Effects of Dietary Nitrate on Vascular Function, Blood Pressure, the Oral Microbiome, and Biomarkers of Systemic Inflammation in Hypertensive Older Adults: a Randomized, Placebo-controlled Crossover Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change in forearm blood flow (FBF) response to acetylcholine
研究概览
简要总结
The risk for cardiovascular diseases (CVD) increases with advancing age. Developing effective lifestyle-based strategies to promote, preserve or restore cardiovascular health with aging is a high priority. The overall aim of this clinical research is to investigate the innovative concept that an increased intake of dietary nitrate (through beetroot juice) could be a feasible adjuvant therapy to treat elevated blood pressure and improve blood vessel function in older adults.
Inorganic dietary nitrate, found in beetroot and green leafy vegetables, is a source of nitric oxide (NO), a signaling molecule that is important for cardiovascular health. NO is also produced in the human body, but the body's production and availability of NO decrease during ageing and CVD. The declined NO availability is associated with impaired blood vessel function, unresolved inflammatory responses, and an increased CVD risk. Dietary nitrate is an additional NO source. Following the intake of nitrate, NO is produced in a pathway that involves commensal bacteria in the mouth. So far, little is known about whether dietary nitrate improves cardiovascular health in older populations with high blood pressure.
The aim of this randomized, placebo-controlled crossover study is to investigate whether the daily intake of nitrate-rich beetroot juice over four weeks translates into improved cardiovascular health-related outcomes in older adults with treated mild high blood pressure. Men and women, between the ages of 55 and 70 years, who have been diagnosed with grade 1 high blood pressure and who are taking two or more blood-pressure lowering medications will be recruited. The study will investigate whether the increased dietary nitrate intake further lowers blood pressure and improves blood vessel function. A specific aim is to examine whether the nitrate intake results in favorable changes in the oral bacteria community and the systemic inflammatory status, and whether these changes correlate with cardiovascular-related outcomes. This research will offer information on the value of dietary nitrate to counteract chronic inflammation, the latter of which plays a role in developing or worsening cardiovascular disorders, such as high blood pressure.
The expected results of this study will provide important new evidence of whether nitrate-rich beetroot juice could be a key component of therapeutic interventions to improve cardiovascular health in individuals with high blood pressure.
详细描述
This clinical research is funded by the Austrian Science Fund (FWF, project number: KLI 858). It is based on close collaborations between the University of Vienna and the Medical University of Vienna, with the Department of Clinical Pharmacology at the Medical University of Vienna as the clinical trial center and Prof. M.D. Michael Wolzt as the trial center's coordinating physician. The sponsor is the University of Vienna, as represented by the Principal Investigator Dr. Oliver Neubauer (Research Platform Active Ageing). International collaborations include Dr. Catherine Bondonno, Prof. Hodgson (both Edith Cowan University) Dr. Jonathan Peake (Queensland University of Technology), and Prof. Richard Woodman (Flinders University) (all Australia).
Wider research context / theoretical framework:
Aging is a major risk factor for cardiovascular disease (CVD). Developing effective strategies to improve cardiovascular health with ageing is a high priority. Emerging data indicate that inorganic dietary nitrate, found in green leafy vegetables and beetroot juice (BRJ), is important for cardiovascular health (Blekkenhorst et al. 2018). These data suggest that small increases in nitrate intake among those with elevated risk for CVD would have a substantial impact, by improving the bioavailability of nitric oxide (NO) through the enterosalivary nitrate- nitrite-NO pathway (involving the oral microbiome). Results from the study group's research suggest beneficial short-term effects of nitrate-rich BRJ on blood pressure and vascular inflammation markers in healthy older adults (Raubenheimer et al. 2017).
Hypotheses / research questions / objectives:
The proposed clinical study is aimed to examine whether the daily consumption of 2×70 mL BRJ over 4 weeks translates into improved clinical outcomes in older adults with treated grade 1 hypertension. The primary hypothesis is that the increased dietary nitrate intake lowers blood pressure and improves vascular function. The secondary hypotheses are that the increased dietary nitrate intake results in changes in the oral microbiome, favorably modulates the systemic inflammatory status, and that these changes correlate with cardiovascular-related outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
The two treatment arm will consist of a 4-week high-nitrate (HI-NI) intervention (using nitrate-rich beetroot juice) and a 4-week low-nitrate (LO-NI) intervention using nitrate-depleted beetroot juice as the placebo. All products will be obtained from the same supplier (James White Drinks Ltd., UK). The nitrate-depleted beetroot juice is generated for research purposes only. The two juices will be indistinguishable by taste, color, smell and packaging. The investigators involved in the data acquisition and analysis will be blind to the trial allocation until the study has been completed and all analyses have been performed.
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ambulant male and females between 55 and 75 years of age, inclusive
- •Resting systolic blood pressure between 130 and 170 mmHg, inclusive
- •Written informed consent
排除标准
- •Diastolic blood pressure >110 mmHg
- •Type 1 or 2 diabetes mellitus or fasting glucose >7.0 mmol/L
- •Any evidence of acute or chronic disease such as symptomatic cardiovascular or peripheral vascular disease, moderate or severe chronic kidney disease (estimated glomerular filtration rate (GFR) <50 ml/min)), or cancer which is not in remission
- •Consumption of ≥5 serves of vegetables per day
- •Consumption of a diet estimated to contain >200 mg/d of nitrate
- •Being vegan or vegetarian
- •BMI ≥35 kg/m2 or <18.5 kg/m2
- •Use of nitric oxide donors, organic nitrites/nitrates, sildenafil and related drugs, anti-coagulation, non-steroidal anti-inflammatory or statin-related drugs
- •Use of antibacterial mouthwash (volunteers willing to cease using antibacterial mouth wash for a period of 4 weeks before randomisation will be included)
- •Use of antibiotics (within previous 2 months)
- •A change in drug therapy likely to influence blood pressure or major secondary outcomes within the previous month, or the likelihood that drug therapy would change during the study
- •Current or recent (within previous 3 months) engagement in regular structured exercise training (more than 2 hours of moderate to more intense exercise per week)
- •Current or recent (within previous 6 months) loss or gain of >6% of body weight
- •Current or recent (<12 months) regular smoking of >5 cigarettes/day
- •Alcohol intake >140 g per week for women or >210 g per week for men and/or binge drinking behaviour
- •Inability or unwillingness to follow the study protocol
- •Pregnancy or lactation
研究组 & 干预措施
High-nitrate (HI-NI) intervention
The 'active treatment' arm will involve daily consumption of 2×70 mL nitrate-rich (HI-NI) beetroot juice (70 mL with breakfast and 70 mL with dinner) over an intervention period of 4 weeks.
干预措施: High-nitrate intervention (Dietary Supplement)
Low-nitrate (LO-NI) intervention
The placebo treatment arm daily consumption of 2×70 mL nitrate-depleted (LO-NI) beetroot juice (70 mL with breakfast and 70 mL with dinner) an intervention period of 4 weeks.
干预措施: Low-nitrate intervention (Dietary Supplement)
结局指标
主要结局
Change in forearm blood flow (FBF) response to acetylcholine
时间窗: Change from baseline FBF at 4 weeks of the LO-NI intervention
Vascular function
Change in 24 hour-ambulatory systolic blood pressure
时间窗: Change from baseline 24 hour-ambulatory systolic blood pressure at 4 weeks of the LO-NI intervention
Blood pressure
Change in forearm blood flow (FBF) response to acetylcholine
时间窗: Change from baseline FBF at 4 weeks of the HI-NI intervention
Vascular function
Change in 24 hour-ambulatory systolic blood pressure
时间窗: Change from baseline 24 hour-ambulatory systolic blood pressure at 4 weeks of the HI-NI intervention
Blood pressure
次要结局
- Change in granulocyte CD11b expression(Change from baseline granulocyte CD11b expression at 4 weeks of the LO-NI intervention)
- Change in forearm blood flow (FBF) response to glyceryltrinitrate(Change from baseline FBF at 4 weeks of the LO-NI intervention)
- Change in granulocyte CD11b expression(Change from baseline granulocyte CD11b expression at 4 weeks of the HI-NI intervention)
- Change in forearm blood flow (FBF) response to glyceryltrinitrate(Change from baseline FBF at 4 weeks of the HI-NI intervention)
研究者
Oliver Neubauer
Dr PhD, PD
University of Vienna