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.

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.

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.