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      Riboflavin lowers blood pressure in hypertensive people with the MTHFR 677TT genotype

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      1 , , 1 , 1
      Archives of Public Health
      BioMed Central
      Genes and nutrition, is personalised nutrition the next realistic step?
      2542014

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          Abstract

          Hypertension, defined as a systolic/diastolic blood pressure of 140/90 mmHg or greater, is estimated to carry a 3-fold increased risk of developing cardiovascular disease (CVD), while treating hypertension significantly reduces CVD events, and stroke in particular. Among the many risk factors involved, there is much recent interest in the role of genetic factors that might predispose to hypertension. Evidence from genome-wide association studies has identified an association between blood pressure and the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), while recent meta-analyses of observational studies show an increased risk of hypertension in people homozygous for the 677C→T polymorphism in MTHFR. Riboflavin (vitamin B2) in the form of FAD acts as a cofactor for MTHFR and we have been studying its modulating role in relation to this polymorphism. The variant enzyme is known from molecular studies to become inactive as a result of having an increased propensity to dissociate from FAD, but our earlier work suggested that supplementation with low-dose riboflavin could stabilise MTHFR activity in vivo in homozygous individuals. In recent years we showed that CVD patients with the relevant MTHFR 677TT genotype (compared to CC or CT genotypes) had significantly higher blood pressure, and that blood pressure was highly responsive to riboflavin intervention, specifically in the TT genotype group [1]. Further investigations confirmed this gene-nutrient interaction in hypertensive patients (with and without overt CVD), and furthermore showed that the blood pressure lowering effect of riboflavin in the TT genotype group was independent of the number and type of antihypertensive drugs that they were taking [2]. Although the precise mechanism linking this polymorphism to hypertension remains to be established, it would appear that the biological perturbation that leads to higher blood pressure in individuals with the MTHFR 677TT genotype is modifiable by correcting the variant MTHFR enzyme through enhancing riboflavin status. Thus riboflavin, targeted specifically at this genetically at-risk group, may offer a personalized non-drug approach to managing hypertension.

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          Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C-->T polymorphism in MTHFR.

          The purpose was to examine the effect of intervention with riboflavin (a cofactor for MTHFR) on blood pressure in patients homozygous (TT genotype) for the common 677C-->T polymorphism in MTHFR. We investigated 197 premature cardiovascular disease patients, prescreened for the MTHFR 677C-->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 1.6 mg per day riboflavin or placebo for 16 weeks. Among patients taking one or more antihypertensive drugs at recruitment (82%), we observed that target blood pressure (<140/90 mmHg) had been achieved in only 37% patients with the TT genotype compared with 59% with the CT and 64% with the CC genotype (P < 0.001). Riboflavin intervention reduced mean blood pressure specifically in those with the TT genotype (from 144/87 to 131/80 mmHg; P < 0.05 systolic; P < 0.05 diastolic), with no response observed in the other genotype groups. Riboflavin is effective in reducing blood pressure specifically in patients with the MTHFR 677 TT genotype. The findings, if confirmed, may have important implications for the prevention and treatment of hypertension.
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            Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: findings of a targeted randomized trial.

            Intervention with riboflavin was recently shown to produce genotype-specific lowering of blood pressure (BP) in patients with premature cardiovascular disease homozygous for the 677C→T polymorphism (TT genotype) in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR). Whether this effect is confined to patients with high-risk cardiovascular disease is unknown. The aim of this randomized trial, therefore, was to investigate the responsiveness of BP to riboflavin supplementation in hypertensive individuals with the TT genotype but without overt cardiovascular disease. From an available sample of 1427 patients with hypertension, we identified 157 with the MTHFR 677TT genotype, 91 of whom agreed to participate in the trial. Participants were stratified by systolic BP and randomized to receive placebo or riboflavin (1.6 mg/d) for 16 weeks. At baseline, despite being prescribed multiple classes of antihypertensive drugs, >60% of participants with this genotype had failed to reach goal BP (≤140/90 mm Hg). A significant improvement in the biomarker status of riboflavin was observed in response to intervention (P<0.001). Correspondingly, an overall treatment effect of 5.6±2.6 mm Hg (P=0.033) in systolic BP was observed, with pre- and postintervention values of 141.8±2.9 and 137.1±3.0 mm Hg (treatment group) and 143.5±3.0 and 144.3±3.1 mm Hg (placebo group), whereas the treatment effect in diastolic BP was not significant (P=0.291). In conclusion, these results show that riboflavin supplementation targeted at hypertensive individuals with the MTHFR 677TT genotype can decrease BP more effectively than treatment with current antihypertensive drugs only and indicate the potential for a personalized approach to the management of hypertension in this genetically at-risk group. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN23620802.
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              Author and article information

              Contributors
              Conference
              Arch Public Health
              Arch Public Health
              Archives of Public Health
              BioMed Central
              0778-7367
              2049-3258
              2014
              6 June 2014
              : 72
              : Suppl 1
              : K2
              Affiliations
              [1 ]Northern Ireland Centre for Food & Health, University of Ulster, Coleraine, BT52 1SA, UK
              Article
              2049-3258-72-S1-K2
              10.1186/2049-3258-72-S1-K2
              4094332
              182c20b7-c6bb-4f75-bba7-6d856d0148f4
              Copyright © 2014 McNulty et al; licensee BioMed Central Ltd.

              This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

              Genes and nutrition, is personalised nutrition the next realistic step?
              Brussels, Belgium
              2542014
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