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The role of dietary nitrate and the oral microbiome on blood pressure and vascular tone

Published online by Cambridge University Press:  07 December 2020

H. S. Alzahrani
Affiliation:
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6DZ, UK Department of Food Science and Nutrition, King Saud University, PO Box 2454, Riyadh 11451, Saudi Arabia
K. G. Jackson
Affiliation:
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6DZ, UK
D. A. Hobbs
Affiliation:
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6DZ, UK
J. A. Lovegrove*
Affiliation:
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6DZ, UK
*
*Corresponding author: Professor J. A. Lovegrove, fax +44 118 3787708, email j.a.lovegrove@reading.ac.uk

Abstract

There is increasing evidence for the health benefits of dietary nitrates including lowering blood pressure and enhancing cardiovascular health. Although commensal oral bacteria play an important role in converting dietary nitrate to nitrite, very little is known about the potential role of these bacteria in blood pressure regulation and maintenance of vascular tone. The main purpose of this review is to present the current evidence on the involvement of the oral microbiome in mediating the beneficial effects of dietary nitrate on vascular function and to identify sources of inter-individual differences in bacterial composition. A systematic approach was used to identify the relevant articles published on PubMed and Web of Science in English from January 1950 until September 2019 examining the effects of dietary nitrate on oral microbiome composition and association with blood pressure and vascular tone. To date, only a limited number of studies have been conducted, with nine in human subjects and three in animals focusing mainly on blood pressure. In general, elimination of oral bacteria with use of a chlorhexidine-based antiseptic mouthwash reduced the conversion of nitrate to nitrite and was accompanied in some studies by an increase in blood pressure in normotensive subjects. In conclusion, our findings suggest that oral bacteria may play an important role in mediating the beneficial effects of nitrate-rich foods on blood pressure. Further human intervention studies assessing the potential effects of dietary nitrate on oral bacteria composition and relationship to real-time measures of vascular function are needed, particularly in individuals with hypertension and those at risk of developing CVD.

Type
Review Article
Copyright
© The Author(s), 2020. Published by Cambridge University Press on behalf of The Nutrition Society

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References

Mathers, CD & Loncar, D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3, e442.CrossRefGoogle ScholarPubMed
Isaura, ER, Chen, YC & Yang, SH (2018) The association of food consumption scores, body shape index, and hypertension in a seven-year follow-up among Indonesian adults: a longitudinal study. Int J Environ Res Public Health 15, 175.CrossRefGoogle Scholar
Weir, S, Juhasz, A, Puelles, J, et al. (2017) Relationship between initial therapy and blood pressure control for high-risk hypertension patients in the UK: a retrospective cohort study from the THIN general practice database. BMJ Open 7, e015527.CrossRefGoogle Scholar
Bryan, N (2018) Functional nitric oxide nutrition to combat cardiovascular disease. Curr Atheroscler Rep 20, 21.CrossRefGoogle ScholarPubMed
Jones, NRV, Tong, TYN & Monsivais, P (2018) Meeting UK dietary recommendations is associated with higher estimated consumer food costs: an analysis using the National Diet and Nutrition Survey and consumer expenditure data, 2008–2012. Public Health Nutr 21, 948956.CrossRefGoogle ScholarPubMed
Siervo, M, Lara, J, Chowdhury, S, et al. (2015) Effects of the Dietary Approach to Stop Hypertension (DASH) diet on cardiovascular risk factors: a systematic review and meta-analysis. Br J Nutr 113, 115.CrossRefGoogle ScholarPubMed
Serra-Majem, L, Roman, B & Estruch, R (2006) Scientific evidence of interventions using the Mediterranean diet: a systematic review. Nutr Rev 64, S27S47.CrossRefGoogle ScholarPubMed
Bhupathiraju, SN, Wedick, NM, Pan, A, et al. (2013) Quantity and variety in fruit and vegetable intake and risk of coronary heart disease. Am J Clin Nutr 98, 15141523.CrossRefGoogle ScholarPubMed
Bahadoran, Z, Mirmiran, P, Kabir, A, et al. (2017) The nitrate-independent blood pressure-lowering effect of beetroot juice: a systematic review and meta-analysis. Adv Nutr 8, 830838.CrossRefGoogle ScholarPubMed
Larsen, FJ, Ekblom, B, Sahlin, K, et al. (2006) Effects of dietary nitrate on blood pressure in healthy volunteers. N Engl J Med 355, 27922793.CrossRefGoogle ScholarPubMed
Broxterman, RM, La Salle, DT, Zhao, J, et al. (2019) Influence of dietary inorganic nitrate on blood pressure and vascular function in hypertension: prospective implications for adjunctive treatment. J Appl Physiol 127, 10851094.CrossRefGoogle ScholarPubMed
D’El-Rei, J, Cunha, AR, Trindade, M, et al. (2016) Beneficial effects of dietary nitrate on endothelial function and blood pressure levels. Int J Hypertens 2016, 6791519.CrossRefGoogle ScholarPubMed
Velmurugan, S, Gan, JM, Rathod, KS, et al. (2016) Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 103, 2538.CrossRefGoogle ScholarPubMed
Lidder, S & Webb, AJ (2013) Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate–nitrite–nitric oxide pathway. Br J Clin Pharmacol 75, 677696.CrossRefGoogle ScholarPubMed
Jackson, JK, Patterson, AJ, MacDonald-Wicks, LK, et al. (2018) The role of inorganic nitrate and nitrite in cardiovascular disease risk factors: a systematic review and meta-analysis of human evidence. Nutr Rev 76, 348371.CrossRefGoogle ScholarPubMed
Blekkenhorst, LC, Bondonno, NP, Liu, AH, et al. (2018) Nitrate, the oral microbiome, and cardiovascular health: a systematic literature review of human and animal studies. Am J Clin Nutr 107, 504522.CrossRefGoogle Scholar
Khambata, RS, Ghosh, SM, Rathod, KS, et al. (2017) Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque. Proc Natl Acad Sci U S A 114, E550E559.CrossRefGoogle ScholarPubMed
Webb, AJ, Patel, N, Loukogeorgakis, S, et al. (2008) Acute blood pressure lowering, vasoprotective and anti-platelet properties of dietary nitrate via bioconversion to nitrate. Hypertension 51, 784790.CrossRefGoogle Scholar
Eggebeen, J, Kim-Shapiro, D, Haykowsky, M, et al. (2016) One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction. JACC Heart Fail 4, 428437.CrossRefGoogle ScholarPubMed
Liu, AH, Bondonno, CP, Russell, J, et al. (2019) Relationship of dietary nitrate intake from vegetables with cardiovascular disease mortality: a prospective study in a cohort of older Australians. Eur J Nutr 58, 27412753.CrossRefGoogle Scholar
Gee, LC & Ahluwalia, A (2016) Dietary nitrate lowers blood pressure: epidemiological, pre-clinical experimental and clinical trial evidence. Curr Hypertens Rep 18, 17.CrossRefGoogle ScholarPubMed
Koutsoumanis, K, Allende, A, Alvarez-Ordóñez, A, et al. (2020) Scientific Opinion on the update of the list of QPS-recommended biological agents intentionally added to food or feed as notified to EFSA (2017–2019). EFSA J 18, 5966.Google ScholarPubMed
Knobeloch, L, Salna, B, Hogan, A, et al. (2000) Blue babies and nitrate-contaminated well water. Environ Health Perspect 108, 675678.CrossRefGoogle ScholarPubMed
World Cancer Research Fund & American Institute for Cancer Research (2017) Diet, nutrition, physical activity and colorectal cancer. Continuous Update Project 2017. https://www.wcrf.org/sites/default/files/Colorectal-Cancer-2017-Report.pdf (accessed December 2020).Google Scholar
Bryan, NS, Tribble, G & Angelov, N (2017) Oral microbiome and nitric oxide: the missing link in the management of blood pressure. Curr Hypertens Rep 19, 33.CrossRefGoogle ScholarPubMed
Govoni, M, Jansson, , Weitzberg, E, et al. (2008) The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide 19, 333337.CrossRefGoogle ScholarPubMed
Hezel, MP & Weitzberg, E (2015) The oral microbiome and nitric oxide homoeostasis. Oral Dis 21, 716.CrossRefGoogle ScholarPubMed
Hyde, E, Luk, B, Tribble, GD, et al. (2014) Characterization of the rat oral microbiome and the effects of dietary nitrate. Free Radic Biol Med 77, 249257.CrossRefGoogle ScholarPubMed
Woessner, M, Smoliga, JM, Tarzia, B, et al. (2016) A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load. Nitric Oxide 54, 17.CrossRefGoogle ScholarPubMed
Al Khodor, S, Reichert, B & Shatat, IF (2017) The microbiome and blood pressure: can microbes regulate our blood pressure? Front Pediatr 5, 138.CrossRefGoogle ScholarPubMed
Ma, L, Hu, L, Feng, X, et al. (2018) Nitrate and nitrite in health and disease. Aging Dis 9, 938945.CrossRefGoogle ScholarPubMed
Goh, CE, Trinh, P, Colombo, PC, et al. (2019) Association between nitrate-reducing oral bacteria and cardiometabolic outcomes: results from ORIGINS. J Am Heart Assoc 8, e013324.CrossRefGoogle ScholarPubMed
Raju, TN (2000) The Nobel chronicles. 1998: Robert Francis Furchgott (b 1911), Louis J Ignarro (b 1941), and Ferid Murad (b 1936). Lancet 356, 346.CrossRefGoogle Scholar
Parthasarathy, DK & Bryan, NS (2012) Sodium nitrite: the “cure” for nitric oxide insufficiency. Meat Sci 92, 274279.CrossRefGoogle ScholarPubMed
Xu, KY, Huso, DL, Dawson, TM, et al. (1999) Nitric oxide synthase in cardiac sarcoplasmic reticulum. Proc Natl Acad Sci U S A 96, 657662.CrossRefGoogle ScholarPubMed
Kelm, M (1999) Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1411, 273289.CrossRefGoogle ScholarPubMed
Hord, NG, Tang, Y & Bryan, NS (2009) Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr 90, 110.CrossRefGoogle ScholarPubMed
Brkić, D, Bošnir, J, Bevardi, M, et al. (2107) Nitrate in leafy green vegetables and estimated intake. Afr J Tradit Complement Altern Med 14, 3141.CrossRefGoogle Scholar
Burleigh, MC, Liddle, L, Monaghan, C, et al. (2018) Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria. Free Radic Biol Med 120, 8088.CrossRefGoogle ScholarPubMed
Kapil, V, Haydar, SMA, Pearl, V, et al. (2013) Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med 55, 93100.CrossRefGoogle ScholarPubMed
Doel, JJ, Benjamin, N, Hector, MP, et al. (2005) Evaluation of bacterial nitrate reduction in the human oral cavity. Eur J Oral Sci 113, 1419.CrossRefGoogle ScholarPubMed
Hyde, ER, Andrade, F, Vaksman, Z, et al. (2014) Metagenomic analysis of nitrate-reducing bacteria in the oral cavity : implications for nitric oxide homeostasis. PLOS ONE 9, e88645.CrossRefGoogle ScholarPubMed
Koch, CD, Gladwin, MT, Freeman, BA, et al. (2017) Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health. Free Radic Biol Med 105, 4867.CrossRefGoogle ScholarPubMed
Iijima, K, Henry, E, Moriya, A, et al. (2002) Dietary nitrate generates potentially mutagenic concentrations of nitric oxide at the gastroesophageal junction. Gastroenterology 122, 12481257.CrossRefGoogle ScholarPubMed
Sobko, T, Huang, L, Midtvedt, T, et al. (2006) Generation of NO by probiotic bacteria in the gastrointestinal tract. Free Radic Biol Med 41, 985991.CrossRefGoogle ScholarPubMed
Petersson, J, Phillipson, M, Jansson, , et al. (2007) Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol 292, 718724.CrossRefGoogle ScholarPubMed
Waldum, HL, Kleveland, PM & Sørdal, ØF (2016) Helicobacter pylori and gastric acid: an intimate and reciprocal relationship. Therap Adv Gastroenterol 9, 836844.CrossRefGoogle ScholarPubMed
Gilchrist, M, Shore, AC & Benjamin, N (2011) Inorganic nitrate and nitrite and control of blood pressure. Cardiovasc Res 89, 492498.CrossRefGoogle ScholarPubMed
Lundberg, JO & Weitzberg, E (2013) Biology of nitrogen oxides in the gastrointestinal tract. Gut 62, 616629.CrossRefGoogle ScholarPubMed
Bos, PMJ, Wedel, M, Hezel, MP, et al. (2017) Nitric oxide microbiota and the nitrogen cycle: implications in the development and progression of CVD and CKD. Free Radic Biol Med 55, 6470.Google Scholar
Lundberg, JO (2008) Nitric oxide in the gastrointestinal tract: role of bacteria. Biosci Microflora 27, 109112.CrossRefGoogle Scholar
Petra, CV, Rus, A & Dumitrașcu, DL (2017) Gastric microbiota: tracing the culprit. Clujul Med 90, 369376.Google ScholarPubMed
Forsythe, SJ, Dolbyt, JM, Websters, ADB, et al. (2018) Nitrate- and nitrite-reducing bacteria in the achlorhydric stomach. J Med Microbiol 25, 253259.CrossRefGoogle Scholar
Tiso, M & Schechter, AN (2015) Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions. PLOS ONE 10, e0119712.CrossRefGoogle ScholarPubMed
Sobko, T, Reinders, C, Norin, E, et al. (2018) Gastrointestinal nitric oxide generation in germ-free and conventional rats. Am J Physiol Gastrointest Liver Physiol 287, G993G997.CrossRefGoogle Scholar
Parham, NJ & Gibson, GR (2000) Microbes involved in dissimilatory nitrate reduction in the human large intestine. FEMS Microbiol Ecol 31, 2128.CrossRefGoogle ScholarPubMed
Sobko, T, Reinders, CI, Jansson, , et al. (2005) Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite. Nitric Oxide 13, 272278.CrossRefGoogle ScholarPubMed
Briskey, D, Tucker, PS, Johnson, DW, et al. (2016) Microbiota and the nitrogen cycle: implications in the development and progression of CVD and CKD. Nitric Oxide 57, 6470.CrossRefGoogle ScholarPubMed
Marsh, PD, Head, DA & Devine, DA (2015) Ecological approaches to oral biofilms: control without killing. Caries Res 49, Suppl. 1, 4654.CrossRefGoogle ScholarPubMed
Ji, B, Yang, K, Zhu, L, et al. (2015) Aerobic denitrification: a review of important advances of the last 30 years. Biotechnol Bioprocess Eng 20, 643651.CrossRefGoogle Scholar
Schreiber, F, Stief, P, Gieseke, A, et al. (2010) Denitrification in human dental plaque. BMC Biol 8, 24.CrossRefGoogle ScholarPubMed
Takaya, N, Catalan-Sakairi, MAB, Sakaguchi, Y, et al. (2003) Aerobic denitrifying bacteria that produce low levels of nitrous oxide. Appl Environ Microbiol 69, 31523157.CrossRefGoogle ScholarPubMed
Sparacino-Watkins, C, Stolz, JF, et al. (2014) Nitrate and periplasmic nitrate reductases. Chem Soc Rev 43, 676706.CrossRefGoogle ScholarPubMed
Herrero, A, Flores, E & Imperial, J (2019) Nitrogen assimilation in bacteria. In Encyclopedia of Microbiology, 4th ed., pp. 280300 [Schmidt, T, editor]. Cambridge, MA: Press, Academic, Elsevier, Inc.Google Scholar
Dodsworth, JA, Hungate, BA & Hedlund, BP (2011) Ammonia oxidation, denitrification and dissimilatory nitrate reduction to ammonium in two US Great Basin hot springs with abundant ammonia-oxidizing archaea. Environ Microbiol 13, 23712386.CrossRefGoogle ScholarPubMed
Tomasova, L, Konopelski, P & Ufnal, M (2016) Gut bacteria and hydrogen sulfide: the new old players in circulatory system homeostasis. Molecules 21, 1558.CrossRefGoogle ScholarPubMed
Higgins, JPT, Sterne, JAC, Savović, J, et al. (2016) A revised tool for assessing risk of bias in randomized trials. Cochrane Database Syst Rev, issue 10, CD201601.Google Scholar
Hooijmans, CR, Rovers, MM, De Vries, RBM, et al. (2014) SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 14, 43.CrossRefGoogle ScholarPubMed
Petersson, J, Carlström, M, Schreiber, O, et al. (2009) Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med 46, 10681075.CrossRefGoogle ScholarPubMed
Pinheiro, LC, Ferreira, GC, Amaral, H, et al. (2016) Oral nitrite circumvents antiseptic mouthwash-induced disruption of entrosalivary circuit of nitrate and promotes nitrosation and blood pressure lowering effect. Free Radic Biol Med 101, 226235.CrossRefGoogle Scholar
Delmastro-Greenwood, M, Hughan, KS, Vitturi, DA, et al. (2015) Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes. Free Radic Biol Med 89, 333341.CrossRefGoogle ScholarPubMed
Montenegro, MF, Sundqvist, ML, Nihlén, C, et al. (2016) Profound differences between humans and rodents in the ability to concentrate salivary nitrate: implications for translational research. Redox Biol 10, 206210.CrossRefGoogle ScholarPubMed
Ahmed, KA, Nichols, AL, Honavar, J, et al. (2107) Measuring nitrate reductase activity from human and rodent tongues. Nitric Oxide 66, 6270.CrossRefGoogle Scholar
Mitsui, T & Harasawa, R (2017) The effects of essential oil, povidone-iodine, and chlorhexidine mouthwash on salivary nitrate/nitrite and nitrate-reducing bacteria. J Oral Sci 59, 597601.CrossRefGoogle ScholarPubMed
Bondonno, CP, Croft, KD, Puddey, IB, et al. (2012) Nitrate causes a dose-dependent augmentation of nitric oxide status in healthy women. Food Funct 3, 522527.CrossRefGoogle ScholarPubMed
Bondonno, CP, Liu, AH, Croft, KD, et al. (2015) Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women. Am J Hypertens 28, 572575.CrossRefGoogle ScholarPubMed
Tribble, GD, Angelov, N, Weltman, R, et al. (2019) Frequency of tongue cleaning impacts the human tongue microbiome composition and enterosalivary circulation of nitrate. Front Cell Infect Microbiol 9, 39.CrossRefGoogle ScholarPubMed
Sundqvist, ML, Lundberg, JO & Weitzberg, E (2016) Effects of antiseptic mouthwash on resting metabolic rate: a randomized, double-blind, crossover study. Nitric Oxide 61, 3844.CrossRefGoogle ScholarPubMed
McDonagh, STJ, Wylie, LJ, Winyard, PG, et al. (2015) The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite concentration and exercise blood pressure. Int J Sports Med 36, 11771185.Google ScholarPubMed
Sandell, MA & Collado, MC (2018) Genetic variation in the TAS2R38 taste receptor contributes to the oral microbiota in North and South European locations: a pilot study. Genes Nutr 13, 30.CrossRefGoogle Scholar
Li, J, Li, M, Rzhetskaya, M, et al. (2014) Comparative analysis of the human saliva microbiome from different climate zones: Alaska, Germany, and Africa. BMC Microbiol 14, 316.CrossRefGoogle ScholarPubMed
Hansen, TH, Kern, T, Bak, EG, et al. (2018) Impact of a vegan diet on the human salivary microbiota. Sci Rep 8, 5847.CrossRefGoogle ScholarPubMed
Eldeghaidy, S, Thomas, D, Skinner, M, et al. (2018) An automated method to detect and quantify fungiform papillae in the human tongue: validation and relationship to phenotypical differences in taste perception. Physiol Behav 184, 226234.CrossRefGoogle ScholarPubMed
Kishi, M, Ohara-Nemoto, Y, Takahashi, M, et al. (2010) Relationship between oral status and prevalence of periodontopathic bacteria on the tongues of elderly individuals. J Med Microbiol 59, 13541359.CrossRefGoogle ScholarPubMed
Vanhatalo, A, Blackwell, JR, L’Heureux, JE, et al. (2018) Nitrate-Responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans. Free Radic Biol Med 124, 2130.CrossRefGoogle ScholarPubMed
Kapil, V, Rathod, KS, Khambata, RS, et al. (2018) Sex differences in the nitrate–nitrite–NO● pathway: role of oral nitrate-reducing bacteria. Free Radic Biol Med 126, 113121.CrossRefGoogle ScholarPubMed
Liddle, L, Burleigh, MC, Monaghan, C, et al. (2019) Variability in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: an assessment of the critical difference. Nitric Oxide 83, 110.CrossRefGoogle ScholarPubMed
Koopman, JE, Buijs, MJ, Brandt, BW, et al. (2016) Nitrate and the origin of saliva influence composition and short chain fatty acid production of oral microcosms. Microb Ecol 72, 479492.CrossRefGoogle ScholarPubMed
Hohensinn, B, Haselgrübler, R, Müller, U, et al. (2016) Sustaining elevated levels of nitrite in the oral cavity through consumption of nitrate-rich beetroot juice in young healthy adults reduces salivary pH. Nitric Oxide 60, 1015.CrossRefGoogle ScholarPubMed
Gordon, JH, LaMonte, MJ, Genco, RJ, et al. (2019) Is the oral microbiome associated with blood pressure in older women? High Blood Press Cardiovasc Prev 26, 217225.CrossRefGoogle ScholarPubMed
Stellato, G, Utter, DR, Voorhis, A, et al. (2017) A few Pseudomonas oligotypes dominate in the meat and dairy processing environment. Front Microbiol 8, 264.CrossRefGoogle ScholarPubMed
Gonzalez, A, Hyde, E, Sangwan, N, et al. (2016) Migraines are correlated with higher levels of nitrate-, nitrite-, and nitric oxide-reducing oral microbes in the American Gut Project cohort. mSystems 1, e00105e00116.CrossRefGoogle ScholarPubMed
Kondo, T, Ueyama, J, Imai, R, et al. (2006) Association of abdominal circumference with serum nitric oxide concentration in healthy population. Environ Health Prev Med 11, 321325.CrossRefGoogle ScholarPubMed
Piva, SJ, Tatsch, E, De Carvalho, JAM, et al. (2013) Assessment of inflammatory and oxidative biomarkers in obesity and their associations with body mass index. Inflammation 36, 226231.CrossRefGoogle ScholarPubMed
Li, R, Lyn, D, Lapu-Bula, R, et al. (2004) Relation of endothelial nitric oxide synthase gene to plasma nitric oxide level, endothelial function, and blood pressure in African Americans. Am J Hypertens 17, 560567.CrossRefGoogle ScholarPubMed
Akram, F, Fuchs, D, Daue, M, et al. (2018) Association of plasma nitrite levels with obesity and metabolic syndrome in the Old Order Amish. Obes Sci Pract 4, 468476.CrossRefGoogle ScholarPubMed
Lundberg, JO, Carlström, M & Weitzberg, E (2018) Metabolic effects of dietary nitrate in health and disease. Cell Metab 28, 922.CrossRefGoogle ScholarPubMed
Henning, SM, Yang, J, Shao, P, et al. (2017) Health benefit of vegetable/fruit juice-based diet: role of microbiome. Sci Rep 7, 2167.CrossRefGoogle ScholarPubMed
Ghosh, TS, Rampelli, S, Jeffery, IB, et al. (2020) Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries. Gut 69, 12181228.CrossRefGoogle ScholarPubMed
Kilian, M, Chapple, ILC, Hannig, M, et al. (2016) The oral microbiome – an update for oral healthcare professionals. Br Dent J 221, 657666.CrossRefGoogle ScholarPubMed
Qu, XM, Wu, ZF, Pang, BX, et al. (2016) From nitrate to nitric oxide: the role of salivary glands and oral bacteria. J Dent Res 95, 14521456.CrossRefGoogle ScholarPubMed
Liccardo, D, Cannavo, A, Spagnuolo, G, et al. (2019) Periodontal disease: a risk factor for diabetes and cardiovascular disease. Int J Mol Sci 20, 1414.CrossRefGoogle ScholarPubMed
Lovegrove, JA, Stainer, A & Hobbs, DA (2017) Role of flavonoids and nitrates in cardiovascular health. Proc Nutr Soc 76, 8395.CrossRefGoogle Scholar
McDonagh, STJ, Wylie, LJ, Morgan, PT, et al. (2018) A randomised controlled trial exploring the effects of different beverages consumed alongside a nitrate-rich meal on systemic blood pressure. Nutr Health 24, 183192.CrossRefGoogle ScholarPubMed
Gago, B, Nyström, T, Cavaleiro, C, et al. (2008) The potent vasodilator ethyl nitrite is formed upon reaction of nitrite and ethanol under gastric conditions. Free Radic Biol Med 45, 404412.CrossRefGoogle ScholarPubMed
Omar, SA, Artime, E & Webb, AJ (2012) A comparison of organic and inorganic nitrates/nitrites. Nitric Oxide 26, 229240.CrossRefGoogle ScholarPubMed