Recommendations on the Use of Resveratrol Figure 1. Flow chart of systematic literature search. The literature search was performed to identify all relevant articles focusing on resveratrol and chemoprevention (A), effect of resveratrol on cardio vascular disease (B), effect of resveratrol obesity and diabetes (C), neuroprotective effect of resveratrol (D) and the anti-inflammatory effect of resveratrol (E). In all five groups, articles with non-english language, review articles and articles showing data from in vitro experiments only are excluded. For chemopreventive effect (A), cardio vascular disease (B), obesity and diabetes (C), also non-chronic animal studies were excluded. doi:10.1371/journal.pone.0019881.g001 stream was low, likely caused by rapid metabolism to glucuronide and sulphate conjugates. In addition to the studies described above, levels of Resv after ingestion of Resv-containing items such as wine or grape juice have been investigated [12–15]. However, the specific effect of Resv is difficult to estimate when given as part of food matrices. Two clinical studies were described by Elliott et al., where the effect of Resv on type 2 diabetic patients was tested at 2.5 or 5.0 g/ day for 28 days [16]. The levels of fasting and postprandial plasma glucose and postprandial serum insulin were statistically signifi- cantly decreased with 5.0 g/day, but the experimental details were not given. The tissue distribution of Resv and its metabolites was estimated in a study where twenty colon cancer patients received 0.5 g or 1.0 g Resv daily for eight days before surgical resection [3]. The level of Resv was found in colon tissue at a level sufficient to elicit anticarcinogenic effects observed in in vitro tests. A recent experiment showed that single doses of 250 and 500 mg Resv significantly increased cerebral blood flow but the cognitive performance was unaltered [17]. Several clinical trials of oral Resv as a pure compound or using Resv-rich products (grapes and grape juice) are under way. In total, 24 clinical studies are listed at the homepage http://clinicaltrials. gov/ [18] having Resv as the major experimental subject or as part of a clinical trial. Therefore, it is our recommendation that clinical trials should focus on biomarkers of cancers, diabetes and metabolic syndromes as well as neurological diseases (Table 7). Based on the limited number of human studies, the working group has concluded that there is not at the moment enough available and scientifically valid data on the effect of Resv to PLoS ONE | www.plosone.org 4 June 2011 | Volume 6 | Issue 6 | e19881