{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:51:01Z","timestamp":1787784661497,"version":"build-2784847793"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020207","name":"Health Commission of Sichuan Province","doi-asserted-by":"publisher","award":["21PJ070"],"award-info":[{"award-number":["21PJ070"]}],"id":[{"id":"10.13039\/501100020207","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"crossref","award":["2022NSFSC1422"],"award-info":[{"award-number":["2022NSFSC1422"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Cadre Research Health Project of Sichuan Province","award":["2021-1303"],"award-info":[{"award-number":["2021-1303"]}]},{"name":"2021 annual project of the General Hospital of Western Theater Command","award":["2021-XZYG-C24"],"award-info":[{"award-number":["2021-XZYG-C24"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec017\">\n<jats:title>Background<\/jats:title>\n<jats:p>Nitrate is a dietary intervention commonly used to enhance exercise capacity, including cardiopulmonary fitness, yet its effectiveness has been recently questioned at high altitudes. This meta-analysis systematically evaluates the effects of dietary nitrate supplements on cardiopulmonary fitness at high altitude, as reflected in the biomarker of cardiopulmonary fitness, paving the way for informed dietary strategies.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec018\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a systematic assessment and meta-analysis of randomized controlled trials to examine the effects of dietary nitrate supplementation on biomarkers of cardiorespiratory health at high altitude. Studies were included if they involved healthy individuals (\u226516 years of age) engaging in endurance activities such as hiking, long-distance running, mountain climbing, or bicycling at high altitude. Outcomes of interest included nitrite levels (NO<jats:sub>2<\/jats:sub>-), maximal oxygen uptake (VO<jats:sub>2max<\/jats:sub>), heart rate (HR), perceived exertion (RPE), and pulse oxygen saturation (SpO<jats:sub>2<\/jats:sub>). Exclusion criteria included duplicate publications, non-human studies, studies with missing data that could not be retrieved, non-randomized clinical trials, and non-original research articles such as conference papers, expert consensus, or reviews. Our search for articles was conducted across PubMed, Scopus, Web of Science, and Embase, without any language restrictions. A random effects model was employed for quantitative data analysis, utilizing Standardized Mean Difference (SMD) and 95% confidence intervals as summary statistics. The methods and results were reported according to the PRISMA2020 statement.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec019\">\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 9 studies with a sample size of 161 cases were included in the analysis. The meta-analysis indicated that dietary nitrate supplement significantly elevated NO<jats:sub>2<\/jats:sub><jats:sup>-<\/jats:sup> concentration (95% CI: 1.38 to 3.12; SMD\u2009=\u20092.25, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.00001; <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2009=\u200970%). However, there was no significant effect observed on VO<jats:sub>2max<\/jats:sub> (95% CI: -0.58 to 0.23; SMD\u2009=\u2009-0.17, <jats:italic>P<\/jats:italic>\u2009=\u20090.76; <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2009=\u20090%), HR (95% CI: -0.31 to 0.23; SMD\u2009=\u2009-0.04, <jats:italic>P<\/jats:italic>\u2009=\u20090.77; <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2009=\u20090%), RPE scores (95% CI: -0.49 to 0.18; SMD\u2009=\u2009-0.16, P\u2009=\u20090.36; <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2009=\u20090%), and SpO<jats:sub>2<\/jats:sub> percentage (95% CI: -0.36 to 0.20; SMD\u2009=\u2009-0.08, <jats:italic>P<\/jats:italic>\u2009=\u20090.58; <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>\u2009=\u20090%).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec020\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The current meta-analysis indicates that dietary nitrate intake is less correlated with cardiopulmonary fitness at high altitudes, and further research is required to clarify its impact on exercise capacity.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0319667","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T17:26:38Z","timestamp":1744219598000},"page":"e0319667","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of nitrate supplements on cardiopulmonary fitness at high altitude: A meta-analysis of nine randomized controlled trials"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-9251","authenticated-orcid":true,"given":"Chao","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanle","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihong","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"issue":"31","key":"pone.0319667.ref001","doi-asserted-by":"crossref","first-page":"27135","DOI":"10.1021\/acsomega.2c01397","article-title":"Study of the Diffusion Law of Harmful Gases in Tunnel Construction on Plateaus and Optimization of Ventilation Parameters","volume":"7","author":"J Liu","year":"2022","journal-title":"ACS Omega"},{"issue":"5","key":"pone.0319667.ref002","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1080\/10245332.2017.1396046","article-title":"Investigation of the differences between the Tibetan and Han populations in the hemoglobin-oxygen affinity of red blood cells and in the adaptation to high-altitude environments","volume":"23","author":"C Li","year":"2018","journal-title":"Hematology"},{"key":"pone.0319667.ref003","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.nut.2018.09.030","article-title":"Performance and altitude: Ways that nutrition can help","volume":"60","author":"AV Caris","year":"2019","journal-title":"Nutrition"},{"key":"pone.0319667.ref004","doi-asserted-by":"crossref","DOI":"10.1007\/978-981-13-2481-9_48","article-title":"Study on 5-km Armed Cross-Country Training in the Plateau Hypoxic Environment","volume-title":"Man-Machine-Environment System Engineering: Proceedings of the 18th International Conference on MMESE 18","author":"S Mu","year":"2019"},{"key":"pone.0319667.ref005","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3389\/fphys.2018.00375","article-title":"The Effects of Altitude Training on Erythropoietic Response and Hematological Variables in Adult Athletes: A Narrative Review","volume":"9","author":"K P\u0142oszczyca","year":"2018","journal-title":"Front Physiol"},{"key":"pone.0319667.ref006","doi-asserted-by":"crossref","unstructured":"Bryan NS, Loscalzo J. Nitrite and nitrate in human health and disease. 2017.","DOI":"10.1007\/978-3-319-46189-2"},{"issue":"6","key":"pone.0319667.ref007","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.freeradbiomed.2003.11.032","article-title":"The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation","volume":"36","author":"MT Gladwin","year":"2004","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"pone.0319667.ref008","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s40798-023-00632-1","article-title":"Limited Effects of Inorganic Nitrate Supplementation on Exercise Training Responses: A Systematic Review and Meta-analysis","volume":"9","author":"AC Hogwood","year":"2023","journal-title":"Sports Med Open"},{"issue":"5","key":"pone.0319667.ref009","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1123\/ijsnem.23.5.522","article-title":"The effect of nitrate supplementation on exercise performance in healthy individuals: a systematic review and meta-analysis","volume":"23","author":"MW Hoon","year":"2013","journal-title":"Int J Sport Nutr Exerc Metab"},{"issue":"11","key":"pone.0319667.ref010","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1007\/s40279-017-0744-9","article-title":"\u201cBeet-ing\u201d the Mountain: A Review of the Physiological and Performance Effects of Dietary Nitrate Supplementation at Simulated and Terrestrial Altitude","volume":"47","author":"OM Shannon","year":"2017","journal-title":"Sports Med"},{"key":"pone.0319667.ref011","doi-asserted-by":"crossref","first-page":"b2700","DOI":"10.1136\/bmj.b2700","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration","volume":"339","author":"A Liberati","year":"2009","journal-title":"BMJ"},{"key":"pone.0319667.ref012","first-page":"366","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","author":"JA Sterne","year":"2019","journal-title":"bmj"},{"key":"pone.0319667.ref013","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2288-5-13","article-title":"Estimating the mean and variance from the median, range, and the size of a sample","volume":"5","author":"SP Hozo","year":"2005","journal-title":"BMC Med Res Methodol"},{"key":"pone.0319667.ref014","doi-asserted-by":"crossref","first-page":"1435494","DOI":"10.3389\/fspor.2024.1435494","article-title":"Nutrition, hydration and supplementation considerations for mountaineers in high-altitude conditions: a narrative review","volume":"6","author":"E Karp\u0119cka-Ga\u0142ka","year":"2024","journal-title":"Front Sports Act Living"},{"issue":"9","key":"pone.0319667.ref015","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.3390\/nu13093183","article-title":"Effects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review","volume":"13","author":"M Macuh","year":"2021","journal-title":"Nutrients"},{"issue":"1","key":"pone.0319667.ref016","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12970-021-00450-4","article-title":"The effects of dietary nitrate supplementation on endurance exercise performance and cardiorespiratory measures in healthy adults: a systematic review and meta-analysis","volume":"18","author":"C Gao","year":"2021","journal-title":"J Int Soc Sports Nutr"},{"key":"pone.0319667.ref017","doi-asserted-by":"crossref","first-page":"102718","DOI":"10.1016\/j.redox.2023.102718","article-title":"Acute beetroot juice reduces blood pressure in young Black and White males but not females","volume":"63","author":"GJ Grosicki","year":"2023","journal-title":"Redox Biol"},{"issue":"4","key":"pone.0319667.ref018","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.scispo.2020.11.006","article-title":"Physiological determinants of VO2max and the methods to evaluate it: A critical review","volume":"36","author":"J Lee","year":"2021","journal-title":"Science & Sports"},{"issue":"4","key":"pone.0319667.ref019","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.3390\/s21041263","article-title":"The Use of Pulse Oximetry in the Assessment of Acclimatization to High Altitude","volume":"21","author":"T D\u00fcnnwald","year":"2021","journal-title":"Sensors (Basel)"},{"issue":"19","key":"pone.0319667.ref020","doi-asserted-by":"crossref","first-page":"6363","DOI":"10.3390\/s21196363","article-title":"Validity of Peripheral Oxygen Saturation Measurements with the Garmin F\u0113nix\u00ae 5X Plus Wearable Device at 4559 m","volume":"21","author":"LM Schiefer","year":"2021","journal-title":"Sensors (Basel)"},{"issue":"6","key":"pone.0319667.ref021","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1139\/apnm-2014-0470","article-title":"Beetroot juice does not enhance altitude running performance in well-trained athletes","volume":"40","author":"JT Arnold","year":"2015","journal-title":"Appl Physiol Nutr Metab"},{"key":"pone.0319667.ref022","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.niox.2016.08.007","article-title":"Effects of dietary nitrate supplementation on symptoms of acute mountain sickness and basic physiological responses in a group of male adolescents during ascent to Mount Everest Base Camp","volume":"60","author":"PJ Hennis","year":"2016","journal-title":"Nitric Oxide"},{"key":"pone.0319667.ref023","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.niox.2016.08.001","article-title":"Dietary nitrate supplementation enhances high-intensity running performance in moderate normobaric hypoxia, independent of aerobic fitness","volume":"59","author":"OM Shannon","year":"2016","journal-title":"Nitric Oxide"},{"issue":"4","key":"pone.0319667.ref024","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1152\/japplphysiol.00293.2017","article-title":"Dietary nitrate supplementation increases acute mountain sickness severity and sense of effort during hypoxic exercise","volume":"123","author":"GMK Rossetti","year":"2017","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0319667.ref025","doi-asserted-by":"crossref","first-page":"272528","DOI":"10.3389\/fphys.2017.00401","article-title":"Effects of dietary nitrate supplementation on physiological responses, cognitive function, and exercise performance at moderate and very-high simulated altitude","volume":"8","author":"OM Shannon","year":"2017","journal-title":"Frontiers in Physiology"},{"issue":"3","key":"pone.0319667.ref026","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/02640414.2018.1504369","article-title":"The effect of beetroot juice supplementation on repeat-sprint performance in hypoxia","volume":"37","author":"GL Kent","year":"2019","journal-title":"J Sports Sci"},{"issue":"1","key":"pone.0319667.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1123\/ijsnem.2020-0198","article-title":"Influence of Dietary Nitrate Supplementation on High-Intensity Intermittent Running Performance at Different Doses of Normobaric Hypoxia in Endurance-Trained Males","volume":"31","author":"GP Robinson","year":"2021","journal-title":"Int J Sport Nutr Exerc Metab"},{"key":"pone.0319667.ref028","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.niox.2021.05.002","article-title":"Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition","author":"AR Marshall","year":"2021","journal-title":"Nitric Oxide"},{"key":"pone.0319667.ref029","doi-asserted-by":"crossref","first-page":"827235","DOI":"10.3389\/fphys.2022.827235","article-title":"Dietary Nitrate Supplementation Does Not Alter Exercise Efficiency at High Altitude - Further Results From the Xtreme Alps Study","volume":"13","author":"PJ Hennis","year":"2022","journal-title":"Front Physiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0319667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T17:26:48Z","timestamp":1744219608000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0319667"}},"subtitle":[],"editor":[{"given":"Julio Alejandro Henriques Castro","family":"da Costa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0319667","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,9]]}}}