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Wightman, Emma, Lodge, John K., Kennedy, David, Bowerbank, Samantha, Cheung, William, Cuthbertson, Lewis and Smith, Darren (2026) The effects of 12-weeks resveratrol supplementation on cognition, gastrointestinal microbiota, and systemic inflammation, in an overweight and obese human population: a randomised, double-blind, placebo controlled, parallel groups trial. Frontiers in Nutrition. ISSN 2296-861X (In Press)
Resveratrol appears to offer greater cognitive benefit to compromised models, such as in type II diabetes mellitus, menopause, and high body mass index (BMI), relative to healthy cohorts. With regards high BMI, hypertension, insulin resistance, oxidative stress, and inflammation have been posited as mechanisms underpinning cognitive decrements, and recent advancements in gut-brain-axis research have linked high BMI with inflammation via gut dysbiosis. Polyphenols have been evidenced to act prebiotically in the gut, to mediate anti-inflammatory effects in animal models, and this presents a mechanism by which resveratrol could bolster cognition in high BMI individuals. The current study investigates whether resveratrol can confer cognitive benefit to individuals with a high BMI, and whether these effects coincide with changes in the gut microbiome, urinary metabolome and biological markers of adiposity (anthropomorphic and blood biomarkers) and inflammation/oxidation. N=99 male and females (35-60 years, mean age 47.51 years), with a BMI between 25-42 kg/m2, received either 500mg Veri-teTM resveratrol, or placebo, daily for 12 weeks. This supplementation period was bookended by visits to the laboratory for urine, blood, and stool sampling, and cognitive testing, which was assessed pre-and post-dose during both the acute and chronic testing visit. Participants in the placebo control group presented with existing differences on cognitive outcomes at baseline, which makes interpretation of apparent improvements in this group relative to resveratrol, problematic. No significant differences were observed within or between groups on any microbiome, urinary metabolome, biological markers of adiposity or inflammation/oxidation markers. The absence of effects on the underlying biological mechanisms rationalised to underpin cognitive improvements in high BMI individuals likely explains the null results in the resveratrol intervention group. Effects attributed to the placebo control condition are explained as the persistence of pre-existing effects in this group of participants, and this may underlie the need to factor pre-enrolment aptitude into randomisation in nutritional intervention trials. The lack of change in the gut microbiome of a healthy human cohort, following 12 weeks of resveratrol supplementation, is a positive indication, showing no deleterious disruption within this environment. Future studies should investigate these effects in those with a disrupted gut microbiome.
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