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

Abstract

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.

Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight

“…Importantly, on inflammatory markers and oxidative stress biomarkers, the effect was mainly observed after VLCKD, while BS showed a slow effect mainly in the more acute phase (3 months after surgical). It suggests that, despite the important weight loss induced by VLCKD or BS, the metabolic status induced by both interventions in a short-term is different and it is probable that the nutritional ketosis induced during de acute phase of VLCKD could protect patients with obesity from other diseases such as type 2 diabetes [65], cardiovascular disease [66], cancer [67e70] and the newly emerged infection COVID-19 [55]. In line with this proposal, it was previously hypothesized that a VLCKD could represent an elective therapy to counteract inflammation-related dermatological diseases such as psoriasis, which shows an important inflammatory component [71].…”

Activation of G protein-coupled receptors by ketone bodies: Clinical implication of the ketogenic diet in metabolic disorders

“…Several studies provided robust evidence of the beneficial effect of KDs in reducing body weight in obesity. Importantly, KD-induced weight loss is generally higher than that achieved with an isocaloric non-ketogenic control diet ( Table 2 ), as shown in several populations including hyperinsulinemic ( 48 ) overweight females ( 75 ), overweight/obese subjects ( 34 , 72 – 74 , 76 , 77 ) and in morbidly obese subjects candidate to bariatric surgery ( 79 ). In addition, weight reduction following a KD is demonstrated to be accompanied by favourable changes in body composition with a higher decrease in waist circumference ( 48 , 75 , 76 ) and fat mass loss ( 72 , 74 ), also in subjects who underwent gastric balloon procedure ( 80 ), vs control diets.…”

“…A recent study conducted in obese individuals randomised to a 8-week VLCKD vs standard diet (both associated to an exercise program) showed a correlation between circulating β-OHB levels and the reduction of visceral fat and inflammatory markers ( 74 ) which define the adiposity state, pointing to a direct role of ketones in the amelioration of metaflammation ( 72 ). These effects should be ascribed to the activation of the β-OHB-GPR109A axis which triggers an anti-inflammatory macrophage phenotype in several animal models ( 50 , 52 , 53 ), ultimately reducing cardiovascular risk.…”

A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression

“…Typically, a KD recommends that only 5% of calories come from carbohydrates, along with 75% from fat and 20% from protein 12 . Due to reducing the inflammatory state, a KD may have a direct beneficial effect on endothelial dysfunction and cardiovascular function 13,14 . However, the mechanisms through which the KD exerts its anti‐vascular dysfunction effects in type 2 diabetic conditions have not been fully elucidated.…”