Pharmacokinetic Profile of Incremental Oral Doses of Dietary Nitrate in Young and Older Adults: A Crossover Randomized Clinical Trial

Abstract

Background Dietary nitrate consumption can increase concentrations of nitrate and nitrite in blood, saliva, and urine. Whether the change in concentrations is influenced by age is currently unknown. Objectives We aimed to measure changes in nitrate and nitrite concentrations in plasma, urine, and saliva and exhaled NO concentrations after single incremental doses of dietary nitrate in young and older healthy adults. Methods Twelve young (18–35 y old) and 12 older (60–75 y old) healthy, nonsmoking participants consumed single doses of 100 g, 200 g, 300 g whole beetroot (BR) and 1000 mg potassium nitrate (positive control) ≥7 d apart in a crossover, randomized clinical trial. Plasma nitrate and nitrite concentrations and exhaled NO concentrations were measured over a 5-h period. Salivary nitrate and nitrite concentrations were measured over a 12-h period and urinary nitrate over a 24-h period. Time, intervention, age, and interaction effects were measured with repeated-measures ANOVAs. Results Dose-dependent increases were seen in plasma, salivary, and urinary nitrate after BR ingestion (all P ≤ 0.002) but there were no differences between age groups at baseline (all P ≥ 0.56) or postintervention (all P ≥ 0.12). Plasma nitrite concentrations were higher in young than older participants at baseline (P = 0.04) and after consumption of 200 g (P = 0.04; +25.7 nmol/L; 95% CI: 0.97, 50.3 nmol/L) and 300 g BR (P = 0.02; +50.3 nmol/L; 95% CI: 8.57, 92.1 nmol/L). Baseline fractional exhaled NO (FeNO) concentrations were higher in the younger group [P = 0.03; +8.60 parts per billion (ppb); 95% CI: 0.80, 16.3 ppb], and rose significantly over the 5-h period, peaking 5 h after KNO3 consumption (39.4 ± 4.5 ppb; P < 0.001); however, changes in FeNO were not influenced by age (P = 0.276). Conclusions BR is a source of bioavailable dietary nitrate in both young and older adults and can effectively raise nitrite and nitrate concentrations. Lower plasma nitrite and FeNO concentrations were found in older subjects, confirming the impact of ageing on NO bioavailability across different systems. This trial was registered at www.isrctn.com as ISRCTN86706442.

Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion

“…Our results for saliva, plasma and urine are consistent with previous reports [ 10 , 11 , 13 , 14 , 27 , 28 ]. However, a novel finding of the present study is the rapid uptake of NO 3 − into skeletal muscle, which was evident at 0.5 h following the ingestion of an acute bolus of KNO 3 .…”

“…The time course of changes in urine [NO 3 − ] differed from the pattern observed in the other compartments, reflecting delayed dynamics for the excretion of NO 3 − . The results indicate that urine [NO 3 − ] was significantly increased 1 h post NO 3 − ingestion and remained elevated for 9 h before returning to baseline at 24 h. These results are consistent with previous literature [ 12 – 14 , 28 ]. It has been reported that up to 75% of ingested NO 3 − is ultimately expelled in the urine [ 31 ].…”

Ageing modifies acute resting blood pressure responses to incremental consumption of dietary nitrate: a randomised, cross-over clinical trial

“…Volunteers provided informed written consent before participating, and the study was approved by the Cambridge Central Research Ethics Committee (16/EE/0376) and registered with ISRCTN (86706442). The primary aim of the trial was to evaluate the pharmacokinetic profile of incremental oral doses of dietary nitrate in young and older adults, which have been reported elsewhere (12) ; this manuscript reports the results from the analyses of secondary outcomes such as BP and microvascular function. The study was conducted in the Clinical Trial Unit of the Newcastle University Royal Infirmary Hospital.…”

“…The data presented are secondary analysis from a larger study for which this study was powered (12) . The sample size calculation for that study was based on an acute (3 h) trial testing the effects of inorganic nitrate supplementation compared to placebo on plasma NO 3 -concentrations in young and older healthy individuals (23) .…”

Acute beetroot juice consumption does not alter cerebral autoregulation or cardiovagal baroreflex sensitivity during lower-body negative pressure in healthy adults

“…Endogenous nitric oxide production can be supplemented with dietary nitrates to increase its bioavailability ( Capper et al, 2022 ). Dietary nitrate supplementation has been shown to lower blood pressure ( Houston and Hays, 2014 ), and improve endothelial function ( Houston and Hays, 2014 ; Sindler et al, 2014 ; Walker et al, 2019 ; Rossman et al, 2021 ) and vascular compliance ( Houston and Hays, 2014 ), in adults who are normotensive or hypertensive ( Lidder and Webb, 2013 ).…”