Riboflavin, MTHFR genotype and blood pressure: implictions for personalised nutrition

Abstract

Hypertension is the most common risk factor for cardiovascular morbidity andmortality affecting approximately 1 billion people worldwide. Recently evidence hascalled for a more rigorous approach to lower blood pressure (BP) to levels below thecurrent threshold. Thus, there is a clear need to identify new strategies for theprevention and treatment of hypertension including targeted, non-pharmacologicalapproaches to reduce BP. A common polymorphism (C677T) in the folatemetabolising enzyme methylenetetrahydrofolate reductase (MTHFR) has beenassociated with hypertension. Furthermore, in three randomised controlled trialspreviously conducted at this centre riboflavin (required as a cofactor for MTHFR)has been shown to effectively lower BP in cardiovascular disease (CVD) andhypertensive patients homozygous for the MTHFR C677T polymorphism (TTgenotype) in premature CVD and hypertensive patients. No previous study hashowever considered the BP lowering effect of riboflavin at a higher dose thanpreviously used (1.6mg/d), or indeed considered how this novel option mighttranslate to patient care. Finally the role of this polymorphism in the development ofhypertension over time has not been previously considered. The aim of this thesistherefore was to investigate the role of the MTHFR C677T polymorphism and itsinteraction with riboflavin, in determining BP in generally healthy adults, and toconsider the implications of this gene-nutrient interaction for a personalised nutritionapproach to managing hypertension. The findings from a 10-year follow up studyprovide evidence that adults with the TT genotype had a higher systolic BP thanthose with the CC/CT genotypes at any given age from 40-65 years. Furthermore,individuals with the TT genotype had a BP in the hypertensive category at a youngerage, an effect that appears to be significantly influenced by riboflavin, with thehighest BP in adults with the TT genotype in combination with low riboflavin status(ẞ =0.155, P <0.034). In a randomised controlled trial, that investigated the BPlowering of riboflavin, preliminary findings suggest that the BP response toriboflavin may be strongest in younger adults (<55 years) and in females, but thisrequires further investigation and no firm conclusions can be made until this trialreaches completion (mid 2016). The GPs and genetically at-risk adults investigatedreported a positive attitude towards the novel role of riboflavin in the prevention andtreatment of hypertension. In conclusion, the MTHFR 677TT genotype is animportant determinant of BP, furthermore in these genetically at risk individualsriboflavin offers a novel preventive and a treatment option for hypertension.

Date of Award	May 2016
Original language	English
Sponsors	Department for Employment and Learning
Supervisor	Mary Ward (Supervisor), Helene McNulty (Supervisor) & Catherine Hughes (Supervisor)