Nutritional Supplements and Nitric Oxide Bioactivity

Study Overview
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Brief Summary
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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.

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

Conditions
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Nitric Oxide, Vascular Function, L-Arginine, Nitrate / Nitrite, Postprandial Metabolism

Intervention / Treatment
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* Dietary Supplement: L-Arginine
* Dietary Supplement: Nitrate / Nitrite
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |