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A randomised controlled trial to investigate ambulatory blood pressure response to riboflavin supplementation in adults with the MTHFR 677TT genotype

Hypertension is the leading cause of preventable premature death, estimated to affect over 1 billion adults worldwide. Meta-analyses of epidemiological studies suggest that the C677 T polymorphism in the gene MTHFR encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with an increased risk of hypertension by 24–87%. Supplementation with riboflavin (a cofactor for MTHFR) can modify this phenotype as demonstrated in a series of randomised controlled trials conducted at this centre. Compared with clinic blood pressure measured at one time-point only, ambulatory blood pressure monitoring (ABPM) measures BP over a 24hr period and provides a more reliable assessment of an individual’s BP. The aim of this study was to utilise ABPM to investigate the effect of riboflavin supplementation on BP in adults with the MTHFR 677TT genotype. Adults 18–65yrs recruited acrossNorthern Ireland to theRIBOGENEstudy (NCT02463513)were screened for theMTHFRTTgenotype and thosewhowere eligible andwilling to participate (n = 81), were stratified by baseline systolic BPand randomised to receive either riboflavin treatment (10 mg/day) or placebo for 16 weeks. Biomarker status of riboflavin wasmeasured using the erythrocyte glutathione reductase activation coefficient (EGRac) assay and BP was measured by both clinic BP and ABPM, in accordance with NICE guidelines. BP response to riboflavin was found to be strongly dependent on baseline BP. Participants with a baseline systolic BP of less than 125 mmHg showed no response to riboflavin supplementation (data not shown). In participants with a baseline systolic BP ≥125 mmHg, riboflavin supplementation resulted in a significant BP lowering of daytime systolic BP by 3·8 mmHg compared to 0·2 mmHg in the placebo group (see Table).