Saturday, September 29, 2012

Everything You Need to Know About Cholesterol, LDL, and Heart Disease

Ah, back to cholesterol.  I know I've written about cholesterol a lot in the past, but this one is a game changer.  This information blows the doors off the current thinking in the cholesterol-heart-disease world, and it'll change the way you think about cholesterol.  (Credit goes to Dr. Peter Attia, whose presentation at AHS 2012 just blew my mind.  His 10-part series The Straight Dope on Cholesterol is here, and the shortened version on Mark's Daily Apple is here and here.)  What if I told you that the standard cholesterol test your doctor orders for you is useless? And what if I said it's not cholesterol that's important for heart disease risk, it's the LDL particle itself?

Okay, now you're probably thinking Hey Burn!  LDL is cholesterol, it's the bad cholesterol!  Ugh.  Before I go any further, we need to go over some basics.  Cholesterol is cholesterol.  There is no "good" and "bad".  Cholesterol is only one thing, and it's vitally important to every cell in your body.  LDL and HDL are something different.  They're not cholesterol at all, rather they are the molecules that carry cholesterol (and other fats) throughout the body to places where it is needed.  Cholesterol can't just float around the blood by itself; it needs a carrier.  Just imagine LDL as the "boat", and think of cholesterol as the "cargo".  Here's a nice little diagram of an LDL particle.  This little guy will be the subject of today's post.

The LDL particle, chock full of cholesterol.

You can see here that the LDL particle is full of cholesterol.  LDL particles can vary in how much cholesterol they hold, and their size is proportional in this way.  Small ones hold smaller amounts of cholesterol, while larger ones hold more cholesterol.

Your LDL cholesterol is meaningless.
But let's talk about lab tests that measure this stuff.  When you get your cholesterol measured, the LDL measurement you get is called LDL-C, and that measures the total amount of cholesterol in your blood that is being carried in LDL particles.  This does have a relationship with heart disease; those with higher LDL-C measurements tend to have higher rates of heart disease.  But it's not perfect.  Depending on who you talk to, anywhere from 20-50% of heart attack victims have normal cholesterol levels.  There's clearly something missing here.

Enter LDL-P, or LDL particle number.  Unlike LDL-C, which measures the amount of cholesterol (cargo), LDL-P measures the number of LDL particles (boats).  Why is this significant?  Because the sizes of LDL particles can vary, as I said before.  You could have an LDL-C of 130 mg/dl, but depending on how much cargo is packed into your boats, you might have lots of small particles, or you might have fewer large particles.  And there's a big difference.

Here's a study, one of several that have tested the long-term predictive value of LDL-P in heart disease.  This one followed 2500 patients for almost 15 years, split them up into four groups, and tracked their survival.  The cut-off points to determine low vs. high were the median values for the population, set at 1,414 nmol/L for LDL-P, and 131 mg/dl for LDL-C.  So for example, "high" LDL-P is over 1,414 nmol/L, and "high" LDL-C is over 131 mg/dl (1).

Okay I'll wade through the bullshit for you... High LDL-P is the best predictor of a heart attack.  LDL-C, the test you get from your doctor, is only accurate when the LDL-P is consistent with it.  Translation... it doesn't matter how much cargo you have in the boats, it's the number of boats that's important.  And the best way to measure that is LDL-P. 

Now think about this for a minute... I mean think critically.  More than anything else, this is what I want you to take away from this article... If it's the number of LDL particles that really matters,  not the amount of cholesterol within them, then cholesterol isn't the problem.  BOOM!  Let that marinate for a few minutes...

Side note for those who geek out on this stuff like me... I've spoken before about large and small LDL particles.  Large, fluffy LDL particles are the good guys, I've said.  Well, that's not quite right.  Although having large LDL particles is likely a good thing, it's not the large particles themselves that are beneficial; it's because having large particles is indicative of having fewer of them in total.  However, in cases where LDL particles are both large and plentiful, like in the genetic disorder Familial Hypercholesterolemia, the risk of heart disease remains very high.  It is the number of particles overall that is most important, not the size.

So what makes my LDL particle number go up or down?
How does our diet affect our LDL-P?  This is still new, so not much research has been done on the subject, but we do know one thing that increases your particle count... sugar.  Specifically, fructose and high-fructose corn syrup are the enemies here; they clearly increase LDL-P (2).  And that includes anything made with high-fructose corn syrup, sugar, brown rice syrup, crystalline fructose, or any of the million names sugar hides under on a food label.  Perhaps worst of all is agave nectar, which can be up to 85% fructose.  Ironically, foods high in sugar are currently allowed on so-called "heart-healthy" diets because they don't increase cholesterol.  With this new information on LDL particle number, whether or not a food increases cholesterol is completely irrelevant.

And what of saturated fat, demonized because it increases cholesterol?  Well I've already addressed this several times, the best of which can be seen here.  But using the data on LDL-P, I have a new angle to work from.  I don't think we know what eating saturated fat, or any other fat for that matter, does to our LDL particle number.  What we do know, however, is that fat from milk and eggs (primarily saturated) makes your LDL particles larger (3,4).  Since large particles are associated with a low total number, this could be beneficial.  Just think about it logically... making the LDL particles larger means that even if these fats do increase cholesterol, they likely do NOT increase the number of particles.  Artery-clogging effect mitigated :).  As if I needed another reason to eat butter.

"I've never heard of LDL-P, you're clearly just some gullible douche blowing smoke up my ass."
That's your reaction at this point in the article.  I don't blame you; there's a lot of misinformation out there.  But chew on this... In March of 2008, both the American College of Cardiology and the American Diabetes Association released a joint statement saying that "the measurement of LDL particle number (LDL-P) is a more accurate method of quantifying cardiovascular risk than traditional measurement of LDL cholesterol (LDL-C) (5)."  This is not bullshit, it's just new.  And here's another paper on LDL-P... this stuff is real (6). 

Yet your doctor doesn't test for it.  A.) Because he's never heard of it, and B.) Because it's expensive.  Currently, there's only one way to test LDL-P, and that's through NMR LipoProfile, which you can order online at various websites at about $129.  As an alternative, though, you can also get a test known as "apo-b" which measures the number of apolipoprotein-b lipoproteins in your blood, of which LDL is the only one.  That's a mouthful.  It's basically another way to measure the same thing, and your doctor may be able to order this one more easily.

So there it is, LDL-P.  The next big thing.  There's so much more detail to this topic that I just couldn't go into, but if you're a complete dork and want to know more, like the mechanisms by which this all works, check out Peter Attia's articles (referenced in the intro) and have at it.  Or listen to Chris Kresser explain it on The Paleo Solution Podcast if that's more your speed.  Same information, different guy.  Thanks for reading, peace I'm out.


  1. IT'S THE BOATS PEOPLE! I cannot wait until this becomes mainstream knowledge.. if it ever does. Also, you mentioned you don't know of any studies that show how saturated fat effects your cholesterol.. WELL Dr. Volek is currently doing a feeding study at UConn that is measuring this amongst other things. The grad student is actually focusing her PhD in this area so hopefully we will know soon! Another great blog post. Seeing Peter give this lecture at AHS was so mind blowing!

  2. Took the NMR test on 5/10/12 so I'll be getting another one soon


    LDL-P 1500

    HDL-C 59

    Triglycerides 36

    Small LDL-P 127

    LDL size 21.1

    LP-IR 6

    Any thoughts and/or comments?

  3. Thank you for putting this out there, Burn!! And making me laugh, too.

  4. Just found this article, which better helped with my understanding of LDL-P (I'm one of those with high LDL-P, high LDL-C but with very low lipoprotein(a)).

    With that said, how do you statistically in absolute terms interpret the graph in this article? Does it mean that after 16 years, there is a 770 out of 1,000 chance that a person with high LDL-P & low LDL-C will not have a cardiac event versus a person with low LDL-P & low LDL-C that has a 910 out of 1,000 chance?

    Or, is it 77 out of 1,000 versus 91 out of 1,000?

    My inkling is that future readers of this article will be helped if you included an actual interpretation of the absolute numbers on this study's results (and for future studies you write about).

    BTW, from my reading of nutrition bloggers, most don't provide an absolute interpretation of these statistical studies that the typical layperson can understand. This is sorely lacking, which your blog could become a source of that would attract more readers...just a thought.

    1. WindyCity,

      Excellent point. That would be useful, but for the purposes of this article I wanted to keep everything as short and concise as possible. It was very difficult to do! But I may have to write a new post and go more in depth on this topic.

      Just based on some quick calculations... according to this study, it looks like a high LDL-C measurement is indicative of concurring high LDL-P about 81.5% of the time. In other words, if you have high LDL-C, you've got about an 18.5% chance that you have nothing to worry about (that your LDL-P is fine).

      I'll probably analyze this further at some point, thanks for the tip.