Identification of potential plant-based functional for protection against salt-induced endothelial dysfunction

Dr Louie, Chun Yu Jimmy   (Principal Investigator (PI))

Dr Wan Jennifer Man Fan   (Co-Investigator)

18

2017-04-01

2018-09-30

119000

Identification of potential plant-based functional for protection against salt-induced endothelial dysfunction

beetroot, blood pressure, celery, endothelial dysfunction, plant extract, vegetables

NutritionFood Science

Physical Sciences (P)

201611160038

Seed Fund for PI Research – Translational and Applied Research

2016

Completed

Hypertension is a common cardiovascular disease in Hong Kong and around the world. It was estimated that around 1 in 3 adults in Hong Kong suffer from some forms of hypertension, and many do not know about it (1). Up to 26% of deaths in Hong Kong could be hypertension-related (1). Strategies that improve blood pressure control are therefore highly beneficial to the society. Endothelial dysfunction refers to the impaired ability of blood vessels to balance between vasodilation and vasoconstriction (2), hence it is closely related to blood pressure control. ED is commonly assessed using flow mediated dilation (FMD) and pulse wave velocity (PWV), alongside measurements of systolic and diastolic blood pressure. FMD and PWV are validated clinical measures of the arterial stiffness (3, 4), where a stiffer artery indicates endothelial dysfunction. High dietary salt intake has been identified as one of the main contributing factors of hypertension and adverse cardiovascular health. Previous studies (5, 6) have demonstrated the adverse effect of a high salt meal on endothelial dysfunction, suggesting that the chronic adverse effect of a high salt diet on vascular health may be a result of daily impairment of endothelial function. Such thesis supports interventions which aim at ameliorating the adverse postprandial effects of high salt foods on endothelial function. Dietary habits of Hong Kong citizens, which include high intake of high salt processed foods (e.g. processed meat), and high frequency of eating out where high salt foods are common (e.g. food with salty gravy), contribute to a habitual high salt intake. The Total Diet Study (7) conducted by the Centre for Food Safety found that more than 60% of the population exceeded the recommended maximum level of intake of salt (5 grams/day). While reduction in dietary salt intake is the most direct strategy for improving endothelial function and vascular health, many people lack the motivation to reduce their salt intake despite efforts from the government and public health agencies. This could mainly be attributed to the common¬¬ perception that foods low/lower in salt are less palatable (8). Clearly an alternative strategy which could protect individuals with high salt intake from adverse vascular¬¬¬ health would be beneficial and welcome by many. Dietary nitrate and nitrite, as well as flavonoids, have been shown to be potential food-based candidates for such strategy. There is strong evidence from both epidemiological and experimental studies to support the beneficial effects of fruit and vegetables (9), a rich source of dietary nitrate (NO3-), nitrite (NO2-) and flavonoids, on blood pressure and vascular health. Dietary nitrate and nitrite are thought to provide exogenous substrates for the production of nitric oxide (NO), a potent vasodilator normally produced endogenously via the action of nitric oxide synthase (NOS). Studies have demonstrated that consumption of foods high in dietary nitrate (e.g. beetroot juice) is able to increase circulating NO levels, independent of endothelial NOS (eNOS) activity (10). Dietary flavonoids (e.g. anthocyanins), on the other hand, have been shown to improve endothelial function by activating the NO-cGMP signaling pathway independent of nitrate (11). While the independent effects of dietary nitrate, nitrite and flavonoids have been examined in several studies, only limited evidence exists regarding their combined effects. Natural dietary sources of nitrate/nitrite often contain flavonoids and other phytochemicals such as betalain in beetroot (12) which may also positively affect endothelial function via an antioxidant-related mechanism. Given nitrate and flavonoids have been demonstrated to improve endothelial function via different mechanisms, synergistic effects among these compounds may be present. This is important for developing a potent combination dietary supplement formulation for protection against salt-induced endothelial dysfunction. We therefore hypothesized that dietary supplementation of nitrate and flavonoids may improve endothelial function; and that there is synergism in their beneficial effects when consumed simultaneously. References: 1. School of Public Health, The University of Hong Kong,. Internet: https://familycohort.sph.hku.hk/en/node/53 (accessed 15th Dec 2016). 2. Hadi HAR, Carr CS, Al Suwaidi J. Endothelial Dysfunction: Cardiovascular Risk Factors, Therapy, and Outcome. Vas Health Risk Management 2005;1(3):183-98. 3. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound Assessment of Flow-Mediated Dilation. Hypertension 2010;55(5):1075-85. doi: 10.1161/hypertensionaha.110.150821. 4. Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, Koji Y, Hori S, Yamamoto Y. Validity, Reproducibility, and Clinical Significance of Noninvasive Brachial-Ankle Pulse Wave Velocity Measurement. Hypertension Res 2002;25(3):359-64. doi: 10.1291/hypres.25.359. 5. Dickinson KM, Clifton PM, Burrell LM, Barrett PHR, Keogh JB. Postprandial effects of a high salt meal on serum sodium, arterial stiffness, markers of nitric oxide production and markers of endothelial function. Atherosclerosis 2014;232(1):211-6. doi: 10.1016/j.atherosclerosis.2013.10.032. 6. Dickinson KM, Clifton PM, Keogh JB. Endothelial function is impaired after a high-salt meal in healthy subjects. Am J Clin Nutr 2011;93(3):500-5. doi: 10.3945/ajcn.110.006155. 7. Centre for Food Safety, Food and Environmental Hygiene Department. The First Hong Kong Total Diet Study: Minerals. Centre for Food Safety, 2014. 8. De Kock HL, Zandstra EH, Sayed N, Wentzel-Viljoen E. Liking, salt taste perception and use of table salt when consuming reduced-salt chicken stews in light of South Africa's new salt regulations. Appetite 2016;96:383-90. doi: http://dx.doi.org/10.1016/j.appet.2015.09.026. 9. Blanch N, Clifton PM, Keogh JB. A systematic review of vascular and endothelial function: Effects of fruit, vegetable and potassium intake. Nutr Metab Cardiovas Dis 2015;25(3):253-66. doi: http://dx.doi.org/10.1016/j.numecd.2014.10.001. 10. Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, et al. Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite. Hypertension 2008;51(3):784-90. doi: 10.1161/hypertensionaha.107.103523. 11. Zhu Y, Xia M, Yang Y, Liu F, Li Z, Hao Y, Mi M, Jin T, Ling W. Purified Anthocyanin Supplementation Improves Endothelial Function via NO-cGMP Activation in Hypercholesterolemic Individuals. Clin Chem 2011;57(11):1524-33. doi: 10.1373/clinchem.2011.167361. 12. Strack D, Vogt T, Schliemann W. Recent advances in betalain research. Phytochemistry 2003;62(3):247-69. doi: http://dx.doi.org/10.1016/S0031-9422(02)00564-2. 13. Hord NG, Tang Y, Bryan NS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr 2009;90(1):1-10. doi: 10.3945/ajcn.2008.27131.