Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism

Am J Clin Nutr. 2001 May;73(5):878-84. doi: 10.1093/ajcn/73.5.878.


Background: High-carbohydrate diets improve plasma cholesterol concentrations but increase triacylglycerol concentrations; the latter effect increases the risk of cardiovascular disease (CVD). Triacylglycerol concentrations increase only during very-high-carbohydrate diets consisting mainly of simple sugars.

Objective: We compared the CVD risk profile, cholesterol metabolism, and glucose tolerance of 7 healthy subjects during 2 isoenergetic diets: a high-fat, low-carbohydrate diet (HF diet) and a moderately high-carbohydrate, low-fat diet (HC diet).

Design: In a randomized crossover study, we measured the effects of the HF diet [40% carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15% polyunsaturated)] and HC diet [55% carbohydrate (mainly complex) and 30% fat (10% saturated, 10% monounsaturated, and 10% polyunsaturated)] (3 wk each) on plasma lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the messenger RNA (mRNA) concentrations of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, the LDL receptor, and the LDL-receptor-related protein (LRP).

Results: Compared with the HF diet, the HC diet lowered total, LDL, and HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL cholesterol; triacylglycerol concentrations were unchanged. Lower cholesterol concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05) and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL receptor mRNA concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and oral glucose tolerance was better (P < 0.05) with the HC diet.

Conclusion: The beneficial effects of the HC diet on glucose tolerance and plasma cholesterol concentrations without increases in triacylglycerol show that this diet had favorable effects on both insulin sensitivity and the plasma lipid profile.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cholesterol / biosynthesis*
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Coronary Disease / epidemiology
  • Cross-Over Studies
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / pharmacology*
  • Energy Intake
  • Energy Metabolism
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • Receptors, Immunologic / genetics*
  • Receptors, LDL / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Transcription, Genetic
  • Triglycerides / blood


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Carbohydrates
  • Dietary Fats
  • Low Density Lipoprotein Receptor-Related Protein-1
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, LDL
  • Triglycerides
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases