British Journal of Nutrition

Full Papers

Human and Clinical Nutrition

Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk

Jordi Merinoa1 c1, Richard Konesa2, Raimon Ferréa1, Núria Planaa1, Josefa Gironaa1, Gemma Aragonésa1, Daiana Ibarretxea1, Mercedes Herasa1 and Luis Masanaa1

a1 Vascular Medicine and Metabolism Unit, Lipids and Atherosclerosis Research Unit, Sant Joan University Hospital, Institut d'Investigació Sanitària Pere Virgili (IISPV), Faculty of Medicine, Universitat Rovira i Virgili, Spanish Biomedical Research Network in Diabetes and Associated Metabolic Disorders (CIBERDEM), Barcelona, Spain

a2 Cardiometabolic Research Institute, 7505 Fannin Street, Suite 210, Houston, TX 77054, USA


Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1·66 (sd 0·41) v. 1·52 (sd 0·22), P= 0·037). These results were particularly strong in patients with the MS (Q1 = 1·82 (sd 0·32) v. Q4 = 1·61 (sd 027); P= 0·021) and T2D (Q1 = 1·78 (sd 0·31) v. Q4 = 1·62 (sd 0·35); P= 0·011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR − 0·85; 95 % CI 0·19, 0·92; P= 0·031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.

(Received February 03 2012)

(Revised April 27 2012)

(Accepted June 10 2012)

(Online publication July 31 2012)

Key Words:

  • Low-carbohydrate diets;
  • Endothelial function;
  • Cardiovascular risk;
  • metabolic syndrome;
  • Type 2 diabetes mellitus


c1 Corresponding author: J. Merino, fax +34 977319984, E-mail:


  Abbreviations: ATPIII, Adult Treatment Panel III; CV, cardiovascular; EF, endothelial function; FMD, flow-mediated dilatation; HDL-C, HDL-cholesterol; LCDS, low-carbohydrate diet score; LDL-C, LDL-cholesterol; MS, metabolic syndrome; PAT, peripheral arterial tonometry; RHI, reactive hyperaemia index; saRHI, small artery reactive hyperaemia index; T2D, type 2 diabetes mellitus