Plant Sterols on Cardiovascular Markers, Microbiota and Sterol Metabolism (Cardiofoodsterol)

Not Applicable

Recruiting

• Conditions: Overweight and Obesity; Cardiovascular Diseases; Hypercholesterolemia; Prediabetic State
• Interventions: Dietary Supplement: Plant sterols 2g/day; Dietary Supplement: Placebo

• Registration Number: NCT06481020
• Lead Sponsor: University of Valencia

Brief Summary

Potential cholesterol-lowering effect of a regular intake of a plant sterol (PS)-containing food supplement, in overweight/obese type 1 or 2, normoglycemic/pre-diabetic, with LDL-cholesterol values \> 115 mg/dl and not pharmacologically treated participants treated with the PS-containing food supplement or placebo supplement.

Detailed Description

Cardiovascular disease (CVD) is the leading cause of death worldwide, with hypercholesterolemia being one of the main risk factors for CVD. The deposition and oxidation of LDL-cholesterol particles triggers a series of molecular events favoring chronic low-grade inflammation, endothelial dysfunction and oxidative stress. This situation promotes atherogenesis thus increasing cardiovascular risk. Obesity favors the secretion of pro-inflammatory mediators and promotes the recruitment of macrophages to adipose tissue, insulin resistance, hyperglycemia and hyperlipidemia, thus increasing the risk of CVD. In addition, obesity has been associated with gut dysbiosis, which in turn is associated with atherosclerosis in some studies. Beneficial effects of PS on LDL-cholesterol and inflammatory, endothelial dysfunction and oxidative stress markers have been reported by several clinical trials. A meta-analysis suggests a lowering effect of PS on body mass index (BMI) in participants with BMI\>25. Furthermore, the consumption of PS has been beneficially associated in in vitro studies with changes in intestinal microbial profile, sterol metabolism and short chain fatty acids (SCFA) production. Therefore, the hypothesis is if the consumption of PS as a food supplementation could reduce cardiovascular risk. The present study aims to evaluate the LDL-cholesterol serum levels after regular intake of a food supplement containing PS (2 g/day) in overweight/obese type 1 or 2 patients, normoglycemic /pre-diabetic and with LDL-cholesterol values \> 115 mg/dl not pharmacologically treated. This is a crossover study with 21 participants (intake of a food supplement containing PS) and 21 participants (intake of excipient-based placebo), with a first intervention period of 8 weeks. After a 6-week washout period, the treatments are switched, with a second intervention period of 8 weeks. In addition, to the LDL-cholesterol lowering assessment, other biochemical, hematological, inflammatory, endothelial dysfunction and oxidative stress parameters are assessed in serum samples. Moreover, sterol and metabolite profiling in serum and feces, microbiota modulation, anthropometric measurements and body composition, bioimpedance, dietary intake and physical activity questionnaire are evaluated. All parameters are evaluated at the beginning (weeks 0 and 14) and at the end of each intervention period (weeks 8 and 22).

Study Timeline

• Study Start: 2024-05-21
• Status Verified: 2024-06
• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-06-26
• Last Update Submitted: 2024-06-26
• Study First Posted: 2024-07-01
• Last Update Posted: 2024-07-01
• Primary Completion: 2024-12
• Study Completion: 2025-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

• BMI: 27-29.9 or 30-39.9
• Plasmatic glucose: < 100mg/dl or 100-125mg/dl
• Glycosylated hemoglobin: < 5.7 or 5.7-6.4
• LDL cholesterol > 115mg/dL
• Serum levels of biochemical and hematological parameters and fat-soluble vitamins within reference ranges.

Exclusion Criteria

• Subjects on cholesterol-lowering pharmacological treatment
• Smokers
• Alcohol consumption above 30 g/day
• Pregnant or lactating women
• Any infection, serious illness or co-morbidity that may affect the bioavailability of PS (e.g., malabsorption, celiac disease, allergies or food intolerances)
• Diseases of the gastrointestinal tract
• Antibiotic, hormonal or anabolic treatment
• Participants consuming foods enriched with PS or food supplements that contain PS
• Participants who follow specialist weight loss diets, vegans or vegetarians

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dietary Supplement	Plant sterols 2g/day	PS-containing dietary supplement Sachet containing a powdered microencapsulated free plant sterols (2 g ingredient/day)
Placebo	Placebo	Sachet containing the powdered excipients of the dietary supplement

Primary Outcome Measures

Name	Time	Method
Changes in plasmatic LDL-c	0, 8, 14 and 22 weeks	LDL-c, calculated by the Friedewald's formula, with repeated measures (at the beginning and at the end of each period the intervention)

Secondary Outcome Measures

Name	Time	Method
Changes in plasmatic total cholesterol	0, 8, 14 and 22 weeks	Total cholesterol, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in plasmatic HDL-c	0, 8, 14 and 22 weeks	HDL-c, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in plasmatic Apo A	0, 8, 14 and 22 weeks	Apo A, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in feces levels of the sterols and metabolites profile	0, 8, 14 and 22 weeks	Profile sterols and metabolites, assessed by gas chromatography coupled with flame ionization detector (GC-FID), with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum interleukin 1β (IL-1β)	0, 8, 14 and 22 weeks	IL-1β, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum interleukin 8 (IL-8)	0, 8, 14 and 22 weeks	IL-8, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in plasmatic 8-isoprostane	0, 8, 14 and 22 weeks	8-isoprostane, assessed by enzyme kits, with repeated measures (at the beginning and the end of each period the intervention)
Changes in oxidized glutathione (GSSG)	0, 8, 14 and 22 weeks	GSSG, assessed by ultra-performance liquid chromatography-MS (UPLC-MS), with repeated measures (at the beginning and the end of each period the intervention)
Changes in plasmatic triglycerides	0, 8, 14 and 22 weeks	Triglycerides, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in plasmatic High-sensitivity C-reactive protein (hsCRP)	0, 8, 14 and 22 weeks	hs CRP, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in plasmatic Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	0, 8, 14 and 22 weeks	HOMA-IR, calculated by mathematical formula from the fasting insulin and fasting glucose levels, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in serum E-Selectin	0, 8, 14 and 22 weeks	E- Selectin, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum endothelin (ET-1)	0, 8, 14 and 22 weeks	ET-1, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention
Changes in plasmatic fibrinogen	0, 8, 14 and 22 weeks	Fibrinogen, assessed by Clauss coagulometric method, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in serum levels of the sterols and metabolites profile	0, 8, 14 and 22 weeks	Profile sterols and metabolites, assessed by gas chromatography coupled with flame ionization detector (GC-FID), with repeated measures (at the beginning and at the end of each period the intervention)
Changes in serum interleukin 10 (IL-10)	0, 8, 14 and 22 weeks	IL-10, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in plasmatic LDL-cholesterol oxidation	0, 8, 14 and 22 weeks	LDL-cholesterol oxidation, assessed by enzyme kits, with repeated measures (at the beginning and the end of each period the intervention)
Changes in Bioelectrical impedance analysis (BIA)	0, 8, 14 and 22 weeks	BIA, assessed by bio-impedance meter, with repeated measures (at the beginning and the end of each period the intervention)
Evaluation of the Mediterranean diet adherence to measure quality of life	0, 8, 14 and 22 weeks	Mediterranean diet adherence screener (MEDAS) is used, consisting in 14 questions (each one 0 or 1 point, final score between 0 and 14). Results are ranged between 0-7 points (low adherence), 7-10 (moderate adherence), and 10-14 (high adherence) With repeated of questionnaire (at the beginning and the end of each period the intervention)
Changes in plasmatic non-HDL cholesterol	0, 8, 14 and 22 weeks	Non-HDL cholesterol, calculated by subtracting HDL-c from total cholesterol, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in plasmatic Apo B	0, 8, 14 and 22 weeks	Apo B, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention
Changes in plasmatic insulin	0, 8, 14 and 22 weeks	Insulin, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention
Changes in serum tumor necrosis factor alpha (TNFα)	0, 8, 14 and 22 weeks	TNFα, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum plasminogen activator inhibitor-1(PAI-1)	0, 8, 14 and 22 weeks	PAI-1, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in the composition of microbiota in feces	0, 8, 14 and 22 weeks	Composition of microbiota, assessed by genetic sequencing and subsequent biostatistical analysis, with repeated measures (at the beginning and the end of each period the intervention)
Changes in plasmatic glucose	0, 8, 14 and 22 weeks	Glucose, assessed by enzymatic-colorimetric methods, with repeated measures (at the beginning and at the end of each period the intervention)
Changes in serum interleukin 12p70 (IL-12p70)	0, 8, 14 and 22 weeks	IL-12p70, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum interleukin 6 (IL-6)	0, 8, 14 and 22 weeks	IL-6, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in serum vascular cell adhesion molecule-1 (VCAM-1)	0, 8, 14 and 22 weeks	VCAM-1, assessed by immunochemical techniques, with repeated measures (at the beginning and the end of each period the intervention)
Changes in plasmatic malondialdehyde (MDA)	0, 8, 14 and 22 weeks	MDA, assessed by ultra-performance liquid chromatography-MS (UPLC-MS), with repeated measures (at the beginning and the end of each period the intervention
Changes in reduced glutathiones (GSH)	0, 8, 14 and 22 weeks	GSH, assessed by ultra-performance liquid chromatography-MS (UPLC-MS), with repeated measures (at the beginning and the end of each period the intervention)
Changes in feces of short-chain fatty acids (SCFAs)	0, 8, 14 and 22 weeks	SCFAs, assessed by high-performance liquid chromatography with an ultraviolet detector (HPCL-UV), with repeated measures (at the beginning and the end of each period the intervention)
Changes in body weight (WT)	0, 8, 14 and 22 weeks	WT, assessed by standard balance scale, with repeated measures (at the beginning and the end of each period the intervention)
Changes in body height (HT)	0, 8, 14 and 22 weeks	HT, assessed by tape measure, with repeated measures (at the beginning and the end of each period the intervention)
Assessment of dietary intake	0, 8, 14 and 22 weeks	Food frequency survey Questionnaire (FFQ) is used, consisting in 136 questions divided into the different food groups (dairy products; eggs, meat and fish; vegetables; fruit; pulses and cereals; oils and fats; bakery and confectionery; miscellaneous; drinks) indicating the average frequency of consumption during the past year, which can be scored as never or almost never, per month (1-3), per week (1, 2-4,5-6), per day (1, 2-3, 4-6, 6+), with repeated of questionnaire (at the beginning and the end of each period the intervention)
Changes in plasmatic levels of cholesterol oxidation products (COPs)	0, 8, 14 and 22 weeks	COPs, assessed by gas chromatography-mass spectrometry, with repeated measures (at the beginning and the end of each period the intervention)
Changes in body circumferences	0, 8, 14 and 22 weeks	Circumferences, assessed by tape measure, with repeated measures (at the beginning and the end of each period the intervention)
Evaluation of the physical activity to measure quality of life	0, 8, 14 and 22 weeks	International physical activity questionnaire-short form (IPAC-SF) is used, consisting in 7 questions. Intensity, frequency and duration of the exercise are evaluated through metabolic equivalent of task (METs). This allows to differentiate 3 levels of physical activity: Low: Not enough activity to achieve the next level; Moderate: 3 or more days of vigorous physical activity for at least 20 minutes per day, 5 or more days of moderate physical activity and/or walking at least 30 minutes per day, or 5 or more days of any combination of walking, moderate or vigorous physical activity achieving at least a total of 600 METs.; High: Vigorous physical activity at least 3 days per week achieving a total of a least 1500 METs, or 7 days of any combination of walking, with moderate and/or vigorous physical activity, achieving a total of a least 3000 METs.; With repeated of questionnaire (at the beginning and the end of each period the intervention)

Trial Locations

Locations (1)

Hospital Universitario y Politécnico La Fe de Valencia; 🇪🇸 Valencia, Spain