Cardiovascular Health
Conditions
Keywords
microbiome, nitrate, diet, dietary nitrate, cardiovascular
Brief summary
A growing body of data shows that the enteral microbiome has an effect on cardiovascular diseases. Exogenous inorganic dietary nitrate mediates cardioprotective effects and has been shown to have an influence on the oral microbiome. The nutritional aspects of these cardioprotective effects are particularly intriguing since nitrate is abundant in our everyday diet. Whether dietary nitrate influences the enteral microbiome and downstream metabolites like short-chain fatty acids (SCFA) and TMAO will be investigated in the present study.
Interventions
DIETARY_SUPPLEMENTNitrate
Dietary inorganic nitrate (0,12 mmol sodium-nitrate/kg BW/day) dissolved in 200 ml tap water. Supplementation for 30 days.
DIETARY_SUPPLEMENTControl
Dietary sodium-chloride (0,12 mmol sodium-chloride/kg BW/day) dissolved in 200 ml tap water. Supplementation for 30 days.
Sponsors
University Hospital, Essen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients aged 40-80 years * no regular medication intake * no chronic diseases
Exclusion criteria
* Regular systemic drug intake * Active smoking * Chronic diseases * Acute diarrhea or vomiting * Short gut syndrome * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of the enteral microbiome composition | 30 days | Changes in enteral microbiome composition in stool samples at baseline and after 30 days of placebo/verum supplementation. The 16S rRNA amplicon reads obtained from an Illumina MiSeq System will be analyzed using pipeline QIIME2 (v. 2019.1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of the oral microbiome composition | 30 days | Changes in oral microbiome composition in oral swabs samples at baseline and after 30 days of placebo/verum supplementation. The 16S rRNA amplicon reads obtained from an Illumina MiSeq System will be analyzed using pipeline QIIME2 (v. 2019.1). |
| Change of circulating SCFA levels | 30 days | Changes in circulating SCFA blood levels at baseline and after 30 days of placebo/verum supplementation will be measured by high-performance liquid chromatography. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of the nitrate-nitrite-NO metabolism | 30 days | Changes of nitrate and nitrite content in plasma measured by ENO-20 analysis at baseline and after 30 days of placebo/verum supplementation. |
| Genetic variants (single nucleotide polymorphism) | 30 days | The effect of the genes NOS3 and GUCY1A3 variation on dietary nitrate response. Genetic polymorphism will be measured by qPCR and analyzed by allelic discrimination. |
| Changes in the oral-enteral microbiome axis | 30 days | Changes in oral-enteral microbiome axis composition in oral swabs and stool samples at baseline and after 30 days of placebo/verum supplementation. The 16S rRNA amplicon reads obtained from an Illumina MiSeq System will be analyzed using pipeline QIIME2 (v. 2019.1). |
| Changes in TMAO levels | 30 days | Changes in TMAO blood levels at baseline and after 30 days of placebo/verum supplementation will be measured by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). |
| Epigenetic changes | 30 days | Changes of DNA methylation analysis by pyrosequencing at baseline and after 30 days of placebo/verum supplementation. |
| Changes in arterial stiffness parameters | 30 days | Changes in cardiovascular function measured by arterial stiffness parameters as pulse wave velocity measured in m/s at baseline and after 30 days of placebo/verum supplementation. |
| Changes in blood pressure | 30 days | Changes in cardiovascular function measured by systolic and diastolic blood pressure in mmHg at baseline and after 30 days of placebo/verum supplementation. |
Countries
Germany
Outcome results
None listed