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

Lookup NU author(s): Tess Capper, Dr Mario Siervo, Dr Tom Clifford, Dr Guy Taylor, Dr Wasim Iqbal, Dr Daniel WestORCiD, Professor Emma Stevenson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. 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 as ISRCTN86706442.

Publication metadata

Author(s): Capper TE, Siervo M, Clifford T, Taylor G, Iqbal W, West D, Stevenson EJ

Publication type: Article

Publication status: Published

Journal: The Journal of Nutrition

Year: 2022

Volume: 152

Issue: 1

Pages: 130-139

Print publication date: 01/01/2022

Online publication date: 09/11/2021

Acceptance date: 27/09/2021

Date deposited: 07/02/2022

ISSN (print): 0022-3166

ISSN (electronic): 1541-6100

Publisher: Oxford University Press


DOI: 10.1093/jn/nxab354

PubMed id: 34718635


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