May 23, 2012

Cholesterol

The straight dope on cholesterol – Part V

by Peter Attia

Read Time 9 minutes

In this post we’ll address the following concept: Does the size of an LDL particle matter?

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?

 

 

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.

 

unadjusted-vs.-adjusted-table

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.

 

Adjustment-for-large-LDL

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?

 

Summary

  • 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.

By NASA Mercury image: JHUAPLVenus image: JPLMars image: HST [Public domain], via Wikimedia Commons

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263 Comments

  1. 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.

    Deborah

  2. 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

    • 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?

  3. 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.

    • 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.

  4. 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?

    • 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.

  5. 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.

    • 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.

  6. Peter,

    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?

  7. 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.

  8. 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,

    Dean

    • 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.

  9. 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.

  10. 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!

  11. 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.

  12. 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.

    Chris

  13. 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
    Lipids
    Total 398
    LDL-C 290
    HDL-C 104
    TRI 58
    Non-HDL-C 294

    Particle
    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

    Inflamation
    Hs-CRP 0.4
    Lp-PLA 303

    Metabolis
    All were optimal except
    Her free fatty acids were 1.40

    Thyroids
    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.
    HELP!

  14. 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:

    http://education.questdiagnostics.com/faq/FAQ134

    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.

  15. 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.???

  16. 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.

  17. 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…

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

  19. 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.

  20. 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.

  21. 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?

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