LDL glycation

1. April 2010 William Davis (11)
The proteins of the body are subject to the process of glycation, modification of protein structures by glucose (blood sugar). In the last Heart Scan Blog post, I discussed how glycated hemoglobin, available as a common test called HbA1c, can serve as a reflection of protein glycation (though it does not indicate actual Advanced Glycation End-products, or AGEs, just a surrogate indicator).

There is one very important protein that is subject to glycation: Apoprotein B.

Apoprotein B, or Apo B, is the principal protein of VLDL and LDL particles. Because there is one Apo B molecule per VLDL or LDL particle, Apo B can serve as a virtual VLDL/LDL particle count. The higher the Apo B, the greater the number of VLDL and LDL particles.

Because Apo B is a protein, it too is subject to the process of glycation. The interesting thing about the glycation of Apo B is that its "glycatability" depends on LDL particle size: The smaller the LDL particle, the more glycation-prone the Apo B contained within.

Younis et al have documented an extraordinary variation in glycatability between large and small LDL, with small LDL showing an 8-fold increased potential.

Think about it: Carbohydrates in the diet, such as wheat products and sugars, trigger formation of small LDL particles. Small LDL particles are then more glycation-prone by up to a factor of 8. Interestingly, HbA1c is tightly correlated with glycation of Apo B. Diabetics with high HbA1c, in particular, have the greatest quantity of glycated Apo B. They are also the group most likely to develop coronary atherosclerosis, as well as other consequences of excessive AGEs.

No matter how you spin it, the story of carbohydrates is getting uglier and uglier. Carbohydrates, such as those in your whole grain bagel, drive small LDL up, while making them prone to a glycating process that makes them more likely to contribute to formation of coronary atherosclerotic plaque.
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Comments (11) -

  • Anonymous

    4/1/2010 1:49:28 AM |

    So, basically one can't eat carbohydrates at all, nor dairy products, nor too much animal fat. So what are you supposed to eat?

  • Ned Kock

    4/1/2010 2:21:36 AM |

    Very interesting post Dr. Davis.

    And that is one more reason to replace refined carbs and sugars in one's diet with saturated fat and dietary cholesterol, which significantly contribute to a shift from Pattern B to A in LDL particles.

    By the way, the usual term that I normally see is "apolipoprotein", but they may be a bias in the literature I have been reading.

  • robbie

    4/1/2010 2:37:02 AM |

    This is really interesting but I only understand about 1/2 of it.  Can you break it down a little for the lay person. I am following your tweets and find them really insightful...  I would love to share more with my followers but none have the background to figure this out and how it relates to our habits. Thanks for making me reach...

  • kdhartt

    4/1/2010 4:00:37 PM |

    Great science on the risk of small LDL particles. Now I wish our health care system made the tests easier to get. An NMR costs twice as much at my doctor's office than if I get blood drawn on my own, and my expensive insurance plan won't pay for it either way.

  • donny

    4/1/2010 5:39:46 PM |

    This is interesting;

    ----------------------------------
    The nonenzymatic glycation of LDL is a naturally occurring chemical modification of apolipoprotein (apo)-B lysine residues by glucose. Once glycated, LDL is only poorly recognized by lipoprotein receptors including the LDL receptor (LDL-R), the LDL-R–related protein (LRP), and scavenger receptors. Glycated LDL (gLDL) is a preferred target for oxidative modifications. Additionally, its presence initiates different processes that can be considered “proatherogenic.” Thus, LDL glycation might contribute to the increased atherosclerotic risk of patients with diabetes and familial hypercholesterolemia. Here we investigate whether lipoprotein lipase (LPL) can mediate the cellular uptake of gLDL. The addition of exogenous LPL to the culture medium of human skin fibroblasts, porcine aortic endothelial cells, and mouse peritoneal macrophages enhanced the binding, uptake, and degradation of gLDL markedly, and the relative effect of LPL on lipoprotein uptake increased with the degree of apoB glycation. The efficient uptake of gLDL by LDL-R–deficient fibroblasts and LRP-deficient Chinese hamster ovary cells in the presence of LPL suggested a mechanism that was independent of the LDL-R and LRP. In macrophages, the uptake of gLDL was also correlated with their ability to produce LPL endogenously. Mouse peritoneal macrophages from genetically modified mice, which lacked LPL, exhibited a 75% reduction of gLDL uptake compared with normal macrophages. The LPL-mediated effect required the association of the enzyme with cell surface glycosaminoglycans but was independent of its enzymatic activity. The uptake of gLDL in different cell types by an LPL-mediated process might have important implications for the cellular response after gLDL exposure as well as the removal of gLDL from the circulation.
    ----------------------------------

    http://diabetes.diabetesjournals.org/content/50/7/1643.abstract

    And this;

    http://diabetes.diabetesjournals.org/content/49/4/597.abstract

    --------------------------------
    Atherosclerosis is the major complication of diabetes. Accumulating evidence indicates that lipoprotein lipase (LPL) produced by macrophages in the vascular wall may favor the development of atherosclerosis by promoting lipid accumulation within the lesion.

    We previously demonstrated that high glucose stimulates in vitro murine and human macrophage LPL production.
    ---------------------------------

    I'm still not sure about the whole high triglycerides and chylomicrons in the absence of high glucose, though. Carbohydrate seems to make cells fat. Liver cells, muscle cells, fat cells.

    Macrophages and smooth muscle cells?

  • Denny Barnes

    4/1/2010 7:47:50 PM |

    Is fructose especially bad in contributing to the glycation of Apo B?  I have read in several sources that fructose creates ten times as many advanced glycation end-products (AGEs) as glucose.  I wonder if it is also similarly implicated in the Apo B glycation process.

  • DrStrange

    4/1/2010 7:59:42 PM |

    I think it would be much more clear and less "inflammatory" to differentiate between "refined carbohydrates" like flour products, and sugars, etc. vs "unrefined, complex" carbs like those in whole, intact grains (not wheat IF you are sensitive to it and as much as 70% of population or more are fine with it)(Don't forget, doctors mostly see the ones that are ill, not the ones that are healthy), legumes, sweet potatoes, etc.  To jump from avoiding flour products to replacing those calories w/ sat. fat is a big step and leaves much out!  What happens if you replace bagels w/ whole, cooked millet for example?

  • particle size reduction

    4/3/2010 3:25:32 PM |

    The only way to control it is to have  a diet that is low on cholesterol. This is the only solution that can be followed for the results to appear.

  • Health Test Dummy

    4/22/2010 5:51:58 PM |

    So, I'm paleo/ primal, with good amounts of coconut oil for my fat. I just had a full lab analysis with my Dr. yesterday and turns out that my Cholesterol is high at 268. Triglycerides were ate 60, HDL at 86 & LDL 170.

    Thank God he was Paleo as well, so I did not have to hear a speech about modifying my diet. What he did say, however, was that in correlation to my other readings (High Platelets and White Blood Cell counts, low RBC, Hemoglobin and Hematocrit as well as low iron saturation) shows my body is fighting a parasite/ infection of some sort, causing obvious inflammation to fend off the 'critter'.

    I was immediately worried, since all naysayers to my high amounts of fat-ingesting diet always think that I will have high cholesterol.

    I will watch with avid curiosity as to this correlation to my infection (most likely my dental carries) and my cholesterol. Sometimes, full homeostasis or the lack-thereof, may show us a better picture in the whole, grand scheme of things.

  • Dick Pious

    2/18/2011 10:03:09 PM |

    Dr. Davis, do you know if an increase in glycosylated LDL due to hyperlipidemia could result in altered (possibly lower) blood glucose readings?

  • Tom Kimball

    11/13/2013 3:04:14 PM |

    I'm looking for cholesterol test that differentiates the LDL number into glycated- and non-glycated LDL

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