Riboflavin and its links to cardiovascular disease

Riboflavin hypothesis

Back in 2003, a study was undertaken to examine how riboflavin can lower blood pressure in cardiovascular disease patients homozygous (TT genotype) for the common 677-T polymorphism in methylenetetrahydrofolate reductase (MTHFR). According to the authors, 10% of people worldwide had this genotype – and in some areas, like Southern Italy, Mexico and China, this number is even higher.¹

Previous studies had shown that there is a link between the polymorphism in MTHFR and hypertension, but until then no other clinical trial had addressed the relationship between this polymorphism and riboflavin in relation to the risk of CVD. As riboflavin is a co-factor for MTHFR, it is often overlooked as a potential modulator of the CVD risk associated with this polymorphism, but emerging science suggests it could correct any genotype-related elevation in blood pressure.

Several papers had already found links between elevated blood pressure and high levels of plasma homocysteine (tHey).² Given previous evidence that showed tHey decreased in those with the TT genotype when supplementing with riboflavin, it has therefore been hypothesized that people with the genotype who had low riboflavin status would have an increased risk of CVD.³

Response to riboflavin

The study looked at 197 premature CVD patients, prescreened for the MTHFR 677-T polymorphism, from an original cohort of 404, to select those with the TT genotype (n=60) and a similar number with heterozygous (CT; n=85) or wild-type (CC; n=75) genotypes. Of these, 181 completed an intervention in which participants were randomized within each genotype group to receive 1.6mg per day of riboflavin or placebo for 16 weeks.

The results showed that riboflavin intervention reduced the mean blood pressure specifically in those with the TT genotype, with no response observed in the other genotype groups. The systolic blood pressure response to riboflavin intervention in patients with MTHFR 677 TT genotype therefore demonstrates that genetically susceptible individuals may benefit the most from riboflavin supplementation. It would take about 10kg of weight loss to achieve similar results of lowered blood pressure through lifestyle factors.

Future benefits

Not only are these findings important for the 10% of the world’s population that has the TT genotype, they also look encouraging for CT (heterozygous genotypes) patients. While the results of this study group were inconclusive, the CT group at baseline showed blood pressure levels and rates of hypertension that were immediate, compared to other genotypes. As there are no worldwide fortification guidelines currently in place, recommendations for supporting cardiovascular health, such as riboflavin supplementation, could benefit the wider population.

For more information, read our whitepaper ‘Micronutrients for pharmaceutical applications’.