Resveratrol intake enhances indoleamine-2,3-dioxygenase activity in humans

BackgroundResveratrol is a polyphenol compound found in various nutrients that was shown to have immunomodulatory, anti-cancerogenic, and cardioprotective effects. The regulation of indoleamine-2,3-dioxygenase (IDO), the rate-limiting enzyme in inflammatory tryptophan metabolism, has been proposed to be involved in resveratrol’s biological effects. These observations, however, rely on in vitro findings and animal studies. Therefore, we assessed the impact of resveratrol on tryptophan metabolism after oral intake in humans.MethodsHealthy volunteers were orally administrated 5 g resveratrol (n = 8) or placebo (n = 2) in a pilot study. IDO activity was determined by analyzing plasma levels of tryptophan and kynurenine. Determination of the immune activation marker neopterin was included in the analysis.ResultsResveratrol administration significantly reduced tryptophan levels 2.5 h (p < 0.001) and 5 h (p < 0.001) after treatment. Kynurenine levels were slightly, but not significantly, elevated 2.5 h after the intervention, which resulted in an 1.33- and 1.30-fold increase of the kynurenine to tryptophan ratio at 2.5 h (p < 0.01) and 5 h (p < 0.01), respectively. Neopterin levels were not affected by resveratrol administration.ConclusionThis is the first evidence of a modulatory effect of orally administered resveratrol on tryptophan metabolism in humans. Since IDO has been shown to play a crucial role in immunity, cancer development and regulation of vascular tone, the modulation of this enzyme might be involved in resveratrol’s diverse biological effects.