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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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifteen healthy males visited the laboratory four times. On two visits, participants consumed 140\u00a0ml nitrate-rich beetroot juice (~\u200914.0mmol nitrate) and, on the other two visits, they consumed 140\u00a0ml nitrate-depleted beetroot juice (~\u20090.03mmol nitrate). Plasma nitrate and nitrite concentrations were measured 2.5\u00a0h post-supplementation. BP was measured pre- and 2.5\u00a0h 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>versus<\/jats:italic>\n                      placebo. The participant-by-condition interaction response variability from the mixed model was \u00b1\u20097mmHg (95%CI: 3 to 9mmHg) for systolic BP and consistent with the treatment effect heterogeneity t\u2009=\u2009\u00b1\u20097mmHg (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 (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.55 to 0.91).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      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:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05514821\" ext-link-type=\"uri\">https:\/\/clinicaltrials.gov\/study\/NCT05514821<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00394-025-03616-x","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T10:39:50Z","timestamp":1740393590000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Inter-individual differences in the blood pressure lowering effects of dietary nitrate: a randomised double-blind placebo-controlled replicate crossover trial"],"prefix":"10.1007","volume":"64","author":[{"given":"Eleanor","family":"Hayes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shatha","family":"Alhulaefi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Siervo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Whyte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Kimble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Matu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Burleigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Easton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Lolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Mathers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8208-6837","authenticated-orcid":false,"given":"Oliver M.","family":"Shannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"3616_CR1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/s41569-021-00559-8","volume":"18","author":"B Zhou","year":"2021","unstructured":"Zhou B, Perel P, Mensah GA, Ezzati M (2021) Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. 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