Safety evaluation of an oak-flavored milk powder containing ellagitannins upon oral administration in the rat

Ellagitannins are phenolic compounds that occur in a number of dietary sources such as walnuts, raspberries, pomegranate, strawberries, and oak-aged wines. Ellagitannins have been acknowledged to have antioxidant and cancer chemopreventive activities. However, ellagitannins have also been considered to be antinutrients and have been reported to provoke adverse effects in animals. In this context, risk assessment studies are demanded to ensure that chemicals present in food do not compromise food safety. Oak-flavored milk can be obtained by thermal treatment of milk in the presence of oak shavings. The oak-flavored milk can be used to impart wood-like flavor to different recipes. The present study evaluated, under a subchronic approach, the safety of an oak-flavored milk powder containing ellagitannins in rats upon repeated oral administration for 96 days. The effect of 30% oak-flavored milk powder in the diet was evaluated. This amount involved a margin of safety equivalent to the daily intake of 134 yogurts by a 70 kg person for 96 days. Growth rate, food utility index, 9 hematological, and 13 serobiochemical parameters as well as the metabolism and tissue distribution of ellagitannins and derived metabolites were studied. Overall, no significant differences were found in oak-milk-fed rats in any blood parameter analyzed. No effect was found on growth rate and food utility index. Urolithin A was identified in feces of rats fed oak-flavored milk and the glucuronide derivative in urine. No metabolites were found in the liver, kidney, or uterus. Histopathological analysis of liver and kidney corroborated the absence of toxicity. Therefore, these results suggest that the intake of the oak-flavored milk powder assayed in this study is safe and does not involve potential hazard to human health.