# Single-ingredient riboflavin (vitamin B2) × Reduction of persistent fatigue in quiescent inflammatory bowel disease Verdict 3090 · Evidence Check Stored-material review date: 2026-10-05 Original evidence date: 2026-09-15 Review-criteria version: NGM-3090-ORAL-B2-QUIESCENT-IBD-FATIGUE-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 with persistent fatigue in quiescent IBD; distinguished from general energy, acute exercise recovery, and correction of confirmed B2 deficiency - Ingredient, formulation and route: A question about adding ordinary oral riboflavin (B2) as a single ingredient; the actual eligible preparation remains unverified - Dose: The dose in an eligible trial of B2 alone remains unverified - Comparator: Question: placebo/no additional treatment under the same usual IBD care; eligible comparative results remain unverified - Measured outcome: Change in a validated persistent-fatigue scale; the scale used in an actual B2 trial remains unverified - Duration: The duration of an eligible trial of B2 alone remains unverified - Questions outside this scope: B1 administration; Observational associations involving vitamers; A combination product without B2; Acute exercise recovery; Correction of confirmed deficiency; IBD clinical events ## Checklist items ### N01 · What question about administration of B2 alone and persistent fatigue is being reviewed? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original question concerns adding ordinary oral riboflavin (B2) alone and reducing persistent fatigue in quiescent IBD. The original manuscript's list of additional claims is empty; other ingredients or exercise recovery were not made into additional claims. - Why unverified: The question in the original manuscript and its inclusion/exclusion boundaries were verified. This status does not mean that an actual effect of B2 administration was verified. - Reason for missing information: The question was verified, but the actual intervention and comparative results of an eligible B2 trial remain unverified. - Required materials and conditions: Persistent fatigue in adults with quiescent IBD, addition of ordinary oral riboflavin alone, a comparator under the same usual care, the fatigue scale, and the boundaries stated in the original manuscript. - Materials to obtain first: Persistent fatigue in adults with quiescent IBD, addition of ordinary oral riboflavin alone, a comparator under the same usual care, the fatigue scale, and the boundaries stated in the original manuscript. - Further research: First state these boundaries as eligibility criteria, then individually compare whether the ingredient, population, and endpoint in each actual study all match. - Conditions for verification: Distinguish the comparative effect of B2 administration from B1 administration, vitamer associations, combination products, and exercise recovery, and link it to a single independent question. - Why this condition is needed: Even when an ingredient name or the word fatigue is the same, a different intervention or patient state means a different question. - Application exceptions: Details of eligible administration that remain unverified are left as part of the question. Doses or endpoints from related studies are not used to fill them in. - Remaining uncertainty: The question was verified, but the actual intervention and comparative results of an eligible B2 trial remain unverified. - Referenced methods: The meanings of the existing family templates C01, C05 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N02 · Does the population in the actual B2 material consist of adults with quiescent IBD? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original question concerns adults with quiescent IBD, but the currently retained materials do not verify direct results for B2 alone in that population. TARIF's population in remission comes from material on B1 administration. - Why unverified: No direct material is available to link the population in remission specified by the question to an actual eligible B2 study population. - Reason for missing information: Remission assessment, disease composition, and eligibility details for an eligible B2 population remain unverified. - Required materials and conditions: IBD diagnosis/type, the definition and assessment timing of remission, age and eligibility criteria, and a characteristics table for the actual population receiving B2. - Materials to obtain first: IBD diagnosis/type, the definition and assessment timing of remission, age and eligibility criteria, and a characteristics table for the actual population receiving B2. - Further research: Prespecify the definition of remission and recruitment criteria, and report the population's B2 comparative results separately. - Conditions for verification: Verify remission status in the actual eligible B2 population, distinguishing it from a general-fatigue population or active disease. - Why this condition is needed: Remission status affects the causes of persistent fatigue and applicability to the current population. - Application exceptions: The presence of a population in remission in a B1 trial does not mean that the population in the material on B2 alone has also been verified. - Remaining uncertainty: Remission assessment, disease composition, and eligibility details for an eligible B2 population remain unverified. - Referenced methods: The meanings of the existing family templates C04, E07 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N03 · What criteria were used to select for persistent fatigue? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The question's outcome is change in a validated persistent-fatigue scale. Fatigue selection criteria and the scale in an actual B2 trial remain unverified; acute muscle soreness and recovery performance in an ultramarathon are different endpoints. - Why unverified: No direct information is available to verify selection for persistent fatigue and the assessment tools in an eligible B2 population. - Reason for missing information: The actual definition of persistence, selection threshold, and baseline fatigue severity remain unverified. - Required materials and conditions: Eligibility criteria concerning fatigue persistence, severity, and assessment tools, and selection records for the actual B2 population. - Materials to obtain first: Eligibility criteria concerning fatigue persistence, severity, and assessment tools, and selection records for the actual B2 population. - Further research: Select a definition of persistent fatigue and assessment tools appropriate to the clinical context, and record fatigue status at recruitment. - Conditions for verification: Verify selection for persistent fatigue and actual measurement of patient symptoms, distinguishing these from discomfort after acute exercise. - Why this condition is needed: Chronic fatigue in patients and acute exercise recovery cannot be combined as the same effect. - Application exceptions: Do not assign arbitrary numerical values to a duration or scale threshold absent from the original text. - Remaining uncertainty: The actual definition of persistence, selection threshold, and baseline fatigue severity remain unverified. - Referenced methods: The meanings of the existing family templates C04, C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N04 · Are baseline B2 status and the population requiring correction of deficiency distinguished? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Baseline vitamin status and deficiency-assessment methods were recorded as unverified in the original manuscript. This question is distinguished from correction of confirmed B2 deficiency; measurement of circulating vitamers was not turned into a diagnosis of deficiency. - Why unverified: No materials on baseline status and deficiency assessment are available for an eligible population receiving B2. - Reason for missing information: B2 status, deficiency-assessment methods, and the distribution of deficient participants remain unverified. - Required materials and conditions: Measurement of B2 status, deficiency-assessment methods, baseline distributions, and whether the actual treated population has deficiency. - Materials to obtain first: Measurement of B2 status, deficiency-assessment methods, baseline distributions, and whether the actual treated population has deficiency. - Further research: Record baseline status and assessment methods, and plan analyses by deficiency status in advance if they are needed. - Conditions for verification: Distinguish general persistent fatigue in quiescent IBD from correction of confirmed B2 deficiency, and verify actual baseline status. - Why this condition is needed: This is needed to avoid confusing associations involving vitamer levels with the application of deficiency treatment. - Application exceptions: Do not use the presence of fatigue or measurement of FMN alone to diagnose B2 deficiency. - Remaining uncertainty: B2 status, deficiency-assessment methods, and the distribution of deficient participants remain unverified. - Referenced methods: The meanings of the existing family templates C04, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N05 · Is the actual administered preparation riboflavin alone? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The question concerns an ordinary oral preparation of riboflavin alone. The molecule, salt, formulation, and manufacturing origin in an actual eligible result remain unverified; measured FMN was kept separate from the molecular form of the administered preparation. - Why unverified: The molecular-form value in the original observation record is null (no value). The ingredient name in the question alone cannot verify the product actually administered. - Reason for missing information: The product composition, salt, formulation, manufacturing source, and batch for eligible B2 remain unverified. - Required materials and conditions: The ingredient's molecular form and salt, formulation, product composition, manufacturing origin and batch, and materials verifying actual administration. - Materials to obtain first: The ingredient's molecular form and salt, formulation, product composition, manufacturing origin and batch, and materials verifying actual administration. - Further research: Compare product composition and molecular form with administration records, and record every active ingredient by arm. - Conditions for verification: Distinguish administration of riboflavin alone from B1, combination products, and analysis of circulating FMN, and verify the identity of the actual product. - Why this condition is needed: If the identity of the pharmacological exposure differs, a contribution cannot be attributed to B2 alone. - Application exceptions: Naming B2 alone in the question does not replace verification of the actual trial product. Classification by plant part used does not apply. - Remaining uncertainty: The product composition, salt, formulation, manufacturing source, and batch for eligible B2 remain unverified. - Referenced methods: The meanings of the existing family templates C05, E02 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N06 · Is the actual administration route in an eligible B2 result oral? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The route specified by the question is oral. The route in an actual eligible B2 result is recorded as null (no value) and unverified in the retained study information. - Why unverified: The oral route specified by the question was verified, but it has not been linked to an actual eligible B2 administration record. - Reason for missing information: No materials verifying the actual route for an eligible result are available. - Required materials and conditions: Sections and administration records specifying the method and route of administration in an eligible trial. - Materials to obtain first: Sections and administration records specifying the method and route of administration in an eligible trial. - Further research: After verifying actual administration methods, classify materials involving different routes separately. - Conditions for verification: Link the oral route specified by the question separately from the route verified in actual eligible material. - Why this condition is needed: This is needed to avoid turning verification of oral B1 administration into verification of the actual route of B2 administration. - Application exceptions: Do not replace the null entry (no value) in the observation record with the oral route specified by the question. - Remaining uncertainty: No materials verifying the actual route for an eligible result are available. - Referenced methods: The meaning of the existing family template C05 was adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N07 · What are the nominal and actual doses in an eligible B2 comparison? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The dose in an eligible trial of B2 alone remains unverified. Numerical values absent from the original text were not imported from B1 or ultramarathon materials. - Why unverified: A nominal or actual dose attributable to a comparison of B2 alone for fatigue in quiescent IBD has not been verified. - Reason for missing information: Materials on dose, frequency, actual exposure, changes, and adherence remain unverified. - Required materials and conditions: The nominal dose, frequency, actual intake, changes, and adherence records for B2 alone. - Materials to obtain first: The nominal dose, frequency, actual intake, changes, and adherence records for B2 alone. - Further research: In a subsequent comparison, specify a dosing strategy supported by evidence and track actual exposure and changes by arm. - Conditions for verification: Verify the actual B2 dose for the eligible population and endpoint, without repurposing doses from related studies. - Why this condition is needed: Doses from related B1 or exercise trials cannot establish the effect or safety range for persistent fatigue in IBD. - Application exceptions: Do not present an unverified actual dose as 0 mg or as no effect at any dose. - Remaining uncertainty: Materials on dose, frequency, actual exposure, changes, and adherence remain unverified. - Referenced methods: The meanings of the existing family templates C05, E02, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N08 · Are the periods of administration, fatigue assessment, and follow-up after discontinuation distinguished? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The duration and fatigue-assessment time points in an eligible trial of B2 alone remain unverified. The time window for acute exercise recovery was not used as a duration for persistent IBD fatigue. - Why unverified: No eligible B2 material is available that links administration duration with the time points for measuring persistent fatigue. - Reason for missing information: The timing of administration, assessment, and follow-up after discontinuation remains unverified. - Required materials and conditions: The duration of eligible B2 administration, the fatigue-assessment schedule, the time of discontinuation, and subsequent follow-up records. - Materials to obtain first: The duration of eligible B2 administration, the fatigue-assessment schedule, the time of discontinuation, and subsequent follow-up records. - Further research: Justify an assessment schedule appropriate to the time course of fatigue, and distinguish administration, assessment, and follow-up after discontinuation. - Conditions for verification: Verify the actual administration period and outcome-measurement time points; do not turn a short-term recovery interval into a duration of persistent fatigue. - Why this condition is needed: Different durations cannot be interpreted as the same effect on fatigue or the same persistent effect. - Application exceptions: Do not specify a common minimum number of weeks or a length of long-term follow-up without original source material. - Remaining uncertainty: The timing of administration, assessment, and follow-up after discontinuation remains unverified. - Referenced methods: The meanings of the existing family templates C06, E08 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N09 · Has the actual comparator for B2 under the same usual IBD care been verified? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The question is a comparison with placebo or no additional treatment under the same usual IBD care. The actual comparator for an eligible B2 result has not been verified. - Why unverified: A planned comparison question exists, but there are no records of the actual implementation of the B2 administration arm and comparator arm. - Reason for missing information: The actual comparator, placebo composition, and usual care by arm remain unverified. - Required materials and conditions: The actual placebo arm or arm with no additional treatment, placebo composition, usual-care policy, and actual treatment by arm. - Materials to obtain first: The actual placebo arm or arm with no additional treatment, placebo composition, usual-care policy, and actual treatment by arm. - Further research: Design a comparison under the same usual-care policy, and disclose placebo composition, actual treatment, and changes. - Conditions for verification: Verify the comparison policy in the question and the actual B2 comparison; do not repurpose the control arm from a B1 trial. - Why this condition is needed: To interpret the intervention's contribution, it is necessary to know what was compared with the arm receiving additional B2. - Application exceptions: Do not describe the placebo/no-additional-treatment comparison in the question as a comparator actually implemented. - Remaining uncertainty: The actual comparator, placebo composition, and usual care by arm remain unverified. - Referenced methods: The meanings of the existing family templates C05, E01, E02 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N10 · Are concurrent vitamins, diet, and IBD treatment distinguished from the contribution of B2? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Arm-level details of concurrent vitamins and total dietary intake in an eligible comparison remain unverified. The B1·B6·B12·magnesium combination was not used as evidence of the contribution of B2 alone. - Why unverified: Actual materials on concomitant use, diet, and changes in an eligible B2 comparison could not be verified. - Reason for missing information: Vitamins, diet, IBD medications, rescue treatment, and adherence by arm remain unverified. - Required materials and conditions: IBD treatment, rescue treatment, concurrent vitamins, total dietary intake, changes, and adherence materials by arm. - Materials to obtain first: IBD treatment, rescue treatment, concurrent vitamins, total dietary intake, changes, and adherence materials by arm. - Further research: Record all relevant exposures and changes by arm, and prespecify the effect of interest and handling methods for the strategy of adding B2. - Conditions for verification: Record actual concomitant use and changes, and examine whether other ingredients or differences in usual care are mixed with the contribution of B2. - Why this condition is needed: This is needed to avoid attributing a B-vitamin combination or dietary differences to the effect of B2 alone. - Application exceptions: Do not impose a requirement that actual changes in every arm must be the same. Compare the effect of interest with the permitted policies. - Remaining uncertainty: Vitamins, diet, IBD medications, rescue treatment, and adherence by arm remain unverified. - Referenced methods: The meanings of the existing family templates C05, E02, H05 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N11 · Have the fatigue scale, units, direction, and measurement time points been verified? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original question's outcome is change in a validated persistent-fatigue scale and concerns patient symptoms and function. The instrument, score direction, and time points in an actual B2 trial remain unverified. - Why unverified: The endpoint specified by the question is fixed, but no direct B2 material is available linking an actual instrument with measured values. - Reason for missing information: Information on the scale, version, units, direction, time points, and validity remains unverified. - Required materials and conditions: The fatigue instrument, version, score direction, units, measurement time points, and basis for validity in an actual B2 trial. - Materials to obtain first: The fatigue instrument, version, score direction, units, measurement time points, and basis for validity in an actual B2 trial. - Further research: Justify a fatigue instrument and measurement schedule appropriate to the population, and disclose the score direction and definition of change. - Conditions for verification: Attribute actual measurements of the selected endpoint to patients' persistent fatigue, keeping them separate from circulating vitamers and exercise performance. - Why this condition is needed: If scales or directions differ, numerical increases and decreases cannot be treated as the same improvement. - Application exceptions: Do not turn the question's requirement for a validated scale into a fact that the instrument actually used has been validated. - Remaining uncertainty: Information on the scale, version, units, direction, time points, and validity remains unverified. - Referenced methods: The meanings of the existing family templates C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N12 · What are the blinding and collection procedures and measurement limitations for fatigue assessment? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The currently retained materials do not link information on assessors, collection procedures, or blinding to an eligible B2 fatigue result. Methods from B1 materials were not imported to verify the adequacy of B2 measurement. - Why unverified: Because the eligible B2 measurement procedures remain unverified, the presence or absence of measurement bias cannot be determined. - Reason for missing information: Assessment blinding, data collection by arm, missing measurements, and measurement limitations remain unverified. - Required materials and conditions: Actual fatigue assessors, self-report procedures, collection by arm, assessment blinding, and records of missing data. - Materials to obtain first: Actual fatigue assessors, self-report procedures, collection by arm, assessment blinding, and records of missing data. - Further research: Standardize fatigue-data collection procedures and document feasible blinding, differences in assessment, and limitations. - Conditions for verification: Verify the actual procedures and differences between arms in subjective fatigue measurement, and do not assume that unknown methods were adequate or failed. - Why this condition is needed: This is needed to distinguish differences in expectations and data collection from differences in patients' symptoms. - Application exceptions: Do not automatically score unverified or infeasible blinding as a flaw. - Remaining uncertainty: Assessment blinding, data collection by arm, missing measurements, and measurement limitations remain unverified. - Referenced methods: The content of the existing family template E03 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N13 · Can allocation, measurement, and analysis denominators for the actual fatigue endpoint be distinguished? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The actual analysis denominator for the primary endpoint is null (no value) and unverified. In the three related reports, the participant-count fields (n) contain references to separate historical numerical records and wording prohibiting substitution; they are not verified numerical participant counts. - Why unverified: The endpoint-analysis denominator is unavailable, and the referenced separate historical numerical file was not opened in this work. - Reason for missing information: Participant counts for allocation, exposure, fatigue measurement, completion, and analysis remain unverified. - Required materials and conditions: Recruitment, allocation, exposure, measurement, completion, and analysis flow in an eligible B2 trial, and participant counts for each endpoint. - Materials to obtain first: Recruitment, allocation, exposure, measurement, completion, and analysis flow in an eligible B2 trial, and participant counts for each endpoint. - Further research: Make participant flow and endpoint-analysis counts by arm available, and link reasons for exclusion to the results. - Conditions for verification: Verify the actual number analyzed for each endpoint in the original material, and do not replace it with the total participant count from a trial of another ingredient. - Why this condition is needed: Confusing the total participant count with the fatigue-analysis denominator changes the interpretation of the effect and the extent of missing data. - Application exceptions: Do not treat a string referring to a historical numerical record as a number that has been read. Do not estimate denominators from rounding or other reports. - Remaining uncertainty: Participant counts for allocation, exposure, fatigue measurement, completion, and analysis remain unverified. - Referenced methods: The content of the existing family templates C07, E04 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N14 · Can the design, allocation, and effect of interest in an eligible B2 comparison be verified? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: S05 is an observational vitamer subanalysis of a B1 trial. Allocation, analysis populations, and the effect of interest for an eligible direct B2 comparison have not been verified. - Why unverified: The design of a related trial does not establish the design of a B2-alone comparison. - Reason for missing information: The design, allocation, concealment, baseline balance, and analysis model for a direct B2 comparison remain unverified. - Required materials and conditions: The actual design, such as parallel or crossover; allocation, concealment, and baseline balance; and the analysis population, model, and between-group contrast. - Materials to obtain first: The actual design, such as parallel or crossover; allocation, concealment, and baseline balance; and the analysis population, model, and between-group contrast. - Further research: Conduct a direct B2 comparison with the effect of interest and design specified and allocation, analysis populations, and handling methods documented. - Conditions for verification: Verify the effect of assignment or adherence and the between-group analysis for the actual B2 intervention, distinguishing them from observational vitamer analyses. - Why this condition is needed: Observational associations and effects of administration, and within-group changes and between-group contrasts, have different causal interpretations. - Application exceptions: Do not fill an unverified eligible design with an assertion of nonrandomization or an ITT analysis. Do not arbitrarily assign not applicable (NA) to a crossover design either. - Remaining uncertainty: The design, allocation, concealment, baseline balance, and analysis model for a direct B2 comparison remain unverified. - Referenced methods: The content of the existing family templates E01, E04 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N15 · Were missing fatigue outcomes, dropouts, and treatment changes reflected in the analysis? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Materials on the denominator, missing data, dropout, and handling of changes for an eligible B2 fatigue endpoint remain unverified. The original judgment also did not turn unverified methods into invented flaws. - Why unverified: Loss of observations and handling methods for the actual fatigue result have not been verified. - Reason for missing information: Missing data, dropouts, treatment changes, handling methods, and sensitivity analyses by arm remain unverified. - Required materials and conditions: Materials on missing fatigue measurements and reasons for dropout by arm, treatment changes, handling of missing data, and sensitivity analyses. - Materials to obtain first: Materials on missing fatigue measurements and reasons for dropout by arm, treatment changes, handling of missing data, and sensitivity analyses. - Further research: Record missing data, dropouts, and treatment changes by arm, and link prespecified handling and sensitivity analyses to the actual fatigue contrast. - Conditions for verification: Verify the extent of actual missing endpoint data and the handling methods, distinguishing missing values from no change. - Why this condition is needed: This is needed to avoid presenting an analysis restricted to people with available results as the overall effect of adding B2. - Application exceptions: Do not classify unverified missing data as 0 dropouts or as an established large bias. - Remaining uncertainty: Missing data, dropouts, treatment changes, handling methods, and sensitivity analyses by arm remain unverified. - Referenced methods: The content of the existing family templates C07, E02, E04, H06 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N16 · Is there a between-group estimate and interval for fatigue change with B2 alone? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Effect values and intervals for the exact B2-alone question have not been verified. The original record of effect-size estimation attempts states that eligible results were unverified and that no new effect approximation was performed. - Why unverified: There is no reported between-group B2 fatigue estimate, dispersion, or CI with which to review magnitude or precision. - Reason for missing information: The between-group effect, dispersion, CI, and denominator remain unverified. - Required materials and conditions: The between-group effect value, units, dispersion, denominator, CI, and analysis definition for the actual fatigue endpoint. - Materials to obtain first: The between-group effect value, units, dispersion, denominator, CI, and analysis definition for the actual fatigue endpoint. - Further research: Report the between-group fatigue estimate, dispersion, denominator, and CI together in a direct comparison, and state what the estimate represents. - Conditions for verification: Link only reported between-group estimates and intervals for the same population, endpoint, and time point; do not reconstruct values from P values or other studies. - Why this condition is needed: Correlations or significance alone cannot establish the direction, magnitude, or precision of the effect of B2 administration. - Application exceptions: Do not turn an unverified effect into 0, equivalence, or an inadequate effect. Do not calculate a new no-effect grade. - Remaining uncertainty: The between-group effect, dispersion, CI, and denominator remain unverified. - Referenced methods: The content of the existing family templates C06, C07, E04, E05 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N17 · Is there a basis for judging a fatigue difference that patients would consider important? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The actual B2 fatigue instrument, effect, interval, and corresponding basis for an important difference remain unverified. No numerical threshold absent from the original text was added. - Why unverified: There is no criterion for the same population and instrument, or direct result, with which to judge the clinical magnitude of the effect. - Reason for missing information: The clinically important difference and corresponding between-group interval remain unverified. - Required materials and conditions: The basis for an important difference appropriate to the actual fatigue instrument and population, the source of the criterion, and the reported effect interval. - Materials to obtain first: The basis for an important difference appropriate to the actual fatigue instrument and population, the source of the criterion, and the reported effect interval. - Further research: Establish the basis for an important difference for each population and fatigue instrument, and compare the criterion set at the planning stage with the actual interval. - Conditions for verification: Compare a justified criterion for fatigue importance with the effect and interval from the same analysis, or record why a judgment cannot be made. - Why this condition is needed: Statistical associations must be distinguished from symptom improvement that matters to patients. - Application exceptions: Do not arbitrarily set a common minimum sample size, duration, or difference on the scale. An unverified criterion does not mean no effect. - Remaining uncertainty: The clinically important difference and corresponding between-group interval remain unverified. - Referenced methods: The content of the existing family template E05 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N18 · Can the prospective plan for the B2 fatigue endpoint be compared with the actual report? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Independent cross-checking of the registry against the primary endpoint remains unverified. The study identifier for S05 contains TARIF-NCT03634735, but the separate registry-number field (nct) is null (no value); this is an identity clue for the B1 study family. - Why unverified: Eligible B2 plans and actual results have not been compared, and a B1 registration string cannot fill the gap. - Reason for missing information: Concordance among B2 registration, protocol, analysis plan, and primary endpoint remains unverified. - Required materials and conditions: Eligible B2 registration, protocol, and analysis plan, and records of changes to the primary endpoint, time points, and analyses. - Materials to obtain first: Eligible B2 registration, protocol, and analysis plan, and records of changes to the primary endpoint, time points, and analyses. - Further research: Compare planning materials and reports for an eligible B2 study, and retain changes to endpoints, timing, and analyses and the reasons for them. - Conditions for verification: Compare the actual B2 plan and report, without repurposing the B1 TARIF registration identity as a B2 plan. - Why this condition is needed: Concordance between the endpoint named by a paper and the preregistered endpoint must be verified separately. - Application exceptions: Do not turn unverified registration concordance into an established finding of nonregistration or selective reporting. - Remaining uncertainty: Concordance among B2 registration, protocol, analysis plan, and primary endpoint remains unverified. - Referenced methods: The content of the existing family templates C09, E06 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N19 · Was the substance actually administered in TARIF B2 or B1? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The actual intervention in S05 is oral thiamine hydrochloride (B1). It is not a comparison of B2 administered alone, so it was excluded from direct efficacy evidence and retained as related material. - Why unverified: The retained case manuscript explicitly states that the intervention was B1 and was not B2 administration, verifying the intervention mismatch. - Reason for missing information: This report does not provide a direct effect of B2 administration. The clinical full text has not been read in this work. - Required materials and conditions: Records showing the ingredient, molecular form, and route actually administered in S05, and the role of the relevant result. - Materials to obtain first: Records showing the ingredient, molecular form, and route actually administered in S05, and the role of the relevant result. - Further research: Compare the intervention section of the original report with the subanalysis, and separately verify whether a B2-administration comparison exists. - Conditions for verification: Do not turn actual B1 administration into a B2 intervention; distinguish whether the intervention is eligible for this question. - Why this condition is needed: A shared B-vitamin label or a population with fatigue alone does not establish that the ingredient is the same. - Application exceptions: Exclude it from direct evidence of a B2 effect because the intervention does not match, while preserving the related observational information. - Remaining uncertainty: This report does not provide a direct effect of B2 administration. The clinical full text has not been read in this work. - Referenced methods: The content of the existing family templates C05, E02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05 ### N20 · Does an association between circulating B2 vitamers and fatigue establish an effect of administration? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: In S05, the B2-related vitamer analysis is an observational subanalysis of participants in a B1 trial. The association may motivate research, but it was not turned into evidence that administering B2 improves persistent fatigue. - Why unverified: The distinction between the observational analysis and actual administration was verified in the retained summary. Direct effect values remain separately unverified. - Reason for missing information: Detailed numerical values and adjustment for vitamer associations, and direct B2-administration results, are not verified in the current input. - Required materials and conditions: Vitamer measurements and observational analyses in S05, the ingredient actually administered, and information on the direction of the association and adjustment. - Materials to obtain first: Vitamer measurements and observational analyses in S05, the ingredient actually administered, and information on the direction of the association and adjustment. - Further research: Review exposures and adjustment in the observational analysis separately from comparisons of B2 administration, and design the direct comparison needed. - Conditions for verification: Distinguish associations involving circulating markers from changes in patients' fatigue following riboflavin administration. - Why this condition is needed: Recasting a biomarker association as a treatment effect changes the causal direction. - Application exceptions: Preserve observational associations as leads for further research, without presenting them as between-group results from actual B2 administration. - Remaining uncertainty: Detailed numerical values and adjustment for vitamer associations, and direct B2-administration results, are not verified in the current input. - Referenced methods: The content of the existing family templates C06, E04, E09 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05 ### N21 · Is the TARIF vitamer analysis being counted as a separate replication for B2? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: S05 is recorded as an observational subanalysis from the TARIF-NCT03634735 family. It was not counted as a separate direct B2 trial or independent replication, and the number of unique participants was not established either. - Why unverified: The retained case manuscript states that it belongs to the same TARIF family. The body of the external registry record was not cross-checked in this work. - Reason for missing information: The full list of reports in the study family and details of participant overlap remain unverified. - Required materials and conditions: Study-family links among TARIF registration, the main report, the vitamer subanalysis, participants, and outcomes. - Materials to obtain first: Study-family links among TARIF registration, the main report, the vitamer subanalysis, participants, and outcomes. - Further research: Check the linkage table for registration, the main report, and the subanalysis, and indicate overlap by endpoint and analysis. - Conditions for verification: Do not count a subanalysis from the same TARIF family as an independent B2 trial or replication. - Why this condition is needed: This is needed to distinguish the number of reports from the number of unique studies and to avoid using a family of studies on another intervention as replication for B2. - Application exceptions: Do not infer original report contents or unique participant counts that are absent from the current input. - Remaining uncertainty: The full list of reports in the study family and details of participant overlap remain unverified. - Referenced methods: The content of the existing family templates C02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05 ### N22 · Does the IBD combination product in S08 contain B2? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The combination intervention in S08 consists of B1·B6·B12 and magnesium, with no B2. Its results were not attributed to a B2 effect or an isolated B1 effect. - Why unverified: The composition and role wording in the currently retained materials explicitly states the absence of B2. This is not an assessment of the combination product's own effect. - Reason for missing information: Detailed effect values for the combination product and isolated effects of individual ingredients remain unverified in the current input. - Required materials and conditions: All active ingredients in S08, the composition by arm, and whether individual ingredients were compared separately. - Materials to obtain first: All active ingredients in S08, the composition by arm, and whether individual ingredients were compared separately. - Further research: Compare the product composition with the actual intervention section, and link only a separable B2 comparison to the B2-alone question. - Conditions for verification: Verify the B1·B6·B12·magnesium composition, and do not attribute results from a combination product without B2 to B2. - Why this condition is needed: This is needed to avoid assuming that a product contains B2 solely because it is called a general B-vitamin complex. - Application exceptions: Do not delete the combination-product results, but do not present them as an effect of B2 or an isolated effect of B1. - Remaining uncertainty: Detailed effect values for the combination product and isolated effects of individual ingredients remain unverified in the current input. - Referenced methods: The content of the existing family templates C05, E02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S08 ### N23 · Is acute exercise recovery in S25 the same outcome as persistent fatigue in IBD? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: S25 assessed acute muscle soreness and recovery performance after ultradistance running. Its population and endpoints differ from those for persistent fatigue in quiescent IBD, so it was not adopted as a direct result. - Why unverified: The retained materials explicitly state the population and endpoint mismatch. The actual exercise-trial full text was not read in this work. - Reason for missing information: Direct numerical results for persistent fatigue in IBD and detailed numerical results from the exercise trial remain unverified in the current input. - Required materials and conditions: A comparison table of the ultramarathon study's population, acute endpoints, and timing against the IBD fatigue question. - Materials to obtain first: A comparison table of the ultramarathon study's population, acute endpoints, and timing against the IBD fatigue question. - Further research: Verify the population, endpoint, and timing at actual locations in the original text, and find a separate direct B2 comparison that meets the question. - Conditions for verification: Distinguish acute muscle soreness and recovery performance from patients' persistent fatigue, without repurposing samples or effects. - Why this condition is needed: Matching the B2 ingredient alone cannot remove differences in disease, endpoint, and timing. - Application exceptions: Do not combine exercise outcomes with persistent-fatigue outcomes in IBD, whether the exercise findings are favorable or unfavorable. - Remaining uncertainty: Direct numerical results for persistent fatigue in IBD and detailed numerical results from the exercise trial remain unverified in the current input. - Referenced methods: The content of the existing family templates C04, C06, E07, E08 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S25 ### N24 · Can funding and independent replication for direct B2 evidence be verified? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The funding fields for the three related reports are recorded as unverified or not used in this page's grade. Direct B2 results remain unverified, and the corresponding independence assessment axis is unverified and null (no value). - Why unverified: There is no material with which to verify funding, conflicts of interest, or independent replication for an eligible B2 report. - Reason for missing information: Funding, product provision, conflicts of interest, and independent study-family relationships for direct evidence remain unverified. - Required materials and conditions: Research funding, product provision, author conflicts of interest, and independent study-family information for eligible B2 reports. - Materials to obtain first: Research funding, product provision, author conflicts of interest, and independent study-family information for eligible B2 reports. - Further research: Verify declarations, product provision, and study-family identity for each eligible report, and cross-check whether replication is independent. - Conditions for verification: Explain independence only on the basis of verified funding and study families, and do not turn unverified information into independent funding or absence of bias. - Why this condition is needed: Even when there are several related reports, independent replication of the same question requires separate verification. - Application exceptions: Do not automatically exclude material because a conflict of interest exists. A statement that funding was not used in grading does not mean there was no funding. - Remaining uncertainty: Funding, product provision, conflicts of interest, and independent study-family relationships for direct evidence remain unverified. - Referenced methods: The content of the existing family templates C10, C02, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N25 · Are the direction and no-difference findings in related materials distinguished from direct B2 results? Verification status: Partly verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Observations from the vitamer analysis in the B1 trial, the combination without B2, and acute exercise recovery were preserved according to their roles. Detailed effect directions or numerical results showing no difference that are absent from the current input were not invented, and the lack of verified directly eligible B2 results was not converted into D·F. - Why unverified: The roles of the related reports and reasons for exclusion were verified, but detailed directions of results and the distribution of directly eligible B2 results remain unverified. - Reason for missing information: Detailed effects, dispersion, and P values in the related reports, and the distribution of eligible B2 results, remain unverified. - Required materials and conditions: The actual endpoints, analyses, direction of results, and eligibility of the three related reports, and direct B2 comparison results. - Materials to obtain first: The actual endpoints, analyses, direction of results, and eligibility of the three related reports, and direct B2 comparison results. - Further research: Compare direct and related materials by endpoint and analysis, and report all available results together, regardless of their direction. - Conditions for verification: Preserve positive, no-difference, and unfavorable findings according to their roles, without aggregating results for other questions as confirmation or refutation of B2. - Why this condition is needed: Reasons for exclusion and effect direction are separate dimensions; positive evidence must not be selectively chosen. - Application exceptions: Do not supply detailed directions, P values, or effect values absent from the current retained summary by guessing what the original paper says. - Remaining uncertainty: Detailed effects, dispersion, and P values in the related reports, and the distribution of eligible B2 results, remain unverified. - Referenced methods: The content of the existing family templates C08, E07 was adapted to this question. The preserved methodological principles serve as a reference; the detailed criteria were designed internally. - Related sources: S05, S08, S25 ### N26 · Which materials were actually read in this work, and what historical full-text access is recorded? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: In this work, the entire retained manuscript and the retained summaries and locations for the three citations were read. The full-text HTML entries for the three materials are historical access declarations in the original manuscript; external full-text access and reading in this work total 0. Individual access dates are absent and remain null. - Why unverified: Actual actions in this work and historical access declarations were recorded separately. This does not mean that clinical full texts were verified or that conditions were met. - Reason for missing information: The original clinical full texts and individual historical access dates are absent from this input. - Required materials and conditions: A list distinguishing retained summaries, citation locations, original-source access levels, individual dates, and reading records for this work for each material. - Materials to obtain first: A list distinguishing retained summaries, citation locations, original-source access levels, individual dates, and reading records for this work for each material. - Further research: If obtaining further materials is permitted, record actual access events, full-text locations, and dates, and compare them with the current summaries. - Conditions for verification: Distinguish reading the retained summaries in full in this work from the fact that access to external clinical full texts was not attempted and they were not read; do not label a link as reading the original text. - Why this condition is needed: Copying a historical declaration of access to a paper's full-text HTML as verification of the full text in this work would create a false reading record. - Application exceptions: If individual historical access dates are absent, leave them as null values and distinguish them from the original review date, 2026-09-15. - Remaining uncertainty: The original clinical full texts and individual historical access dates are absent from this input. - Referenced methods: The meanings of the existing family templates C03, C09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: S05, S08, S25 ### N27 · To what verification scope is the lack of verified directly eligible results limited? Verification status: Partly verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original judgment has the limited meaning that directly eligible results could not be verified in the documented search. It was not an exhaustive search of primary databases worldwide, and no new clinical search was performed in this work. - Why unverified: The bounded meaning of statements of absence and the cutoff date were verified, but the old search logs and full search scope were not directly cross-checked. - Reason for missing information: The comprehensiveness of the original search strategies, coverage of all databases and unpublished material, and coverage of material after the current date remain unverified. - Required materials and conditions: The original evidence cutoff, scope of the documented search, selection reasons, unverified areas, and whether a new search was performed in this work. - Materials to obtain first: The original evidence cutoff, scope of the documented search, selection reasons, unverified areas, and whether a new search was performed in this work. - Further research: In a subsequently permitted investigation, document the scope of searches, registrations, unpublished material, and corrections, and select each item using the current eligibility conditions. - Conditions for verification: Do not extend the original record's lack of verified eligible results to an absence of all human research worldwide or an effect of 0. - Why this condition is needed: This is needed to align the scope of clinical conclusions with the search scope. - Application exceptions: Because the referenced historical search records were not actually read, do not describe this as complete verification of search strategies or databases. - Remaining uncertainty: The comprehensiveness of the original search strategies, coverage of all databases and unpublished material, and coverage of material after the current date remain unverified. - Referenced methods: The meaning of the existing family template C09 was adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: S05, S08, S25 ### N28 · How should the original ?, null values, and unused axes be interpreted? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original grade is ?, and the score is null in the retained summary. The question's B/P is retained; R/I/E/B/C and the strength-axis count (strength_count) are null, the strength-axis list (strength_axes) is [], the override reason (override_reason) is an empty string, and some flags are false. The original true value of no_human_study is a historical record of the bounded lack of verified eligible results. - Why unverified: The original values and data types were directly compared. This is not a new calculation of the original judgment or verification of a clinical effect. - Reason for missing information: Assessment axes left unused in the original record because no eligible effect estimate had been verified were not newly filled in. - Required materials and conditions: The original text showing the original grade, score, B/P axes, null values, empty and false values, and their bounded meanings. - Materials to obtain first: The original text showing the original grade, score, B/P axes, null values, empty and false values, and their bounded meanings. - Further research: When updating evidence, preserve the original values and distinguish actual new evidence and condition changes from an event in which the original judgment is reconsidered. - Conditions for verification: Preserve the original judgment and data types without carrying them over as verification statuses, efficacy probabilities, or new scores in the new table. - Why this condition is needed: Unverified information and 0, empty strings and null values, and the clinical endpoint of the question and an actual effect value have different meanings. - Application exceptions: Do not present document quality A or technical confidence in identity assignment as clinical efficacy grades either. - Remaining uncertainty: Assessment axes left unused in the original record because no eligible effect estimate had been verified were not newly filled in. - Referenced methods: The meanings of the existing family templates C01, C09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: ### N29 · How were adverse events collected for the same exposure to B2 alone in IBD? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The dose, duration, and adverse-event denominators for this exact B2-alone question remain unverified, and the original safety status is unknown. Safety in a B1 trial or the essential nutritional role of B2 was not converted into safety of B2 treatment. - Why unverified: There are no direct materials verifying event definitions, collection, comparison, denominators, and follow-up for the same B2 exposure. - Reason for missing information: Events, timing, comparisons, participant/event counts, exposure denominators, omissions, and discontinuations remain unverified. - Required materials and conditions: Adverse-event definitions, occurrence/worsening, collection, discontinuations, severity, and exposure denominators for the same population, dose, and duration. - Materials to obtain first: Adverse-event definitions, occurrence/worsening, collection, discontinuations, severity, and exposure denominators for the same population, dose, and duration. - Further research: Define and systematically collect events under the same conditions as the eligible exposure, and report the number of people with events, the number of events, exposure denominators, and discontinuations. - Conditions for verification: Verify events, denominators, duration, and the scope of collection in direct B2 safety data; do not inherit safety findings from other ingredients. - Why this condition is needed: An efficacy summary or the essential nutritional role of a nutrient is not evidence of the safety of high-dose treatment. - Application exceptions: Do not present unverified adverse-event information as no events or safety. Keep gaps in efficacy and harms separate. - Remaining uncertainty: Events, timing, comparisons, participant/event counts, exposure denominators, omissions, and discontinuations remain unverified. - Referenced methods: The meanings of the existing family templates E10, H01, H02, H03, H04, H06, H09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: S05, S08, S25 ### N30 · Have interactions between IBD medications or other exposures and B2 been verified? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original record states that no separate comprehensive search of all drug interactions was conducted. Details of actual concomitant treatment by arm also remain unverified; this was not interpreted as no interactions. - Why unverified: The original status is no separate search performed, and no new interaction investigation was performed in this work either. - Reason for missing information: Comprehensive information on IBD medications, concurrent exposures, alternative causes, and interactions remains unverified. - Required materials and conditions: Medications and concurrent exposures in the same population, the scope of interaction investigations, events, and temporal relationships. - Materials to obtain first: Medications and concurrent exposures in the same population, the scope of interaction investigations, events, and temporal relationships. - Further research: In a subsequent safety investigation, record actual medications, exposures, timing, and alternative causes together, and design the necessary comparisons. - Conditions for verification: Record the distinction between no comprehensive search being performed and no known interactions, and actually verify information on concurrent exposures. - Why this condition is needed: This is needed to avoid attributing events due to IBD medications or other causes solely to B2. - Application exceptions: Do not newly list interactions or conclude that there is no risk. - Remaining uncertainty: Comprehensive information on IBD medications, concurrent exposures, alternative causes, and interactions remains unverified. - Referenced methods: The meanings of the existing family templates E10, H05, H08, H09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: S05, S08, S25 ### N31 · Does the assessment distinguish whether assay interference was investigated from whether there was an effect on fatigue? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: No separate systematic search of assay interference has been conducted. Persistent fatigue in patients and circulating vitamers are distinct; the current materials do not establish either the absence or detection of interference. - Why unverified: The original text records that no separate search was performed; the actual assay and interference assessment have not been verified. - Reason for missing information: The scope of interference investigations, assay methods, and effects remains unverified. - Required materials and conditions: The scope of investigations of interference in B2/vitamer assays, the actual measurement methods, and materials verifying interference. - Materials to obtain first: The scope of investigations of interference in B2/vitamer assays, the actual measurement methods, and materials verifying interference. - Further research: When interpreting biochemical markers, separately verify the actual assay and whether interference is present, and distinguish them from clinical fatigue. - Conditions for verification: Do not present the absence of a separate search as absence of interference or as actual detection of interference. - Why this condition is needed: Limitations of vitamer measurement must not automatically be converted into a clinical effect on fatigue or a diagnosis of deficiency. - Application exceptions: Do not impose assay-interference research uniformly as a mandatory efficacy condition for a patient-symptom question. - Remaining uncertainty: The scope of interference investigations, assay methods, and effects remains unverified. - Referenced methods: The meanings of the existing family templates C06, E03 were adapted to this question. Preserved methodological principles serve as references; the detailed conditions were designed internally. - Related sources: S05, S08, S25 ### N32 · Can questions about optimal dose, persistence of effects, and subgroups also be answered directly? Verification status: Unverified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: Because the eligible B2 dose, duration, and baseline status remain unverified, optimal dose, maintenance after discontinuation, and effects in particular subgroups could not be verified either. - Why unverified: There are no direct comparison, follow-up, or subgroup materials that answer this extension. - Reason for missing information: Dose comparisons, long-term follow-up, prespecified subgroups, and interactions remain unverified. - Required materials and conditions: Direct B2 dose comparisons, follow-up after discontinuation, and separate estimates for prespecified subgroups and interactions. - Materials to obtain first: Direct B2 dose comparisons, follow-up after discontinuation, and separate estimates for prespecified subgroups and interactions. - Further research: If the extended question is needed, separately design prespecified dose contrasts, follow-up, subgroup hypotheses, and appropriate interaction analyses. - Conditions for verification: Distinguish direct materials for the narrow persistent-fatigue question from extensions to optimal dose, persistence, and subgroups. - Why this condition is needed: When the principal effect remains unverified, the dose, particular patient groups, and maintenance of effects cannot be established. - Application exceptions: Do not impose all extension studies as mandatory conditions for the initial narrow question. Do not recommend unsupported doses or durations. - Remaining uncertainty: Dose comparisons, long-term follow-up, prespecified subgroups, and interactions remain unverified. - Referenced methods: The meanings of the existing family templates E08, H08 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: S05, S08, S25 ### N33 · Does the fatigue question also include IBD relapse, hospitalization, and improvement in disease activity? Verification status: Not applicable Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The current independent claim concerns persistent fatigue in patients; it does not include claims about IBD relapse, hospitalization, or improvement in disease activity. The effect on fatigue itself also remains unverified. - Why unverified: Because effects on separate clinical events are outside the scope of the current original claim, those event trials are not applied as mandatory conditions for the fatigue result. - Reason for missing information: Effects, denominators, and follow-up for separate events were not verified for this question. - Required materials and conditions: The boundary distinguishing the fatigue scope of the original question from separate questions about disease activity, events, and quality of life. - Materials to obtain first: The boundary distinguishing the fatigue scope of the original question from separate questions about disease activity, events, and quality of life. - Further research: If a separate event question is added, review event definitions, denominators, duration, and comparisons separately under new boundaries and conditions. - Conditions for verification: Do not extend changes in a scale of persistent fatigue in patients to improvement in other IBD clinical events. - Why this condition is needed: This is needed to prevent endpoint expansion, but it does not impose all event trials on the current fatigue question. - Application exceptions: The current table reviews only the persistent-fatigue question. Direct event evidence is required only when making a separate claim about clinical events. - Remaining uncertainty: Effects, denominators, and follow-up for separate events were not verified for this question. - Referenced methods: The meanings of the existing family templates C01, C06, E09 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: ### N34 · What materials, if obtained, would prompt reconsideration of the gaps in the fatigue question? Verification status: Verified Reading scope: The retained judgment summaries were actually read. Access to external clinical papers was not attempted, and those papers were not read in this work. - Current findings: The original policy is to update when eligible evidence, full texts, registry results, or corrections to numerical values, units, or identities are verified, preserving previous values, reasons, sources, and dates. Creation of this table is not modification of the original judgment, new research, or public distribution. - Why unverified: The update conditions and the policy of disclosing current uncertainty were verified in the retained original text. - Reason for missing information: No actual event of new clinical evidence, correction, or acquisition of full text occurred in this work. - Required materials and conditions: A list of updates linked to the current conditions: direct B2 evidence, full texts, registry results, and corrections to numerical values, units, or identities. - Materials to obtain first: A list of updates linked to the current conditions: direct B2 evidence, full texts, registry results, and corrections to numerical values, units, or identities. - Further research: Apply the precise identity, results, and date of new material to the existing conditions again; if the boundary changes, revise and freeze the conditions first. - Conditions for verification: Distinguish addition of new evidence, revision of the question or conditions, modification of the original judgment, and publication events, preserving previous values and reasons. - Why this condition is needed: The current unverified state must not be treated as permanently established, and the mere existence of new material must not be treated as satisfying the conditions. - Application exceptions: The original empty list of publication prerequisites (publication_prerequisites) or historical publication status does not constitute authorization for distribution or evidence of completion in this work. - Remaining uncertainty: No actual event of new clinical evidence, correction, or acquisition of full text occurred in this work. - Referenced methods: The meanings of the existing family templates C09, C01 were adapted to this question. The preserved methodological principles serve as references; the detailed conditions are internally designed. - Related sources: ## Evidence and sources ### S05 B-vitamins and metabolites in quiescent IBD with fatigue treated with oral thiamine (2023) [Official source](https://link.springer.com/article/10.1186/s10020-023-00741-3) Materials actually read: The relevant evidence/citation records and narrative summaries in the retained manuscript were actually read in this work; access to the external papers' full texts was not attempted, and they were not read Findings recorded in the summary: The trial intervention is oral thiamine hydrochloride. The B2-related vitamer analysis is an observational ancillary analysis within the same TARIF family, not a B2-administration trial. Record level: Summary of a related report recorded in the currently retained summaries; not direct verification of the clinical full text in this work Independent replication: Vitamer associations in a B1-administration trial; no B2 administration; not counted as a direct replication of B2 alone for persistent fatigue in quiescent IBD | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical paper | Current public availability is unverified; the original manuscript declares access to the paper's full-text HTML | Access not attempted in this work | Unread | Only the historical access declaration in the retained summaries was read in this work. Separate full texts or original attachments were not obtained or read. | | Retained summary of the preserved judgment | Original bytes currently preserved locally | Local input read successfully | Read | The current evidence/citation records and related KO/EN sentences were read; this is distinct from reading clinical full texts. | ### S08 Vitamin B complex plus magnesium and fatigue in IBD (2026) [Official source](https://www.nature.com/articles/s41598-026-49880-7) Materials actually read: The relevant evidence/citation records and narrative summaries in the retained manuscript were actually read in this work; access to the external papers' full texts was not attempted, and they were not read Findings recorded in the summary: The combination intervention contains B1·B6·B12 and magnesium. The results were not attributed to an effect of B2 or an isolated effect of B1. Record level: Summary of a related report recorded in the currently retained summaries; not direct verification of the clinical full text in this work Independent replication: B1+B6+B12+Mg; a combination without B2; not counted as a direct replication of B2 alone for persistent fatigue in quiescent IBD | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical paper | Current public availability is unverified; the original manuscript declares access to the paper's full-text HTML | Access not attempted in this work | Unread | Only the historical access declaration in the retained summaries was read in this work. Separate full texts or original attachments were not obtained or read. | | Retained summary of the preserved judgment | Original bytes currently preserved locally | Local input read successfully | Read | The current evidence/citation records and related KO/EN sentences were read; this is distinct from reading clinical full texts. | ### S25 Hoffman et al. — riboflavin and ultramarathon recovery (2017) [Official source](https://link.springer.com/article/10.1186/s40798-017-0081-4) Materials actually read: The relevant evidence/citation records and narrative summaries in the retained manuscript were actually read in this work; access to the external papers' full texts was not attempted, and they were not read Findings recorded in the summary: The ultramarathon recovery trial assessed acute muscle soreness and recovery performance. Its population and endpoints differ from those for persistent fatigue in quiescent IBD. Record level: Summary of a related report recorded in the currently retained summaries; not direct verification of the clinical full text in this work Independent replication: Acute muscle soreness and recovery after ultradistance exercise; not persistent fatigue in IBD; not counted as a direct replication of B2 alone for persistent fatigue in quiescent IBD | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Full text of a clinical paper | Current public availability is unverified; the original manuscript declares access to the paper's full-text HTML | Access not attempted in this work | Unread | Only the historical access declaration in the retained summaries was read in this work. Separate full texts or original attachments were not obtained or read. | | Retained summary of the preserved judgment | Original bytes currently preserved locally | Local input read successfully | Read | The current evidence/citation records and related KO/EN sentences were read; this is distinct from reading clinical full texts. | ## 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. · Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full. - 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. · Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full. - 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, deviations, missing data, measurement, and selective reporting. · Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full. - 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. · Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full. - 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. · Actual copies and hashes of the original methodological text from 1585 were reused. The model for this work read the preserved principles defining the families; it did not read the methodological HTML body, browse new web material, or apply the official method in full. ## What the statuses mean - Verified: Verification of the specified question, materials, attribution, or original records. Separate from establishing a clinical effect. - Partly verified: Some actual information has been verified, but the materials and results needed for the entire condition remain unverified. - Unverified: Direct information for judging the condition has not been verified in the current input. This does not mean 0, absence, or no effect. - Unread: The material itself was not actually read in this work. Separate from reading a summary. - Not applicable: A decision that an extension outside the specified current question scope does not apply. ## Change history 2026-11-01 · Public page/materials 1.0. A public display and data were created from the existing 34 items. No new clinical search, change to verification status, or scoring was performed.