Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet

Nutrients. 2021 Dec 23;14(1):33. doi: 10.3390/nu14010033.


Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600-800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (-5.3 [-6.9 to -3.6] kg/m2, p < 0.001), total body fat (-7.0 [-10.7 to -3.3] %, p = 0.003), and IWQOL-Lite score (-41.4 [-75.2 to -7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.

Keywords: multidisciplinary approach; obesity; pronokal method; vasa vasorum; very low calorie ketogenic diet; weight loss.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Adventitia / pathology
  • Biomarkers / blood
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology
  • Cholesterol, HDL / blood
  • Diet, Ketogenic / methods*
  • Diet, Reducing / methods*
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Male
  • Middle Aged
  • Obesity / blood*
  • Obesity / diet therapy*
  • Obesity / pathology
  • Plaque, Atherosclerotic / blood
  • Quality of Life
  • Surveys and Questionnaires
  • Ultrasonography / methods
  • Vasa Vasorum / diagnostic imaging
  • Vasa Vasorum / pathology*
  • Vascular Cell Adhesion Molecule-1 / blood


  • Biomarkers
  • Cholesterol, HDL
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1

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