Trial Information

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

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.