Carbohydrate-LDL double whammy

Carbohydrates in the diet trigger formation of small LDL particles. Because carbohydrates, such as products made from wheat, increase triglycerides and triglyceride-containing lipoproteins (chylomicrons, chylomicron remnants, VLDL, and IDL), LDL particles (NOT LDL cholesterol) become triglyceride-enriched. Triglyceride-enriched LDL particles are "remodeled" by the enzyme, hepatic lipase, into triglyceride-depleted, small LDL particles.

The list of reasons why small LDL particles are more atherogenic, i.e., plaque-causing, is long:

--Small LDL particles, being smaller, more readily penetrate the endothelial barrier of the arterial wall.
--Small LDL particles are more adherent to glycosaminoglycans in the artery wall.
--Small LDL particles are poorly taken up by the liver LDL receptor, but enthusiastically taken up by macrophage receptors of the sort in your artery walls.
--Because of their poor liver clearance, small LDL persists in the bloodstream far longer than large LDL.
--Small LDL particles are more oxidation-prone. Oxidized LDL are more likely to trigger inflammatory phenomena and be taken up by macrophages in the artery wall.

Let me add another reason why small LDL particles are more likely to cause plaque: They are more likely to undergo glycation. (More on glycation here.)

Glycation occurs when glucose (sugar) molecules in the blood or tissue modify proteins, usually irreversibly. Small LDL particles are uniquely glycation-prone. (This is likely due to a conformational change of the apoprotein B in the small LDL particle, exposing lysine residues along apo B that become glycated.)

Here's a great demonstration of this phenomenon by Younis et al:

"LDL3" is the small type. Note that small LDL particles are 4-5 times more glycated than large LDL. That's a big difference.

Once glycated, small LDL is especially resistant to being taken up by the liver. Like annoying in-laws, they hang around and hang around and . . . The longer they hang around, they more opportunity they have to contribute to plaque formation.

So, carbohydrates trigger formation of small LDL particles. Once formed, small LDL particles are glycated when blood sugar increases. While LDL can be glycated even when blood sugars are in the normal range (90 mg/dl or less), glycation goes berserk when blood sugars go higher, such as a blood sugar of 155 mg/dl after a bowl of steel-cut oatmeal.

Comments (14) -

  • Tony

    7/9/2010 4:06:01 PM |

    I used diet and supplements instead of a statin to control my cholesterol, and my recent VAP test indicated I had "large buoyant" LDL. We know statins reduce LDL and inflammation, but do they affect particle size?

  • Red Sphynx

    7/9/2010 4:26:18 PM |

    Does increasing dietary fiber have a significant effect on the abundance of of LDL3, or its oxidation or glycation?

    My reasoning is that the gut reabsorbs cholesterol and returns it to the gall bladder.  The gall bladder taps the liver for the make-up cholesterol.  The liver draws LDL out of the blood when it needs cholesterol.  Sooo... fiber decreases re-absorption of cholesterol  This  ought to, eventually, decrease the time that LDL3 particles circulate before the liver grabs them.

    But I don't know if it works out that way, or if the effect is negligible.  Can you say?

  • Hans Keer

    7/9/2010 5:09:58 PM |

    As far as I'm concerned, you cannot say enough bad things about carbohydrates, but unfortunately they are not responsible for the formation of chylomicrons and chylomicron remnants. Chylomicrons consist mainly of dietary fat.

  • Anonymous

    7/9/2010 10:49:58 PM |

    Assuming you can't measure your LDL particle sizes, would a low (<2) Triglicerides  ratio to HDL be a good indicator whether you have predominately Pattern A (awesome) or B (bad)?


    7/10/2010 12:18:03 AM |

    Hi Can someone please tell me if
    ALL BRAN cereal being all bran and insoluble fiber is the same as eating wheat products?  


  • Randy

    7/10/2010 8:51:13 AM |

    Hi Doctor Davis,

    I have two questions.

    1. How would you compare rice (unpolished but non brown) to other carbohydrates (non gluten based)?

    2. How far does the fermenting/sourdough making process make wheat or other gluten containing carbs a healthier choice?


  • Anonymous

    7/10/2010 1:58:31 PM |

    A question for Dr Davis: Do you screen for pregnenolone deficiency?  If so, do you recommend pregnenolone supplements, in addition or in lieu of dhea?

    As a male, age 60+, I read TYP and  got the calcium scoring exam, which fortunately was zero percent.  Also had the carotid artery ultrasound which said no plaque (visual inspection).

    Got me to wondering why I (apparently) have no plaque.

    Well, twenty years ago when I was suffering arthritis joint pain I read Dr. Regelson's book the Super-Hormone Promise. (Still available on Amazon.) He discussed using pregnenlone as an arthritis treatment. So, I got the blood test and I discovered that I had a 100% deficiency of pregnenolone!

    I've been taking 500 mg a day of LEF's pregnenolone ever since. Blood levels back to normal immediately and no joint pain. (Re hormones, I also take 25 mg dhea and about 10 mg of melatonin at night.)

    My speculation is that perhaps supplementing my hormones at an earlier age, when serious deficiencies were starting to develop, helped keep my arteries healthy. On the other hand, it could be something else of course. Just my two cents!

  • Anonymous

    7/10/2010 4:27:18 PM |

    I got a good chuckle from the in-laws reference.  Thanks!


  • Anna

    7/10/2010 6:52:39 PM |



    If you are consuming All Bran cereal, you are consuming wheat, though the bran doesn't have the starchiness that refined wheat and whole wheat flour have.  But the bran presents other problematic properties.  

    If you must supplement with a refined fiber product (for regularity, belief that high fiber diets are healthful, etc.), consider instead soluble fiber such as inulin and/or pectin (and whole foods which contain soluble fiber, such as onions, leeks, apples, sunchokes, etc.).  

    See Dr. Art Ayer's (Ph.D. researcher, not an MD) blog Cooling Inflammation  for fascinating discussions on feeding and promoting healthy gut bacteria populations ("inner gardens") with soluble fiber.

  • Anonymous

    7/11/2010 5:36:05 PM |

    happy to see denise mingers study featured here. Smile

    wheat asides, milk pasteurised or uht causes a pretty massive immune system flare up for me.

  • Anonymous

    7/13/2010 4:06:07 PM |

    Dr. Davis, I emailed you on this but figured I'd post this study in response to this.

    Can you comment on the following study ?

    4) Schaefer EJ.  Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. JAMA. 1995 Nov 8;274(18):1450-5.

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    7/15/2010 3:48:53 PM |

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  • Anonymous

    7/22/2010 11:36:58 AM |

    can you decipher this new research for us? older women with low HDL are nore likely to be depressed, as well as more likely to have heart problems. Older men (over 65)with low LDL are more likely to be depressed, especially if their serotonin transport gene doesn't work efficiently.
    Research from ESPRIT study in Biological Psychiatry Journal (