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LDL Subclasses and CVD Risk

Ronald M. Krauss, MD

Director, Atherosclerosis Research, Children’s Hospital Oakland Research Institute; Guest Senior Scientist, Dept. of Genome Sciences, Lawrence Berkeley National Laboratory; Adjunct Professor, Dept. of Nutritional Sciences, UC-Berkeley

The atherogenic dyslipidemia seen in patients with the metabolic syndrome includes elevated plasma triglyceride levels, reduced high-density lipoprotein (HDL) cholesterol (C) and increased small, dense cholesterol depleted low-density lipoprotein (sdLDL) particles. Lowering sdLDL levels can reverse the risk of cardiovascular disease (CVD).

Approximately one-third of men and one-fifth of postmenopausal women have LDL phenotype B, a lipoprotein profile characterized by a predominance of sdLDL particles that is associated with a two-to-three-fold increase in CVD risk. Low fat/high-carbohydrate diets can induce expression of phenotype B in a large proportion of otherwise healthy individuals.

The study

Recently, we tested the effects on this lipoprotein profile of moderate dietary carbohydrate reduction (54% vs. 39% vs. 26% of energy) both before and after weight loss (~7%) in 178 overweight or obese, but otherwise healthy men. In addition, effects of lower (9% of energy) vs. higher (15%) saturated fat intake were tested in conjunction with the 26% carbohydrate diet.


The effect of carbohydrate

The 26% carbohydrate/low-saturated fat diet reduced atherogenic lipid measurements, including triglyceride, sdLDL mass and total/HDL-C ratio and increased LDL particle size compared with the 54% carbohydrate diet. Lipoprotein changes with higher vs. lower saturated fat on the 26% carbohydrate diet were similar. Although LDL-C was reduced to a greater extent with low saturated fat, there were no differences in reductions of sdLDL. The lesser reduction in LDL-C with high saturated fat was due to greater offsetting increases in larger, more cholesterol-enriched LDL particles.

The effect of weight loss

Following diet-induced weight loss and stabilization, all these variables showed significantly greater changes. LDL-C was significantly more reduced in the group that remained on the 54% carbohydrate vs. the group on the 26% carbohydrate diet.


Similar improvements in atherogenic dyslipidemia can be achieved by both reduced carbohydrate intake in the absence of weight loss and by weight loss on a higher carbohydrate diet.


  • There is no significant effect of saturated fat on levels of small, dense LDL particles.
  • Reduced carbohydrate intake results in lower levels of small, dense LDL particles and improvements in other features of atherogenic dyslipidemia.
  • Studies consistently show that carbohydrate intake (especially glycemic load) is more strongly related to CV risk than is saturated fat intake.


  1. Krauss RM. 2001. Dietary and genetic effects on low-density lipoprotein heterogeneity. Annu Rev Nutr 21:238-295.
  2. Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. 2006. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 83:1025-1031.

Keywords: metabolic syndrome , weight loss

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