Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans: A double-blind, placebo-controlled, crossover investigation ☆ , ☆☆ Emma L. Wightman a , Crystal F. Haskell-Ramsay a , Kevin G. Thompson b,1 , Jamie R. Blackwell c , Paul G. Winyard d , Joanne Forster a , Andrew M. Jones c , David O. Kennedy a, ⁎ a Brain, Performance and Nutrition Research Centre, School of Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, United Kingdom b Sport, Exercise and Wellbeing Research Centre, School of Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, United Kingdom c School of Sport and Health Sciences, St. Luke's Campus, University of Exeter, Exeter EX1 2LU, United Kingdom d Peninsula College of Medicine and Dentistry, St. Luke's Campus, University of Exeter, Exeter EX1 2LU, United Kingdom HIGHLIGHTS • Dietary nitrate is reduced endogenously via nitrite to nitric oxide. • The effects of nitrate rich beetroot juice on frontal cerebral blood-flow were tested. • Nitrate modulated the hemodynamic response to task performance in the frontal cortex. • Performance on one of three tasks (serial 3s subtractions) was improved. • Plasma nitrite was increased. abstract article info Article history: Received 12 March 2015 Received in revised form 20 May 2015 Accepted 29 May 2015 Available online 31 May 2015 Keywords: Beetroot Near-Infrared Spectroscopy Cerebral blood flow Nitric oxide Nitrite (NO 2 - ) Nitrate (NO 3 - ) Cognition Nitrate derived from vegetables is consumed as part of a normal diet and is reduced endogenously via nitrite to nitric oxide. It has been shown to improve endothelial function, reduce blood pressure and the oxygen cost of sub-maximal exercise, and increase regional perfusion in the brain. The current study assessed the effects of di- etary nitrate on cognitive performance and prefrontal cortex cerebral blood-flow (CBF) parameters in healthy adults. In this randomised, double-blind, placebo-controlled, parallel-groups study, 40 healthy adults received ei- ther placebo or 450 ml beetroot juice (~5.5 mmol nitrate). Following a 90 minute drink/absorption period, par- ticipants performed a selection of cognitive tasks that activate the frontal cortex for 54 min. Near-Infrared Spectroscopy (NIRS) was used to monitor CBF and hemodynamics, as indexed by concentration changes in oxy- genated and deoxygenated-haemoglobin, in the frontal cortex throughout. The bioconversion of nitrate to nitrite was confirmed in plasma by ozone-based chemi-luminescence. Dietary nitrate modulated the hemodynamic re- sponse to task performance, with an initial increase in CBF at the start of the task period, followed by consistent reductions during the least demanding of the three tasks utilised. Cognitive performance was improved on the serial 3s subtraction task. These results show that single doses of dietary nitrate can modulate the CBF response to task performance and potentially improve cognitive performance, and suggest one possible mechanism by which vegetable consumption may have beneficial effects on brain function. © 2015 Published by Elsevier Inc. 1. Introduction The ubiquitous signalling molecule nitric oxide (NO) plays a modula- tory role in a host of key physiological processes, including mitochondrial and platelet function, host defence mechanisms [1,2], neurotransmission, peripheral and cerebral vaso-dilation [3,4], and the neurovascular cou- pling of neural activity to local cerebral blood-flow (CBF) [5–7]. In most tissues NO is synthesised from L-arginine and is rapidly oxidised to nitrite (NO 2 - ) and nitrate (NO 3 - ) [8]. However, evidence suggests that circulating Physiology & Behavior 149 (2015) 149–158 ☆ Clinicaltrials.gov ID: NCT01169662. ☆☆ Sources of support: The research described herein was internally funded, and all ma- terials were purchased from the open market. ⁎ Corresponding author at: Brain, Performance and Nutrition Research Centre, Northumbria University, Newcastle NE1 8ST, UK. E-mail address: david.kennedy@northumbria.ac.uk (D.O. Kennedy). 1 Current address: University of Canberra, National Institute of Sport Studies, Australia. http://dx.doi.org/10.1016/j.physbeh.2015.05.035 0031-9384/© 2015 Published by Elsevier Inc. Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/phb