What’s Already Known On This Topic?

High blood pressure (or hypertension) is the leading risk factor contributing to death worldwide, primarily from heart disease and stroke. Effective lowering of blood pressure, even by small amounts, is however proven to reduce these events, and can thus save lives in middle and older age. Along with the well-recognized nutrition and lifestyle factors that contribute to higher blood pressure, there is much interest in the role of genetic factors. This aspect is receiving greater attention in recent years with the emergence of “genome-wide association studies” or GWAS, an approach that involves rapidly scanning complete sets of DNA from large numbers of people to find genetic variations linked with a particular disease.

Using this approach scientists have found that the MTHFR gene, which is involved in the body’s handling of the B-vitamin folate (more commonly known as folic acid), appears to be implicated in blood pressure. In particular, about 10% of the world’s population have two bad copies of the MTHFR gene (having inherited one variant copy from each parent): they have what is known as the TT genotype. International research shows that the TT genotype in MTHFR can increase a person’s risk of having hypertension by as much as 80%; correspondingly, their risk of having a stroke or a heart attack is increased by up to 40% (1). The TT genotype affects an estimated 10% of people globally, but can be much higher in certain countries such as Mexico (32%) and northern China (20%).

“The good news from our findings is that riboflavin offers a simple, cost-effective personalized approach for treating and preventing the higher blood pressure that occurs in people with the TT genotype in MTHFR”

What’s New About Our Research?

We have been studying the role of the MTHFR gene in blood pressure, both in patients with existing hypertension and in healthy adults, and the results are intriguing. Consistent with other published research, our work shows that having the TT genotype in MTHFR certainly does result in considerably higher blood pressure. What is entirely novel however, is that our work has revealed a very important interaction between this gene and nutrition (and one vitamin in particular). This means that inheriting the variant MTHFR gene does not have to be bad news for your blood pressure.

Novel work undertaken by our team at Ulster University, shows that riboflavin (also known as vitamin B2), another B-vitamin that is closely linked with folate in the body, plays a critical role in normalizing blood pressure in people with the TT genotype in MTHFR. In a series of randomized trials conducted in hypertensive patients, we showed that targeted riboflavin supplementation specifically in those with this genetic variant resulted in marked lowering of blood pressure, regardless of the effect of any blood pressure-lowering drugs the person may be taking (2, 3). In other research, over 6,000 healthy Irish adults showed that better nutritional status of riboflavin can protect against the development of hypertension in the 12% of Irish adults with the TT genotype who are at an increased risk of developing high blood pressure (1). This is a clear example of what scientists call a gene-nutrient interaction, the nutrient works to lower blood pressure only if the person has the relevant gene.

Why Our Findings Are Important

The good news from our findings is that riboflavin offers a simple, cost-effective personalized approach for treating and preventing the higher blood pressure that occurs in people with the TT genotype in MTHFR.

• For hypertensive patients with the TT genotype, riboflavin supplementation can offer a simple, non-drug treatment to effectively lower blood pressure.

• For sub-populations worldwide with this genetic risk factor, better riboflavin status (achieved through supplements or fortified foods) may prevent or delay the onset of high blood pressure. Thus, riboflavin, targeted at those with the TT genotype in MTHFR, offers a personalized treatment or preventative strategy for hypertension.

New Directions For Our Research

We are conducting further investigations of this novel gene-nutrient interaction in blood pressure. Our new work is focusing on preventing hypertension in pregnancy; this is an important condition because it presents major risks to the health of both mother and baby. We are also undertaking separate studies using ambulatory blood pressure monitoring, an approach which measures blood pressure over a full 24-hour period and is therefore more meaningful than a one-off clinic blood pressure reading as per routine practice.

References

1. McNulty H, at al. MTHFR genotype and blood pressure: a personalized approach to prevention and treatment of hypertension. Molecular Aspects of Medicine. 2017;53:2–9.

2. Horigan G, et al. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C>T polymorphism in MTHFR. Journal of Hypertension. 2010;28:478–486.

3. Wilson CP, et al. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial. Hypertension. 2013;61:1302–1308.