Unforgiving small LDL particles

Small LDL particles are triggered by carbohydrates in the diet: Eat carbohydrates, small LDL particles go up. Cut carbohydrates, small LDL particles go down.

A typical scenario would be someone starts with, say, 2000 nmol/L small LDL (by NMR) because they've been drinking the national Kool Aid of eating more "healthy whole grains" and consuming somewhere around 200 grams carbohydrates per day, including the destructive amylopectin A of wheat. This person slashes wheat followed by limiting other carbohydrates and takes in, say, 40-50 grams per day. Small LDL: 200 nmol/L.

In other words, reducing carbohydrate exposure slashes the expression of small LDL particles, since carbohydrate deprivation disables the liver process of de novo lipogenesis that forms triglycerides. Abnormal or exaggerated postprandial (after-eating) lipoproteins that are packed with triglycerides are also reduced. Because triglycerides provide the first lipoprotein "domino" that cascades into the formation of small LDL particles, carbohydrate reduction results in marked reduction in small LDL particle formation.

So let's say you are doing great and you've slashed carbohydrates. Small LDL particles are now down to zero--no small LDL whatsoever. What LDL particles you have are the more benign large variety, say, 1200 nmol/L (LDL particle number), all large, none small. You are due for some more blood work on Thursday. On Tuesday, however, you have four crackers because, what the heck, you've been doing great, you've lost 43 pounds, and have been enjoying dramatic correction of your lipoprotein abnormalities.

Your next lipoprotein panel: LDL particle number 1800 nmol/L, small LDL 700 nmo/L--substantially worse, with a major uptick in small LDL.

That's how sensitive small LDL particles can be to carbohydrate intake. And the small LDL particles can last for up to several days, since small LDL particles are not just smaller in size, they also differ in conformation, making them unrecognizable by the normal liver receptor. The small LDL particles triggered by the 4 crackers therefore linger, outlasting the normal-conformation large LDL particles that are readily cleared by the liver.

This phenomenon is responsible for great confusion when following lipoprotein panels, since a 98% perfect diet can yield dismaying results just from a minor indulgence. But, buried in this simple observation is the notion that small LDL particles are also extremely unforgiving, being triggered by the smallest carbohydrate indulgence, lasting longer and wreaking their atherosclerotic plaque havoc.

Comments (39) -

  • ChrisB

    10/21/2011 3:45:39 PM |

    Great Article.  As I'm sure you know by now, I've been kind of a lipidpanelaholic since having a MI 2 yrs ago.  The hardest information to find is that of how long it takes for lipids to respond to diet changes and how sensitive they can be to even the smallest amount of carbs.

  • Howard

    10/21/2011 4:44:48 PM |

    Are you sure that sort of response is not due to gluten/gliadin/lectin/transfat? Four crackers doesn't sound to me like much of a carb load, but for a gluten-sensitive person like me, that could set off some inflammation.

  • Marc

    10/21/2011 7:08:35 PM |

    Dr. Davis,
    How does alcohol fit in to the above "equation"? Specifically wine.


  • Sam Sinderson

    10/22/2011 12:12:39 AM |

    I have been on a wheat-free and carb restricted diet for about 7 weeks, and being concerned that I might be Apo E4, and therefor need to also limit saturate fat as you explained in an earlier blog, I asked my doctor to order a small LDL test.  No independent lab here that I consulted knew what that was, nor obviously did my doctor, since he just ordered "small LDL".  The local hospital lab finally found the following, which is what I will have blood drawn for tomorrow:
    Lipoprotein Fractionation Panel 1, Ion Mobility
    Which includes:
    Choesterol; HDL Cholesterol; Triglicerides; :Lipoprotein (a); Lipoprotein Fractionation Panel 2, Ion Mobility (LDL, Total; LDL, Medium and Small; LDL, VerySmall; HDL, Large; LDL Peak Diameter, LDL Phenotype)

    I hope that this is what I need.  Probably it is overkill, but in this case apparently my Medicare Advantage plan will cover it since it has been more than 3 months, since I had a simple panel done.

    Is there a simpler test for small LDL?  By the way the CPT codes are 80061, 83695, 83704

  • Fat Guy Weight Loss

    10/22/2011 4:41:38 AM |

    Sounds like cheat days may not be that good of an idea...

  • Dr. William Davis

    10/22/2011 12:39:39 PM |

    Yes, it does cast cheat days in a new light!

  • Dr. William Davis

    10/22/2011 12:45:11 PM |

    That's it, Sam.

    It shouldn't be that hard. The information is actually fairly straightforward and provides crucial information.

  • Dr. William Davis

    10/22/2011 12:51:45 PM |

    Hi, Marc--

    Alcohol does indeed slow or stop weight loss, especially if more than a serving or two are consumed. So it pays to minimize during a weight loss effort.

  • Dr. William Davis

    10/22/2011 12:56:34 PM |

    Probably not, Howard, since those components have not been associated with triggering of small LDL. The trans fat component can indeed trigger small LDL, but it seems to occur even with foods minus trans fats.

    However, I am impressed that gluten/gliadin/lectin rolled off your tongue!

  • STG

    10/22/2011 1:36:14 PM |

    The problem is carb creep. I experienced this a few months ago when I received the results of my HbA1c test. I was still in the prediabetic range and it was higher than the HbA1c test I had a few years earlier. I didn't get it? I thought I was consuming less carbs then I was. When I actually looked at my diet there were carbs creeping in: dark chocolate and small "safe starches" (e.g, potatoes, yams). Another factor that may have impacted my blood sugar was the stress of travel/visiting family during that three month time period. My understanding is that elevated cortisol levels can raise blood sugar. In any case, my recent HbA1c is in normal range. I think this is because I eliminated even small amounts of dark chocolate and "safe starches" (see Jimmy Moore's comments about safe starches).

  • jethro

    10/22/2011 2:01:01 PM |

    How low should we go in carbohydrates to avoid increasing small LDL?

  • Davide

    10/22/2011 3:01:26 PM |

    I'm not sure that wheat has this acute effect on everybody. In fact, I know it doesn't happen with me. I keep a close eye on my lipids and my small LDL particles remain "relatively" low despite the fact that I consume wheat/sugar products. Then again,  my blood sugar does not significantly rise after carbohydrates, so maybe that's why. If I eat a massive plate of pasta, a glass of fruit juice, and dessert, my blood sugar may (keyword, "may") rise to 120, if that, but then it goes down to about 80 about 45 minutes after the meal. No joke. In other words, I'm thinking this effect may have to do with the degree of people's volatility to rising blood sugars. Just a guess.

    Fyi, I'm the apo E/4 person who's LDL amount/particle number (226, 2,000) is extremely sensitive to saturated fats and thus I'm always lost in the conundrum of balancing fats with carbs. Difficult!

  • Teresa

    10/22/2011 3:05:34 PM |

    I know that if weight loss is involved, it can take a few months after weight stabilizes for lipids to normalize.  If minimal or no weight loss is involved, how long does it take?

  • Fat Guy Weight Loss

    10/22/2011 5:31:19 PM |

    With the example about 4 crackers would be as low as 10g carbs.  Curious of the overall effects of say 10g carbs of sweet potatoes....

  • Dr. William Davis

    10/23/2011 11:49:09 PM |

    Then it depends on which parameter you are talking about, Teresa.

    Small LDL requires just days to respond, while triglycerides require weeks to months, while HDL requires months to years.

  • Dr. William Davis

    10/23/2011 11:51:13 PM |

    Hi, Davide--

    No doubt: Individual tolerances to various foods, including carbohydrates, can differ. And the apo E4 person has a tougher time of it.

  • Dr. William Davis

    10/23/2011 11:53:40 PM |

    Unfortunately, Jethro, there's no quick and easy way to decide this, since individual sensitivity varies.

    Although imperfect, you can use HbA1c, an index of glucose and not of small LDL, to gauge whether you've been triggering higher blood sugars that often parallel the triggering of small LDL particles. You could, of course, obtain lipoprotein testing 48 hours after ingesting a known amount of carbohydrates, e.g., 20 grams, but that is logistically difficult.

    That all said, most people can get away with 15 grams carbohydrates per meal, while some can't tolerate more than 10, yet others do fine with 30+ grams.

  • Dr. William Davis

    10/23/2011 11:54:15 PM |

    Excellent point, STG! And I like the "carb creep"!

  • Barbara

    10/24/2011 12:14:06 AM |

    Did you see this, Dr. Davis?


  • Teresa

    10/24/2011 1:14:14 AM |

    And it takes years to unlearn all the inaccurate stuff learned in school, and to find and learn the good stuff that is out there.  Thanks.

  • Stephanie

    10/24/2011 2:27:52 PM |

    How does one check to see if they are apo E4?

  • ChrisB

    10/25/2011 1:19:25 PM |

    How does it affect lipid results?

  • steve

    10/25/2011 10:52:06 PM |

    Dr Davis:  What is the small LDL profile for native populations that consume tons of of carbs and no signs of heart disease; also, the Japanese consume lots of carbs- easily 3 cups of rice per day which is about 120 carbs from rice alone.  Low level of CAD; what are their levels of small LDL.  I know for myself ApoE 3/3 that carbs do affect the small LDL level i have and in any event in the absence of a statin i produce tons of LDL particles large or small depending upon carb levels.  I believe genetics plays a large role.

  • Dr. William Davis

    10/26/2011 3:19:22 AM |

    No doubt, Steve.

    However, I'm unaware of lipoprotein assessment done to answer these questions. That would be interesting, however.

  • Dr. William Davis

    10/26/2011 3:21:50 AM |

    Yes, agreed, Teresa: New lessons to learn every day in this Information Age!

  • Dr. William Davis

    10/26/2011 3:23:44 AM |

    Thanks, Barbara. No, I hadn't seen this. But I'm not the least bit surprised!

    I find it wonderfully satisfying that the puzzle pieces are falling in place, just like that 1000-piece jigsaw puzzle we struggled to put together, with the last few pieces fit just perfectly!

  • Dee

    10/28/2011 1:57:49 PM |

    Dr. Davis,
    Have you heard or read about Lumbrokinase helping to lower small "a" particles?
    Just wondering.

  • Tim

    10/28/2011 7:14:08 PM |

    Dr. Davis,

    There seems to be a lot of mention of the E4 ApoE genotype.  What about those of us that are E2/E4?  Any different instructions for us?


  • Dr. William Davis

    10/29/2011 10:48:39 PM |

    With this very tough pattern, you are best following lipoproteins and glucose measures like HbA1c to gauge response to various dietary manipulations. The basic diet approach, however, is largely the same; it just may require some adjustments, e.g., fat intake.

  • Dr. William Davis

    10/29/2011 10:49:12 PM |

    Sorry, Dee, no info.

    Where did you hear this?

  • Dee

    10/30/2011 5:20:26 PM |

    Here is the quote.  Appently it just helps lower the LP[a]  and does not have any terrrble side effects.  I may try it, nothing else is working.  My little a is 43 and rising in spite of all I do.

    "The one nutraceutical that has shown promising clinical results in actually lowering Lp(a) is a lumbrokinase product made by Canada RNA Biochemical called Boluoke. Like its chemical cousin nattokinase, lumbrokinase is an enzyme that helps break up fibrin—a fibrous protein that helps form blood clots—to avoid too much clotting and keep blood flowing optimally."



  • Sam Sinderson

    10/31/2011 7:32:29 PM |

    I have my results.  My PCP reported these to me "for my records" with no further comment.  Maybe he can't interpret them?
    Total Cholesterol: 231 (My PCP surely would think this is high.)
    I find it strange that they did not report LDL direct, though perhaps it is not done because of the breakdown below.  
    Calculated LDL: 133 H MG/DL
    HDL: 85 Mg/dl  This is higher than I have ever had measured.
    Triglycerides: 64 Mg/Dl  Even Simvastatin only got it down to 84.  I conclude that I am not Apo E4.
    The range after \ below  is the range they cite, I presume, as normal.
    Lipoprotein Innocent: <10  NMOL/L \ <75  I presume this is a good result.
    LDL, Total: 2268 H NMOL/L  \ 440-1600
    LDL, medium and small: 651 NMOL/L \ 144-787
    LDL, Very Small: 277 NMOL/L \ 75-419
    HDL large: 9315 H NMOL/L  \ 469-5258
    LDL Peak Diameter: 227.5 Angstrom  \216.-234.3
    LDL Phenotype A  Pattern A     I believe this to be the preferred pattern, low small LD and Triglycerides.  Ref: Obesity (2009) 17 9, 1768–1775. doi:10.1038/oby.2009.146--Reversal of Small, Dense LDL Subclass Phenotype by Normalization of Adiposity
    Patty W. Siri-Tarino1, Paul T. Williams2, Harriet S. Fernstrom1, Robin S. Rawlings1 and Ronald M. Krauss1

    Does this calculate to large LDL = 2268-651 =1617 (Not including medium)?
    When should I do this test again?

  • Dr. William Davis

    11/1/2011 2:03:32 AM |

    Hi, Sam--

    The "pattern A" comment is misleading. About 40% of your LDL particles are small, too much.

    It means going back to the strategies to reduce small LDL, such as wheat elimination and limiting carbohydrate exposure. It is worth repeating about 2 months after weight has stabilized following a diet change.

  • Sam Sinderson

    11/1/2011 12:49:43 PM |

    I have been on a no-wheat, limited, very-low carb, diet now for 6 to 7 weeks already.  I cringe to think of what the numbers may have been before.  I initially lost about 12 pounds in less than 2 weeks to get to 148, I am 72-in tall, and have stabalized there by eating more high-fat non-carb stuff.  You say 40% small.  You must be using the medium and small (640) over total (2268) to get 40%.  Apparently medium and small includes the very small, which must be a fraction of small?  How long should it take for the very small to approach zero?  Isn't that the more important number?  I will be out of the country for 2 weeks.


  • Dr. William Davis

    11/2/2011 1:43:14 AM |

    Yes, exactly, Sam: Combine medium and small.

    Dietary and weight changes usually exert effects on small LDL within a few weeks, much faster than most other parameters.

  • pb

    2/6/2012 3:47:25 PM |

    Get a VAP test....this measures your small particle/large particle LDL.
    labcorp code 804500

  • pb

    2/6/2012 3:51:39 PM |

    I am going to try to get a VAP test.  No doctors know of it....only folks on the web.  Why?  It seems like a very important test to measure your LDL properly.  Can someone elaborate on this further?

  • Dr. William Davis

    2/7/2012 3:18:11 AM |

    Easy, Pb: There are no drugs--read: "no financial incentive"--to treat the abnormalities generally uncovered by lipoprotein testing like VAP. Thus, no push to get it tested.