Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: A randomized controlled study

Atherosclerosis. 2018 Dec:279:52-61. doi: 10.1016/j.atherosclerosis.2018.10.013. Epub 2018 Oct 17.


Background and aims: The effects of a low carbohydrate/high fat (LCHF) diet on health are debated. This study aims to explore the effects of a diet with less than 20 g carbohydrates per day (LCHF) on plasma low density lipoprotein cholesterol (LDL-C) in young and healthy adults. The secondary aim is the assessment of lipid profile and peripheral blood mononuclear cells (PBMC) gene expression.

Methods: This was a randomized controlled parallel-designed intervention study. Participants were either assigned to a three-week LCHF diet or a control group continuing habitual diet ad libitum, in both groups.

Results: In total, 30 healthy normal weight participants completed the study. Nine subjects did not complete it due to adverse events or withdrawn consent. In the LCHF diet group (n = 15), plasma LDL-C increased from (mean ± SD) 2.2 ± 0.4 mmol/l before intervention to 3.1 ± 0.8 after, while in the control group (n = 15), LDL-C remained unchanged: 2.5 ± 0.8 mmol/l (p < 0.001 between groups). There was a significant increase in apolipoprotein B, total cholesterol, high-density lipoprotein cholesterol, free fatty acids, uric acid and urea in the LCHF group versus controls. Plasma levels of triglycerides, lipoprotein (a), glucose, C-peptide or C-reactive protein (CRP), blood pressure, body weight or body composition did not differ between the groups. PBMC gene expression of sterol regulator element binding protein 1 (SREBP-1) was increased in the LCHF group versus controls (p ≤ 0.01). The individual increase in LDL-C from baseline varied between 5 and 107% in the LCHF group.

Conclusions: An LCHF diet for three weeks increased LDL-C with 44% versus controls. The individual response on LCHF varied profoundly.

Keywords: Atkins Diet; Cardiovascular risk factors; Cholesterol; Diet; Fat; Fatty acids; LDL; Saturated fatty acids.

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Biomarkers / blood
  • Cholesterol, LDL / blood*
  • Diet, Carbohydrate-Restricted*
  • Diet, High-Fat*
  • Diet, High-Protein Low-Carbohydrate*
  • Female
  • Gene Expression Regulation
  • Healthy Volunteers
  • Humans
  • Lipid Metabolism / genetics*
  • Male
  • Proprotein Convertase 9 / blood
  • Young Adult


  • Biomarkers
  • Cholesterol, LDL
  • PCSK9 protein, human
  • Proprotein Convertase 9