CHAMGAP
Verdict No. 3123 · Search date 2026-09-16 · Methodology v1.0

Riboflavin , reported single-ingredient oral supplementation,
does it really help with 16-week research-visit peripheral cuff systolic blood pressure in hypertensive MTHFR 677TT adults?

30-Second Summary
C
Evidence Grade C · 46 · Safety caution
ChatGPT source review and self-verification · Codex technical integration
The CI, between-group MCID and separate treated/untreated effects remain unverified. This is a completed current value, open to revision when new information appears. Single-assistant self-review is not independent external clinical peer review, journal certification or exhaustive-search assurance.
Trial-specific harm denominators and counts are unverified. General NIH consumer information is not evidence of zero events in this trial. Orange urine/tears in an NHS migraine leaflet is context at a different dose, not an observed outcome here. Caution does not mean harm was demonstrated. It separately marks incomplete trial harms reporting and long-term/special-population safety in the context of hypertension care. This page does not advise stopping, reducing or replacing antihypertensive therapy, self-diagnosing MTHFR genotype, or self-dosing riboflavin. The study dose is not personal dosing advice. [S01, S11–S13]
What the
research shows
One trial in hypertensive MTHFR 677TT adults, predominantly taking antihypertensives but including a small untreated fraction, reported lower systolic pressure with 1.6 mg/day for 16 weeks versus placebo. The direction-normalized between-group result is −5.6 mmHg (P=0.033). This is investigator-measured research-visit cuff pressure (office-type; exact physical site unverified), not ambulatory or self-measured home-series pressure. With the evidence limitations, the current grade is C and fixed score 46. [S01–S02]
What the
ads claim
No commercial advertising sample was researched, so no claim is made about what actual advertisements say. This page does not establish treatment of all hypertension, stroke prevention or replacement of antihypertensive medication.

Four separate assessment dimensions

Effect direction and sizeOriginal Table3 mean(SEM) values are141.8(2.9)→137.1(3.0) with riboflavin and143.5(3.0)→144.3(3.1) mmHg with placebo. The reported overall reduction is5.6±2.6 mmHg; the variance type for that overall contrast is not separately established, so CI=null. The −5.5 difference calculated from rounded arm means is descriptive, not a replacement causal estimate for the reported −5.6. [S01]
Evidence certaintyConfidence in the locked question is limited; not formal GRADE certification.
ApplicabilityThis is not an effect for every hypertensive adult, every MTHFR genotype, or an exclusively treated subgroup. Participants were selected for TT from an older TUDA cohort without overt cardiovascular disease. [S01]
SafetyTrial-specific harm denominators and counts are unverified. General NIH consumer information is not evidence of zero events in this trial. Orange urine/tears in an NHS migraine leaflet is context at a different dose, not an observed outcome here. Caution does not mean harm was demonstrated. It separately marks incomplete trial harms reporting and long-term/special-population safety in the context of hypertension care. This page does not advise stopping, reducing or replacing antihypertensive therapy, self-diagnosing MTHFR genotype, or self-dosing riboflavin. The study dose is not personal dosing advice. [S01, S11–S13]

The axes are B/S/R1/I1/E~/CX/B2. B is the claim type, not an efficacy grade B. No validated clinical threshold was verified, so magnitude was classified using a statistical convention: the reported between-group contrast divided by pooled baseline between-person SD is approximately−0.286. This is not an author-reported SMD, paired dz or validated MCID, and does not exclude clinical benefit. The unchanged calculator validates C; the zero-strength fixed anchor is46. [S01; supplied rubric cases28,45]

*

Useful facts when choosing a product

  • The reported intervention is oral riboflavin1.6 mg/day for16 weeks. Administration count per day, exact chemical form, manufacturer, excipients and batch are unverified. It is not equated with FMN/FAD, multivitamins, injections or dietary exposure. [S01–S02]
  • Baseline EGRac mean(SD) is1.37(0.26) with riboflavin and1.31(0.11) with placebo. Individual deficiency prevalence and total dietary intake are unverified; neither universal deficiency nor universal adequacy is inferred. [S01]
  • Overall pill-count adherence was reported as99%; arm-specific values are unverified. Actual antihypertensive medication changes and regimen stability were not verified. [S01]
ID

Chamgap Semantic Classification Code

Permanent code issued

S.riboflavin.oral-tablet-1-6mg-day-16weeks.adults-hypertension-mthfr677tt-no-overt-cvd-office-type-research-visit-sbp-16weeks.reduce.placebo-usual-background-care

Substances > Riboflavin (vitamin B2) > Oral tablet 1.6 mg/day for 16 weeks > Research-visit peripheral cuff SBP in hypertensive MTHFR 677TT adults > Reduce > Placebo plus usual background care

The reported between-group effect of −5.6 mmHg (P=0.033) is retained, while the exact CI and analyzed arm counts remain unverified; it is not relabeled as ambulatory/home BP, other genotypes or cardiovascular events. The code identifies the intervention and claim; it never contains the evidence grade, score, or safety result.

Download semantic index (JSON) · Codebook v1

Exact Claim Classification

These independent facets prevent evidence from different forms, routes, populations, effects, and comparators from being mixed.

Intervention classS · Supplement or nutraceutical
Canonical ingredient or interventionRiboflavin (vitamin B2), reported single-ingredient supplementation
Source or part usedManufacturing origin and chemical certificate unverified; plant part not applicable
Formulation or processingReported ordinary riboflavin tablets; exact chemical form, excipients, release profile, product and batch unverified; not FMN/FAD or B-complex equivalence
RouteOral, supported by registry instruction to take tablets and trial pill-box administration
Dose1.6 mg/day supplemental riboflavin; administration count, total diet and co-nutrient intake unverified
Duration16 weeks of supplementation; longer-term persistence unverified
PopulationAdults with hypertension and MTHFR 677TT, without overt CVD, recruited from TUDA aging cohort; mean age 69.1 years; predominantly treated with a small untreated fraction; treated-only effect unverified
Effect or conditionEffect on investigator-measured research-visit peripheral cuff systolic blood pressure (office-type; exact physical site unverified), not general hypertension treatment, genotype screening or cardiovascular events
Primary endpointInvestigator-measured research-visit peripheral cuff SBP treatment×time contrast at 16 weeks in mmHg (office-type; exact physical site unverified); not ambulatory, self-measured home series, central, daytime or nighttime SBP
ComparatorPlacebo plus existing usual background care; medication changes and placebo matching details unverified
Duplicate-detection keyS|riboflavin-reported-ordinary-single|oral-tablet|1.6mg-day|16weeks|adult-older-TUDA-hypertension-MTHFR677TT-no-overt-CVD-predominantly-treated-mixed|research-visit-peripheral-cuff-SBP-office-type-site-unverified-change-mmHg-16weeks|placebo-usual-background-care|clinical-efficacy
01

What the research actually shows

This is not an effect for every hypertensive adult, every MTHFR genotype, or an exclusively treated subgroup. Participants were selected for TT from an older TUDA cohort without overt cardiovascular disease. [S01] Among 91 randomized participants (46 riboflavin,45 placebo),3 dropouts were handled with LOCF and4 SBP outliers were excluded. The authors’ ITT label does not mean an unfiltered all-randomized analysis. Actual analyzed arm denominators, exact confidence interval, concealment implementation and prospective single-SBP hierarchy remain unverified. [S01–S02] Original Table3 mean(SEM) values are141.8(2.9)→137.1(3.0) with riboflavin and143.5(3.0)→144.3(3.1) mmHg with placebo. The reported overall reduction is5.6±2.6 mmHg; the variance type for that overall contrast is not separately established, so CI=null. The −5.5 difference calculated from rounded arm means is descriptive, not a replacement causal estimate for the reported −5.6. [S01]

02

Why this is classified as C (46)

The axes are B/S/R1/I1/E~/CX/B2. B is the claim type, not an efficacy grade B. No validated clinical threshold was verified, so magnitude was classified using a statistical convention: the reported between-group contrast divided by pooled baseline between-person SD is approximately−0.286. This is not an author-reported SMD, paired dz or validated MCID, and does not exclude clinical benefit. The unchanged calculator validates C; the zero-strength fixed anchor is46. [S01; supplied rubric cases28,45]

Counterpoint. Registration on2012-02-02 followed first recruitment on2010-05-01; the registered primary is broadly blood pressure. Governmental and DSM funding were mixed, with related patents and DSM-affiliated authors. These limitations are not converted into evidence of no clinical effect or fabrication. [S01–S02]

Rejudgment record. One directly eligible family; independent same-boundary replication unverified — Supplied rubric and unchanged calculator; tier2 statistical magnitude; zero-strength fixed anchor

Stored scoring profile
EndpointSSurrogate marker - laboratory or imaging measures
Case application: S: BP surrogate, not an event or patient-reported treatment goal.
ReplicationR1Single confirmatory trial
Case application: R1: one directly eligible randomized family, not an assertion of fully prospective confirmatory evidence.
IndependenceI1Mixed funding sources
Effect sizeE~Statistically positive but below the threshold
PrecisionCXNo pooled confidence interval could be confirmed
Case application: CX: CI unverified. Cohen convention is not used to exclude clinical benefit.

Stored derived and displayed grades match; this is not a current recalculation or validity check (C).

Review performed and remaining limitations

Single-assistant original-source, registry, numeric and bilingual self-review; not independent external peer review.

The CI, between-group MCID and separate treated/untreated effects remain unverified. This is a completed current value, open to revision when new information appears. Single-assistant self-review is not independent external clinical peer review, journal certification or exhaustive-search assurance.

Preliminary RoB 2-informed review — not a complete formal assessment
RandomizationSBP-stratified randomization reported; sequence generation and concealment implementation unverified.
Deviations from assigned interventionsMedication changes, maintained blinding and placebo matching incompletely verified.
Missing outcome dataLOCF for3 dropouts;4 SBP outliers excluded, not unfiltered ITT.
Outcome measurementSame blinded researcher, A&D UA-787 and repeated cuff readings; exact physical site, posture and rest unverified.
Selection of the reported resultRetrospective registration, broad BP primary; prospective SAP and single-SBP hierarchy unverified.
Reasons for the certainty judgment — not formal GRADE
Risk of biasB2: small sample, postrandomization exclusions and reporting gaps.
InconsistencyNo independent same-boundary replication verified; different populations and measurement types not forcibly pooled.
IndirectnessRestricted to TT, predominantly treated mixed cohort, older participants, office-type research visits and16 weeks.
ImprecisionExact CI and between-group clinical threshold unverified.
Publication biasNot quantitatively assessed; access limitations remain.

Search scope and limitations. 53 general-web queries through2026-09-16;3 failed native search attempts; exact queries retained for reproducibility.

03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Wilson et al. 2013 targeted oral-riboflavin trial in hypertensive adults with MTHFR 677TTSBP-stratified randomized placebo-controlled parallel trial; participant, BP-assessor and laboratory blinding reported; 16 weeks91 randomized (46 riboflavin, 45 placebo); LOCF for three dropouts and four SBP outliers excluded; actual analyzed arm denominators unverifiedMixed public/nonprofit and DSM support, with DSM-affiliated authors and related patent holders reported; authors stated funders had no role in design, conduct, analysis or interpretationInvestigator-measured research-visit peripheral cuff SBP at 16 weeks (A&D UA-787, repeated readings); office-type with exact site, posture and rest unverified; not ambulatory or home-series BPRiboflavin 141.8 (SEM 2.9) to 137.1 (3.0), placebo 143.5 (3.0) to 144.3 (3.1) mmHg; reported between-group effect −5.6 mmHg, P=0.033; exact CI unverifiedOnly directly eligible family at the locked boundary; not generalized to all hypertension, other genotypes, treated-only effects, cardiovascular events or medication replacement
§

Receipt — 20 References

Evidence access cutoff: 2026-09-16. Each citation states its actual access level (full-text transcription, abstract, index, or other) and remaining limitations. Bibliographic checking does not certify the study results or treatment efficacy.

Wilson et al. Blood Pressure in Treated Hypertensive Individuals With the MTHFR 677TT Genotype… Hypertension 2013;61:1302–1308
Direct original trial; decisive SBP extraction Access state and limitations are distinguished in sources.json.
checked
ISRCTN23620802 official registry PDF
Registration, timing and outcome comparison Access state and limitations are distinguished in sources.json.
checked
Horigan et al. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C→T polymorphism in MTHFR. J Hypertens 2010;28:478–486
Different CVD cohort, separate boundary Access state and limitations are distinguished in sources.json.
checked
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;95:766–772
Same-CVD-cohort reintervention linkage, limited fulltext access Access state and limitations are distinguished in sources.json.
checked
Hughes et al. A randomised controlled trial to investigate ambulatory blood pressure response… Proceedings of the Nutrition Society 2018;77(OCE3)
Ambulatory abstract, different dose and measurement Access state and limitations are distinguished in sources.json.
checked
Ward et al. P3566 Ambulatory blood pressure response… EHJ 2019;40 Suppl1
Ambulatory companion abstract, not separate replication Access state and limitations are distinguished in sources.json.
checked
Amenyah et al. DNA methylation of hypertension-related genes… Int J Cardiol 2021;322:233–239
Prior-trial biosample reanalysis, not a new SBP trial Access state and limitations are distinguished in sources.json.
checked
Jobe et al. Effect of riboflavin supplementation on blood pressure… rural Gambia. F1000Research 2020;9:1034
Gambia protocol, not a verified result Access state and limitations are distinguished in sources.json.
checked
Barlow R. Functional and health consequences of insufficiency of riboflavin and vitamin B6 in adults. Ulster doctoral thesis, Oct2024
Thesis abstract, treatment-separated SBP result unverified Access state and limitations are distinguished in sources.json.
checked
Bradbury et al. Riboflavin supplements for blood pressure lowering in adults. Cochrane 2025
Review for discovery/context only Access state and limitations are distinguished in sources.json.
checked
NIH ODS Riboflavin Fact Sheet for Consumers, updated 2022-05-11
General official safety context, not trial event counts Access state and limitations are distinguished in sources.json.
checked
Torbay and South Devon NHS Foundation Trust. Vitamins and supplements that can help with migraine and headache, version May2024
Different-dose patient information, not trial-specific harms Access state and limitations are distinguished in sources.json.
checked
NIH ODS Riboflavin Health Professional fact sheet
Direct access failed, search excerpt only Access state and limitations are distinguished in sources.json.
checked
Zhang et al. The relationship between riboflavin and hypertension with MTHFR genotype. APJCN 2025
Observational association, not randomized supplementation Access state and limitations are distinguished in sources.json.
checked
Cao et al. MTHFR C677T TT genotype associated with poor blood pressure control in H-type hypertension without folic acid. Front Pharmacol 2026-09-04
2026 observational study, not a riboflavin effect Access state and limitations are distinguished in sources.json.
checked
NCT02463513 RIBOGENE candidate registry
Candidate registry link, official content unverified Access state and limitations are distinguished in sources.json.
checked
NCT05488106 InteRVENE candidate registry
Candidate registry link, current results unverified Access state and limitations are distinguished in sources.json.
checked
NCT03151096 Gambia registry
Protocol registration ID, current status unverified Access state and limitations are distinguished in sources.json.
checked
Amenyah et al. Epigenetic effects… PNS 2018
Epigenetic abstract candidate, original access unavailable Access state and limitations are distinguished in sources.json.
checked
Pharmacological blood pressure lowering for primary and secondary prevention… Lancet 2021
Clinical-threshold discovery attempt, not adopted as current MCID Access state and limitations are distinguished in sources.json.
checked
Restricted to 16-week research-visit peripheral cuff SBP in hypertensive MTHFR 677TT adults without overt CVD; not ambulatory/home BP, all hypertension or cardiovascular events.
Technical integration by: Codex · Evidence date: 2026-09-16 · Corrections: 1

Correction log — 1

Corrections applied to this verdict, in chronological order. Changes are logged, not erased.

  • 2026-09-16 · Pre-delivery editorial corrections — Mixed treatment status, physical measurement site, SD/SEM, denominators, table conflicts, registration and trial linkage were explicitly corrected or retained. Prior verdicts were not changed.

Cite this verdict

Riboflavin and 16-week systolic blood pressure in MTHFR 677TT hypertension Evidence Grade C card
[Chamgap] Riboflavin and 16-week systolic blood pressure in MTHFR 677TT hypertension — Evidence Grade C·46. 20 cited sources checked. Source: https://chamgap.com/en/verdicts/heart/oral-riboflavin-mthfr-677tt-hypertension-office-sbp-16-weeks/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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What this document does and does not do

Chamgap is an information source. It reports what research has and has not confirmed; it does not tell readers what to take or buy. That decision belongs to readers and, when needed, medical or legal professionals. This verdict reflects literature available up to the search date and may change as new research appears. Nothing here is medical advice.