Inter-individual differences in the blood pressure lowering effects of dietary nitrate: a randomised double-blind placebo-controlled replicate crossover trial.

2025-02-24
European journal of nutrition 64(2)
- Eleanor Hayes
- Shatha Alhulaefi
- Mario Siervo
- Eleanor Whyte
- Rachel Kimble
- Jamie Matu
- Alex Griffiths
- Marc Sim
- Mia Burleigh
- Chris Easton
- Lorenzo Lolli
- Greg Atkinson
- John C Mathers
- Oliver M Shannon

PubMed: 39992469
DOI: 10.1007/s00394-025-03616-x

Study Design

Type: Randomized Controlled Trial (RCT)
Population: Fifteen healthy males
Methods: On two visits, participants consumed 140 ml nitrate-rich beetroot juice (~14.0 mmol nitrate) and, on the other two visits, they consumed 140 ml nitrate-depleted beetroot juice (~0.03 mmol nitrate). Plasma nitrate and nitrite concentrations were measured 2.5 h post-supplementation. BP was measured pre- and 2.5 h post-supplementation
Blinding: Open-label

Rigorous Journal

Purpose

Dietary nitrate supplementation increases nitric oxide (NO) bioavailability and reduces blood pressure (BP). Inter-individual differences in these responses are suspected but have not been investigated using robust designs, e.g., replicate crossover, and appropriate statistical models. We examined the within-individual consistency of the effects of dietary nitrate supplementation on NO biomarkers and BP, and quantified inter-individual response differences.

Methods

Fifteen healthy males visited the laboratory four times. On two visits, participants consumed 140 ml nitrate-rich beetroot juice (~ 14.0mmol nitrate) and, on the other two visits, they consumed 140 ml nitrate-depleted beetroot juice (~ 0.03mmol nitrate). Plasma nitrate and nitrite concentrations were measured 2.5 h post-supplementation. BP was measured pre- and 2.5 h post-supplementation. Between-replicate correlations were quantified for the placebo-adjusted post-supplementation plasma nitrate and nitrite concentrations and pre-to-post changes in BP. Within-participant linear mixed models and a meta-analytic approach estimated participant-by-condition treatment response variability.

Results

Nitrate-rich beetroot juice supplementation elevated plasma nitrate and nitrite concentrations and reduced systolic (mean:-7mmHg, 95%CI: -3 to -11mmHg) and diastolic (mean:-6mmHg, 95%CI: -2 to -9mmHg) BP versus placebo. The participant-by-condition interaction response variability from the mixed model was ± 7mmHg (95%CI: 3 to 9mmHg) for systolic BP and consistent with the treatment effect heterogeneity t = ± 7mmHg (95%CI: 5 to 12mmHg) derived from the meta-analytic approach. The between-replicate correlations were moderate-to-large for plasma nitrate, nitrite and systolic BP (r = 0.55 to 0.91).

Conclusions

The effects of dietary nitrate supplementation on NO biomarkers and systolic BP varied significantly from participant to participant. The causes of this inter-individual variation deserve further investigation.

Trial registration

https://clinicaltrials.gov/study/NCT05514821 .

Research Insights

Beetroot→Reduced Diastolic Blood Pressure
Nitrate-rich beetroot juice supplementation elevated plasma nitrate and nitrite concentrations and reduced systolic (mean:-7mmHg, 95%CI: -3 to -11mmHg) and diastolic (mean:-6mmHg, 95%CI: -2 to -9mmHg) BP versus placebo.
Effect
Beneficial
Effect size
Moderate
Dose
140 ml nitrate-rich beetroot juice (~14.0 mmol nitrate)
Beetroot→Reduced Systolic Blood Pressure
Nitrate-rich beetroot juice supplementation elevated plasma nitrate and nitrite concentrations and reduced systolic (mean:-7mmHg, 95%CI: -3 to -11mmHg) and diastolic (mean:-6mmHg, 95%CI: -2 to -9mmHg) BP versus placebo.
Effect
Beneficial
Effect size
Moderate
Dose
140 ml nitrate-rich beetroot juice (~14.0 mmol nitrate)