# Single-ingredient riboflavin (vitamin B2) × Reduction of hs-CRP in adults with elevated hs-CRP

Verdict 3089 · Evidence Check

Stored-material review date: 2026-10-05  
Original evidence date: 2026-09-15  
Review-criteria version: NGM-v3089-ORAL-RIBOFLAVIN-ELEVATED-HSCRP-1.0  
Public page/material preparation date: 2026-11-01

Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect.

## Assessment scope

- Population: Adults defined by elevated hs-CRP; results for different underlying diseases are not combined
- Ingredient, formulation and route: The question concerns a conventional oral B2 single-ingredient preparation; it is not automatically combined with a specialized colonic-release formulation
- Dose: The dose in an eligible trial involving participants with elevated hs-CRP remains unverified
- Comparator: Question: placebo/no additional treatment on top of the same usual care; comparative results for the relevant population and assay remain unverified
- Measured outcome: Change in high-sensitivity CRP concentration; distinguished from conventional CRP, other inflammatory markers, and clinical anti-inflammatory efficacy
- Duration: The duration of an eligible trial involving participants with elevated hs-CRP remains unverified
- Questions outside this scope: Conventional CRP, other inflammatory/redox markers, clinical anti-inflammatory efficacy/events, specialized colonic-release formulations, combinations/B1, acute exercise recovery, IBD fatigue 3090, correction of confirmed deficiency, and optimal dose/long-term effects are separate questions. The existing 374/1456 are reused IDs in the original metadata; their individual manuscripts were not read in this work.

## Checklist items

### N01 · Which high-sensitivity CRP comparison is being defined?

Verification status: Met  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: One main claim was selected: reduction of hs-CRP in adults with elevated hs-CRP. The list of subclaims is empty, and dose/duration remain unverified for the question.
- Why unverified: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
- Reason for missing information: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
- Required materials and conditions: Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care
- Materials to obtain first: Definition of the question: a conventional oral B2 single-ingredient preparation, adults with elevated hs-CRP, change in high-sensitivity CRP, and placebo/no additional treatment on top of the same usual care
- Further research: Compare the population, ingredients, endpoints, and comparison boundaries in the obtained manuscript and candidate studies.
- Conditions for verification: Link the original effect wording and the actual scope of inclusion and exclusion to the same source location.
- Why this condition is needed: This is needed to avoid mixing general discussion of CRP with a single comparison question.
- Application exceptions: Conventional CRP, redox associations, clinical anti-inflammatory efficacy, and IBD fatigue are separate questions.
- Remaining uncertainty: Verifying the definition of the question does not mean that a direct effect has been demonstrated.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed
- Related sources: S12, S13, S14, S21

### N02 · Has actual oral administration of B2 alone been verified in an eligible result?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The question being judged is defined as riboflavin/oral, but the actual molecule/route values in the preserved study information are empty and unverified, and the list of linked sources is empty.
- Why unverified: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
- Reason for missing information: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
- Required materials and conditions: Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison
- Materials to obtain first: Verification of the actual molecule, salt/derivative, route of administration, and single-ingredient composition in the relevant comparison
- Further research: Link formulation and administration documentation to the population/results tables to verify actual oral exposure to B2 alone.
- Conditions for verification: Verify the actual molecule and route for an eligible result using administration documentation.
- Why this condition is needed: This is needed to avoid mistaking B2 as specified in the question for an actual administration record from an eligible study.
- Application exceptions: Do not turn B1, B-vitamin combinations, or associations with blood vitamers into evidence of B2 administration.
- Remaining uncertainty: Verifying the direction of the question is separate from obtaining evidence of actual exposure in an eligible result.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application
- Related sources: S12, S13, S14, S21

### N03 · Are the release profile, manufacture/purity, and batch of the relevant eligible preparation known?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The question concerns a conventional oral B2 single-ingredient preparation; the manufacturing origin and the release profile of an eligible preparation remain unverified. S14's detailed release formulation has not been directly verified either.
- Why unverified: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
- Reason for missing information: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
- Required materials and conditions: The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation
- Materials to obtain first: The exact chemical form, release profile, manufacture/origin, purity, batch, and excipients of the conventional oral single-ingredient preparation
- Further research: Obtain product/trial-preparation documentation and review differences in applicability between conventional and specialized-release formulations.
- Conditions for verification: Verify the specifications of the preparation actually used for an eligible result.
- Why this condition is needed: This is needed to avoid automatically combining results for specialized colonic-release preparations with those for conventional B2.
- Application exceptions: Plant-part classification is not applicable, but this does not remove the unverified status of manufacture and formulation.
- Remaining uncertainty: Wording about a product name or ingredient in the question alone does not certify its actual specifications.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed
- Related sources: S12, S13, S14, S21

### N04 · Can the eligible dose be distinguished from the 10 and 100 mg in related trials?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The records of S12 in older adults at 10 mg/day and S13 in Crohn disease at 100 mg/day are preserved, but the dose for an eligible population with elevated hs-CRP remains unverified.
- Why unverified: Do not repurpose nominal doses from other populations as actual doses for the current question.
- Reason for missing information: Do not repurpose nominal doses from other populations as actual doses for the current question.
- Required materials and conditions: Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies
- Materials to obtain first: Nominal/actual dose, frequency, adherence, and total exposure in an eligible comparison, and administration records from related studies
- Further research: Compare administration and actual doses in eligible arms using medication/preparation records and records of concomitant intake.
- Conditions for verification: Verify actual exposure in the relevant eligible arms separately from nominal doses in related studies.
- Why this condition is needed: This is needed to avoid using doses from other populations as demonstrated or recommended doses for participants with elevated hs-CRP.
- Application exceptions: 10 mg/day and 100 mg/day are records from related studies, not an optimal-dose comparison.
- Remaining uncertainty: Do not repurpose nominal doses from other populations as actual doses for the current question.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed
- Related sources: S12, S13

### N05 · Can the eligible duration be distinguished from the 28 days and 3 weeks in related studies?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The recorded durations of S12 at 28 days and S13 at 3 weeks are verified within that limited scope. Duration and follow-up for an eligible population with elevated hs-CRP remain unverified.
- Why unverified: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
- Reason for missing information: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
- Required materials and conditions: Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies
- Materials to obtain first: Administration, assessment, and follow-up periods in an eligible study, and the actual time points in candidate studies
- Further research: Link administration/follow-up and assessment time points using the schedule, assessment plan, and results tables.
- Conditions for verification: Verify the administration/assessment periods for each outcome in an eligible comparison.
- Why this condition is needed: This is needed to avoid fixing the short duration of another study as the appropriate duration for the selected question.
- Application exceptions: Do not newly set a common minimum number of weeks or participants.
- Remaining uncertainty: Do not extend the 28 days/3 weeks to a directly eligible duration or to long-term effects.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed
- Related sources: S12, S13

### N06 · Have the selection criteria and underlying diseases for participants with elevated hs-CRP been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: Selection for elevated levels has not been verified for S12; S13 is a before-and-after comparison in Crohn disease, and S21 involves healthy participants. Results in a population meeting the fixed question remain unverified.
- Why unverified: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
- Reason for missing information: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
- Required materials and conditions: The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions
- Materials to obtain first: The actual threshold for elevated hs-CRP, repeat testing, diagnoses, age, inclusion/exclusion criteria, and baseline distributions
- Further research: Obtain eligibility criteria, baseline tables, and assay records to compare population concordance and reasons for exclusion for each candidate.
- Conditions for verification: Verify the criteria for the actual comparison population selected for elevated levels using a high-sensitivity assay.
- Why this condition is needed: This is needed to avoid equating general older-adult, Crohn disease, or healthy populations with a population selected for elevated levels.
- Application exceptions: Do not combine results from different underlying diseases into a single population for application.
- Remaining uncertainty: Preserve the distinctions in eligible populations without erasing the existence of related human studies.
- Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed
- Related sources: S12, S13, S14, S21

### N07 · Have both the high-sensitivity assay and selection for elevated levels been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The original unresolved-items record states that results meeting both the high-sensitivity assay requirement and selection for elevated hs-CRP remain unverified. S12·S13 have assay/selection limitations, while S21 concerns a different endpoint/population.
- Why unverified: The presence of CRP information does not mean that an hs-CRP effect has been verified.
- Reason for missing information: The presence of CRP information does not mean that an hs-CRP effect has been verified.
- Required materials and conditions: The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population
- Materials to obtain first: The hs-CRP assay name, sensitivity, specimen, and units, together with selection for elevated levels in the same population
- Further research: Compare the original assay methods with baseline assay tables to verify whether a result meets the high-sensitivity criteria.
- Conditions for verification: Link the actual assay and population selection to the same study/result.
- Why this condition is needed: This is needed to avoid arbitrarily substituting high-sensitivity CRP for conventional CRP.
- Application exceptions: Do not infer units or high-sensitivity status from figures or product names.
- Remaining uncertainty: The presence of CRP information does not mean that an hs-CRP effect has been verified.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application
- Related sources: S12, S13, S14, S21

### N08 · Have placebo/no additional treatment and shared care been verified for an eligible result?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The question specifies placebo/no additional treatment on top of the same usual care. S12's placebo record does not establish eligibility of the population/assay, and S13 has no concurrent randomized comparator.
- Why unverified: Results from an eligible comparison for the current question cannot be replaced with a related study design.
- Reason for missing information: Results from an eligible comparison for the current question cannot be replaced with a related study design.
- Required materials and conditions: The composition and schedule of concurrent comparator arms, shared care, and changes by arm
- Materials to obtain first: The composition and schedule of concurrent comparator arms, shared care, and changes by arm
- Further research: Link comparator/shared-care documentation to the results and review the meaning of the between-group difference.
- Conditions for verification: Verify the actual comparator content and differences in care for the selected population/assay.
- Why this condition is needed: This is needed to avoid confusing the comparison specified by the question with the actual comparator.
- Application exceptions: Do not turn an uncontrolled before-and-after study into a concurrently assigned placebo comparison.
- Remaining uncertainty: Results from an eligible comparison for the current question cannot be replaced with a related study design.
- Referenced methods: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application
- Related sources: S12, S13, S14, S21

### N09 · Have the distinct studies and outcome relationships underlying the four reports been established?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The four bibliographic records are linked to the stored study identifiers Tavares-riboflavin-2009, RISE-UP, RIBOGUT, and NCT05803811. Direct eligible replication and linkage of the original participants have not been verified.
- Why unverified: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
- Reason for missing information: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
- Required materials and conditions: Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication
- Materials to obtain first: Bibliography → trial/study family → endpoint/time point/analysis linkage, and whether there is duplication
- Further research: Link registry, paper, and study identifiers to review repeated citations of the same result and separate reports.
- Conditions for verification: Compare actual identifiers to distinguish verified study-family relationships from those that remain undetermined.
- Why this condition is needed: This is needed to avoid turning the number of stored source identifiers/bibliographic records into the number of independent direct replications.
- Application exceptions: Do not create counts of unique participants or independent studies when they remain undetermined.
- Remaining uncertainty: Do not tally the 4 reports as 4 eligible studies, 4 independent replications, or a total number of participants.
- Referenced methods: M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application
- Related sources: S12, S13, S14, S21

### N10 · Has reading the summaries in this work been distinguished from historical access levels?

Verification status: Met  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: S12 is a historical record of a publisher abstract; S13, an indexed author abstract/figure legends; S21, an institutional abstract; and S14, a registry shell. Only the preserved summaries were read in this work, with 0 external lookups.
- Why unverified: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
- Reason for missing information: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
- Required materials and conditions: Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates
- Materials to obtain first: Actual acquisition/reading for each material; historical abstract/figure-legend/institutional-abstract/registry-shell access; locations and dates
- Further research: If follow-up work is authorized, obtain the original file contents (bytes), source locations, and access dates for each material, and record actual reading histories separately.
- Conditions for verification: Link the records while distinguishing reading the currently preserved summaries from the fact that access to each external original material has not been attempted and the material has not been read in this work.
- Why this condition is needed: This is needed to avoid promoting a link or the originally recorded access level into a claim that the full text was read in this work.
- Application exceptions: Do not re-record a historical failure to access registry results as a failed access attempt in this work.
- Remaining uncertainty: The original full texts, registry results, and separate logs/numerical files remain unread. There is no field for individual original-source access dates; the recorded verification date is the original review date for the materials as a whole.
- Referenced methods: Material-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading and the hyperlink rules are internally designed; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed
- Related sources: S12, S13, S14, S21

### N11 · Have the cutoff date and search limitations for the current materials been linked?

Verification status: Met  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The search cutoff in the original revision policy and the recorded verification date are 2026-09-15; there is no top-level evidence-cutoff field. The stated limitation is that the original search was not an exhaustive search of primary databases worldwide. Only this preserved-summary conversion was performed in the current work.
- Why unverified: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
- Reason for missing information: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
- Required materials and conditions: The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed
- Materials to obtain first: The existing search cutoff and verification date, the current summary-review date, the input scope, and the record that no search was performed
- Further research: In a separately authorized update, compare the actual search logs and registration/correction status with the original cutoff date.
- Conditions for verification: Separate the original dates and the documents' search scope from the scope of work actually performed now.
- Why this condition is needed: This is needed to avoid exaggerating the preservation conversion as an up-to-date, exhaustive literature search.
- Application exceptions: Do not identify the merely named tasks/R01-007/ or historical search records as files actually read in this work.
- Remaining uncertainty: Statements of absence mean that eligible results remain unverified within the fixed question and the documents' search scope.
- Referenced methods: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and are internally designed
- Related sources: S12, S13, S14, S21

### N12 · Has the actual comparative design for the same question been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: A placebo trial of conventional CRP, a before-and-after study in Crohn disease, and an analysis in healthy participants exist, but comparative results for an eligible population with elevated hs-CRP have not been verified.
- Why unverified: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
- Reason for missing information: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
- Required materials and conditions: The actual parallel, crossover, cluster/randomized design for an eligible population/assay
- Materials to obtain first: The actual parallel, crossover, cluster/randomized design for an eligible population/assay
- Further research: Review the design and population/assay concordance across the protocol, Methods section, and results tables.
- Conditions for verification: Directly link the design in the methods to the relevant eligible result.
- Why this condition is needed: This is needed to avoid substituting the design label of a related trial for an eligible causal comparison.
- Application exceptions: Do not assign a not-applicable status to crossover/cluster designs because the design is unverified.
- Remaining uncertainty: Do not turn gaps in design details into a conclusion of poor design or 0 human studies.
- Referenced methods: M08 §8.1–8.2.3; internal application
- Related sources: S12, S13, S14, S21

### N13 · Have sequence generation, allocation concealment, and baseline balance been verified for an eligible comparison?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The currently retained summary does not provide sequence-generation information, allocation concealment, or a baseline table corresponding to an eligible result. The original unused bias assessment axis is also empty.
- Why unverified: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
- Reason for missing information: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
- Required materials and conditions: Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results
- Materials to obtain first: Allocation procedures, sequence generation, concealment, baseline distributions, and linkage to results
- Further research: Obtain the Methods section, allocation records, and baseline table to review gaps in confounding/allocation information for each outcome.
- Conditions for verification: Verify whether allocation/baseline documentation for an eligible comparison supports each result.
- Why this condition is needed: This is needed to avoid certifying the adequacy of allocation solely from the label placebo.
- Application exceptions: Do not fill gaps in information from the original Methods by inventing a conclusion that bias has been established.
- Remaining uncertainty: This is unverified within the preserved materials; it does not establish that the entire paper leaves the information unreported or determine the magnitude of bias.
- Referenced methods: M08 §8.1–8.2.3; internal application
- Related sources: S12, S13, S14, S21

### N14 · Have concurrent treatments and all vitamins in the eligible arms been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The value in the concurrent-vitamin record within the preserved nutrition information is empty and unverified. Details of all concurrent vitamins and treatments by arm for an eligible comparison have not been retained.
- Why unverified: Do not impose a rule that changes in the two arms must necessarily be identical.
- Reason for missing information: Do not impose a rule that changes in the two arms must necessarily be identical.
- Required materials and conditions: Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm
- Materials to obtain first: Usual treatment, concurrent vitamins/supplements, medication changes, and rescue treatment by arm
- Further research: Compare medication, supplementation, and rescue-treatment records with the analysis plan to review the contribution of concomitant treatment and the treatment policies actually compared.
- Conditions for verification: Link concomitant treatment/changes by arm in the eligible comparison to the effect of interest.
- Why this condition is needed: Needed to avoid mistaking differences in shared care for the contribution of B2 alone.
- Application exceptions: Do not fill unverified concurrent-vitamin information with an exposure value of 0.
- Remaining uncertainty: Do not impose a rule that changes in the two arms must necessarily be identical.
- Referenced methods: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application
- Related sources: S12, S13, S14, S21

### N15 · Have baseline B2, total dietary intake, actual intake, and adherence been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: Values for baseline nutritional status, total dietary/all-supplement exposure, and the eligible dose are empty/unverified; concurrent exposure also remains unverified.
- Why unverified: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
- Reason for missing information: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
- Required materials and conditions: Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm
- Materials to obtain first: Deficiency status/measurement, dietary B2, other supplementary exposure, and actual medication intake/adherence by arm
- Further research: Obtain baseline nutritional tests and intake/medication records to review gaps in analyses of total exposure and adherence.
- Conditions for verification: Link the population's baseline status, total intake, and actual amount to administration records.
- Why this condition is needed: Needed to avoid turning the nominal B2 amount into total exposure or an effect of correcting deficiency.
- Application exceptions: Do not combine results from a confirmed-deficiency population outside the question as effects of additional supplementation.
- Remaining uncertainty: Do not fill in actual exposure for an eligible result solely with the nominal amount from a related trial.
- Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application
- Related sources: S12, S13, S14, S21

### N16 · Have changes in high-sensitivity CRP been distinguished from clinical anti-inflammatory efficacy?

Verification status: Met  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The selected endpoint is change in high-sensitivity CRP concentration. The preserved nutrition information records it as a laboratory surrogate and states that it is not extended to clinical-event prevention.
- Why unverified: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
- Reason for missing information: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
- Required materials and conditions: The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events
- Materials to obtain first: The actual selected endpoint, units, and direction, and boundaries separating it from other inflammatory markers/clinical events
- Further research: Link the original outcome definition to clinical results tables to review what belongs to the same question and what belongs to a separate question.
- Conditions for verification: State the distinction between the selected hs-CRP change and ordinary CRP/other markers/clinical outcomes.
- Why this condition is needed: Needed to avoid extending a laboratory surrogate to disease treatment or event prevention.
- Application exceptions: The original B/S describes the endpoint of the fixed question; it is not certification of an observed eligible clinical trial.
- Remaining uncertainty: Verification of this boundary does not mean that a direct hs-CRP reduction effect or clinical anti-inflammatory efficacy has been verified.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.4; internally defined limits on extensions
- Related sources: S12, S13, S14, S21

### N17 · Have sample collection, timing, blinding, and precision for the eligible assay been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: Verification of the high-sensitivity assay is still outstanding, and details of the relevant eligible measurement procedures, timing, and blinded assessment have not been verified either.
- Why unverified: Units in the ordinary-CRP figure were not converted without verification.
- Reason for missing information: Units in the ordinary-CRP figure were not converted without verification.
- Required materials and conditions: The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements
- Materials to obtain first: The actual hs-CRP assay, specimen/measurement procedures, assessment time points, conditions by arm, and blinding of those taking measurements
- Further research: Compare the assay SOP, collection time points, and blinding documents with the original results.
- Conditions for verification: Verify the actual measurement conditions and differences between arms for the selected result.
- Why this condition is needed: Needed to distinguish measurement differences from intervention differences.
- Application exceptions: Do not automatically judge unverified blinding as failed or adequate.
- Remaining uncertainty: Units in the ordinary-CRP figure were not converted without verification.
- Referenced methods: M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed
- Related sources: S12, S13, S14, S21

### N18 · Has the actual analysis denominator for each hs-CRP result been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The summary describes S12 as a study of 42 participants and S13 as a study of 70 participants. The analysis-sample-size record in the preserved study information is empty/unverified, and the preserved source states that assignment counts must not replace unverified outcome-specific counts (n).
- Why unverified: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
- Reason for missing information: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
- Required materials and conditions: Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points
- Materials to obtain first: Numbers by arm (n) at recruitment/allocation, administration, measurement, completion, and analysis, and the outcome time points
- Further research: Use results tables, flow diagrams, and analysis materials to link denominators at each stage to reasons for exclusion.
- Conditions for verification: Verify the analysis denominators by arm corresponding to the selected result.
- Why this condition is needed: Needed to avoid repurposing 42·70 as eligible analysis denominators.
- Application exceptions: Do not turn a historical numerical record merely named in the preserved source into material with available values by opening it in this work.
- Remaining uncertainty: The total number of participants in a related study and the analysis count (n) for the currently eligible endpoint are separate quantities.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application
- Related sources: S12, S13, S14, S21

### N19 · Have the reasons for missing data and attrition, and the methods used to handle them, been verified for an eligible result?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The current manuscript contains no material that establishes missing data/attrition and handling methods corresponding to an eligible analysis denominator.
- Why unverified: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
- Reason for missing information: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
- Required materials and conditions: Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm
- Materials to obtain first: Losses, exclusions, discontinuations, missing measurements, and analytical handling/sensitivity analyses by arm
- Further research: Link flow diagrams, plans for handling missing data, and analysis records to review limitations on interpretation of the results.
- Conditions for verification: Verify information on observation losses and their analytical handling for the relevant result.
- Why this condition is needed: Needed to avoid turning unverified information into complete follow-up or an absence of events.
- Application exceptions: Do not calculate the number of dropouts, their reasons, or their impact from the existing sample size.
- Remaining uncertainty: This is a gap within the currently preserved materials, not confirmation that the entire original paper leaves the information unreported or that it failed.
- Referenced methods: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application
- Related sources: S12, S13, S14, S21

### N20 · Have the eligible between-group effect and analysis population/adjustment been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: S13 is a before-and-after comparison without a concurrent control, and S21 is an association analysis. The analysis population/model/effect for an eligible hs-CRP comparison has not been verified.
- Why unverified: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
- Reason for missing information: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
- Required materials and conditions: Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses
- Materials to obtain first: Effects of assignment/adherence, between-group change/final values, ITT/PP, and adjusted/cross analyses
- Further research: Compare analysis plans, models, and results tables by arm to distinguish the effect of interest from the preserved results.
- Conditions for verification: Link the effect definition and actual analysis for the same question to the result.
- Why this condition is needed: Needed to avoid using uncontrolled before-and-after change and a between-group causal effect as the same value.
- Application exceptions: Do not fill in ITT, an adjustment model, or dispersion from names alone.
- Remaining uncertainty: Do not turn a before-and-after reduction or a correlation into a direct treatment effect versus placebo.
- Referenced methods: M08 §8.2.2, M15 §15.3.1; internal application
- Related sources: S12, S13, S14, S21

### N21 · Have the effect value and units for the same eligible result been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The effect estimate for the fixed question has not been verified, and the original calculation and numerical-check records are empty lists. Units in the ordinary-CRP figure and numbers in the S14 search overview were not adopted.
- Why unverified: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
- Reason for missing information: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
- Required materials and conditions: hs-CRP values by arm, changes, units, dispersion, time points, and original results tables
- Materials to obtain first: hs-CRP values by arm, changes, units, dispersion, time points, and original results tables
- Further research: Compare original numerical tables and assay units to record the exact comparison values and what remains unverified.
- Conditions for verification: Attribute only verified original values to their corresponding population, assay, comparison, and time point.
- Why this condition is needed: Needed to avoid arbitrarily repurposing ordinary-CRP values or numbers from search overviews.
- Application exceptions: Do not perform new effect calculations/unit conversions or reverse calculations from rounded values.
- Remaining uncertainty: Do not replace nonsignificance or an empty value with an effect of 0 or a numerical value of 0.
- Referenced methods: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application
- Related sources: S12, S13, S14, S21

### N22 · Have the original CI, dispersion, and denominator for the relevant effect been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The eligible effect and CI have not been verified, and the precision assessment axis is empty. A nonsignificant ordinary-CRP result is not a precisely established null effect for the current question.
- Why unverified: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
- Reason for missing information: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
- Required materials and conditions: The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate
- Materials to obtain first: The reported CI, dispersion, denominator, and model for the same between-group hs-CRP estimate
- Further research: Link the estimate, dispersion, interval, and denominator in the relevant results table/model to review the range of effects compatible with them.
- Conditions for verification: Verify the original reported interval and its basis corresponding to the same estimate.
- Why this condition is needed: Needed to avoid declaring a precisely estimated null effect or treatment effect from significance and sample size alone.
- Application exceptions: Do not reconstruct intervals from P values, assignment counts, or the SD for a different endpoint.
- Remaining uncertainty: The original uncalculated precision assessment was not changed into a new CX/E0 or an effect of 0.
- Referenced methods: M15 §15.3.1–15.3.3; internal application
- Related sources: S12, S13, S14, S21

### N23 · Is there a justified criterion for the importance of a change in high-sensitivity CRP?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: An eligible effect has not been verified, and this document does not provide a threshold for an important difference or a basis for interpretation for the same comparison.
- Why unverified: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
- Reason for missing information: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
- Required materials and conditions: The basis for an important difference in the same population/assay and duration, and the corresponding interval
- Materials to obtain first: The basis for an important difference in the same population/assay and duration, and the corresponding interval
- Further research: Obtain the basis for clinical/patient importance and interpretation of the surrogate to review the scope of applicability of the results.
- Conditions for verification: Verify the relationship between the original basis for importance and the interval for the same comparison.
- Why this condition is needed: Needed to avoid automatically interpreting a significant difference as a clinically meaningful anti-inflammatory effect.
- Application exceptions: Do not propose an arbitrary hs-CRP reduction, minimum n, or duration.
- Remaining uncertainty: Do not reassess an unverified criterion as an inadequate effect or an unfavorable finding.
- Referenced methods: M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally defined limits on extensions
- Related sources: S12, S13, S14, S21

### N24 · Have the prospective plans for the eligible primary endpoint, analysis, and time points been cross-checked?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The registered-primary-endpoint record in the preserved study information is empty/unverified, and S14 records a historical basic registry page and failure to render the body. Independent cross-checking of the eligible primary endpoint/plan remains unverified.
- Why unverified: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
- Reason for missing information: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
- Required materials and conditions: Cross-checking official registration, protocol, SAP, and changes against actual results
- Materials to obtain first: Cross-checking official registration, protocol, SAP, and changes against actual results
- Further research: Link official registration versions, protocols/SAPs, and actual results to review changes and areas that have not been cross-checked.
- Conditions for verification: Compare the same eligible result with the primary endpoint, analysis, and time points in the original plan.
- Why this condition is needed: Needed to avoid treating a basic registry page as a plan with verified planned/actual endpoints.
- Application exceptions: Material not obtained does not establish nonregistration or selective reporting.
- Remaining uncertainty: Do not record endpoints as established or a results body as read solely because the record is labeled as a basic registry page.
- Referenced methods: M08 Table 8.2.a, M04 §4.6.3; internal application; material-collection and selection principles in M04 §4.5–4.6; separation of access from reading and the rules governing hyperlinks are internally designed
- Related sources: S14

### N25 · Is the nonsignificant result in S12 a direct result for this question?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The result that no significant CRP difference was reported in the placebo trial in older adults with 42 participants, 10 mg/day, and 28 days has been preserved. Selection for elevated hs-CRP and a high-sensitivity assay have not been verified.
- Why unverified: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
- Reason for missing information: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
- Required materials and conditions: The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12
- Materials to obtain first: The actual high-sensitivity assay, selection for elevated levels, original result values/intervals, and denominator in S12
- Further research: Use the original abstract/Methods/results tables to cross-check the assay/selection criteria and the actual scope of the nonsignificant result.
- Conditions for verification: Verify whether the original population/assay/results in S12 meet the fixed eligibility criteria.
- Why this condition is needed: Needed to avoid hiding a related result showing no significant difference or transferring it to a precisely established null effect on hs-CRP.
- Application exceptions: The ordinary-CRP record for 42 participants, a 10 mg dose, and 28 days is not direct evidence of efficacy for the current question.
- Remaining uncertainty: Do not interpret this nonsignificance as an hs-CRP effect of 0, equivalence, or replicated evidence against the effect.
- Referenced methods: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application
- Related sources: S12

### N26 · Is the CRP result in S13 efficacy established through a concurrent comparison?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: S13 is a before-and-after comparison in 70 people with Crohn disease, using 100 mg/day for 3 weeks, with no concurrent randomized control. Some results concern a fecal-calprotectin subgroup.
- Why unverified: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
- Reason for missing information: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
- Required materials and conditions: The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP
- Materials to obtain first: The actual population/assay, comparison, timing, and endpoint/subgroup results in RISE-UP
- Further research: Link the original abstract/figure captions, Methods, and results tables to review distinctions between before-and-after comparisons, subgroups, and controls.
- Conditions for verification: Verify the extent to which the actual design/population/assay answers the selected question.
- Why this condition is needed: Needed to avoid turning uncontrolled before-and-after changes and a fecal-calprotectin subgroup into an hs-CRP effect.
- Application exceptions: Do not automatically adopt the record of 70 participants, 100 mg, and 3 weeks as an eligible randomized comparison or analysis denominator.
- Remaining uncertainty: Preserve the before-and-after CRP material without repurposing it as a between-group hs-CRP treatment effect in the same population.
- Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application
- Related sources: S13

### N27 · Is the redox/CRP association in S21 a direct reduction effect?

Verification status: Partly verified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The redox analysis and correlation with CRP in healthy RIBOGUT participants are not a randomized treatment effect of B2 in a population selected for elevated hs-CRP.
- Why unverified: Retain differences in population/endpoint/design without deleting the original analysis.
- Reason for missing information: Retain differences in population/endpoint/design without deleting the original analysis.
- Required materials and conditions: The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT
- Materials to obtain first: The actual population, administration/design, and definitions of the redox/CRP analyses in RIBOGUT
- Further research: Compare the institutional abstract with the original analysis/results to review the boundary between an association and a randomized comparison estimate.
- Conditions for verification: Verify whether the direction, endpoint, and population of the actual analysis match the causal question posed by the comparison.
- Why this condition is needed: Needed to avoid reversing a correlation in healthy participants into a treatment effect in a population with elevated levels.
- Application exceptions: Do not generate a new hs-CRP reduction value from an association or mechanism.
- Remaining uncertainty: Retain differences in population/endpoint/design without deleting the original analysis.
- Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application
- Related sources: S21

### N28 · Have the actual population, formulation, and results of NCT05803811 been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The historical S14 record documents the basic registry page at the official study URL and a failure to render the body; the results and detailed release formulation could not be directly verified. Numerical values from the introductory information were not adopted.
- Why unverified: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
- Reason for missing information: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
- Required materials and conditions: The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports
- Materials to obtain first: The body of the official registry record, results tables, release formulation, population/assay, denominator, and linked reports
- Further research: If follow-up work is permitted, obtain the official version/results and links to papers, and review the formulation, selection criteria, effect, and denominator.
- Conditions for verification: Verify the registry's exact results and their eligibility for the fixed question using the actual documents.
- Why this condition is needed: This is needed to avoid presenting search-result snippets or a registry address as evidence that actual results were obtained.
- Application exceptions: Do not turn a historical record of failed access into an absence of research or a failed access attempt in the current work.
- Remaining uncertainty: Do not judge the overall effect or the absence of research from a single original record of inaccessible material.
- Referenced methods: Data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M08 Table 8.2.a, M04 §4.6.3; application for this assessment; M04 §4.6.3, M15 §15.3.1–15.3.3; distinctions between statuses were designed for this assessment
- Related sources: S14

### N29 · Have actual research funding, product provision, and author/institutional interests been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: Funding information for the four evidence records is unverified or was not used in this page's grade. The independence assessment axis for the current eligible result also has an empty value.
- Why unverified: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
- Reason for missing information: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
- Required materials and conditions: Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report
- Materials to obtain first: Actual research funding, product provision, author employment/declarations, and independent study-family relationships for each report
- Further research: Obtain the original funding/conflict-of-interest declarations (Funding/COI) and institutional/study-family information to distinguish funding from relationships between reports and replications.
- Conditions for verification: Compare the original declarations/funding for each material with the scope in which research independence has been verified.
- Why this condition is needed: This is needed to avoid upgrading unverified funding to a finding of independence or absence of bias.
- Application exceptions: Do not automatically exclude results merely because funding was provided.
- Remaining uncertainty: Do not newly fill in the originally undetermined funding information as I1 verification of independence or as confirmed dependence on a manufacturer.
- Referenced methods: Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items; M04 §4.6.1–4.6.2, M15 §15.3.1; application for this assessment
- Related sources: S12, S13, S14, S21

### N30 · Have the original ?/empty values and the no-human-study flag with its bounded scope (no_human_study) been preserved exactly?

Verification status: Met  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The original record contains grade ?, an empty score, B/S, and empty values for the remaining unused axes. The true value of the no-human-study flag (no_human_study) is limited to the failure to verify directly eligible results in the document search. No F/E0 was created.
- Why unverified: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
- Reason for missing information: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
- Required materials and conditions: The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time
- Materials to obtain first: The original grade, score, unused assessment axes, eligible scope, and literal wording of the search judgment at that time
- Further research: If new eligible material becomes available within a separately permitted scope, review it while distinguishing the original judgment/conditions from the new event.
- Conditions for verification: Preserve ?, empty values in the retained summaries, Boolean values/empty strings, and the bounded scope at their original locations and in their original bytes.
- Why this condition is needed: This is needed to avoid turning an uncalculated value into no effect, 0 studies worldwide, or a condition-fulfillment rate for the new table.
- Application exceptions: Do not upgrade the historical judgment in the original verdict into a new scoring result in the current work.
- Remaining uncertainty: Do not turn original empty values into the number 0, absence, or the absence of all related human studies.
- Referenced methods: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment
- Related sources: S12, S13, S14, S21

### N31 · Has the candidate concerning B6–B2 metabolic interactions been verified as a result of B2 administration?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The unresolved additional-lead record (unresolved/additional_lead) records that the original text of the candidate concerning B6–B2 metabolic interactions could not be verified in the earlier review and that the candidate was not adopted as evidence of an effect of B2 administration; the list of linked sources is empty.
- Why unverified: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
- Reason for missing information: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
- Required materials and conditions: The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location
- Materials to obtain first: The actual candidate's bibliographic record, original text, molecule/administration/population/endpoint, and result location
- Further research: If follow-up work is permitted, establish the identifier and compare the original text with the question to review whether to include it.
- Conditions for verification: Use the candidate's actual original text to verify whether it concerns an effect of B2 administration.
- Why this condition is needed: This is needed to avoid counting a merely identified, unverified candidate as a new human efficacy study.
- Application exceptions: Do not invent a source identifier (source_id), number, or paper for the empty list of linked sources.
- Remaining uncertainty: The candidate's original text or registry has not been newly read, and no new search has been performed; it is not made into a fifth report.
- Referenced methods: The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/result linkage is an application for this assessment; data-collection and selection principles in M04 §4.5–4.6; the distinction between access and reading and the rules governing hyperlinks were designed for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment
- Related sources: 

### N32 · Have eligible differences by underlying condition or baseline B2 status been compared?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The current fixed question does not combine results across underlying conditions. Direct results for eligible comparisons or for modification of the B2 effect by baseline status and condition remain unverified.
- Why unverified: Do not infer differences in treatment response from contextual results in different populations.
- Reason for missing information: Do not infer differences in treatment response from contextual results in different populations.
- Required materials and conditions: Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison
- Materials to obtain first: Prespecified subgroups, interactions, separate results, and baseline nutritional status within the same comparison
- Further research: If follow-up work is permitted, compare prespecified hypotheses and separate results concerning population/baseline differences.
- Conditions for verification: Check whether direct evidence from separate subgroup results or interaction analyses supports the extended claim.
- Why this condition is needed: This is needed to avoid using differences between older adults, people with Crohn disease, and healthy participants as verification of subgroups in response to B2.
- Application exceptions: Do not impose all subgroup studies as mandatory requirements for the principal question.
- Remaining uncertainty: Do not infer differences in treatment response from contextual results in different populations.
- Referenced methods: M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed
- Related sources: S12, S13, S14, S21

### N33 · Does the selected question include the optimal dose and persistence after discontinuation?

Verification status: Not applicable  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The current table addresses the fixed question of hs-CRP change; optimal dose and maintenance after discontinuation/long-term persistence are not added as separate mandatory claims.
- Why unverified: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
- Reason for missing information: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
- Required materials and conditions: Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term
- Materials to obtain first: Separate extended questions and materials for direct dose comparisons and follow-up after discontinuation/over the long term
- Further research: If an extension is requested, review direct dose comparisons and treatment-discontinuation/follow-up materials as a separate question.
- Conditions for verification: Distinguish whether separate claims about optimal dose/maintenance fall within this table's question scope.
- Why this condition is needed: This is needed to avoid imposing all extension studies as additional mandatory requirements for the narrow hs-CRP comparison.
- Application exceptions: Do not present the unverified original duration as though the optimal duration or long-term effects have already been verified.
- Remaining uncertainty: Not applicable is not a judgment that long-term data are absent, that an intervention is safe, or that there is no effect.
- Referenced methods: M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification were designed for this assessment
- Related sources: S12, S13, S14, S21

### N34 · Does the hs-CRP question include disease treatment or event prevention?

Verification status: Not applicable  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: The current question concerns the change in hs-CRP concentration itself. Clinical anti-inflammatory effects or event prevention are not additional mandatory claims in this table.
- Why unverified: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
- Reason for missing information: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
- Required materials and conditions: Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP
- Materials to obtain first: Separate boundaries between clinical anti-inflammatory effects, disease activity, quality of life/events, and the selected change in hs-CRP
- Further research: If the scope is extended, review direct clinical events and patient-important outcomes as an independent question/sheet.
- Conditions for verification: State whether the fixed question concerns a change in a numerical value or a separate clinical effect.
- Why this condition is needed: This is needed to avoid unconditionally imposing a clinical-event trial as a requirement for a change in a surrogate marker.
- Application exceptions: Do not remove the current question or extend it to clinical effects merely because it concerns a surrogate marker.
- Remaining uncertainty: This does not mean that clinical effects, anti-inflammatory treatment, or safety have now been verified.
- Referenced methods: M03 §3.2.4; extension boundaries developed for this assessment
- Related sources: S12, S13, S14, S21

### N35 · Have harms/discontinuations for the same population, product, and duration been verified?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: Safety for the relevant eligible population, product, and duration remains unverified. Short-term tolerability in other populations was not extended to long-term safety, and the original safety status is unknown.
- Why unverified: Unverified harms do not mean AE 0 or safety.
- Reason for missing information: Unverified harms do not mean AE 0 or safety.
- Required materials and conditions: AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures
- Materials to obtain first: AE collection, participant/event denominators, discontinuations, duration, concomitant use/vulnerable groups for eligible exposures
- Further research: Link harm-collection, discontinuation, denominator, and follow-up information to outcomes/exposures to review applicability over the long term and to vulnerable groups.
- Conditions for verification: Verify the actual harm data and scope of collection for the same population/product/duration.
- Why this condition is needed: This is needed to avoid turning tolerability in a short trial in another population into long-term safety.
- Application exceptions: Do not change the original unknown safety status and short-term contextual materials into a new safety grade.
- Remaining uncertainty: Unverified harms do not mean AE 0 or safety.
- Referenced methods: M19 §19.1.2–19.2.4; application for this assessment; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for individual study designs were designed for this assessment
- Related sources: S12, S13, S14, S21

### N36 · Has any separate verification of interference/interactions actually been performed, and within what scope?

Verification status: Unverified  
Reading scope: The exact preserved summary was actually read; original source materials/external full texts were not read in this work

- Current findings: In the nutritional extraction record (nutrition_extraction), the assay-interference and drug-interaction fields (assay_interference and drug_interactions) have empty values and are marked as not separately searched. This is a historical record that no separate systematic/comprehensive search was conducted.
- Why unverified: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
- Reason for missing information: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
- Required materials and conditions: Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed
- Materials to obtain first: Data on hs-CRP assay interference and interactions involving the relevant exposure/drugs, and the scope of searches performed
- Further research: If an extension is permitted, separately review interference and interaction data for the actual assay and concomitant exposures.
- Conditions for verification: Check whether the actual materials and review scope support statements about interference/interactions.
- Why this condition is needed: This is needed to avoid interpreting the absence of a separate search as absence of an influence.
- Application exceptions: Do not turn the question into one about assay bias itself or record an area not searched as failed access.
- Remaining uncertainty: Only the currently retained summaries were read; do not turn this into a finding of no influence or no drug interactions.
- Referenced methods: M08 Table 8.2.a, M03 §3.2.4; application for this assessment; M19 §19.1.2–19.2.4; application for this assessment; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user's scope and were designed for this assessment
- Related sources: S12, S13, S14, S21

## Evidence and sources

### S12

Tavares et al. — riboflavin, homocysteine and C-reactive protein in older adults (2009)

[Official source](https://link.springer.com/article/10.1007/s12603-009-0081-2)

Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread  
Findings recorded in the summary: The placebo-controlled trial in older adults involved 42 participants, B2 10 mg/day, and 28 days; it did not report a significant difference in CRP. Selection for elevated hs-CRP and use of a high-sensitivity assay were not verified.  
Record level: The explicitly stated scope of the retained summaries; not current verification of external results  
Independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Bibliographic information, linked summaries, and historical records in the retained summaries | Preserved locally | Obtained | Summary read | Exact locations and values/SHA; not the bytes of the original clinical full text |
| External entry point for article/publisher abstracts or full texts | Unverified (current external lookups: 0) | Access not attempted | Unread | An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history. |

### S13

von Martels et al. — RISE-UP riboflavin study in Crohn disease (2020)

[Official source](https://pubmed.ncbi.nlm.nih.gov/31873717/)

Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread  
Findings recorded in the summary: RISE-UP is a before-and-after comparison in 70 participants with Crohn disease who received B2 100 mg/day for 3 weeks. There was no concurrent randomized control group, and some results were for fecal calprotectin subgroups.  
Record level: The explicitly stated scope of the retained summaries; not current verification of external results  
Independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Bibliographic information, linked summaries, and historical records in the retained summaries | Preserved locally | Obtained | Summary read | Exact locations and values/SHA; not the bytes of the original clinical full text |
| External entry point for the article or PubMed abstract/full text | Unverified (current external lookups: 0) | Access not attempted | Unread | An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history. |

### S14

Clinical trial record NCT05803811

[Official source](https://clinicaltrials.gov/study/NCT05803811)

Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread  
Findings recorded in the summary: According to the historical record, the registry results and detailed release formulation could not be directly verified. Numerical values from the search overview were not adopted.  
Record level: The explicitly stated scope of the retained summaries; not current verification of external results  
Independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Bibliographic information, linked summaries, and historical records in the retained summaries | Preserved locally | Obtained | Summary read | Exact locations and values/SHA; not the bytes of the original clinical full text |
| ClinicalTrials.gov registry webpage and unobtained results body | Unverified (current external lookups: 0) | Access not attempted | Unread | An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history. |

### S21

Bourgonje et al. — riboflavin and systemic redox status (2022)

[Official source](https://research.rug.nl/en/publications/the-effect-of-riboflavin-supplementation-on-the-systemic-redox-st/)

Materials actually read: The bibliographic information and summaries in the currently retained materials were actually read; external original materials remain unread  
Findings recorded in the summary: RIBOGUT's redox analysis and CRP correlations in healthy participants do not constitute a randomized treatment effect of B2 in a group with elevated hs-CRP.  
Record level: The explicitly stated scope of the retained summaries; not current verification of external results  
Independent replication: The distinction concerns 4 bibliographic records and 4 stored study identifiers (study_id); it does not certify 4 directly eligible studies, a unique participant count, or independent replication.

| Material | Public availability | Access status | Actually read | Notes |
|---|---|---|---|---|
| Bibliographic information, linked summaries, and historical records in the retained summaries | Preserved locally | Obtained | Summary read | Exact locations and values/SHA; not the bytes of the original clinical full text |
| Institutional article-abstract webpage and linked full text | Unverified (current external lookups: 0) | Access not attempted | Unread | An external entry point is provided, but the material is currently unread. Historical records concerning abstracts/figure captions/institutional abstracts/basic registry pages and historical failures to access results are not treated as current access history. |

## Review criteria and methods

These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score.

- M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly document the question, eligibility conditions, and reasons for changes, and distinguish intervention variants. · Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool
- M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports; do not omit studies solely because results are unreported. · Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool
- M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the outcome and effect of interest when reviewing randomization, attrition, missing data, measurement, and selective reporting. · Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool
- M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect values, intervals, importance, and applicability. Sample size alone does not determine precision. · Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool
- M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations, and follow-up from efficacy questions. Case reports do not establish incidence. · Reuse of the methodological principles/versions preserved for 1585 and 5 actual HTML copies; no new reading of the full methodological text or execution of an official tool

## What the statuses mean

- Partly verified: Some information in the retained summaries is verified, but gaps remain regarding the eligible population, assay, preparation, and results
- Unverified: The specified necessary materials could not be established within the currently preserved scope; this does not mean an effect of 0, 0 studies worldwide, or safety
- Review incomplete: The original sources were not cross-checked or searched within the permitted scope
- Not reported: A scope-limited status indicating that the item was not stated in the specific material/section that was read
- Inaccessible: Used only for materials that could not be accessed despite an actual attempt. Not assigned to clinical materials in this work
- Insufficient evidence meeting the criteria: Used only when related studies within the defined scope have been reviewed and the evidence is insufficient to answer the criterion. It is not applied across the board in this work
- Not applicable: Separate clinical-event/optimal-dose/long-term extensions are not imposed as additional mandatory requirements for the selected hs-CRP change question
- Conflicting data: Used when materials that are difficult to reconcile for the same question, time point, and analysis have been compared. Not assigned merely because numerical values in reviews differ
- Met: The specified question/scope/attribution/preservation linkage has been verified; distinguished from certification of direct hs-CRP efficacy or full-text reading

## Change history

2026-11-01 · Public page/materials 1.0. A public display and data were created from the existing 36 items. No new clinical search, change to verification status, or scoring was performed.