Insights From a Short-Term Protein–Calorie Restriction Exploratory Trial in Elective Carotid Endarterectomy Patients

Abstract

Background: Open vascular surgery interventions are not infrequently hampered by complication rates and durability. Preclinical surgical models show promising beneficial effects in modulating the host response to surgical injury via short-term dietary preconditioning. Here, we explore short-term protein–calorie restriction preconditioning in patients undergoing elective carotid endarterectomy to understand patient participation dynamics and practicalities of robust research approaches around nutritional/surgical interventions. Methods: We designed a pilot prospective, multicenter, randomized controlled study in patients undergoing carotid endarterectomy. After a 3:2 randomization to a 3-day preoperative protein–calorie restriction regimen (30% calorie/70% protein restriction) or ad libitum group, blood, clinical parameters, and stool samples were collected at baseline, pre-op, and post-op days 1 and 30. Subcutaneous and perivascular adipose tissues were harvested periprocedurally. Samples were analyzed for standard chemistries and cell counts, adipokines. Bacterial DNA isolation and 16S rRNA sequencing were performed on stool samples and the relative abundance of bacterial species was measured. Results: Fifty-one patients were screened, 9 patients consented to the study, 5 were randomized, and 4 completed the trial. The main reason for non-consent was a 3-day in-hospital stay. All 4 participants were randomized to the protein–calorie restriction group, underwent successful endarterectomy, reported no compliance difficulties, nor were there adverse events. Stool analysis trended toward increased abundance of the sulfide-producing bacterial species Bilophila wadsworthia after dietary intervention ( P = .08). Conclusions: Although carotid endarterectomy patients held low enthusiasm for a 3-day preoperative inpatient stay, there were no adverse effects in this small cohort. Multidisciplinary longitudinal research processes were successfully executed throughout the nutritional/surgical intervention. Future translational endeavors into dietary preconditioning of vascular surgery patients should focus on outpatient approaches.

Short-Term Ketogenic Diet Induces a Molecular Response That Is Distinct From Dietary Protein Restriction

“…Short 4- or 5-day cycles of FMD have also been shown to improve measures of cardiometabolic health in humans ( 45 ), and to improve late-life health, included delayed cancer incidence, in mice ( 46 ). Preconditioning with short-term PR also effectively protects against ischemic surgical stress in mouse models ( 7 , 47 ) and a combination of calorie restriction and PR has been shown to be safe in humans prior to surgery ( 48 , 49 ). Given the recent clinical interest in shorter-term KD and PR diets, it is important to understand the mechanism by which these interventions improve health and stress resistance to fully harness their therapeutic potential.…”

Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial

“…Here, we present the results of a randomized controlled trial in outpatient preoperative dietary restricted versus ad-libitum-fed patients scheduled for vascular surgery. This work expands on our previously published pilot study assessing the safety of such a short-term pre-operative PCR in inpatient vascular surgery patients [30]. Although the runtime of the trial and enrollment was shortened substantially due to the COVID-19 pandemic, we were still able to consent 19 individuals in 10 months.…”

“…In a prior pilot study, patients undergoing elective carotid endarterectomy [30] underwent a pre-operative PCR intervention while being closely monitored as inpatients for three days prior to scheduled surgery to assess the safety of this specific diet in this fragile population. All patients completed the study without experiencing any adverse events or dietary compliance issues.…”

Efficacy of Restricting Dietary Protein Intake Combined with Buyang Huanwu Decoction in Treating Diabetic Nephropathy and Its Effect on Patients’ Inflammatory Factor Levels

“…Diabetic nephropathy (DN), a microvascular complication of diabetes, is a chronic kidney disease caused by diabetes and an important trigger of renal failure [ 1 , 2 ]. Its pathogenesis is not fully defined yet, but it is generally believed that blood glucose, blood pressure, and the course of the disease are all key factors leading to structural and functional damage to the kidney.…”