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  • Biochemistry behind the assertion that small, dense LDL particles are atherogenic and associated with a high refined carbohydrate diet.

    All of the information here has been taken directly from the references quoted below.

    First let me warn you that biochemistry is one of the most difficult sciences…

    LDL (low-density lipoprotein) is the major carrier of cholesterol in human plasma. The lipoprotein class comprises a number of distinct subfractions, and is usually divided into different sized particles – large, intermediate and small.

    The subfraction of small dense LDL particles (sdLDL) are retained preferentially by the artery wall, are readily oxidized and carry an enzyme believed to have an important role in atherosclerosis – lipoprotein-associated phospholipase A(2).

    Generation of sdLDL occurs by intravascular lipoprotein remodelling as a result of disturbances such as Type II diabetes and metabolic syndrome.
    The key predisposing factor is the development of hypertriglyceridaemia, and in particular elevated levels of large, triacylglycerol-rich VLDL (very-low-density lipoprotein).

    This leads to the formation of slowly metabolized LDL particles, which are subject to exchange processes that remove cholesteryl ester from the particle core and replace it with triacylglycerol. LDL, so altered, is a potential substrate for hepatic lipase; if the activity of the enzyme is high enough, lipolysis will generate smaller, denser particles.

    Abstract from a study done in the Netherlands:
    High carbohydrate (CHO) intakes stimulate hepatic saturated fatty acids (SAFA) synthesis and conservation of dietary SAFA .
    Hepatic de novo lipogenesis from CHO is also stimulated during eucaloric dietary substitution of SAFA by CHO with high glycaemic index in normo-insulinaemic subjects and during hypocaloric high-CHO/low-fat diets in subjects with the metabolic syndrome.
    The accumulation of SAFA stimulates chronic systemic low-grade inflammation through its mimicking of bacterial lipopolysaccharides and/or the induction of other pro-inflammatory stimuli.
    The resulting systemic low-grade inflammation promotes insulin resistance, reallocation of energy-rich substrates and atherogenic dyslipidaemia that concertedly give rise to increased CVD risk. We conclude that avoidance of SAFA accumulation by reducing the intake of CHO with high glycaemic index is more effective in the prevention of CVD than reducing SAFA intake per se.

    What does all this mean?
    As I’ve probably already said on nearly every post on this blog – cut down on your consumption of sugar, bread, pasta and rice, and don’t worry about how much butter, eggs and nuts that you are eating.


    Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein
    Packard CJ
    Department of Pathological Biochemistry, Glasgow Royal Infirmary
    Biochem Soc Trans. 2003 Oct;31(Pt 5):1066-9

    Saturated fat, carbohydrate, and cardiovascular disease
    Patty W Siri-Tarino, Qi Sun, Frank B Hu, Ronald M Krauss
    Department of Atherosclerosis Research Children’s Hospital Oakland Research Institute Oakland, CA, USA
    Am J Clin Nutr. 2010 March; 91(3): 502–509. Published online 2010 January 20. doi: 10.3945/ajcn.2008.26285
    PMCID: PMC2824150

    Small dense LDL and VLDL predict common carotid artery IMT and elicit an inflammatory response in peripheral blood mononuclear and endothelial cells
    Norata GD, Raselli S, Grigore L, Garlaschelli K, Vianello D, Bertocco S, Zambon A, Catapano AL
    Department of Pharmacological Sciences, University of Milan
    Atherosclerosis. 2009 Oct;206(2):556-62. Epub 2009 Mar 25

    Saturated fat, carbohydrates and cardiovascular disease
    Kuipers RS1, de Graaf DJ, Luxwolda MF, Muskiet MH, Dijck-Brouwer DA, Muskiet FA
    University Medical Center Groningen, Groningen, The Netherlands
    Neth J Med. 2011 Sep;69(9):372-8

    Improvements in LDL particle size and distribution by short-term alternate day modified fasting in obese adults
    Varady KA, Bhutani S, Klempel MC, Lamarche B
    Department of Kinesiology and Nutrition, University of Illinois at Chicago
    Br J Nutr. 2011 Feb;105(4):580-3. doi: 10.1017/S0007114510003788. Epub 2010 Sep 30

    Association of fasting and nonfasting serum triglycerides with cardiovascular disease and the role of remnant-like lipoproteins and small dense LDL
    Stalenhoef AF, de Graaf J
    Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
    Curr Opin Lipidol. 2008 Aug;19(4):355-61. doi: 10.1097/MOL.0b013e328304b63c

    Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects
    Guay V, Lamarche B, Charest A, Tremblay AJ, Couture P
    Institute on Nutraceuticals and Functional Foods, Laval University, Québec, Canada.
    Metabolism. 2012 Jan;61(1):76-83. doi: 10.1016/j.metabol.2011.06.002. Epub 2011 Aug 3

    Revisiting dietary cholesterol recommendations: does the evidence support a limit of 300 mg/d?
    Fernandez ML, Calle M.
    Department of Nutritional Sciences, the University of Connecticut
    Curr Atheroscler Rep. 2010 Nov;12(6):377-83. doi: 10.1007/s11883-010-0130-7

    Three Reasons to Abandon Low-Density Lipoprotein Targets
    An Open Letter to the Adult Treatment Panel IV of the National Institutes of Health
    Rodney A. Hayward, MD and Harlan M. Krumholz, MD, SM

    Posted in Biochemistry.

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