Dietary Nitrate and Cardiovascular Health

Physiological Effects of Oral Nitrate on Vascular Function

An expanding number of studies suggest a therapeutic role for nitrate and nitrite, most notably in treatment and prevention of cardiovascular disease including ischemia-reperfusion (IR) injury and hypertension. The nutritional aspects of these cardioprotective effects are particularly intriguing since nitrate and nitrite are abundant in our everyday diet.

Whether increasing the circulating pool of nitric oxide and nitrite by dietary nitrate offers a novel mechanistic approach to regulate mobilization of circulating angiogenic cells and thus regenerative processes in cardiovascular medicine is not known. Thus, in the present study, we tested whether oral application of nitrate leads to an enhanced number of circulating angiogenic cells and whether this is associated with an improvement in endothelial function.

Study Overview

• Status: Completed
• Conditions: no Medications
• Intervention / Treatment: Dietary supplement: Dietary nitrate; Dietary supplement: Water

Detailed Description

Administration of a single dose of nitrate intervention or water alone to healthy volunteers. Before and up to 4 hours (short-term)/6 days (long-term) after ingestion, marker of vascular function are measured in plasma and by using high-resolution ultrasound.

Measurements are taken before and up to 4 h after double blind cross-over per os administration of a single dose of nitrate intervention (150 ml tab water with 150 umol/kg sodium-nitrate) or water control (100 ml Chapelle mineral water) to healthy volunteers. Circulating angiogenic cells are measured as CD34+/KDR+ and CD133+/KDR+ mononuclear cells in blood by flow cytometry and plasma is analyzed for nitrate and nitrite, as well as mobilization markers and cytokines including stromal cell derived factor, vascular endothelial growth factor and stem cell factor. All measurements are performed after >12h overnight fasting.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Duesseldorf, NRW, Germany, 40225
      • Heinrich-Heine-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 36 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 20 years
• refrain from nitrate containing food ingestion during trial

Exclusion Criteria:

• > 36 years
• poor endothelial function
• acute infection
• any chronic heart or pulmonary disease
• arrhythmias
• acute or chronic renal failure
• cardio-vascular risk factors: diabetes mellitus, hypertension, hyperlipidemia
• intake of nutrition supplements (l-arginine, creatinine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dietary nitrate; 150 ml tab water with 150 umol/kg sodium-nitrate	Dietary supplement: Dietary nitrate; 150 ml tab water with 150 umol/kg sodium-nitrate; Other Names: sodium nitrate
Placebo Comparator: Water; 150 ml Chapelle mineral water	Dietary supplement: Water; 150 ml Chapelle mineral water; Other Names: H2O

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Circulating angiogenic cells	4 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Cytokines	4 hours
Endothelial function	4 hours

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Study Director: Malte Kelm, MD, PhD, University of Duesseldorf; Study Chair: Tienush Rassaf, MD, PhD, University of Duesseldorf; Principal Investigator: Christian Meyer, MD, University of Duesseldorf; Principal Investigator: Christian Heiss, MD, University of Duesseldorf

Publications and helpful links

Helpful Links

• Link to the homepage of the Division of Cardiology, Pneumology, and Angiology at the University of Duesseldorf

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 16, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 2010

Study Record Updates

• Last Update Posted (Estimate): November 8, 2013
• Last Update Submitted That Met QC Criteria: November 7, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Dietary nitrate
• Other Study ID Numbers: Protective dietary nitrate