Nitrate-Rich Fruit and Vegetable Supplement Reduces Blood Pressure in Normotensive Healthy Young Males without Significantly Altering Flow-Mediated Vasodilation: A Randomized, Double-Blinded, Controlled Trial

Karen L Sweazea, Carol S Johnston, Brendan Miller, Eric Gumpricht, Karen L Sweazea, Carol S Johnston, Brendan Miller, Eric Gumpricht

Abstract

Nitric oxide (NO) is a primary vasodilatory factor released from endothelial cells of the peripheral vasculature. NO production is stimulated through enzymatic-dependent mechanisms via NO synthase and from dietary intake of nitrate-containing foods or supplements. We evaluated the efficacy of a nitrate-rich fruit and vegetable liquid supplement (FVS, AMPED NOx, Isagenix International LLC) versus a juice low in nitrates (prune juice, PRU) on circulating nitrates/nitrites as well as cardiovascular parameters in 45 healthy normotensive men (18-40 y). Blood pressure, flow-mediated dilation (FMD), and plasma nitrates and nitrites were measured at baseline and after two weeks of supplementation (2 oz/d). Subjects also completed questionnaires on sleep quality and mood since these measures have been associated with endothelial function. In contrast to PRU, FVS significantly increased plasma nitrates and nitrites (+67%, p < 0.001) and decreased diastolic blood pressure (-9%, p=0.029) after two weeks. The change in FMD for FVS supplementation versus PRU supplementation was not significant (+2% vs. -9%, respectively, p=0.145). Changes in sleep quality or total mood state did not differ between groups after the 2-week study. Thus, the nitrate-rich FVS supplement increased plasma NO and reduced diastolic blood pressure in young normotensive men, but increased plasma NO was not associated with improvements in FMD, mood, or sleep. This trial is registered with ClinicalTrials.gov NCT03486145.

Figures

Figure 1
Figure 1
Consort diagram.
Figure 2
Figure 2
Two-week change in (a) plasma nitrates/nitrites and (b) diastolic blood pressure in individual participants consuming two ounces of a fruit and vegetable blend (FVS; n=23) or prune juice (PRU; n=22).

References

    1. Webb A. J., Patel N., Loukogeorgakis S., et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. 2008;51(3):784–790. doi: 10.1161/hypertensionaha.107.103523.
    1. Siervo M., Lara J., Ogbonmwan I., Mathers J. C. Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. Journal of Nutrition. 2013;143(6):818–826. doi: 10.3945/jn.112.170233.
    1. Blekkenhorst L. C., Sim M., Bondonno C. P., et al. Cardiovascular health benefits of specific vegetable types: a narrative review. Nutrients. 2018;10(5):p. 595. doi: 10.3390/nu10050595.
    1. Bondonno C. P., Blekkenhorst L. C., Liu A. H., et al. Vegetable-derived bioactive nitrate and cardiovascular health. Molecular Aspects of Medicine. 2018;61:83–91. doi: 10.1016/j.mam.2017.08.001.
    1. Lidder S., Webb A. J. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway. British Journal of Clinical Pharmacology. 2013;75(3):677–696. doi: 10.1111/j.1365-2125.2012.04420.x.
    1. Nabrzyski M., Gajewska R. The content of nitrates and nitrites in fruits, vegetables and other foodstuffs. Roczniki Panstwowego Zakladu Higieny. 1994;45(3):167–180.
    1. Förstermann U., Sessa W. C. Nitric oxide synthases: regulation and function. European Heart Journal. 2012;33(7):829–837. doi: 10.1093/eurheartj/ehr304.
    1. Rajapakse N. W., Mattson D. L. Role of L-arginine in nitric oxide production in health and hypertension. Clinical and Experimental Pharmacology and Physiology. 2009;36(3):249–255. doi: 10.1111/j.1440-1681.2008.05123.x.
    1. Versari D., Daghini E., Virdis A., Ghiadoni L., Taddei S. Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care. 2009;32(2):S314–S321. doi: 10.2337/dc09-s330.
    1. Lundberg J. O., Weitzberg E., Gladwin M. T. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nature Reviews Drug Discovery. 2008;7(2):156–167. doi: 10.1038/nrd2466.
    1. Rocha B. S., Gago B., Barbosa R. M., Laranjinha J. Dietary polyphenols generate nitric oxide from nitrite in the stomach and induce smooth muscle relaxation. Toxicology. 2009;265(1-2):41–48. doi: 10.1016/j.tox.2009.09.008.
    1. Cosby K., Partovi K. S., Crawford J. H., et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nature Medicine. 2003;9(12):1498–1505. doi: 10.1038/nm954.
    1. Cosby Harris R. A., Nishiyama S. K., Wray D. W., Richardson R. S. Ultrasound assessment of flow-mediated dilation. Hypertension. 2010;55(5):1075–1085. doi: 10.1161/hypertensionaha.110.150821.
    1. Joris P. J., Mensink R. P. Beetroot juice improves in overweight and slightly obese men postprandial endothelial function after consumption of a mixed meal. Atherosclerosis. 2013;231(1):78–83. doi: 10.1016/j.atherosclerosis.2013.09.001.
    1. Kapil V., Khambata R. S., Robertson A., Caulfield M. J., Ahluwalia A. Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study. Hypertension. 2015;65(2):320–327. doi: 10.1161/hypertensionaha.114.04675.
    1. Google Trends for beet juice, May 2017, .
    1. The Grocer. Beetroot’s use as an ingredient up 20% due to superfood status. May 2017. .
    1. Jones A. M. Influence of dietary nitrate on the physiological determinants of exercise performance: a critical review. Applied Physiology, Nutrition, and Metabolism. 2014;39(9):1019–1028. doi: 10.1139/apnm-2014-0036.
    1. Cooper D. C., Tomfohr L. M., Milic M. S., et al. Depressed mood and flow-mediated dilation: a systematic review and meta-analysis. Psychosomatic Medicine. 2011;73(5):360–369. doi: 10.1097/psy.0b013e31821db79a.
    1. Ohno Y., Hashiguchi T., Maenosono R., et al. The diagnostic value of endothelial function as a potential sensor of fatigue in health. Vascular Health and Risk Management. 2010;2010(6):135–144. doi: 10.2147/VHRM.S8950.
    1. Aziz M., Ali S. S., Das S., et al. Association of subjective and objective sleep duration as well as sleep quality with non-invasive markers of sub-clinical cardiovascular disease (CVD): a systematic review. Journal of Atherosclerosis and Thrombosis. 2016;24(3):208–226. doi: 10.5551/jat.36194.
    1. Montero D., Padilla J., Diaz-Cañestro C., et al. Flow-mediated dilation in athletes: influence of aging. Medicine & Science in Sports & Exercise. 2014;46(11):2148–2158. doi: 10.1249/mss.0000000000000341.
    1. Green D. J., Rowley N., Spence A., et al. Why isn’t flow-mediated dilation enhanced in athletes? Medicine & Science in Sports & Exercise. 2013;45(1):75–82. doi: 10.1249/mss.0b013e318269affe.
    1. Godin G., Shephard R. J. A simple method to assess exercise behavior in the community. Canadian Journal of Applied Sport Sciences. 1985;10(3):141–146.
    1. Adkisson E. J., Casey D. P., Beck D. T., Gurovich A. N., Martin J. S., Braith R. W. Central, peripheral and resistance arterial reactivity: fluctuates during the phases of the menstrual cycle. Experimental Biology and Medicine. 2010;235(1):111–118. doi: 10.1258/ebm.2009.009186.
    1. Harris R. A, Tedjasaputra V., Zhao J., Richardson R. S. Premenopausal women exhibit an inherent protection of endothelial function following a high-fat meal. Reproductive Sciences. 2012;19(2):221–228. doi: 10.1177/1933719111418125.
    1. Dalli E., Segarra L., Ruvira J., et al. Brachial artery flow-mediated dilation in healthy men, men with risk factors, and men with acute myocardial infarction. Importance of occlusion-cuff position. Revista Española de Cardiología. 2002;55(9):928–935. doi: 10.1016/s0300-8932(02)76731-6.
    1. Bahra M., Kapil V., Pearl V., Ghosh S., Ahluwalia A. Inorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteers. Nitric Oxide. 2012;26(4):197–202. doi: 10.1016/j.niox.2012.01.004.
    1. Berry M. J., Justus N. W., Hauser J. I., et al. Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. Nitric Oxide. 2015;48:22–30. doi: 10.1016/j.niox.2014.10.007.
    1. Kayano S., Kikuzaki H., Yamada N. F., et al. Antioxidant properties of prunes (Prunus domestica L.) and their constituents. BioFactors. 2004;21(1–4):309–313. doi: 10.1002/biof.552210160.
    1. Bondonno C. P., Liu A. H., Croft K. D., et al. Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women. American Journal of Hypertension. 2015;28(5):572–575. doi: 10.1093/ajh/hpu192.
    1. WHO. WHO STEPwise Approach to Surveillance (STEPS) Geneva, Switzerland: World Health Organization; 2008.
    1. Corretti M. C., Anderson T. J., Benjamin E. J., et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. Journal of the American College of Cardiology. 2002;39(2):257–265. doi: 10.1016/s0735-1097(01)01746-6.
    1. Thijssen D. H. J., Black M. A., Pyke K. E., et al. Assessment of flow mediated dilation in humans: a methodological and physiological guideline. American Journal of Physiology-Heart and Circulatory Physiology. 2011;300(1):H2–H12. doi: 10.1152/ajpheart.00471.2010.
    1. Tinken T. M., Thijssen D. H., Black M. A., Cable N. T., Green D. J. Time course of change in vasodilator function and capacity in response to exercise training in humans. Journal of Physiology. 2008;586(20):5003–5012. doi: 10.1113/jphysiol.2008.158014.
    1. Woodman R. J., Playford D. A., Watts G. F., et al. Improved analysis of brachial artery ultrasound using a novel edge-detection software system. Journal of Applied Physiology. 2001;91(2):929–937. doi: 10.1152/jappl.2001.91.2.929.
    1. Kelm M. Nitric oxide metabolism and breakdown. Biochimica et Biophysica Acta (BBA)-Bioenergetics. 1999;1411(2-3):273–289. doi: 10.1016/s0005-2728(99)00020-1.
    1. McNair D., Lorr A., Droppleman L. EITS Manual for the Profile of Mood States. San Diego, CA, USA: Education and Industrial Testing Service; 1971.
    1. Nyenhuis D. L., Yamamoto C., Luchetta T., Terrien A., Parmentier A. Adult and geriatric normative data and validation of the profile of mood states. Journal of Clinical Psychology. 1999;55(1):79–86. doi: 10.1002/(sici)1097-4679(199901)55:1<79::aid-jclp8>;2-7.
    1. Buysse D. J., Reynolds C. F., III, Monk T. H., Berman S. R., Kupfer D. J. The pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Research. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Bondonno C. P., Yang X., Croft K. D., et al. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radical Biology and Medicine. 2012;52(1):95–102. doi: 10.1016/j.freeradbiomed.2011.09.028.
    1. Neaton J. D., Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Archives of Internal Medicine. 1992;152(1):56–64. doi: 10.1001/archinte.1992.00400130082009.
    1. Semlitsch T., Jeitler K., Berghold A., et al. Long-term effects of weight-reducing diets in people with hypertension. Cochrane Database of Systematic Reviews. 2016;(3) doi: 10.1002/14651858.cd008274.pub3.CD008274
    1. Gay H. C., Rao S. G., Vaccarino V., Ali M. K. Effects of different dietary interventions on blood pressure: systematic review and meta-analysis of randomized controlled trials. Hypertension. 2016;67(4):733–739. doi: 10.1161/hypertensionaha.115.06853.
    1. Yokoyama Y., Nishimura K., Barnard N. D., et al. Vegetarian diets and blood pressure: a meta-analysis. JAMA Internal Medicine. 2014;174(4):577–587. doi: 10.1001/jamainternmed.2013.14547.
    1. Onakpoya I. J., Spencer E. A., Thompson M. J., Heneghan C. J. The effect of chlorogenic acid on blood pressure: a systematic review and meta-analysis of randomized clinical trials. Journal of Human Hypertension. 2015;29(2):77–81. doi: 10.1038/jhh.2014.46.
    1. MacMahon S., Peto R., Cutler J., et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. The Lancet. 1990;335(8692):765–774. doi: 10.1016/0140-6736(90)90878-9.
    1. Lewington S., Clarke R., Qizilbash N., Peto R., Collins R., Prospective Studies Collaboration Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. The Lancet. 2002;360(9349):1903–1913. doi: 10.1016/S0140-6736(02)11911-8.
    1. Gilchrist M., Winyard P. G., Aizawa K., Anning C., Shore A., Benjamin N. Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes. Free Radical Biology and Medicine. 2013;60:89–97. doi: 10.1016/j.freeradbiomed.2013.01.024.
    1. Hobbs D. A., George T. W., Lovegrove J. A. The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies. Nutrition Research Reviews. 2013;266(2):210–222. doi: 10.1017/s0954422413000188.
    1. Lara J., Ashor A. W., Oggioni C., Ahluwalia A., Mathers J. C., Siervo M. Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis. European Journal of Nutrition. 2016;55(2):451–459. doi: 10.1007/s00394-015-0872-7.
    1. Greenland P., Alpert J. S., Beller G. A., et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2010;56(25):e50–e103. doi: 10.1016/j.jacc.2010.09.001.
    1. Atkinson G., Batterham A. M. The clinical relevance of the percentage flow-mediated dilation index. Current Hypertension Reports. 2015;17(2):p. 4. doi: 10.1007/s11906-014-0514-0.
    1. Kuhnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Review of Nutrition and Dietetics. 1976;24:117–191. doi: 10.1159/000399407.
    1. Manach C., Scalbert A., Morand C., Remesy C., Jimenez L. Polyphenols: food sources and bioavailability. American Journal of Clinical Nutrition. 2004;79(5):727–747. doi: 10.1093/ajcn/79.5.727.
    1. Velmurugan S., Kapil V., Ghosh S. M., et al. Antiplatelet effects of dietary nitrate in healthy volunteers: involvement of cGMP and influence of sex. Free Radical Biology and Medicine. 2013;65:1521–1532. doi: 10.1016/j.freeradbiomed.2013.06.031.
    1. Kapil V., Milsom A. B., Okorie M., et al. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension. 2010;56(2):274–281. doi: 10.1161/hypertensionaha.110.153536.
    1. Cooper D. C., Milic M. S., Tafur J. R., et al. Adverse impact of mood on flow-mediated dilation. Psychosomatic Medicine. 2010;72(2):122–127. doi: 10.1097/psy.0b013e3181cdbfc0.
    1. Behl M., Bliwise D., Veledar E., et al. Vascular endothelial function and self-reported sleep. American Journal of the Medical Sciences. 2014;347(6):425–428. doi: 10.1097/maj.0b013e31829bc950.
    1. Cooper D. C., Ziegler M. G., Milic M. S., et al. Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep. Journal of Sleep Research. 2014;23(1):84–93. doi: 10.1111/jsr.12083.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner