Consuming High Doses of Blueberry Polyphenols is Safe but Induces Dose-Dependent Shifts in Metabolism

Fruit and vegetable derived polyphenols have been linked with many health benefits. In light of this, many consumers are seeking to increase their intake of polyphenols, with many turning to dietary supplements that contain concentrated doses of purified polyphenols. However, the safety of this consumption modality is not known, nor are the dose-dependent metabolic changes that may be present, especially when considering colonically generated phenolic metabolites. Using blueberry polyphenols as a model, we explored these phenomena in a rat model. Animals were dosed with blueberry polyphenols at levels up to 20 times what would be consumed in 1-2 servings of whole blueberries in an adult human. In the first study, animals were acutely dosed with blueberry polyphenols and urine and plasma pharmacokinetics measured. In the second study, animals were repeatedly dosed for 90d, with urinary metabolites monitored throughout the study and a complete necropsy performed following standard guidelines. In both studies, metabolite excretion patterns were similar: cinnamic acids accounted for a majority of the observed metabolites, followed by hippuric acids and then phenylpropionic acids (PPA). A dose-dependent shift in metabolite production was observed; as the dose increased, the relative amounts of PPA increased while hippuric acids decreased. No adverse or toxic effects were found, and, though there were several statistically significant differences in toxicological endpoints, all measured parameters remained in the normal range for these animals and thus were not deemed biologically significant. These results indicate that high doses of blueberry polyphenols, as may be present in dietary supplements, are safe for consumption. These results also demonstrate dose-dependent shifts in metabolism that may impact gut function and affect the health benefits derived from blueberry polyphenols.