The two kinds of small LDL

You won't find this in any publication nor description (at least ones that I've come across) about the ubiquitous small LDL particles. It's an observation I've made having obtained thousands of advanced lipoprotein panels of the sort that break lipoproteins down by size. I've discussed this issue previously here. But small LDL is so ubiquitous, not addressed by conventional strategies like statin drugs or fat restriction (it is made worse, in fact, by reducing fat in the diet), that it is worth keeping at the top of everyone's consciousness.

(Because most of the lipoprotein analyses performed in my office are done via NMR, I will discuss in terms relevant to NMR. This does not necessarily mean that similar observations cannot be made with centrifugation, i.e, VAP from Atherotech, or gel electropheresis from Berkeley, Boston Heart Lab, Spectracell, and others).

There are two basic varieties of small LDL particles:

1) Genetically-programmed--e.g., via cholesteryl-ester transfer protein (CETP) activity
2) Acquired--via carbohydrate consumption


It means that people with acquired small LDL from carbohydrate consumption can reduce small LDL to zero with reduction of carbohydrates, especially the most small LDL-provoking foods of all: wheat, cornstarch, and sucrose.

It also means that people who have small LDL for genetically-determined reasons can only minimize, not eliminate, small LDL. By NMR, we struggle to keep small LDL in the 300-600 nmol/L range when genetically-determined. (People typically start with 1400-3000 nmol/L small LDL particles prior to diet changes and other efforts.) We can only presumptively identify genetically-determined small LDL when all the appropriate efforts have been made, including reduction in weight to ideal, yet small LDL persists.

Here is where we need better tools: when you've done everything possible, yet small LDL persists.

While we break LDL particles (NOT LDL cholesterol, the crude and misleading way of viewing atherosclerosis causation) down by size, it's really about all the undesirable characteristics that accompany small size:

--Distortion of Apo B conformation--i.e., the primary protein that directs LDL particle fate is distorted, making it less likely to be cleared by the liver but more likely to be taken up by inflammatory (macrophages) in the artery wall, creating plaque. It means that small LDL particles linger for a longer time than larger particles.

--Small LDLs are more oxidation-prone. Oxidized LDL are more avidly taken up by inflammatory macrophages.

--Small LDLs are more glycation-prone.

--Small LDLs are more adherent to structural tissues, e.g., glycosaminoglycans, that reside in the artery wall.

You and I cannot measure such phenomena, so we resort to distinguishing LDL particles by size.

The drug industry believes it may have a solution to small LDL in the form of CETP-inhibiting drugs, like anacetrapib. In the way of nutritional solutions beyond carbohydrate reduction, weight loss/exercise, niacin, vitamin D normalization, and omega-3 fatty acid supplementation, there are exciting but very preliminary data surrounding the possibility that anthocyanins may inhibit CETP activity. Having toyed with this concept for the past 6 months, I remain uncertain how meaningful the effect truly is, but it is harmless, since we obtain anthocyanins from foods colored purple or purplish, such as blackberries, blueberries, cherries, red leaf lettuce, red cabbage, etc.

I welcome any unique observations on this issue.

Comments (17) -

  • Tommy

    12/27/2010 3:37:38 PM |

    "But small LDL is so ubiquitous, not addressed by conventional strategies like statin drugs or fat restriction (it is made worse, in fact, but reducing fat in the diet)"

    Just to be clear about the above quote. You say "it is made worse, in fact, but reducing fat." Did you mean "by" reducing fat?

    Also, if that is the case, is that because of the fat itself or because less fat means replacing it with carbs?

  • Jonathan Byron

    12/27/2010 4:50:45 PM |

    In addition to CETP inhibition, some other benefits of red/blue/purple foods (that also include polyphenols other than the anthocyanins - elligitanins, etc) include:

    1) inhibition of amylase - less of a blood sugar spike after eating starchy foods, less aberrant glycation and AGEs.
    http://www.ncbi.nlm.nih.gov/pubmed/15796622

    2) Estrogenic activity - anthocyanin stimulates the beta-estrogen receptors in blood vessels and bone, not much activity in the alpha receptors in breast, uterus.
    http://www.ncbi.nlm.nih.gov/pubmed/20049322

    3) Phosphodiesterase inhibition!
    http://www.ncbi.nlm.nih.gov/pubmed/15769121

  • Peter

    12/27/2010 5:09:05 PM |

    I was surprised that Ron Krauss, who did a lot of research on small particle LDL and recently published a mega-study supposedly showing saturated fat is unrelated to heart disease, made these comments in a recent interview:

    People should limit saturated fat to 10% of their diet, though some can get away with more.

    Optimal carbs intake: 35 to 40%.

    People used to get heart disease from high cholesterol, but now its mainly high carbs.

    The interview is here, and those ideas are toward the end:

    http://www.meandmydiabetes.com/2010/03/26/ldl-cholesterol-ron-krauss-md/

    I would love to know if you have any comment.

  • Geoffrey Levens

    12/27/2010 5:20:51 PM |

    This is worth knowing about! Low cost (relatively) lab tests without needing a doc visit/prescription

    https://summitcountymedicalsociety.prepaidlab.com/

    All tests performed by LabCorp

  • steve

    12/27/2010 9:35:35 PM |

    sometimes it comes down to our health being all about our genetics. As a result of the recomendations of this blog with regard to wheat and sugar elimination, normalizing vitamin D i have taken down my LDL from 1810, all small to 609 of which 346 are small; i can only lower my particles with statins- diet alone will not do it.  My understanding of the research is that at low levels, size does not matter. I will note that when my particles were sky high i thought i was follwoing a very healthy low fat, grain oriented diet.  Now, i eat now grains and have a fair amount of mono fats from avocado and olive oil, some sat fat from lean meats, poultry and eggs, and hope i have minimized the progression of artery plaque that shocked me when i found out i had it when i followed healthy heart diet, exercise and maintained a very lean body weight.  Gentics are tough to overcome, but the risks can be minimzed via diet and meds.

  • Might-o'chondri-AL

    12/28/2010 6:12:34 AM |

    Different segments of the same carotid artery can apparently be affected by a different gene. Each segment is itself susceptable to different pathological processes, like shear rate of the near inner arterial wall. Artherosclerosis at different arterial segments seem to predict if pathological event will be ischemic stroke or myocardial infarction.

    The North Manhattan Study tried to tweak 145 genes modulated by 702 single nucleotide polymorphisms. That study and the San Antonio, Erasmo Rucphen and Framingham have led to opinions that 30% to 60% of the thickness of the carotid artery's intima-media is geneticly inherited. Then for carotid plaque +/- 28% is passed on geneticly.

    Sex of the individual and racial ethnicity are other genetic variables. Doc Davis' clinical observation is telling us something equally important about small LDL's genetic variation.

  • Ryan

    12/28/2010 2:47:00 PM |

    Is small LDL the "VLDL" on blood results?

  • Dr. William Davis

    12/28/2010 2:55:38 PM |

    Hi, Tommy--

    Yes, indeed. Just a typo.

    Probably both.

  • Dr. William Davis

    12/28/2010 2:57:59 PM |

    Hi, Jonathan--

    Excellent! Yes, the conversation surrounding anthocyanins is becoming increasingly interesting.



    Hi, Peter--

    I don't personally know Ron Krauss, but I too have been puzzled by the fact that his public comments don't seem to reflect his research findings. If he were to echo the important findings of his research, he would indeed be a low-carb, high-fat advocate.

  • Dr. William Davis

    12/28/2010 2:59:31 PM |

    Steve--

    Wonderful results! The diet approach works, no doubt about it.


    Hi, Ryan--

    No, two different things.

  • Anonymous

    12/29/2010 5:50:28 AM |

    Hello Dr.Davis,
    Your comments sound very similar to Dr Ray Strand...do you read his work? If not, I think you would enjoy his thoughts. His website is www.drraystrand.com
    Cheers,
    Sue in BC Canada

  • Brent

    12/29/2010 4:02:25 PM |

    Question for all you Small Particle techies out there.  Always had "Good" lipid panels, even though overweight and borderline type 2 under control with a low carb diet.

    Numbers usually average:
    Total Cholesterol 125
    LDL  65
    HDL  45
    Tri  90  

    Just got first particle size test done, results in VAP format:  

    LDL-1Innocent 3
    LDL-2Innocent 0
    LDL-3(B) 36
    LDL-4(B) 34

    I know particle size goes down as the LDL- number goes up, but how do these numbers translate to the NMR numbers Dr. Davis listed as a target for those of us genetically pre-disposed to pattern B LDL?

  • Anonymous

    12/29/2010 9:22:31 PM |

    ^I'm interested in the same thing

  • David

    12/30/2010 8:30:59 PM |

    Brent,

    Your small LDL makes up 96% of your total LDL particles. This is a severe pattern.

    Also, your HDL is too low and your triglycerides are a tad too high. Dr. Davis' Track Your Plaque goal of 60-60-60 is a good rule of thumb. LDL down to 60, HDL up to 60, trigs down to 60.

    If you're currently following a low-carb diet and still have all of this small LDL, your small LDL pattern is probably the genetic type that Dr. Davis talks about here.

    David

  • Lyndall

    7/10/2011 3:29:30 AM |

    ThatÂ’s not just logic. ThatÂ’s ralley sensible.

  • Rocky

    7/10/2011 9:56:07 PM |

    IJWTS wow! Why can't I think of thnigs like that?

  • hcvepozwjly

    7/13/2011 2:43:00 PM |

    A9UICM , [url=http://ulbfgwnayluy.com/]ulbfgwnayluy[/url], [link=http://brcwwrkirppg.com/]brcwwrkirppg[/link], http://ongtrzqlozlv.com/

Loading