Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years

Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years.

Women have a natural protection that gives them greater longevity. One hypothesis most commonly used is the estrogen protection in the premenopausal period. However many studies of various forms of hormone replacement therapy proved ineffective in promoting additional protection for women. Thus, it is discussed other ways of protection associated with longevity in women. Of these, the sirtuin system was found in several animal studies to be associated with longevity. This system also showed, through the involvement of several metabolic pathways, an important protection against the process of atherosclerosis. But the activity of this system in humans is unknown and if it is more active in women than in men. The study's main objectives are to analyze this system in healthy 24 women and 24 men aged 55 to 65 years, and their influence on the main metabolic pathways related to longevity and the process of atherosclerosis. The research protocol includes analysis of the influence of sirtuin (SIRT1) in vascular reactivity, lipid profile, antioxidant capacity, markers of inflammation and homeostasis, before and after the interventions with caloric restriction or resveratrol administration. It is expected of this study mechanistic conclusion for longevity and possible clinical applications in the mechanism of atherosclerosis prevention.

Study Overview

• Status: Completed
• Conditions: Lipid Metabolism Disorders; Vascular System Injuries; Endothelial Disfunction
• Intervention / Treatment: Drug: Resveratrol; Behavioral: Caloric restriction

Detailed Description

After a washout period of 15 days without medication, men and women will be randomized to the group of calorie restriction or resveratrol so that in 24 individuals (12 women and 12 men) will be given a hypocaloric diet (1000 calories per day) and the remaining 24 individuals (12 women and 12 men), a daily pill of 500mg of resveratrol. In the two moments, after the washout period and before the intervention (baseline) and after 30 days of intervention (final) will evaluate the clinical, laboratory and vascular reactivity of all subjects.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-900
    • INCOR - Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical history, physical examination and electrocardiogram normal

Exclusion Criteria:

• premenopausal women (less than 1 year of natural amenorrhea)
• Body mass index ≥ 35 kg/m2
• Smoking
• Severe hypertension (diastolic blood pressure ≥ 110 mmHg)
• Severe dyslipidemia (triglycerides ≥ 500mg/dL, total cholesterol ≥ 300mg/dL)
• Diabetes
• Previous using previous statins or hormone replacement therapy. Other exclusion criteria are: chronic renal failure (serum creatinine ≥ 2.0 mg / dl), hepatic, endocrine, hematologic, respiratory or metabolic clinically significant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: men with resveratrol; 12 men will receive a pill with 500mg of resveratrol daily for 30 days	Drug: Resveratrol; 1 pill daily containing 500 mg/d of resveratrol for 30 days
Experimental: women with resveratrol; 12 women will receive a pill with 500mg of resveratrol daily for 30 days	Drug: Resveratrol; 1 pill daily containing 500 mg/d of resveratrol for 30 days
Active Comparator: men with caloric restriction; 12 men will follow a 1000 calories per day diet for 30 days	Behavioral: Caloric restriction; Diet of 1000kcal per day for 30 days
Active Comparator: women with caloric restriction; 12 women will follow a 1000 calories per day diet for 30 days	Behavioral: Caloric restriction; Diet of 1000kcal per day for 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Direct Evaluation of the Sirtuin 1 Gene Expression	The Sirtuin 1 gene expression was measured by real time PCR in peripheric blood. Unit of measure was arbitrary unit. "Arbitrary unit was relative to the control gene expression (control gene = 1)".	30 days post-treatment
Sirtuin	Sirtuin plasma levels before and 30 days post-treatment	30 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - serum HDL, LDL, lipoprotein(a), C reactive protein, glucose.	30 days post-treatment
Influence of the Sirtuin 1 System on Apolipoproteins AI and B.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - apolipoproteins AI and B	30 days post-treatment
Influence of the Sirtuin 1 System on Estradiol	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estradiol	30 days post-treatment
Influence of the Sirtuin 1 System on Platelet Aggregation.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - platelet aggregation by ADP and norepinephrine.	30 days post-treatment
Influence of the Sirtuin 1 System on Biomarkers	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - non-esterified fatty acids, insulin, luteinizing hormone, follicle stimulating hormone.	30 days post-treatment
Influence of the Sirtuin 1 System on Estrone and Norepinephrine.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estrone, norepinephrine.	30 days post-treatment
Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: RAGE gene expression; "Arbitrary unit was relative to the control gene expression (control gene = 1)"	30 days post-treatment
Influence of the Sirtuin 1 System on Thromboelastography Clot Formation.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -dynamics of clot formation: clot onset time and clot complet	30 days post-treatment
Influence of the Sirtuin 1 System on Thromboelastography.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - slope of clot formation dynamics	30 days post-treatment
Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography.	For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -max elasticity of clot on thromboelastography	30 days post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences Between Men and Women.	We will also compare women vs men baseline and final data.	30 days

Collaborators and Investigators

• Sponsor: InCor Heart Institute
• Investigators: Principal Investigator: Antônio de Pádua Mansur, PHD, InCor Heart Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 17, 2012
• First Posted (Estimate): August 20, 2012

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: atherosclerosis; resveratrol; calorie restriction; longevity; vascular reactivity; sirtuin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Wounds and Injuries; Metabolic Diseases; Lipid Metabolism Disorders; Vascular System Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: 788012; 2012/01051-5 (Other Grant/Funding Number: FAPESP - SAO PAULO RESEARCH FOUNDATION)