Intervention With Riboflavin to Improve Vascular Health and ENdothelial Functioning in Genetically at- Risk Adults

Study Overview
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Brief Summary
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High blood pressure is the leading risk factor for heart disease and stroke. Approximately 12% of the population have a particular genetic factor (known as the TT genotype) which increases the risk of high blood pressure. Previous studies conducted at this centre have shown that taking the B-vitamin riboflavin, for up to 3 months, decreases blood pressure in adults with the TT genotype. It is currently not known how riboflavin lowers blood pressure in those with the TT genotype but it could be as a result of altering blood levels of nitric oxide. Nitric oxide causes blood vessels to expand, leading to improved blood vessel function, an important predictor of cardiovascular health. However, the effect of riboflavin supplementation on nitric oxide and blood vessel function has not been previously studied. Furthermore, it is unclear whether taking riboflavin over a shorter period of time or at doses higher than 1.6 mg/d can also lower blood pressure and improve blood vessel function in this at risk group. Therefore, the aim of this study is to assess the effects of riboflavin supplementation on blood pressure, biomarkers of nitric oxide bioavailability and blood vessel function. It is hypothesised that riboflavin supplementation will increase nitric oxide bioavailability, leading to reduced blood pressure and improved blood vessel function and, and that a higher riboflavin dose will lead to greater reductions in blood pressure.

Official Title
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Intervention With Riboflavin to Improve Vascular Health and ENdothelial Functioning in Genetically at- Risk Adults (InteRVENE Study)

Conditions
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Blood Pressure, Hypertension

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Riboflavin 1.6mg/d
* Dietary Supplement: Riboflavin 5mg/d
* Dietary Supplement: Riboflavin 20mg/d


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Aged 60 years and below Pre-screened for MTHFR 677TT genotype (TTs and CCs individuals only invited) Exclusion Criteria: Consumer of B-vitamin supplements Consuming medication that interferes with B-vitamin metabolism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double blind placebo controlled parallel design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br>* Placebo<br>|
| Active Comparator: Dose 1<br> | Dietary Supplement: Riboflavin 1.6mg/d<br>* Riboflavin 1.6mg/d<br>|
| Active Comparator: Dose 2<br> | Dietary Supplement: Riboflavin 5mg/d<br>* Riboflavin 5mg/d<br>|
| Active Comparator: Dose 3<br> | Dietary Supplement: Riboflavin 20mg/d<br>* Riboflavin 20mg/d<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure | Branchial blood pressure | Change over 16 weeks | 
| Diastolic blood pressure | Branchial blood pressure | Change over 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | Measured by Flow Mediated Dilation | Change over 16 weeks | 
| Nitric oxide bioavailability | Plasma nitrite and nitrate oxide analysed by a Sievers gas-phase chemiluminescence nitric oxide analyser | Change over 16 weeks | 
| Erythrocyte glutathione reductase activation coefficient (EGRac)(Vitamin B2 marker) | Measured on automatic analyser | Change over 16 weeks | 
| Pyridoxal phosphate (Vitamin B6 marker) | Measured on HPLC | Change over 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MTHFR, Blood Pressure, Methylenetetrahydrofolate Reductase, Riboflavin, Flow-Mediated Dilation, Nitric Oxide