The Role of Riboflavin in Resistant Hypertension: A Novel Approach to Treating and Managing High Blood Pressure

Science 02/18/2020

5min read

By:  DSM Pharma Solutions Editors

Genotype-targeted treatments have been demonstrated to significantly modify disease-specific risk factors.

Hypertension affects one billion people worldwide and is a leading risk factor for heart attack and stroke responsible for around 9 million annual deaths.1 Despite a wide range of medications available, ~15% of hypertensive patients globally fail to control the condition despite the use of multiple anti-hypertensives.2,3,4,5 Such resistant hypertension increases the risk for subsequent complications and death, and the economic and societal burden is high.6 Hypertension control is an important public health concern given the high prevalence of hypertension and the risk associated with untreated, inadequately treated and uncontrolled hypertension.7

The role of genetics in resistant hypertension is well established. In recent years, genome-wide association studies have identified a region near the gene encoding the folate-metabolizing enzyme MTHFR among eight loci associated with blood pressure. Individuals carrying this genotype are often hypertensive patients who fail to achieve blood pressure control with available antihypertensive treatment. With an estimated global prevalence of 10%, this 677TT homozygous subgroup represents a large proportion of patients who could potentially be targeted with gene-specific therapeutic approaches as a first line therapy.8

Emerging evidence indicates that riboflavin has a genotype-specific effect on blood pressure in (MTHFR) 677C→T patients. The therapeutic effect of oral riboflavin administration has been found to be independent of the concurrent use of antihypertensive therapies: In 3 randomized control trials in hypertensive patients with the 677 TT genotype daily consumption of 1.6 mg riboflavin resulted in the blood pressure decline 6 to 13 mm Hg.9,10,11

Despite the availability of affordable therapies, treatment with commonly used antihypertensive medicines may not work in specific patients (e.g. (MTHFR) 677C→T genotype). Thus, the inclusion of riboflavin in clinical practice may have significant implications in achieving safe and cost-effective blood pressure treatment targets in patients with genetic predispositions.


[1] WHO. A global brief on hypertension- Silent killer, global public health crisis, World health day 2013. Geneva, Switzerland; 2013.

[2] P. Sarafidis et al. Resistant hypertension - its identification and epidemiology. Nature Reviews Nephrology 2012;9:51.

[3] S. Daugherty et al. Incidence and Prognosis of Resistant Hypertension in Hypertensive Patients. Circulation 2012;125:1635-42.

[4] C. Cuspidi et al. High prevalence of cardiac and extracardiac target organ damage in refractory hypertension. Journal of Hypertension 2001;19:2063-70.

[5] J. Noubiap et al. Global prevalence of resistant hypertension: a meta-analysis of data from 3.2 million patients. Heart 2018.

[6] The high cost of treatment-resistant hypertension. 2015.

[7] Q. Gu et al. Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension. Circulation 2012;126:2105-14.

[8] B. Wilcken et al. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide. J Med Genet;40(8):619-625.

[91] G. Horigan et al. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C-T polymorphism in MTHFR. J Hypertens 2010;28(3):478-486.

[10] C. Wilson et al. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: a 4-y follow up. AJCN 2012;95(3):766-772.

[11] C. Wilson et al. Blood pressure treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin. Findings of a targeted randomized trial. Hypertension 2013;61(6):1302-1308.