The Straight Dope on Cholesterol: 10 Things You Need to Know – Part 2

This is a guest post by Peter Attia and is a summary based on a 10-part series of the same name that you can find at The Eating Academy.

To read The Straight Dope on Cholesterol: 10 Things You Need to Know – Part 1 click here.

To start at the beginning of Peter’s 10-part series click here.

Now, Peter…

6. Inflammation makes it worse, but the inciting event is the LDL particle getting past the endothelium.

Because there is no experiment or clinical trial we can carry out to unambiguously resolve the exact role of inflammation in this process (and, by extension, the role of LDL particles), we rely on so-called “natural experiments.”

Such “natural experiments,” which help elucidate this role, are those of people with genetic alterations leading to elevated or reduced LDL-P. Let’s consider an example of each:

  1. Cohen, et al. reported in the New England Journal of Medicine in 2006 on the cases of patients with mutations in an enzyme called proprotein convertase subtilisin type 9 or PCSK9. Normally, this proteolytic enzyme degrades LDL receptors on the liver.  Patients with mutations (“nonsense mutations” to be technically correct, meaning the enzyme is somewhat less active) have less destruction of hepatic LDL receptors. Hence, they have more sustained expression of hepatic LDL receptors, improved LDL clearance from plasma, and therefore fewer LDL particles. These patients have very low LDL-P and LDL-C concentrations (5-40 mg/dL) and very low incidence of heart disease. Note that a reduction in PCSK9 activity plays no role in reducing inflammation.
  2. Conversely, patients with familial hypercholesterolemia (known as FH) have the opposite problem. While there are several variants and causes of this disease, the common theme is having decreased clearance of apoB-containing particles, often but not always due to defective or absent LDL receptors, leading to the opposite problem from above. Namely, these patients have a higher number of circulating LDL particles, and as a result a much higher incidence of atherosclerosis.

So why does having an LDL-P of 2,000 nmol/L (95th percentile) increase the risk of atherosclerosis relative to, say, 1,000 nmol/L (20th percentile)? In the end, it’s a probabilistic game. The more particles – NOT cholesterol molecules within the particles – you have, the more likely the chance a LDL-P is going to ding an endothelial cell, squeeze into the sub-endothelial space, and begin the process of atherosclerosis.

7. LDL particles (LDL-P), not LDL cholesterol content (LDL-C), is what drives sterols into artery walls – Don’t confuse the “boats” and the “cargo.”

There are several examples of long-term studies examining the predictive power of LDL-C versus LDL-P with respect to cardiovascular disease. This study followed a Framingham offspring cohort of about 2,500 patients over a median time period of almost 15 years in each of the four possible groups (i.e., high-high, high-low, low-high, and low-low) and tracked event-free survival. In this analysis the cut-off points for LDL-P and LDL-C were the median population values of 1,414 nmol/L and131 mg/dL, respectively. So, “high” implies above these values; “low” implies below these values. Kaplan-Meier survival curves are displayed over a 16 year period – the steeper the slope of the line the worse the outcome (survival).

The same patterns observed in the other studies are observed here:

  1. High LDL-P is the best predictor of adverse cardiac events.
  2. LDL-C is only a good predictor of adverse cardiac events when it is concordant with LDL-P; otherwise it is a poor predictor of risk.

Interestingly the persons with the worst survival had low (below median) LDL-C but high LDL-P. The patients most likely to have high LDL-P with unremarkable or low LDL-C are those with either small LDL particles, or TG-rich/cholesterol poor LDL particles, or both (e.g., insulin resistant patients, metabolic syndrome patients, T2DM patients). This explains why small LDL particles, while no more atherogenic on a per particle basis than large particles (see point #9), are often a marker for something sinister.

8. People with metabolic syndrome are at even greater risk of LDL-C/LDL-P discordance.

Concordance is a statistical term that refers to variables that predict the same thing. Conversely, discordance refers to variables that do not predict the same thing. When LDL-C (what most doctors measure in your blood test) and LDL-P (what most doctors do not measure in your blood test) predict the same risk, they are said to be concordant. When they do not, they are said to be discordant. In the latter case, LDL-P is the one to follow.

To illustrate the prevalence of discordance between LDL-C and LDL-P, consider the figure below.

This figure shows data from patients with LDL-C between 100 and 118 mg/dL (i.e., second quartile of risk: 25th to 50th percentile) without metabolic syndrome (top) and with metabolic syndrome (bottom). In the patients without metabolic syndrome, LDL-C under-predicts cardiac risk 22% of the time. However, when you look at the patients with metabolic syndrome, you can see that 63% of the time their risk of cardiac disease is under-predicted.

The data above were collected from nearly 2,000 patients with diabetes who presented with “perfect” standard cholesterol numbers: LDL-C < 70 mg/dL; HDL-C > 40 mg/dL; TG <150 mg/dL. However, only in 22% of cases were their LDL-P concordant with LDL-C. That is, in only 22% of cases did these patients have an LDL-P level below 700 nmol/L.

Remember, LDL-C < 70 mg/dL is considered VERY low risk – the 5th percentile. Yet, by LDL-P, the real marker of risk, 35% of these patients had more than 1,000 nmol/L and 7% were high risk. When you do this analysis with the same group of patients stratified by less stringent LDL-C criteria (e.g., <100 mg/dL), the number of patients in the high risk group is even higher.

As a general rule, the more “metabolically deranged” an individual is, the greater this discordance between LDL-C and LDL-P, as shown in the figure below. The axis of this figure is adjusted so that the red bars and the blue bars should be of the same height when LDL-C and LDL-P are concordant.

9. A smaller LDL particle is no more or less atherogenic than a large one – a particle is a particle.

Particle size is something many folks fixate on, and there is no doubt that smaller LDL particles are associated with greater risk.  But, on a particle-by-particle basis are they, in fact, more atherogenic? Let’s find out.

This figure (one of the most famous in this debate) is from the Quebec Cardiovascular Study, published in 1997, in Circulation. You can find this study here.

This is kind of a complex graph if you’re not used to looking at these. It shows relative risk – but in 2 dimensions. It’s looking at the role of LDL size and apoB (a proxy for LDL-P). What seems clear is that in patients with low LDL-P (i.e., apoB < 120 mg/dl), size does not matter. The relative risk is 1.0 in both cases, regardless of peak LDL size.  However, in patients with lots of LDL particles (i.e., apoB > 120 mg/dl), smaller peak LDL size seems to carry a much greater risk – 6.2X.

If you just looked at this figure, you might end up drawing the conclusion that both size and number are independently predictive of risk. Not an illogical conclusion…

What is not often mentioned, however, is what is in the text of the article:

“Among lipid, lipoprotein,and apolipoprotein variables, apo B [LDL-P] came out as the best and only significant predictor of ischemic heart disease (IHD) risk in multivariate stepwiselogistic analyses (P=.002).”

“LDL-PPD [peak LDL particle diameter] – as a continuous variable did not contribute to the risk of IHD after the contribution of apo B levels to IHD risk had been considered.”

What’s a continuous variable? Something like height or weight, where the possible values are infinite between a range. Contrast this with discrete variables like “tall” or “short,” where there are only two categories. For example, if I define “tall” as greater than 6 feet, the entire population of the world could be placed in two buckets: Those who are “short” (i.e., less than 6 feet tall) and those who are “tall” (i.e., those who are 6 feet tall and taller). This figure shows LDL size like it’s a discrete variable – “large” or “small” – but obviously it is not. It’s continuous, meaning it can take on any value, not just “large” or “small.” When this same analysis is done using LDL size as the continuous variable it is, the influence of size goes away, and only apoB (i.e., LDL-P) matters.

This effect has been observed subsequently, including the famous Multi-Ethnic Study of Atherosclerosis (MESA) trial, which you can read here. The MESA trial looked at the association between LDL-P, LDL-C, LDL size, IMT (intima-media thickness – the best non-invasive marker we have for atherosclerosis), and many other parameters in about 5,500 men and women over a several year period.

This study used the same sort of statistical analysis as the study above to parse out the real role of LDL-P versus particle size, as summarized in the table above.

This table shows us that when LDL-P is NOT taken into account (i.e., “unadjusted” analysis), an increase of one standard deviation in particle size is associated with 20.9 microns of LESS atherosclerosis, what one might expect if one believes particle size matters. Bigger particles…less atherosclerosis.

However, and this is the important part, when the authors adjusted for the number of LDL particles (in yellow), the same phenomenon was not observed. Now an increase in LDL particle size by 1 standard deviation was associated with an ADDITIONAL 14.5 microns of atherosclerosis, albeit of barely any significance (p=0.05).

Let me repeat this point: Once you account for LDL-P, the relationship of atherosclerosis to particle size is abolished (and may even trend towards moving in the “wrong” direction – i.e., bigger particles…more atherosclerosis).

10. The greatest way to reduce your risk of atherosclerosis is to make sure your boats are carrying the right cargo – that way you’ll need fewer of them.

LDL particles traffic not only cholesterol ester but also triglycerides. Each and every LDL particle has a variable number of cholesterol molecules which, because of constant particle remodeling, is constantly changing.  In other words, of the several quadrillion LDL particles floating in your plasma, no two are carrying the exact same number of cholesterol molecules. It takes many more cholesterol-depleted LDL particles than cholesterol-rich LDL particles to traffic a given cholesterol mass (i.e., number of cholesterol molecules) per volume of plasma (i.e., per dL). Core cholesterol mass is related to both LDL particle size (the volume of a sphere is a third power of the radius – it can take 40-70% more small particles than large LDL particles to traffic a given cholesterol mass) and the number of TG molecules per LDL particle.

TG molecules are larger than cholesterol ester molecules, so as the number of TG molecules per particle increases, the number of cholesterol molecules will be less – in a very non-linear manner. Regardless of size, it takes many more TG-rich LDL particles (which are necessarily cholesterol-depleted) to traffic a given cholesterol mass than TG-poor LDL particles.  The persons with the highest LDL particles typically (though not always) have small LDL particles that are TG-rich. These are incredibly cholesterol-depleted LDL particles.

Let’s start with what we know, then fill in the connections, with the goal of creating an eating strategy for those most interested in delaying the onset of cardiovascular disease.

There are several short-term studies that have carefully examined the impact of sugar, specifically, on cardiovascular risk markers. Let’s examine one of them closely. In 2011 Peter Havel and colleagues published a study titled Consumption of fructose and HFCS increases postprandial triglycerides, LDL-C, and apoB in young men and women. If you don’t have access to this journal, you can read the study here in pre-publication form. This was a randomized trial with 3 parallel arms (no cross-over). The 3 groups consumed an isocaloric diet (to individual baseline characteristics) consisting of 55% carbohydrate, 15% protein, and 30% fat. The difference between the 3 groups was in the form of their carbohydrates.

Group 1: received 25% of their total energy in the form of glucose

Group 2: received 25% of their total energy in the form of fructose

Group 3: received 25% of their total energy in the form of high fructose corn syrup (55% fructose, 45% glucose)

The intervention was relatively short, consisting of both an inpatient and outpatient period, and is described in the methodology section.

Keep in mind, 25% of total energy in the form of sugar is not as extreme as you might think. For a person consuming 2,400 kcal/day this amounts to about 120 pounds/year of sugar, which is slightly below the average annual sugar consumption in the United States. In that sense, the subjects in Group 3 can be viewed as the “control” for the U.S. population, and Group 1 can be viewed as an intervention group for what happens when you do nothing more in your diet than remove sugar, (which was the first dietary intervention I made in 2009).

Despite the short duration of this study and the relatively small number of subjects (16 per group), the differences brought on by the interventions were significant. The figure below shows the changes in serum triglycerides via 3 different ways of measuring them. Figure A shows the difference in 24-hour total levels (i.e., the area under the curve for serial measurements – hey, there’s our integral function again!). Figure B shows late evening (post-prandial) differences. Figure C shows the overall change in fasting triglyceride level from baseline (where sugar intake was limited for 2 weeks and carbohydrate consumption consisted only of complex carbohydrates).

The differences were striking. The group that had all fructose and HFCS removed from their diet, despite still ingesting 55% of their total intake in the form of non-sugar carbohydrates, experienced a decline in total TG (Figure A, which represents the daily integral of plasma TG levels, or AUC). However, that same group experienced the greatest increase in fasting TG levels (Figure C). Post-prandial TG levels were elevated in all groups, but significantly higher in the fructose and HFCS groups (Figure B). The question this begs, of course, is which of these measurements is most predictive of risk?

Historically, fasting levels of TG are used as the basis of risk profiling (Figure C), and according to this metric glucose consumption appears even worse than fructose or HFCS. However, recent evidence suggests that post-prandial levels of TG (Figure B) are a more accurate way to assess atherosclerotic risk, as seen here, here, and here.

The figure below summarizes the differences in LDL-C, non-HDL-C, apoB, and apoB/apoA-I (remember, apoB and apoA-I are good surrogates for LDL-P and HDL-P, respectively).

Again, the results were unmistakable with respect to the impact of fructose and HFCS on lipoproteins, and by extension the relative lack of harm brought on by glucose in isolation. [Removal of glucose and fructose/HFCS would have been a very interesting control group.]

In just a short period of time these dietary interventions had a profound impact on the markers of cardiovascular risk.

So, there you have it – everything you need to know about cholesterol in the length of time it takes to go to the grocery store, buy some high-cholesterol bacon and eggs, cook it, eat it, and savor it. Now it’s your turn to be the judge. Is the conventional wisdom about cholesterol being bad really true?

About the Author

If you'd like to add an avatar to all of your comments click here!

120 thoughts on “The Straight Dope on Cholesterol: 10 Things You Need to Know – Part 2”

Leave a Reply

Your email address will not be published. Required fields are marked *

    1. I don’t think the fact that a man who ate 25 eggs/day without any ill effects proves anything. By the same logic, would the discovery of a 90-year old man in perfect health who smoked three packs of cigarettes a day since he was 18 prove that cigarettes are healthy?

      1. A 90 year old man that smoked 3 packs of cigs a day since he was 18 would NOT be in perfect health. My grandfather smoked a pack or more a day from 14 years old and he looked TERRIBLE until he died of lung cancer at 78.

  1. The “boats” and “cargo” analogy is working great for me. Thank you, Dr. Attia!

    1. This whole article including part 1 is way over my head. I’m not a doctor.

      1. Everything you need to know about cholesterol EXCEPT what to eat & do to prevent & reverse arterial plaque, coronary calcium & heart disease & heart attacks. He just didn’t use enough charts & graphs in these 2 articles to provide the answers.

        1. Conrack, Peter doesn’t have any explicit recommendations in this article. The data presented suggests, however, that in order to decrease the number of boats (ie. LDL-P), by way of reducing your triglycerides (TG), one strategy is to eliminate, or reduce, sugar from your diet. That’s it. No reading between the lines needed.

          However, there may be several strategies to reduce the number of boats (possibly by reducing omega-6 oils, increasing saturated fat intake, etc, who knows), but the last section only alludes to one strategy–sugar reduction or elimination (yeah, Yudkins). Maybe Peter will suggest other strategies at his site as his series continues there. I’d love to hear what else he has to say.

          Thanks Peter for all your work.

        2. Horrible pair of articles. It fails to explain it in a simple way for the laymen, and is incomplete and biased from a purely scientific stand. The comments gleefully insisting on eliminating all sugar from the diet are even more misdirected than mainstream nutritionism, with its cries to erase all cholesterol.
          Don’t you people see you are the same? I expect a PALEO diet adopter to realize that the ice age didn’t last millions of years and most of the time fruits and vegetables were available, as opposed to white sugar and HFCS. A hint: investigate the different digestive pathways of refined and natural sugars before writing the next fanatic nutritional recommendation.

      2. Neither am I. I didn’t even go to college…maybe it helps when you read these things all the time.

        It is a bit technical but I think I get most of it.

        I would rather not take a test on it though…please don’t make me teacher! 😛

      3. I like the boats and cargo analogy. However,I do agree that for most lay people, this article is over the top. We need it broken down into something like 7th grade English for the masses to understand.

        1. those reading at a 7th grade level, probably wouldn’t bother with an article like this anyways.

          It was a little thick, but a quicker second re-read kind of clears up any confusion.

    1. Thanks for dumbing down for me…You should write blogs.

      What I wanted to ask is if I feel good, look good naked, and perform well, I shouldn’t have clogged arteries right? 😉

  2. Maybe I missed it, and I went to the series (9 parts are up, waiting for Part X). How does one measure their LDL-P? The NMR blood lipid test?

    1. Correct, NMR is the only way to measure LDL-P, though measurement of apoB (which does not require NMR) is a very good proxy.

      1. Does VAP not show that too? I thought both VAP and NMR showed that?

  3. “ingesting 55% of their total intake in the form of non-sugar carbohydrates”

    that was group 1, which ate 55% of calories as carbohydrates, and 25% of calories was glucose. that would make 30% of calories non-glucose, and presumably non-sugar, but that 25% as glucose is very much sugar.

    1. mARK,

      I believe he is referring to “sugar” as the generic, table sugar form and not the broad sense.

      I hate the confusion generated when referring to sugar so I always try to refer to its specific form (i.e. glucose, fructose, sucrose, HFCS).

      I think it would be more clear if it read, “ingesting 55% of their total intake in the form of non-sucrose (i.e. non-fructose) carbohydrates.”

      1. they are all bad when over done – read Dr. A’s site – he tells you to quit it all

      2. I think it’s more confusing to refer to sugar by its specific form. I would rather sugar, of any form be called what it is – sugar. Sugar is sugar, Its all bad for you.

  4. Fascinating stuff, thanks Dr Attia for this great – and very readable – article.

    It poses a few interesting questions;

    What is the effect of eating short chain fatty acids, (e.g. coconut oil) that don;t get transported as triglycerides?

    What is the effect of fructose eaten as part of whole fruit, (or honey) instead of refined fructose/HFCS

    And, this would seem to suggest that eating (long chain) fats at the same time as fructose is a really bad idea! Most sweet fruits have very little fat, but most junk food, of course, is loaded with both!

    And, what is the effect of fructose eaten as part of whole fruit, (or honey) instead of refined fructose/HFCS?

    We and up at the same place as always – embrace the animal fats, eat whole foods, and easy on the sweet fruit – where have we heard that before?

  5. So I commented yesterday, after reading the first part of this post, about the possiblity that size of LDL made a difference. This post shows that this is not the truth. So, again, I learned something new and adjusted what I thought I did know.

  6. I have a bit of difficulty following some of the science, but I think I understand the conclusion, which is really what matters most. At the end of the day, avoid processed food like the plague in part because it almost always contains added sugar or HFCS (or something similar) not to mention Omega 6 oils which also may be pretty harmful.

    Eat real food and odds are you are going to do a whole lot better than if you are eating something out of a package or can.

  7. The sum of the square roots of any two sides of an isosceles triangle is equal to the square root of the remaining side… and that’s how Primal living works folks! Don’t make me repeat it because I can’t 🙂

    1. It is the sum of the squares, NOT square roots. The sum of the squares of the sides of a right triangle equals the square of the hypotenuse. Pythagorus says so.

      1. Ahhhh I’m out of school stop torturing me with that !!! I’m done not going back leave me be !!!!

  8. Thanks for providing all the science, but I couldn’t follow much of it really. Could you do another post where you summarize the information in layman’s terms and more importantly, clearly eclucidate what conclusions you think we should be drawing. Also, precisely what areas do you think CW is wrong? Thanks.

    1. I think a huge part of the reason for the two cholesterol posts in the first place is so that people can look at the science and the evidence and make up their own minds. Mark or Dr. Attia or the Wizard of Oz can “elucidate what conclusions you think we should be drawing” and “what areas do you think CW is wrong,” but what makes them any more convincing those people espousing the conventional approach? Mark is lean and muscular and Dr. Attia wears a lab coat and they both have a bunch of charts and diagrams, so they must be right. But so do plenty of the other guys.
      I think the only way for us to decide for ourselves, even if the science is over our heads, is to look at our lifestyles and see what doesn’t work for us. I’ve become used to a sedentary lifestyle with daily peaks and valleys of energy and lethargy, with at least one daily episode where I find it impossible to keep my eyes open in the middle of the day. Obviously what I had been doing wasn’t working, even if my diet was mostly what CW recommended. I tried jogging and other cardio, but it was hard on my body. So now I am trying the PB (about 6 weeks) and it’s had an immediate impact – my energy level is stable throughout the day, I don’t have cravings, and I enjoy daily walks with a little heavy lifting thrown in every couple of days. I’m not about to start worrying about whether my LDL particles are big or little, but I’ll have my bloodwork done in a month or two to see what kind of changes there are. I felt like I was getting dangerously close to metabolic syndrome and that I am now taking steps to avoid that. One person’s opinion about lifestyle seems to be winning out over another’s. The rest of the recommendations and conclusions to be drawn are available in the daily blogs and the books. But they’re still just opinion based on the same (or similar) evidence that’s available to us all. At the risk of insulting Mark Sisson, I don’t think he’s any smarter than the rest of us. He’s just educated himself about the reasons why certain lifestyle changes worked for him and he’s willing to share that.

  9. Whoa… too much information. I’m completely lost.

    Anyone want to have a go at a summary? What’s the take home message? Is it:

    – Standard cholesterol tests give you a figure for Total Cholesterol (TC), which includes HDL cholesterol and LDL cholesterol.
    – HDL is good.
    – But the total amount of LDL cholesterol doesn’t matter. What matters is how many particles it is carried in. (In other words, it’s not the total amount of cargo, it’s the number of boats that matters. The same total amount of cargo can be carried by more or less boats.)
    – Ideally, you want few boats, each carrying loads of cholesterol cargo.
    – However, if the cholesterol cargo is diluted by loads of triglycerides, then you will have more boats.
    – And that’s bad because it increases the chances of one of the boats breaking through the endothelium.
    – SO eat stuff that minimises triglycerides… like s/low-carb?

    Is that it? (I’m not quite sure where the different buoyant / VLDL / LDLa apoB particles come in…)

    If so, how do you measure the number of particles? In the absence of a proper clinical test, is it good enough to follow Chris Kresser’s advice:

    “the most important number on a conventional lipid panel is the relationship between triglycerides and HDL. (Divide triglyercids by HDL to get it.) If that number is less than 2, this suggests you have mostly large, buoyant LDL – which is not a risk factor for heart disease. If that number is higher than 3, it suggests you have mostly small, dense LDL – which most certainly is a risk factor for heart disease.”

      1. I believe Chris Kresser is modifying his stance on LDL particle density as being the strongest predictor for heart disease risk.

        In his new cholesterol program, Chris will talk about a ton of new things in relation to cholesterol, one of which is “Oxidized LDL particle number”.

        Chris’s perspective now represents that it is the numerous LDL particles that suggests the stronger predictor for heart disease risk.

        When those LDL particles become “oxidized” that’s when the immune system(s) goes on alert and things could (do) get sketchy.

  10. Intuitively, it is hard to believe that when there are “several quadrillion LDL particles” (boats) in your blood supply that a section of blood vessel would be sensitive to a slightly higher number of “boats” (higher LDL-P). It seems to me that the nature of the boat has more to do with the ability to penetrate the epithelial lining than the sheer number of boats. So the argument is this: with more particles you are perhaps more likely to have more penetration-capable LDL particles; however, this is not necessarily true. In theory, you could have a very high LDL-P, with all the particles incapable of penetration.

    1. The theory seems plausible, and so was considered in evaluating the results, but the facts say otherwise.

      “Among lipid, lipoprotein,and apolipoprotein variables, apo B [LDL-P] came out as the best and only significant predictor of ischemic heart disease (IHD) risk in multivariate stepwiselogistic analyses (P=.002).”

      “Let me repeat this point: Once you account for LDL-P, the relationship of atherosclerosis to particle size is abolished”

      1. OK

        What about people with high LDL-P that do not manifest problems? The graph shows that of those followed, 80% with “high” LDL-P were “event free” for 16 years. Why does high LDL-P NOT affect the majority of the population? Something is missing in this model. Also, it is easy to trick yourself with “corrections” to the data.

        1. I am not a “real” scientist, I do not run any studies.

          I have no proof and I may be completely off base, but all I have is just my theory….

          …the body allows the boats to penetrate.

          1.) I theorize that every boat has the ability to penetrate, the body doesn’t allow it when it isn’t necessary.

          2.) If a person, generally has high LDL, it hints that there is something bad happening in the bad. The presence of high LDL is not a bad thing in of itself. The reason there is a high level of LDL IS THE BAD THING.

          3.) Inflammation and oxidative/free radical damage are those reasons.

          4.) Basically our immune system has 2 giant parts, a defense system and a healing system.

          5.) Defense system kills foreign invaders, and sometimes kills what it “thinks are foreign invaders”.

          6.) After the killing is over, there’s a lot of wreckage and collateral damage.

          7.) Healing system helps repair and clean up after the killing/battles are over.

          8.) High LDL presence in the blood stream is just a natural occurrence in the body…a natural response to unhealthiness.

          9.) When there is too much collateral damage to fix and clean up, the body tries to make cholesterol’s job easier and allows the LDL boats to penetrate the endothelium of the blood vessels.

          10.) Some of those LDL boats have been working too hard or have been out in the blood stream too long and gotten themselves “oxidized” or b) some of the LDL boats are still carrying “non-competely” dead free radicals.

          11.) When those LDL boats gain access and penetrate and dock themselves in the blood vessel walls…the immune system kicks up again and tries to complete its job. Then you are left with “scar tissue” or plaque build up.

          The reason I believe in this theory is because the human body, brain etc. are designed with purpose.

          I just do not believe that the LDL boats randomly dock themselves into our blood vessel walls. I believe that our body wants them to do it to complete a process.

  11. My brain hurts. Time to go back to some relaxing computer programming.

    1. Agree … back to work for me, will continue reading at home when the information overload fog dissipates a little 🙂

  12. So we get blood test done why? If the right things aren’t even being tested. And what is doesn’t give a whole picture. Then what is the point. Hence why any doctors career is called a “practice” A little scary if you ask me and also why I am my own health advocate and will remain to be. And our ancestors hold the answers.

    1. Ditto what Tobie said.

      I’ve just got to say, I’m normally an information junkie, don’t mind taking as long as necessary to read a good, informative article, but this (these) post(s) lost me somewhere in the first paragraph. A shorter, more concise post, in layman’s terms, is definitely called for here. Can’t educate people if you aren’t speaking their language 🙂

      1. I totally agree Wendy. This is very hard for me to grasp and I’ve read both posts many times. Would really appreciate an easy-to-understand executive summary.

      2. The distinctions being made between LDL, cholesterol and other measures is being discussed because recent research makes it appear cholesterol doesn’t matter. And maybe some other considered-reliable measures weren’t accurate risk predictors either.

        What DOES seem to matter is [AN]OTHER factor which people were not previously emphasizing.

        It’s called LDL-P– and it IS associated with heart problems later to some degree; whereas older things we looked at are NOT important.

        If I understand correctly, that is the general gist of what all them SCIUNCE people are saying.

        1. So why take statin medication? if it does no good / does not assist in this who controversy?

      3. Go to www dot brianpeskin dotcom, under the banner hover the cursor on ‘Publications’ then ‘Original’ then click on ‘2011 Anti-Aging Therapeutics Volume XII (pdf) and read excerpted chapters 29 & 30 for a plain english, common sense explanation that CVD & arteial plaque are caused by the already OXIDIZED ADULTERATED industrially processed omega-6 polyunsaturated vegetable oils that all the experts have been pushing on people as being “healthier” than natural saturated fats.

        And remember you got the answers to ALL your questions from Brian Peskin, not Peter Attia.

    2. Agreed. Reading about this stuff is all well and fine, but don’t take it to heart, and don’t obsess over ideal blood test results. The stress will kill you long before your cholesterol does.

      Best to follow a healthy paleo diet, get some exercise, have some fun. Stay away from doctors as much as possible, because you’re right–they do “practice”, which is a lot different than getting it right every time. Enjoy life because it’s short, and there’s nothing we can do about that.

    3. Blood testing can show what you want to know. I think both VAP and NMR tests show ApoB ie LDL-P.

      Someone earlier said just NMR so I’m not sure if that is true.

      Also someone said dividing triglycerides by HDL gives you a good proxy so even a standard cholesterol test might be useful with that in mind.

      My first blood test ever showed a 2.11 ratio while my most recent showed a 3.0…somewhat weird as I thought my diet improved between those times…

      I don’t know. I’ll have another set of results within the next few weeks to look at.

      1. Good points?I would word that as any pseorn who really doesn’t write on blogs much (in truth, this can be my first post), I don’t assume the time period lurker’ is very changing into to a non-posting reader. It’s no longer your fault in the slightest degree , but perhaps the blogosphere may get a hold of a greater, non-creepy title for the 90% people that enjoy reading the content .

  13. Gotta love the line, “metobolically deranged”. Me thinks if you eat Primal, your derangement will be rearanged!

    1. With havin so much written ceontnt do you ever run into any issues of plagorism or copyright infringement? My site has a lot of unique ceontnt I’ve either written myself or outsourced but it seems a lot of it is popping it up all over the internet without my permission. Do you know any methods to help reduce ceontnt from being stolen? I’d really appreciate it.

  14. I still don’t know if one can get rid of plaque in the arteries. Once it is there, is it always there? Did I miss something? Even though I sorta get it, the science is obviously difficult for me to follow.

    1. Fortunately, the arrival of atherosclerotic plaque is not a one-way street. Lifestyle modification (e.g., smoking cessation, removal of sugar and refined carbs) and medical intervention can actually reverse the build up of plaque.

      1. Peter, thank you for stating this. I’ve been wondering if the body does “go in reverse” to correct the damage that’s been done by the CW-driven SAD, I just haven’t had a chance to do much reading on it yet!

        I love reading your work at the Eating Academy! Between your information and MDA, I’ve changed my diet, which has resulted in a 250+ point decrease in my TG number (TG=99 two weeks ago!). I’m telling anyone and everyone about it!

      2. By “medical intervention” to reverse the buildup of plaque, are you referring to statin Drugs?

        1. In regards to arterial plaque, I tend to think of it this way….

          When you get a cut on your skin and you do all the necessary things to help heal it, most likely you end up with a scab or maybe a scar if the cut is fairly deep.

          Now, over time, does that scab just stay there….does it build up?

          Do the scars grow longer or do the scars tend to heal and try its best to look like your normal skin with maybe a little discoloration if your healing optimally?

          If you are healing well optimally, your arterial plaque should also….not continue to build up. The plaque, should, in fact, shed….just like the scab.

          Normally, the scabs just naturally “fall off” (unless you pick at it and scratch it off).

          The new cells that are forming underneath actually pushes the dead scab off.

          That’s what should happen in the arterial walls.

          And I believe, HDL has an important role in this natural process.

        2. I believe Lipitor is the only statin with “anti-plaque” properties and it is only a very minor one.

          Lipitor would probably have no effect on advanced arterial plaque build up.

    2. The answer is a yes. That is in essence the reversal of heart disease. HDL probably plays a roll in removing some of the damage.

      As well as things that lower the inflammation/immune response.

      Eating well ala Primal Blueprint and good exercise ala Body by Science should do well.

  15. A high cholesterol diet it unhealthy for me due to my experience of eating different foods. I don’t eat meat because it makes me feel badly. The same goes for many of my friends, many of whom are good athletes. Therefore I can assume reasonably that primal eating is unhealthy for some people. Maybe it’s because of cholesterol or maybe its from something else…

    1. What kind of meat have you tried eating…and do you just think this is unhealthy or have you tried it?

      1. I ate exclusively local pastured meats from the farmers market. I know they are unhealthy for me because after I eliminated them from my diet and I becaume leaner, faster, more energized, and my acne finally went away. Anytime I started eating meat again bad things came back up. Thats the case for me, doesn’t mean it is for everyone, probably means that it is for at least some other people.

  16. I’d love to see a similarly brilliant analysis on the factors associated with hypertension!

    1. I have pretty much obliterated high blood pressure after ignoring it until it nearly killed me.
      So, get “The High Blood Pressure Hoax” by Dr. Sherry Rogers and change your life. A pre-owned far infrared sauna will be a part of the solution. Best of Luck.

  17. (Apologies, I’m repeating this to get responses emailed – pls ignore the last post, thank you 🙂 )

    I’d love to see a similarly brilliant analysis on the factors associated with hypertension!

    1. Me too, after a year of primal and some huge changes, I still have to take medication for hypertension. I really don’t understand the processes involved and how I can manage it.

  18. Too much information. All we need is a summary. I’m not a pre-med student, but just trying to do the right things… :o)

  19. I’m a fairly smart fellow as are the people commenting above, but unless I have completely misunderstood the general interest level of most of the people who probably read this site, this two part series, while informative, was far to clinical to actually walk away with any definitive information on WHAT TO DO. I think the information is brilliantly researched and articulated, but Dr…. know your audience. Were you presenting this for peer review?

    1. the article clearly states what to do: lay off fructose, sugar, and in general any foods that are high glycemic, i.e. high starch/carb e.g. wheat products, in fact grains; potatoes, low fat dairy etc ..

    2. Well, hopefully there will be a summary or conclusions, but personally, I LOVE that this article was a little more thorough.

      It’s so easy to find websites and people telling you what you should do and assuring you that the facts support it, but so much harder to actually find the evidence to tell if what people are suggesting is true or logical.

  20. Great post Dr. Attia.
    Your explanation is spot-on and will prove to be useful to my patients and my residents alike. For those who wish to have these values tested, I recommend an NMR Lipoprofile This test can be obtained via common commercial labs (Quest Diagnostics or LabCorp) and is covered by most insurance plans and medicare.

    1. Any thoughts on VAP? I thought it also did these numbers. I guess I need to look up descriptions.

      I also thought there was something called electropheresis something…don’t remember what that may have been more specific than standard.

  21. When I went primal, my cholesterol shot through the roof. Pre-primal, I ate very little meat, a lot of beans, soy, low- fat. I also ate a lot of sugar, because I craved sugar all the time. I had borderline high cholesterol at that time, with high HDL & high LDL. Post-primal, I am eating whole foods, high protein, no sugars, a lot of veggies, little fruit. I no longer crave sugar, feel good, have energy. In other words, I would never go back to CW. However, during a routine physical required by my job, my cholesterol was very high….high HDL & High LDL. Obviously I have familial hypercholesteremia. Yet, my BP was 90/60; my heart rate is in the 50’s, and my CRP was extremely low, meaning there is no inflammation in the body. My blood sugar was normal, I’m normal weight. If I am going to flip out over some number because CW says that number is what is going to kill me, I’d be returning to CW so that I could feel awful again. No thank you. I’d rather live…..then drop dead 🙂

  22. Thanks for the analysis. The reason we can have “simple take-home messages” is because we have the detailed science like this to back it up.

    1. Take home message? Keep fructose to a minimum, especially HFCS. This syncs up nicely with Dr Robert Lustigs work on the unique harm done by consuming fructose in quantity.

      1. Only thing I don’t like about Lustig is hes a huge statist…I’m leaning anarcho-capitalist.

        His ideas of the government intervening bother me. I’d rather the government stay out its got its hands in too much already.

  23. Maybe you could title one of these “Cholesterol for Dummies” and include some simple cartoon drawings for those of us whose eyes glaze over at the sight of arcane chemical graphs.

  24. I too consider myself to be pretty smart (degree in computer science and math; been working as a software engineer for 20 years, now a systems analyst) but I can’t get into this. My eyes start to glaze over after a few sentences. I like that Mark posted it especially for those that enjoy this level of depth. But I too would like a ‘for dummies’ version of the info. Thanks again for all you do, Mark!

    1. Its interesting how different people can be…I don’t have any degrees only finished High School and yet I find it interesting and didn’t have a problem finishing it.

      Interesting. Maybe a time preference thing and it takes time to get through an article like this so peoples eyes glaze over.

      Too bad learning to speed read isn’t easy 😛 Might help with that.

  25. Dummies version: Evidence says that Apo-b and TG are the major concerns in predicting risk, all others basically don’t matter anymore. To keep those two low, avoid fructose and corn syrup and you will prevent disease. Dietary fat literally has no effect on these markers. Only sugar does. This is why paleo, or any low GI diet is healthy and why white rice is okay too. Glucose had a very good response on these bad markers. Fructose I think in moderation needs to be tested this same way, but while still in whole food form, which greatly changes its effects metabolically.

    1. To clarify, TG only rise to bad levels when there is excessive sugar. Too much glucose is bad too, it’s just a much better carb when eating as a whole food in moderation. Your liver turns fructose into TG directly, so it’s worse. high TG makes apoB rise (more boats clogging the river up) which makes hear diseases

    2. Very good summary doctor.

      Regarding fat, you said: “Dietary fat literally has no effect on these markers. Only sugar does.” I was unable to find any reference to the effect of fat intake on TG levels in the two posts. Could you tell me where to find the reference?

      One aspect of fat intake that greatly increases CHD risk is excess dietary linoleic acid (LA) which elicits endothelial dysfunction which leads to atherosclerosis according to several recent articles about “lectin-like oxidized LDL receptor-1” (LOX-1) which is an endothelial receptor for oxidized low-density lipoprotein (ox-LDL).

      In one recent study, endothelial cells incubated with LA had reduced glutathione levels, increased ox-LDL and inflammatory IL-6 levels and altered expression of endothelial nitric oxide synthase (ENOS). In effect, excessive dietary LA increases inflammation (by increasing Rho-a)which results in increased TG and reduced HDL-C.

      It was found that cholesterol “attenuates linoleic acid-induced endothelial cell activation”!

      Another study found that LOX-1 recognizes not only oxLDL but other pathogenic lipoproteins, platelets, leukocytes and CRP. As results, LOX-1 not only mediates endothelial dysfunction but contributes to to atherosclerotic plaque formation, thrombogenesis, leukocyte infiltration and myocardial infarction, which determine mortality and morbidity from atherosclerosis.”

      Intake of LA should be minimized to reduce CHD risk.

  26. Thank you for posting this! This is something I could show to my doctor if the need arises.

  27. I’m a good unsweetened girl but my ApoB still shots through the roof. CRP at its lowest anyway but my doctors will keep on focefeed me statins. I guess you can’t have it all, is the only thing not working in my monthly testing.

  28. For those of you looking for methods to prevent/combat atherosclerosis…

    Do yourselves a huge favor and google Linus Pauling, Matthias Rath and Vitamin C and Lysine. They were granted a US patent based on real scientific evidence showing these substances can reverse arterial plaques.

  29. So it was concluded that LDL-C levels are directly proportional to the amount of complex carbohydrates consumed?
    Also, I am confused as to what exactly is the direct cause of cholesterol related diseases. Is it particle size, particle number, or overactive LDL-C and P receptors?

  30. Not enough effort has been made here to make the 2 parts concise and understandable. I’m not a scientist and what I usually love about MDA is Mark’s ability to digest complex science into easily digestible chunks 8)

  31. Something to consider is that dietary factors are not the only thing that leads to immune dysfunction, inflammation etc.

    Stress is also a big time “killer”, but the dying can be subtle.

    Diet is an important component, but sometimes we also gotta have fun!

    Mark Sisson does a great job promoting Play. We just not only hear him, but also listen.

  32. I am a devoted low-carber for a while, had in the past read tons about all omega3,6,9,cholestorol,ldl,apo,oxidization etc….

    This is an excellent summary. Everyone complaining its not for the layman – then maybe the layman should not read the “EVERYTHING you need to know version” 🙂

  33. hello there and thank you for your info – I have certainly picked up something new from right here. I did however expertise several technical points using this site, since I experienced to reload the web site many times previous to I could get it to load properly. I had been wondering if your web hosting is OK? Not that I am complaining, but sluggish loading instances times will sometimes affect your placement in google and can damage your high-quality score if ads and marketing with Adwords. Anyway I’m adding this RSS to my e-mail and can look out for a lot more of your respective exciting content. Ensure that you update this again soon.|

  34. I am shocked at all the comments complaining that the articles were too hard to read. What are you, neanderthals? ( : …sorry, had to throw that one in!… Look, the articles were pretty clear, and really couldn’t have been any more concise without losing important information. I don’t have any academic background in these sciences, and I got them pretty easily. If you had trouble understanding them, re-read them again! That’s what people do who want to understand something complicated. The world is complicated. And what’s up with all the “don’t make me go back to school!” comments? Do you actually want to understand how things work or you just want to remain lazy and ignorant? Life is not just about using your body. It’s also about using your brains. Use your brains folks. It’s really not so hard. Thanks Peter, for the pretty clear and thorough explanation. I’m sorry so many people are too lazy to exercise their brains a little bit, but then still have the energy to whine about it being too hard.

  35. This was super interesting to read. But one thing is making me confused. The last four graphs seem to suggest that regular sugar (glucose) is far better then fructose (in terms of TG, apoB…)? Just seems utterly wrong to me. Is white sugar better than an apple al of a sudden? Am I misstaking the meaning of glucose here? Is it strach and not regular sugar? Google search calls glucose sugar…

  36. Extremely valuable info. I just embarked on a classic form Atkins diet (high saturated fat) and ended up here after searching for high fat diet & estrogen. The AMA brainwashing is so sadly complete that in most places people assume Atkins is high protein, even researchers. Johns Hopkins has recently begun to test a very high fat version of Atkins on epileptic adults after success with children. Dr. Kossoff has a vid on youtube about Modified Atkins Diet. Ya, worst acronym ever but at least it’s in use. Peace.

  37. “Now an increase in LDL particle size by 1 standard deviation was associated with an ADDITIONAL 14.5 microns of atherosclerosis, albeit of barely any significance (p=0.05)”

    how come p=0.05 is insignificant?
    As I know 0.05 is usually considered significant (and even 0.1 can be sometimes though of as significant).

  38. The surprising thing I got from this was that diet and lifestyle have an insignificant impact on cholesterol levels. I am not convinced that this is true as my levels swing wildly in direct correlation to dietary interventions. Meat and saturated fat = high LDL and veg and unsaturated fat = low LDL. Im about to repeat my vegan experiment after my perfect cholesterol levels on a vegan diet went through the roof on LCHF. Damn shame, I was loving all that meat and butter, now I got to go eat salad and falafel for 3 months or my docs gonna put me on statins

  39. Hi,

    I liked these articles, and in spite of me being pretty savvy, scientifically, and medically – whew, they were rough going!!

    I really LIKED the scientific, and medical detail in here, and the fact that the author tried to gloss over the many, many intricate details – that would have made it completely incomprehensible, ro anyone, except a spevialist in the same field – but even so, it’s prettyrough going, even for the highly educated average punter.

    On the other hand, dumbing it down, to make it into an “executive summary”, as someone has suggested – I feel, would have ruined it!!

    What it REALLY needs, is an “Executive Sumary” – what in medical literature, would probably be called, and “Extract” – at the beginning, to outline what you are talking about, in broad brushstrokes, and less technical terms, and give an outline, of where we start off, the journey, and what YOU are trying to show, and communicate to us – and the conclusions that you have drawn, and the deietary suggestions that you would suggest, because of that.
    And THEN get into the more technical aspects, and proof, and the process that you have used, and how you arrived at those conclusions.
    This way, WE get a chance to come up to speed, and have a clue, as to WHAT you are trying to say, and the overall lay of the land, and where we are going – before we get overwhelmed, with technical jargon (albeit necessary, for clarity – sometimes you just HAVE to call a ring-modulator, a ring-modulator…), and technical details.

    Even for those, that crave this level of technical detail, this is helpful – and for those that don’t, or can’t comprehend this level of language – it gives them enough information, to be beneficial.

    Call it an “Introduction” if you like – as YOU work with it everyday, obviously, YOU know, all the surrounding information, and background – and many of US, do not.

    To delve into this, “Cold Turkey” is pretty daunting, even for somone used to sophisticated technical explanations, as I am.

    Just a suggestion, that I think would help many!!

    Other than the missing “Introduction” section – excellent articles!!

    Thank You VERY MUCH!!

  40. Old article but still good. Unless I missed it – i don’t see any recommendation for the amount of cholesterol we should be consuming via our diet..any feedback on that point