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

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.

Study Overview

• Status: Completed
• Conditions: Blood Pressure
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Riboflavin; Dietary supplement: Folic acid

• Study Type: Interventional
• Enrollment (Actual): 2564
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Co.Londonderry
    • Coleraine, Co.Londonderry, United Kingdom, BT52 1SA
      • Human Intervention Studies Unit, Ulster University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Dietary supplement: Placebo
ACTIVE_COMPARATOR: Riboflavin; 1.6 mg riboflavin / day for 24 weeks	Dietary supplement: Riboflavin; 1.6 mg riboflavin / day for 24 weeks
EXPERIMENTAL: Folic Acid; 0.4 mg folic acid/ day for 24 weeks	Dietary supplement: Folic acid; 0.4 mg folic acid / day for 24 weeks
EXPERIMENTAL: Riboflavin + Folic Acid; 1.6mg Riboflavin + 0.4 mg Folic Acid / day for 24 weeks	Dietary supplement: Riboflavin; 1.6 mg riboflavin / day for 24 weeks; Dietary supplement: Folic acid; 0.4 mg folic acid / day for 24 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Ulster

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 28, 2011
• Primary Completion (ACTUAL): August 15, 2019
• Study Completion (ACTUAL): August 15, 2019

Study Registration Dates

• First Submitted: February 17, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (ACTUAL): February 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Folic acid; Blood pressure; Riboflavin; Central hemodynamics; Methylenetetrahydrofolate reductase (MTHFR); Folate polymorphism
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Disease Attributes; Disease Susceptibility; Hypertension; Genetic Predisposition to Disease; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid; Riboflavin
• Other Study ID Numbers: REC/11/0081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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