Skip to main content
Erschienen in: European Journal of Nutrition 2/2016

01.03.2016 | Original Contribution

Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis

verfasst von: Jose Lara, Ammar W. Ashor, C. Oggioni, A. Ahluwalia, John C. Mathers, Mario Siervo

Erschienen in: European Journal of Nutrition | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Background

Diets rich in inorganic nitrate are associated with lower blood pressure, an effect that may be mediated by an improvement of endothelial function (EF). Therefore, a systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted to examine the effects of inorganic nitrate and beetroot supplementation on measures of EF.

Methods

MEDLINE, EMBASE and Scopus databases were searched from inception until November 2014. Specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing inorganic nitrate or beetroot supplementation with placebo control groups; and (3) trials reporting effects of these interventions on outcomes of vascular function. Random-effect models were used to assess the pooled effect sizes showed as standardised mean differences (SMD).

Results

Nine crossover trials and three parallel trials met our inclusion criteria. The trials were conducted between 2008 and 2014 and included a total of 246 participants with 10–64 participants per study. The duration of each intervention ranged from 1.5 h to 28 days. Inorganic nitrate and beetroot consumption was associated with an improvement in vascular function (SMD 0.36; 95 % CI 0.16, 0.56; P < 0.001). The effect on EF was significantly associated with the dose of inorganic nitrate (β = 0.04, SE = 0.01, P < 0.001), age (β = −0.01, SE = 0.004, P = 0.02), baseline BMI (β = −0.04, SE = 0.02, P = 0.05) and systolic BP (β = −0.01, SE = 0.005, P = 0.02).

Conclusions

Inorganic nitrate and beetroot supplementation was associated with beneficial effects on EF. These effects appear to be reduced in older subjects and in subjects with greater cardiometabolic risk.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Vallance P, Webb DJ (2000) Vascular endothelium in human physiology and pathophysiology. Routledge, LondonCrossRef Vallance P, Webb DJ (2000) Vascular endothelium in human physiology and pathophysiology. Routledge, LondonCrossRef
2.
Zurück zum Zitat Moncada S, Higgs EA (2006) Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176:213–254CrossRef Moncada S, Higgs EA (2006) Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176:213–254CrossRef
3.
Zurück zum Zitat Haynes WG, Webb DJ (1998) Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 16:1081–1098CrossRef Haynes WG, Webb DJ (1998) Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 16:1081–1098CrossRef
7.
Zurück zum Zitat Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S (2009) Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 32:S314–S321. doi:10.2337/dc09-S330 CrossRef Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S (2009) Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 32:S314–S321. doi:10.​2337/​dc09-S330 CrossRef
12.
Zurück zum Zitat Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R (2009) Increase in fasting vascular endothelial function after short-term oral l-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr 89:77–84. doi:10.3945/ajcn.2008.26544 CrossRef Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R (2009) Increase in fasting vascular endothelial function after short-term oral l-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr 89:77–84. doi:10.​3945/​ajcn.​2008.​26544 CrossRef
15.
16.
Zurück zum Zitat Cunnington C, Van Assche T, Shirodaria C, Kylintireas I, Lindsay AC, Lee JM, Antoniades C, Margaritis M, Lee R, Cerrato R, Crabtree MJ, Francis JM, Sayeed R, Ratnatunga C, Pillai R, Choudhury RP, Neubauer S, Channon KM (2012) Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease. Circulation 125:1356–1366. doi:10.1161/circulationaha.111.038919 CrossRef Cunnington C, Van Assche T, Shirodaria C, Kylintireas I, Lindsay AC, Lee JM, Antoniades C, Margaritis M, Lee R, Cerrato R, Crabtree MJ, Francis JM, Sayeed R, Ratnatunga C, Pillai R, Choudhury RP, Neubauer S, Channon KM (2012) Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease. Circulation 125:1356–1366. doi:10.​1161/​circulationaha.​111.​038919 CrossRef
17.
Zurück zum Zitat Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H (1994) Stomach NO synthesis. Nature 368:502CrossRef Benjamin N, O’Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie H (1994) Stomach NO synthesis. Nature 368:502CrossRef
18.
Zurück zum Zitat Lundberg JO, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–1546CrossRef Lundberg JO, Weitzberg E, Lundberg JM, Alving K (1994) Intragastric nitric oxide production in humans: measurements in expelled air. Gut 35:1543–1546CrossRef
19.
Zurück zum Zitat Larsen F, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E (2006) Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 28:2792–2793CrossRef Larsen F, Ekblom B, Sahlin K, Lundberg JO, Weitzberg E (2006) Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 28:2792–2793CrossRef
20.
Zurück zum Zitat Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A (2008) Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 51:784–790. doi:10.1161/HYPERTENSIONAHA.107.103523 CrossRef Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A (2008) Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 51:784–790. doi:10.​1161/​HYPERTENSIONAHA.​107.​103523 CrossRef
21.
Zurück zum Zitat Gladwin MT, Schechter AN, Kim-Shapiro DB, Patel RP, Hogg N, Shiva S, Cannon RO, Kelm M, Wink DA, Espey MG, Oldfield EH, Pluta RM, Freeman BA, Lancaster JR, Feelisch M, Lundberg JO (2005) The emerging biology of the nitrite anion. Nat Chem Biol 1:308–314CrossRef Gladwin MT, Schechter AN, Kim-Shapiro DB, Patel RP, Hogg N, Shiva S, Cannon RO, Kelm M, Wink DA, Espey MG, Oldfield EH, Pluta RM, Freeman BA, Lancaster JR, Feelisch M, Lundberg JO (2005) The emerging biology of the nitrite anion. Nat Chem Biol 1:308–314CrossRef
22.
Zurück zum Zitat Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, Cabrales P, Fago A, Feelisch M, Ford PC, Freeman BA, Frenneaux M, Friedman J, Kelm M, Kevil CG, Kim-Shapiro DB, Kozlov AV, Lancaster JR Jr, Lefer DJ, McColl K, McCurry K, Patel RP, Petersson J, Rassaf T, Reutov VP, Richter-Addo GB, Schechter A, Shiva S, Tsuchiya K, Van Faassen EE, Webb AJ, Zuckerbraun BS, Zweier JL, Weitzberg E (2009) Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol 5:865–869CrossRef Lundberg JO, Gladwin MT, Ahluwalia A, Benjamin N, Bryan NS, Butler A, Cabrales P, Fago A, Feelisch M, Ford PC, Freeman BA, Frenneaux M, Friedman J, Kelm M, Kevil CG, Kim-Shapiro DB, Kozlov AV, Lancaster JR Jr, Lefer DJ, McColl K, McCurry K, Patel RP, Petersson J, Rassaf T, Reutov VP, Richter-Addo GB, Schechter A, Shiva S, Tsuchiya K, Van Faassen EE, Webb AJ, Zuckerbraun BS, Zweier JL, Weitzberg E (2009) Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol 5:865–869CrossRef
23.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J, Altman DG, The PG (2009) Preferred Reporting Items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097CrossRef Moher D, Liberati A, Tetzlaff J, Altman DG, The PG (2009) Preferred Reporting Items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097CrossRef
24.
Zurück zum Zitat Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC (2011) The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. doi:10.1136/bmj.d5928 Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC (2011) The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. doi:10.​1136/​bmj.​d5928
25.
Zurück zum Zitat Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. In: Interventions CHfSRo (ed)the cochrane collaboration. www.cochrane-handbook.org. Higgins J, Green S (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. In: Interventions CHfSRo (ed)the cochrane collaboration. www.​cochrane-handbook.​org.
26.
Zurück zum Zitat DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRef DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188CrossRef
28.
29.
Zurück zum Zitat Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A (2010) Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 56:274–281. doi:10.1161/HYPERTENSIONAHA.110.153536 CrossRef Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A (2010) Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension 56:274–281. doi:10.​1161/​HYPERTENSIONAHA.​110.​153536 CrossRef
30.
Zurück zum Zitat Bahra M, Kapil V, Pearl V, Ghosh S, Ahluwalia A (2012) Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers. Nitric Oxide 26:197–202. doi:10.1016/j.niox.2012.01.004 CrossRef Bahra M, Kapil V, Pearl V, Ghosh S, Ahluwalia A (2012) Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers. Nitric Oxide 26:197–202. doi:10.​1016/​j.​niox.​2012.​01.​004 CrossRef
31.
32.
Zurück zum Zitat Ghosh SM, Kapil V, Fuentes-Calvo I, Bubb KJ, Pearl V, Milsom AB, Khambata R, Maleki-Toyserkani S, Yousuf M, Benjamin N, Webb AJ, Caulfield MJ, Hobbs AJ, Ahluwalia A (2013) Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential. Hypertension 61:1091–1102. doi:10.1161/HYPERTENSIONAHA.111.00933 CrossRef Ghosh SM, Kapil V, Fuentes-Calvo I, Bubb KJ, Pearl V, Milsom AB, Khambata R, Maleki-Toyserkani S, Yousuf M, Benjamin N, Webb AJ, Caulfield MJ, Hobbs AJ, Ahluwalia A (2013) Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential. Hypertension 61:1091–1102. doi:10.​1161/​HYPERTENSIONAHA.​111.​00933 CrossRef
33.
Zurück zum Zitat Hobbs DA, Goulding MG, Nguyen A, Malaver T, Walker CF, George TW, Methven L, Lovegrove JA (2013) Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men: a randomized controlled trial. J Nutr 143:1399–1405. doi:10.3945/jn.113.175778 CrossRef Hobbs DA, Goulding MG, Nguyen A, Malaver T, Walker CF, George TW, Methven L, Lovegrove JA (2013) Acute ingestion of beetroot bread increases endothelium-independent vasodilation and lowers diastolic blood pressure in healthy men: a randomized controlled trial. J Nutr 143:1399–1405. doi:10.​3945/​jn.​113.​175778 CrossRef
35.
Zurück zum Zitat Ashor AW, Jajja A, Sutyarjoko A, Brandt K, Qadir O, Lara J, Siervo M (2014) Effects of beetroot juice supplementation on microvascular blood flow in older overweight and obese subjects: a pilot randomised controlled study. J Hum Hypertens. doi:10.1038/jhh.2014.114 Ashor AW, Jajja A, Sutyarjoko A, Brandt K, Qadir O, Lara J, Siervo M (2014) Effects of beetroot juice supplementation on microvascular blood flow in older overweight and obese subjects: a pilot randomised controlled study. J Hum Hypertens. doi:10.​1038/​jhh.​2014.​114
36.
Zurück zum Zitat Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A (2014) Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. doi:10.1161/HYPERTENSIONAHA.114.04675 Kapil V, Khambata RS, Robertson A, Caulfield MJ, Ahluwalia A (2014) Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. doi:10.​1161/​HYPERTENSIONAHA.​114.​04675
37.
Zurück zum Zitat Rammos C, Hendgen-Cotta UB, Sobierajski J, Bernard A, Kelm M, Rassaf T (2014) Dietary nitrate reverses vascular dysfunction in older adults with moderately increased cardiovascular risk. J Am Coll Cardiol 63:1584–1585. doi:10.1016/j.jacc.2013.08.691 CrossRef Rammos C, Hendgen-Cotta UB, Sobierajski J, Bernard A, Kelm M, Rassaf T (2014) Dietary nitrate reverses vascular dysfunction in older adults with moderately increased cardiovascular risk. J Am Coll Cardiol 63:1584–1585. doi:10.​1016/​j.​jacc.​2013.​08.​691 CrossRef
38.
Zurück zum Zitat Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD (1985) Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol 110:1582–1591. doi:10.1152/japplphysiol.00071.2011 CrossRef Kenjale AA, Ham KL, Stabler T, Robbins JL, Johnson JL, Vanbruggen M, Privette G, Yim E, Kraus WE, Allen JD (1985) Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. J Appl Physiol 110:1582–1591. doi:10.​1152/​japplphysiol.​00071.​2011 CrossRef
39.
Zurück zum Zitat Percival RS, Challacombe SJ, Marsh PD (1991) Age-related microbiological changes in the salivary and plaque microflora of healthy adults. J Med Microbiol 35:5–11CrossRef Percival RS, Challacombe SJ, Marsh PD (1991) Age-related microbiological changes in the salivary and plaque microflora of healthy adults. J Med Microbiol 35:5–11CrossRef
41.
Zurück zum Zitat Zweier JL, Samouilov A, Kuppusamy P (1999) Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta 1411:250–262CrossRef Zweier JL, Samouilov A, Kuppusamy P (1999) Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta 1411:250–262CrossRef
42.
Zurück zum Zitat Lyons D, Roy S, Patel M, Benjamin N, Swift CG (1997) Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age. Clin Sci (Lond) 93:519–525CrossRef Lyons D, Roy S, Patel M, Benjamin N, Swift CG (1997) Impaired nitric oxide-mediated vasodilatation and total body nitric oxide production in healthy old age. Clin Sci (Lond) 93:519–525CrossRef
43.
Zurück zum Zitat Siervo M, Lara J, Ogbonmwan I, Mathers JC (2013) Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. The Journal of nutrition 143:818–826. doi:10.3945/jn.112.170233 CrossRef Siervo M, Lara J, Ogbonmwan I, Mathers JC (2013) Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. The Journal of nutrition 143:818–826. doi:10.​3945/​jn.​112.​170233 CrossRef
Metadaten
Titel
Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis
verfasst von
Jose Lara
Ammar W. Ashor
C. Oggioni
A. Ahluwalia
John C. Mathers
Mario Siervo
Publikationsdatum
01.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 2/2016
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-015-0872-7

Weitere Artikel der Ausgabe 2/2016

European Journal of Nutrition 2/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.