Dietary nitrate supplementation improves cerebral haemodynamic function in males

Background and aims: Beetroot juice (BJ) is a natural source of nitrate, which can be reduced into nitrite and ultimately nitric oxide (NO), leading to an increase in circulating NO (1). Because of its vasodilatory properties, NO can lower blood pressure even in normotensive subjects (2). Amongst other signalling pathways, it has also been suggested to modulate mitochondrial respiration, supporting recent observations of ergogenic effects of dietary nitrate supplementation, such as BJ, on aerobic performance (3). Following the aforementioned vascular pathway, one can speculate that the effects of an increase in NO are not limited to the systemic circulation and could extend to the brain, hence inducing an increase in cerebral perfusion and oxygenation. Therefore, the aim of this study was to determine the impact of dietary nitrate supplementation in the form of BJ on the resting cerebral hemodynamic function. 
Methods: 10 healthy males (age: 26±1 years; height: 182±1 cm; weight: 80±2 kg) consented to this double-blind randomized placebo-controlled trial. Middle cerebral artery velocity (MCAv, Transcranial Doppler) and changes in frontal cortical oxygenation (cO2Hb, near-infrared spectroscopy) were recorded continuously during a 5-minute baseline period, followed by a 3-minute hypercapnea (5% CO2 in balanced O2 and N2), before and 3.5 hours after the ingestion of 500ml of either BJ (containing ≈5.2mmol of nitrate; Beet It, James White Drinks, Ipswich, UK) or a low-calorie blackcurrant juice cordial (negligible nitrate content). Trials were separated by a week and the participants' diet was monitored during a 3-day lead-in period. Exhaled NO (ozone-based chemiluminescence) was measured before and 2 hours post-ingestion. Haemodynamic data were averaged over the last 30 seconds of the respective stage. Data were analysed using a 2-way repeated measures ANOVA (time x drug) and paired samples t-tests. Significance was set at P ≤ 0.05 and data are presented as mean±SD. 
Results: BJ raised the exhaled NO concentration 2h post ingestion (Figure 1A). The increase in cO2Hb in response to the hypercapnic challenge was greater post BJ (P<0.05) than placebo (Figure 1B). However, the hypercapnia-induced alteration in MCAv was not different post supplementation (BJ vs. Placebo). The alterations in NO and cO2Hb post-supplementation were positively correlated (P=0.05) (Figure 2). 

Conclusion: The present results demonstrate for the first time that dietary nitrate supplementation increases cerebral oxygenation but without altering perfusion during hypercapnea. While the underlying mechanisms remain to be fully unravelled, this observation has clear implications not only from a physical performance point of view, but also for the clinician. Indeed, increased oxygenation can be seen as being a neuroprotective mechanism possibly able to prevent the development of dementia in later life.