Effects of Nitrate in Vegetables on Blood Pressure in Subjects With Prehypertension (DINO)

Diet and Nitric Oxide (DINO): A Study on the Effects of Dietary Nitrate on Blood Pressure in Subjects With Prehypertension

The purpose of this study is to examine the effect of different vegetables on cardiovascular function in subjects with moderately increased blood pressure. Specifically we are comparing the effects of vegetables with a high natural content of inorganic nitrate with those of vegetables with a low nitrate content.

Study Overview

• Status: Completed
• Conditions: Hypertension; Cardiovascular Disease
• Intervention / Treatment: Other: High nitrate vegetables; Other: Low nitrate vegetables; Dietary supplement: Low nitrate vegetables + nitrate

Detailed Description

Recent studies indicate that dietary-derived inorganic nitrate can affect blood pressure in humans by converting into nitric oxide bioactivity. Here we will study if vegetables that naturally contain high amounts of nitrate (green leafy vegetables) can lower blood pressure and whether any effect is attributed to the nitrate anion. High nitrate vegetables are compared with vegetables low in nitrate (e.g. tomatoes, sweet pepper). After a 2 week run in period where all subjects receive vegetables low in nitrate, the participants are randomized to one of three interventions. One third of the patients receive high-nitrate vegetables + a placebo pill (KCl), one third receives low-nitrate vegetables + placebo and the third group receives low-nitrate vegetables + a nitrate pill (KNO3). The nitrate content in the pill is precisely matched to the nitrate content in the high-nitrate vegetable group.

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 17177
    • Karolinska Institutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age 50-70 years Systolic blood pressure >130 at screening visit 2

Exclusion Criteria:

Systolic blood pressure <120 or >159 mm Hg at screening 2 Systolic blood pressure > 169 mm Hg at screening 1 Chronic kidney disease Chronic rheumatic disease Insulin treated diabetes mellitus Atrial fibrillation Major cardiovascular event within 6 months Inflammatory bowel disease Malignancy, actively treated within 6 months Hepatitis Polycytemia Vera

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High nitrate vegetables; During 5 weeks subjects receive 100-150 g of a leafy green vegetable (High nitrate vegetables) per day and placebo pills containing 300 mg KCl (2 x 150 mg).	Other: High nitrate vegetables; vegetables naturally high in nitrate
Placebo Comparator: Low nitrate vegetables; During 5 weeks subjects receive 100-150 g of tomatoes/sweet pepper (Low nitrate vegetables) per day and placebo pills containing 300 mg KCl (2 x 150 mg).	Other: Low nitrate vegetables; vegetables naturally low in nitrate
Active Comparator: Low nitrate vegetables + nitrate; During 5 weeks subjects receive 100-150 g of tomatoes/sweet pepper (Low nitrate vegetables) per day and nitrate pills containing 300 mg KNO3 (2 x 150 mg).	Dietary supplement: Low nitrate vegetables + nitrate; pill containing KNO3; Other Names: potassium nitrate (KNO3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Change in ambulatory Systolic Blood Pressure From Baseline	Measure how 24h ambulatory SBP changes over 5 weeks with the different interventions	5 weeks intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Change in ambulatory diastolic Blood Pressure From Baseline	Measure how 24h ambulatory DBP changes over 5 weeks with the different interventions	5 weeks intervention
Difference in Change in office diastolic blood pressure (DBP)	BP is measured during a hospital visit every week during intervention	Once every week for 5 weeks
Difference in Change in flow mediated dilatation (FMD)	FMD is measured before and after the interventions	5 weeks intervention
Difference in Change in office Systolic Blood Pressure From Baseline	Measure how clinic SBP changes weekly over 5 weeks with the different interventions	5 weeks intervention
Difference in Change in Daytime Ambulatory systolic Blood Pressure From Baseline	Measure how 24h ambulatory daytime SBP changes over 5 weeks with the different interventions	5 weeks intervention

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: Karolinska University Hospital
• Investigators: Principal Investigator: Jon Lundberg, MD, PhD, Karolinska Institutet

Publications and helpful links

General Publications

• Sundqvist ML, Larsen FJ, Carlstrom M, Bottai M, Pernow J, Hellenius ML, Weitzberg E, Lundberg JO. A randomized clinical trial of the effects of leafy green vegetables and inorganic nitrate on blood pressure. Am J Clin Nutr. 2020 Apr 1;111(4):749-756. doi: 10.1093/ajcn/nqaa024.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): January 30, 2019
• Study Completion (Actual): January 30, 2019

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 27, 2016

Study Record Updates

• Last Update Posted (Actual): March 25, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Prehypertension
• Other Study ID Numbers: DINO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED