Changes in polyphenol serum levels and cognitive performance after dietary supplementation with Concord grape juice in veterans with Gulf War Illness

Aims: We investigated whether the consumption of Concord grape juice (CGJ) was associated with increased bioavailability of serum metabolites and their potential impact on cognitive performance in Veterans with Gulf War Illness (GWI). Main methods: Twenty-six veterans were selected from a cohort of 36 enrolled in a 24-week randomized, double-blind, Phase I/IIA clinical trial exploring whether the consumption of Concord grape juice (CGJ) was tolerable and safe in Veterans with GWI and improved cognitive function and fatigue. These 26 veterans were selected based on their completion of the entire 24-week protocol and documented adherence to the study beverage ≥80%. Differences in serum metabolite levels between CGJ and placebo at midpoint and endpoint were evaluated using two-way repeated measures ANOVA with post hoc Sidak's multiple comparison test. Bivariate correlations to assess for possible relationships between change in serum metabolite levels and change in cognitive function as measured by the Halstead Category Test-Russell Revised Version (RCAT) were also conducted. Key findings: Seventy-six metabolites were identified and quantified in this study, with three (cyanidin-glucuronide, me-cyanidin-glucuronide, and me-malvidin-glucuronide) found to be significantly higher (p < 0.05) in the CGJ group compared to placebo at 24 weeks. Significant associations between changes in cognitive function and changes in serum levels of epicatechin-sulphate (r = 0.48, p = 0.01) and petunidin-glucuronide (r = 0.53, p < 0.01) from baseline to 24 weeks were also observed. Significance: Our data suggest that dietary supplementation with CGJ is associated with increased bioavailability of specific phenolic metabolites, some of which may be correlated with cognitive performance.