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.

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01668836

Enrollment

Registered

2012-08-20

Start date

2012-08-31

Completion date

2014-12-31

Last updated

2016-04-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Endothelial Disfunction, Lipid Metabolism Disorders, Vascular System Injuries

Keywords

sirtuin, atherosclerosis, longevity, calorie restriction, resveratrol, vascular reactivity

Brief summary

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.

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.

Interventions

DRUGResveratrol

1 pill daily containing 500 mg/d of resveratrol for 30 days

BEHAVIORALCaloric restriction

Diet of 1000kcal per day for 30 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

55 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
Direct Evaluation of the Sirtuin 1 Gene Expression	30 days post-treatment	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).
Sirtuin	30 days post-treatment	Sirtuin plasma levels before and 30 days post-treatment

Secondary

Measure	Time frame	Description
Influence of the Sirtuin 1 System on Estradiol	30 days post-treatment	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
Influence of the Sirtuin 1 System on Platelet Aggregation.	30 days post-treatment	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.
Influence of the Sirtuin 1 System on Biomarkers	30 days post-treatment	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.
Influence of the Sirtuin 1 System on Estrone and Norepinephrine.	30 days post-treatment	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.
Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression	30 days post-treatment	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)
Influence of the Sirtuin 1 System on Thromboelastography Clot Formation.	30 days post-treatment	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
Influence of the Sirtuin 1 System on Thromboelastography.	30 days post-treatment	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
Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography.	30 days post-treatment	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
Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein.	30 days post-treatment	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.
Influence of the Sirtuin 1 System on Apolipoproteins AI and B.	30 days post-treatment	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

Other

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

Countries

Brazil

Participant flow

Participants by arm

Arm	Count
Men With Resveratrol 12 men will receive a pill with 500mg of resveratrol daily for 30 days Resveratrol: 1 pill daily containing 500 mg/d of resveratrol for 30 days	12
Women With Resveratrol 12 women will receive a pill with 500mg of resveratrol daily for 30 days Resveratrol: 1 pill daily containing 500 mg/d of resveratrol for 30 days	12
Men With Caloric Restriction 12 men will follow a 1000kcal/day diet for 30 days Caloric restriction: Diet of 1,000kcal per day for 30 days	12
Women With Caloric Restriction 12 women will follow a 1000kcal/day diet for 30 days Caloric restriction: Diet of 1,000kcal per day for 30 days	12
Total	48

Baseline characteristics

Characteristic	Men With Resveratrol	Women With Resveratrol	Men With Caloric Restriction	Women With Caloric Restriction	Total
abdominal circumference	100.9 cm STANDARD_DEVIATION 13.9	92.7 cm STANDARD_DEVIATION 8.7	96.5 cm STANDARD_DEVIATION 7.6	92 cm STANDARD_DEVIATION 7	95.5 cm STANDARD_DEVIATION 10
Age, Continuous	58.4 years STANDARD_DEVIATION 3.6	58.5 years STANDARD_DEVIATION 3.4	57.7 years STANDARD_DEVIATION 3.5	59.5 years STANDARD_DEVIATION 3.7	58.5 years STANDARD_DEVIATION 3.5
Apolipoprotein A1	1.37 g/L STANDARD_DEVIATION 0.21	1.53 g/L STANDARD_DEVIATION 0.19	1.34 g/L STANDARD_DEVIATION 0.11	1.72 g/L STANDARD_DEVIATION 0.25	1.49 g/L STANDARD_DEVIATION 0.24
Apolipoprotein B	0.91 g/L STANDARD_DEVIATION 0.18	1.04 g/L STANDARD_DEVIATION 0.28	0.97 g/L STANDARD_DEVIATION 0.25	1.04 g/L STANDARD_DEVIATION 0.27	0.99 g/L STANDARD_DEVIATION 0.25
Body mass index	28.5 Kg/m^2 STANDARD_DEVIATION 4.4	26.5 Kg/m^2 STANDARD_DEVIATION 3.4	26.2 Kg/m^2 STANDARD_DEVIATION 3.5	25.5 Kg/m^2 STANDARD_DEVIATION 3.7	26.7 Kg/m^2 STANDARD_DEVIATION 3.8
Clot complete	103.83 seconds STANDARD_DEVIATION 13.67	80.83 seconds STANDARD_DEVIATION 12.01	100.17 seconds STANDARD_DEVIATION 14.32	152.64 seconds STANDARD_DEVIATION 211.01	108.45 seconds STANDARD_DEVIATION 102.45
Clot onset time	38.25 seconds STANDARD_DEVIATION 4.16	30.75 seconds STANDARD_DEVIATION 9.58	38.25 seconds STANDARD_DEVIATION 4	91.64 seconds STANDARD_DEVIATION 177.95	48.83 seconds STANDARD_DEVIATION 86.58
C-reactive protein	1.13 mg/dL STANDARD_DEVIATION 0.67	3.47 mg/dL STANDARD_DEVIATION 2.38	1.63 mg/dL STANDARD_DEVIATION 1.01	2.31 mg/dL STANDARD_DEVIATION 2.44	2.13 mg/dL STANDARD_DEVIATION 1.92
Diastolic blood pressure	83.9 mmHg STANDARD_DEVIATION 12	78.5 mmHg STANDARD_DEVIATION 9.3	84.8 mmHg STANDARD_DEVIATION 9.9	80.6 mmHg STANDARD_DEVIATION 12.3	82 mmHg STANDARD_DEVIATION 10.8
Estradiol	36.4 pg/mL STANDARD_DEVIATION 10.5	38.6 pg/mL STANDARD_DEVIATION 16.4	43.4 pg/mL STANDARD_DEVIATION 12.3	25.9 pg/mL STANDARD_DEVIATION 8.3	36.0 pg/mL STANDARD_DEVIATION 13.5
Estrone	17.6 pg/mL STANDARD_DEVIATION 18.3	12.4 pg/mL STANDARD_DEVIATION 17.4	3.1 pg/mL STANDARD_DEVIATION 0	5.11 pg/mL STANDARD_DEVIATION 6.7	10.0 pg/mL STANDARD_DEVIATION 14.7
follicle stimulating hormone	4.12 microUI/mL STANDARD_DEVIATION 2.2	60.8 microUI/mL STANDARD_DEVIATION 20.4	6.22 microUI/mL STANDARD_DEVIATION 3.53	75.8 microUI/mL STANDARD_DEVIATION 18.7	36.8 microUI/mL STANDARD_DEVIATION 35.1
glucose	95.8 mg/dL STANDARD_DEVIATION 14.1	96.3 mg/dL STANDARD_DEVIATION 13.8	91.8 mg/dL STANDARD_DEVIATION 12.6	95.4 mg/dL STANDARD_DEVIATION 8.5	94.8 mg/dL STANDARD_DEVIATION 12.2
HDL-cholesterol	43.6 mg/dL STANDARD_DEVIATION 10.2	54.8 mg/dL STANDARD_DEVIATION 15.2	43.5 mg/dL STANDARD_DEVIATION 9	67.2 mg/dL STANDARD_DEVIATION 18.2	52.3 mg/dL STANDARD_DEVIATION 16.5
heart rate	63.6 beats/minute STANDARD_DEVIATION 7.9	65.6 beats/minute STANDARD_DEVIATION 9.1	63.9 beats/minute STANDARD_DEVIATION 10.7	60.8 beats/minute STANDARD_DEVIATION 8.3	63.6 beats/minute STANDARD_DEVIATION 9
Insulin	53.7 microUI/L STANDARD_DEVIATION 33.7	77.1 microUI/L STANDARD_DEVIATION 62.2	69.3 microUI/L STANDARD_DEVIATION 57.1	44.3 microUI/L STANDARD_DEVIATION 28.9	61.5 microUI/L STANDARD_DEVIATION 48.2
LDL-cholesterol	125.5 mg/dL STANDARD_DEVIATION 29.9	140.8 mg/dL STANDARD_DEVIATION 28.7	127.6 mg/dL STANDARD_DEVIATION 34	149.8 mg/dL STANDARD_DEVIATION 37.6	135.5 mg/dL STANDARD_DEVIATION 32
lipoprotein (a)	16.2 mg/dL STANDARD_DEVIATION 20.1	24.1 mg/dL STANDARD_DEVIATION 29.7	31.8 mg/dL STANDARD_DEVIATION 44.7	23.9 mg/dL STANDARD_DEVIATION 17.4	24.0 mg/dL STANDARD_DEVIATION 29.5
luteinizing hormone	3.34 microUI/mL STANDARD_DEVIATION 1.67	20.9 microUI/mL STANDARD_DEVIATION 7.53	4.46 microUI/mL STANDARD_DEVIATION 1.95	29.9 microUI/mL STANDARD_DEVIATION 9.05	14.7 microUI/mL STANDARD_DEVIATION 12.7
Max Elasticity	1598.50 Pascal STANDARD_DEVIATION 398.18	2202.98 Pascal STANDARD_DEVIATION 391.5	1639.82 Pascal STANDARD_DEVIATION 383.97	2164.64 Pascal STANDARD_DEVIATION 275.91	1895.88 Pascal STANDARD_DEVIATION 456.53
Nonesterified fatty acid	25.73 mmol/L STANDARD_DEVIATION 16.55	18.64 mmol/L STANDARD_DEVIATION 14.12	29.75 mmol/L STANDARD_DEVIATION 49.34	24.17 mmol/L STANDARD_DEVIATION 20.92	24.67 mmol/L STANDARD_DEVIATION 28.69
norepinephrine	267.8 pg/mL STANDARD_DEVIATION 148.9	270.8 pg/mL STANDARD_DEVIATION 88.6	286.3 pg/mL STANDARD_DEVIATION 126.8	420.9 pg/mL STANDARD_DEVIATION 171	306.7 pg/mL STANDARD_DEVIATION 144.5
Platelet aggregation by adenosine diphosphate (ADP)	86.13 % STANDARD_DEVIATION 4.06	88.90 % STANDARD_DEVIATION 5.87	84.20 % STANDARD_DEVIATION 7.8	88.45 % STANDARD_DEVIATION 3.65	86.92 % STANDARD_DEVIATION 5.74
Platelet aggregation by epinephrine	84.23 % STANDARD_DEVIATION 3.9	83.42 % STANDARD_DEVIATION 10.22	66.88 % STANDARD_DEVIATION 25.92	81.20 % STANDARD_DEVIATION 18.27	78.93 % STANDARD_DEVIATION 17.72
RAGE (receptor for advanced glycation end-products) gene expression RT-PCR	11.3 arbitrary unit STANDARD_DEVIATION 1.24	12.7 arbitrary unit STANDARD_DEVIATION 1.65	10.9 arbitrary unit STANDARD_DEVIATION 1.68	10.5 arbitrary unit STANDARD_DEVIATION 1.76	11.3 arbitrary unit STANDARD_DEVIATION 1.74
Region of Enrollment Brazil	12 participants	12 participants	12 participants	12 participants	48 participants
Sex: Female, Male Female	0 Participants	12 Participants	0 Participants	12 Participants	24 Participants
Sex: Female, Male Male	12 Participants	0 Participants	12 Participants	0 Participants	24 Participants
Sirtuin	0.95 ng/mL STANDARD_DEVIATION 0.46	1.16 ng/mL STANDARD_DEVIATION 0.9	1.65 ng/mL STANDARD_DEVIATION 1.4	1.65 ng/mL STANDARD_DEVIATION 2.21	1.35 ng/mL STANDARD_DEVIATION 1.39
Sirtuin-1 gene expression by real time polimerase chain reaction RT-PCR	10.4 arbitrary unit STANDARD_DEVIATION 1.28	11.6 arbitrary unit STANDARD_DEVIATION 1.38	11.4 arbitrary unit STANDARD_DEVIATION 1.26	10.6 arbitrary unit STANDARD_DEVIATION 1.15	11.0 arbitrary unit STANDARD_DEVIATION 1.33
Slope	100.83 Pascal/min STANDARD_DEVIATION 38.42	165.42 Pascal/min STANDARD_DEVIATION 60.43	108.17 Pascal/min STANDARD_DEVIATION 43.98	158.36 Pascal/min STANDARD_DEVIATION 37.85	132.66 Pascal/min STANDARD_DEVIATION 53.47
Systolic blood pressure	136.9 mmHg STANDARD_DEVIATION 15	126 mmHg STANDARD_DEVIATION 14.5	133.2 mmHg STANDARD_DEVIATION 16.6	125.6 mmHg STANDARD_DEVIATION 14.1	130.6 mmHg STANDARD_DEVIATION 15.4
total cholesterol	192.8 mg/dL STANDARD_DEVIATION 28.1	222.7 mg/dL STANDARD_DEVIATION 32.5	197.3 mg/dL STANDARD_DEVIATION 36.2	235.1 mg/dL STANDARD_DEVIATION 44.9	212.0 mg/dL STANDARD_DEVIATION 39.1
Triglycerides	126.5 mg/dL STANDARD_DEVIATION 63	121.6 mg/dL STANDARD_DEVIATION 72.4	131.0 mg/dL STANDARD_DEVIATION 77.9	91.4 mg/dL STANDARD_DEVIATION 37.4	117.6 mg/dL STANDARD_DEVIATION 64.4

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	0 / 12	0 / 12	0 / 12	0 / 12
serious Total, serious adverse events	0 / 12	0 / 12	0 / 12	0 / 12

Outcome results

Primary

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).