Riboflavin Lowers Blood Pressure: A Review of a Novel Gene-nutrient Interaction

Hypertension, defined as a systolic/diastolic blood pressure of 140/90 mmHg or greater, is estimated to carry a three-fold increased risk of developing cardiovascular diseases (CVDs). Evidence from genome-wide association studies has identified an association between blood pressure and the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR). Recent meta-analyses of observational studies show an increased risk of hypertension in people homozygous for the 677C→T polymorphism in MTHFR. Riboflavin in the form of flavin adenine dinucleotide (FAD) acts as a cofactor for MTHFR, and the variant enzyme is known from molecular studies to become inactive for having an increased propensity to dissociate from FAD. Our findings revealed that CVD patients with MTHFR 677TT genotype (compared to CC or CT genotype) have significantly higher blood pressure, and that blood pressure was highly responsive to intervention with riboflavin, resulting in significant lowering, specifically in the TT genotype group. Further investigations confirmed this gene-nutrient interaction in hypertensive patients (with and without overt CVD), and showed that the blood pressure lowering effect of riboflavin in the TT genotype group was independent of antihypertensive drug use. Although the precise mechanism linking this polymorphism to hypertension remains to be established, it would appear that the biological perturbation, which leads to higher blood pressure in individuals with MTHFR 677TT genotype, is modifiable by correcting the variant MTHFR enzyme through enhancing riboflavin status. Thus riboflavin, targeted specifically at this genetically at-risk group, may offer a personalised non-drug approach to managing hypertension. Keywords: Blood pressure, Hypertension, MTHFR, Personalised medicine, Riboflavin