“About 70% of the resveratrol dose given orally as a pill is absorbed; nevertheless, oral bioavailability of resveratrol is low because it is rapidly metabolized in intestines and liver into conjugated forms: glucuronate and sulfonate.[27] Only trace amounts (below 5 ng/mL) of unchanged resveratrol could be detected in the blood after 25 mg oral dose.[27] Even when a very large dose of resveratrol (2.5 and 5 g) was given as an uncoated pill, the concentration of resveratrol in blood failed to reach the level necessary for the systemic cancer prevention.[28] However, resveratrol given in a proprietary formulation SRT-501 (3 or 5 g), developed by Sirtris Pharmaceuticals, reached 5–8 times higher blood levels. These levels did approach the concentration necessary to exert the effects shown in animal models and in vitro experiments.[2]
In humans[27][28] and rats,[29][30][31] less than 5% of the oral dose is being observed as free resveratrol in blood plasma. The most abundant resveratrol metabolites in humans, rats, and mice are trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate.[32] Walle suggests sulfate conjugates are the primary source of activity,[27] Wang et al. suggests the glucuronides,[33] and Boocock et al. also emphasized the need for further study of the effects of the metabolites, including the possibility of deconjugation to free resveratrol inside cells. Goldberd, who studied the pharmacokinetics of resveratrol, catechin and quercetin in humans, concluded “it seems that the potential health benefits of these compounds based upon the in vitro activities of the unconjugated compounds are unrealistic and have been greatly exaggerated. Indeed, the profusion of papers describing such activities can legitimately be described as irrelevant and misleading. Henceforth, investigations of this nature should focus upon the potential health benefits of their glucuronide and sulfate conjugates.”[34]“

Astrid
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