4-weeks of Daily Nitrate-rich Beetroot Juice Consumption Augments Cerebral Autoregulation in Older Adults with Metabolic Syndrome

Metabolic syndrome (MetS) constitutes a cluster of cardiometabolic risk factors that contribute to vascular dysfunction, which are both linked to accelerated cognitive decline. MetS is highly prevalent in older adults (~1-in-2 meet criteria), thus necessitating preventative strategies to reduce risk of cognitive decline and disease in our rapidly growing aging population. Dynamic cerebral autoregulation (dCA) is a homeostatic mechanism which maintains steady blood flow in the brain despite changes in arterial blood pressure and regulated through changes in microvascular tone. dCA is an important mechanism for maintaining cerebral blood flow that could lead to neuronal damage if disrupted and may be targeted to improve cognitive performance in MetS. Beetroot juice (BR) is a safe and well studied nutraceutical effective in improving microvascular function and cerebral blood flow by increases in systemic bioavailability of the vasoprotective molecule, nitric oxide, through the exogenous nitrate (NO3 - )–nitrite (NO2 - )–nitric oxide (NO) pathway. The purpose of this randomized, placebo-controlled, double-blind, parallel-arm clinical trial was to determine the effects of 4-weeks daily BR consumption on dCA in older adults with MetS. We hypothesized that older adults with MetS consuming 4-weeks of daily nitrate-rich beetroot juice (BR nitrate 300 mg NO 3 − /70 mL; age: 68 ± 6 years, n = 12) would significantly improve dCA compared to those consuming nitrate-depleted beetroot juice (BR placebo ∼ 0 mg/70 mL; age: 64 ± 5 years, n = 10). dCA was measured in several frontal brain regions using transfer function analysis (TFA) which relates changes in arterial blood pressure (mmHg) measured by finger photoplethysmography (input) to changes in cerebral blood flow as indexed by functional near infrared spectroscopy (fNIRS) derived oxyhemoglobin (HbO) signal (output). For TFA, participants completed 6 minutes of paced breathing at 0.1 Hz to perturb blood pressure, the frequency in which dCA is most efficient. Outcomes included TFA derived gain and phase-shift at 0.1 Hz, in which lower and higher values represent better dCA, respectively. Repeated measures ANOVA was used to test for the effects of ‘treatment’, ‘time’, and ‘treatment x time’. Changes in plasma nitrate were significantly greater in individuals that received BR nitrate compared to BR placebo following 4-weeks (∆BR nitrate : 57 ± 34 uM; ∆BR placebo : -5 ± 21 uM, p < 0.001). With gain, there was a significant ‘treatment x time’ interaction for the left orbitofrontal cortex (∆BR nitrate : -0.0006 ± 0.0034 HbO/mmhg; ∆BR placebo : +0.0023 ± 0.0021 HbO/mmhg, p = 0.05). For phase-shift, there was significant ‘treatment x time’ interaction for the left premotor cortex (∆BR nitrate : +16.3 ± 21.8°; ∆BR placebo : -20.0 ± 25.8°, p = 0.02) and the left orbitofrontal cortex (∆BR nitrate : +12.1 ± 32.2°; ∆BR placebo : -26.0 ± 34.5°, p = 0.023). Collectively, BR nitrate significantly decreased gain and increased phase in frontal regions of the brain compared to BR placebo , likely through improved NO bioavailability. These findings suggest that 4-weeks of inorganic nitrate-rich beetroot juice supplementation is effective in improving dCA in MetS, highlighting the clinical potential of this juice for improving cerebrovascular function. Further study is needed to determine if improvements in dCA translates to improved cognitive performance in older adults with MetS. Huck Endowment for Nutritional Research in Family and Community Medicine at Penn State College of Medicine and University Park This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.