Nutritional Supplements and Nitric Oxide Bioactivity

The Effects of Nutritional Supplements on Postprandial Nitric Oxide Bioactivity in Abdominally Obese Men

Obese people have a disturbed postprandial metabolism and thereby a decreased postprandial vascular function. Nitric oxide plays an important role in the postprandial vascular function. Multiple studies already focused on various nutritional compounds to improve the postprandial vascular function by increasing the nitric oxide bioactivity. However, the vast majority of the trials has been performed with relatively high doses of the individual components, which are problematic to convert into daily food measures, thereby preventing translation of these findings. Well-designed trails studying the effect of feasible amounts of nutritional supplements on the bioactivity of nitric oxide and vascular function are missing.

Study Overview

• Status: Completed
• Conditions: Vascular Function; Nitric Oxide; Postprandial Metabolism; Nitrate / Nitrite; L-Arginine
• Intervention / Treatment: Dietary supplement: L-Arginine; Dietary supplement: Nitrate / Nitrite; Dietary supplement: Placebo

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

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ER
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men
• Aged between 40-70 years
• Waist circumference ≥ 102
• Fasting plasma glucose < 7.0 mmol/L
• Fasting serum total cholesterol < 8.0 mmol/L
• Stable body weight (weight gain or loss < 3 kg in the past three months)
• Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
• No difficult venipuncture as evidenced during the screening visit
• No current smoker
• No diabetic patients
• No familial hypercholesterolemia
• No abuse of drugs
• No more than 3 alcoholic consumptions per day
• No use of medication known to treat blood pressure, lipid or glucose metabolism
• No use of an investigational product within another biomedical intervention trial within the previous 1-month
• No severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
• Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue- scraping on the morning of each experimental test day

Exclusion Criteria:

• Women
• Fasting plasma glucose ≥ 7.0 mmol/L
• Fasting serum total cholesterol ≥ 8.0 mmol/L
• Current smoker, or smoking cessation <12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• More than 3 alcoholic consumptions per day
• Unstable body weight (weight gain or loss > 3 kg in the past three months)
• Use medication known to treat blood pressure, lipid or glucose metabolism
• Use of an investigational product within another biomedical intervention trial within the previous 1-month
• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
• Not willing to give up being a blood donor from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study
• Not or difficult to venipuncture as evidenced during the screening visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High L-arginine; During this experimental day, men will receive a high-fat shake with a high dose of L-arginine.	Dietary supplement: L-Arginine; Acute intervention (3 hours)
Experimental: Medium L-arginine + Nitrate / Nitrite; During this experimental day, men will receive a high-fat shake with a medium dose of L-arginine enriched with nitrate and nitrite.	Dietary supplement: L-Arginine; Acute intervention (3 hours); Dietary supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Experimental: Low L-arginine + Nitrate / Nitrite; During this experimental day, men will receive a high-fat shake with a low dose of L-arginine enriched with nitrate and nitrite.	Dietary supplement: L-Arginine; Acute intervention (3 hours); Dietary supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Experimental: Nitrate / Nitrite; During this experimental day, men will receive a high-fat shake with nitrate and nitrite.	Dietary supplement: Nitrate / Nitrite; Acute intervention (3 hours)
Placebo Comparator: Placebo; During this experimental day, men will receive a high-fat shake without supplement.	Dietary supplement: Placebo; Acute intervention (3 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitric oxide bioavailability	Flow-mediated vasodilation (FMD) of the brachial artery	Change from baseline at 2 hours after supplement intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitric oxide bioavailability	Plasma cyclic guanosine monophosphate (cGMP)	During 3 hours following supplement intake
Vascular function markers	Retinal microvascular calibers	Change from baseline at 2 hours after supplement intake
Cardiometabolic risk markers (1)	Plasma markers for low-grade systemic inflammation (CRP)	Change from baseline at 2 hours after supplement intake
Cardiometabolic risk markers (2)	Plasma markers for endothelial dysfunction (NOx)	Change from baseline at 2 hours after supplement intake
Cardiometabolic risk markers (3)	Office blood pressure	Change from baseline at 2 hours after supplement intake
Postprandial metabolism (1)	Serum lipid metabolism	During 3 hours following supplement intake
Postprandial metabolism (2)	Plasma glucose metabolism	During 3 hours following supplement intake

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Nutricia Research

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: METC 18-3-010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No