Increasing nitric oxide availability via ingestion of nitrate-rich beetroot juice improves vascular responsiveness in individuals with Alzheimer's Disease

Poor vascular function and reduced nitric oxide (NO)-bioavailability have been recognized to be involved in aging and Alzheimer's Disease (AD). A non-pharmacological treatment that is gaining clinical interest in the context of vascular function is dietary inorganic nitrate (NO₃^-) supplementation which increases NO-bioavailability through the NO₃^- -nitrite (NO₂^-) - NO pathway. This treatment has been demonstrated to improve vascular function in several clinical populations, but no study has investigated the effects in individuals with AD. Therefore, changes in plasma NO₃^- and NO₂^- and vascular responsiveness (hyperemic response to single-passive leg movement (ΔPLM)) were measured in individuals with AD (n = 10, 76 ± 9 years), healthy elderly (OLD, n = 10, 75 ± 6 years), and young individuals (YN, n = 10, 25 ± 4 years) before (T0) and hourly for 4 h (T1, T2, T3, and T4) after ingestion of either NO₃^--rich beetroot juice (BR) or a placebo (PLA). No changes in NO₃^- and NO₂^-, nor ΔPLM were detected in any group following PLA intake. Plasma NO₃^- and NO₂^- increased significantly in all three groups at T1 (p < 0.001) and remained elevated for the rest of the trial. The same trend was found in ΔPLM, which significantly increased in all three groups over the time (p < 0.001). However, AD exhibited significantly lower ΔPLM values at any time point compared to YN (p < 0.001) and OLD (p < 0.001). These data suggest that AD-individuals included in this study were able to reduce NO₃^- to NO₂^- and to increase NO-mediated vascular responsiveness as non-AD-individuals. Other mechanisms, beyond NO-bioavailability, may be involved in vascular dysfunction in patients with AD. This research suggests that an acute administration of inorganic nitrate is not enough to revert chronically adapted vascular properties and completely restore vascular responsiveness in AD.