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The personal blog of Peter Attia, M.D.

The straight dope on cholesterol – Part V

The straight dope on cholesterol – Part V

In Part I, Part II, Part III and Part IV of this series, we addressed these 6 concepts:

     #1What is cholesterol?

     #2What is the relationship between the cholesterol we eat and the cholesterol in our body?

     #3Is cholesterol bad?

     #4 How does cholesterol move around our body?

     #5 How do we measure cholesterol?

     #6How does cholesterol actually cause problems?

In this post we’ll continue to build out the story with the next concept:

     #7Does the size of an LDL particle matter?


Quick refresher on take-away points from previous posts, should you need it:

  1. Cholesterol is “just” another fancy organic molecule in our body but with an interesting distinction: we eat it, we make it, we store it, and we excrete it – all in different amounts.
  2. The pool of cholesterol in our body is essential for life.  No cholesterol = no life.
  3. Cholesterol exists in 2 formsunesterified or “free” (UC) and esterified (CE) – and the form determines if we can absorb it or not, or store it or not (among other things).
  4. Much of the cholesterol we eat is in the form of CE. It is not absorbed and is excreted by our gut (i.e., leaves our body in stool). The reason this occurs is that CE not only has to be de-esterified, but it competes for absorption with the vastly larger amounts of UC supplied by the biliary route.
  5. Re-absorption of the cholesterol we synthesize in our body (i.e., endogenous produced cholesterol) is the dominant source of the cholesterol in our body. That is, most of the cholesterol in our body was made by our body.
  6. The process of regulating cholesterol is very complex and multifaceted with multiple layers of control.  I’ve only touched on the absorption side, but the synthesis side is also complex and highly regulated. You will discover that synthesis and absorption are very interrelated.
  7. Eating cholesterol has very little impact on the cholesterol levels in your body. This is a fact, not my opinion.  Anyone who tells you different is, at best, ignorant of this topic.  At worst, they are a deliberate charlatan. Years ago the Canadian Guidelines removed the limitation of dietary cholesterol. The rest of the world, especially the United States, needs to catch up.  To see an important reference on this topic, please look here.
  8. Cholesterol and triglycerides are not soluble in plasma (i.e., they can’t dissolve in water) and are therefore said to be hydrophobic.
  9. To be carried anywhere in our body, say from your liver to your coronary artery, they need to be carried by a special protein-wrapped transport vessel called a lipoprotein.
  10. As these “ships” called lipoproteins leave the liver they undergo a process of maturation where they shed much of their triglyceride “cargo” in the form of free fatty acid, and doing so makes them smaller and richer in cholesterol.
  11. Special proteins, apoproteins, play an important role in moving lipoproteins around the body and facilitating their interactions with other cells.  The most important of these are the apoB class, residing on VLDL, IDL, and LDL particles, and the apoA-I class, residing for the most part on the HDL particles.
  12. Cholesterol transport in plasma occurs in both directions, from the liver and small intestine towards the periphery and back to the liver and small intestine (the “gut”).
  13. The major function of the apoB-containing particles is to traffic energy (triglycerides) to muscles and phospholipids to all cells. Their cholesterol is trafficked back to the liver. The apoA-I containing particles traffic cholesterol to steroidogenic tissues, adipocytes (a storage organ for cholesterol ester) and ultimately back to the liver, gut, or steroidogenic tissue.
  14. All lipoproteins are part of the human lipid transportation system and work harmoniously together to efficiently traffic lipids. As you are probably starting to appreciate, the trafficking pattern is highly complex and the lipoproteins constantly exchange their core and surface lipids.
  15. The measurement of cholesterol has undergone a dramatic evolution over the past 70 years with technology at the heart of the advance.
  16. Currently, most people in the United States (and the world for that matter) undergo a “standard” lipid panel, which only directly measures TC, TG, and HDL-C.  LDL-C is measured or most often estimated.
  17. More advanced cholesterol measuring tests do exist to directly measure LDL-C (though none are standardized), along with the cholesterol content of other lipoproteins (e.g., VLDL, IDL) or lipoprotein subparticles.
  18. The most frequently used and guideline-recommended test that can count the number of LDL particles is either apolipoprotein B or LDL-P NMR, which is part of the NMR LipoProfile.  NMR can also measure the size of LDL and other lipoprotein particles, which is valuable for predicting insulin resistance in drug naïve patients, before changes are noted in glucose or insulin levels.
  19. The progression from a completely normal artery to a “clogged” or atherosclerotic one follows a very clear path: an apoB containing particle gets past the endothelial layer into the subendothelial space, the particle and its cholesterol content is retained, immune cells arrive, an inflammatory response ensues “fixing” the apoB containing particles in place AND making more space for more of them.
  20. While inflammation plays a key role in this process, it’s the penetration of the endothelium and retention within the endothelium that drive the process.
  21. The most common apoB containing lipoprotein in this process is certainly the LDL particle. However, Lp(a) and apoB containing lipoproteins play a role also, especially in the insulin resistant person.
  22. If you want to stop atherosclerosis, you must lower the LDL particle number.


Concept #7 – Does the size of an LDL particle matter?

There are few, if any, topics in lipidology that generate more confusion and argument that this one.  I’ve been leading up to it all month, so I think the time is here to address this issue head on.  I’ve read many papers and seen many lectures on this topic, but the one that stole my heart was a lecture given by Jim Otvos at the ADA 66th Scientific Sessions in Washington, DC.   Some of the figures I am using in this post are taken directly or modified from his talk or subsequent discussions.

At the outset of this discussion I want to point out two clinical scenarios to keep in mind:

  1. The most lethal lipoprotein disorder is familial hypercholesterolemia, which I have discussed in previous posts.  Such patients all have large LDL particles, but most of these patients die in childhood or early adulthood if not treated with medications to reduce particle number.
  2. Conversely, diabetic patients and other patients with advanced metabolic syndrome have small LDL particles, yet often live well into their 50s and 60s before succumbing to atherosclerotic diseases.

The common denominator is that both sets of patients in (1) and (2) have high LDL-P.  What I’m going to attempt to show you today is that once adjusted for particle number, particle size has no statistically significant relationship to cardiovascular risk.  But first, some geometry.


“Pattern A” versus “Pattern B” LDL

The introduction of gradient gel electrophoresis about 30 years ago is what really got people interested in the size of LDL particles.  There is no shortage of studies of the past 25 years demonstrating that of the following 2 scenarios, one has higher risk, all other things equal.  [This is a big disclaimer and I went back and forth for a while before deciding to include this point.  It is an uncharacteristic oversimplification. If you’ve been reading this blog for a while, you’ll know I’m rarely accused of that sin – but I’m about to be].

Here’s the example: Consider 2 patients, both with the same total content of cholesterol in their LDL particles, say, 130 mg/dL.  Furthermore, assume each has the “ideal” ratio of core cholesterol ester-to-triglyceride (recall from Part I and III of this series, this ratio is 4:1).  I’m going to explain in a subsequent post why this assumption is probably wrong as often as it’s right, but for the purpose of simplicity I want to make a geometric point.

  1. LDL-C = 130 mg/dL, Pattern A (large particles) – person on the left in the figure below
  2. LDL-C = 130 mg/dL, Pattern B (small particles) – person on the right in the figure below

Under the set of assumptions I’ve laid out, case #2 is the higher risk case.  In other words, at the same concentration of cholesterol within LDL particles, assuming the same ratio of CE:TG, it is mathematically necessary the person on the right, case #2, has more particles, and therefore has greater risk.

Bonus concept: What one really must know is how many cholesterol molecules there are per LDL particle.  It always requires more cholesterol-depleted LDL particles than cholesterol-rich LDL particles to traffic cholesterol in plasma, and the number of cholesterol molecules depends on both size and core TG content.  The more TG in the particle, the less the cholesterol in the particle.

So why does the person on the right have greater risk?  Is it because they have more particles?  Or is it because they have smaller particles?

This is the jugular question I want to address today.

Small vs. large particles

If you understand that the person on the right, under the very careful and admittedly overly simplified assumptions I’ve given, is at higher risk than the person on the left, there are only 4 possible reasons:

  1. Small LDL particles are more atherogenic than large ones, independent of number.
  2. The number of particles is what increases atherogenic risk, independent of size.
  3. Both size and number matter, and so the person on the right is “doubly” at risk.
  4. Neither feature matters and these attributes (i.e., size and number) are markers for something else that does matter.

Anyone who knows me well knows I love to think in MECE terms whenever possible.  This is a good place to do so.

I’m going to rule out Reason #4 right now because if I have not yet convinced you that LDL particles are the causative agent for atherosclerosis, nothing else I say matters.  The trial data are unimpeachable and there are now 7 guidelines around the world advocating particle number measurement for risk assessment. The more LDL particles you have, the greater your risk of atherosclerosis.


But how do we know if Reason #1, #2, or #3 is correct?

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.

Relative risks

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, you’ll recall from previous posts).  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 (i.e., Reason #3, above).  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 or equal to 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 below.


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 even trends towards moving in the “wrong” direction – i.e., bigger particles, more atherosclerosis).

Let me use another analysis to illustrate this point again.  If you adjust for age and sex, but not LDL-P [left graph, below], changes in the number of LDL particles (shown in quintiles, so each group shows changes by 20% fractions) seem to have no relationship with IMT (i.e., atherosclerosis).

However, when you adjust for small LDL-P [right graph, below], it becomes clear that increased numbers of large LDL particles significantly increase risk.


I’ve only covered a small amount of the work addressing this question, but this issue is now quite clear.  A small LDL particle is no more atherogenic than a large one, but only by removing confounding factors is this clear.   So, if you look back at the figure I used to address this question, it should now be clear that Reason #2 is the correct one.

This does not imply that the “average” person walking around with small particles is not at risk.  It only implies the following:

  1. The small size of their particles is probably a marker for something else (e.g., metabolic derangement due to higher trafficking of triglycerides within LDL particles);
  2. Unless you know their particle number (i.e., LDL-P or apoB), you actually don’t know their risk.

Let’s wrap it up here for this week.  Next week we’ll address another question that’s probably been on your mind: Why do we need to measure LDL-P or apoB?  Isn’t the LDL-C test my doctor orders enough to predict my risk?



  • At first glance it would seem that patients with smaller LDL particles are at greater risk for atherosclerosis than patients with large LDL particles, all things equal.  Hence, this idea that Pattern A is “good” and Pattern “B” is bad has become quite popular.
  • To address this question, however, one must look at changes in cardiovascular events or direct markers of atherosclerosis (e.g., IMT) while holding LDL-P constant and then again holding LDL size constant.  Only when you do this can you see that the relationship between size and event vanishes.  The only thing that matters is the number of LDL particles – large, small, or mixed.
  • “A particle is a particle is a particle.”  If you don’t know the number, you don’t know the risk.


(To Part VI »)


About the Author:

Peter Attia, M.D., is a physician in private practice in NYC and CA. His practice focuses on longevity and healthspan. His clinical interests are nutrition, lipidology, endocrinology, and a few other cool things.


  1. LeonRover  May 23, 2012

    This is a nice presentation.

    Thank you for the work.

    Have I understood correctly that the biological mechanism proposed as a result of these is:

    That current coronary risk is measured by IMT
    and that FUTURE IMT increases because present Particle Number is what mathematians describe as a first derivative?


    • Peter Attia  May 23, 2012

      IMT is a powerful non-invasive way to measure and assess current status of atherscloerosis.

    • Randy Harris  May 23, 2012

      Is an IMT ultrasound test a better choice than calcium scan as a test for current atherosclerosis status? I plan to get an NMR in 6 months and am considering something like the IMT or Calcium scan as well.

    • Peter Attia  May 23, 2012

      The look at really different things. IMT is looking at carotid artery plaque. Calcium scan looks at calcium build up in coronary arteries. Each has a benefit and detriment.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      But no way is CIMT as imformative as total LDL-P or apoB A positive IMT implies subclinical atherosclerosis – likely the apoB and LDL-P were elevated for years before the vessel wall became abnormal enough to cause a positive IMT

    • JohnJ  June 7, 2012

      There is so much to discover about this disease;


      The guilty party is not the smooth muscle cells within blood vessel walls, which for decades was thought to combine with cholesterol and fat that can clog arteries. Blocked vessels can eventually lead to heart attacks and strokes, which account for one in three deaths in the United States.


      For the first time, we are showing evidence that vascular diseases are actually a kind of stem cell disease,” said principal investigator Song Li, professor of bioengineering and a researcher at the Berkeley Stem Cell Center. “This work should revolutionize therapies for vascular diseases because we now know that stem cells rather than smooth muscle cells are the correct therapeutic target.”

      The finding that a stem cell population contributes to artery-hardening diseases, such as atherosclerosis, provides a promising new direction for future research, the study authors said.

      “This is groundbreaking and provocative work, as it challenges existing dogma,” said Dr. Deepak Srivastava, who directs cardiovascular and stem cell research at the Gladstone Institutes in San Francisco, and who provided some of the mouse vascular tissues used by the researchers. “Targeting the vascular stem cells rather than the existing smooth muscle in the vessel wall might be much more effective in treating vascular disease.”


      “If your target is wrong, then your treatment can’t be very effective,” said Dr. Shu Chien, director of the Institute of Engineering in Medicine at UC San Diego, and Li’s former adviser. “These new findings give us the right target and should speed up the discovery of novel treatments for vascular diseases.”

    • Dr Tim Smith  October 7, 2013

      Hello Peter,
      Apologies in advance for the length of this post.
      Thanks very much to yourself and Dr Dayspring for exponentially increasing my knowledge of cholesterol metabolism. Like yourself but to a lesser degree, I have been immersed in the references related to this topic for the last 9 months or so. I am in agreement with most points of your arguments.Particularly with regard to LDL-C as a poor marker for risk as well as lipid responses to carbohydrate restriction. However, the Apo-B and LDL-P story has left me with persistent questions with respect to risk applications in my own patients.
      In this section V you refer to 4 possible assumptions dismissing option 4 ( size and number indicate something else) as well as minimizing the role of systemic inflammation. While I agree that APO-B and LDL-P seem more precise as a marker for hard outcomes (events, deaths, etc.), I remain unconvinced about the inherent atherogenicity of the the APO-B containing lipo-proteins themselves with respect to either their number or the greater reactivity of certain subtypes. I derive this doubt mainly from Dr Daysprings intricate descriptions of the highly regulated trafficking of these particles. I am sorry if I am being pedantic with language, but you both refer to LDL particles as being able to “penetrate” the arterial endothelium( gaining access to the subendothelial space)once particle number reaches a certain concentration. Am I to believe that arterial endothelium simply succumbs to passive diffusion once that arbitrary threshold is reached? If this is the case please can you help clarify? As I understand it, APO-B particles are thought to enter the artery by way of either trancytosis or intracellular transport.
      I would assume that like most organs and tissues in the body, arterial cells would have receptors to transport various insoluble metabolites across cell membranes. Indeed this is the case. Arterial endothelial cells express the LDL receptor(LDL-r) that binds to Apo-B particles. As you have described, every cell has the ability to synthesise its own cholesterol. One could assume that like most other cells, arteries would up-regulate LDL-r when more cholesterol was required and down-regulate when to much is available. What role or mechanism can particle number have in this scenario?
      This brings me back to my initial mention of inflammation. My particular interest lies in the initiating event in the atherosclerotic process. This is a chicken and egg argument that has never been solved convincingly. So, does the presence of “atherogenic” lipoproteins within the arterial cell spark the attraction of the 1st monocyte/macrophage and thereby initiate the the typical inflammatory cascade that leads to the production of a foam cell (known as the retention hypothesis)? Alternatively, is it that inflammation was already present and cholesterol and lipoproteins merely offer themselves as “building blocks” to the dubious motivations the that macrophage/foam cell?
      If the later were the case, one could generate an alternate hypothesis where by the inflammatory signalling might up-regulate LDL-r in order to gather more “building blocks”. As fanciful as this may sound, its plausibility has been confirmed in a 2012 study:
      (Inflammation Disrupts the LDL Receptor Pathway and Accelerates the Progression of Vascular Calcification in ESRD Patients)
      What then to make of LDL particles in the ” inflammation comes 1st hypothesis”. Taken at a localised level, this atherogenic intra-arterial inflammatory process might, in its effort to obtain more cholesterol, deplete the various LDL particles of there cholesterol and spit them back out into circulation (small dense LDL and oxidised LDL for instance). Could this be a substantial factor in the plasma levels of small LDL? Perhaps on a system wide basis?
      What about particle number in this hypothesis? This same process might also lead to some additional particles in circulation but I am doubtful that arterial ” recycling” would shift measured LDL-P numbers significantly. However, “systemic” inflammation could mediate a similar process in other body tissues, say visceral fat for instance. So we might use metabolic syndrome as an example. LDL-P might increase as peripheral tissues deplete LDL particles of their contents to aid in an adaptive response to an inflammatory stimulus (hyperglycaemia/insulin resistance). Thus the liver might increase LDL particle output in response to cholesterol depleted Apo-B lipoproteins circulating in the plasma. So in effect this would not be a problem of decreased clearance but more of increased production of LDL particles.
      What then to make of familial hypercholesterolaemia. The lack of LDL-r function is mainly described as it relates to the liver. Perhaps you can help answer whether there is a difference in LDL-r between the liver and the arterial endothelium. Maybe peripheral tissues in FH are just doing their part to aid in cholesterol clearance with unfortunate consequences within vascular tissue. In any case, I am yet to be convinced that FH is a good proxy for arguments for or against LDL-P risk. Particle number is increased by default not by design in this situation.
      So what clinical relevance can all my nitpicking have? I want to believe the LDL-P/APO-B story and hopefully apply it as a powerful risk assessment guide in the treatment of my patients. However, is it anymore powerful than HDL/trig ratios or CRP? If the LDL-P is discordant with other favourable patterns do I still start the patient on a statin? If already on a statin do I start a use a bile acid resin if LDL-P remains high? Probably not if the statin is mainly operating as an anti-inflammatory agent irrespective of its cholesterol effects. Is LDL-P more relevant to established CAD than primary prevention? Can guidelines and targets really be formed if LDL-P is really just the smoke and not the fire?
      To believe the LDL-P risk story I need a better mechanism than a simple concentration gradient, especially in a highly regulated receptor mediated environment. Otherwise, I fear we may fall into the same logical traps as the saturated fat and total cholesterol debates.

    • Peter Attia  October 7, 2013

      Tim, I appreciate your rigor and in a rare act of violating my rule of how much time I allow myself to address questions… here goes (PLEASE note, I won’t be able to respond again on this thread, but I will re-visit some of these themes in part X of the cholesterol series one day):

      I am sorry if I am being pedantic with language, but you both refer to LDL particles as being able to “penetrate” the arterial endothelium( gaining access to the subendothelial space)once particle number reaches a certain concentration. Am I to believe that arterial endothelium simply succumbs to passive diffusion once that arbitrary threshold is reached? If this is the case please can you help clarify? As I understand it, APO-B particles are thought to enter the artery by way of either trancytosis or intracellular transport.

      A: There are both endothelial gaps (spaces between “irritated” or damaged endothelial cells) and there a number of endothelial receptors (mostly types of scavenger receptors) that internalize lipoproteins – both LDL particles and remnant particles carrying apoB. Normal LDL receptors do not play a major role in endothelia.

      I would assume that like most organs and tissues in the body, arterial cells would have receptors to transport various insoluble metabolites across cell membranes.

      A: Insoluble (hydrophobic) or amphipathic lipids can also enter via diffusion. Much cholesterol gets in to black via microscopic plaque hemorrhages (which introduce cholesterol laden RBC). Many are unaware that RBCs are a significant pool of cholesterol (on their membranes).

      Indeed this is the case. Arterial endothelial cells express the LDL receptor(LDL-r) that binds to Apo-B particles. As you have described, every cell has the ability to synthesise its own cholesterol. One could assume that like most other cells, arteries would up-regulate LDL-r when more cholesterol was required and down-regulate when to much is available. What role or mechanism can particle number have in this scenario?

      A: Unlike the liver and intestine there is no LDLr-modifying regulatory pool of cholesterol in enndothelial cells – they like most cells synthesize all the cholesterol they need. But for sure the more LDL-P the easier it is for any expressed LDLr to “find their prey” – meaning ligands. A fishing net will capture a lot more fishes if lots of fish are present.

      This brings me back to my initial mention of inflammation. My particular interest lies in the initiating event in the atherosclerotic process. This is a chicken and egg argument that has never been solved convincingly. So, does the presence of “atherogenic” lipoproteins within the arterial cell spark the attraction of the 1st monocyte/macrophage and thereby initiate the the typical inflammatory cascade that leads to the production of a foam cell (known as the retention hypothesis)?

      A: Yes, see all of the Ira Tabas review articles on this topic: atherogenesis requires apoB-entry and then the maladaptive inflammatory process that begins. He has shown that the initial event in atherosclerosis is apoB particle entry.

      Alternatively, is it that inflammation was already present and cholesterol and lipoproteins merely offer themselves as “building blocks” to the dubious motivations the that macrophage/foam cell?

      A: If there is an underlying vasculitis of other etiology, then the process is facilitated and lipoprotein entry occurs at lesser concentrations.

      If the later were the case, one could generate an alternate hypothesis where by the inflammatory signalling might up-regulate LDL-r in order to gather more “building blocks”. As fanciful as this may sound, its plausibility has been confirmed in a 2012 study:
      (Inflammation Disrupts the LDL Receptor Pathway and Accelerates the Progression of Vascular Calcification in ESRD Patients)
      What then to make of LDL particles in the ” inflammation comes 1st hypothesis”. Taken at a localised level, this atherogenic intra-arterial inflammatory process might, in its effort to obtain more cholesterol, deplete the various LDL particles of there cholesterol and spit them back out into circulation (small dense LDL and oxidised LDL for instance). Could this be a substantial factor in the plasma levels of small LDL?

      A: No that does not seem to occur to any appreciable degree. Small LDLs are generated during lipolysis in plasma due to many factors, mostly core TG, CEPT activity and lipase activity.

      Perhaps on a system wide basis?
      What about particle number in this hypothesis? This same process might also lead to some additional particles in circulation but I am doubtful that arterial ” recycling” would shift measured LDL-P numbers significantly. However, “systemic” inflammation could mediate a similar process in other body tissues, say visceral fat for instance. So we might use metabolic syndrome as an example. LDL-P might increase as peripheral tissues deplete LDL particles of their contents to aid in an adaptive response to an inflammatory stimulus (hyperglycaemia/insulin resistance).

      A: Other tissues outside of steroidogenic tissues do not rely on LDL particles for sterols. They have no need for a cholesterol delivery — that is why there is no LDL-C required for life, cholesterol outside of LDL particles is sufficient.

      Thus the liver might increase LDL particle output in response to cholesterol depleted Apo-B lipoproteins circulating in the plasma. So in effect this would not be a problem of decreased clearance but more of increased production of LDL particles.

      A: The liver does not make LDL particles.

      What then to make of familial hypercholesterolaemia. The lack of LDL-r function is mainly described as it relates to the liver.

      A: There are numerous causes of FH and many have nothing to do with a lack of LDL function (whatever that is).

      Perhaps you can help answer whether there is a difference in LDL-r between the liver and the arterial endothelium.

      A: Liver and likely the proximal gut have much more LDLr expression.

      Maybe peripheral tissues in FH are just doing their part to aid in cholesterol clearance with unfortunate consequences within vascular tissue.

      A: That is true with fibroblasts expressing scavenger receptors and internalizing LDL particles in areas where xanthomas occur – but not in other tissues.

      In any case, I am yet to be convinced that FH is a good proxy for arguments for or against LDL-P risk. Particle number is increased by default not by design in this situation.

      A: Particle number is increased due to a multitude of pathological processes in FH.

      So what clinical relevance can all my nitpicking have? I want to believe the LDL-P/APO-B story and hopefully apply it as a powerful risk assessment guide in the treatment of my patients. However, is it anymore powerful than HDL/trig ratios or CRP?

      A: Actually it is, although all of those have high correlation, they are incredibly discordant in many folks, especially IR folks. That has been shown in multiple studies. So in places where LDL-P can’t be measured easily (e.g., Canada, Europe), apoB is probably best bet. Thereafter, sure, look at these markers, but understand the further one goes from particles, the more likely there is a chance of missing something. Is this chance large? Probably not, especially in non-IR patients.

      If the LDL-P is discordant with other favourable patterns do I still start the patient on a statin?

      A: Tough to say. First, you’d want to know other factors (e.g., apoE status, dietary pattern, sterol pattern). If you are evidenced based, though, you probably ought to act if LDL-P crosses a high risk threshold. In my personal practice, I do take a pretty nuanced approach and don’t necessary turn to meds in this setting if everything is great (e.g., no IR, very low CRP, very low MPO/LpPLA2), but I may look at and track other studies, such as CIMT.

      If already on a statin do I start a use a bile acid resin if LDL-P remains high?

      A: Depends on synthesis and absorption status and a host of other abnormalities as to which is the better second line drug – in most ezetimibe (zetia) would be the choice.

      Probably not if the statin is mainly operating as an anti-inflammatory agent irrespective of its cholesterol effects.

      A: I know of no clinical trial evidence supporting that the benefit of statins is anti-inflammatory – that is just a plausible hypothesis at this time.

      Is LDL-P more relevant to established CAD than primary prevention?

      A: Both are LDL-P diseases AFCAPS TexCAPS was primary prevention and apoB was the best marker of risk and establish a goal of treatment.

      Can guidelines and targets really be formed if LDL-P is really just the smoke and not the fire?

      Guidelines are based on evidence that exists and many now utilize apoB/LDL-P in a variety of functions.

      To believe the LDL-P risk story I need a better mechanism than a simple concentration gradient, especially in a highly regulated receptor mediated environment. Otherwise, I fear we may fall into the same logical traps as the saturated fat and total cholesterol debates.

      A: Perhaps, but that will take years of studies to “prove” anything in medicine. In my humble opinion – which you can freely choose to disregard without hurting my feelings — in 2013 ignoring LDL-P, at least in most people, may not be the best strategy for mitigating heart disease.

  2. Tom Ramsey  May 23, 2012

    Thank you for writing such interesting pages. I look forward to them.

    • tim smith  October 8, 2013

      Thanks very much for your gracious response. I am humbled, as I am only a “weekend white belt armchair lipidologist”. Your explanation regarding endothelial permiability does alleviate many of my concerns. More homework for me I guess. Here in Australia, APO-B ( LDL-P unavailable ) is not even on the radar . Naturally stepping outside established guidelines with few colleagues doing the same is bound to produce some professional anxiety. I only desire to cover as many bases as possible in order to do so. I certainly will not disregard any of your opinions which are extremely reasonable and well thought out.

  3. Bhasker  May 23, 2012

    CommentDear sir,’. Very enlightening.must admit that quite Difficult to understand initially.I would like to know hOw prof .Dean Ornish was successful with low fat diet

    • Peter Attia  May 23, 2012

      Read my post on Why Weight Watchers is Actually a Low Carb Diet. I specifically address this question.

    • Gretchen  May 23, 2012

      I think the Ornish results showing improvement were not from diet alone, at least the initial results were. The program included very low fat PLUS a stress reduction program, emotional support from group meetings, and probably other healthy things like stopping smoking.

      Yet people cite his results and attribute them to diet alone.

  4. Chris  May 23, 2012

    So when you say “you must lower the LDL particle number. Period.” you are referring to LDL-P right?

    • Peter Attia  May 23, 2012

      Correct. LDL-P = LDL particle number.

  5. Thomas Dayspring aka "Dr Lipid"  May 23, 2012

    Peter is right on: 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 riskexists. 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 thatis what drives risk. Likewise if one’s LDLs are pathologically carying TG instead of cholesterol (i.e. a cholesterol depleted LDL)it will take many more such cholesterol-depleted LDLs to carry a given acholesterol 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

    • Tony  May 23, 2012

      Great post, but I have to ask, what is a normal LDL-P number and how would one go about lowering it?

    • Peter Attia  May 23, 2012

      “Normal” as defined by 50th percentile is about 1200-1300 nmol/L. We’ll discuss treatment in subsequent posts.

    • Bruce Blakely  May 23, 2012

      I’m still having trouble with the concentration gradient aspect (particle number “driving” LDLs into the artery wall). A table in part III states that a good LDL-P is given as <1000 nmol/L and a risky LDL-P is 1300 nmol/L. This is way less than 2-fold concentration difference. When you are talking about this kind of mass-action mechanism, that's not very much.
      Seems to imply that the "design" of the endothelium really has us on the knifes-edge of keeping LDL out of the wall and rather catastrophically letting way too much in.

    • steve  May 23, 2012

      Thanks to you Dr.Dayspring and Dr.Attia, the nonsense that pervades the internet in believing that so long as you large LDL, no matter the number, all is ok.

    • Jim  May 24, 2012

      Dr Dayspring,
      I have read you talk about the delipidation of VLDL causing high LDL-p which are small and CE poor,TG rich. Is that the mechanism by which fish oil can increase LDL?would statin plus or minus zetia still be the appropriate treatment?

    • JPM  May 25, 2012

      Another great post, Peter. Thank you.

      My NMR results for LDL-P were 1130. The LabCorp report shows anything over 1000 as “high.” LP-IR score was 5. How worried should I be about about coming in at 1130?

    • Peter Attia  May 25, 2012

      1130 is about 25-30th percentile. Obviously, LP-IR score of 5 is very low (good).

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      To Jim> Fish oils containing DHA and EPA at high doses reduce TG and increase LDL-C and are neutral of LDL-P. Thus the LDL-C rise has no clinical meaning. Those with high dose EPA with no DHA do decrease LDL-P ~8%. Check out Vascepa a soon to be approved n3 FA product

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      Well the 50th percentile cutpoint is not normal if one is trying to prevent atherosclerosis. The 20th percentile cutpoint would be considered desirable: that is 80 mg/dL for apoB and < 1000 nmol/L for LDL-P

  6. Greg O  May 23, 2012

    Great series, I have learned so much.

    One question that I have had that may relate to Reason #4 above is the role of oxidation.

    Specifically I am referring to Chris Masterjohn’s statements I have heard on different podcasts that seem to imply that oxidation of a LDL particle was a pre-requisite for that particle to be part of the oxidation process.

    In Part IV you stated “not long after an LDL particle gets into the sub-endothelial space … it is subject to oxidative forces”.

    Could you please clarify this point for me?


    • Peter Attia  May 23, 2012

      Once in the S-E space, assuming the LDL particle is retained, the immune cells react to the presence of the particle and it’s sterol cargo, which results in an inflammatory cascade, including oxidation.

  7. David Nelsen  May 23, 2012

    Peter, do you have a model that fits this situation? Off the top of my head I could guess that the more particles, the greater chance that they could end up where don’t want them to go. In this realm I assume that it dosn’t matter how high your good HDL is, as it gets overwhelmed by the sheer volume of particles to clear. I found out this week that my LDL-P was close to 1500, while LDL-C was 116. Will you be commenting in future posts as to the best modulators of LDL-P? I have a few guesses…. 🙂 Thanks, Dave

    • Peter Attia  May 23, 2012

      Last week The Lancet published a great series addressing the HDL question. We have a pretty good understanding of what’s happening on the LDL side. Not true on the HDL side. I enjoyed their series on this so much, that I’m going to have write about it. Maybe part VII or VIII?

    • Debbie  May 23, 2012

      Yes, please address HDL – especially life-long high. This series has enabled me to have more than a simple-minded conversation with my doctors on this subject. I think he was surprised to hear me utter “apoB.” Thank you!

    • Claudia  May 23, 2012

      This was in ScienceNews Friday:

      It mentions The Lancet.

      “Good cholesterol may not be what keeps the heart healthy –
      By themselves, higher levels of HDL don’t explain lower cardiovascular risk”

  8. LynneC  May 23, 2012

    So, in essence, you are maintaining that the presence of small LDL is a surrogate for something else that is contributing to atherosclerosis?

    And a small sticking point. As a 50 year old with hzFH (I have the corneal arcus and tendon xanthomas to prove it!), I can emphatically assure you that I did not die in my 30’s or 40’s from untreated hypercholesterolemia. We don’t ‘all’ die an early death. 😉

    • Peter Attia  May 23, 2012

      Good point. I stand corrected. Of course, it depends on which variant of FH, but I’ll make a modification to the wording of that 🙂

  9. count bitcoin  May 23, 2012

    a side: Attia is a character from my favorite hbo series all time: Rome. Anyone not seen it is deprived and possibly and unrelatedly depraved.

    a propo: assuming a man age 67 with type 2 diabetes and just completed successful radiation therapy for stage 1 prostate cancer, could you lay out what you expect the levels of pertinent apo b and ldl p would likely be on his nmr if you had to guess?

    More simply, this profile describes a relative of mine and i suggested he get an nmr at his next doc appt. What would you look for in his levels given the intensely high insulin levels be undoubtably has due to injecting it daily? What realistic goals should he have towards the results, eg, what should he shoot for as a diabetic, visa-viz his nmr results.

    Writing on a kindle so excuse the crappiness of my phrasing of these questions.

    • Peter Attia  May 23, 2012

      I would have no idea what such results would show. Sorry. One way to know – measure them.

  10. Bob Johnston  May 23, 2012

    As a science wonk I love all this background we’re getting but I’m wondering if later in the series there will be a post that I can show to my friends and family that their slavish adherence to the belief that LDL-C and HDL numbers is a waste of time and that they must get an advanced lipid panel showing their LDL-P in order to truly gauge their cardiovascular health. Don’t get me wrong, I love all this info but I’m already a believer that the conventional wisdom is dead wrong. Getting someone like my dad to read the series just isn’t going to happen but I’m sure I could get him to read a single post. Thanks!

    • Peter Attia  May 23, 2012

      Absolutely, Bob. You will write the 3 page summary of this 9 part series and share with your family, friends, and the rest of us to do the same. Thank you. 🙂

    • John M  May 23, 2012

      Better yet a special message to physicians. Something the doc would listen to when not inclined to listen to my own sketchy description.

    • Peter Attia  May 23, 2012

      John, that will be your assignment. Let Bob do the “friends & family” version. You do the “doc” version.

    • Debbie  May 23, 2012

      But then there is the issue of what to when the advanced lipid profile shows risk, as in high apoB. This is what I’m dealing with now. My neighbor – a retired radiologist – says to absolutely not take a statin. Other doctors say absolutely take a statin.

    • Randy Harris  May 23, 2012

      I want to get my physician to read this series on Cholesterol!

    • Peter Attia  May 23, 2012

      Make it happen! I want that of everyone’s physician.

    • Maryann  May 23, 2012

      Hi Peter! I’d love to read the 20 page summary of Gary’s book WWGF that you wrote for your family. That would be a great addition to the Media section 🙂

    • Trisha Eldridge Gilkerson  May 30, 2012

      I’m currently trying to work on a “friends and family” version. I’ve taken a lot of info from these posts as well as a bit from other reading I’ve done. I have family and friends who cut fat and cholesterol and are on statins in hopes of lowering cholesterol. I’m anxious to share some of this info with them, but I know many won’t be able to really understand all of the science in these posts (I love it though!). If anyone would like to see a copy and/or proof it to make sure I am accurately representing ideas I’d be delighted. I’m not going into all of the science. My aspiration is to get into enough of the science for the non-science minded to understand some of the background without overwhelming.

  11. John M  May 23, 2012

    Peter, thanks again. Had my annual with my GP yesterday and discussed my now 3-months of VLC-HF diet, my progress on weight loss (from 185 >> 166, so far), and my newly normal blood pressure (was high enough to medicate before). He was all sorts of skeptical about my diet, and advised me to “moderate”. I rather suggested he use me as his n=1 observation and see how things go. I asked for the NMR lipid panel, and he didn’t know anything about it. Thinks the standard panel is fine (and my cholesterol numbers have always been good on this panel) anyway. I didn’t press, but wish I had a way. Want to know my particle count, thanks to your teaching!!

    • David Nelsen  May 23, 2012

      John, as an N = 1, I have been LCHF for about 4 months. I tested my LDL-P and it was close to 1500 with an LDL-C of 116. I had to educate my GP but she’s on board now. You own your own health and not your GP so you need to go back and insist on the NMR lipid test. I am working actively now to lower LDL-P with my GP onboard. I hoped eating LCHF would resolve any LDL-P issues, but it’s going to take more than that. See Tara Dall’s video series on Lecturepad.org for various case studies and why and when intervention is needed.

    • Gretchen  May 23, 2012

      None of my physicians would prescribe an NMR test, so I paid for it myself. You don’t need a prescription. Then none of my physicians understood it.

    • Peter Attia  May 23, 2012

      Hopefully, in time, this will not be the case. Remember (everyone), if you want your docs to understand this, you have two choices:

      1. Give them resources to learn it (e.g., Lecturepad.org).
      2. If they refuse to do so, you have the right to find a new doctor.

    • moreporkplease  May 23, 2012

      Second the suggestion to listen to the Tara Dall lecture on lecturepad.org. It’s surprisingly accessible (well, after you’ve read all these posts here at least). Then you’ll be able to compare yourself to the case studies she gives and know when you possibly might ask your doctor for 1 – metformin; 2 – a statin; 3 – both.

      Note that she repeats several times that diet & lifestyle changes are her preferred treatment. (Hint.) One of her slides even lists “low carb diet” as an intervention.

    • lorraine  May 24, 2012

      Also send your doctor to Jim Otvos’ ADA Scientific Sessions (2008) talk here:


  12. Chris  May 23, 2012

    Very interesting and informative article. What conclusions can one derive as it relates to diet? The “Fat Head” documentary brings forth the theory of dense and non-dense LDL particles, further stating that carbs create dense LDL particles. Is there any truth to that? How does one lower his LDL number?

    Thank you!

    • Peter Attia  May 23, 2012

      Carb reduction is certainly associated with a shift towards more Pattern A, but as far as what is lowering risk, it’s not the size of the particle. Presumably it’s that each particles is more importantly carrying more cholesterol and less TG, which means fewer particles.

    • Ed  May 29, 2012

      so are you saying that TG and particles are tightly interlinked? VLDL production is primarily a result of the need to export TG from the liver and hence high TG correlates to high LDL-P?

    • Peter Attia  May 29, 2012

      That is a large driver of discordant LDL-P and LDL-C, as you’ll see this week. But there are many reasons, including genetic ones, that lend to higher than ideal LDL-P.

  13. tess  May 23, 2012

    this series has been VERY educational! among other things, it’s always nice to know what kinds of tests we SHOULD be getting, as opposed to what is standard.

  14. Dorian  May 23, 2012


    One of your charts shows the “correlation between LDL size and LDL-P = -0.64”, which seems to be a pretty strong inverse correlation. So, “all else being equal” (ahem), is it fair to say that those with smaller LDL size will have higher LDL-P, and those with higher LDL size will have lower LDL-P?

    I’m guessing that neither LDL size nor LDL-P is causative in this correlation, but rather a different cause is causing this correlation — i.e. something else is causing LDL size and LDL-P to move in an inverse relationship. Is this guess on track?

    Thanks for the great posts.

    • Peter Attia  May 23, 2012

      Yes, there is a correlation, but would you bet your life on a 0.64? Maybe if it were 0.99 we could have the discussion. This correlation is largely a result of the epidemic of metabolic syndrome.

    • lorraine  May 24, 2012

      The take home for me from this and some related references is that it’s the folks with discordant LDL-C and LDL-P who won’t see their risk without particle number measured. These are the folks that don’t fit the correlation.

      Interesting to me from Otvos’ review of some of the population studies is that even with factoring for particle, waist size still held up as a risk for hard CV outcome.

  15. Bruce Blakely  May 23, 2012

    Maybe this is starting to come together…

    How about this:
    LDL-C = LDL-P X (cholesterol/particle). So if the amount of cholesterol/particle decreases, the particle number will go up. The amount of cholesterol/particle decreases if cholesterol is displaced by something else, namely too much triglyceride.

    So you can (in theory) reduce LDL-P by increasing the amount of cholesterol/particle (presumably by decreasing triglycerides) or by reducing LDL-C. I’m guessing that reducing triglycerides is “easier” and has other benefits as well.

    I think the piece I was missing is that high triglyceride displaces cholesterol from LDL – time to go back to re-read Part I-III and sort this out. Right now I’m not real clear on the relationship of cholesterol and triglyceride in the various types of particles (LDL and HDL).

    • Peter Attia  May 23, 2012

      You’re on the right track, Bruce. When the liver is exporting TG at a geometric rate (such as in the case of someone eating a lot of sugar, simple carbs, or alcohol), the ratio of CE:TG decreases in the lipoprotein particle. Ero, you need more particles to traffic the same amount of cholesterol.

    • Patrick  May 24, 2012


      In your reply you mention the liver’s response to alcohol: do you mean “a lot” of alcohol? Or does alcohol consumption, however much, always cause the the “liver [to export] TG at a geometric rate”?

      Do you drink alcohol, and if so, how does it affect ketosis?



    • Peter Attia  May 24, 2012

      I’ll cover this in subsequent posts. Too much for a quick answer. Search through old comments, though, as I’ve answered this question 8 or 9 times over the last few months in one form or another.

    • greensleeves  May 25, 2012

      Alcohol kicks most people outta ketosis – your body will stop burning fat to burn off the liquor first, Dr. Phinney has said. So at best, it reduces your fat-burning time. It’s a pain to sit around thinking – “darn, I’m metabolizing this wine when I could be chewing through 250 calories of ugly junk on my trunk instead!” Basically, I’ve stopped drinking. Burn fat, burn!

  16. Sam Y  May 23, 2012

    Is there a fluid dynamics explanation for why LDL-P is so much more important? Is it that the tendency for particles to spread themselves uniformly within the blood makes a much bigger difference than the relative difference in particle size?

    • Peter Attia  May 23, 2012

      That’s a good question. I don’t think I know the answer.

    • Sam  May 24, 2012

      I did some research. And there have been quite a few papers on fluid dynamics models for solutes in the blood. Most of the models that are used for particle-artery wall equations use a diffusion equation with a generic term “concentration.” <One paper explains that "concentration" in the context of diffusion is linearly correlated with partial pressure. SIAM J. NUMER. ANAL. c 2001 Vol. 39, No. 5, pp. 1488–1511

      Partial Pressure! – That is only affected by moles, not mass.

      Another paper Med Eng Phys. 2010 Oct;32(8):867-77. Epub 2010 Jul 2. proposes that LDL accumulation occurs when the right combination of LDL Concentration (read Molarity) combine in the artery.

      So I guess, in summary, if we assume that the process by which LDL particles are driven into the S-E space is a gradient driven process, then only an increase in LDL-P would increase the gradient and drive more particles into the S-E space.

  17. FrankG  May 23, 2012

    Many thanks for this important work Dr Attia

    I get (and have done so for some time) that LDL-C is effectively a useless test — despite the fact that it is used as the basis for a great many (the vast majority?) statin prescriptions. Here in Nova Scotia, Canada, LDL particle count is rarely done and my Endo. is not even authorized to order an ApoB test – despite it being recognised in the lipid guidelines.

    I do think that the work carried out looking into LDL particle size was an important step along the way to establishing that LDL-C is not useful. I accept that size is not just large and buoyant or small and dense but on a continuum.

    I also get the fact that the chief predictor of risk is LDL particle count (LDL-P) rather than size.

    But I am still not sure where or if you show that: increased LDL particle count is a cause of CVD rather than a marker for some other process?

    You say >>The trial data are unimpeachable and there are now 7 guidelines around the world advocating particle number measurement for risk assessment. The more LDL particles you have, the greater your risk of atherosclerosis.<< so I will have to go back and reread the earlier posts to look for the trial data that I must have skipped over but surely particle count measurement for risk assessment does not preclude the possibility that LDL-P is a marker rather than the cause?

    It may be a moot point as I’m hoping a future post will explain what influences LDL-P… and I suspect that diet (rather than medication) will play a crucial role.

    • Peter Attia  May 23, 2012

      It’s not a moot point. It is THE point. The mechanism of atherosclerosis very clear and it is entirely initiated by the LDL-P (you may consider re-reading part IV of this series). Next week I’ll address the ability of LDL-C to predict risk. It’s certainly not useless, but it’s a gamble. At least one third of patient have a low-normal LDL-C and yet high-risk LDL-P. This is called discordance, and it will be the focus of Part VI.

  18. John Dawson  May 23, 2012

    Hi John M. I sympathize. I’ve been trying to get the heart post transplant group at Cleveland Clinic into a dialogue on adding LDL(P) to my testing, but so far they are blowing me off. I have no doubt there are doctors at the Clinic that are conversant with LDL(P), I just am not dealing with them (yet). Interestingly, my home area GP is supportive. Go figure.

  19. Mike N.  May 23, 2012

    The question that has sat unanswered in my mind since early in this series, and now burns more fiercely than ever: why does the body make unhealthy numbers of lipoprotein particles, and what can we do to correct the problem? Lifestyle? diet? exercise? Is there some imbalance or other aberration in the body that the body is trying to correct with the copious production of lipoprotein particles? If so, THAT is what needs to be addressed. I hope this knowledge has been developed and that you will address it. I can’t find the answers.

    • Peter Attia  May 23, 2012

      We’ll get there…Lots of questions here, only some of which can be answered with current knowledge.

  20. David  May 23, 2012

    This is very interesting. I changed my diet about 6 months ago. At that point, my LDL-P was 930, with 45% being small LDL. At that point, my diet was low carb and grain-free, and centered around fish and vegetables. After reading Gary Taubes, I then added saturate fat — meat and coconut oil, fairly liberally — only to find my LDL-P go up to 1500 after four months on this diet. (My HDL went from 59 to 71, and all the small LDL-P disappeared.)

    This doesn’t comport with some of your earlier posts. Any thoughts on what might be going on? I think I need to go back to avoiding saturated fat, unless there is another plausible explanation. (FWIW, I’m ApoE 2/3.)

    • Peter Attia  May 23, 2012

      Hard to know without a great deal more information. Make sure when you do a repeat NMR you have them look at absorption/synthesis markers. HDL, Inc. does this very detailed assay.

    • Corey  May 23, 2012

      David, try having them do a test for ApoE genotype. From what I’ve read, different genotypes (2/2,3/3,4/4) will influence whether or not saturated fat will impact your LDL levels.

    • Ed  May 26, 2012


      Good question. I’ve been mulling this too. My Apo-B almost doubled since going VLC, while every other health marker improved dramatically (weight, blood pressure, TG, HDL). I’m focused on trying to understand the LDL-R activity in all this.

      Theory 1… prolonged carbohydrate restriction may result(evidence in rat and human models) a quasi-starvation response and reduced metabolic rate. This metabolic rate reduction is mediated by thyroid hormones, which turn out to be an important requirement for the expression of LDL-receptor. Thus, low T3 or high rT3 will lower your clearance of LDL particles.

      Theory 2: Increased saturated fat might also downregulate LDL-R activity. I’ve been trying to understand the relationship between LDL-R and various fatty acids and I came across several references that saturated fat would increase LDL via downregulation in LDL-R activity. This would directly lead to an increase in LDL-P and LDL-C.

    • GrassFed  May 26, 2012

      What do you mean by “liberal” use of meat & coconut oil David? Taubes is suggesting 4-6 oz max protein each meal and maybe 2 tablespoons of coconut oil a day. If anyone is eating more than that, they’re overdoing it. No one is saying you can eat 2 lbs of meat a day and 6 tablespoons coconut. That’s crazy unless you’re Michael Phelps. 🙂 How much are you really eating?

    • Victoria  May 26, 2012

      Did you lose weight? Phinney and Volek’s “Art and Science of Low Carbohydrate Living” says there’s “a transient rise in serum total and LDL cholesterol that can occur with major weight loss.”

      “It turns out that along with the triglyceride stored in adipose tissue, our fat cells also contains a small amount of dissolved cholesterol. After about 30 pounds of weight loss, the shrinkage of these cellular fat droplets proceeds to the point that some of this cholesterol has to be released into the serum.”

      They also say it should return to baseline after weight loss stops.

    • David  May 27, 2012

      Thanks for all the comments. To answer: This is my second NMR after starting to eat meat again. The first one came out similarly, with an LDL-P of about 1300, and the second one was LDL_P of 1500. Corey, My ApoE is 2/3. Ed, very interesting; my TSH has gone from 1.5 to 2.2, though the T3 and T4 are middle range. Maybe the low carb has a negative effect on thyroid. An interesting hypothesis! Grass Fed, no, I don’t eat that much meat; maybe four ounces of grass-fed beef 3-4 times per week, and 1-2 tablespoons of coconut oil per day. Victoria, I went from a BMI of 22.5 to 21.5 — not much of a weight loss at all, so that’s not the culprit.

    • Ed  May 29, 2012


      If you are interested in the thyroid connection, there are a few great blogpost discussions on Jaminets website discussing LDL, Thyroid and the Carbohydrate connection. It’s a great read and there is too much anecdotal as well as published evidence to ignore this effect, especially on a VLC diet.

      I’ve been working on this assumption and had my thyroid tested. Turns out you can drive a semi truck through the reference ranges for TSH, FT3 and FT4. I also got my rT3 checked. All my nums were all within reference range (Peter- who the F??? decides on a reference range), but when you look at thyroid blogs they will tell you that the ratio of FT3/rT3 should definitely be greater than 20, and mine was 14… So depending on how you interpret the numbers, you come to different conclusions.

    • Peter Attia  May 29, 2012

      Folks, I cannot address this point adequately in a few sentences. So let me ask of you all one favor: Relax on this topic until I’ve had a chance to shed some slight on it. There is a lot of confusion out there, and some outright incorrect information, but I need to really explain it in the same way (don’t worry, it won’t take nearly as long) I’m doing with cholesterol.

    • Fiona Shepherd Davis  September 14, 2012

      David, I have had a similar change in my NMR since starting low carb. I am curious to know if you have found any answers to your questions. Have you changed your diet, decreased saturated fat? Thanks!

  21. Joe  May 23, 2012

    Dear Dr. Attia: Great series of posts! Then the only way to get one’s LDL-P is through an NMR test? If so, would you consider Acessa Lab as a decent online lab?


    • Peter Attia  May 23, 2012

      If and only if they have Liposcience do the NMR part. No other company has FDA approval to do this. The other option is to have an approved ApoB test as reasonable proxy.

  22. steve  May 23, 2012

    I suggest that soon you will be taking and passing the certifying exam for Lipidologist! We non M.D.’s will know more than our docs and might pass a junior level exam!
    IMT is not perfect in assessing coronary artery disease. I have a normal IMT score with no plaque ,but CAD determined through CAC score. While it appears that small particles may not matter, I just wonder a bit given that my plaque buid up is in a narrower smaller artery, but not in the main larger ones which are plaque free. All this in the face of lots of small LDL(now corrected with meds) The carotid artery and architecture of the heart are different and it may be that if you have issues with the IMT you will have issues in the heart, but just because the IMT is clear does not mean no issues with the heart. The more I learn the more I become convinced that genetics play an overwhelming role in this disease. Will be interested in your take on diet and sat fat in regard to this subject because one view can be if size of particles do not matter can be that diet does not matter if particle number is at acceptable level. Be interested in your thoughts!

  23. Joe  May 23, 2012

    Dr. Attia:

    I checked with Accesa, and they process NMR through a company called LabCorp., not Liposcience. I checked the web site of Liposcience, and they apparently do not process requests online, etc. So my question is, if this test is so critical, why is it so hard to get one? My doctor just blinks his eyes when I say NMR.

    Any suggestions?


    • Peter Attia  May 23, 2012

      Get an apoB test instead.

    • Gretchen  May 24, 2012

      I had my NMR done several years ago through LabCorps. They do it through LipoScience. It cost $98.

      I don’t understand why Berkeley Heart Labs won’t do any tests without a prescription.

    • Ed  May 26, 2012


      No prescription needed in most states. My doctor wouldnt order an NMR and I didnt want to push him. He let me get my thyroid panels but wouldnt prescribe rT3, so I had some tests via labcorp and some tests via directlab. Turns out Directlab uses labcorp so I got both sets of tests at the same blood draw… the only diff is that the prescription goes through insurance and the results go to my doc… and I get the results from directlab directly (and my doc doesnt get the info). How F&&&ked up is that? Oh well… at least you can do it.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      Labcorp sends the blood to LipoScience — so get the LDL-P via Accesa.

    • Jennifer  July 20, 2012

      Dear Joe,
      the LipoScience website says that LabCorp (with a certain order number) sends those NMR tests to LipoScience. I think that’s what they’re saying. So you may be able to get it through your Accessa LabCorp thing after all.

    • Scott Connerly  October 15, 2013

      Quest’s DirectPay program has a comprehensive wellness test that includes, amongst other things, Total cholesterol, High Density Lipoprotein Cholesterol (HDL), calculated Low Density Lipoprotein Cholesterol (LDL), Triglycerides, calculated cholesterol/HDL ratio.


  24. Stuart  May 23, 2012


    Nothing you have written in the previous posts comes even close to establishing this “I’m going to rule out Reason #4 right now because if I have not yet convinced you that LDL particles are the causative agent for atherosclerosis, nothing else I say matters.” Weak associations, no matter how many times it appears is not causation. The seat belt analogy is not a valid analogy. The MESA study that you have done a nice job rehashing was interpretted in a manner consistant with the funding source and the authors interests. Concentration gradient may likely be a factor once damage begins, particularly when the LDL-p are damaged, but it is not root cause for the initial damage. Undamaged LDL-p, regardless of the concentration, don’t damage the healthy artery.

    • Peter Attia  May 23, 2012

      Stuart, what experiment would you suggest to resolve this? In other words, in a human, how would you manipulate the variables DIRECTLY in a controlled manner? The role of LDL in atherosclerosis is, unfortunately, in the same category as seat belts and smoking. It’s very difficult to do the PERFECT experiment. However, the associations are very strong – much stronger than the associations in nutrition. When a RR difference is 1.3 (“strong” by nutrition standards), it’s hard to make a link. But when it’s 10x AND you have no other way to do the experiment, it becomes more compelling. Ultimately, though, I would ask you, if you’d don’t buy the role of LDL-P reduction in the treatment of atherosclerosis, what treatment are you proposing to reduce atherosclerosis?

    • Stuart  May 25, 2012

      Ultimately it is nutrition. Damage to the artery is caused by many things but it is minimized by adequate nutrition and avoiding toxins. There is no evidence that decreasing LDL-p with conventional treatment descreases overall mortality.

    • Peter Attia  May 25, 2012

      “There is no evidence that decreasing LDL-p with conventional treatment descreases overall mortality.” Categorically false, but I’ll let your peers call you out on this.

  25. Mitch  May 23, 2012

    An apoB test appears to be more affordable than the NMR test. Is it an acceptable subsitute? What are the reference ranges?

  26. Nathan Winn  May 23, 2012

    Hello Dr. Attia: Thanks for the informing posts. I understand that dietary fat can increase Pattern A LDL. If so, is there a ceiling point to which the increase will cease or will it continue to increase leading to an elevated particle number? After reading your personal diet it is unlikely to be the latter however, I would like to hear your input on the matter.



    • Peter Attia  May 24, 2012

      Reducing carb and specifically sugar intake, even in the presence of very high amounts of fat does push most people more to the pattern A side, but this is a side issue and is only relevant if LDL-P is being reduced.

    • Jon  May 27, 2012

      With respect to this point, doesn’t there seem to be a correlation (though maybe not always, or maybe only in some people) between more pattern A LDL-p and overall lower levels of LDL-p (because larger particles are carrying more cholesterol, reducing the amount of particles needed to carry the cholesterol around the body), or am I reading this into the posts mistakenly?

      Also, given some peoples’ comments regarding seeing increases in LDL-p in their NMR tests despite being low carb high fat, I am interested to know what your experience has been with your LDL-p levels througout your journey. Were they high to begin with, low; did they go up at any point, down; where were you in your most recent NMR test?

      And lastly, since it seems as though your research (or review of the research of the leaders in the field) has led you to believe LDL-p is the single most important, and possibly the only relvant, factor to assess risk of artherosclerosis (I hope I’m correct in that assumption), if reducing carb and sugar intake is not lowering LDL-p, independent of the amount and/or type of fat consumed, then a) why is this relevant to the War on Insulin and low carb high fat nutrition, b) what would need to be done in conjunction with low carb to achieve a reduction in LDL-p, and c) what’s the point of going low carb to reduce metabolic disease risk factors if you raise LDL-p and put yourself at higher risk of artherosclerosis?

      Sorry for all the compound questions, and if some or all of this will be addressed in later posts I’ll certainly be reading. Thanks Peter!

    • Peter Attia  May 27, 2012

      Jon, you’re correct that there is a strong correlation between particle size and particle number. In most cases, those with many particles have small particles. Plenty of exceptions, but this is the rule of thumb. My point this post was that there is nothing “special” about a small particle, in terms of atherogenic “ability.” In other words, 1,500 small LDL particles are no more or less harmful than 1,500 large particles. In part VI, which I’m writing now, this point will be made more clear, as will the superiority of LDL-P for predicting heart disease.
      Unfortunately, my understanding of this topic was diminutive in 2009 when I began my “transformation,” so I do not know how bad my LDL-P was 3 years ago. I would not be surprised, given my other biomarkers, if I was north of 2,000 nmol/L, but I’m not willing to go back to my previous way of eating for 6 months to find out.

    • Jon  June 4, 2012

      Well I certainly wouldn’t expect you to do that, given the risks you believe it would entail! Maybe you can ask this guy though!


      Quite a transformation. Although, I do recall you saying in an interview I listened to that you may be moving out of ketosis for some self-experimentation regarding athletic performance this summer. Would be interested to know what impact that has on LDL-p. Regardless, looking forward to reading on and getting the rest of the info, thanks!

  27. Corey  May 24, 2012

    My doctor uses Spectracell, which gives me a breakdown of LDL particle counts. How does this compare with the NMR test, as far as validity? Is one better than the other?


    • Peter Attia  May 24, 2012

      Unfortunately not. If your doctor get get your blood to Liposcience, get an apoB direct measurement instead.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      Spectracell uses ultracentrifugation with particle staining. It is a nonvalidated methodolgy – Do not use it. Get the NMR at any Labcorp

  28. Adam  May 24, 2012

    Just Adding my thanks for supplying such detailed and fascinating information. Much appreciated.

    As an aside, I’ve heard another low carb, high fat proponent place particular importance on HbA1c levels, something I’m not overly familiar with. Is it a significant risk factor or does it pale in comparison to LDL-P? Is it likely that they’re not correlated in a non-diabetic person?

    By the way, it seems that in Australia information on NMR is scarce. I’m pretty sure a few Universities have the equipment to do them, but as for being used for the general public – it doesn’t appear so. If anyone here has information to the contrary, I’d be interested to hear it.

    I had an Apo B test done 5 years ago and I’m in the process of ordering another. Both times the docs were puzzled as to why I was requesting it – I presume because they knew very little about it. I’m crossing my fingers that I’m not one of the people whose Apo B increases with increased saturated fat intake. I’m loving my sausages and bacon too much to quit now.

    Thanks again.

    • Peter Attia  May 24, 2012

      A1c measures the amount of glucose on hemoglobin molecules, which is a different issue. I’m not sure of the correlation between A1c and LDL-P, but I’m sure someone has analyzed. If you can’t get NMR from Liposcience, get measured apoB.

  29. Lizzy L  May 24, 2012

    I’m in SF Bay area — East Bay side. Anyone know where to get an NMR? Is there a competent lab. Quest doesn’t do it. From your comments, Peter, it appears that LabCorp is not reliable. Kaiser doesn’t do it, but my cardiologist sent me a prescription. Anyone know?

    Mike N. at 20, you are asking my question — what do we do? I’ve had one heart attack, six years ago. I know I have 40% blockage in my LAD. I take a statin, and I exercise. I’m thin. I limit my carbs to under 200 g daily — a moderate amount compared to the standard American diet. Suppose my NMR shows high LDL-P: what do I do?

    Looking forward to further posts.

    • Peter Attia  May 24, 2012

      Lizzy, check this website for a potential lipidologist near you: http://www.lipidboard.org/lookup

    • lorraine  May 24, 2012

      Lizzy, You can order the LipoProfile NMR from Liposcience by ordering retail through Life Extension Foundation. They use LabCorp to collect your blood sample. I’m a Life Extension member and just got off the phone with their blood lab, and they confirmed that upon collection of your blood at Lab Corp, your specimen is sent to Liposcience. I called because yours was the second post I read that mentioned there was something funky with LabCorp.

      Life Extension reports your results to you, although I always also get a report from Lab Corp.

      The test is $98 for members and includes a lipid profile as well. It’s closer to $200 for non-members. The $75.00 membership is worth it to me just for the savings on labs because I always want to look at more stuff than a doc typically wants to order.

      For others interested in this, if you are in NJ, NY, RI and MA, there’s some mess with prohibitions against third party billing, so you can’t pay Life Extension or any other retail provider of labs for blood work and then go to their contractor (Lab Corp etc) in those states. Most other retail providers (HealthcheckUSA/Directlabs etc) won’t even take customers from these 4 states, but Life Extension Foundation has a work around. I live right on the Delaware River, so I just go over the border to PA where it’s no problem even though I’m a NJ resident. Those residing in the 4 states mentioned and not close to a state without this prohibition have a little more complicated procedure to follow, but can still get this test and all their lab needs done thru Life Extension.

      Here’s the link to the particle test thru Life Extension


    • Ed  May 26, 2012

      directlabs.com ($129… no membership)… uses labcorp facilities.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      Any LabCorp will do the NMR LipoProfile

  30. Maryann  May 24, 2012

    Hi Dr. Peter,

    I saw Dr. Dayspring’s lecture about why we should not be supplementing with phytosterols. There is a USA Today article out today linking calcium supplements with heart attacks. I have heard this before. Women are often advised to supplement calcium to avoid osteosporosis. Is this calcium depositing in our arteries as the “calcium score” previously discussed? Thank you very much, maryann

    • Peter Attia  May 24, 2012

      I’m not sure about the cause and effect mechanism of calcium supplementation.

    • Debbie  May 24, 2012

      Oh great –

    • Jeffrey of Troy  May 25, 2012

      The recommendation on calcium has been too high. Calcium and magnesium need to be in a ratio; at least as much cal as mag, but not more than twice as much. For example, if 400 mg mag, then at least 400 mg cal, but not more than 800 mg cal.

      Also, cal is constricting, mag is relaxing; you need both, but not at the same time. Get cal from food or supps morning and/or afternoon, mag before bed.

    • Claudia  May 25, 2012

      Maryann, where did you see that lecture, on LECTUREPAD? Do you have the link?

    • Maryann  May 25, 2012

      Hi Claudia, The lecture is “Cholesterol Absorption and Synthesis Markers”. The entire 4-part lecture builds the foundation for the recommendation; but you can find the conclusion in lecture 4 beginning at slide 22. The body has a built-in mechanism to reject phytosterols and prevent their absorption. Some people are hyper-absorbers, in whom this natural defense system is not functioning. Supplementing with phytosterols in a person who hyperabsorbs results in very premature atherosclerosis. Before supplementing, a patient should be tested to see if they are vulnerable to hyper-absorption; however, the bottom line is that there is no data to suggest that phytosterols reduce CAD risk. (Plant stanols, however, are not absorbed and their use may be indicated.) The ubiquitous addition of phytosterols to food products, and the intentional consumption of supplements, is a risk factor for premature atherosclerosis in an unsuspecting population.

    • Claudia  May 25, 2012

      Thanks so much Maryann, ever so kind. I’ll have a look.

    • Stuart  May 25, 2012

      Take look at vitamin K2. It ultimately spurs the enzymes that carboxylate MGla and osteocalcin that direct the calcium and minerals to the right places. This may be a major factor in preventing heart disease and likely much more important than LDL-p.

    • Peter Attia  May 25, 2012

      I approve all comments, include those I don’t agree with. This is an example of one such comment. To say vit K is more important in preventing heart disease than lowering LDL-p is like saying the music choice on the Titanic was more important to saving lives than the lifeboats.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      Maryann: I am impressed with your understanding of my sterol lecture. If you want to take it to the next level visit: http://www.biomarkerbliki.org/bliki-completed-chapters-noncholesterol-sterols-stanols-overview.html

      Dr Lipid

    • Ed  May 26, 2012

      I doubt it’s the most important factor but Stuart may have a point about K2 supplementation and coronary calcification…. consider:

      Nutr Metab Cardiovasc Dis. 2009 Jan 27.
      A high menaquinone reduces the incidence of coronary heart disease in women.
      Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT.

      Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands; Department of Human Nutrition, Wageningen University, The Netherlands.

      BACKGROUND AND AIM: Vitamin K dependent proteins have been demonstrated to inhibit vascular calcification. Data on the effect of vitamin K intake on coronary heart disease (CHD) risk, however, are scarce. OBJECTIVE: To examine the relationship between dietary vitamins K(1) and K(2) intake, and its subtypes, and the incidence of CHD. METHODS AND RESULTS: We used data from the Prospect-EPIC cohort consisting of 16,057 women, enrolled between 1993 and 1997 and aged 49-70 years, who were free of cardiovascular diseases at baseline. Intake of vitamin K and other nutrients was estimated with a food frequency questionnaire. Multivariate Cox proportional hazards models were used to analyse the data. RESULTS: After a mean+/-SD follow-up of 8.1+/-1.6 years, we identified 480 incident cases of CHD. Mean vitamin K(1) intake was 211.7+/-100.3mug/d and vitamin K(2) intake was 29.1+/-12.8mug/d. After adjustment for traditional risk factors and dietary factors, we observed an inverse association between vitamin K(2) and risk of CHD with a Hazard Ratio (HR) of 0.91 [95% CI 0.85-1.00] per 10mug/d vitamin K(2) intake. This association was mainly due to vitamin K(2) subtypes MK-7, MK-8 and MK-9. Vitamin K(1) intake was not significantly related to CHD. CONCLUSIONS: A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD. However, more research is necessary to define optimal intake levels of vitamin K intake for the prevention of CHD.

      PMID: 19179058

    • Peter Attia  May 26, 2012

      I think it’s time for folks to re-read the post: http://eatingacademy.com/nutrition/irisin-the-magic-exercise-hormone
      Why? Because some folks seem to be forgetting about the concept of “ordered terms.” IF Vit K plays a role in this, it’s a higher-order. I realize folks like to quibble over this stuff, but let’s get the first- and second-order term right. Then we can debate the merits of the 9th- versus 11th-order terms.

    • Maryann  May 28, 2012

      Dear Dr. Dayspring,
      Thank you so much! I have no science or math background, so if I understand anything at all it is due to your considerable skill as a teacher. I really enjoyed your lecture immensely and I thank you very much for the link you sent me. I also read “Understanding the Entire Lipid Profile” and learned a lot and enjoyed it. I am presently reading your “Moving Beyond LDL-C…” case report. If it is not too much trouble, could you please tell me what a half life is?

      Would everyone benefit from taking Benecol; and is there a way to undo damage that may have occurred by mega doses of phytosterols?

      When I finished your lecturepad series, I drew a conclusion and I am wondering if I extrapolated it correctly. Many people use the supplement Red Yeast Rice (1200mg twice per day)as a natural alternative to a statin. Since it acts like a statin in the body, I imagine that this would need to be monitored in the same way that you monitor statins; because in cases where the patient experiences increased absorption on a statin, monotherapy is inappropriate, and combination therapy would be needed. In the same way that phytosterol supplementation can range from innocuous to potentially dangerous, it seems that Red Yeast Rice supplementation might be also have the same potential to be harmful. Am I correct?

      Thank you very much, Maryann

    • Peter-NZ  May 30, 2012

      Isn’t arterial plaque mostly calcium? Vit K2 does a good job of directing calcium to the bones (with help from vits A and D) while preventing calcification of the arteries. Maybe you should read up on the topic before assigning such a low priority to K2 and calcium.


    • Peter Attia  May 30, 2012

      Sure plaques contain calcium, but reducing plasma levels of calcium is a very downstream way to address the problem. I’m not suggesting it wouldn’t be interesting to see a trial that compared LDL-P reduction alone vs. LDL-P reduction PLUS vit K, but my instinct tells me the addition of K2 would have a small impact, if any. Furthermore, I have never seen (which doesn’t mean anything other than me saying that) convincing data that K2 alone can reduce death from cardiovascular disease.
      In your haste to provide a sarcastic comment (“Maybe you should read up on the topic…”), Peter-NZ, you’ve missed the point. The question isn’t whether people with heart disease have low levels of vit K, which some do. Nor is the question if supplementing vit K can increase osteoclast activity, which it obviously does. The question is, or should be, does giving vit K to someone reduce their risk of heart disease? If I’m missing the trial that has made this clear, please share it with me.
      Here’s the problem with your logic, Peter-NZ. Let’s say you reduce the concentration of plasma calcium by 10%, is that preventing sufficient calcium from getting into the artery wall when all other factors are present? What about reducing the volume of circulating macrophages by 10% via plasmapheresis? Would that do the trick? I don’t know. The study hasn’t done. But the in medicine it’s very rare that minor alterations — and let’s be clear, that’s what you’re arguing for — of DOWNSTREAM factors can stop a problem of this magnitude. You’ve got to address the problem at the UPSTREAM driver.
      While this analogy is not perfect, I could say the same thing about tuberculosis. These patients die from calcium-containing granulomas in their lungs and elsewhere in their body. What should we do to stop this? Reduce their calcium levels by 10 or 20%? It doesn’t help. The only treatment is killing the bacteria, mycobacterium tuberculosis, that CAUSES the problem to start.

    • Peter-NZ  May 30, 2012

      Forgive me if I came across sarcastic, my comment suggesting you to familiarise yourself with K2 and CHD was not meant that way. Here is the study I base my argument on:


    • Peter Attia  May 30, 2012

      Peter, I appreciate your apology. I am familiar with this study, but it does suffer the same problems many such studies suffer from. It is an observational study without intervention. In other words, we have no way of knowing if the differences they observed in the populations were CAUSED by differences in vit-K proteins, OR if that is just a correlation and a MARKER for some other cause.
      Sometimes observational studies are helpful, especially for identifying problems that should be studied prospectively with controlled experiments. But typically, the “effect” is much larger. In this study the hazard ratios are quite small, suggesting *IF* vit K has anything to do with it, the effect is very small.
      I’m not against this type of work for some questions, such as the role of smoking in lung cancer (where a study may be unethical) or LDL-P in heart disease (where the perfect experiment is metaphysically impossible – read Part VI of this series to see why), but a question like this could by addressed rigorously. And it should before we start over-dosing on vit K.

      All of this said, I still stand 100% by my previous assertion and the analogy to tuberculosis. I do not believe the impact of vit K in most people is significant.

    • Peter-NZ  May 30, 2012

      I hear you Peter but may I ask why you consider the RRs for the mid and top terciles (0.73/0.43 for CHD mortality and 0.71/0.48 for severe aortic calcification) to be insignificant?

      On another topic, blood triglycerides are an independent risk factor for heart disease. Do you know how this fits in with your cholesterol theory (which is nicely put together)?

    • Peter Attia  May 31, 2012

      It’s less about the RR value and more about the idea that in observational studies, unless the RR is quite large, it’s very tough to draw conclusions. If this were a well controlled randomized experiment with perfect compliance, that would be a different story. Basically, the less control over the experiment, the greater demand you’d made on the RR to *suggest* (never prove) the association.
      As far as TG go, it’s actually not clear they are an INDEPENDENT risk factor. In fact, many deep, deep, in the know would argue that once other variables are correct for, they are not. However, they are certainly a very strong predictor and marker of risk. The story fits perfectly, regardless of independent or dependent predictive power, though. More TG means less CE in apoB trafficking particles. Less CE per particle almost always points to…more particles to move the same amount of CE.

    • Peter-NZ  May 31, 2012

      Cheers Peter. How muck stock do you put on trials with rats where K2 inhibit arterial calcification?


    • Peter Attia  May 31, 2012

      I hope everyone is reading this one. This is one of the few comments I write for everyone. It’s a good question, Peter, but here’s a better question: Ask yourself (this is a personal question, for which I can’t provide insight), which is bigger risk you take:

      1. NOT taking vit K, assuming the results of this trial WOULD hold up as valid in well-controlled prospective randomized experiment? OR
      2. Taking vit K, assuming the opposite?

      In essence, this is the question EVERYONE should be asking themselves about ALL drug (or diet) therapy.

    • Peter-NZ  May 31, 2012

      As a general question it’s a valid one but doesn’t really apply to me or even vit K. I get my K2 (MK-7)from natto and in Japan natto consumption, which varies by region, is associated with better regional CV health (I know, one can always say it’s something else). MK-4 is used there as a therapeutic tool in very large doses, 45 mg (not 45 mcg), per day to treat osteoporosis without ill effects. Vit K may be toxic to those who cannot process high doses (kidney patients, newborns) or those on blood thinners. I would worry more about overdosing on Vits A & D from pills. Incidentally, Vit D seems to manifest it’s toxicity by depleating Vit K which means high vit K(2) protects from vit D overdose.

  31. Lizzy L  May 24, 2012

    Thanks, Peter. Appreciated.

  32. Charlie Taylor  May 24, 2012

    Does anyone know how & where to get an apoB test in the UK, privately if possible (to avoid hassle of GP appointments)?

  33. Drew  May 24, 2012

    help peter iam totaly confused after years of trying to uderstand that ldl and total cholesteol doe not matter andthe most importiant is tg to be low hdl to be hi.
    IAM EATING Hi fat mediam protien low carb
    coconut oil lard ghee raw milk and meat all from grass feed animials and eggs 4 aday . I have had two stadard cholesterol test first one was tg 0.7 ldl 4.12 hdl 1.75 total 6.1 2 test tg 0.8 ldl 4.55 hdl 1.61 totol 7.5.HAVE i incress my heartdesease risk ijust finnished talling my doctor ldl does not matter after all th reserch that i have read. what am i doing wrong.

    • Peter Attia  May 24, 2012

      Drew, I’m helping as much as I can. I can’t really play doctor for everyone, on top of writing a blog 20 hours a week, on top of 2 full time jobs, on top of all other obligations. Sorry, man.

    • Maryann  May 25, 2012

      I am really grateful for your heroic efforts Peter. If you said you also had a part-time job as a Navy Seal…it wouldnt suprise me 🙂 I hope that you and your wife have some vacation time planned soon! Thank you so much, maryann

  34. FrankG  May 24, 2012

    Can someone please provide a conversion factor for apoB? Here in Canada it is given in g/L rather than nmol/L — with the guidelines setting a target of <0.80g/L

    Many thanks

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      80 gmL is 80 mg/dL which is the 20th percentile cutpoint. ApoB is not reported in molar concentration. It is a normal value. LDL-P is in nmol/L and LDL-P has nothing to do with apoB – apoB is a protein on LDL particles and LDL-P is a measurement of the entire particle. ApoB and LDL-P are two very different ways of counting LDL particle concentration

  35. Vasco Névoa  May 24, 2012

    Thanks again for a very well written and explained article, Peter.

    I do have one question: what is the value of ApoB for the highest risk quintile on that last picture? (if the study doesn’t show ApoB, then let us know the respective LDL-P and how we can convert between LDL-P and ApoB, please.)

    I understand that absolute values only make sense within the conditions of the specific trial, but I’ve been looking to contextualize my ApoB counts and this looks like a good place to start.

    • Peter Attia  May 24, 2012

      I believe the top quintile in MESA was above 1,600 nmol/L, but if you dig through the paper you can find the exact number.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      You cannot covert apoB to LDL-P but you can look at poopulation studies and see what the various equivalent cutpoints are: visit this website for the values in the Framingham Offspring Study


  36. Mark Breckenridge  May 24, 2012

    I don’t think I’ve ever felt like a blog post is taking an eternity to finish like this one. LOL Thanks for your great work!

    • Peter Attia  May 24, 2012

      If you think it takes an eternity to read…imagine how it feels to write.

  37. Vasco Névoa  May 24, 2012

    I’m still not sold on the whole “concentration gradient is what drives ApoB-containing particles into the artery wall” idea.

    Granted, you’ve shown us the studies that clearly show a positive correlation between ApoB particle number and CVD risk.

    But I think that this is not enough information and that it is perfectly possible to have some very serious confounding factors that obscure these clinical and observational trials.

    Beating the not-so-dead horse again, I believe that infection has a lot more bearing on the subject than you’re willing to believe.

    Reading the definition of the Chronic endothelial injury hypothesis, it becomes clear how common lifelong infections like Helicobacter Pylori (extremely common in the carb-munching western population) can slowly but cumulatively chip away our endothelial surface, exposing us to higher CVD risk. And they don’t even have to be clinically detectable – most of us have more pathogenic bacteria than we should in our digestive tracts, and yet we carry on blissfully ignorant of the fact.

    There was even a study that proved that eradication of bacterial infection restores endothelial function.

    This whole picture (pathogens releasing toxins in blood that disrupt endothelial cell function allowing ApoB carrying particles to penetrate artery wall) makes a lot more sense to me than just “there’s so many particles that they just pierce the wall”. Unless you assume that LDLs burrowing into the artery wall is something that is quite natural to happen all the time. From an evolutionary point of view, I find that extremely hard (improbable) to swallow.

  38. steve  May 24, 2012

    You mention your using HDL labs for NMR test and some other tests. What other tests would make sense besides NMR. Thanks.

    • Peter Attia  May 24, 2012

      I will, in a subsequent post, review the labs done by HDL. You’ll get a sense of what is out there and how it can enable better decision making.

  39. Ray  May 24, 2012

    Love your work and appretiate it more than you know. You’ll still get to the role omega-3/6 have in all of this?

    • Peter Attia  May 24, 2012

      Yes, that series is on the list, also. Hopefully it won’t be as long as this one.

  40. Jill  May 24, 2012

    If the endothelial layer is healthy and strong the particles won’t penetrate.

    • Peter Attia  May 25, 2012

      I don’t know if this is true. I think a healthy endothelial layer is less likely to be penetrated, but if the gradient of particles is high enough, I don’t know that none get across.

    • Vasco Névoa  May 25, 2012

      “If the endothelial layer is healthy and strong the particles won’t penetrate.”

      Now THAT is something worth investigating. 🙂
      Does anyone have any hard info on this?

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      You do not have to have endothelial dysfunction for apoB particles to penetrate. However once they do the maladaptive inflammatory process poccurs and endothelial dysfunction soonfollows the apoB invasion

  41. Margaretrc  May 25, 2012

    Another awesome installment. I’m looking forward to the installment that discusses how one can reduce LDL-P, preferably without drugs. Or does that fall under the category of things you can’t do here?

    • Peter Attia  May 25, 2012

      I will definitely address strategies — pharmacological and otherwise — to lower LDL-P.

  42. Vasco Névoa  May 25, 2012

    Do we know what drives up the ApoB-containing particle number?

    Is there a blood test that can count the oxidized LDL?

    • Peter Attia  May 25, 2012

      Certain gene types. For example, about 25% of the population carries one allele of the apoE3 gene and one copy of apoE4; 1-2% of the population is apoE4/4. I’ll cover this in a subsequent post. Obviously, nutrition plays a role. IR makes things worse.
      There are many blood tests that address this, MPO, Lp-PLA2 are probably the best. Again, I’ll address it later.

    • Thomas Dayspring aka "Dr Lipid"  May 26, 2012

      What drives apo B is easy — over-production or decreased hepatic clearance of apoB particles (95% of which are LDLs)

  43. Obee  May 25, 2012

    This would seem to vindicate the statin makers.

    • Peter Attia  May 25, 2012

      It’s less about the “tool” (i.e., the statin) and more about the application (i.e., how and when it is used). I’m not here to vilify or vindicate a drug maker. But if you have a hammer, it’s best to use for hitting nails, not cleaning windows. Using statins to lower LDL-C is missing the point.

    • JohnJ  May 27, 2012

      Peter your effort is commendable but your analogy is not the most appropriate. Is not a hammer is the atomic bomb on a process that as you have explain very well is very complex and needed by the entire body. Processes that we knew very little for a disease were the etiology is still not well understood. People are using an atomic bomb that is affecting every cell in the body and the pharmaceutical companies makes them think that they are immunized against CVD, so they can keep their unhealthy living. That for a small reduction of absolute risk of a heart attack, but not mortality. I will not say never like Zoe Harcombe


      But I will try everything else, including holistic medicine before throwing a nuclear bomb on my body and hoping it will not have any other ill effect on the rest of my body on the long run.

    • Peter Attia  May 27, 2012

      All fair points, John, and as I said the analogy isn’t perfect, especially at the molecular level. My point was that most doctors use statins to treat LDL-C. As you’ll see in part VI of this series, that is the wrong parameter to treat. In fact, that is part of the reason the efficacy of statins is only “good” and not “great.” Too much noise is being generated by these trials because of the treatment goals. In subsequent posts I’ll try to give readers an idea of how and when statins should be used. Hence, the hammer. True, they probably do much more than “just” block HMG-CoA reductase, but that is the main nail they hit. Very few drugs, do just one thing, but it doesn’t mean they are bad.

  44. Vasco Névoa  May 25, 2012

    Here’s something very interesting… Endothelial dysfunction: the early predictor of atherosclerosis. And it’s got the full text publicly available. 🙂 And it’s written in understandable English! 😀

    Basically, anything that lowers bio-availability of nitric oxide at the endothelium cells will cause the artery to become “leaky” to lipid particles with ApoB proteins and allow the whole process of atherosclerosis to start.

    The triggering factors seem to be hyperglycaemia, hyperlipidemia (with oxLDL), established hypertension, smoking, inflammation, and the inevitable ageing.

    The more I read about these things, the more anti-oxidants seem to be the answer to the decaying vascular health at many levels. Resveratrol keeps popping up, so I’m glad I like my occasional glass of red wine. 🙂

    • Peter Attia  May 25, 2012

      Unless you’re drinking 18 glasses of red wine per day (in which case you’ve got bigger issues), the dose of resveratrol you’re getting doesn’t come close to what is reported to have any benefit in the literature, though.

  45. charles grashow  May 25, 2012


    Had blood taken on 5/10 (1 week after my once every 3 week shot of 400mgs Test Cypionate – in a doctors office paid for by my insurance)

    Have been doing IF (16 hour fast – 8 hour feeding window) for appx 5 weeks prior to the blood test.

    hs-CRP was 18.48mg/L – high is anything over 3.0mg/L

    In August 2011 my Cardio CRP (From Quest Labs) was 1.4mg/L

    Could the IF be causing the hs-CRP to spike?

    To the NMR test results – I’m fooling a moderate carb paleo diet. Daily carbs include a mashed sweet potato after my workout and 1 banana and some frozen berries with my protein smoothie (usually a can of high fat coconut milk OR 8 ozs of whole fat grass fed milk and 6-8ozs of whole fat grass fed milk yogurt)

    LDL-P 1500 nmol/L – Boderline High is 1300-1599 nmol/L

    LDL-C 188 mg/dl – High is 160-189 mg/dL

    HDL-C 59 mg/dL S/B >=40 so this is OK

    Triglycerides 36 mg/dL S/B =30.5 so this is low

    Small LDL-P 127 nmol/L S/B 20.5 so this is OK

    LP-IR (Insulin Resistance Score) 6 S/B <=45

    Your thoughts

    • charles grashow  May 25, 2012


      Small LDL-P 127 nmol/L S/B <=527

    • moreporkplease  May 25, 2012

      “Could the IF be causing the hs-CRP to spike?”

      Yes, but first I’d ask you if you might have any undiagnosed gum disease you don’t know about. When was the last time you had your teeth cleaned? Do you have any gum pockets? You might have systemic inflammation due to gum disease, leaky gut, an allergy, even too much exercise. If you are overweight with a big apple shape and moobs, it could be your own visceral fat that’s inflaming you. . . many factors at play here, you should try tracking them down 1 by 1 with your doctor, for sure.

  46. Dan  May 25, 2012

    It ended up being a VAP that got tested when GammaDynaCare ran my “lipoprotein subfractionation”, including direct LDL, etc. I also got apoB, apoA1 (separate and apart from the VAP which are calculated measures), homocysteine, hsCRP, and all the nitty-gritty in the VAP. I did not get Lp-plA2 which is disappointing (see Mike Cobble’s latest blog post at cobble’s corner). Anyway, I pretty much confirmed I am a hyper-absorber. LDL went off the scale. After initiating rosuvastatin 10 mg OD and cutting out virtually all saturated fat and dietary cholesterol, LDL levels have dropped more than 80%, and triglycerides have continued to go down. So now we are looking at low carb and healthy lean protein food sources. This is pretty much the Lyon Diet Study deja vu all over again (apologies to Yogi Berra). Namely the only RCT ever to show hard endpoint reductions (including cancer) in a nutritional setting. Weight loss has continued and I am glad I did not have to take an intestinal cholesterol blocker (as they are much less evidence-based). From my point of view, unrestricted saturated fat and dietary cholesterol could potentially harm someone with an underlying genetic predisposition to hypercholesterolemia, or a hyper-absorber. You are so right to recommend lipid monitoring – don’t worry what the critics say. If I could recommend three tests in our age/sex cohort then BP testing, lipid testing and a testicular examination would cover >99% of all preventive medicine needs.

  47. Ed  May 26, 2012

    Great series, great links with good references.

    I’m 100% on board with the concept that all things equal, LDL-P seems to have a very compelling association with atherosclerosis. A good strategy for people worried about CVD would be to lower your LDL-P. I get that.

    But after reading as many of your references as possible, I have to agree with Vasco about the concept of gradient. I’m not suggesting that this isn’t a plausible explanation, just that there may be other factors involved.

    Relying solely on LDL-P concentration as the key variable in atherosclerosis would essentially suggest ignoring other risk factors that have widely associated with increased heart disease risk, including blood pressure, hba1c, LDLox, HDL, endothelial health, diabetes, smoking, etc.

    You gave two interesting examples at extreme ends of the LDL-P spectrum to make your point. Both are related to LDL-R expression. In one case, FH patients can’t express enough LDL_R and hence clearance is poor. In the other case, an enzyme mutation causes LDL-R to be overactive, resulting in rapid clearance of particles.

    So, is the change in CVD a result of a change in LDL-P, or a change in the half-life of the LDL particle? Increases and decreases in clearance activity will influence the amount of time that LDL-P circulates around in the bloodstream before it gets removed, and will ultimately show up as changes in LDL-P.

    But is it the gradient that is causing LDL-P to stick, or is it the increases in half-life of particles?

    The longer the particle sticks around, the more chance these particles have to interact with vessels and perhaps get stuck. Will these particles get stuck if the vessels are healthy? Another way to think about it… is a damaged particle (oxidized or glycated) more likely to get stuck into the artery (or actually pulled into the artery to protect the endothelial cells)? I think this is the gist of Masterjohn’s arguments, and I think might have a point.

    Anyway, I think the arguments you present make a compelling case that ALL THINGS BEING EQUAL, you would want to have lower LDL-P than higher LDL-P if you want to reduce CVD risk (but prob not infections). But since all things arent equal, can you offset the risks associated with high LDL-P by having lower blood pressure, not smoking, keeping your blood vessels healthy via good glucose control, etc?

    • Peter Attia  May 26, 2012

      Interesting question, Ed. Sounds like you’re suggesting that in addition to poor LDL-P clearance leading to increased LDL-P concentration, there could be (another) confounding variable – particle age? If this could be accurately measured it would actually be possible to do the same sort of analysis that was done to parse out size vs. particle count. One could look at age vs. number. So I don’t think the age issue is how you’ve described it. You are just reiterating the gradient model. Remember, these particles are in constant circulation “buzzing” by the endothelium. The only time they stop is when they violate the barrier.
      Poor clearance –> more particles IS the reason for these 2 cases I’ve given. I think you’re suggesting poor clearance –> more particles AND change in particle “quality” AND BOTH may account for the increased risk. That’s a hypothesis worth testing.

  48. Ed  May 26, 2012

    One thing that seems abundantly clear from the literature is that the body makes attempts to regulate LDL. The fact that the LDL-P lowering by statins is caused by an upregulation in LDL-R because it senses it is running low on cholesterol (because it cant produce enough and cant pull enough in via extra gut absorption) is an example.

    Now consider this… I’ve searched pubmed for the impact of saturated fats on ldl-receptor expression, and there are a few papers suggesting that saturated fat increases LDL-C concentrations via downregulation in LDL-R. Now why would he body do that? Conversely, increased dietary PUFA intake, upregulate LDL-R expression. Now why would the body do that?

    Maybe there is no good reason, but could it be that the body assumes its safe to send out SFA laden particles into the bloodstream for longer periods of time, while fragile PUFA-packed lipoproteins need to be recycled as quickly as possible?

    So Peter, where do you come out on PUFA vs SFA? If you are in the LDL-P camp, it would suggest favoring PUFA over SFA consumption… but if you are in the big particle, TC/HDL ratio camp, this would favor SFA consumption.

    • Peter Attia  May 26, 2012

      I don’t have enough clear data beyond a few studies to really say definitively if PUFA vs. SFA vs. MUFA has a differential impact on LDL-P. Some idea of what they do to LDL-C, and as Dr. Dayspring pointed out, in some cases we know because of specific trails (e.g., EPA, DHA) that they have no impact on LDL-P.

  49. Barkeater  May 26, 2012

    Dr. Attia.

    Good series. Don’t let my quibbles lead you to think I don’t like it. And, much as I have long hoped that big fluffy LDL is no problem, it is time that the paleo – low carb world hear that the evidence points in the other direction. Maybe not irrefutably, but we see the assertion that small LDL is the sole problem all over the place, flat-footed and presented as established fact.

    Which brings me to my quibble. Throughout your series I think you are overstating the role of lipids as the causative agent of athersclerosis. No doubt high LDL-P is associated with significant risk, no doubt. But it isn’t a death sentence, and other factors are very important, and we don’t know how it plays a role or to what degree it is causative.

    Example: You say: “The most lethal lipoprotein disorder is familial hypercholesterolemia, which I have discussed in previous posts. Such patients all have large LDL particles, but most of these patients die in childhood or early adulthood if not treated with medications to reduce particle number.”

    You told LynneC above you would fix statements of this type. Fix that one. If you mean homozygous FH, OK. But 99% of FHers (like LynneC and like me) are heterozygouts, and our FH has perhaps been a survival advantage up to recent times. I have now spent several days looking for proof of various assertions that HtFH is a giant risk for CAD. In some familiies, yes. For me, it is a risk but probably not as bad as smoking, or smoking plus T2DM, or smoking plus LP(a). (My Framingham risk is 9% in next ten years; not that Framingham is that great.)

    I am very anxious to see what you say about statins. Your mentor Dr. Dayspring loves them, even though he has difficulty tolerating them. If LDL-P is the 800-pound-gorilla cause of CAD, how come statins still have a 70% (or higher if you figure that the studies have been biased to find bigger positive effects) residual risk. How come other cholesterol lowering agents don’t seem to reduce CAD? How come statins seem to have the same modest benefits in reducing heart attacks (if not mortality) in people with low LDL numbers as well as high LDL numbers?

    LDL-P is important, but my quibble is that you are overstating its contribution to risk. CAD is a multi-factorial ailment. I look forward to your future posts – my comment here (not seeking a response here) is to suggest to you that you will need nuanced answers.

    • Peter Attia  May 26, 2012

      Great points in here. Yes, when I speak about FH, I’m talking about homozygotic patients, not heterozygotic patients. Though, heterozygoes have more risk than “wild type.” To your big question about statins, I would say the biggest problem is that they are — in at least 90% of cases — being used to treat (i.e., lower) LDL-C. As you see in this week’s post, doing this is not a judicious way to use them. I’ll come back to the example I’ve given several times. A hammer is a very good tool for pounding nails into wood. When you start using a hammer to wash your windows — that is, when you use a good tool for a job it wasn’t really made for — the results may not look so good. No doubt statins are great at lowering LDL-C (so many silly analogy is not perfect), but the point is, who cares if they lower LDL-C?

  50. Russ C  May 27, 2012

    Excellent series. Learning a lot and can’t wait for more. Have a good library of VAP tests now (with ApoB), so will make next test an NMR and see how it compares and what new things I learn.

    That said, as seems to be the case with at least Vasco and Ed, I do not believe you have yet proven the closing emphatic declaration of point #22 – i.e. “Period.” Their questions seem like it points to opportunity for credible further inquiry.

    Whereas you’ve made it clear that inflammation does take place in response to the penetration of the endothelium by an ApoB lipid particle, and whereas it seems plausible that particle concentration gradient is a factor, the issue seems to lie in whether something else is also an important forcing function on the initial attraction/penetration. The leading hypothesis seems to be associated with inflammation, perhaps caused by glucose or infection or some other variable(s).

    So whereas I can see that human experiments are indeed difficult (i.e. the seat belt problem), do you think there is something to learn from animal experiments that explored effects both known inflammatory and anti-inflammatory agents in a controlled setting?

    • Peter Attia  May 27, 2012

      I’m not disputing that factors beyond LDL-P can exacerbate the problem of atherosclerosis, and perhaps I’ve misunderstood some of the comments. There is no dispute that inflammation plays a role, but where? Are we suggesting that taking 50 mg of prednisone per day (sure to suppress all inflammation in the body) is going to reduce atherosclerosis? Inflammation is a very diffuse and complex pathway. The reductionist approach does not seem to work. Ask any patient who has had an organ transplant. We need to globally suppress their immune response to prevent organ rejection, and with that comes many other problems.
      I am all for lowering inflammation through food choices, and we certainly see a reduction in diffuse markers of inflammation (e.g., CRP, ESR, WBC) with carb- and especially sugar-restricted diets. So I think glucose and even infectious agents can play a role. But nothing in this arena has been more studied the role of apoB and LDL-P, so perhaps I’m just a bit confused by the opposition to these data. It’s probably my fault for not doing a good enough job explaining it. See if your question still holds after part VI this week.

    • greensleeves  May 30, 2012


      “There is no dispute that inflammation plays a role, but where?”

      Ok, now I see the miscommunication. Uffe Ravnskov and others who are skeptical of the lipid hypothesis and who don’t think cholesterol matters tend as a group to argue that those people you call “LDL discordant” – those who have the worst heart attacks out of the blue – also seem to have very high inflammation. Thus they ask which the better risk marker, the LDL-P, or the inflammation? It’s true that the LDL-P has been better studied, but that doesn’t mean it is actually the better risk marker, right?

      So i think the folks above are trying to ask you if you have thought about this question: which is the better marker? And do you think inflammation needs to be studied more? That’s all. 🙂

    • Peter Attia  May 30, 2012

      In large, unsegregated populations, inflammatory markers like hs-CRP, are good markers for cardiovascular disease risk. But, as you’ll see in subsequent posts, it provides little guidance is terms of treatment. If someone has a high hs-CRP, what is the first line of treatment? I’ll get into this more later.

    • Russ C  June 2, 2012

      Just getting back on after a busy week…

      Actually, I think the underlying question is a bit different. So far, the evidence seems solid that the process kicked off following invasion of the LDL leads to significant inflammation. It also seems plausible that pre-existing inflammation will likely exacerbate the problem (with which you seem to agree) with LDL-P count as a driving factor (seems logical).

      The question that seems to me worthy of further study is whether some pre-existing state (i.e. inflammation, …?) is a pre-requisite to get the whole thing started. In other words, if there were low/no inflammation, could you do just fine with a high LDL-P? Perhaps there is even a linear correlation – i.e. iso-risk lines that increase safe LDL-P levels as inflammation decreases (realizing latter may be hard to reliably measure)?

      Off to read Part VI 🙂

  51. Thefatnurse RN  May 27, 2012

    Dr. Attia thank you for your work. I just want some clarification on some things.

    In your summer video for JumpstartMD you mentioned that your small dense LDLs stayed the same when you went low carb but your large buoyant LDLs increased. You mentioned these large buoyant LDLs being less harmful in that video series one year ago.

    However, now that it is becoming clear that the particle size doesn’t matter and that it’s the actual numbers themselves…doesn’t that mean you were at a higher risk on low carb since you pointed out that your small dense LDL-P stayed the same but your large LDL-P increased making total LDL-P #s increase?

    • Peter Attia  May 27, 2012

      Yes, unfortunately, when I was doing my self-experiments I did not know enough about lipidology to know I should have been tracking my LDL-P. That said, we can’t really conclude much from my VAP, since we have no idea what happened to apoB or LDL-P during this change.

  52. Nick  May 28, 2012

    Does the VAP test have any place in helping one understand the LDL-P number? On the VAP test they refer to apoB100 (I’m not sure I’m following, but it seems you are using LDL-P and apoB interchangeably?). I think that you are saying the ratio does not matter but perhaps the size does.

    I’m trying to understand if this is supposed to be the same particle being discussed in the post? It says it is being measured, but is it actually just a calculation? I can see that NMR is the way to test next time, but is the VAP useful at all in the absence of an NMR?

    Still trying to sort out the post with my non-science background!

    Many thanks.

    • Peter Attia  May 28, 2012

      Nick, the apoB reported in VAP is not actually measured. It’s estimated. Hence, it serves little purpose. I think I addressed in this in part III of this series. If apoB is measured directly, yes, it can be used as a good proxy for LDL-P. Keep up the good work. This will all make sense eventually. It took me a while a learn it well, also.

    • Debbie  May 28, 2012

      What is VAP, exactly?

    • Peter Attia  May 28, 2012

      Read part III of this series.

  53. Larry Sumners  May 28, 2012

    On my last blood test my apo-b was in the 40 percentile however my ldl-p was high (1800). I thought that there was a direct relationship between the two. Makes me wonder how accurate the blood test were. Is it possible to have this kind of disconnect?

    • Peter Attia  May 28, 2012

      Depends if you had a measured apoB or an estimated one (via VAP). If the latter, discordance is more common. If the former, it’s less common but it does happen. In this case, risk tracks LDL-P.

  54. Jim  May 28, 2012

    Dr lipid,
    If cholestanol alone is in hyperabsortion range on Crestor with ldlp 95% can zetia decrease ldlp significantly.?

  55. Chris  May 28, 2012

    You’re a powerful force for good, keep up the great work! [Same for Dr. Dayspring if he’s reading] Everybody knows you don’t give medical advice over the internet so let me describe a hypothetical situation and ask two questions.

    Imagine a 55ish male, 6ft 240lbs, who’s eaten low-carb/high-fat paleo for a couple of years. He’s still got a stubborn 20 lbs of subcutaneous fat to lose but overall he loves it, has lost weight, is slowly building muscle, feels great etc. Let’s he say takes no medications at all and is generally in mild ketosis (by ketostick measurement). With tight glucose control, he’s winning the war on insulin!

    An educated layman, he’s very interested in health in general and lipid metabolism in particular. So he’s following the discussion and decides to get an NMR, anticipating a moderate to low-risk LDL-P number. He looks at his triglyceride/HDL ratio (110/50 = 2.2) and is happy. Then his jaw hits the floor as he sees an LDL-P count of 2400!

    Hypothetical NMR results:

    LDL-P 2400

    Cholesterol Total 280 mg/dL
    LDL-C 210 mg/dL
    HDL-C 50 mg/dL
    Triglycerides 110 mg/dL

    Small LDL-P 790 nmol/L
    HDL-P (Total) 31.4 umol/L

    LDL Size 21.2 nm

    Here are the two questions:

    1) Does being keto or fat-adapted make a difference? I.e., would a high particle count be ‘risky’ for a glucose-burner but ‘less risky’ or ‘not risky’ for a fat-burner?

    2) How do you lower the number of LDL-P? Would dialing up the carbs (ugh!) and ‘balancing’ the metabolism make sense? Increase carbs, and probably body fat, to lower CVD risk?

    • Peter Attia  May 28, 2012

      An LDL-P of 2400 in a person already compliant with a low-sugar, low-carb diet needs medication to be fixed. Likely apoE problem (i.e., 3/4 or 4/4 allele), suggesting multi-drug therapy.

  56. steve  May 29, 2012

    If you already have some artery plaque like many over 50 who have been subjected to the SAD diet do, how low should LDL particle count be? Also, how would you know that your plan of diet and meds to get to the particle goal is actually preventing the further increase in plaque creation in coronary arteries? Also, is reversal possible: we all have seen the Crestor commercials!

    • Peter Attia  May 29, 2012

      Yes, this process is partially reversible – both with medication and dietary change. Unfortunately (though not surprisingly) the older you are, the more longstanding the damage, and the greater the damage, the harder it is to reverse.

    • steve  May 29, 2012

      Very true, but there are people in their 80’s and 90’s with very high calcium scores some as high as 1,000, so if CAD not to high for a younger person and progression can at least be stopped there is significant hope that the 40-60 yr old can live event free in to their 80’s or 90’s.
      We will all die one day of either cancer or heart disease; the goal is postpone that until being very old.
      Thanks! Look forward to your thoughts on diet and meds to address this. Am guessing carb restriction of some kind will be in order. Also, be interesting to learn how low LDL particles need to be if there is already some disease.

    • Peter Attia  May 29, 2012

      Slight modification: The goal is to maximize lifespan (in my opinion), it’s to optimize it. There is a difference.

  57. Jeff Johnson  May 29, 2012

    Goal: Search the earth and find out who has the high LDL-P (Virus): Resident Evil ?)-

    Inoculate said victims with Big Pharma Sta tins and Niacin

    This whole thing is beginning to resemble something from the – ‘Resident Evil’ movie

  58. Kypros  May 29, 2012

    Great post! Thanks for your hard work. Much appreciated! How is the cook book going? Release date? : )

    • Peter Attia  May 29, 2012

      I would like to have something ready in a year…sorry for the delay. I’m having a hard time keeping up with blog, let alone other commitments. I do seem to come up with a few new amazing recipes every week, though.

  59. Maryann  May 30, 2012

    Hi Peter, I believe you have the kick-off meeting this week. Is this why you changed your name to The Eating Academy? Blessings and success to you all, Maryann

    • Peter Attia  May 30, 2012

      Yes, kick-off meeting is on Friday. Name change is actually unrelated, I just haven’t had the time to shift over. I’ll will be migrating this blog onto a separate site called eatingacademy.com, which I’ll explain in the next few weeks.

    • Ro  October 1, 2013

      Hi Maryanne,

      I’d really like to read what you have amassed together regarding Cholesterol, if possible?
      I think I’d appreciate your aim to make laymen’s sense of this often scientifically jargen laden subject.

      Many thanks to you and all who have advanced the subject.

    • Maryann  October 1, 2013

      I am not sure what you are referring to; did you mean to ask someone else for this information?

  60. Ted  June 6, 2012

    Total layman reporting to ask annoying questions:

    If my understanding is correct, familial hypercholesterolemia is caused by a genetic defect resulting in under-expressed and/or functionally compromised LDL receptors on the hepatocytes, meaning that not only will LDL-P be high, but these large-buoyant LDL particles will remain in circulation for much longer than large-buoyant LDL particles in a person without this genetic defect of the LDL receptor, thus prolonging their exposure to oxidative factors in the bloodstream. On the other hand, in diabetics and those with advanced metabolic syndrome, their small-dense LDL particles have intrinsically less affinity for the LDL receptor than large-buoyant LDL particles, and thus will stay in circulation for longer than large-buoyant LDL particles, but still not nearly as long as large-buoyant LDL particles in those with a genetic defect in the LDL receptor. So doesn’t it make perfect sense than those with FH tend to succumb to heart disease much earlier in life than diabetics or advanced metabolic syndrome sufferers, even though they have large-buoyant LDL profiles, and even though under normal circumstances small-dense LDL is more prone to oxidation and thus more atherogenic than large-buoyant LDL? Isn’t the plasma half-life of particles, and by extension their rate of oxidation and glycation, just as important if not more important than particle number?

    • Peter Attia  June 6, 2012

      Ted, nothing annoying about this question. You are correct about the phenotype of FH and how their pathology exists, despite large LDL particles. Your second claim, however, is not true. Jim Otvos has very elegantly shown than particle-to-particle, a single small LDL is no more or less atherogenic than a large LDL particle. As you note, of course, small particles are a strong marker for metabolic syndrome and the higher particle count that comes with it.

    • Ted  June 13, 2012

      But wouldn’t a small LDL particle’s reduced affinity for the LDL receptor alone make it more atherogenic by virtue of its increased half-life?

    • Peter Attia  June 13, 2012

      Good question. I don’t know the answer. The data don’t say so, but it’s possible.

  61. John  June 8, 2012


    This is slightly off-topic, but may be important information.



    • Peter Attia  June 8, 2012

      Responded to this report in a comment to Part VI.

  62. Deborah  July 22, 2012

    Hi Dr Attia,

    I apologize for the infodump I’m about to give you. A little background: I’ve been low-carb/high-fat for over a decade now, and my bloodwork shows all the great things that has given me (along with the weight loss). My glucose, triglycerides and cholesterol are all perfect. My question is concerning my husband – a 36 year old, healthy, active man, 6″2 and about 155lbs. He’s never had health problems, is naturally thin. When we met, I started telling him about low-carb and now he eats a predominantly low-carb high-fat diet. I’ve no idea what his bloodwork was like before he started eating this way, but a recent check-up gave him great triglycerides, great glucose, great HDL but very elevated LDL. His GP is now saying he’s heading straight for a heart attack. I know in my heart and brain that this isn’t true as he is eating very healthily, but it’s hard to fight the establishment. He has a follow-up appt with the dr on Tuesday. This time I’m going to go with, but I’m not a scientist and although I’ve read many books (including Good Calories, Bad Calories twice) I don’t have all the answers at the tip of my tongue. Obviously my husband doesn’t have to take meds etc but right now his ‘medical record’ has “refusing medication” on it. The actual numbers on his test were:

    Glucose 76
    Triglycerides 73
    HDL 59.2
    LDL 283

    I know enough to know that just LDL doesn’t say anything and it’s the density/number etc that counts but I don’t know if that test is even available where we live (Israel). I feel that if we did have that test done it would show good things because my husband eats high-fat, moderate protein and moderate carb, although I’d imagine his carb count is probably closer to 100g a day than lower than that because he’s not *totally* low-carb.

    Other than printing out all your posts on cholesterol and presenting them to the doctor (which I may well do, and I’m planning on lending her my copy of GCBC too), do you have any advice on how to approach her? Advice on what to say? And separately, as a question to you, the real medical expert, do you think, just looking at those numbers, that my husband should cut carbs further? Do anything else? Or, since he’s young and in good health and eating well, should we just ‘trust’ that if we did that detailed lipoprotein panel we’d find good news?

    Thank you SO much for taking the time to reply to this.


    • Peter Attia  July 24, 2012

      Is it worth looking for a more open-minded doctor?

  63. Jeff  August 6, 2012

    Thank you so much for your in-depth articles. Great reading even if a lot of it is over my head.
    First, I recently had the more in-depth blood work done at the “Berkeley Heart Lab”. I cannot interpret the numbers they give to the numbers you have in your articles. Numbers like “LDL I” LDL IIA”, “LDL IIAB” or “Q-LDL IIIA_IIIB” and nothing about VLDL. Is there a some parallel conversion of these levels that map to levels mentioned in your articles.
    Second, On the Paleo diet I adhere to about 90% (always a little cheating) I have brought my Total Cholesterol down from ~200 to 114 but, while my LDL went down (73), so did my HDL (33 which is flagged as low). Do you have suggestions to raise my HDL’s.

    Thanks, Jeff

    • Peter Attia  August 7, 2012

      Best way to raise HDL-C seems to be a combination of increased fat intake and reduced carb intake. That said, I’m not a big fan of just chasing the number, especially HDL-C which doesn’t mean much directly, and is more of a marker. If everything else is good, and you feel great, why chase it?

  64. Fiona Shepherd Davis  September 17, 2012

    Peter, Is there any chance you will have time to post why LDL-P may go up on low carb? I suspect it could be related to the coconut oil and I have stopped that and will retest. My LDL-P went up about 200 points, all of my other NMR markers are outstanding, LDL particle size was stable. Thank you.

    • Peter Attia  September 17, 2012

      Fiona, I’m still trying to figure it out (along with apparently everyone else who’s paying attention to this). Lots of ideas, some of which I think make great sense, but unfortunately no science yet to confirm.

  65. wrick  January 8, 2013

    Thank you for the detailed information.

    My wife has an ApoB measurement of 122 mg/dl and ApoA1 of 212 mg/dl. We had always been told that her high ApoA1/HDL ‘protects’ her from CHD.

    From what I can understand from this series, you would not see the ApoA1/HDL as a significant benefit, correct?

    And from the discussion above, her ApoB of 122 would be borderline high per the Quebec study, but not something that would require statin drugs or other treatment to lower, correct?

    • Peter Attia  January 9, 2013

      I can’t give medical advice, unfortunately. True, we like to see apoB/apoAI ratios as low as possible, but apoB and LDL-P are probably more predictive. Folks are now looking at LDL-P to HDL-P as a better ratio than B/AI.

  66. chris kimpton  February 18, 2013

    Hi Peter, please keep the posts coming they are really informative and i look forward to more. I have recently seen the light in that all my previous attempts at low carb i was doing it wrong. Having read ‘the art and science’ recently and worked with a friend who is diabetic i am now properly on nutritional ketosis and loving it. i am consuming more kcal than ever before but the weight just keeps dropping. Yesterday i did my first triathlon in complete ketosis on just a high fat coffee – fantastic, especially watching all those people forcing down gels etc.
    Anyway, on the topic of colesterol, i want to share my experience with people who i think would benefit the most from going keto. The hardest group are those on colesterol meds. Can you help to point me in the direction of an answer to the following question? Should the meds be dropped before starting out, after keto-adaption or only after the blood work shows improvement? Ideally i would suggest that someone just ask their doctor but i think most cardiologists will hold a cross to the idea of a high fat diet.

    • Peter Attia  February 19, 2013

      Glad to hear how you’re doing. Do not tweak meds without the help and guidance of your doc. In my patients I do not suggest med tweaking until diet has started to take effect, but it’s case-by-case, of course.

  67. Mike  July 5, 2013


    in a previous post you indicated someone who was already on a low-carb high fat and having an LDL-P of 2400 would likely need medication to treat.

    How long would you expect it to take for the benefits of a low-carb high-fat diet to affect LDL-P? In other words, how long would you give diet (and exercise?) before advising medication, in someone overweight (and losing), absent other risk factors and prior cardiovascular disease?

    • Peter Attia  July 5, 2013

      Can’t answer that question without knowing a lot more. These are case-by-case decisions.

  68. Mike  July 5, 2013

    Also, and I’m sure this will be covered in the post on treating high LDL-P, but can low-carb high-fat cause LDL-P to go up?

    I have VAP test results from a year ago; my LDL-C was 111 a year ago, and is now 203 via NMR LipoProfile — the only change (that I’m aware of) is being on a low carb diet for the past 2 months. Now I really wish I had numbers before I started doing low-carb and losing weight.

  69. Dean  November 1, 2013

    Dr. Attia,
    V. impressed by your passion to “search for the truth”, taking also the unusual path of n intelligent guinea-pig. Subscribed to your Web this AM. Pls. check info.
    Being a former world class athlete, currently a VERY active 80+ yr. male, I’ve been on a -slightly – similar path [but profess. in a “smaller league” than yours] for the past 68 yr. since I started to compete at the age of 12 in Europe. Outstanding BP & HR until 10 yrs ago.
    Interested in preventing/reversing CAD’s.
    Current pers. data:
    5′-11″, 155 Lbs [+/- 2 lb for the past 60 yr.], waist 30-31″, chronically fit [VO2Max =~40(mL•kg-1•min-1) /H. Heyward/Cooper Inst.
    NMR’s LDL-P=670-890, HDL = 65-85, Trig.= 45-65, LPIR = 6-20; ApoB/Apo-A1 =0.3-0.7.

    Familiar w/Pauling, Shelton, Campbell, Fuhrman, Esselstyn, Weil, Ornish, Otvos, Waldius, etc.

    Ate wrongly first 40 yr., misleaded for next 20, acceptable following next 10, better & testing for the past 10 yr. [mainly fresh/raw fruits, beget., low fat, med. cargos.
    Health “hick-ups”: LVMI 10 yrs ago, AFIB for the past 7 yrs., still excel. fitness level.
    After applied research + engineering, coached profess. alpine skiers in the World Cup, Olympics etc.
    Believe & tested the effect of Vol. & Intens. of exerc. on Lipids [J.Otvos…]

    Appreciate your opinion on comparison between CAD risks of Chinese, Indian, Korean, W.European, N. American populations. G. Walldius’ compr. study V. interesting in this regard.

    Thanks and keep up your outstanding work,


    • Peter Attia  November 2, 2013

      Dean, it’s so difficult (impossible?) to make any statement about CVD risk in populations based on ecology or epidemiology. It is metaphysically impossible to extract cause and effect, only correlation which, with such low hazard ratios, tells us little at best.

  70. Ramin  December 20, 2013

    Hi Doc,
    I am 46 years old male with familial history of high lipid profile. My recent tests show:
    LDL-P 2053
    HDL-P 25.6
    LDL particle size 20.9
    Large VLDL particle number 7.4
    Large HDL particle number 0.9
    VLDL size 50
    HDL size <8.3
    LP-IR 73

    My LDL-C was always high (150-170); fasting glucose always 105-112, A1C 5.4-5.9.
    I have this stupid belly fat that does not want to go away.
    After looking at the numbers, do you have any suggestions? I started taking Niacin 500 mg/day and 500 mg of Artichoke Extract. I don’t want to go on statin drug for as long as I can.
    Thank you.

  71. charlie  March 15, 2014

    Sorry to nit-pick, but if you Def.: “tall” = h > 6′, you don’t get “bucket of short” = {h = 6′}.
    You get “bucket of short” = {h 6′}. Either the Def., or the buckets descriptions should be fixed. Hereby I appeal to your (often well demonstrated) mathematical rigour. Great series anyway!

  72. Mark  April 9, 2014

    Hi Peter,

    Thank you for all your hard work on this blog. My partner recently had a lipid test done that indicated a high Apo-B, but his triglycerides are very low, as is the c reactive protein. If one has a high level of Apo-B but a good ratio of Apo-B to Apo-A1, does the high Apo-B result still indicate a significant risk marker for CVD? The Apo-B result was a little confusing, given the outstanding triglyceride and c-reactive protein results. I’m in the process of researching this as I know the Dr is going to recommend statins based on the results. Not sure you would still answer on this thread but any advice or resources is great appreciated.

    • Peter Attia  April 10, 2014

      I’ll address this in part X of this series.

  73. Christoph Darjanto  July 18, 2014

    Dear Peter,

    I have been reading and studying your blog earnestly for the past 2 months. I have familial hypercholesterolemia (My dad had got 3 stents implanted in 2005):

    “The most lethal lipoprotein disorder is familial hypercholesterolemia, which I have discussed in previous posts. Such patients all have large LDL particles, but most of these patients die in childhood or early adulthood if not treated with medications to reduce particle number.”

    Having disgested some of the theory and statistic in some other sources, I started my journey of low-carb diet for the past 4 weeks. I live in Jakarta Indonesia, where understanding of nutritions is like 20 years behind.

    My question: How should I do my diet? Still going low-carb until reaching ketosis with high amount of fat intake?

    Appreciate your reply.


  74. ken  July 21, 2014

    My wife dealt with many bouts of sinus infections and was given may doses of antibiotics. She then began having serious gut issues. She switched to a pure paleo eating meats, veggies, butter, coconut oil, etc. things got worse and she eventually was diagnosed with ulcerative colitis earlier this year. They wanted to start here on steroids but she decided to go with a GERD diet with bone broth, cooked carrots and broccoli coconut oils and other GERD foods. She has stopped all grains, sugar, hi carb foods. Trying to stick with It’s been 3-4 months and she has improved greatly. Also her achy hands and feet have stopped aching. Her allergies were gone too. She lost weight and overall the colitis symptoms (mucus and runny stools) and began having regular stools and everything seems to be working right. She has always had higher cholesterol thinking it’s due to FH. Like above the 200’s. she is 49 years old 5’2 120 lbs her BP is like 100/60 and pulse is usually in the 60’s. she is in great shape. She recently had here blood work done so we could see if she had the big fluffy partials. We got the results back and we were very shock.
    Here are the results
    Total 398
    LDL-C 290
    HDL-C 104
    TRI 58
    Non-HDL-C 294

    Apo B 198
    LDL-p 3150
    sdLDL-C 65
    SDldl-c 23
    Apo A-1 170
    HDL-P 48.4
    HDL2-C 50
    Apo B:Apo A-1 ratio 1:16
    Lp (a) 22

    Hs-CRP 0.4
    Lp-PLA 303

    All were optimal except
    Her free fatty acids were 1.40

    TSH 1.96
    T4 7.1
    T4 free 1.27
    T3 88

    Were kinda super concerned now.
    Could it also be SIBO and or H. pylori leaky gut?
    I know you cant answer personal questions but we need some help here and be directed to who we can talk to in the Portland Oregon area.

  75. Ken  October 16, 2015

    Sorry for late comment, 3 years after the post, but I just came across this. Thank you to Drs. Attia and Dayspring for your work in this field. This is extremely important information, and very difficult to filter out the noise from all the contradictory opinions.

    First, just to let everyone know that Quest now has a test called Cardio IQ that provides LDL-P. They even give you a nice, 21st century color graph, showing the measured particles across the spectrum of sizes. It uses “ion mobility” instead of NMR, which, from their FAQ, seems it might be as good or better:


    Now, I am a bit confused as to my own LDL-C, LDL-P, and particle sizes, which I hope someone can clarify… My LDL-C is 146. My LDL-P is 1155. But, my LDL Peak Size is 213.2A (21.32nm). So, I have a small particle size, fairly low particle count, but high total LDL-C. My TG is 197, so a bit high, which should crowd out some LDL-C. The only explanation I can see for this arithmetic is that my small LDL particles are very DENSE with LDL-C. Is that the missing part of the equation, the density of the LDL-C on the LDL particles? Seems the density could be calculated, knowing the LDL-C, LDL-P, TG, and particle size.

    I hope someone can clarify, as it is puzzling. If one just multiplies a low LDL-P count times a small LDL particle, with High TG, the product should be a low LDL-C. But, my LDL-C is high. If it helps, here is more info:

    53yo Male with familial history of CHD, atherosclerosis. Can not tolerate statins (muscle pain, memory loss. Feel like an 80yo man with rusty joints when on statins). Niacin is effective in lowering my TG, and perhaps raising HDL, but, Dr. Dayspring has pointed out that, while niacin lowers your numbers, there is not any correlation to better outcomes for niacin patients. Total-C:226, LDL-C: 146, HDL: 41, TG: 197, Ratio: 5.5, Non-HDL: 185, LDL-P: 1155, LDL Small: 290, LDL-Medium: 270, HDL Large 3553, apoB: 119, LP(a): 96

    Note the troubling HDL particle size. HDL-Large is very low, mostly HDL-Small, and total HDL low. So, both LDL and HDL particles are small. According to Quest, high-risk is defined as HDL-Large below 6996 nmol/L. Mine is half that, which is off the chart bad.

    Thank you in advance for any clarifications.

  76. Douglas Sichler  October 28, 2015

    After reading and reading I still don’t know if having small cholesterol particles is better or worse for you than having large cholesterol particles.???

  77. Kelly  April 6, 2016

    One big and important question. If one has too many Apo-B particles, what can be done to lower or change them? I’ve read that it is possible for them to become more Apo-A, thus, less dangerous. I’m not a doctor, just a person whose doctors is trying to lower my LDL particle counts, which are the bad ones. Thank you.

  78. Maurice  January 11, 2017

    If anyone can help out, would be greatly appreciated… since I been on a Ketogenic Diet.. my Apolipoprotein B went up to 230, and my lipoprotein (a) is at 99, what am I doing wrong, am I consuming too much Saturated Fats.. is it the grass fed butter, or the Caprylic Acid C8 from Brain Octane…

  79. Joe Scott  July 3, 2017

    Are there additional posts on familial hypercholesterolemia and when statins are appropriate ?

  80. Joe Scott  July 3, 2017

    Are there articles or posts that disucuss familial hypercholesterolemia and guidlindes specific to dietary cholesterol intake and need for statins ?

  81. Peter Attia  May 23, 2012

    Not entirely…remember Pattern A vs. Pattern B is not the causative issue. Pattern B is a marker for folks more particles, but the size isn’t causing the problem. The problem with LDL’s (vs. HDL’s) is that they not only penetrate the endothelium, but they often remain there AND deposit their cholesterol there. HDL’s do not.

  82. Drew  May 24, 2012

    why did my tg and ldl go up hdl went down

  83. Vasco Névoa  May 24, 2012

    Hmm… so HDLs don’t get gobbled up in foam cells? Why is that?

  84. Douglas Sichler  October 31, 2015

    Dr., Are LDL particles large or small or should I say can they be large or small particles?

  85. Thomas Dayspring aka "Dr Lipid"  May 26, 2012

    When TG rise, they invade HDL particles and knocks their cholesterol out. The TG-rich HDL is subject to catbolism and renal excretion of apoA-I (the HDL surface structural protein)

  86. Ed  May 29, 2012

    Dr Lipid,

    Do you have a lecture up on VLDL formation? I am interested to understand the LDL precursor birth, and the role of TG. TG tends to be high for those on high carbohydrate diets, and mine (predictably) dropped like a stone when I started carbohydrate restriction.

    Since VLDL production is a key to LDL-P, lets explore this…

    1) Why is TG so high in a fasted state when you eat a high carb diet or are insulin resistant?

    2) Can excess denovo lipogenesis account for the magnitude of TG increases in a high carb diet?

    3) Can elevated TG represent signs of fatty liver on the way to healing? Presumably the liver would need to export excess TG out via VLDL…

    4) Is the liver mopping up excess circulating NEFA and wrapping them into TG and sending them out in apoB particles? I’ve heard some suggestion that TG rises in the mornings for insulin resistant people because fat cells dump as much NEFA as they can during low insulin states (overnight) to help feed insulin resistant cells like muscle cells during the day. Does the liver mop up excess NEFA and repackage them into VLDL?

    5) Or some other reasons?

  87. Peter Attia  May 24, 2012

    They do not get oxidized as LDL’s do, and do not bind to arterial wall proteoglycans nor are they internalized by macrophages the way the apoB species are.

  88. Thomas Dayspring aka "Dr Lipid"  May 26, 2012

    LIkely they carry antioxidative proteins and are not subject to reactive oxygen species. The surface receptrs on a macrophage look for oxidized lipoproteins


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