Dietary nitrate supplementation improves reaction time in type 2 diabetes: Development and application of a novel nitrate-depleted beetroot juice placebo

Abstract

BackgroundIn this substudy of the effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes, we report the development of a novel nitrate depleted beetroot juice for use clinical trials and determine if dietary nitrate supplementation improved cognitive function in patients with type 2 diabetes mellitus. MethodsBeetroot juice was treated with the anion exchange resin Purolite A520e. UV–vis-spectrophotometry, and a blind taste test were performed along with determination of sugar content, measurement of ascorbate and dehydroascorbate, the ionic composition of juice and Proton NMR. Subsequently, 27 patients, age 67.2±4.9years, (18 male) were recruited for a double blind, randomised, placebo-controlled crossover trial. Participants were randomised to begin in either order beetroot juice (nitrate content 7.5mmol per 250ml) or placebo (nitrate depleted beetroot juice nitrate content 0.002mmol per 250ml). At the end of each 2week supplementation period cognitive function was assessed using E-prime, E-Studio software with 5 separate tests being performed. The tests utilised in the present study have been adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB). ResultsThe differences in the UV–vis spectra were comparable to the natural variation found in differing cultivars. There were no discernable differences in taste, sugar content, or Proton NMR. Ascorbate and dehydroascorbate were undetectable in either juice. After 2weeks of beetroot juice simple reaction time was significantly quicker in the active arm at 327±40ms versus 341.8±52.7ms in the placebo arm, mean difference 13.9±25.6ms (95% CI 3.8–24.0ms), p=0.009. No other measures of cognitive function differed between treatment arms. ConclusionWe have developed an effective placebo beetroot juice for use in trials of supplementation of dietary nitrate. Two weeks supplementation of the diet with 7.5mmol of nitrate per day caused a significant improvement in simple reaction time in individuals with T2DM.