Anti-inflammatory and Antioxidant Effects of Resveratrol on Healthy Adults.

Redox Status Clinical Trial

Official title:

Double-blind Cross-over Randomised Controlled Trial on the Anti-inflammatory and Antioxidant Effects of Resveratrol on Healthy Adults.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01492114
• Other study ID #: sbo2011
• Status: Completed
• Phase: Phase 3
• First received: December 12, 2011
• Last updated: July 6, 2012
• Start date: July 2011
• Est. completion date: March 2012

Study information

• Verified date: July 2012
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This research will investigate the hypothesis that resveratrol when given orally to healthy adult smokers induces a decrease in the inflammatory and oxidative mediators which characterize the low-grade systemic inflammatory state and the oxidants-antioxidants imbalance of tobacco users.

Description:

The effect of resveratrol in humans is still not well defined. The number of studies on resveratrol has increased extraordinarily since 1997, when its anticancer effect has been reported. However, most of these studies are in-vitro or animal studies. Preclinical observations in humans suggest that resveratrol is safe and has potential in the treatment of obesity and insulin resistance in humans.

In particular, it improves insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway. Studies on toxicity of resveratrol in humans demonstrated that this compound is well tolerated and no adverse effect has been found with higher dosage (5g/day). Resveratrol is available to people over-the-counter in health food stores and the internet as a dietary supplement. In humans, resveratrol is efficiently absorbed after oral administration; however, rapid phase II metabolism drastically limits its plasma bio-availability. The high concentrations of resveratrol in colorectal tissues, in excess of that required for activity in vitro, supports the colon as a target organ. The efficacy of resveratrol in other tissues may be largely dependent on whether its metabolites have significant activity or are able to regenerate resveratrol either locally or systemically (e.g. some metabolites, mainly sulfate-conjugated resveratrol, show biological effects in cellular models).

There are only a few studies evaluating the anti-inflammatory properties of resveratrol in humans. An extract of Polygonum Cuspidatum containing resveratrol given for 6-weeks to 10 healthy subjects was able to significantly suppress plasma concentrations of inflammatory cytokines (C-reactive protein, interleukin-6, tumor necrosis factor-α). Similarly, a nutritional supplement containing resveratrol plays an acute antioxidant and antiinflammatory effects in the postprandial state after a high-fat, high-carbohydrate meal in 10 healthy females.

The anti-inflammatory and antioxidant effects of resveratrol may be particularly interesting for smokers. Resveratrol increases the NO bioavailability and the inhibition of cyclooxygenase and 5-lipoxygenase activity of Cox-1 and it prevents the vascular leucocyte migration into damaged organs by decreasing the expression of endothelial vascular adhesion molecules and of pro-inflammatory genes. The inflammatory responses induced by oxidized LDL (low-density lipoproteins) are partially avoided by the addition of reveratrol and the authors concluded that it could affect vascular inflammation or/and injury not only as antioxidant, but also as modulator of inflammatory redox signalling pathways.

However, there are currently no published demonstrations of therapeutic or protective effects of resveratrol in appropriately designed clinical trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: March 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 50 Years

Eligibility

Inclusion Criteria:

• age 20-50 years

• actual smoking (=5 cigarettes/die)

• mean alcohol consumption <30g/day

• absence of known hyperglycaemia, hypertension, cardiovascular disease, impaired renal function, liver disease, or any other systemic conditions -no use of any drug -oestrogen excluded-

• not being on a particular diet and/or vitamin or other nutrient or integrator supplementation during the least 6-months

Exclusion Criteria:

• actual pregnancy -known hyperglycaemia, hypertension, cardiovascular disease, impaired renal function, liver disease, or any other systemic chronic or acute conditions, use of any drug -oestrogen excluded-

• being on a particular diet and/or vitamin or other nutrient or integrator supplementation during the last six months

• mean alcohol consumption =30g/day

• body mass index (BMI)>30 kg/m2

• subject unable to give his/her informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Chronic Subclinic Inflammation
• Inflammation
• Redox Status

Intervention

Dietary Supplement:
• Resveratrol
Subjects in the group "resvetarol first" will be submitted to: 30 days of treatment with Transmax (resveratrol, 500 mg, Biotivia Bioceuticals LLC), one tablet/day in the morning at fasting; then to 30 days of wash-out (no supplementation), and then to 30 days of treatment with placebo (one tablet/day in the morning at fasting).
• resveratrol
Subjects in the group "Placebo first" will be submitted to: 30 days of treatment with placebo, one tablet/day in the morning at fasting; than to 30 days of wash-out (no supplementation), and then to 30 days of treatment with Transmax (resveratrol, 500 mg) (one tablet/day in the morning at fasting).

Locations

Country	Name	City	State
Italy	Simona Bo	Turin

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C-reactive protein	To evaluate before-after changes in circulating concentrations of C-reactive protein (CRP), an inflammation marker, in smokers submitted to resveratrol supplementation when compared to smokers treated with placebo	At baseline and every 30 days for three months	No
Secondary	TAS (total antioxidant status)	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: TAS (total antioxidant status.	At baseline and every 30-days for three months	No
Secondary	4-hydroxynonenal	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: 4-hydroxynonenal	At baseline and after 30-days for three months	No
Secondary	nitrotyrosine	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: nitrotyrosine.	At baseline and every 30-days for three months	No
Secondary	endothelial nitric oxide synthase (eNOS)-polymorphism	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: endothelial nitric oxide synthase (eNOS)-polymorphism	At baseline and every 30-days for three months	No
Secondary	superoxide dismutase (SOD2)-polymorphism	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: superoxide dismutase (SOD2)-polymorphism.	At baseline and every 30-days for three months	No
Secondary	catalase-polymorphism	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -markers of oxidative stress: catalase-polymorphism	At baseline and every 30-days for three months	No
Secondary	interleukin-6	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -other markers of inflammation: interleukin-6.	At baseline and every 30-days for three months	No
Secondary	pentraxin 3	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -other markers of inflammation: pentraxin 3.	At baseline and every 30-days for three months	No
Secondary	tumor necrosis factor-a	To evaluate before-after changes in circulating fasting concentrations of the following parameters: -other markers of inflammation: tumor necrosis factor-a.	At baseline and every 30-days for three months	No