Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

Abstract

Clinical deficiency of the B-vitamin riboflavin (vitamin B 2 ) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5-13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.Riboflavin: Methylenetetrahydrofolate reductase: MTHFR C677T: Blood pressure:Personalised nutrition Riboflavin (vitamin B 2 ) is a water-soluble B-vitamin defined chemically as 7,8-dimethyl-10-1′-D-ribityl isoalloxazine. It acts as a precursor for FMN and FAD (1) . Clinical riboflavin deficiency is not generally considered to be a problem in the developed world but in recent years evidence has shown that sub-optimal status may be more widespread than generally perceived based on studies reporting the functional biomarker, erythrocyte glutathione reductase activation coefficient (EGRac) generally considered as the gold standard index of status. Few international data are however available based on EGRac and reports on riboflavin status are more commonly based solely on dietary intake data. Although riboflavin is required for numerous metabolic reactions its role (in the form of FAD) as a cofactor for the folatemetabolising enzyme, methylenetetrahydrofolate reductase (MTHFR) has recently received particular attention. Homozygosity (MTHFR 677TT genotype) for a common polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide (2) , has been associated with an increased risk of CVD (3) and more recently with hypertension (4) . Emerging evidence from intervention trials supports a novel role for riboflav...

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“…Of the six independently associated nutrient intakes, alcohol, tryptophan and riboflavin elicited large effects, in line with previously reported literature [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ].…”

“…RIBOFLAVIN: Riboflavin, also known as vitamin B₂, is a water-soluble vitamin found in food, predominantly milk and egg products [ 41 ], and also used as a dietary supplement. The effect of riboflavin in reducing BP has been previously reported [ 32 ]. Riboflavin acts on BP in a gene-nutrient interaction involving the gene encoding methylenetetrahydrofolate reductase [ 33 ], potentially stabilising variants within this gene to restore 5-methyltetrahydrofolate concentrations to improve nitric oxide bioavailability, a potent vasodilator in BP control [ 32 ].…”

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“…Individuals carrying the 5,10-methylenetetrahydrofolate reductase ( MTHFR ) 677TT polymorphism, which is reported to be found in some populations, have a ≤32% higher risk of CVD and hypertension. A number of recent randomized controlled trials (RCTs) showed that riboflavin supplementation can significantly reduce systolic blood pressure by 5–13 mm Hg in these genetically at-risk adults ( 55 ).…”