Blood Pressure
Conditions
Keywords
Blood pressure, Central hemodynamics, Methylenetetrahydrofolate reductase (MTHFR), Folate polymorphism, Riboflavin, Folic acid
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTRiboflavin
1.6 mg riboflavin / day for 24 weeks
DIETARY_SUPPLEMENTFolic acid
0.4 mg folic acid / day for 24 weeks
DIETARY_SUPPLEMENTPlacebo
Sponsors
University of Ulster
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure | Change from baseline to 24 weeks | Office blood pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse wave analysis | Change from baseline to 24 weeks | Measured using SphygmoCor device |
| Pulse wave velocity | Change from baseline to 24 weeks | Measured using SphygmoCor device |
| Red blood cell riboflavin | Change from baseline to 24 weeks | Measured using erythrocyte glutathione reductase activity coefficient (EGRAC) |
| Central blood pressure | Change from baseline to 24 weeks | Measured using SphygmoCor device |
| Serum homocysteine | Change from baseline to 24 weeks | Measured using an immunoassay |
| Plasma vitamin B6 | Change from baseline to 24 weeks | Measured by High Performance Liquid Chromatography |
| Red blood cell folate | Change from baseline to 24 weeks | Measured by microbiological assay |
Countries
United Kingdom
Outcome results
None listed