Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.

Study Overview
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Brief Summary
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Approximately 12% of the world's population have a have a common C677T polymorphism in the gene encoding the folate metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the polymorphism (TT genotype) causes an increased requirement for the B-vitamins folic acid and riboflavin and more importantly results in an increased risk of developing high blood pressure (BP). Previous work from our Centre has demonstrated significantly higher BP in those with the TT genotype. This work has been conducted in cohorts with premature cardiovascular disease (CVD) and hypertension without overt CVD, but the effect in younger, healthier individuals is unexplored. To date our studies have also focused on BP as the primary outcome, but newer markers of vascular health including central pressure and hemodynamics have emerged as superior prognostic indicators of CVD. The effect of the TT genotype on these measures is an area for investigation and may help us understand the mechanism linking the genotype with BP, which is currently unknown. As adults with the TT genotype have increased requirements for riboflavin and folic acid, and BP in TT adults appears to be riboflavin dependent, the influence of these vitamins on central measures is an area for consideration. Study Design This is an observational study investigating the blood pressure profiles of healthy adults aged 18-65 years, stratified by MTHFR genotype. Apparently healthy adults will be recruited from workplaces and the general community across Northern Ireland and screened for the polymorphism via buccal swab. Those with the TT genotype and a similar number of non-TT (i.e. CC/CT) genotype individuals will be contacted and asked to come to a one-off appointment. Brachial BP will be assessed by an electronic BP monitor, central BP and central haemodynamics (augmentation index, augmentation pressure and pulse wave velocity) will be assessed by SphygmoCor XCEL. In addition, anthropometric measurements, health and lifestyle infromation and a blood sample will be obtained. Data will be statistically analysed using SPSS software to if determine differences between gentoype groups exist.

Official Title
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Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.

Conditions
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Blood Pressure

Intervention / Treatment
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* Dietary Supplement: Riboflavin
* Dietary Supplement: Folic acid
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MTHFR 677TT genotype, aged at least 18 years old Exclusion Criteria: Taking supplements containing B-vitamins Pregnant or planning to conceive Taking medications interfering with folate metabolism Renal or gastrointestinal disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Riboflavin<br>1.6 mg riboflavin / day for 24 weeks | Dietary Supplement: Riboflavin<br>* 1.6 mg riboflavin / day for 24 weeks<br>|
| Experimental: Folic Acid<br>0.4 mg folic acid/ day for 24 weeks | Dietary Supplement: Folic acid<br>* 0.4 mg folic acid / day for 24 weeks<br>|
| Experimental: Riboflavin + Folic Acid<br>1.6mg Riboflavin + 0.4 mg Folic Acid / day for 24 weeks | Dietary Supplement: Riboflavin<br>* 1.6 mg riboflavin / day for 24 weeks<br>Dietary Supplement: Folic acid<br>* 0.4 mg folic acid / day for 24 weeks<br>|
| Placebo Comparator: Placebo<br> | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Office blood pressure | Change from baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central blood pressure | Measured using SphygmoCor device | Change from baseline to 24 weeks | 
| Pulse wave analysis | Measured using SphygmoCor device | Change from baseline to 24 weeks | 
| Pulse wave velocity | Measured using SphygmoCor device | Change from baseline to 24 weeks | 
| Red blood cell riboflavin | Measured using erythrocyte glutathione reductase activity coefficient (EGRAC) | Change from baseline to 24 weeks | 
| Red blood cell folate | Measured by microbiological assay | Change from baseline to 24 weeks | 
| Serum homocysteine | Measured using an immunoassay | Change from baseline to 24 weeks | 
| Plasma vitamin B6 | Measured by High Performance Liquid Chromatography | Change from baseline to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Central hemodynamics, Methylenetetrahydrofolate reductase (MTHFR), Folate polymorphism, Riboflavin, Folic acid