Dietary interventions for fetal growth restriction – therapeutic potential of dietary nitrate supplementation in pregnancy
Open accessAbstract
Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short‐ and long‐term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid l‐arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the ‘alternative NO pathway’. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non‐pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth. image
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Clinical studies confirm that nitrate supplementation improves endothelial function, reduces blood pressure, and enhances tissue perfusion; there is also potential for benefits in cardiovascular and pregnancy-related conditions.
“Clinical studies confirm that nitrate supplementation improves endothelial function, reduces blood pressure, and enhances tissue perfusion. There is also potential for benefits in cardiovascular and pregnancy-related conditions [83,84,85].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [85]
Beetroot is one of the richest dietary sources of inorganic nitrate (250-400 mg/100 g fresh weight), depending on agronomic and storage conditions.
“Depending on agronomic and storage conditions, it is also one of the richest dietary sources of inorganic nitrate (250–400 mg/100 g fresh weight) [80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [85]
Cites
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · see citing works
Inorganic 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 · see citing works
Webb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · cited 1× · see citing works
“…nitrate supplementation have also been shown in terms of enhancing exercise performance and blood flow in both humans and animal models (Ferguson et al. 2013; Jones, 2014), as well as reducing myocardial damage caused by acute ischaemia–reperfusion injury (Webb et al. 2004; Salloum et al. 2015).”
BackgroundLidder, S., & Webb, A. J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04420.x · Cited by 360 · cited 1× · see citing works
“Bioactivation of dietary nitrate (found in abundance in green leafy vegetables and beetroot; Lidder & Webb, 2013) involves firstly its reduction to nitrite, predominantly via bacterial nitrate reductase enzymes in the oral cavity.”
BackgroundDiagnosis and management of fetal growth restriction
Bamfo, J. E. A. K., & Odibo, A. O. (2011) · Journal of Pregnancy · doi:10.1155/2011/640715 · Cited by 178 · see citing works
Reconciling the nutritional and glucocorticoid hypotheses of fetal programming
Cottrell, E. C., Holmes, M. C., Livingstone, D. E., Kenyon, C. J., & Seckl, J. R. (2012) · The FASEB Journal · doi:10.1096/fj.12-203489 · Cited by 102 · cited 2× · see citing works
“, 2013), caloric restriction (Lederman & Rosso, 1980) and macro- or micronutrient deficiencies (Cottrell et al., 2012; Liu et al., 2013) have contributed significantly to our understanding of pathways by which a poor maternal diet can affect maternal health, placental development and fetal growth.”
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Neurodevelopment at Age 10 Years of Children Born <28 Weeks With Fetal Growth Restriction
Korzeniewski, S., Allred, E., Joseph, R., Heeren, T., Kuban, K., O'Shea, T. M., & Leviton, A. (2017) · Pediatrics · doi:10.1542/peds.2017-0697 · Cited by 66 · see citing works
Volino-Souza, M., de Oliveira, G. V., & Alvares, T. (2018) · British Journal of Nutrition · doi:10.1017/s0007114518002441 · Cited by 33 · see citing works
“Low FMD values in pregnancy are associated with health complications of the mother and fetus, such as pre-eclampsia and FGR.”
BackgroundInfluentialMolema, F., Gleich, F., Burgard, P., van der Ploeg, A. T., Summar, M. L., Chapman, K. A., Lund, A. M., Rizopoulos, D., Kölker, S., Williams, M., et al. (2019) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2019.02.003 · Cited by 34 · see citing works
Prophylaxis and treatment of foetal growth restriction.
Nawathe, A., & David, A. (2018) · Best Practice & Research: Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2018.02.007 · Cited by 26 · see citing works
Nitric oxide metabolism in the human placenta during aberrant maternal inflammation
Mukosera, G. T., Clark, T. C., Ngo, L., Liu, T., Schroeder, H. J., Power, G. G., Yellon, S. M., Parast, M. M., & Blood, A. B. (2020) · The Journal of Physiology · doi:10.1113/jp279057 · Cited by 18 · see citing works
“the whole placenta following its endogenous synthesis under physiological or pathophysiological conditions, or following its pharmacological application during pregnancy (Cottrell & Sibley, 2015; Cottrell et al. 2017).”
BackgroundInfluentialLi, Y., & Liu, J.-Q. (2020) · Medicine · doi:10.1097/md.0000000000018897 · Cited by 17 · see citing works
Nitrate-rich dietary supplementation during pregnancy: The pros and cons.
Bahadoran, Z., Mirmiran, P., Azizi, F., & Ghasemi, A. (2018) · Pregnancy Hypertension · doi:10.1016/j.preghy.2017.12.010 · Cited by 16 · see citing works
Recurrence Risk of Fetal Growth Restriction
Blue, N. R., Pagé, J., & Silver, R. M. (2021) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/j.ogc.2021.03.002 · Cited by 15 · see citing works
Iron nitrosyl complexes are formed from nitrite in the human placenta
Mukosera, G. T., Principe, P., Mata‐Greenwood, E., Liu, T., Schroeder, H. J., Parast, M. M., & Blood, A. B. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102078 · Cited by 11 · see citing works
“(2022) 298(7) 102078 described previously (Kanady et al.”
BackgroundMethodInfluentialStress during pregnancy and its life‐long consequences for the infant
Fowden, A. (2017) · Journal of Physiology · doi:10.1113/jp274444 · Cited by 9 · see citing works
Does the Oral Microbiome Play a Role in Hypertensive Pregnancies?
Willmott, T., McBain, A. J., Humphreys, G. J., Myers, J., & Cottrell, E. C. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00389 · Cited by 10 · see citing works
“In terms of translating these findings into pregnancy research, beetroot juice is more attractive as an intervention due to it being potentially more acceptable than traditional anti-hypertensive chemotherapeutic medications (Fisk and Atun, 2008; Cottrell et al., 2017).”
BackgroundSelf-citationTropea, T., Nihlen, C., Weitzberg, E., Lundberg, J., Wareing, M., Greenwood, S., Sibley, C., & Cottrell, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094500 · Cited by 4 · see citing works
“From a translational perspective, interventions that increase circulating nitrite concentrations, such as dietary nitrate supplementation, may provide a reservoir of NO-generating potential within the placenta [26].”
BackgroundSelf-citationKurhaluk, N., Kołodziejska, R., Buyun, L., Kamiński, P., & Tkaczenko, H. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27083461 · Cited by 3 · see citing works
“There is also potential for benefits in cardiovascular and pregnancy-related conditions [83–85].”
Kardol, L. R., Rhaman, A., Kelty, E., Morgan, S., Russell, D. J., Gebremedhin, A., Bourke, S., & Wyrwoll, C. (2025) · International Journal of Hygiene and Environmental Health · doi:10.1016/j.ijheh.2025.114712 · Cited by 3 · see citing works
Cassiani, A., Aloia, T., Sousa-Vidal, É. K., Podgaec, S., Piccinato, C. D. A., & Serrano-Nascimento, C. (2024) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-4292-2024-0085 · Cited by 3 · see citing works
Andonotopo, W., Bachnas, M. A., Prabowo, W., Yuliantara, E. E., Pramono, M. B. A., Dewantiningrum, J., Lukas, E., Sanjaya, I. N. H., Wiradnyana, A. A. G. P., Kusuma, A. A. N. J., et al. (2026) · MGM Journal of Medical Sciences · doi:10.4103/mgmj.mgmj_24_26 · Cited by 1 · see citing works
Perchard, R., Garner, T., Higgins, L. E., Murray, P., Roslan, A., Johnstone, E. D., Stevens, A., & Clayton, P. E. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48020238 · Cited by 1 · see citing works
“NO synthesis is catalysed by endothelial nitric oxide synthase (eNOS) enzymes [28], which are expressed in vascular endothelial cells.”
Self-citationKloss, O., Jebb, M., Chartrand, L., Chudley, A., Eskin, M. N. A., & Suh, M. (2022) · Nutrients · doi:10.3390/nu14153233 · Cited by 1 · see citing works
“Precarious access to financial resources, food, and goods creates an unfavorable dietary environment for an expecting mother and a child, leading to a multitude of negative health consequences such as low birth weights [13], damage to fetal development [14], maternal and fetal malnutrition [3], obesity [15], and intra…”
BackgroundRISING STARS: Bumps and bacteria: influence of the maternal microbiota on pregnancy outcomes
Willmott, T., & Cottrell, E. C. (2024) · Journal of Endocrinology · doi:10.1530/joe-23-0360
Self-citationDeshpande, M., Kajale, N., Raiturker, A. P., Gupte, S., Patankar, L., & Khadilkar, A. (2026) · Nutrition & Food Science · doi:10.1108/nfs-02-2025-0064
INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE
Pham, M. S., Nguyen, V., & Tran, D. (2018) · Journal of Medicine and Pharmacy · doi:10.34071/jmp.2018.6.25a
INTRAUTERINE GROWTH RETARDATION - A REVIEW ARTICLE
Minh, S. P., Quoc, H. N. V., & Dinh, V. T. (2018) · Volume 8 Issue 6 · doi:10.34071/jmp.2018.6.25
- Authors
- Cottrell, E., Tropea, T., Ormesher, L., Greenwood, S., Wareing, M., Johnstone, E., Myers, J., & Sibley, C.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Cottrell, Elizabeth
- ORCID
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2017-02-27
- Volume
- 595
- Issue
- 15
- Pages
- 5095-5102
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC5538211
- OpenAlex
- W2572195918
- Cited by
- 26
- References
- 0
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 1 · 2018: 5 · 2017: 2
- FWCI
- 0.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- British Heart Foundation (FS/15/31/31418)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- fetal growth restriction, nitrate supplementation, nitric oxide bioavailability, pregnancy, L-arginine, nitric oxide synthase, maternal diet, fetal growth, blood flow
- MeSH terms
- Animals, Diet, Female, Fetal Growth Retardation, Humans, Nitrates, Nitric Oxide, Placenta, Pregnancy, Uterus, Dietary Supplements, Maternal Nutritional Physiological Phenomena
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