Project Details
Abstract
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
Wider research context / theoretical framework
Ageing 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. 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 our research suggest beneficial short-term effects of nitrate-rich BRJ on blood pressure and vascular inflammation markers in healthy older adults.
Hypotheses / research questions / objectives
We propose a clinical study 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. Our primary hypothesis is that the increased dietary nitrate intake lowers blood pressure and improves vascular function. Our 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.
Approach / methods
This randomized, placebo-controlled crossover study will involve two 4-week treatment periods, consisting of interventions with nitrate-rich BRJ and nitrate-depleted BRJ, separated by a 4-week washout period. Thirty- five men and women, between the ages of 55 and 70 years, who have been diagnosed with grade 1 hypertension will be recruited. Twenty-nine participants will be required to complete the study, based on power/sample size calculations with the forearm blood flow (FBF) response to acetylcholine and 24 h- ambulatory systolic blood pressure as the primary endpoints. Principal secondary endpoints are the number of CD11b-expressing blood granulocytes and the FBF response to glyceryltrinitrate. Among various additional secondary and exploratory endpoints, we will measure plasma nitrate and nitrite and a broad range of inflammation biomarkers. Furthermore, we will analyze the oral microbiome.
Level of originality / innovation
Beneficial effects of nitrate have predominantly been observed in healthy populations, but evidence of cardiovascular benefits and anti-inflammatory effects in clinical populations is limited. With this study, we address the need to determine the efficacy of dietary nitrate to improve cardiovascular health and counteract chronic low-grade inflammation in humans at risk of CVD.
Wider research context / theoretical framework
Ageing 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. 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 our research suggest beneficial short-term effects of nitrate-rich BRJ on blood pressure and vascular inflammation markers in healthy older adults.
Hypotheses / research questions / objectives
We propose a clinical study 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. Our primary hypothesis is that the increased dietary nitrate intake lowers blood pressure and improves vascular function. Our 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.
Approach / methods
This randomized, placebo-controlled crossover study will involve two 4-week treatment periods, consisting of interventions with nitrate-rich BRJ and nitrate-depleted BRJ, separated by a 4-week washout period. Thirty- five men and women, between the ages of 55 and 70 years, who have been diagnosed with grade 1 hypertension will be recruited. Twenty-nine participants will be required to complete the study, based on power/sample size calculations with the forearm blood flow (FBF) response to acetylcholine and 24 h- ambulatory systolic blood pressure as the primary endpoints. Principal secondary endpoints are the number of CD11b-expressing blood granulocytes and the FBF response to glyceryltrinitrate. Among various additional secondary and exploratory endpoints, we will measure plasma nitrate and nitrite and a broad range of inflammation biomarkers. Furthermore, we will analyze the oral microbiome.
Level of originality / innovation
Beneficial effects of nitrate have predominantly been observed in healthy populations, but evidence of cardiovascular benefits and anti-inflammatory effects in clinical populations is limited. With this study, we address the need to determine the efficacy of dietary nitrate to improve cardiovascular health and counteract chronic low-grade inflammation in humans at risk of CVD.
| Status | Not started |
|---|
Collaborative partners
- University of Vienna (lead)
- Medizinische Universität Wien
- Sozialmedizinisches Zentrum Süd – Kaiser-Franz-Josef-Spital
- Queensland University of Technology
- Flinders University
- Edith Cowan University
Keywords
- inorganic nitrate-nitrite-nitric oxide pathway
- oral microbiome
- chronic low-grade inflammation
- vascular integrity
- hypertension
- cardiovascular health