The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by oxidative stress and pro-inflammatory stimuli and controls the expression of numerous genes involved in the inflammatory response. Dampening NF-kappaB activation and thereby limiting the inflammatory response have been suggested as a potential strategy to prevent chronic inflammatory diseases. In cultured monocytes, anthocyanins isolated from bilberries and black currants (Medox) efficiently suppressed LPS-induced activation of NF-kappaB. Furthermore, we studied the effect of anthocyanin supplementation (Medox, 300 mg/d for 3 wk) in a parallel-designed, placebo-controlled clinical trial (n = 120 men and women aged 40-74 y). Differences were observed in several NF-kappaB related inflammatory mediators in the Medox group compared to placebo. The changes in the NF-kappaB-controlled pro-inflammatory chemokines IL-8, "regulated upon activation, normal T cell expressed and secreted," (RANTES) and IFNalpha (an inducer of NF-kappaB activation) in the Medox group (45, 15, and 40% decreases from baseline, respectively) differed from those in the placebo group (20, 0, and 15% decreases from baseline, respectively) (P < 0.050). Similarly, changes in IL-4 and IL-13, 2 cytokines that mediate pro-inflammatory responses and induce NF-kappaB activation, in the Medox group (60 and 38% decreases from baseline, respectively) tended to differ from those in the placebo group (4 and 6% decreases) (P = 0.056 and, P = 0.089, respectively). These data suggest that anthocyanin supplementation may have a role in the prevention or treatment of chronic inflammatory diseases by inhibition of NF-kappaB transactivation and deceased plasma concentrations of pro-inflammatory chemokines, cytokines, and inflammatory mediators.