Intermittent vs. continuous wild blueberry feeding alters inflammation and behavior in aged rats

Authors: Shukitt Hale, Barbara; Fisher, Derek; CAHOON, DANIELLE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MILLER, MARSHALL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CAREY, AMANDA - Simmons University; ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Medicinal Food
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/30/2025
Publication Date: 4/28/2025
Citation: Shukitt Hale, B., Fisher, D.R., Cahoon, D.S., Miller, M.G., Carey, A.N., Zheng, T. 2025. Intermittent vs. continuous wild blueberry feeding alters inflammation and behavior in aged rats. Journal of Medicinal Food. https://doi.org/10.1089/jmf.2025.0001.
DOI: https://doi.org/10.1089/jmf.2025.0001

Interpretive Summary: Previous studies have shown the benefits of blueberries when eaten every day, especially for improving memory. However, the ideal intake of blueberries is currently unknown. To evaluate the beneficial effects of blueberries relative to the frequency of consumption, a study was conducted where rats either ate 1) no blueberries (control diet); 2) blueberries every day; or 3) blueberries intermittently (3 days on, 4 days off) for 2 months. The rats fed blueberries intermittently showed better performance in fine motor coordination and memory, compared to control-fed rats. Inflammation was reduced in both groups fed blueberries. Based on these findings, blueberries may not have to be consumed daily to elicit beneficial effects, possibly due to the retention of their nutrients in tissue and circulation.

Technical Abstract: Previous studies have shown that continuous daily consumption of polyphenolic-rich blueberries (BB) reduced neuroinflammation and improved age-related declines in motor and cognitive function in rodents and humans, but the optimal intake of BBs is currently unknown. To evaluate the beneficial effects of BBs on neuroinflammation and motor and cognitive function relative to the frequency of consumption, the diets of aged F344 rats (18 mo; n = 15/group) were supplemented with either a continuous control diet, a continuous 2% wild BB diet, or an intermittent (3 days on, 4 days off) 2% wild BB diet for 2 months prior to behavioral testing. Because neuroinflammation has been identified as a major contributing factor to the behavioral declines seen in aging and neurodegenerative diseases, serum was collected pre-diet and at the end of the study to assess whether diet-induced changes in serum can alter the production of inflammatory stress signals in activated HAPI rat microglial cells in vitro. Serum from rats continuously and intermittently fed BBs had beneficial effects by reducing the expression of inflammatory enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in microglia, but only continuous feeding attenuated nitrite production. Intermittent BB-fed rats performed better on the rotarod and committed fewer errors in the radial arm water maze on Day 2 compared to control-fed animals. Based on these findings, BBs may not have to be consumed daily to elicit beneficial effects, possibly due to the retention of polyphenols and their metabolites in tissue and circulation.