate mainstream advice, like the existence of bad (LDL) and good (HDL) cholesterol, or that LDL and HDL are even cholesterol at all (they’re not, they’re vessels that transport cholesterol through the bloodstream, which it turns out, is a very important distinction). However, the more educated professionals have, for quite some time now, abandoned the unfounded and flat out dangerous Lipid Hypothesis, which has prevailed in the medical community and therefore public consensus since the 1970’s.

This hypothesis basically states that serum cholesterol levels are a direct predictor of atherosclerosis and heart disease. Combine that with a similar and often mistakenly rolled-into-one hypothesis called The Diet Heart Hypothesis, which states that the more cholesterol and saturated fat we eat, the higher our cholesterol gets, and the more likely we are to get heart disease.

These were not bad hypotheses at the time given the limited amount of information and the inadequate testing methods available. Instead of rigorously testing these hypotheses before launching them as gospel, however, they (or in a combined form, "it") was embraced prematurely and almost every governmental public health organization hopped on board demonizing saturated fat and promoting the ingestion of a substantial increase in dietary grains.

The way this played out in history is actually pretty interesting, amusing, and infuriating all at the same time, and you can read more about it here, and here, but I’m sure it won’t come as a major surprise that the whole thing has been motivated by money, and a couple of logical fallacies known as Confirmation Bias, and plenty of The Sunk Cost Fallacy.

Back to the abandonment of the Lipid Hypothesis and the Diet Heart Hypothesis; taking the next steps beyond that level of understanding is where things start to get interesting.

Let's look at the development of more sensitive blood lipid testing methods, like the Vertical Auto Profile (VAP). As of 2007 when Atherotec made the VAP publically available, we have been able to easily identify different subclasses of LDL particles, namely type-A (large/buoyant) and type-B (small/dense).

Think of "type-A" as fluffy cotton balls and "type-B" as little marbles. I've taught this concept with these visual models in several seminars and it seemed to stick with the audience, so we're running with it.

Quite a bit of recent research looked at these distinctions between type A & B, and it was preliminarily determined that only type-B (the marbles) were dangerous. The science savvy hopped on board with this right away (including myself) and started making this a major focus in the discussion of heart disease prevention and how we looked at blood tests.

As the field continues to progress, we have come upon even more accurate information and better testing methods. It's no secret that your iPhone would have cost about $3.6M twenty years ago, but what is truly disturbing, is that your doctor talking to you about cholesterol is basically a guy at the Apple Genius Bar looking at your brand new MacBook Pro, giving you advice based on what he's been taught about the 1995 Macintosh Desktop.

One new type of testing is called an NMR panel (Nuclear Magnetic Resonance), click here for a sample report. It turns out that even type-A (fluffy/bouyant) LDL particles can be atherogenic, which doesn’t necessarily nullify the theory of type-B particles being a relevant risk factor, but it requires some re-evaluation.

With an NMR test, we can now look directly at the actual number of LDL particles (think of them as the number of boats carrying cargo through the bloodstream, known as LDL-P) instead of the current testing which just looks at LDL cholesterol (think of this as how much cargo the boats are carrying, known as LDL-C or just LDL).

One boat (LDL-P), packed full of cargo (LDL-C)

An LDL-P boat looking for some cholesterol (LDL-C)

Current research demonstrates this (LDL-P measurement) is likely a far better predictor of heart disease risk and atherogenic potential than LDL-C or even particle size. The small/dense theory is not without merit, it just probably acts as a potential proxy for LDL-P values. The problem is, and I’ve seen this several times, that they don’t always match up as expected.

Here’s a comment on this particular matter on Peter Attia’s blog from one of my favorite cholesterol experts, Dr. Thomas Dayspring:

“If you have too many small LDLs or too many big LDLs you are at risk for CHD. If you have all small LDLs but total LDL-P is normal, there is no risk. If you have normal numbers of very large LDLs your LDL-C might be high but LDL-P will be fine and thus no risk exists. Peter nicely illustrates that if you have small LDLs, it will take 40-70% more LDLs to traffic a given mass of cholesterol, hence untreated folks with small LDLs always have a high LDL-P and that is what drives risk. Likewise if one’s LDLs are pathologically carrying TG instead of cholesterol (i.e. a cholesterol depleted LDL) it will take many more such cholesterol-depleted LDLs to carry a given cholesterol mass. Risk is related to particle number not to the amount of cholesterol within the LDL particles, because it is particle number that drives the LDLs into the artery.”

ApoB is another important reading to look at, as each LDL-P can have only one ApoB protein bound to its cell wall, so measuring ApoB can give us an idea of the LDL-P number, although it is not as exact as true LDL-P measurement.

From a nutrition perspective, carbohydrate intake directly relates to both triglyceride and HDL levels.

Eat more carbs and HDL goes down, triglycerides go up.

Bad news. However, I’ve seen several people replace their starchy carb intake with good fats, and while their Triglyceride:HDL ratio improves, their small/dense LDL doesn’t budge, yet their LDL-P drops. This is likely uncommon, but it just tells us these proxies are not foolproof, just a guess with a decent probability.

And in this case, going off of the LDL pattern type (small/dense or large/bouyant) would be detrimental, as the HDL/Trig ratio and LDL-P values improved which is what is really important.

Research also demonstrates that reducing fat intake in the diet can often encourage a decrease in LDL-C, at the expense of shifting the particle size to the small/dense type, and actually raising LDL-P. Keeping lots of good fat (including saturated fat) in the diet while reducing carbohydrate intake typically has the exact opposite effect, LDL-C might go up a little, but the particle size shifts to large/buoyant type-A, and LDL-P goes down. So yes, a low fat diet can often make numbers look better on paper, if you’re looking at the wrong numbers in the first place.

To summarize, its better to have more data than not enough, and if LDL-P is above optimal, that should outweigh all other values on a lipid test. If you don’t have your LDL-P number, but you have a VAP test, you might be able to get a decent guess by looking at your LDL pattern size. If you just have the basic cholesterol test your doctor typically gives you, you might be able to get a decent guess at your heart disease risk by looking at your Triglyceride:HDL ratio (1:1 is optimal, 2:1 is passable, anything above that is likely trouble). Note, this is not the same as the fucking useless "Cholesterol to HDL" ratio you will find on your lab printout. But the Trig:HDL ratio is still a guess, a proxy, and NMR testing is inexpensive and easy to get, you can order the test here for $127 and go to a local lab to get it drawn.

From my experience, many physicians will tell their patients (you) that more in-depth cholesterol testing like the VAP and NMR are unnecessary. This would be entirely true if the Lipid Hypothesis had any sort of validity, which it doesn’t.

One doctor told a client of mine that there is no point in doing the NMR test because it wouldn’t change the treatment recommendations beyond what would be advised from the basic cholesterol test (in the mind of the doctor, either I’m going to prescribe you statins or I’m not), which is basically admitting a complete lack of understanding of the data (I actually hear this exact statement from doctors all the time about all advanced lab testing, like thyroid, adrenals, sex hormones, etc).

If your doctor tells you this, order the test yourself from Direct Labs or Life Extension and find a qualified professional to interpret it for you and give you recommendations. There’s lots of great, progressive people out there willing to help, see my resources at the end of the article for some ideas.

Obviously cholesterol and its relationship to heart disease is an emerging science, and we are learning more every year. We don’t know everything yet, but what we are rapidly learning is what we can rule out. At this point, we can confidently rule out total cholesterol (TC) and LDL-C as relevant information. However some doctors still consider extremely high LDL-C a reliable proxy for high LDL-P, stating that LDL-C is therefore not useless, but it’s still based on likelihood of what the LDL-P value would be, so why not test it in the first place? HDL particles being thought of as simply “good” cholesterol is outdated. High HDL-C can be problematic as well! Particle size (type-A or type-B) is interesting to look at, but again it is likely only a risk factor as it relates to predictability of LDL-P number.

Also, I should mention, that due to genetic makeup (specific ApoE genotypes in particular, which are actually easy to test for), or other factors, some people will notice a worsening of LDL-P on a lower carbohydrate, higher fat diet. ApoE 3/4 or ApoE 4/4 markers are super uncommon, but they can explain why you're responding poorly to a ketogenic diet. So get your bloodwork done and work with a knowledgeable professional when making dietary changes, particularly if you’re doing it for the purpose of disease avoidance and life extension.

So how does this high LDL-P number act as a predictor for heart disease risk? That involves inflammation, oxidation, aggregation, and another article for another time.

Want to get more in depth? Check out the Depasi Fitness webinar on Lipidology.

For more general information on the topic, see the following great resources:

Peter Attia’s awesome video on cholesterol:

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