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Limited Effects of Inorganic Nitrate Supplementation on Exercise Training Responses: A Systematic Review and Meta-analysis
Abstract
Background: Inorganic nitrate (NO 3−) supplementation is purported to benefit short-term exercise performance, but it is unclear whether NO 3− improves longer-term exercise training responses (such as improvements in VO 2peak or time to exhaustion (TTE)) versus exercise training alone. The purpose of this systematic review and meta-analysis was to determine the effects of NO 3− supplementation combined with exercise training on VO 2peak and TTE, and to identify potential factors that may impact outcomes. Methods: Electronic databases (PubMed, Medscape, and Web of Science) were searched for articles published through June 2022 with article inclusion determined a priori as: (1) randomized placebo-controlled trials, (2) exercise training lasted at least three weeks, (3) treatment groups received identical exercise training, (4) treatment groups had matched VO 2peak at baseline. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using restricted maximum likelihood estimation between pre- and post-training differences in outcomes. Moderator subgroup and meta-regression analyses were completed to determine whether the overall effect was influenced by age, sex, NO 3− dosage, baseline VO 2peak, health status, NO 3− administration route, and training conditions. Results: Nine studies consisting of eleven trials were included: n = 228 (72 females); age = 37.7 ± 21 years; VO 2peak: 40 ± 18 ml/kg/min. NO 3− supplementation did not enhance exercise training with respect to VO 2peak (SMD: 0.18; 95% CI: -0.09, 0.44; p = 0.19) or TTE (SMD: 0.08; 95% CI: − 0.21, 0.37; p = 0.58). No significant moderators were revealed on either outcome. Subset analysis on healthy participants who consumed beetroot juice (BRJ) revealed stronger trends for NO 3− improving VO 2peak (p = 0.08) compared with TTE (p = 0.19), with no significant moderators. Sunset funnel plot revealed low statistical power in all trials. Conclusions: NO 3− supplementation combined with exercise training may not enhance exercise outcomes such as VO 2peak or TTE. A trend for greater improvement in VO 2peak in healthy participants supplemented with BRJ may exist (p = 0.08). Overall, future studies in this area need increased sample sizes, more unified methodologies, longer training interventions, and examination of sex as a biological variable to strengthen conclusions.
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“However, systematic reviews highlight the limited number of studies and their heterogeneity in participant level, exercise protocols, dosages, and supplementation strategies [58,99].”
From Use of Nutritional Strategies, Bioactive Compounds, and Dietary Supplements in Young Athletes: From Evidence to Potential Risks—A Narrative Review (2025) · cites this paper as [99]
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The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
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Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans
Larsen, F. J., Schiffer, T. A., Borniquel, S., Sahlin, K., Ekblom, B., Lundberg, J. O., & Weitzberg, E. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.004 · Cited by 689 · cited 1×
“…beneficial role in several physiological processes linked to exercise performance, including increased blood flow and O 2 delivery [4, 5], increased microvascular PO 2 [6], improved muscular contractility [7, 8], and reduced O 2 cost of exercise [9–11] by enhancing mitochondrial function [12].”
BackgroundInorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO
Kapil, V., Milsom, A. B., Okorie, M., Maleki-Toyserkani, S., Akram, F., Rehman, F., Arghandawi, S., Pearl, V., Benjamin, N., Loukogeorgakis, S., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.153536 · Cited by 621 · cited 1×
“Whether NO 3– dose should be normalized to bodyweight has key implications in females due to the typically lower body mass compared to males and higher basal NO 2 − levels [55].”
BackgroundVanhatalo, A., Bailey, S. J., Blackwell, J. R., DiMenna, F. J., Pavey, T. G., Wilkerson, D. P., Benjamin, N., Winyard, P. G., & Jones, A. M. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00206.2010 · Cited by 529
THE PHYSIOLOGICAL MEANING OF THE MAXIMAL OXYGEN INTAKE TEST1
Mitchell, J. H., Sproule, B. J., & Chapman, C. B. (1958) · Journal of Clinical Investigation · doi:10.1172/jci103636 · Cited by 516
Mandsager, K., Harb, S., Cremer, P., Phelan, D., Nissen, S. E., & Jaber, W. (2018) · JAMA Network Open · doi:10.1001/jamanetworkopen.2018.3605 · Cited by 501 · cited 1×
“VO 2peak improves with exercise training via multifaceted improvements in oxygen delivery (e.g., stroke volume, blood volume) and oxygen utilization (e.g., a-vO 2 difference), and is a predictor of both endurance capacity and mortality/morbidity [18].”
BackgroundLansley, K. E., Winyard, P. G., Fulford, J., Vanhatalo, A., Bailey, S. J., Blackwell, J. R., DiMenna, F. J., Gilchrist, M., Benjamin, N., & Jones, A. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01070.2010 · Cited by 404
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Carlsson, S., Wiklund, N. P., Engstrand, L., Weitzberg, E., & Lundberg, J. O. N. (2001) · Nitric Oxide · doi:10.1006/niox.2001.0371 · Cited by 189
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Cited by
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Tian, C., Jiang, Q., Han, M., Guo, L., Huang, R., Zhao, L., & Mao, S. (2025) · Nutrients · doi:10.3390/nu17121958 · Cited by 16
De Zan, D., Eletti, F., Fiore, G., Di Girolamo, E., Bozzini, G. G. M., Perico, V., Tosi, M., Norsa, L., Zuccotti, G., & Verduci, E. (2025) · Nutrients · doi:10.3390/nu17132194 · Cited by 11
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Metadata
- Authors
- Hogwood, A. C., Anderson, K. C., Ortiz de Zevallos, J., Paterson, C., Weltman, A., & Allen, J. D.
- ORCID
- Hogwood, Austin C.
- Venue
- Sports Medicine - Open
- Published
- 2023-09-11
- Volume
- 9
- Issue
- 1
- ISSN
- 2198-9761
- Cited by
- 14
- References
- 19
- Language
- en
- Licence
- creativecommons.org/licenses/by/4.0 (tdm)
- creativecommons.org/licenses/by/4.0 (vor)
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