Stratified Treatment of Hypertension

Blood Pressure in Treated Hypertensive

Individuals With the MTHFR 677TT Genotype
Is Responsive to Intervention With Riboflavin
Findings of a Targeted Randomized Trial
Carol P. Wilson, Helene McNulty, Mary Ward, J.J. Strain, Tom G. Trouton, Birgit A. Hoeft,
Peter Weber, Franz F. Roos, Geraldine Horigan, Liadhan McAnena, John M. Scott
AbstractIntervention with riboflavin was recently shown to produce genotype-specific lowering of blood pressure (BP)
in patients with premature cardiovascular disease homozygous for the 677CT 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 mmHg).
A significant improvement in the biomarker status of riboflavin was observed in response to intervention (P<0.001).
Correspondingly, an overall treatment effect of 5.62.6 mmHg (P=0.033) in systolic BP was observed, with pre- and
postintervention values of 141.82.9 and 137.13.0 mmHg (treatment group) and 143.53.0 and 144.33.1 mmHg
(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 RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN23620802.(Hypertension.
2013;61:1302-1308.) Online Data Supplement
Key Words: blood pressure

hypertension

MTHFR

ypertension affects more than 1 billion individuals globally1 and is estimated to be responsible for 7.6 million
premature deaths.2 Drug35 and lifestyle6,7 interventions to lower
blood pressure (BP), even by small amounts, have been proven
to decrease cardiovascular disease (CVD) risk. Multiple lifestyle and genetic factors are thought to contribute to the development and progression of hypertension. A large number of
genetic variants, each contributing modestly to BP variability,
seem to be implicated.8 Recent genome-wide association studies in >150000 individuals have identified several genetic loci
associated with BP variation.9,10 One study identified an association between BP and common variants in 8 genetic loci,
including one near the gene encoding the folate-metabolizing
enzyme methylenetetrahydrofolate reductase (MTHFR).10
In general agreement with this observation, evidence from a

personalized medicine

riboflavin

recent meta-analysis of observational studies shows a strong

association of the MTHFR 677CT polymorphism with
hypertension.11
The frequency of the homozygous mutant MTHFR 677TT
genotype is reported to be 10% worldwide, ranging from
4% to 18% in the United States, 20% in northern China to
as high as 32% in Mexico.12 The MTHFR enzyme catalyzes
the conversion of 5, 10-methylenetetrahydrofolate into
5-methyltetrahydrofolate which, in turn, is required for the
remethylation of homocysteine to methionine. The common
677CT variant in MTHFR results in a thermolabile enzyme
with decreased activity, typically leading to elevated plasma
homocysteine in vivo.13 Molecular studies demonstrate that
the decreased activity of the variant enzyme is attributable to
the loss of its riboflavin (ie, FAD; flavin adenine dinucleotide)

Received January 15, 2013; first decision March 26, 2013; revision accepted March 26, 2013.
From the Northern Ireland Centre for Food and Health, University of Ulster, Coleraine, Northern Ireland (C.P.W., H.M., M.W., J.J.S., G.H., L.M.);
Cardiac Unit, Antrim Area Hospital, Northern Health and Social Care Trust, Antrim, Northern Ireland (T.G.T.); School of Biochemistry and Immunology,
Trinity College Dublin, Dublin, Ireland (J.M.S.); and DSM Nutritional Products Ltd, Kaiseraugst, Switzerland (B.A.H., P.W., F.F.R.).
The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.
111.01047/-/DC1.
Correspondence to Mary Ward, Northern Ireland Centre for Food and Health, University of Ulster, Cromore Rd, Coleraine, BT52 1SA, Northern Ireland.
E-mail mw.ward@ulster.ac.uk
2013 American Heart Association, Inc.
Hypertension is available at http://hyper.ahajournals.org

DOI: 10.1161/HYPERTENSIONAHA.111.01047

1302

Wilson et al Targeted Treatment of Hypertension With Riboflavin 1303

cofactor,14,15 whereas supplementation with riboflavin
seems to restore MTHFR activity resulting in a significant
homocysteine-lowering response in humans.16 This effect is
found only in individuals with the MTHFR 677TT genotype
with no response evident in the homozygous wild-type CC or
heterozygous CT genotype groups and, therefore, demonstrates
a genotype-specific effect of riboflavin.16 We first linked
riboflavin status with BP in relation to this polymorphism
in a cohort of premature patients with CVD.17 Patients with
the TT genotype had significantly higher BP compared with
those without the polymorphism and, moreover, were highly
responsive to riboflavin supplementation, an effect that was
not found in patients with CC or CT genotypes.17 When we
followed these high-risk patients 4 years later, those with the
TT genotype remained hypertensive, despite the occurrence
(during the follow-up period) of marked changes in the
number and type of drugs prescribed, and target BP levels
were again achieved only in response to riboflavin.18
The aforementioned studies17,18 focused on a highly selected
cohort of patients with premature CVD who may not be representative of hypertensive individuals generally. It is not known
whether riboflavin can produce genotype-specific lowering of
BP in patients with hypertension without overt CVD. The aim
of this study, therefore, was to investigate the potential of riboflavin as a targeted treatment for hypertension in individuals
with the MTHFR 677TT genotype.

Methods
Participants
Individuals with hypertension prescreened for the MTHFR 677TT
genotype were recruited from an ongoing observational study,
namely the Trinity Ulster and Department of Agriculture (TUDA)
aging cohort study (Figure 1). Potential participants were excluded
if they had a history of gastrointestinal, hepatic, renal, or hematological disorders, or were taking B-vitamin supplements, anticonvulsant
therapy, or any other drugs known to interfere with folate/B-vitamin
metabolism. The minimum sample size to detect an effect of riboflavin on systolic BP (and accounting for a possible 10% dropout
rate) was estimated to be 40 subjects per treatment group based on
power calculations from a previous study.18 The type I error rate was
0.05 with desired power of 0.80. Ethical approval was granted by
the Office for Research Ethics Northern Ireland (ORECNI Ref: 09/
NIR01/68), and all patients provided written informed consent.

Study Design
The study was conducted as a randomized controlled trial (Figure
1). Participants were stratified by systolic BP (low, 134; medium,
135152; high, 153 mmHg) and subsequently randomized within
each stratum to receive either riboflavin (1.6 mg/d) or placebo for
16 weeks. To maximize compliance, patients were given supplements
on an 8-weekly basis in 7-day pill boxes and asked to return these
with any untaken pills remaining. Participants were invited to attend a
total of 2 appointments, at the start and end of the trial. Relevant clinical and lifestyle information, including currently prescribed BP medication, were retrieved from records (collected as part of the TUDA
study). At both sampling points, drug details and supplement usage
were reconfirmed with participants.

Procedures
To minimize measurement variability, BP measurements were performed pre- and postintervention by the same researcher, at the same
location for each participant and at the same time of day, approximately, in accordance with appropriate clinical guidelines,19 using an
A&D UA-787 digital BP monitor (Cardiac Services, Belfast, United

Kingdom) and appropriate cuff. The participants, and the researcher

conducting the BP measurements, were blind to treatment group
allocation.
At each sampling time point, one 30-mL blood sample was collected. Sample preparation and fractionation were performed within
0.5 to 2.5 hours of the time of sampling, and fractions were stored at
80C until analysis. Blood samples were analyzed by standard laboratory assays for plasma total homocysteine20 and red cell folate.21
Riboflavin status was determined using the erythrocyte glutathione
reductase activation coefficient (EGRac), a functional assay which
measures the activity of the enzyme glutathione reductase in washed
red cells before and after in vitro reactivation with its prosthetic group
FAD22; EGRac is calculated as a ratio of FAD-stimulated to unstimulated enzyme activity, with values 1.3 generally indicative of suboptimal riboflavin status. All samples were analyzed blind, in duplicate,
within 2 years of collection, and quality controls were provided by
repeated analysis of pooled samples covering a wide range of values.

Statistical Analysis
All statistical analyses were performed using the SPSS statistical
package for the social sciences (version 19.0, SPSS UK Ltd, Chersey,
United Kingdom). Analyses were conducted with an intention to treat
approach with the last observation carried forward method used to
impute missing values for any dropouts (n=3). Outliers were determined via the box plot algorithm of SPSS (see the online-only Data
Supplement) and were excluded from the subsequent parametric
analysis to meet the assumptions of normal distribution (4 subjects
for systolic BP and 4 for diastolic BP).
Differences in baseline characteristics between the treatment
groups were analyzed using independent t tests for linear variables
and 2 tests for categorical parameters. Responses to intervention
were examined using repeated measures ANOVA. The time treatment interaction was used to assess the effect of treatment versus placebo over time, the main outcome of the trial. The between-patient
factor was the intervention group (placebo versus riboflavin), and
the within-patient factor was time (pre and post). 2 Tests were used
to compare the proportion of patients achieving goal BP (140/90
mmHg) between the treatment groups. Descriptive statistics are expressed as meanSEM or SD throughout the article. In all analyses,
P values <0.05 were considered significant.

Results
A total of 157 individuals were identified with the MTHFR
677TT genotype from an available sample of 1427 participants with hypertension enrolled in the TUDA study (11%
frequency of the TT genotype). Some 91 of the 157 hypertensive individuals with the TT genotype agreed to participate in
this trial (Figure 1). Examination of baseline characteristics
(Table 1) showed that participants were predominantly male
with a mean age of 69 years and had a mean body mass index
in the obese category. Despite almost all participants (>90%)
being prescribed antihypertensive therapy at the time of sampling, only one third of the participants had achieved goal BP
(140/90 mmHg) at baseline.
A detailed breakdown of antihypertensive drug use and
drug combinations by treatment group is shown (Table 2),
with 35% of patients identified as taking 3 medications.
Achievement of goal BP was low even in those individuals
taking multiple medications. Of those participants taking 3
antihypertensive medications, 44% achieved goal BP.
The biomarker and BP responses to riboflavin intervention
are shown in Table 3. A significant time treatment interaction
was observed for the biomarker EGRac (repeated measures
ANOVA; P<0.001), indicating a significant improvement
in riboflavin status (ie, a decrease in EGRac) in response to

1304HypertensionJune 2013

Figure 1. Flow diagram of study design and completion rates. Trinity Ulster Department of Agriculture (TUDA) study1. Analyzed as per
intention to treat (ITT)2. BP indicates blood pressure.

treatment and providing confirmation of the generally excellent compliance of participants with the intervention protocol (estimated by pill-counting to be 99%). Correspondingly,
a significant time treatment interaction was observed for
systolic BP (P=0.033), with pre- and postintervention values of 141.82.9 and 137.13.0 mmHg (treatment group)
and 143.53.0 and 144.33.1 mmHg (placebo group). The
decrease in diastolic BP was not significant (P=0.291). After
intervention, a greater proportion (P=0.052) of participants in
the treatment group (57%) compared with the placebo group
(30%) had achieved goal BP. Responses to intervention were
compared between the treatment and placebo groups and overall treatment effects of 0.1310.029 (P<0.001) for EGRac,
and correspondingly of 5.62.6 mmHg (P=0.033) for systolic
BP, were observed (Figure 2).

Discussion
This study demonstrates for the first time that BP in treated
individuals with hypertension with the MTHFR 677TT genotype, but without overt CVD, is responsive to riboflavin. In
these patients taking routine antihypertensive drugs, hypertension control rates increased (from 32% preintervention to

almost 60% postintervention) in response to riboflavin intervention. The findings, therefore, demonstrate that the achievement of goal BP (140/90 mmHg) in this genetically at-risk
group may be greatly enhanced by the coadministration of
riboflavin with routine antihypertensive drug therapy.
The MTHFR 677CT polymorphism has previously been
investigated in relation to BP. Although some observational
studies have failed to show any relationship, the totality of
evidence seems to suggest that there is a significant association between this polymorphism and BP,11,23,24 with more
recent evidence from intervention trials indicating that this
association is riboflavin-dependent.17,18 The findings reported
here contribute to the emerging evidence by showing that the
modulating effect of riboflavin on BP in those with MTHFR
677TT genotype is not confined to high-risk patients with
CVD but may apply to individuals with hypertension generally with this genetic variant. Despite the fact that 92% of
participants were taking antihypertensive therapy, with the
majority being prescribed 2 medications, mean systolic BP
at baseline was found to be 143 mmHg, with only 32% of participants achieving the target of 140 mmHg. This observation compares with hypertension control rates of 50% among

Wilson et al Targeted Treatment of Hypertension With Riboflavin 1305

Table 1. Baseline Characteristics of Participants
Variable

All (n=91)

Placebo (n=45)

Riboflavin (n=46)

P Value

Age, y

69.1 (6.6)

68.5 (6.3)

69.8 (7.0)

0.34

Men, %
BMI, kg/m2

67

69

65

0.88

30.0 (4.7)

30.1 (4.2)

29.9 (5.2)

0.81

Smoker, %

1.00

Alcohol consumer, %

64

67

61

0.72

Diabetes mellitus, %

15

13

17

0.81

Systolic BP, mmHg

142.6 (19.5)

143.5 (19.7)

141.8 (19.4)

0.69

Diastolic BP, mmHg

83.9 (10.9)

86.1 (10.7)

81.9 (10.8)

0.07

Blood pressure

Antihypertensive medication use, %

92

98

87

0.12

Participants achieving goal BP, %*

32

23

40

0.16

1.34 (0.20)

1.31 (0.11)

1.37 (0.26)

0.15

B-vitamin status
EGRac
Plasma homocysteine, mol/L

17.1 (6.3)

17.1 (6.5)

17.0 (6.2)

0.95

Red cell folate, nmol/L

726 (347)

714 (336)

737 (361)

0.75

Data expressed as mean (SD) unless otherwise indicated. Statistical significance for comparison between treatment groups by independent t tests or 2 as
appropriate. BMI indicates body mass index; BP, blood pressure; and EGRac, erythrocyte glutathione reductase activation coefficient (biomarker of riboflavin status; a
higher value indicates lower status).
*The treatment of hypertension is aimed at achieving the goal BP of 140/90 mmHg.19

treated adults in general in the United States.25 Riboflavin

supplementation lowered mean systolic BP by >5 mmHg
in these hypertensive individuals and changed the mean BP
from being within the hypertensive category at baseline to
achievement of goal BP postintervention. This suggests that
the excess risk of hypertension linked with this genetic factor
can be overcome by riboflavin, either by improving the clinical responsiveness to routine antihypertensive therapy or by
an unrelated mechanism.
There is a continuous relationship between BP and CVD mortality, with 1 meta-analysis of 61 prospective studies (including 1 million adults), estimating that a 2-mmHg decrease in
systolic BP is associated with a 10%-reduction in stroke risk.26
Thus, the 5-mmHg decrease in systolic BP that we observed in
response to riboflavin is clinically relevant and could translate

into a reduction in stroke risk by >20%, specifically in individuals with the MTHFR 677TT genotype. The extent of response
to riboflavin observed here is less marked than the 9.2-mmHg
decrease in systolic BP that we previously reported in patients
with premature CVD with this genotype.18 This difference in
response is not unexpected, given that we previously investigated highly selected patients with CVD (identified by a previous myocardial infarction or angina), who might not have been
representative of patients with hypertension generally and were
on average 15 years younger than the current participants. With
increasing age, the genetic contribution to hypertension (and
its responsiveness to targeted treatment) may be attenuated to
some extent by other age-related factors.
The annual cost of antihypertensive medication represents
a large and increasing proportion of healthcare expenditure

Table 2. Antihypertensive Medication Use Among Participants

Drug Treatment*

All Participants, n (%)

% Achieving Goal BP

Treatment, n (%)

Placebo, n (%)

43 (51)

20 (49)

23 (52)

CCB

40 (47)

24 (59)

16 (39)

ACE inhibitors

35 (41)

15 (37)

20 (45)

-Blockers

32 (38)

16 (39)

16 (36)

ARB

26 (31)

13 (32)

13 (30)

-Blocker

11 (13)

2 (5)

9 (20)

Drug class
Diuretic

Drug combination
No medication

6 (7)

5 (11)

1 (2)

1 medication

29 (32)

26

12 (26)

17 (38)

2 medications

24 (26)

26

14 (30)

10 (22)

3 medications

32 (35)

44

15 (33)

17 (38)

ACE indicates angiotensin-converting enzyme; ARB, angiotensin II receptor blockers; BP, blood pressure; and CCB, calcium-channel blockers.
*The treatment of hypertension is aimed at achieving the goal blood pressure of 140/90 mmHg.19

1306HypertensionJune 2013
Table 3. Response to Riboflavin Intervention in Patients With
the MTHFR 677TT Genotype
Response Indicator

Placebo (n=45)

Riboflavin (n=46)

P Value*

EGRac
Before

1.31 (0.03)

1.37 (0.03)

After

1.32 (0.02)

1.25 (0.02)

<0.001

Systolic BP, mmHg

Before

143.5 (3.0)

141.8 (2.9)

After

144.3 (3.1)

137.1 (3.0)

Before

86.1 (1.7)

81.9 (1.6)

After

86.7 (1.7)

80.9 (1.6)

0.291

Before

23

41

0.131

After

30

57

0.052

0.033

Diastolic BP, mmHg

Attainment of goal BP, %

Data expressed as mean (SEM). BP indicates blood pressure; and EGRac,

erythrocyte glutathione reductase activation coefficient.
*Time treatment interaction (repeated measures ANOVA, comparing the
effect of treatment vs placebo over time).
EGRac, biomarker of riboflavin status; a higher value indicates lower status.
Individual BP values are the average of 2 readings from the reference arm
measured according to clinical guidelines19; if a difference of >5 mmHg in
diastolic BP or >10 mmHg in systolic BP was observed, a third measurement
was taken and the 2 measurements in closest agreement were used.
2 test was used to compare differences in the achievement of goal BP
(140/90 mmHg) between the treatment groups.

in many countries and was estimated several years ago at $15

billion in the United States alone.27 The majority of individuals with hypertension often require 2 antihypertensive agents
from different drug classes,2830 but BP control remains low
among treated patients globally.31 The health consequences of
undertreating hypertension are considerable and estimated to
account for 34% of strokes in older adults.32 The present results
support the case for personalized medicine in hypertension,
first proposed many years ago,33 but now possible only with
the availability of molecular tools to identify small population
subgroups with similar genetic characteristics who are more
likely to respond favorably to targeted therapeutic interventions.34 Individuals homozygous for this polymorphism (up to
30% in populations worldwide) are likely to respond suboptimally to present antihypertensive drugs but may benefit from
targeted treatment with riboflavin.
Elucidation of a mechanism to explain the role of this genenutrient interaction in BP is not yet clear but must in some
way involve MTHFR through loss of function in the variant form and the ability of supplemental riboflavin to restore
normal enzyme activity in vivo,16 consistent with the known
molecular characteristics from in vitro studies.14,15 A plausible
mechanism linking MTHFR with BP, in turn, might involve
the potent vasodilator nitric oxide (NO). Concentrations of
5-methyltetrahydrofolate (the product of the MTHFR reaction) in vascular tissue seem to be associated with NO regulation and endothelial function and are lower in patients with
the MTHFR 677TT genotype.35,36 By stabilizing the variant
MTHFR enzyme, it is possible that riboflavin supplementation
could restore 5-methyltetrahydrofolate concentrations in vascular cells, improve NO bioavailability, and in turn lower BP,

Figure 2. Comparison of responses of erythrocyte glutathione

reductase activation coefficient (EGRac; A) and systolic blood
pressure (B) to intervention with riboflavin (1.6 mg/d) or placebo
in patients with the MTHFR 677TT genotype over 16 weeks.
Riboflavin status was measured as EGRac, a functional biomarker
assay for riboflavin, with higher values indicating lower status.
Values are mean changes (SEM) between preintervention and
postintervention. The P values refer to the treatment time
interaction of the repeated measures ANOVA, that is, the efficacy of
the treatment vs placebo over time. BP indicates blood pressure.

specifically in patients with the TT genotype. Further investigation of mechanisms is clearly required, but at this time,
we think it unlikely that the elevated homocysteine phenotype
typically associated with this polymorphism (and shown previously to be responsive to riboflavin)16,17 is implicated. Despite
the significant associations between plasma homocysteine and
BP reported in several observational studies, intervention studies to lower homocysteine have shown little or no corresponding BP response37 and suggest that there is no causative link
between homocysteine concentrations per se and hypertension.
An unanswered question is the extent to which early optimization of riboflavin status (ie, before commencing routine antihypertensive treatment) can prevent the progression
toward hypertension in this genetically at-risk group, and
whether individuals with the TT genotype who have optimal
riboflavin status are less likely to develop hypertension compared with individuals with the same genotype who have poor
riboflavin status. Furthermore, a riboflavin dose of 1.6 mg/d
for 16 weeks was used in this and in our previous trials, therefore further work is required to determine whether a greater
BP-lowering response can be achieved with a higher dose or

Wilson et al Targeted Treatment of Hypertension With Riboflavin 1307

longer treatment duration, and whether riboflavin in combination with folic acid or 5-methyltetrahydrofolate could be more
effective than riboflavin alone.
In conclusion, despite being prescribed multiple classes of
antihypertensive medication, the majority of individuals with
hypertension with the MTHFR 677TT genotype failed to have
well-controlled BP and, as such, remained at an increased and
sustained cardiovascular risk. Supplementation with riboflavin in this genotype group was effective in lowering in BP and
consequently improved BP control rates. Riboflavin may be a
safe and effective means of obtaining goal BP in patients with
hypertension with the MTHFR 677TT genotype, with potentially important implications for the primary prevention of
stroke; however, large clinical trials are required to investigate
the translation of these novel findings to disease end points.

Perspectives
Riboflavin offers a novel, targeted approach to lower BP in
patients with hypertension homozygous for a common genetic
variant in folate metabolism, namely the 677CT polymorphism in MTHFR. Combination antihypertensive therapy as
currently prescribed seems to be associated with poor control
rates in patients with this genotype, whereas the addition of
supplemental riboflavin can greatly enhance the achievement
of goal BP. The link between MTHFR genotype and hypertension may help to explain how this common genetic trait
results in an excess risk of CVD, especially stroke, whereas the
genotype-specific responsiveness of BP to riboflavin offers an
explanation for the known variability in the excess CVD risk
according to geographical location, consistent with differences
in riboflavin status between populations. Dietary intakes (and
biomarker status) of riboflavin vary greatly from countries, such
as the United States, with generally higher intakes attributable
to mandatory food fortification with riboflavin to Asian countries where intakes are generally low. The precise mechanism
linking this polymorphism to hypertension remains to be established. The present results, however, suggest that the biological
perturbation that leads to higher BP is modifiable by correcting
the variant MTHFR enzyme through enhancing riboflavin status. Neither the genetic predisposition to hypertension nor its
responsiveness to riboflavin are well-recognized in relation to
the MTHFR 677CT polymorphism but could be important
in an era of personalized medicine whereby treatment can be
tailored to patient subgroups based on genetic characteristics.

Acknowledgments
We thank the patients for their participation in this research. We also
thank Shauna Harte for her administrative support.

Sources of Funding
This work was supported, in-part, by governmental funding from the
Northern Ireland Department for Employment and Learning which
funded the PhD studentship for C.P. Wilson and the Irish Department
of Agriculture, Food and the Marine and Health Research Board under
its FIRM (Food Institutional Research Measure) initiative and, in-part,
by DSM Nutritional Products Ltd. None of these entities were involved
in the design, implementation, analysis, or interpretation of the data.

Disclosures
There is a patent granted in Europe and pending elsewhere by all authors (except for Drs Wilson, Trouton, McAnena, Hoeft, Weber, and

Roos) on the use of riboflavin in the treatment of hypertension. The

other authors have no conflicts to report.

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Novelty and Significance

What Is New?

Blood

pressure in treated hypertensive individuals with the MTHFR

677TT genotype responds significantly to riboflavin.
The results offer a personalized nondrug approach to blood pressure treatment targeted at a patient subgroup sharing a common genetic characteristic.

What Is Relevant?

Failure to optimize riboflavin, specifically in this genotype group,

is likely to limit the achievement of goal blood pressure with

a ntihypertensive treatment, placing these patients at increased cardiovascular risk.

Summary
Supplementation with riboflavin lowers blood pressure in treated
hypertensive individuals with the MTHFR 677TT genotype.