Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance
Open accessAbstract
Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in myriad physiological processes, including the regulation of vascular tone, neurotransmission, mitochondrial respiration, and skeletal muscle contractile function. NO may be produced via the canonical NO synthase–catalyzed oxidation of l -arginine and also by the sequential reduction of nitrate to nitrite and then NO. The body’s nitrate stores can be augmented by the ingestion of nitrate-rich foods (primarily green leafy vegetables). NO bioavailability is greatly enhanced by the activity of bacteria residing in the mouth, which reduce nitrate to nitrite, thereby increasing the concentration of circulating nitrite, which can be reduced further to NO in regions of low oxygen availability. Recent investigations have focused on promoting this nitrate–nitrite–NO pathway to positively affect indices of cardiovascular health and exercise tolerance. It has been reported that dietary nitrate supplementation with beetroot juice lowers blood pressure in hypertensive patients, and sodium nitrite supplementation improves vascular endothelial function and reduces the stiffening of large elastic arteries in older humans. Nitrate supplementation has also been shown to enhance skeletal muscle function and to improve exercise performance in some circumstances. Recently, it has been established that nitrate concentration in skeletal muscle is much higher than that in blood and that muscle nitrate stores are exquisitely sensitive to dietary nitrate supplementation and deprivation. In this review, we consider the possibility that nitrate represents an essential storage form of NO and discuss the integrated function of the oral microbiome, circulation, and skeletal muscle in nitrate–nitrite–NO metabolism, as well as the practical relevance for health and performance.
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Dietary nitrate increases NO bioavailability via the nitrate-nitrite-NO pathway, particularly in conditions of hypoxia or high metabolic demand characteristic of ageing muscle.
“Dietary nitrate, which is found in high concentrations in vegetables such as beetroot, increases NO bioavailability via the nitrate-nitrite-NO pathway, particularly in conditions of hypoxia or high metabolic demand, which are characteristic of ageing muscle [41,59,185,186].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [185]
Safety concerns regarding dietary nitrate primarily relate to its potential conversion into nitrosamines (NOCs).
“Safety concerns regarding dietary nitrate primarily relate to its potential conversion into nitrosamines, also known as N-nitroso compounds (NOCs) [185,188].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [185]
Vegetables provide antioxidants and bioactive compounds that enhance NO bioavailability and inhibit nitrosamine formation.
“vegetables provide antioxidants and bioactive compounds that enhance NO bioavailability and inhibit nitrosamine formation [185,188].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [185]
These mechanisms are particularly relevant in older adults with reduced endogenous antioxidant capacity and impaired NO signalling.
“mechanisms that are particularly relevant in older adults with reduced endogenous antioxidant capacity and impaired NO signalling [185,288].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [185]
Fresh and minimally processed vegetables retain native nitrate content and vitamin C, betalains and flavonoids, which stabilise nitrite, limit oxidative degradation of NO and support S-nitrosothiol formation.
“Fresh and minimally processed vegetables retain not only their native nitrate content but also vitamin C, betalains and flavonoids, which stabilise nitrite, limit oxidative degradation of NO and support S-nitrosothiol formation”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [185]
The apparent lack of effect of nitrate supplementation in elite endurance athletes may be a function of their athletic status (e.g., superior background NO production or reduced number of Type II muscle fibres) as well as an interaction with the conditions of use.
“The apparent lack of effect in elite endurance athletes may be a function of their athletic status (e.g., due to a superior background NO production or reduced number of Type II muscle fibres in which nitrate supplementation might be most suited to targeting conditions of hypoxia or acidosis [19,56,61,62]) as well as an interaction with the conditions of use.”
From Neither beetroot juice supplementation nor increased carbohydrate oxidation enhance economy of prolonged exercise in elite race walkers (2021) · cites this paper as [56]
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Self-citationBeetroot Juice Increases Human Muscle Force without Changing Ca2+-Handling Proteins
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- Authors
- Jones, A. M., Vanhatalo, A., Seals, D. R., Rossman, M. J., Piknova, B., & Jonvik, K. L.
- Affiliations
- University of Exeter (GB)
- University of Colorado Boulder (US)
- National Institutes of Health (US)
- Maastricht University Medical Centre (NL)
- Corresponding author
- Jones, Andrew M.
- ORCID
- Venue
- Medicine & Science in Sports & Exercise
- Published
- 2020-07-29
- Volume
- 53
- Issue
- 2
- Pages
- 280-294
- ISSN
- 0195-9131 (ISSN-L)
- 1530-0315
- OpenAlex
- W3046780524
- Cited by
- 156
- References
- 156
- Citations by year
- 2026: 26 · 2025: 30 · 2024: 30 · 2023: 28 · 2022: 29 · 2021: 13
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Medicine & Science in Sports & Exercise (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- National Institute on Aging (R37AG013038, T32AG000279)
- National Heart, Lung, and Blood Institute (R21HL107105)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK115524)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- dietary nitrate, nitric oxide metabolism, nitrate-nitrite-NO pathway, oral microbiota, nitrite, exercise performance, blood pressure, hypertension, endothelial function, arterial stiffness, beetroot juice, sodium nitrite, nitric oxide synthase, vascular tone
- MeSH terms
- Animals, Biological Availability, Blood Circulation, Cardiovascular Diseases, Endothelium, Vascular, Homeostasis, Humans, Mouth, Nitrates, Nitric Oxide, Risk Factors, Exercise, Muscle, Skeletal, Dietary Supplements, Microbiota
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